مهرسا عدالت

آنالیز بیوانفورماتیک داده های بیانی در بیماری مولتیپل اسکلروزیس

مقدمه : مولتیپل اسکلروزیس یک بیماری نورودژنراتیو خود ایمنی است که شیوع آن از سال ۱۹۹۰ در سراسر جهان افزایش یافته است. MS یک بیماری تحلیل برنده غلاف میلین سلولهای عصبی در سیستم عصبی مرکزی است. در مطالعه حاضر، فناوری ریزآرایه و ابزارهای بیوانفورماتیکی برای شناسایی ژنها و مسیرهای تعامل بین آنها به منظور بررسی مکانیسم های مولکولی مشترک استفاده گردید. علاوه بر این، بر اساس نتایج این تجزیه وتحلیل، پیشبینی داروها برای درمان MS نیز انجام گرفت. روش کار : داده های ریزآرایه از پایگاه NCBI از قسمت GEO مربوط به داده های GSE41890 که حاوی اطلاعات مرتبط با بیان ژن در ۶۸ نمونه، استخراج و سپس دو گروه نرمال (سالم) و تیمار (MS) باهم مقایسه شدند. برای آنالیز داده ژن‌های بیان شده متفاوت (DEGs) از زبان برنامه نویسی R استفاده گردید. سپس شبکه مولکولی مورد نظر ترسیم گردید. شبکه تعامل پروتئین-پروتئین با STRING ترسیم شد. تجزیه و تحلیل ماژول شبکه PPI با استفاده از Cytoscape انجام شد. در نهایت، HUB ژن غربال شده در سطح پروتئین بررسی گردیدند. ساختار سه بعدی پروتئین ها از پایگاه داده www.rcsb.org دانلود شدند. به منظور بررسی برهمکنش پروتئین-دارو networkanalyst استفاده گردید. بررسی قابلیت فارماکو داروها با استفاده از پایگاه داده swissadme انجام شد. در نهایت با استفاده از نرم افزار PyRX عملیات داکینگ انجام شد. نتایج : در مجموع 1190 DEG شناسایی شد که عمدتاً در ایمنی سلولی، چرخه سلولی، تکثیر سلولی و انتقال سیگنال نقش داشتند. شبکه PPI شامل 67 گره و 629 برهمکنش بود. ده ژن برتر شامل KIF11، CCNA2، CDK1،BUB1، CDCA8، DLGAP5، TTK، KIF20A، TPX2، SPAG5 می باشند. سه هدف پروتئینی و پنجاه و یک داروی کاندید شناسایی شدند که به ترتیب حدود 11 دارو برای KIF11، 33 دارو برای CCNA2 و 7 دارو برای CDK1 استخراج شدند. به طور کلی ترکیب 99443535، 5005498 و 4566 به ترتیب به KIF11، CDK1 و cyclinAمتصل شدند.

مولتیپل اسکلروزیس، ریزآرایه، ژن، تعامل پروتئین-پروتئین، داکینگ

فاطمه علمی, مریم میترا علمی, فاطمه علمی, آرمیتا هدی

Assessment of Fish Skin Grafts in the Burn Wound Healing through Synchrotron FT-IR Microspectroscopy

The application of fish skin grafts in the management of burn injuries has garnered significant interest recently due to their distinctive properties. This research focuses on the healing process of wounds in a rat model following third-degree burns. During the healing phase, the rat skin exhibits various structural and molecular alterations, particularly concerning proteins and lipids. In this study, synchrotron radiation Fourier-transform infrared microspectroscopy (SR-FTIRM) was employed to examine the dermal region of rat skin post third-degree burns. The experiment involved three groups of rats: one group received treatment with white fish skin, another with carpio fish skin, and a control group with untreated wounds. The analysis of collagen fiber orientation, determined by the ratio of amide I to amide II (integrated intensities: 1600-1710 cm-1/1492-1598 cm-1), revealed that the group treated with white fish skin exhibited the most organized arrangement of fibers. Gaining insights into such structural characteristics may significantly improve our comprehension of wound healing mechanisms and tissue regeneration.

Fish skin graft: Burned wound healing: Collagen: Synchrotron radiation FT-IR microspectroscopy

Anahita Khammari, Sattar Khashkhashi-Moghadam, Anahita Khammari, Seyed Shahriar Arab, Ali Akbar Saboury

The conformational transition of prion to β-strands in prion fibrillation from molecular dynamics simulations

Prion diseases, such as Creutzfeldt–Jakob disease, Gerstmann-Straussler-Scheinker syndrome, and fatal familial insomnia, are caused by the conversion of the cellular prion protein (PrPC) into an insoluble, beta-sheet-rich, infectious isoform (PrPSc) [1]. Structurally, this transformation involves the transition of the second and third α-helices in the prion C-terminal region into β-strands, which are stabilized by a disulfide bond in prion fibrils [2]. Through targeted molecular dynamics simulations, we identified critical regions in the prion sequence that initiate fibril formation under physiological conditions. Notably, regions 172-176, 190-200, and 220-224 showed early deformation and loss of structure during simulations. We also realized the prion C-terminal mutations disrupt hydrophobic interactions, destabilize electrostatic interactions and salt bridges, cause side-chain interference, or damage the hydrogen bond networks that enhance structural instability and promote amyloid fibril formation. This study provides molecular insights into the early stages of the prion fibrillation mechanism.

α-β structural transition, Prion fibril formation, aggregation-prone sites, Targeted molecular dynamics simulation.

زهرا زحمتکش سرایدشتی

بررسی اثرات ضد میکروبی و ضدبیوفیلمی ترکیبات موثر گیاهی بر باکتری استرپتوکوکوس موتانس : مطالعه بیوانفورماتیکی

پوسیدگی دندان یکی از شایع&amp:#172:ترین و پرهزینه&amp:#172:ترین بیماری&amp:#172:های عفونی مرتبط با بیوفیلم در سراسر جهان است. استرپتوکوک موتانس به دلیل توانایی سنتز مواد پلیمری خارج سلولی و ایجاد شرایط اسیدی به عنوان عامل اصلی پوسیدگی دندان شناخته شده است. افزایش مقاومت میکروارگانیسم&amp:#172:ها به آنتی بیوتیک&amp:#172:ها به یک نگرانی علمی تبدیل شده است. تا به امروز، بسیاری از ترکیبات ثانویه گیاهی با فعالیت&amp:#172:های بیولوژیکی متنوع شامل فعالیت&amp:#172:های ضد باکتری، ضد قارچ و ضد سرطانی شناسایی شده&amp:#172:اند. بنابراین در این مطالعه، عوامل ضد میکروبی گیاهی غربالگری شد و تاثیر این ترکیبات در مهار آنزیم گلوکوزیل ترانسفراز S. mutans به عنوان عامل ایجاد بیوفیلم و پلاک دهانی از طریق داکینگ مولکولی مورد مطالعه قرار گرفت. در این مطالعه با استفاده از غربالگری مجازی تمامی ترکیبات گیاهی شامل سه گروه اصلی فلاوونوئیدها، ترپینوئیدها و آلکالوئیدها استخراج شدند.

پوسیدگی دندان، استرپتوکوک موتانس، ترکیبات ثانویه گیاهی، گلوکوزیل ترانسفراز، فلاوونوئیدها، ترپینوئیدها و آلکالوئیدها

میترا پیرحقی

The Potential of Cell-Penetrating Peptides in Neurodegenerative Disease Management and Drug Delivery

Cell-penetrating peptides (CPPs), also referred to as Trojan peptides or protein translocation domains, have emerged as a highly promising platform for intracellular delivery of polar and hydrophilic therapeutic agents, including peptides, proteins, and oligonucleotides. These peptides offer a noninvasive, efficient solution to the limitations associated with conventional delivery methods, such as low efficacy, high toxicity, and poor bioavailability. CPPs can traverse biological membranes to facilitate the transport of therapeutic molecules into challenging tissues, notably the central nervous system, by crossing the blood-brain barrier. This capability positions CPPs as valuable candidates for treating neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease [1]. Moreover, CPPs exhibit potential in mitigating pathological protein aggregation, a common feature of neurodegenerative conditions characterized by amyloid formation. Recent findings from our group demonstrate that the CPP-derived peptide p216 effectively targets and neutralizes toxic α-synuclein oligomers associated with Parkinson’s disease, thereby reducing oligomer-induced cytotoxicity. These results highlight the versatility of CPPs as a robust tool for advancing both basic research and therapeutic strategies in the treatment of neurodegenerative disorders [2].

Cell-penetrating peptides, blood-brain barrier, neurodegenerative disease, protein aggregation

Zahra Setayesh-Mehr

The effects of two fractions isolated from scorpion venom on inhibiting proliferation and inducing apoptosis in the HepG2 cancer cell line

Scorpion venom inhibits and suppresses cancer cells through various mechanisms, including the induction of apoptosis. In this study, the in vitro activity of two fractions, F2 and F4, obtained from Hemiscorpius lepturus venom was investigated using the HPLC method. In the first step, the cytotoxicity of the two isolated fractions, F2 and F4, against the HepG2 cancer cell line was assessed using the MTT assay. Thus, the cells were treated with various concentrations of F2 and F4 (0-50 µg/mL) for 24 hours. In the second step, cell death was evaluated through the real-time PCR technique to analyze the expression levels of genes involved in apoptosis. During the gene expression measurement phase, cancer cells were treated with each of two concentrations of F2 (15 µg/ml and 20 µg/ml) and F4 (30 µg/ml and 35 µg/mL) for 24 hours. The results showed that increasing the concentration of the purified fractions was associated with a significant decrease in cell viability (p < 0.05). Notably, F2 at a concentration of 20.41 µg/mL and F4 at a concentration of 37.54 mL induced 50./. cell death. Gene expression analysis indicated that increasing the concentration of both fractions was associated with a significant increase in the expression of Bax and cytochrome c genes, while the expression of Bcl-2 was significantly decreased (p < 0.05). In general, it seems that the cytotoxic effect of the two fractions obtained from scorpion venom appears to be associated with their ability to induce apoptosis via the mitochondrial pathway. Consequently, H. lepturus scorpion venom may be a promising natural extract for further research in liver cancer treatment strategies.

Scorpion venom, Hemiscorpius lepturus, Viability, Apoptosis, Gene expression

Zahra Setayesh-Mehr

اثر ضد تکثیری سم عقرب ایرانی Hemiscorpius lepturus در شرایط برون تنی بر روی رده سلول سرطانی Caco2

سم برخی از گونه¬های عقرب باعث ایجاد آپوپتوز و توقف تکثیر در سلول¬های سرطانی می¬شود. از این ویژگی مهم می¬توان در جداسازی ترکیبات دارای اهمیت درمانی در تحقیقات سرطان بهره برد. در مطالعه حاضر، اثرات سیتوتوکسیسیتی دو فرکشن 2 و 4 (F2 و F4) جداسازی شده توسط HPLC از سم عقرب Hemiscorpius lepturus در شرایط برون¬تنی مورد ارزیابی قرار گرفت. ابتدا سمیت سلولی با استفاده از سنجش MTT بررسی شد. پس از کشت سلول¬های Caco2 در تست MTT، غلظت‌های مختلف F2 و F4 ( µg/ml180-0)، به هر چاهک اضافه و به مدت 24 ساعت تیمار شدند. سپس فرآیند آپوپتوز سلولی با اندازه¬گیری بیان ژن¬های Bax، کاسپازهای 3 و 9 توسط تکنیک Real Time PCR مورد بررسی قرار گرفت. نتایج نشان داد که با افزایش غلظت هر دو فرکشن، درصد زنده¬مانی سلول¬های سرطانی تیمار شده با F2 و F4 نسبت به سلول¬های سرطانی بدون تیمار کاهش معناداری داشت (p<0.05). میزان IC50 برای F2 و F4، به ترتیب، µg/ml 24/80 و µg/ml 64/74 بدست آمد. نتایج بدست آمده از بیان ژن نشان داد که بیان ژن¬های Bax، کاسپازهای 3 و 9 سلول¬های سرطانی تیمار شده با دو فرکشن نسبت به سلول¬های سرطانی بدون تیمار افزایش معناداری داشت (p<0.05). در نهایت، افزایش بیان ژن-های کاسپاز و Bax به دنبال تیمار با هر دو فرکشن خالص سازی شده از سم عقرب، خاصیت آپوپتوتیک F2 و F4 را تایید کرد. این نتایج نشان می دهد که سم عقرب H. lepturus می¬تواند منبع بالقوه¬ای جهت جداسازی مولکول-های موثر در فرآیند ضدتکثیر و آپوپتوز سلول¬های سرطانی باشد.

سم عقرب، Hemiscorpius lepturus، MTT، آپوپتوز، بیان ژن

سروش بهجتی حسینی, سروش بهجتی حسینی, پیام ارغوانی, علی اکبر موسوی موحدی

Biophysical Impacts of Ionic Strength and Salt Type on Gelation of Soy Protein Isolate

This study investigates the impact of salt capacity on Soy Protein Isolate (SPI) gelation, a crucial process in food and biomaterial development. The significance of metal salts as powerful crosslinkers to form hydrogels is of interest in biomaterial science. We found that SPI gelation relies on protein denaturation and aggregation into a three-dimensional network, influenced by pH, temperature, and ionic strength. It was indicated that chloride salts can improve SPI gelation potential. The research examined the role of Li+, Na+, K+, Ca2+, Mg2+, Mn2+, Fe3+, and Al3+ cations in SPI gel formation using three SPI concentrations (10, 15, and 20 mg/mL) at pH 2.0, heated at 85°C for varying times. Factors affecting gel formation were analyzed both separately and simultaneously, with a visual assessment conducted to determine gel formation. The results indicated that a minimum SPI concentration of 15 mg/mL is necessary for gel formation, with a minimum processing time of 4 hours. For monovalent cations, no gel formation at 50 mM occurred. In contrast, both monovalent and divalent salts enabled gel formation at concentrations of 100 and 150 mM. The gelation capability of Mg2+ and Mn2+ was more pronounced. Notably, none of the trivalent cations led to SPI gelation. These findings underscore the significance of salt type and concentration in modulating SPI gelation, providing valuable insights for applications in food and biomaterial science.

Soy protein isolate, Gel formation, Metal salts, Crosslinker

Zahra Setayesh-Mehr

بررسی اثرات آنتی¬اکسیدانی دو فرکشن استخراجی از سم عقرب در شرایط برون¬تنی

به دلیل عدم بروز علائم جانبی، استفاده از آنتی¬اکسیدان¬های استخراجی از منابع طبیعی توجه بسیاری از محققین را به خود جلب کرده است. مطالعه حاضر به منظور بررسی فعالیت دو فرکشن استخراجی از سم عقرب Hemiscorpius lepturus (F2 و F4) انجام شد. بدین¬منظور، دو فرکشن در معرض ارزیابی¬های مختلف آنتی اکسیدان برون¬تنی از قبیل 1،1-دی فنیل-2-پیکریل هیدرازیل (DPPH)، 2،2-آزینو-بیس (3-اتیل بنزوتیازولین-6-سولفونیک اسید) (ABTS· +)، و رادیکال¬های آزاد هیدروکسیل قرار گرفتند. نتایج نشان داد که با افزایش غلظت، قدرت حذف رادیکال¬ها توسط هر دو فرکشن افزایش داشت و اختلاف چندانی میان توانایی حذف رادیکال توسط دو فرکشن و کنترل مثبت وجود نداشت. مقادیر IC50 دو فرکشن F2 و F4، به ترتیب، جهت حذف رادیکال DPPH، برابر با µg/ml 49/17 و 10/15، جهت حذف رادیکال ABTS، µg/ml 90/20 و 43/20 و جهت حذف رادیکال هیدروکسیل µg/ml 69/26 و 75/25 گزارش شدند. به طور کلی، نتایج مطالعه حاضر نشان داد، می¬توان دو فرکشن F2 و F4 استخراجی از سم عقرب H. lepturus را به عنوان عوامل آنتی¬اکسیدانی جدید معرفی کرد که می¬توانند تحت بررسی¬های بیشتر قرار بگیرند.

فرکشن، سم عقرب، Hemiscorpius lepturus، آنتی¬اکسیدان، برون¬تنی

Zahra Setayesh-Mehr

بررسی فرکشن های استخراجی از سم عقرب بر فعالیت آنزیم کاتالاز در سلول های جنینی کلیه انسان HEK293

در این مطالعه، اثر فرکشن:های استخراجی از سم عقرب Hemiscorpius lepturus بر روی سلول های جنینی کلیه انسان HEK293 در حضور و عدم حضور H2O2 بررسی شد. درصد زنده مانی سلول&amp:#172:های کشت داده شده با استفاده از تست MTT اندازه گیری شد. بدین&amp:#172:منظور غلظت&amp:#172:های مختلف دو فرکشن F2 و F4 (&amp:#181:g/ml 0-35) تهیه شدند. علاوه بر این، آنزیم کاتالاز از سلول&amp:#172:ها استخراج و سپس فعالیت آن اندازه گیری گردید. نتایج مطالعه نشان داد که درصد زنده&amp:#172:مانی سلول&amp:#172:های HEK293 تیمار شده با F2 و F4 در شرایط حضور و عدم حضور H2O2 وابسته به دوز کاهش یافت. میزان کاهش درصد زنده&amp:#172:مانی در غلظت &amp:#181:g/ml 35، برای هر دو فرکشن F2 و F4، 45/22 درصد در شرایط عدم حضور H2O2 و 5/18 درصد در شرایط حضور H2O2 نسبت به نمونه کنترل بدون تیمار بود. هر دو فرکشن F2 و F4، کاهش فعالیت آنزیم کاتالاز را خنثی نمودند، به&amp:#172:طوری&amp:#172:که توانستند میزان فعالیت آنزیم کاتالاز را در شرایط حضور نسبت به عدم حضور H2O2 افزایش دهند. میزان افزایش فعالیت آنزیم کاتالاز برای سلول&amp:#172:های تیمار شده با F2 و F4، به ترتیب، در شرایط عدم حضور H2O2 (28 و 61 درصد) و در شرایط حضور H2O2 (47 و 63 درصد) بود. به طور کلی، نتایج مطالعه حاضر نشان داد که F2 و F4 استخراج شده از سم عقرب، از طریق بروز فعالیت آنتی&amp:#172:اکسیدانی خود سبب افزایش درصد زنده&amp:#172:مانی و همچنین افزایش فعالیت آنزیم کاتالاز گردد.

فرکشن، سم عقرب، Hemiscorpius lepturus، HEK293، آنتی اکسیدان

اعظم جباری, مرتضی جباری

UIO66-NH2@PANI nanocomposite for the adsorption of antiradical biomolecule quercetin: A kinetic and thermodynamic insight

In this study, the UIO66-NH2@PANI nanocomposite was synthesized using a straightforward step-by-step self-assembly method and tested for its selective adsorption of the biomolecule quercetin. The synthesized nanocomposite underwent comprehensive analysis using FTIR and TGA techniques. The adsorption kinetics and thermodynamics of the magnetic nanocomposite for quercetin were rigorously investigated. The results indicated that the experimental data for adsorption kinetics was well-described by the pseudo-second-order kinetic model. Additionally, the effect of temperature analysis revealed that the adsorption of quercetin onto UIO66-NH2@PANI is a spontaneous process (∆G°: <: 0) and exothermic (ΔH°: <: 0).

Biomolecule quercetin, kinetics, nanocomposite, Thermodynamics, Adsorption

عباس نیکویی, عباس نیکویی, اباصلت حسین زاده کلاگر, محمدتقی هدایتی

Missense NEXN-rs1166698 Gene Polymorphism May Correlate to Protein Structural Disruptions in Cardiomyocytes: An In-Silico Study

Nexilin, encoded by the NEXN gene, is a vital actin-binding protein that plays a crucial role in maintaining the structural integrity of cardiomyocytes [1]. Disruptions in its structure may contribute to cardiac dysfunction [2]. In this in silico study, we focused on the structural impact of the rs1166698 single nucleotide polymorphism (SNP) (G>A, Gly181Arg) within the NEXN gene. Using bioinformatics tools such as SIFT, PolyPhen-2, and Mutation Assessor, we assessed the Gly181Arg substitution and found it deleterious, indicating potential disruption in protein function. Structural stability analysis performed by I-Mutant, iStable, and MUpro predicted a significant reduction in nexilin`s stability due to this mutation, suggesting that the protein may lose its ability to maintain proper mechanical support in heart cells. Furthermore, secondary structure predictions from PSIPRED and GOR-IV showed that the Gly181Arg substitution may alter the folding pattern of nexilin, affecting its structural conformation and potentially leading to functional impairments. As nexilin plays a critical role in anchoring actin filaments, these structural alterations could disrupt the cytoskeletal organization in cardiomyocytes, contributing to arrhythmogenic conditions [3]. Therefore, this study identifies the rs1166698 polymorphism as a potentially significant factor in nexilin dysfunction, warranting further investigation into its role in protein structure and arrhythmia development.

Missense SNP, NEXN gene, protein stability, protein structure, rs1166698.

محبوبه اسلامی مقدم

Effect of asymmetric and symmetric bidentate ligands in the structure of anticancer platinum complexes in cancer treatment

To design and synthesize new anticancer Pt drugs, the structure and bioactivity relationship is investigated with the change of ligands and also metal center. The presence of monodentate or bidentate ligands containing symmetric and asymmetric donates, and non-leaving groups, including aliphatic or aromatic compounds can affect the biological activity of these related metallodrugs. In this study, some Pt(II)/Pt(IV) complexes have been prepared where ligand can be NH3, N^N donor like 2,2′-bipyridine, 1,10′-phenanthroline, or R, R diamine-cyclohexane, and also O^O oxalate derivatives, asymmetric N^O amino acid derivatives, and then characterized. The stability, water solubility, and lipophilicity of these complexes were evaluated and compared with clinical Pt drugs such as cisplatin, carboplatin, and oxaliplatin. The in-vitro anticancer activities of these compounds were examined against several cancerous cell lines. Data show that due to less steric effect, and the presence of a length aliphatic hydrocarbon chain in the complex structure, more toxicity on cancerous cell lines is expected. Regarding different solubility and lipophilicity behaviors, the accumulation of complexes and clinical Pt drugs in each cancerous cell was investigated. According to data, using bulky ligands leads to lipophilicity modification and less cytotoxic activity, while aromatic groups cause more anticancer ability. Chain and cyclic aliphatic bio-ligands may reduce the bio-efficacy of these compounds. Based on the all-mentioned conclusions, these candidates will be investigated selectively further in in-vivo studies and chemotherapy and cancer treatment.

Pt(II)/Pt(IV) complexes, Clinical Pt drugs, Cytotoxicity, Solubility, Lipophilicity.

فاطمه میرآب, علی اکبر صبوری, میترا پیرحقی

Gut Microbiota and Parkinson`s Disease: A Double-Edged Sword

Parkinson`s disease (PD) is a neurodegenerative disorder characterized by the abnormal accumulation of α-synuclein (α-Syn) in the brain. Recent research highlights the significant role of the gut microbiota, the diverse community of microbes living in the intestines, in modulating α-Syn pathology. This review explores the bidirectional communication along the microbiota-gut-brain axis, focusing on the impact of two gut microbiota metabolites—functional bacterial amyloids (FuBA) and vitamins—on neurodegenerative diseases, particularly PD. FuBA, proteinaceous structures produced by bacteria, contribute to PD pathogenesis by promoting α-Syn aggregation and biofilm formation, which are crucial processes in the development and progression of PD. On the other hand, vitamins, essential micronutrients produced by the gut microbiota, offer neuroprotection through their anti-amyloidogenic, antioxidant, and anti-inflammatory properties. Vitamins such as B vitamins and vitamin K can help reduce oxidative stress, promote neurogenesis, and modulate immune responses, all of which are essential for maintaining brain health. Understanding the complex interplay between the gut microbiota, α-Syn aggregation, and neurodegeneration provides valuable insights into the pathogenesis of PD. Targeting the gut microbiota with therapies aimed at modulating FuBA production or enhancing vitamin synthesis could represent promising avenues for the prevention and treatment of PD. By manipulating the gut microbiome, it may be possible to influence α-Syn aggregation, reduce neuroinflammation, and improve overall brain function in individuals at risk for or diagnosed with PD.

Gut microbiota, functional bacterial amyloids, vitamin, α-Synuclein, Parkinson’s disease

محیا محمدظاهری, علی اکبر صبوری, علی اکبر مرآتان, فاطمه ممشلی, زهرا موسوی جراحی, عطیه قاسمی

Inhibition of A53T Alpha-Synuclein Fibrillation by Quercetin and Deep Eutectic Solvents

The aggregation of the alpha-synuclein protein, particularly the A53T mutant, is strongly linked to neurodegenerative diseases like Parkinson’s disease. Inhibiting alpha-synuclein fibrillation is a promising therapeutic strategy. Quercetin, a bioactive flavonoid known for its antioxidant and anti-aggregative properties, has limited solubility in aqueous environments, hindering its therapeutic use. Recently, deep eutectic solvents (DES) are eco-friendly solvents that can enhance the solubility of hydrophobic compounds. This study investigates the inhibitory effects of quercetin dissolved in DES on A53T alpha-synuclein fibrillation. Using fluorescence microscopy and fibrillation kinetics, we assess the ability of this combination to reduce protein aggregation, suggesting a potential therapy for neurodegenerative diseases. Fluorescence microscopy results demonstrated that quercetin dissolved in DES significantly curbs the fibrillation of A53T alpha-synuclein, as indicated by the reduced formation of fibrils. Furthermore, kinetic analysis revealed that quercetin dissolved in DES prolonged the lag phase of fibrillation from 7 hours to 12 hours, indicating a marked delay in the aggregation process. These findings suggest that quercetin, when combined with DES, can effectively impede the initial stages of protein fibrillation. Our research highlights the therapeutic potential of quercetin in DES for protein misfolding disorders, offering new avenues for research in treating neurodegenerative diseases such as Parkinson’s disease.

Alpha-synuclein: Parkinson’s disease: Fibril: Quercetin: Deep eutectic solvents

مهران عرفانی, پونه مکرم

Low Expression of Tumor Suppressor ARID1A Correlates with Reduced Expression of E‑cadherin in Colorectal Cancer

Metastasis is a major cause of death in Colorectal cancer (CRC) patients, and the Epithelial mesenchymal transition (EMT) has been known to be a crucial event in cancer metastasis. Downregulated expression of AT-rich interaction domain-containing protein 1A (ARID1A), a bona fide tumor suppressor gene, plays an important role in promoting EMT and CRC metastasis, but the underlying molecular mechanisms remain poorly understood. Here, we evaluated the correlation between ARID1A expression and EMT‐associated markers, E-cadherin and β-catenin, in human CRC. We measured the transcription levels of ARID1A, E-cadherin and β-Catenin via real time quantitative PCR (qPCR) in 30 pairs of colorectal cancer tissues and their matched non-tumor adjacent tissues. Interestingly, we found an obvious correlation between the expression of ARID1A and E-cadherin in colorectal cancer tissue samples, however, the correlation coefficient was not perfect (r = -0.526). β-Catenin transcription levels was not found to correlate with ARID1A. Thus, ARID1A downregulation may promote CRC metastasis through decreasing EMT‑related protein E-cadherin and promoting epithelial cell movement.

Colorectal cancer, ARID1A, E-cadherin, β-catenin

محمدحسین خدابنده‌لو, محمدحسین خدابنده‌لو, شیرین محمدیان, علی اکبر موسوی موحدی

Developing 3D Bio-printer for Fabrication of Microfluidic Systems in Protein-Ligand Interaction

3D bioprinter engineered for the rapid and precise fabrication of microfluidic and millifluidic systems, and designed to enhance studies of protein-ligand interactions. This system integrates microfluidic-optimized nozzles with sub-micrometer precision, enabling swift biofabrication with biocompatible materials, significantly reducing the time and complexity associated with traditional lithographic or soft lithography techniques. The primary advantage of this bioprinter is its ability to quickly prototype fluidic channels and experimental setups, which facilitates real-time studies of biomolecular interactions in controlled, physiologically relevant conditions. Early experiments demonstrate that the printer can generate intricate fluidic environments faster but lower reproducibility compared to conventional methods. This rapid fabrication process not only accelerates experimental workflows but also enables high-throughput screening applications, such as drug discovery and protein engineering. By simulating protein-ligand binding dynamics more efficiently, this system offers superior versatility for studies in structural biophysics and biochemistry, making it an invaluable tool for advancing biomolecular research.

3D bioprinter, rapid biofabrication, microfluidic systems, protein-ligand interaction, high-throughput screening.

ساجده لطیفی, اباصلت حسین زاده کلاگر, محمد کریمیان, محمد تقی هدایتی

Missense EPHX1- rs1051740 Gene Polymorphism May Correlate to pre-eclampsia: An In silico Study

Epoxide hydrolase (EH) is a critical biotransformation enzyme that converts epoxides from aromatic compounds` degradation to trans-dihydrodiols that can be conjugated and excreted from the body. EPHX1 is involved in the metabolism of xenobiotics and steroids and also plays a role in repair following oxidative injury. Mutations in this gene cause pre-eclampsia (PE), epoxide hydrolase deficiency, or increased epoxide hydrolase activity. In silico studies can help to identify the functional role of single nucleotide polymorphisms (SNPs) in the structure and stability of EPHX1 protein and to predict their relationship with PE. This study investigated, missense SNPs of the EPHX1 gene and their effects on PE. At first, all missense SNPs of the EPHX1 gene, located on chromosome 1q42.12, were monitored. Missense SNPs with a minor allele frequency (MAF)≥ 0.1 were selected in the NCBI-dbSNP database. The effect of the selected SNP based on functional, structural, and stability aspects of the protein was investigated by the following twelve online software: SIFT, Polyphen-2, PANTHER, SNPs&GO, PhD-SNP, Mutation Assessor, PROVEAN, I-mutant, iStable, MUpro, PSIPRED, and HOPE. Analysis of missense SNP by SIFT, Polyphen-2, PANTHER, and PROVEAN showed that rs1051740 (T>C, Tyr113His), could be a deleterious SNP for the function of EPHX1. The prediction of the effects of this SNP by I-mutant, IStable, MUpro, and PSIPRED also showed that substituting Tyr113His may decrease the stability of the protein. On the other hand, The HOPE analysis tool illustrated that the rs1051740 variant could disturb the protein motifs. Our findings suggest that the EPHX1 gene may be involved in the development of PE and rs1051740 may have deleterious impacts on the function of this gene.

Epoxide hydrolase 1, Genetic Polymorphism, In silico studies, Missense SNPs, Preeclampsia

نیکو محبعلی زاده, نیکو محبعلی زاده, پیام ارغوانی, المیرا رضائی پژوهش, علی اکبر موسوی موحدی

Hydrophobic amino acids functionalized SPION as a powerful tool for insulin nanofibril bioseparation

Superparamagnetic iron oxide nanoparticles (SPIONs) have garnered significant interest due to their unique superparamagnetic properties and high surface-area-to-volume ratio, which enhance molecular interactions and facilitate efficient absorption and penetration across various applications. A key feature of SPIONs is their ability to lose magnetization when the external magnetic field is removed, making them ideal for targeted applications and easy removal after use. In this study, SPIONs with an iron oxide core were synthesized via co-precipitation and functionalized with different hydrophobic amino acids to target insulin fibrils formed under stress conditions. Among them, SPIONs functionalized with optimum hydrophobicity were selected. Due to their iron content, these nanoparticles exhibit low toxicity and good biocompatibility with the human body, akin to the iron in hemoglobin. The behavior of the functionalized SPIONs with insulin fibrils was investigated using spectroscopy and fluorescence microscopy. Results demonstrated high selectivity of the SPIONs for insulin fibrils, effectively separating them while exhibiting no such affinity for native insulin. Additionally, the efficacy of SPIONs in the presence of a molecular crowding agent—mimicking the high concentration of fibrillated protein in cellular environments—was confirmed, further highlighting their potential for therapeutic applications.

Insulin, fibrils, hydrophobicity, superparamagnetic iron oxide nanoparticles, amino acid, bioseparation

بیتا ضمیری, نیلوفر منزوی, بیتا ضمیری

Studying the interaction between four-stranded nucleic acid structures and Actinomycin-D and Berberine

The binding phenomenon between non-canonical nucleic acid structures, specially four-stranded structures such as G-quadruplexes and i-motifs, with small molecules has garnered significant interest in recent years since it can result in the design of therapeutic systems which target unusual nucleic acids involved in disease pathogenesis. This study investigates the binding interaction between Actinomycin D, a chemotherapeutic agent, and Berberine, a natural alkaloid found in plants, with G-quadruplexes and i-motifs fomed by four repeats of the C9orf72 repeat whose expansion is known to cause ALS/FTD. The binding phenomenon has been monitored via UV spectroscopy where we have shown that both Actinomycin D and Berberine exhibit binding with G-quadruplexes and i-motifs reflected in the change in absorbance. Based on the observed hyperchromocity and the dissociation constants calculated, Actinomycin D and Berberine are shown to have slightly higher affinity for the i-motifs formed under acidic conditions.

G-quadruplexes, i-motifs, Berberine, Actinomycin D, Drug-DNA binding

ملیحه آزادپرور, مریم بیدخوری, میترا خیرآبادی, سکینه کاظمی نورعینی, ملیحه آزادپرور

شبیه سازی بر هم کنش گروهی از ترکیبات مهاری بر دمین آمینی کپسید ویروس HTLV-1 با روش In Silico

ویروس HIV-1 و HTLV-1 هر دو متعلق به خانواده رتروویریده ها هستند. ویروس (HTLV-1) منجر به بیماری هایی نظیر لنفوم سلولهای T بالغ (ATL) و سندروم التهابی پیشرفته عصبی به نام TSP/HAM ، آرتروپاتی در مفاصل و التهاب در چشم می شود. همچنین ویروس( HIV-1 ) مسئول ابتلا به سندروم نقص ایمنی اکتسابی (AIDS) می باشد . کپسید(P24) ساختاری ضروری برای شکل گیری ویروس کامل و تکثیر ویروس است که متاسفانه تاکنون هیچ ترکیب مهاری جهت ممانعت از عملکرد این ساختار پروتئینی در ویروس HTLV-1 مطرح نگردیده است. در تحقیق حاضر باتوجه به هم خانواده بودن و تشابه حتمی دو ویروس HIV-1 و HTLV-1 ، گروهی از ترکیبات مهاری که در مطالعات تجربی حاکی از اثرگذاری مناسب بر دمین آمینی کپسید ویروس HIV-1 بودند بوسیله شبیه سازی داکینگ مولکولی و دینامیک مولکولی بر کپسید HTLV-1 مورد ارزیابی قرار گرفتند که اثرات مهاری موثری را بر ناحیه آمینی کپسید این ویروس نشان دادند.

کپسید، مهارکننده،HTLV-1 ،HIV-1

ملیحه آزادپرور, الهه شکراللهی, میترا خیرآبادی, مریم بیدخوری, ملیحه آزادپرور

Anti HTLV compounds from fungal metabolites as protease inhibitor: in silico study

There is no curative treatment for patients infected with HTLV. HTLV protease is important in activities such as replication cycle and virus maturity. The fungal metabolites as bioactive molecules could potentially be considered as a good source of discovery of new medicines. The present study aimed to investigate the inhibitory effect of fungal metabolites on HTLV-1 protease. Twenty fungal secondary metabolites from five different chemical groups were selected based on the inhibitory effects on HIV protease, including Colossolactones, Lanostane type Triterpenoids, Farnesyl Hydroquinones, Steroquinones, Cytochalasins, while indinavir was considered as the control. Human T-cell lymphoma virus protease (PDB code: 3LIN) was selected as the receptor for subsequent computational docking and molecular dynamic simulation study with Autodock and Gromacs, respectively. Results of the docking and molecular dynamic simulation study suggested a favorable binding mode of Colossolactone IV, Colossolactone II, Ganoderiol F, and Schisanlactoneto the HTLV protease concerning indinavir. Analysis of hydrogen bond pattern and RMSF plot revealed a nearly similar ligand-receptor interaction for ColossolactoneIIandGanoderiol Fin complex with HTLV protease in comparison with indinavir. Colossolactone II and IV derived from Colossum Ganoderma and Ganoderiol F derived from Ganoderma Lucidum exhibited an anti-HTLV protease effect that has been proposed to be able to be developed as a drug.

HTL-V1 protease, inhibitor, fungal metabolites

افروز انبارکی, عارفه سید عربی

The volatile compounds α-asarone and β-caryophyllene promote disassembly and dis-aggregation of tau fibrils and natural aggregates

Aggregation and assembly of hyperphosphorylated tau into neurofibrillary tangles (NFTs) is one of the main pathological hallmarks of Alzheimer’s disease (AD) and other tauopathies. A critical step in the formation of NFTs involves the conversion of soluble tau into insoluble fibrils and aggregates. Disassembly and disaggregation of tau fibrils and aggregates into the non-toxic tau oligomeric species is recognized as a viable therapeutic strategy. In the current study, the effects of the volatile compounds α-asarone (ASA) and β-caryophyllene (BCP) were assessed for their potential to promote the disassembly and dis-aggregation of tau fibrils and aggregates. SDS-PAGE analysis revealed that both ASA and BCP, at certain concentrations, could convert the high molecular weight tau species into their low molecular weight counterparts or monomeric forms. The ThT fluorescence intensities of the pre-formed tau fibrils and aggregates diminished in the presence of the volatile compounds ASA and BCP. Furthermore, circular dichroism spectroscopy analysis indicated that ASA and BCP substantially diminished the β-sheet structure of the tau samples, concomitantly increasing the α-helix or random coil contents. Additionally, atomic force microscopy images illustrated that ASA and BCP possess the capacity to convert tau fibrils or aggregates into tau intermediate oligomers. MTT assays indicated that these tau oligomers formed in the presence of ASA and BCP were less toxic to the SH-SY5Y neuroblastoma cells, in comparison to the not-treated positive control sample. All results revealed the potential protective effects of ASA and BCP on tau fibrils and aggregates. Consequently, the volatile compounds ASA and BCP warrant further investigation due to their neuroprotective and therapeutic activities against AD and other tauopathies.

α-asarone, β-caryophyllene, Disassembly, Dis-aggregation, tau protein, Alzheimer’s disease

رویا تدین, کیوان جهان فر, جمشید خان چمنی, عبدالحمید طباطبایی فر, ایمان رازقیان جهرمی, سمانه ذولقدری جهرمی

FIRIA: A Novel Non-Invasive Technique for Breast Cancer Diagnosis

Functional Infrared Resonance Imaging Assay (FIRIA), a novel non-invasive technique for medical diagnosis, was recently introduced by Jahanfar. In this study, we modeled the FIRIA signals associated with 17 inflammatory factors using Ab Initio Quantum Chemistry softwares. Our objective was to investigate the potential of FIRIA imaging for diagnosing and monitoring breast cancer using these factors. We obtained the molecular structures of the 17 inflammatory factors from the PubChem databases and the RCSB Protein Bank. After making structural corrections, we utilized the GAMESS software with the DFTB method, applying the OB2W0PT3 parameter. Subsequently, we modeled the FIRIA signals at five different lateral resolutions using Python. Statistical analyses of these 17 signals across all resolutions revealed significant differences in their signal patterns, allowing for clear differentiation between them. Among the modeled FIRIA signals, the most notable variations were found in interferon-gamma, plasmin, thrombin, and tryptase, which had an average RMSD of 4.99. Conversely, the lowest variation was observed in prostaglandin, leukotriene B4, 5-hydroxyeicosatetraenoic acid, and histamine, with an average RMSD of 2.28. Notably, we found that as the resolution increased, the RMSD values and the distinctions between the signals also rose. The findings highlight the high potential of the FIRIA imaging method for diagnosing crucial inflammatory factors and emphasize the feasibility of employing FIRIA for the diagnosis and monitoring of breast cancer and other cancers or diseases where these inflammatory factors hold clinical significance.

Radiology, Non-Invasive Diagnosis, Breast Cancer, Infrared Imaging, FIRIA

باقر دوائیل, فائزه موسوی موحدی, علی اکبر موسوی موحدی

Characterizing Minor Peak in DSC Thermograms of HSA: Unveiling Thermal Transition Insights

Previous studies on Human Serum Albumin (HSA) DSC thermogram have been reports of either two distinct Tm or just a single Tm. This study analyzes their DSC thermograms by examining the differential thermodynamic behaviors of HSA and HSA-Fatty Acid (HSA-FA) complexes. Notably, minor peaks in the DSC profiles underscore subtle thermal transitions. the minor peak in the DSC thermogram seems to belong to the protein`s domain I (DI). The melting temperature (Tm) variations between HSA and HSA-FA reveal significant insights into their stability and interaction mechanisms. These findings highlight the nuanced impact of fatty acid binding on the thermal properties of HSA, offering valuable implications for biochemical and pharmaceutical applications.

HSA, DSC thermogram of HSA, minor peak

حسین کیوانشکوه, خانم دکتر محبوبه سالامی مقدم

Platinum(IV) prodrugs based on carboplatin with biological approaches to improve drug delivery

Carboplatin is a derivative of cisplatin: with a similar intercellular mechanism and different structure and cytotoxicity. It was approved by the FDA in the 1980s and since then it has been widely used to treat various types of tumors. However, there are serious inconveniences as some patients develop resistance during treatment, limiting the full potential of the drug. Consequently, the discovery of novel metallodrugs with different structural and mechanistic profiles for drug development plays an important role in cancer drug discovery. [1-3] In this study, a new binuclear carboplatin (IV) derivative was synthesized using diamine as a bridging ligand and then characterized by spectroscopic methods. The reduction behavior in the presence of ascorbic acid was investigated by using electronic absorption monitoring. Regarding in-vitro evaluation of this new carboplatin derivative, more toxicity has been shown against MCF-7 cell lines than carboplatin. The cell death mechanism`s activity was investigated by using Flow cytometry which determined apoptosis cell death. In addition, DNA interaction and molecular docking display groove binding on sites of the DNA skeleton as a main target in chemotherapy.

Binuclear Pt(IV) complex, Anticancer drug, DNA binding, Molecular docking

مریم صادقی, خانم دکتر محبوبه اسلامی مقدم

Synthesis, Characterization, Reduction, and Cytotoxicity of Anticancer Platinum (IV) Prodrugs Containing Amine as an axial ligand

Abstract Platinum (II)-based drugs are widely used for tumor treatment: however, severe side effects and the emergence of resistance limit their clinical effectiveness [1,2]. Pt(IV) derivatives have been developed to address these issues, offering enhanced stability and solubility [3]. In this study, we designed and synthesized Pt(IV) complexes incorporating carboplatin with an amine axial ligand. The proposed structures of these complexes were confirmed using 1H NMR, 13C NMR, 195Pt NMR, FT-IR, CV, and LC-MS methods. We employed density functional theory (DFT) to examine the geometries of the complexes. The reduction of Pt(IV) complexes by ascorbic acid in phosphate-buffered saline at room temperature was analyzed using UV-Vis monitoring. We also investigated the interactions between Pt(IV) complexes and ct-DNA through UV-Vis spectroscopy and molecular docking simulations. Compared to carboplatin, the synthesized compound exhibited improved water solubility due to the increased polarity of the carboxylate ligands. Additionally, the biological properties of these complexes were analyzed, revealing that those containing succinic acid and amine groups exhibit cytotoxicity comparable to oxaliplatin, likely due to higher cellular accumulation attributed to increased lipophilicity. Our findings suggest that the newly synthesized Pt(IV) complexes represent a promising class of potential anticancer agents that could be explored as clinical drugs soon [4].

: Pt(IV) complex, Axial ligands, Amine, Anticancer drug, Cytotoxicity

صبا غطاوی, صبا غطاوی, طیبه زارعی کریانی, احسان کامرانی, احمد همایی

Design and Development of Bio-Based Coatings Using Protease Enzymes to Prevent Microorganism Growth on Marine Surfaces

Marine biofouling on surfaces such as ship hulls and other maritime equipment results in increased fuel consumption, decreased speed, and elevated maintenance expenses. Although chemical antifouling paints are commonly employed to combat this challenge, numerous formulations contain toxic substances detrimental to marine ecosystems. In contrast, protease enzymes present a viable eco-friendly alternative to inhibit the proliferation and accumulation of microorganisms on these surfaces. Protease enzymes were chosen as bioactive antifouling agents due to their ability to degrade proteins, which directly affects the biological integrity of microorganisms. A series of laboratory and field evaluations have shown that coatings exhibiting protease activity effectively hinder the adhesion and growth of bacteria, algae, and various marine organisms on treated surfaces. In conclusion, protease-based bio-coatings not only exhibit significant effectiveness in reducing fouling but also mitigate negative impacts on marine ecosystems, leaving no harmful byproducts upon degradation. So, protease enzymes is a pioneering strategy for the formulation of sustainable antifouling coatings, emphasizing the potential of enzyme-based solutions to alleviate the environmental consequences of antifouling practices within the maritime sector.

Bio-Based Coatings, Protease Enzymes, Biofouling, Antifouling, Marine Surfaces

سید محسن اصغری

بهبود فعالیت ضد توموری داروی شیمی درمانی لاپاتینیب از طریق بارگذاری در آلبومین سرم انسان

مقدمه: سرطان سینه سه‌گانه منفی (TNBC) به‌ویژه نوعی مهاجم از سرطان است که به علت فقدان گیرنده‌های هورمونی و بیان HER2 به‌ سختی قابل درمان است. استراتژی‌های درمانی سنتی کارایی محدودی دارند و اغلب با عوارض جانبی قابل توجهی همراه هستند. لاپاتینیب، یک مهارکننده تیروزین کیناز، در برابر TNBC پتانسیل مناسبی نشان داده است؛ با این حال، کاربرد بالینی آن به دلیل حلالیت پایین و سمیت سیستمیک محدود شده است. این مطالعه سیستم تحویل داروی جدیدی را بررسی می‌کند که هدف آن ارتقای شاخص درمانی لاپاتینیب از طریق کپسوله کردن با آلبومین سرم انسانی(HSA) است، که به‌عنوان حامل زیست‌سازگار و غیرسمی با ظرفیت بالای اتصال به دارو شناخته می‌شود. اهداف: این پژوهش بهبود کارآیی درمانی و انتخاب‌پذیری لاپاتینیب برای درمان TNBC را با استفاده از HSA به‌عنوان پلتفرم تحویل هدف قرار داده است. با کپسوله کردن لاپاتینیب در نانوذرات HSA، مطالعه به ارتقای حلالیت آن، ایجاد آزادسازی کنترل‌شده دارو و کاهش سمیت سیستمیک معمولاً مرتبط با شیمی‌درمانی می‌پردازد. روش‌ها: لاپاتینیب از طریق برهمکنش‌های هیدروفوبیک در HSA وارد شد و کمپلکس‌های HSA-LAP حاصله با استفاده از روش‌های طیف‌سنجی (طیف‌سنجی UV و فلورسانس)، میکروسکوپ نیروی اتمی (AFM)، و میکروسکوپ الکترونی عبوری (TEM) برای ارزیابی یکپارچگی ساختاری و کارایی بارگذاری دارو شناسایی شدند. در آزمایش‌های سلولی، سمیت سلولی با استفاده از آزمون MTT بر روی سلول‌های سرطان سینه 4T1 برای تعیین مقادیر IC50 ارزیابی شد. این مطالعه همچنین شامل آزمون‌های آپوپتوز (رنگ‌آمیزی Annexin V/PI و فعال‌سازی کاسپاز) و آزمون‌های ترمیم زخم برای بررسی خواص ضد مهاجرتی بود. کارآیی درون‌ تنی با استفاده از مدل موش BALB/c، اندازه‌گیری سرکوب رشد تومور و افزایش بقا بود. مطالعات توزیع زیستی (Biodistribution) با نشان‌گذاری رادیویی HSA-LAP با تکنسیوم-99 (99mTc) قابلیت تجمع HAS-LAP در تومور را آشکار ساخت. نتایج: فرآیند کپسوله‌سازی با حفظ یکپارچگی ساختاری HSA و تغییرات جزئی همراه بود. آزمون‌های کشت سلولی نشان داد که HSA-LAP اثرات ضد تکثیر و پرو-آپوپتوزی بیشتری روی سلول‌های TNBC نسبت به لاپاتینیب آزاد دارد، با کاهش قابل توجه مقادیرIC50 (05/1) میکروگرم/میلی‌لیتر برای HSA-LAP در مقابل 5.47 میکروگرم/میلی‌لیتر برای (LAP). علاوه بر این، ترکیب با VGB3، یک پپتید متصل شونده به گیرنده های VEGFR1 و VEGFR2، موجب تقویت این اثرات و کاهش چشمگیر IC50 به 0.2 میکروگرم/میلی‌لیتر و افزایش قابل توجه نرخ‌های آپوپتوز به 50.2./. شد. در مدل درون‌تنی، رشد تومور با HSA-LAP به میزان 59./. و با ترکیب VGB3 به 89./. کاهش یافت. اثرات ضد توموری با افزایش نرخ بقا نسبت به گروه شاهد همراه بود. بررسی توزیع زیستی (Biodistribution) نشان دهنده تجمع ترجیحی HSA-LAP توسط بافت‌های تومور بود که نشان‌دهنده قابلیت‌های بهبود یافته هدف‌گیری و ماندگاری است. نتیجه‌گیری: این یافته‌ها پتانسیل HSA را به‌عنوان یک سیستم موثر در تحویل لاپاتینیب تأیید می‌کنند و به‌طور قابل‌توجهی قدرت ضدسرطانی آن را علیه TNBC افزایش می‌دهند. این تحقیق به مزایای استفاده از HSA در فرمولاسیون دارو اشاره دارد و پروفایل‌های تحویلی بهینه‌ای ارائه می‌کند که سمیت سیستمیک را کاهش می‌دهد. علاوه بر این، نتایج مؤثر درمان ترکیبی با VGB3 نیازمند بررسی و توسعه بیشتر است که می‌تواند رویکردی تحول‌آفرین در درمان زیرگروه‌های تهاجمی سرطان سینه ارائه دهد.

لاپاتینیب، آلبومین سرم انسانی، سرطان سینه سه‌گانه منفی، سیستم‌های تحویل دارو، درمان ترکیبی

مژگان رزاقی, Mozhgan Razzaghi, Ahmad Homaei, Roohullah Hemmati, Dariush Saberi, Soudabeh Kavousipour

Stabilization of Recombinant α-Amylase Using a Cellulose/Gold Hybrid Nanosupport

α-Amylase is one of the most widely used commercial enzymes across various industries. The demand for industrial enzymes is expected to continue growing due to the increasing global population, the depletion of natural resources, and the urgent need for environmentally sustainable alternatives in industrial processes. In this study, the gene encoding α-amylase from Bacillus aquimaris MKSC 6.2 (BaqA) was subcloned into the expression vector pET28a(+) and successfully expressed in E. coli BL21 (DE3). The synthesis of cellulose nanocrystals/gold nanoparticles (CNC/AuNPs) hybrid was accomplished using a hydrothermal treatment without toxic chemicals. Recombinant BaqA was covalently attached to a cysteine-modified nanosupport through a Schiff base reaction using glutaraldehyde linkages. The successful synthesis of the designed nanohybrid and the enzyme stabilization process were confirmed by FT-IR, DLS, intrinsic fluorescence, UV-Vis spectroscopy, FESEM, and EDX techniques. The enzyme in its free form exhibited maximum activity at pH 10 and a temperature of 70 °C. The optimal temperature for the immobilized enzyme increased to 80 °C, while the optimal pH remained unchanged. This catalytic platform significantly enhanced chemical and thermal stability, as well as enzyme stability under critical pH conditions. After a four-week storage period, the immobilized α-amylase retained 67.5./. of its initial activity, whereas the free α-amylase only maintained 17./. of its initial activity. The immobilized α-amylase demonstrated a catalytic efficiency of 0.488 mM⁻¹ s⁻¹, which is more than double that of the free form, which had a catalytic efficiency of 0.254 mM⁻¹ s⁻¹. Following eleven consecutive uses, the immobilized enzyme retained 75./. of its initial activity. Based on the obtained results, the produced nanoenzyme could serve as a suitable candidate for industrial applications under harsh and critical conditions.

α-Amylase, Recombinant, Hybrid nanoparticles, Stability, Immobilization, Reusability

مژگان رزاقی, Mozhgan Razzaghi, Ahmad Homaei, Elaheh Mosaddegh

Biochemical pathways in Penaeus vannamei protease stabilization via ZnS nanoparticle mediation

Zinc sulfide (ZnS) nanoparticles have gained extensive attention in biomedical and biotechnological research due to their biocompatibility and non-toxic properties, positioning them as ideal platforms for various therapeutic and industrial applications. This study investigates the potential of ZnS nanoparticles synthesized via chemical precipitation as a support for immobilizing protease enzyme derived from Penaeus vannamei shrimp. Immobilizing enzymes on nanoparticle surfaces often leads to improved stability and performance, addressing common challenges in enzyme applications, such as decreased catalytic efficiency over time. Advanced characterization techniques, including Fourier-transform infrared (FT-IR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM), were employed to comprehensively assess the ZnS nanoparticles before and after enzyme immobilization. These methods provided insights into particle size, surface structure, and morphological changes post-immobilization, which are essential for optimizing immobilized enzyme functionality. Results demonstrated a significant enhancement in the thermal and long-term stability of the immobilized protease enzyme compared to its free form. Additionally, immobilization improved the enzyme`s resistance to extreme pH levels, advantageous for industrial applications. Notably, the immobilized enzyme exhibited an increase in optimal operating temperature, while kinetic parameters remained largely unaffected, indicating minimal loss in catalytic efficiency. These findings suggest that ZnS nanoparticle-supported enzymes have promising potential for diverse industrial applications, offering enhanced enzyme stability and resilience under challenging operational conditions.

ZnS nanoparticles, Protease enzyme, Iimmobilization, Stability, Catalytic efficiency

ملیحه آزادپرور, ملیحه آزادپرور, حسین اصغر رهنمای علی آباد, میترا خیرآبادی

بررسی خواص اپتو الکترونی و زیستی ترکیب هیپوکسیلونول با استفاده از نظریه تابعی چگالی و داکینگ مولکولی

این مقاله به بررسی خواص اپتو الکترونی و زیستی هیپوکسیلونول-اف می پردازد. اهمیت این دارو به دلیل فعالیتهای بیولوژیکی بالقوه ای است که شامل خواص ضد ویروسی، ضد باکتریایی و ضد سرطانی می شود. محاسبات الکترونی و اپتیکی با استفاده از نظریه تابعی چگالی و روش پتانسیل کامل امواج تخت تقویت شده خطی انجام شده است.همچنین، داکینگ مولکولی برای بررسی اثر مهارکنندگی این ترکیب بر روی پروتئازهای HIV و HTLV انجام شده است. محاسبات الکترونی نشان می دهد که هیپوکسیلون- اف یک عایق با گاف نواری غیر مستقیم حدود 2.03 الکترون ولت هست که میزان پایداری ترکیب را نشان می دهد. اوربیتالهای p اتم کربن نقش فعالی در سطح فرمی دارند و در برقراری پیوند با سایر ترکیبات مشارکت دارند. این ترکیب جذب بالایی در ناحیه فوق فرابنفش دارد. همچنین نشان داده می شود پیوند بین لیگاند هیپوکسینولول-اف با پروتئاز HTLV در انرژی پایین تری رخ می دهد. انرژی پیوند حاصل از محاسبات داکینگ با نمودار چگالی حالت نظریه تابعی چگالی همخوانی دارد.

HIV ، HTLV ، هیپوکسیلونول-اف، نظریه تابعی چگالی، داکینگ مولکولی، خواص الکترونی و اپتیکی

زهرا حق پرس, زهرا حق پرس, پیام ارغوانی, علی اکبر موسوی موحدی

Microfluidic chips efficacy to induce BSA aggregation at room and physiological temperature

Microfluidic chips are valuable tools for studying protein aggregation, allowing investigation into the effects of various variables on protein aggregation, including chemical and physical factors. This study examined bovine serum albumin (BSA) aggregation in both a conventional vial system and a microfluidic chip. While BSA aggregation in vials has been well-characterized, our focus was on exploring temperature-dependent aggregation within the microfluidic environment. By employing biophysical techniques, we demonstrated the formation of amyloid-like BSA aggregates at physiological pH across a range of temperatures: 70°C (above the melting point, Tm = 65°C), 37°C, and 25°C. Notably, unlike the vial system where aggregation was primarily observed at elevated temperatures, the microfluidic chip facilitated aggregation even at room and physiological temperatures, with more pronounced aggregation at 37°C. This work provides valuable insights into the mechanisms underlying protein aggregation and highlights the potential of microfluidic technologies for studying complex biological processes.

Amyloid-like structures, microfluidic chip, physiological temperature, BSA aggregation

احمد امیری

Pioneering Application of Click Chemistry for Protein Modification in Iran: HSA -Biopolymer Scaffold Fabrication via Bioorthogonal Reaction

This research demonstrates the potential of click chemistry for protein modification and the development of a new protein-based material. For the first time in IRAN, we utilized a copper-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction to fabricate a new protein-biopolymer scaffold based on a covalent bioconjugation strategy. Combining protein engineering, click chemistry and polymer science, we designed to manufacture a new protein-biopolymer scaffold that holds promise in various applications, including biotechnology and medicine. This research opens up new avenues for exploring click-mediated proteins with promising applications.

Human serum Albumin (HSA), Biopolymer, Click Chemistry, copper-catalyzed azide-alkyne cycloaddition (CuAAC)

احمد امیری, احمد امیری, صدیقه عابدان زاده, علی اکبر موسوی موحدی

Pioneering Application of Click Chemistry for Protein Modification in Iran: HSA -Biopolymer Scaffold Fabrication via Bioorthogonal Reaction

This research demonstrates the potential of click chemistry for protein modification and the development of a new protein-based material. For the first time in IRAN, we utilized a copper-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction to fabricate a new protein-biopolymer scaffold based on a covalent bioconjugation strategy. Combining protein engineering, click chemistry and polymer science, we designed to manufacture a new protein-biopolymer scaffold that holds promise in various applications, including biotechnology and medicine. This research opens up new avenues for exploring click-mediated proteins with promising applications.

Human serum Albumin (HSA), Biopolymer, Click Chemistry, copper-catalyzed azide-alkyne cycloaddition (CuAAC)

زهرا گیلان‌دخت, کیانا قلیزاد منوری, حمیدرضا ملاصالحی, زهرا گیلان‌دخت

Targeted Colorimetric Assay for Rapid Detection of Moraxella catarrhalis through Spectroscopic Analysis

Moraxella catarrhalis (M. catarrhalis) is a β-lactam resistant respiratory pathogen posing diagnostic challenges and lacks an available vaccine. This study introduces a rapid molecular and colorimetric assay, which is essential for timely diagnosis and improved infection management. The ompCD gene, encoding an outer membrane protein, was targeted as a nucleobiomarker in M. catarrhalis and compared with 9 other Gram-positive and Gram-negative bacteria. M. catarrhalis and the other strains were cultured in BHI and TSB media at 36°C, respectively. Following incubation, DNA was extracted using the boiling method and PCR-amplified with specific primers. The amplicons were confirmed by gel electrophoresis and assessed using a colorimetric method through spectrophotometry with the Neutral Red indicator. The sensitivity of the method was evaluated using a decimal serial dilution of the extracted M. catarrhalis DNA. M. catarrhalis was harvested at the stationary phase after 48 h, while the other strains were harvested after overnight incubation. Gel electrophoresis of the PCR amplicons revealed a distinct band in the range of 200-300 bp specific to M. catarrhalis, which was not observed in the other strains. In the colorimetric assay, M. catarrhalis exhibited a distinct orange-red color, contrasting with the deep red observed in the other strains. Optical density (OD) was measured at the range of 400-700 nm. Spectroscopic analysis revealed distinct peaks at 450 nm and 570 nm for M. catarrhalis, showing higher absorbance at 450 nm (0.358) and lower absorbance at 570 nm (0.249). In contrast, the other strains exhibited the opposite pattern, with lower absorbance at 450 nm and higher absorbance at 570 nm. The specificity for the tested bacteria was 100 percent. The sensitivity of the method was measured as 0.05 ng/μL. In conclusion, the colorimetric assay for M. catarrhalis detection is more effective than conventional methods, enabling the possibility of faster therapeutic prescriptions.

Moraxella catarrhalis, Respiratory Pathogen, ompCD gene, Colorimetry Detection

محمد حسین حقیر ابراهیم آبادی, محمد حسین حقیر ابراهیم آبادی, یحیی سفید بخت

Identification of Potential COVID-19 Mpro Inhibitors through Covalent Drug Docking, Molecular Dynamics Simulation, and MMGBSA Calculation

The viral main protease (Mpro) is a key drug target due to its integral role in the life cycle of SARS-CoV-2. Given the urgent need for effective therapeutics against COVID-19, extensive research has focused on the development of inhibitors targeting this enzyme. This study focuses on the exploration of covalent docking for Mpro inhibition. Using computational methods, the interactions between potential inhibitors and SARS-CoV-2 Mpro are investigated. Using protein structures (7JKV and 7TDU), fragment-based ligand selection and covalent docking via SeeSAR were performed. Pharmacokinetic properties, toxicity assessments using SwissADME and molecular dynamics simulations were performed using GROMACS. Molecular dynamics simulations were performed and parameters such as RMSD, RMSF, and MM/GBSA were analyzed for two specific ligands. These inhibitors exhibit pharmacological properties that may affect drug interactions and metabolism in vivo. In addition, the toxicity profiles of covalent ligands highlight complex interactions across physiological systems and underscore the need for comprehensive safety evaluations prior to therapeutic considerations.

COVID-19, Main Protease (Mpro), Computational Drug Design, Covalent Drug Design.

زهرا شیبه, sadighe jafarypour, پریسا ابراهیمی, علی اکبر صبوری

The study of salt concentration effect on α-synuclein fibril structure in the presence of an electric field

Aggregation of the intrinsically disordered protein α-synuclein is the primary cause of Parkinson`s disease and related neurodegenerative disorders. Multiple studies have shown that electric fields at various voltages have significant effects on the secondary structure of proteins. Moreover, the influence of salt concentration is crucial in the aggregation process of α-synuclein. In this study, we conducted two all-atom molecular dynamics simulations for 60 nanoseconds on α-synuclein fibrils to elucidate the structural features of protein fibrils under the influence of an electric field (0.4 V/nm) and a low salt concentration (50 mM). We prepared two systems under the effect of an electric field and introduced salt concentration to one of them. This comprehensive approach provided valuable insights into the role of salt concentration and electric fields in shaping the structure of α-synuclein fibrils. The results indicate that the number of hydrogen bonds decreases under the influence of an electric field, suggesting instability of the beta structures, which are crucial for fibril consistency. Additionally, the number of helices and coils increases. Nevertheless, the ratio of helix to coil under the combined effect of salt and an electric field is higher than that observed without the application of salt concentration. Overall, this study has the potential to enhance our understanding of the molecular mechanisms underlying neurodegenerative diseases and may contribute to the development of novel therapeutic strategies targeting α-synuclein fibrils.

Electric field: Salt concentration: α-Synuclein: Aggregation, Parkinson’s disease

مونا نورآذران, مونا نورآذران, رضا یوسفی, فائزه موسوی موحدی, علی اکبر موسوی موحدی

Conformational changes of αB-crystallin upon the effect of its glycation by methylglyoxal

αB-crystallin is one of the main types of soluble proteins in the eye lens, which in addition to its structural role also has chaperone activity. Due to its long lifetime, this protein is susceptible to many post-translational modifications. Among the types of post-translational modifications, non-enzymatic glycation of αB-crystallin is particularly important because it is involved in age-related and diabetic cataracts. The concentration of methylglyoxal in human blood plasma is approximately 80 nM, while its concentration in the lens is reported to be close to 2 μM. In addition, its concentration increases several-fold in hyperglycemia caused by diabetes. Methylglyoxal is converted to D-lactate in the lens by the enzyme glyoxalase 1, but the activity of this enzyme also decreases with age. This study investigated the effect of methylglyoxal on the conformation, aggregation, and stability of αB-crystallin using various techniques such as fluorescence, UV-vis, and SDS-page. The results show that glycation of αB-crystallin with methylglyoxal leads to partial unfolding of the αB-crystallin and causes cross-links between the amino acids arginine and lysine of αB-crystallin by forming AGEs. The result of these cross-links is the formation of high molecular weight protein aggregates, and as the concentration of methylglyoxal increases, higher molecular weight protein aggregates are formed. These aggregates are much more stable than native αB-crystallin due to their covalent cross-links. The increase in Tm of the protein with increasing concentration of methylglyoxal also indicates the stability of the protein aggregates. The final result of this modification can lead to αB-crystallin aggregation and opacity of the eye lens.

αB-crystallin, glycation, aggregation, methylglyoxal

فائضه ثمری, فائضه ثمری, مهدیه خیری, فاطمه صداقتی

Fluorescence investigation on the interaction of phyto-synthesized ZnO NPs with bovine serum albumin

The environmentally friendly synthesis of nanoparticles has garnered significant interest due to the increasing need for safe, cost-effective, and sustainable technologies in nanomaterial production [1]. This study presents a novel and eco-conscious method for synthesizing zinc oxide nanoparticles (ZnO NPs) utilizing Ficus religiosa leaf extract as a renewable, non-toxic, and effective stabilizer. The successful formation of the biosynthesized ZnO NPs was confirmed through UV–Vis spectroscopy, X-ray diffraction (XRD), and field emission scanning electron microscopy (FE-SEM). Furthermore, a fluorescence-based technique was developed for the rapid and straightforward assessment of the interaction between the phyto-synthesized ZnO NPs and bovine serum albumin (BSA), a crucial carrier protein, under simulated physiological conditions at pH 7.4. This method is characterized by its ease of use, reliability, and practicality [2]. The experimental findings demonstrated that the intrinsic fluorescence of BSA could be quenched by the phyto-synthesized ZnO NPs. The Stern-Volmer plot exhibited a nonlinear trend with an initial upward curvature, likely resulting from a combination of static and dynamic quenching mechanisms [3]. The quenching constants and binding parameters, including binding constants and the number of binding sites, were determined using the fluorescence quenching data. Additionally, synchronous fluorescence spectroscopy indicated slight alterations in the local polarity surrounding the tryptophan and tyrosine residues during their interaction with the ZnO NPs [4]. The biological implications of this research are significant, as albumin functions as a carrier for various ligands. Consequently, this study could offer a new approach to investigate the biological toxicity of green synthesized ZnO NPs at the protein level.

Green synthesis, ZnO nanoparticles, Bovine serum albumin, Fluorescence spectroscopy.

وحیده عبدی, وحیده عبدی, زهرا قاسمی, ایمان سوری نژاد

رهایش داروی کوئرستین با استفاده از نانوکپسول های کیتوزان-آلژینات

کوئرستین یک فلاونوئید است که به وفور در گیاهان خوراکی، میوه ها و سبزیجات وجود دارد و به دلیل خاصیت آنتی اکسیدانی خود بسیار مورد توجه قرار گرفته است. کوئرستین علیرغم طیف وسیعی از خواص دارویی، به دلیل حلالیت آبی کم، فراهمی زیستی پایین و بی ثباتی در محیط فیزیولوژیکی، در کاربردهای بالینی با مشکلاتی مواجه است. یک رویکرد برای غلبه بر این مشکلات، کپسوله کردن کوئرستین در حامل های تشکیل شده از پلی ساکاریدهای طبیعی است. پلی ساکاریدها پلیمرهای زیستی هستند که به طور گسترده برای اهداف زیست پزشکی و دارویی استفاده می شوند. در میان این گونه پلی ساکاریدها، کیتوزان و آلژینات به طور گسترده به عنوان حامل ذرات برای کپسوله سازی و رها سازی کنترل شده ترکیبات زیست فعال مورد استفاده قرار می گیرند. پلی ساکاریدهای آلژینات و کیتوزان به دلیل خواص زیست تخریب پذیر، زیست سازگار، غیر سمی و چسبندگی زیستی به طور گسترده در سیستم های دارورسانی مورد استفاده قرار می گیرند. نانوکپسول های آلژینات- کیتوزان از داروی کپسوله شده، در برابر تخریب آنزیمی محافظت می کنند، دارو را به اندام هدف می رسانند و اجازه آزادسازی کنترل شده دارو را می دهند. مطالعات گسترده ای در مورد سیستم دارو رسانی تا به امروز انجام شده است. در میان آنها، ساخت سیستم های دارو رسانی با اندازه نانو و استفاده از آنها برای تحویل موثر و کنترل شده دارو یک زمینه تحقیقاتی نوظهور و امیدوار کننده است. با توجه به یافته های این پژوهش، نانوکپسول های ساخته شده می-تواند به عنوان گزینه مناسبی جهت تحویل هوشمند دارو در نظر گرفته شود.

کوئرستین، کیتوزان - آلژینات، نانو کپسول، رهایش دارو

زهره غیاثی, داوود عاجلو

Potential of Neratinib and Other Compounds as Tyrosine Kinase Inhibitors in Cancer Treatment: Virtual Screening and Molecular Dynamics Analysis

Cancer is a life-threatening ailment characterized by the uncontrolled proliferation of cells. Because cancer is not just a single disease, it is unlikely that there will ever be a single cure for it. At present, no proper therapy is available for the disease, and it is increasing day by day with a high mortality rate. Therefore, the need for drugs to combat this disease has increased. Worldwide collaborative efforts from scientists are underway to determine cancer and reduce mortality rates. Tyrosine kinase inhibitors (TKIs) are widely used in tumor treatment. The screened compounds were followed for SP docking, Extra precision (XP) docking, MM-GBSA analysis, induced-fit (IFD) docking, and MD simulation The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of all compounds were analyzed and a final selection was made based on the Lipinski rule of five. Then, ADME/T profiles were determined to validate the pharmacokinetics and pharmacodynamics properties of the hit compounds. the promising ADME properties of the selected compounds emphasize their potential as attractive candidates for cancer treatments. The ligand neratinib revealed the highest docking score of -12.154 kcal/mol. To further validate the interactions of top-scored receptors and ligands, a molecular dynamics study of 4 ns was carried out. This indicated that the protein-ligand complex was stable throughout the simulation period, and minimal backbone fluctuations ensued in the system. Post-MM-GBSA analysis of molecular dynamics data showed a free binding energy of -68.391 kcal/mol. This molecule may emerge as a promising ligand against cancer and thus needs further detailed investigations. These virtual investigations revealed four compounds having binding free energies of − 68.391, − 68.314, − 54.021, and − 51.873 kcal/mol respectively as calculated by the MM-GBSA method. The MD simulation studies confirmed the stability of protein-ligand complexes.

ADMET, MM-GBSA, molecular dynamics, Molecular docking

مهرناز شیخ حسینی, سیده زهرا موسوی نژاد

مطالعه ویژگیهای بیوشیمیایی آلبومین سرم گاوی با استفاده از ابزارهای بیوانفورماتیک

آلبومین یک ماکرومولکول حامل است که می‌تواند از منابع مختلفی از جمله سفیده تخم مرغ، آلبومین سرم گاوی و آلبومین سرم انسانی بدست آورده شود. آلبومین سرم گاوی با وزن مولکولی تقریباً 8/66 کیلو دالتون و ساختار قلبی شکل است که دارای خواص اتصال منحصر به فردی هستند. علاوه بر این، وجود چندین مکان اتصال در ساختار آن، این پروتئین را به عنوان ماکرومولکول‌ زیستی اصلی حامل، عامل توزیع و تحویل مواد مختلف، یون‌ها، اسیدهای چرب و مولکول‌های کوچک مانند داروها، معرفی می کنند. در این مطالعه به بررسی ویژگی های ساختاری پروتئین آلبومین سرم گاوی و همچنین بررسی پتانسیل برقراری میانکنش آلبومین سرم گاوی از طریق میانکنش های دی سولفیدی و هیدروفوب با استفاده از ابزارهای بیوانفورماتیک از جمله PYMOL ، spdbviewer و molegro virtual docker پرداخته شد. نتایج نشان داد آلبومین سرم گاوی، واجد 583 آمینواسید، دو زنجیره با نام‌های زنجیره A و زنجیره B، و سه دمین (I, II, III) می‌باشد. این پروتئین توانایی برقراری پیوند دی سولفیدی از طریق 17 پیوند دی سولفیدی درون مولکولی و یک آمینواسید سیستئین آزاد در جایگاه 34 را دارا می‌باشد. همچنین به دلیل دارا بودن آمینواسیدهای هیدروفوب خصوصا در فضای داخلی پروتئین، امکان برقراری میانکنش هیدروفوب با لیگاندهایی که توانایی برقراری این میانکنش در ساختار مولکولی آن‌ها وجود داشته باشد، امکان پذیر است. بنابراین با مطالعه بیوانفورماتیکی بر روی آلبومین سرم گاوی و تایید توانایی برقراری میانکنش دی سولفیدی و هیدروفوب با لیگاندهای واجد شرایط، می توان از این پروتئین برای مطالعات آزمایشگاهی از جمله اتصال این پروتئین با لیگاندهای دارویی و افزایش اثربخشی و در دسترس قرارگرفتن آن‌ها استفاده کرد.

آلبومین سرم گاوی، بیوانفورماتیک، دی سولفید، لیگاند، میانکنش، هیدروفوب.

ناهید زمانی مقدم, امیرحسین لطیفی, الناز حسینی, پیام ارغوانی, احمد امیری, علی‌اکبر موسوی موحدی, علی‌اکبر صبوری

Optimization of Quercetin Concentration for Studying Liquid-Liquid Phase Separation

Liquid-liquid phase separation (LLPS) of proteins is crucial for understanding the mechanisms of protein aggregation. LLPS acts as an initial stage in protein aggregation, enabling proteins to transition from a uniform solution to distinct phases or concentrated droplets. This study examines the effects of varying concentrations of quercetin on the structural properties of bovine serum albumin (BSA) and aims to identify optimal conditions for studying LLPS. To determine suitable quercetin concentrations for analyzing BSA`s structural integrity and interactions, we utilized fluorescence spectroscopy and circular dichroism (CD) spectroscopy. Changes in the protein`s secondary structure were evaluated using CD in the far-UV range, while alternations in its tertiary structure were examined through the intrinsic fluorescence of tryptophan and ANS (8-anilino-1-naphthalenesulfonic acid). Our findings reveal that quercetin concentrations of 4.5 μM and 45 μM have minimal affect on the tertiary structure of the BSA monomer, establishing these concentrations optimal for LLPS studies. Additionally, the role of these concentrations can be explored in the context of protein droplet formation during phase separation and the resulting aggregates.

Liquid-liquid phase separation, Liquid droplet, Quercetin, BSA

سید پیمان شریعت پناهی, سید پیمان شریعت پناهی, بهرام گلیایی, علی سامع, شهرزاد هادی چگینی

به سوی کنترل نوسانات کلسیم، به عنوان ساعت سلولی، به وسیله میدان‌های مغناطیسی

نوسانات کلسیم در سلولها به طور مشابه با سیگنالهای ساعت در ریزپردازنده ها عمل می‌کنند و فعالیتهای سلولی را از طریق فرکانس خود تنظیم می‌نمایند. این نوسانات که توسط مسیرهای سیگنال‌دهی، به‌ویژه در فضای بین میتوکندری و شبکه آندوپلاسمی کنترل می‌شوند، زمان‌بندی بیان ژن و سایر فرآیندهای سلولی را تعیین می‌کنند. نوسانات کلسیم با فرکانس بالا، عملکردهای سلولی را تسریع می‌کنند و بیان ژن و فعالیت‌های متابولیکی سریع را به همراه دارند. برعکس، در سلول‌های پیر، فرکانس نوسانات کلسیم کاهش می‌یابد که منجر به کاهش سرعت فرآیندهای سلولی می‌شود، مشابه کاهش سرعت ساعت در ریزپردازنده‌ها. این کاهش در فرکانس نوسانات به‌طور مؤثر &amp:quot:زمان&amp:quot: سلولی را کند می‌کند و بر کارایی و عملکرد کلی سلول تأثیر می‌گذارد. درک دینامیک نوسانات کلسیم و فرکانس آنها، بینش‌هایی در مورد پیری سلولی و اهداف درمانی بالقوه برای اختلالات سلولی مرتبط با پیری مانند دیابت ارائه میدهد. این دانش می‌تواند به توسعه استراتژی‌هایی برای حفظ عملکرد سلولی و کاهش اثرات پیری بر فرآیندهای سلولی کمک کند. نوسانات کلسیم درون سلول نتیجه یک مکانیزم بازخورد مثبت در کانال‌های IP3 روی شبکه آندوپلاسمی هستند. این کانالها عمدتاً توسط گونه‌های واکنش‌پذیر اکسیژن (ROS) که عمدتاً در میتوکندری تولید می‌شوند، کنترل می‌گردند. علاوه بر این، فرکانس نوسانات کلسیم می‌تواند توسط میدان‌های مغناطیسی خارجی که به‌طور مستقیم بر تولید ROS در میتوکندری تأثیر می‌گذارند، تنظیم شود. مطالعات ما نشان داده‌اند که میدان‌های الکترومغناطیسی می‌توانند سطوح ROS را تحت تأثیر قرار دهند و در نتیجه مسیرهای سیگنال‌دهی کلسیم را تغییر دهند. این تنظیم، راه‌های درمانی بالقوه‌ای برای کنترل فرآیندهای سلولی و رسیدگی به بیماری‌های مرتبط با اختلال در سیگنال‌دهی کلسیم ارائه می‌دهد. در چند سال گذشته، ما تحقیقات همگرایی در مورد دینامیک نوسانات کلسیم و اثرات ROS و میدان‌های مغناطیسی بر این پدیده انجام داده‌ایم. نتایج نشان‌دهنده قابلیت امیدوارکننده‌ای برای کنترل نوسانات کلسیم به عنوان ساعت سلولی هستند.

نوسانات کلسیم. میدان‌های مغناطیسی. میتوکندری. زیست شناسی کوانتومی. ساعت سلولی

Majid Majid, Majid Mahdavi

Multispectral, molecular docking and molecular dynamic simulation studies of DNA binding of a β-ionone-derived ester

β-Ionone is the end-ring counterpart of β-carotenoids, which are widely found in fruits and vegetables. In this research, interaction between DNA and a β-Ionone-derived ester, (E)-4-(2,6,6-trimethylcyclohex-1-enyl) but-3-en-2-ylpyrazine-2-carboxylate (4-TM. P), have been elucidated by various methods, such as ultraviolet-visible spectroscopy, fluorescence assays, viscosity measurements, molecular docking, and dynamic simulation. Analyses of multi-spectroscopy and viscosity assays strongly implies the groove binding of 4-TM. P to Ct-DNA. The fluorescence emission spectra of 4-TM. P values for the different Ct-DNA concentrations at 298 K showed an interaction between 4-TM. P and Ct-DNA, leading to quenching of the intrinsic fluorescence of 4-TM. P. Moreover, a fluorescence enhancement indicated a static process characterized by complex formation between 4-TM. P and Ct-DNA. The viscosity measurements demonstrated the binding mechanism between 4-TM. P and Ct-DNA because it offers unequivocal evidence of their interaction. Molecular docking simulation using AutoDock4.2 revealed that 4-TM. P was placed at the minor groove of the B-DNA, confirming the above experimental results. The dynamic stability of the complex was also confirmed using molecular dynamic simulation analyses.

β-Ionone, DNA interaction, Docking, Dynamic simulation.

آفاق محمدی گزافرودی, حمیدرضا ملاصالحی

روش های مبتنی بر هیبریداسیون و تقویت جهت شناسایی microRNAs

شناسایی MicroRNAها (miRs,miRNAs)به عنوان مولکول های کلیدی در تنظیم بیان ژن و فرآیندهای بیولوژیکی،اهمیت بسیاری در تحقیقات زیست پزشکی و تشخیص بیماری ها دارد. روش های مختلفی برای شناسایی miRNA توسعه یافته اند که هر یک مزایا و معایب مختص به خود را دارند. در این مقاله مروری به بررسی روش های مبتنی بر هیبریداسیون شامل northing blottingوmicroarray و تکنیک های بر پایه تقویت شامل RCA, SDA, HCR, LAMP, EXPAR, DSN, CHAو RT_qPCR ،میپردازیم. این مقاله هم چنین به مقایسه روش ها با بررسی مزایا و معایب آنها میپردازد و چالش ها و فرصت های تحقیقات آینده را مورد بحث قرار میدهد. نتایج این مطالعه نشان میدهد که ترکیب روش های هیبریداسیون و تقویت میتواند به بهبود دقت و حساسیت شناسایی miRNA کمک کند و زمینه ساز توسعه تکنیک های نوین در این حوزه باشد.

miRNA، هیبریداسیون،تقویت سیگنال، شناسایی miRNA، تکنیک های مولکولی

مرگان حق شناس, مریم توحیدی, بنفشه رستگاری

Synthesis of nanoporous metal-organic framework based on tartrate as a new carrier for the delivery of Palbociclib drug

The synthesis of biocompatible nanoporous metal-organic framework (MOF) based on tartrate was performed in the presence of protein and palbociclib (Pal) as a template for the biomineralization process and, an anticancer drug, respectively. The synthesis of MOF was completed in a single step at room temperature in aqueous media. To the best of our knowledge, this is the first report about the one-pot encapsulation of Pal in a biocompatible framework in a green solvent. This method enables high Pal loading in the framework structure (ca. 86./.) at a short time of 15 min. The effect of protein concentration was investigated on the size, morphology, and crystallinity of the synthesized structures. The products were characterized with scanning electron microscopy, X-ray diffraction, Fourier transform infrared, and UV-vis spectroscopy techniques. The release rate of Pal from MOF was studied at different pH values. In vitro drug release of Pal was slower in alkaline medium (pH 7.4) compared to acidic medium (pH 5.5). The cytotoxicity of different structures was evaluated by the standard 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on the two cell lines (NIH/3T3 (normal cell), and B16 (cancer cell)). These results suggested that the designed drug loaded MOF can have a promising effect on the treatment of cancer cells.

Bio Metal-Organic Framework (MOF), Drug delivery, Palbociclib

ساجده حبیبی, Sajedeh Habibi, Zohreh Zahraei

Alpha Amylase inhibitory plants

Alpha-amylase is a low molecular weight endohydrolase enzyme that catalyzes the hydrolysis of starch and, ultimately, the production of glucose. This enzyme is considered one of key enzymes and its inhibition can play a significant role in the treatment of diabetes. By controlling the catalytic activity of this enzyme, we can expect a reduction in glucose production in the post-meal phase, which can be a therapeutic advantage for people with diabetes. Today, the importance of using natural sources as inhibitors of alpha-amylase enzyme compared to chemical inhibitors has been much considered due to fewer side effects. Plant`s inhibitory effects on this enzyme can be attributed to their secondary metabolites, such as phenolics, terpenoids, flavonoids and coumarin phytochemicals. Some plant extracts, especially extracts rich in proanthocyanidin, can inhibit enzymes such as alpha-amylase, which can help control and treat diabetes.

Alpha_amylase, Inhibition, Herbal extract, Diabetes

سماء دیده ور تبریزی, ناصر پولادی

بررسی تغییرالگوی اتصال فاکتورهای مختلف رونویسی و پیرایشی با تغییر آللی پلیمورفیسم های ژن Fas

بسیاری از SNP های غیر کد کننده در مناطق نظارتی مانند مناطق پروموتر قرار دارند و از این رو می توانند با تغییر میل اتصال پروتئین های تنظیمی، بر بیان ژن تأثیر بگذارند. FAS یک گیرنده سطح سلولی است که در اثر میان‌کنش با لیگاند خود (FASL) آبشار سیگنال مرگ سلولی را راه‌اندازی می&#172:کند و اختلال در آن موجب القای تومورزایی می‌شود. هدف این مطالعه بررسی تغییرالگوی اتصال فاکتورهای مختلف رونویسی و پیرایشی با تغییر آللی پلیمورفیسم های ژن Fas با روش In silico می باشد. مواد و روش ها: برای این تحلیل از نرم افزارهای آنلاین مانند AliBAba،2 Spliceaid و Haploreg استفاده شد. پلی مورفیسم های پروموتری rs2234767 و rs1800682 ژن Fas استفاده گردید. نتایج: نتیجه به‌دست آمده نشان می دهند که بر اثر تغییر نوکلئوتید Aبه G در چندشکلی -670 A/G ژن FAS پروتئین های CFOS,GATA2, CEBPB, TBP, POL2, STAT3 قابلیت اتصال پیدا می کنند. بر اثر تغییر نوکلئوتید Gبه A در چندشکلی1377G/A ژن FAS پروتئین های EBF1,OCT2,POU2F2 قابلیت اتصال پیدا می کنند. SRp55 که یکی از رایج ترین فاکتورهای پیرایش است با تغییر آللی در پلی مورفیسم rs1800682 ژن Fas قدرت اتصال پیدا می کند. بحث: تغییرات در قابلیت اتصال پروتئین‌های تنظیمی مثل فاکتورهای رونویسی و پیرایشی می‌تواند به درک بهتر مکانیسم‌های مولکولی که منجر به بیماری‌های مختلف می‌شود، کمک کند و به عنوان یک نشانه بیولوژیکی یا هدف درمانی در آینده مورد توجه قرار گیرد.

ژن FAS ، پلی مورفیسم، rs1800682، فاکتور رونویسی

یاشار نجفی, Yashar Najafi, Aysuda Mohamadzadeh, *Manijeh Sabokdast Nodehi, *Shohreh Ariaeenejad

Immobilization of alkaline protease PersiProtease1 by CLEA method

Proteases are essential enzymes extensively employed in numerous industrial processes, including food production, detergent manufacturing, pharmaceuticals, and leather processing, where they play a pivotal role in enhancing efficiency, product quality, and sustainability by facilitating the breakdown of proteins under diverse conditions. Nonetheless, the industrial use of proteases is constrained by challenges such as reduced stability under harsh conditions, high production costs, and difficulties in enzyme recovery and reuse, which hinder their long-term and cost-effective application in various sectors. Enzyme immobilization has proven to be a viable strategy to address many of these challenges. Among different immobilization techniques, the Cross-Linked Enzyme Aggregates (CLEA) method stands out for enhancing enzyme stability through cross-linking enzyme molecules with bifunctional agents, without the need for external carriers or coatings. In this study, the alkaline protease PersiProtease1 was immobilized using the CLEA method. The immobilization involved using 55./. (w/v) saturated ammonium sulfate as the precipitant and 25./. (w/v) glutaraldehyde as the cross-linker, maintaining the reaction at 25°:C for 17 hours. The immobilized enzyme exhibited a stability increase of over two-fold compared to the free enzyme, demonstrating the CLEA method`s efficacy in enhancing enzyme performance. These findings highlight promising applications in biodiesel production, wastewater treatment, textile and leather processing, detergent formulation, and pharmaceutical industries.

Cross-Linked Enzyme Aggregates, Enzyme Immobilization, Glutaraldehyde, Industrial Application, Protease

شکوه رضایی, Shokouh_rezaei, Saman Hosseinkhani, Yahya Sefidbakht

Structural Insights into kinase domain of RIP1

The receptor-interacting protein kinase 1 (RIP1) plays a crucial role in cellular signaling pathways, particularly in regulating apoptosis and necroptosis [1]. Understanding the structural dynamics of kinase domain of RIP1 is essential for elucidating its functional mechanisms and therapeutic potential [2, 3]. This study aims to compare the structural characteristics of the native RIP1 kinase domain with the S166A mutant variant, utilizing molecular dynamics simulations (Gromacs-2019.2) to analyze key biophysical properties. Results reveal significant differences in the root mean square deviation (RMSD), radius of gyration (Rg), and root mean square fluctuation (RMSF) between the native and mutant forms. The RMSD analysis indicates a more stable conformation for the native kinase domain, while the S166A mutant exhibits increased fluctuations, suggesting a potential loss of structural integrity. The S166A mutant results in decreased hydrogen bond numbers (H-bonds) and a lower Rg value, suggesting a less compact and stable conformation than the native structure. Additionally, the analysis of the solvent-accessible surface area (SASA) further corroborates these findings, indicating enhanced exposure of hydrophobic regions in the mutant. In conclusion, our findings provide valuable insights into the structural implications of the S166A mutation in the kinase domain of RIP1. These results underscore the importance of specific residues in maintaining the stability and functionality of the kinase domain, offering potential avenues for targeted therapeutic strategies in diseases associated with dysregulated RIP1 activity.

RIP1, Kinase Domain, MutantS166A, MD simulation

فاطمه حاجی پور

درمان هدفمند ماده موثر گیاهی پاپاورین در مسیر پیام رسان ERK-MAPK سلول های سرطان پستان در سطح in-silico و in-vitro

سرطان سینه بیماری مهلکی است که سالانه موجب مرگ و ناتوانی صدها زن در سراسر دنیا می شود.گیاه خشخاش حاوی آلکالوییدهای دارویی مهمی از جمله مورفین، کدیین،پاپاورین می باشد که دارای ارزش اقتصادی بالایی در صنایع داروسازی است که تاکنون استراتژی های مختلفی جهت تجاری کردن استحصال آنها به کار گرفته شده است.به منظور انجام این تحقیق 3 پروتیین MEK2, MEK1, BRAF استفاده شدند که به منظور بررسی دوز موثره ماده گیاهی مورد تحقیق بر روی رده های سلولی تست MTT انجام شد که پس از شمارش، رده های سلولی داخل پلیت 96 خانه ای کشت داده شد و بعد با محلول رنگ MTT رقیق شده،مخلوط و انکوبه شد.ریل تایم PCR روشی کاربردی برای تکثیر cDNA استخراج شده از RNA می باشدکه در این تحقیق بکار برده شد.خلوص نمونه RNA با روش جذب نوری یا اسپکنروفتومتری بررسی گردید.و منحنی ذوب و تکثیر هر ژن رسم و بررسی شد.در بررسی ترکیب پاپاورین بر روی MEK2, MEK1, BRAF از روش داکینگ استفاده شد.بعد از روش داکینگ ساختار سه بعدی کمپلکس لیگاند-رسپتور و نوع اتصال آن مورد مطالعه قرار گرفت.نمودار ها رسم و وارد محاسبات آماری بیوانفورماتیکی قرار گرفت.این تحقیق نشان داد که ماده موثره پاپاورین موجود در گیاه خشخاش می تواند در مسیر ERK-MAPK سلول های سرطان پستان نقش درمانی داشته باشد.

سرطان پستان، MEK1 ، پاپاورین، ERK-MAPK.

ملیحه آزادپرور, ملیحه آزادپرور, حسین اصغر رهنمای علی آباد, میترا خیرآبادی

بررسی خواص اپتو الکترونی و زیستی ترکیب هیپوکسیلونول با استفاده از نظریه تابعی چگالی و داکینگ مولکولی

این مقاله به بررسی خواص اپتو الکترونی و زیستی هیپوکسیلونول-اف می پردازد. اهمیت این دارو به دلیل فعالیتهای بیولوژیکی بالقوه ای است که شامل خواص ضد ویروسی، ضد باکتریایی و ضد سرطانی می شود. محاسبات الکترونی و اپتیکی با استفاده از نظریه تابعی چگالی و روش پتانسیل کامل امواج تخت تقویت شده خطی انجام شده است.همچنین، داکینگ مولکولی برای بررسی اثر مهارکنندگی این ترکیب بر روی پروتئازهای HIV و HTLV انجام شده است. محاسبات الکترونی نشان می دهد که هیپوکسیلون- اف یک عایق با گاف نواری غیر مستقیم حدود 2.03 الکترون ولت هست که میزان پایداری ترکیب را نشان می دهد. اوربیتالهای p اتم کربن نقش فعالی در سطح فرمی دارند و در برقراری پیوند با سایر ترکیبات مشارکت دارند. این ترکیب جذب بالایی در ناحیه فوق فرابنفش دارد. همچنین نشان داده می شود پیوند بین لیگاند هیپوکسینولول-اف با پروتئاز HTLV در انرژی پایین تری رخ می دهد. انرژی پیوند حاصل از محاسبات داکینگ با نمودار چگالی حالت نظریه تابعی چگالی همخوانی دارد.

HIV ، HTLV ، هیپوکسیلونول-اف، نظریه تابعی چگالی، داکینگ مولکولی، خواص الکترونی و اپتیکی

صدیقه عابدان زاده

Organopalladium(II) complex bearing curcumin: Synthesis, characterization and biomolecular binding studies

In the last decades, a significant amount of research has been carried out designing and discovering new metallodrugs with lower level of limitations of Cisplatin, a first metal-based antitumor agent with worldwide use in cancer treatment. To achieve a new metal complex with improved antitumor activity and decreased cytotoxicity, both the metal center and the surrounding organic ligands play key roles. In the current study, C^N-cyclometalated Pd(II) complex (C^N=2-phenylpyridine) bearing curcumin, a golden nutraceutical agent, as a bioactive ligand was synthesized and characterized using elemental analysis, FT-IR, and NMR techniques. To better understand the mechanism of action, the binding behavior of complex toward the relevant biomacromolecular targets were studied using UV-Vis and fluorescence spectroscopic techniques. Biophysical study toward DNA and protein biomacromolecules revealed high affinity of complex. The new synthesized curcumin-bearing organopalladium(II) complex indicated potential anticancer activity which can be further studied to be considered as a potent metal-based agent.

Organometallic complex: Palladium: Curcumin: Biological activity

آزاده بیگمرادی جبالبارزی, آزاده بیگمرادی, احمد همایی, روح الله همتی

جداسازی، خالص سازی و تعیین ویژگی های بیوشیمیایی آنزیم کیتیناز از میگوی Penaeus merguiensis

Penaeus merguiensis (با نام متداول میگوی موزی) یکی از مهمترین گونه های سخت پوست پرورشی در سراسر جهان برای صنعت شیلات و آبزی پروری است. آنزیم کیتیناز یک گروه از آنزیم های هیدورلیتیکی بوده که به هیدرولیز کیتین می پردازد. این آنزیم توسط طیف وسیعی از موجودات دریایی و خشکی تولید می شود و کاربرد وسیعی در صنایع گوناگون از جمله غذایی، دارویی و کشاورزی دارد. در پژوهش حاضر آنزیم کیتیناز از میگوی P. merguiensis جداسازی، تخلیص و تعیین ویژگی گردید. خصوصیات بیوشیمیایی نشان داد که کیتیناز عنوان یک آنزیم مونومر با وزن مولکولی kDa 52 با حداکثر فعالیت در ºC 40 و pH برابر 6 می باشد. علاوه بر این، آنزیم تا ºC 60 و در محدوده pH 5 تا 8 نیز پایدار بود. بررسی¬های سینتیکی برای کیتین کلوئیدیVmax ، Km و Kcat به ترتیب مقادیر µM 18/78، µM.min-1 07261/0 و s-1 37/43 را نشان داد.

داسازی، تخلیص، بیوشیمی، سینتیک، Penaeus merguiensis

محمد بهنام راد, محمد بهنام راد, هدایت الله قورچیان

CRISPR/Cas-based impedimetric biosensor for detection of SARS-CoV-2

In this study, we designed a CRISPR/Cas-based impedimetric biosensor which operates as follows: The 20-mer poly adenine probes are immobilized on the surface of a gold working electrode, and their free thiolated tails are bound with gold magnetic nanoparticles. We designed a single guide RNA (sgRNA) targeting the conserved region of ORF1ab in the SARS-CoV-2 virus. In the presence of target, the sgRNA binds to the target sequence and activates Cas12a. The collateral nuclease activity of Cas12a, once activated, cleaves the immobilized probe. Consequently, the gold magnetic nanoparticles are released and adsorbed onto the gold electrode surface using an external magnet. The absorption of nanoparticles increases the physical surface area of the gold electrode, facilitating redox ion electron transfer, and decreasing the charge transfer resistance. We utilized a low-cost polytetrafluoroethylene setup equipped with three electrodes for the impedimetric detection of target nucleic acid. The amplification-free setup demonstrates high specificity and sensitivity for detecting SARS-CoV-2 samples with a detection limit of 8.3 fM and a linear responce range for concentrations from 0.7 to 175 pM. Due to its simplicity and low reagent cost, this electrochemical biosensing platform, utilizing CRISPR/Cas and gold magnetic nanoparticles, shows great potential as a reliable biosensor for detection of nucleic acid-based targets.

Biosensor, Impedimetric detection, SARS-CoV-2, CRISPR/Cas

هدایت اله قورچیان, هدایت اله قورچیان

ژنوسنسور الکتروشیمیایی غیر تهاجمی برای تشخیص باکتری سی دیفیسیل

کلستریدیوئیدس دیفیسیل یا به اختصار سی دیفیسیل، یک باکتری بی هوازی و اسپورساز است که عمدتاً از طریق آزادسازی دو نوع سم (آ و ب) عفونت گوارشی ایجاد می کند. با توجه به اینکه در درمان عفونت¬های میکروبی، یکی از رایج¬ترین روش¬ها، تجویز آنتی¬بیوتیک است، مصرف خودسرانه، نادرست و بیش از حد آنتی-بیوتیک¬ها در بیماران رایج شده است که می¬تواند عواقب ناگواری در پی داشته باشد. یکی از اولین و جدی-ترین مشکلاتی که مصرف بی¬رویة آنتی¬بیوتیک ایجاد می¬کند، از بین بردن میکروب¬های فلور طبیعی روده است که زمینه را برای رشد و تکثیر میکروب¬های فرصت طلب مانند سی دیفیسیل که از طریق آب و غذای آلوده وارد بدن می شوند، فراهم می¬کند. بدین ترتیب در اثر رشد و کلونی¬سازی میکروب¬های بیماری¬زا در روده، عملکرد طبیعی این اندام دچار اختلال شده که یکی از اولین علایم آن اسهال می¬باشد. این عارضه را اصطلاحاً اسهال مرتبط با آنتی بیوتیک می نامند. بنا براین، اندازه گیری این باکتری در مقادیر بسیار کم می تواند به درمان به موقع بیمار کمک نماید. اخیرا در آزمایشگاه ما برای آشکار سازی این باکتری یک ژنوسنسور الکتروشیمیایی غیر تهاجمی ساخته شده است که با استفاده از ولتامتری پالس تفاضلی می تواند این باکتری را با حد تشخیص 0.2 فمتومولار، و گستره پاسخ خطی 0.5 تا 1900 فمتومولار، شناسایی نماید. در بررسی حاضر این ژنوسنسور با دیگر بیوسنسور های الکتروشیمیایی گزارش شده در منابع مقایسه شده و برتری ها و محدودیت های آن مورد ارزیابی قرار می گیرد.

کلستریدیوم دی فیسیل، ژنوسنسور الکتروشیمیایی، کاتیون هگزافروسنیوم، اکسید گرافن احیا شده، پروتئین لایه سطحی

مسعود رسولیان

The volatile constituents of rose, saffron and cardamom suppress the fibrillation of tau and not HEWL through the formation of non-toxic tau oligomers

The formation of fibrillar structures of tau is correlated with taupathies including Alzheimer’s disease (AD). This study has aimed to find ways to prevent tau fibril formation. Here, we used dietary compounds including cinnamon (CN), damask rose (Rose), saffron (Saf) and green cardamom (Car), to evaluate the effects of their volatile constituents, on hen egg white lysozyme (HEWL), as a model protein (commonly used for fibrillation studies), as well as the brain-related tau protein. The study was done using different spectroscopic techniques as well as SDSPAGE, AFM and MTT assay. While the results suggested that the volatile constituents were unable to prevent HEWL fibril formation, most of the dietary compounds, in particular Saf, Rose and Car, were able to interfere with the mature fibril formation, by either maintaining the native form of tau or resulting in the entrapment of non-toxic oligomeric forms of tau. Moreover, the neurotoxicity analysis of tau samples on neuroblastoma SHSY5Y cells indicated that tau treated with Saf, Rose and Car were the least toxic. Overall, the findings indicate that the potential therapeutic impacts of the volatile constituents of Rose, Car and in particular Saf, may demonstrate significant efficacy in addressing neurodegenerative diseases such as AD.

Natural dietary compounds, Volatile constituents, Tau protein, Fibrillation, Alzheimer’s disease, HEWL

مریم ساجدمرنی, مریم ساجدمرنی, اکرم صادقی, سهیلا طالش ساسانی, شهره آریائی نژاد

پتانسیل زیست پالایی اکتینومیست‌های جدا شده از خاک ریزوسفری بیابان لوت

زیست‌پالایی به وسیله میکروارگانیسم‌ها یک روش ایمن برای حذف آلاینده‌های صنعتی است. خاک بیابان به دلیل شرایط جوی خاص، از جمله تغییرات شدید دمایی، شوری وpH قلیایی، بستر مناسبی برای کشف باکتری‌هایی با متابولیت‌های ثانویه کاربردی، برای پاکسازی محیط زیست است؛ طبق مطالعات، آنزیم لاکاز مشتق شده از باکتری‌ها، کارایی بالایی در تجزیه ترکیبات فنلی دارد. همچنین، برخی از مکانیسم های احیا کننده و آنتی اکسیدانی قادر به تجزیه سموم شیمیایی هستند. در این مطالعه 21 نمونه خاک از پنج ناحیه دهبکری، راین، ماهان، بردسیر و سربیژن کویر لوت، از ریزوسفر دو گیاه خارشتر (Alhagi persarum) و شکر تیغال (Echinops ) جمع‌آوری شد. جدایه‌های با ظاهر پودری از نمونه‌های خاک ریزوسفری بر روی آب آگار جداسازی و پس از کشت در محیط اختصاصی ISP2 از نظر رنگ آمیزی گرم، مقاومت به شوری (NaCl 10./.)، تولید آنزیم لاکاز، آنزیم کاتالاز، خاصیت آنتی‌کسیدان و تولید سیدروفور بررسی شدند. همه 420 جدایه‌ بدست آمده از نظر ساختار دیواره گرم مثبت بودند. میسیلیوم‌های رویشی این جدایه ها رشته‌ای و طیف رنگی متنوع، از سفید تا ارغوانی داشتند. نتایج به‌دست آمده تا این زمان نشان‌ دهنده این است که 52 درصد جدایه ها تولید کننده آنزیم کاتالاز، 4 درصد مقاوم به شوری، 31 درصد تولید کننده آنزیم لاکاز و 96 درصد آن‌ها تولید کننده سیدروفور هستند. بررسی خاصیت آنتی اکسیدانی جدایه‌ها ادامه دارد. با توجه به نتایج حاصل جدایه‌های غربال شده اجزای لازم زیستی جهت فعالیت زیست‌پالایی و تجزیه سموم ارگانوفسفره که اغلب به صورت حشره‌کش شیمیایی وارد خاک های کشاورزی و موجب آلودگی محیط زیست می شوند را دارند. مطالعه تاثیر باکتری‌های منتخب بر روی کاهش غلظت باقیمانده این سموم در خاک در حال انجام است.

ریزوسفر، کویر لوت، اکتینومیست، آنزیم، زیست‌پالایی

فرزانه چاکری, Zohreh Zahraei

Protease enzyme applications and ways to improve its performance

Protease enzymes can hydrolyze peptide bonds. Proteases are widely used in commercial, medical and research processes. Proteases make up 60./. of the total market of industrial enzymes. Several proteases of animal origin, such as pepsin, trypsin and proteases of plant origin, such as papain, were discovered and characterized in the early 1800s or the early 1900s, and later microbial proteases were also considered and due to several advantages associated with them quickly became popular. Increasing protease efficiency is critical for various applications, including industrial processes, food production, and biomedicine. Recent research has focused on several strategies to optimize protease performance, including immobilization techniques, engineering methods, and cold-adapted enzymes.

Protease, Enzyme immobilization, Protease application, Cold-resistant protease

آریا تجلی, احمد امیری, سودابه شکراللهی صورتی

Theoretical and experimental study of anticancer properties of carboxamide ligand

tetrahydrobenzo[d]thiazole-2,6-diyl)dipicolinamide [H2BPT] which was inspired by biological systems synthesized using green chemistry methods in an ionic liquid solvent. The chemical structure of this compound was confirmed using techniques such as 1H-NMR, IR, UV-Vis, and X-Ray. The interaction of this compound with ct-DNA and human serum albumin (HSA) was studied through fluorescence spectroscopy, CD, and UV-Vis. The results indicated that the binding of the compound to the protein was static and led to a reduction in the alpha-helix structure in albumin. Additionally, at low concentrations, it caused DNA structural distortion, indicating therapeutic efficacy at lower doses. Molecular docking simulations and ADMET studies further confirmed and analyzed the interaction between the compound and biological macromolecules.

carboxamide, human serum albumin, DNA, molecular docking, density functional theory, ADMET

Hoda Keshmiri Neghab

Biophysics of light-sensing proteins and their applications in Optogenetics

Rhodopsins are photoreceptive proteins and key tools in optogenetics. Although rhodopsin was originally named as a red-colored pigment for vision, the modern meaning of rhodopsin encompasses photoactive proteins containing a retinal chromophore in animals and microbes. Animal and microbial rhodopsins respectively possess 11-cis and all-trans retinal, respectively. As cofactors bound with their animal and microbial rhodopsin (seven transmembrane α-helices) environments, 11-cis and all-trans retinal undergo photoisomerization into all-trans and 13-cis retinal forms as part of their functional cycle. While animal rhodopsins are G protein coupled receptors, the function of microbial rhodopsins is highly divergent. Many of the microbial rhodopsins are able to transport ions in a passive or an active manner. These light-gated channels or light-driven pumps represent the main tools for respectively effecting neural excitation and silencing in the emerging field of optogenetics. A wide variety of light-sensing proteins that are found in plants and microorganisms and that provide natural resources for engineering optogenetic tools are briefly reviewed. We include microbial rhodopsins, which absorb blue/green light: phytochromes, which absorb red/far-red light: UV-A/blue-absorbing flavoproteins (cryptochromes, LOV-domain proteins, BLUF-domain proteins): and the recently discovered UV-B sensor UVR8. Among them, the significance of channelrhodopsins, photoactivated adenylyl cyclases, biophysics of rhodopsins and their relationship to optogenetics are reviewed.

Optogenetics, Photoreceptor, Light sensing protein

نگین وجدانی رنجبر, سودابه شکراللهی صورتی, احمد امیری

Study of the interaction between a new Schiff-base ligand and human serum albumin by voltammetry and spectroscopy methods and molecular docking

Human serum albumin, the most abundant plasma carrier protein, has long been the center of attention of pharmaceutical industry due to its ability to bind a diverse range of metabolites and drugs. This astonishing binding capacity often seriously impacts pharmacokinetic properties of drugs [1]. In this work new Schiff-base ligand, 1,1`-((1E,1`E)-(naphthalene-1,5-diylbis(azanylylidene))bis(methanylylidene))bis(naphthalen-2-ol) (SNL), was synthesized and the interaction between this ligand and human serum albumin (HSA) was investigated by fluorescence and absorption spectroscopies. A marked decrease in the fluorescence intensity of this compound was observed at 475 nm upon addition of HSA when excitation wavelength was set at 370 nm in pH 7.4 Tris–HCl buffer solution. Reversely, the intrinsic fluorescence of HSA could be quenched by Schiff-base ligand. The quenching mechanism was suggested as static quenching according to the Stern–Volmer equation and the UV–vis absorption spectral change upon addition of HSA[2]. The binding constants Kb and the number of binding sites (n=1) were calculated. Molecular docking results revealed that the primary HSA-SNL binding sites are in the subdomain IA of the HSA structure.

Schiff-base, human serum albumin, anticancer potential, molecular properties, molecular docking

صدیقه سادات جعفری پور

Microfluidic Device Development to study Electric Field Effect on Planar Lipid Bilayers

Various membrane models replicate essential features of biological membranes, including elasticity and fluidity. Planar bilayers have been created using traditional methods, such as the black lipid membrane technique. Recently, micro-fabricated devices featuring horizontally oriented planar lipid bilayers have been developed with combined optical and electrical outputs. Electric fields play important roles in various biological processes, including embryonic development, wound healing, and cancer metastasis. Disruption of epithelial layers can generate lateral electric fields that promote electrotaxis, aiding in tissue repair. Strong electric pulses can induce electroporation, creating temporary membrane pores that facilitate drug delivery. In this study, we designed a microfluidic device using PDMS polymer. We optimized both the bilayer reconstitution method and the aperture design. The optimized 3D–microchip consists of a bottom channel connected to a micromachined upper cone. The capacitance of the bilayer(350 µm diameter) was found to be 500 pF by measuring the impedance. The nonlinear response of the system impedance was studied for different frequencies (100-500 kHz) of the applied voltages. Furthermore, we observed that the membrane`s lifespan with a composition of DOPC/DOPS/DOPE (60:10:30) is influenced by the frequency and intensity of the electric field. The bilayer was destroyed by increasing the applied voltage and reducing frequency.

Electric field: Microfluidic device: Planar lipid bilayers: Membrane Capacitance

زینب نظریان سامانی, زینب نظریان سامانی, سامان حسینخانی, یحیی سفیدبخت

Inhibition of ACE2 by Beta-defensin-1: A Novel Strategy Against SARS-CoV-2

Beta-defensin-1, an antimicrobial peptide, is considered to be of great importance in our innate immune response. Being a small molecular peptide, it is a wide-range antimicrobial peptide. Conversely, the angiotensin-converting enzyme 2 (ACE2) is utilized by the SARS-CoV-2 virus as the principal entrance to human cells. Due to the importance of these two molecules in COVID-19, this paper focused on the relationship between beta-defensin-1 and ACE2. This study principally aimed at investigating how beta-defensin-1 interacts with the ACE2 enzyme. We attempted to analyze how this interaction affects the function of ACE2 and how, in turn, it protects the host cells from being infected with SARS-CoV-2. For this reason, first of all, PDB structures of ACE2-RBD were retrieved using code 2AJF as well as the beta-defensin-1 structure with code 1IJV from the RCSB database. Energy interaction and molecular docking between beta-defensin and ACE2 were carried out using computational techniques. After that, the resulting interactions were analyzed with the help of molecular dynamics (MD) simulations in order to examine the stability and more details of the interaction. The results obtained demonstrate that beta-defensin-1 interacts with both active and binding sites of the ACE2 enzyme. This binding may also lead to the inhibition of enzyme function, making the targeting of host cells by the virus impossible. This inhibition takes place because of non-covalent associations like hydrogen bonds and van der Waals interactions. Beta-defensin-1 shows great potent ACE2 enzyme inhibition effects, as revealed in our study. Beta-defensin-1 might be a useful drug for treating COVID-19 by preventing the entry of the virus. These results bring new challenges to peptide-based drugs.

beta-defensin-1, ACE2, SARS-CoV-2, COVID-19, molecular dynamics, enzyme inhibition

درسا جمالی, دکتر احمد امیری

Investigating Human Serum Albumin Interaction with H2bpb: Spectroscopic Analysis and Molecular Docking Approaches

Human Serum Albumin (HSA), as one of the main plasma proteins, is crucial in transporting drugs and biomolecules throughout the body. Its interactions with pharmaceutical compounds, such as carboxamides, can significantly impact the bioavailability and efficacy of these compounds. This study investigates the interaction between HSA and a specific Carboxamide. For this purpose, N, N`-(1,2-phenylene) dipicolinamide (H2bpb), was synthesized via triphenylphosphite (TPP) and tetrabutylammonium bromide (TBAB) and characterized with Fourier-transform infrared (FT-IR) spectroscopy. Spectroscopic techniques, including absorbance titration and Circular Dichroism spectroscopy, were employed to analyze this interaction and determine the binding mechanisms. Using Molecular Docking, the binding site on HSA was identified IIA. The results reveal that the bonding between HSA and the studied Carboxamide is primarily mediated by van der Waals forces and π-π stacking interactions, which lead to slight conformational changes in the protein’s secondary structure. These findings offer valuable information for designing new drugs and optimizing existing ones, ultimately enhancing drug delivery methods mediated by HSA.

Human Serum Albumin, Carboxamides, Binding Affinity, Molecular Docking.

مسلم مومن

Predicting osteoarthritis (OA) using deep convolutional neural network (DCNN) and transcriptome profile

Osteoarthritis (OA) is a progressive joint disease characterized by cartilage degradation, bone remodeling, and inflammation, leading to pain and loss of mobility. Accurate prediction and early diagnosis of OA remain critical for effective intervention. Recent advancements in deep learning, particularly Deep Convolutional Neural Networks (DCNNs), have revolutionized the field of medical imaging by enabling precise pattern recognition in complex data such as MRI and X-ray scans. Additionally, transcriptome analysis provides valuable molecular insights into gene expression changes associated with OA progression. In this study, we attempted to predict OA by enriching DCNN-based models with transcriptome data to improve prediction accuracy and diagnosis. We hypothesized that by leveraging both DL techniques and gene expression molecular information, we could offer a comprehensive solution for identifying OA at its early stages and guiding personalized treatment strategies. Our results demonstrate that it is possible to accurately predict OA using gene expression data and deep neural networks, even with a limited sample size.

Osteoarthritis, Deep Convolutional Neural Networks, Transcriptome Analysis, Prediction Accuracy, Personalized Treatment Strategies

مسعود رحیم پور قدیم, لیلا حسنی, زینب حاتمی

The effect of Mutations caused by oxidative DNA damage on the binding of anticancer drug mitoxantrone to the G-quadruplex structure

G-quadruplexes are unique DNA structures formed by sequences rich in guanine that play a role in regulating gene expression. 8- oxo-dG is the most prevalent oxidized form of the nucleotides that causes G >: T transversion. This mutation is involved in the pathogenicity of ROS-related diseases. This research investigates the effect of guanine to thymine mutations on the interaction between the anticancer drug mitoxantrone and the four-stranded DNA structure, known as a G-quadruplex, in the promoter region of the c-Myc gene. Mitoxantrone is a topoisomerase II inhibitor that disrupts DNA replication and repair in cancer cells, thereby hindering cell proliferation. Utilizing absorption and fluorescence spectrometry along with gel electrophoresis, we investigated how G to T mutations on the tetrad planes influence on the binding of mitoxantrone to c-Myc G-quadruplex. The results of native PAGE indicated that the mutations change migration pattern and electrophoretic mobility of the G-quadruplex structure implying conformational change of the structure upon the mutatins. The percentage of hypochromicity and Stern-Volmer quenching constant of mitoxantrone changes upon the mutations. In addition, the mutations influence on the stability of the interaction in the presence of urea. In conclusion, our findings reveal that specific mutations in guanine caused by oxidative stress alter interaction between the anticancer drug and non-B DNA G-quadruplex structure. These results provide valuable insights for targeted drug design against G-quadruplexes, with implications for enhancing therapeutic approaches in the oxidative stress condition of the cancer cells.

G-quadruplexes, c-Myc, Mitoxantrone, Absorption spectroscopy, Fluorescence spectroscopy, Gel electrophoresis

ملیکا نیک سرشت, احمد امیری

Exploring the synthesis, characterization and Anti-cancer properties of a Mononuclear Co(III) Schiff Base complex with HAS interaction

Schiff bases are promising biologically intriguing substances that have a variety of medicinal applications, such as antibacterial, anti-inflammatory, and antipyretic effects. FT-IR, UV-Vis, and elemental analysis are among the spectroscopic methods which are used in this study to synthesize and analyze the [Co(III)(H2L) (1-MeIm)2]Clo4 Schiff base complex. One of our Schiff-bases molecules was found to attach to human serum albumin (HSA) via fluorescence quenching experiments. The binding affinity of the matching complex to HSA has been examined using fluorescence titration studies. It was determined that the computed Kq values were 8.2×1011. Worth noting that these compounds` Kq values are higher than 2.0×1010 M−1s−1. We can infer that static quenching is the main reason of the fluorescence quenching for these Schiff bases. Additionally, we may utilize Scatchard`s equation to get the number of binding sites and the binding constant for static quenching. The in vitro cytotoxicity of the metal complex on the SW-480 cancer cell line was evaluated using the MTT test. The complex exhibited more activity against SW-480 than fluorouracil (FU), with an IC50 value of 0.006μM.

HSA, Schiff base, Anti cancer

یاسمن زندیه, یاسمن زندیه, کیمیا علیوردی نسب, الهه معتمدی, مرضیه قلاسی, شهره آریائی نژاد

Optimization of Bioactive Peptide Production from Soy Protein Using Recombinant Protease Enzyme: Evaluation of Physicochemical and Functional Properties

Plant-derived proteins and peptides have garnered significant interest owing to their versatile functional properties, which go beyond their basic nutritional value. The enzymatic hydrolysis of plant proteins is a controlled and cost-effective method for enhancing these properties. Additionally, the enzymatic breakdown of indigestible carbohydrate components in feed improves digestibility and bioavailability. In this study, soybeans were defatted with n-hexane and subsequently processed using an alkaline extraction method to isolate soy proteins. The protein concentration was quantified using the Bradford assay. The extracted protein was subjected to enzymatic hydrolysis using varying concentrations of recombinant protease to produce bioactive peptides. The degree of hydrolysis was measured and the antioxidant properties of the peptides were assessed using ABTS radical scavenging and reducing power assays. The results demonstrated a significant increase in antioxidant activity, with up to 74./. ABTS radical scavenging activity and a reducing power value of 0.347 at 700 nm. These findings suggest that soy-derived proteins and peptides have the potential to enhance the functional properties of both human and animal feeds. These bioactive components can potentially contribute to the nutritional value and functional performance of both human and animal feeds by improving the bioavailability of essential nutrients, offering protective effects against oxidative stress, and enhancing the overall health and growth performance of livestock.

Recombinant protease, Soy protein, Bioactive peptides, Antioxidant activity, Reducing power, Enzymatic hydrolysis

سمانه غفرانی, احمد امیری

Interaction Studies of Copper (II) Complex with Human Serum Albumin (HSA) and anti-cancer properties

The investigation of interactions between drugs and plasma proteins has become a compelling area of research in the fields of chemical biology and pharmacology. Metal-based pharmaceuticals present potential advantages over their organic counterparts, exhibiting modified pharmacological and toxicological properties. A binuclear Schiff base copper(II) complex, [Cu2(HL)2(μ-Br)2].(H2O), with HL1 being the tridentate ligand 2-(((1-hydroxy-2-methylpropan-2-yl)imino)methyl-4-nitrophenol, was synthesized and characterized utilizing various spectroscopic techniques. Interaction between HSA and the copper(II) complex was investigated by Circular Dichroism and Molecular Docking. MTT assay results indicated that the copper complex demonstrates significant cytotoxicity. These findings suggest that the synthesized complex exhibits promising anticancer properties.

Molecular Docking, MTT assay, Copper complex, Circular Dichroism

پریسا رضوانی نیا, احمد امیری

Synthesis and Identification of CoIII Complex and Protein Binding by Fluorescence and CD Spectroscopy

Schiff bases are biologically significant compounds with various medicinal applications, including antibacterial, anti-inflammatory, and antipyretic properties [1,2]. In this study, FT-IR spectroscopy is utilized to synthesize and analyze the [CoIII(H2L)(morpholine)2]ClO4 Schiff base complex. The binding affinity of this complex to human serum albumin (HSA) was assessed through fluorescence titration studies, revealing a calculated Kq value of 6.1 ×: 10 11. One of our Schiff base molecules was shown to bind to HSA, as demonstrated by fluorescence quenching and CD spectroscopy were employed to analyze this interaction and determine the binding mechanisms. Since the Kq values for these compounds exceed 2.0 ×: 10 10 M−1s−1 [3], we can conclude that the observed fluorescence quenching in these Schiff bases is due to static quenching.

Cobalt Complex, Schiff Base, HSA, anticancer, interaction, CD

سید فرزاد حسینی, احمد امیری

Interaction of a New Schiff Base Ligand with Human Serum Albumin: Insights from Spectroscopy and Molecular Modeling

Research on the supramolecular interactions between drugs or organic compounds and biological macromolecules has greatly enhanced our understanding of the structures and functions of these bio-macromolecules and various biophysical processes. Human serum albumin (HSA) plays a crucial role in this context, as it binds to most drugs, allowing them to circulate in plasma and reach target tissues. HSA primarily regulates the distribution of these drugs. Consequently, drug-protein binding is a key factor in pharmacokinetics, influencing the drug’s in vivo half-life, unbound concentration, distribution, and elimination. HSA, the most abundant protein in human blood plasma, has a high affinity for numerous endogenous and exogenous compounds, acting as a solubilizer and transporter for drugs and other organic molecules to their intended targets. In this study, a new Schiff base ligand (L1), has been synthesized and characterized by UV–Vis and FT-IR. The interaction between this ligand and HSA was studied through fluorescence spectroscopy and circular dichroism. The intrinsic fluorescence of HSA was quenched by the ligand, which was rationalized in terms of the static quenching mechanism. The results show that this compound can obviously bind to HSA molecules. According to fluorescence quenching calculations, the bimolecular quenching constant (Kq), and apparent quenching constant (KSV) at 27 °:C were obtained. The binding constant, Kb, is 110.69 L.mol−1 and the number of binding sites (n) is 1. Furthermore, the CD spectra show that the random coil and antiparallel parts of the secondary structure have trends inverse to the helix part in the presence of Schiff base ligand.

Schiff base, human serum albumin, anticancer potential, molecular properties, molecular docking

زینب حاتمی, دکتر سولماز کیا، دکتر لیلا حسنی ،آقای مسعور رحیم پور قدیم

The effect of guanine oxidation on the interaction of the doxorubicin whit four-stranded DNA

Four-stranded structure are guanine-rich sequences that are involved in the expression of proto-oncogene such as c-Myc.Doxorubicin is an anticancer drug belonging to the anthracycline family, which exerts its biological effect by inhibiting the topoisomerase II enzyme, chromatin instability and DNA breaks. In this research, the effect of guanine oxidation on the interaction of doxorubicin with the four-stranded structure of the NHE III region of the c-Myc gene promoter has been investigated. Absorption spectroscopy, Fluorescence emission and polyacrylamide gel electrophoresis were used to evaluate the interaction.The results of spectroscopy showed that the oxidation of guanine in the tetrad plane of the four-stranded structure causes a change in the binding of doxorubicin.The results of absorption spectroscopy indicated that percentage of the drug hypochromicity decreases upon addition of the oxidized G-quadruplex DNA structure in compared with the wild type structure. Fluorescence spectra implied that emission of doxorubicin decreases upon interaction of the both forms of G-quadruplex DNA, but the oxidation of guanine in the tetrad plane causes a remarkable decrease in the DNA concentration where binding saturation occurs. The binding constant of the G-quadrulex to doxorubicin and Stern-Volmer quenching constant decrease due to oxidation of the guanine nucleotide. In addition, the oxidation influences on stability of the interaction in the presence of urea and the electrophoretic mobility of the DNA structure in native polyacrylamide gel. Consequently, our results imply that oxidative stress can mediate cancer initiation and development by molecular damage of the nucleotideshas remarkable effect on the interaction between doxorubicin anticancer drug and the G-quadruplex non-B DNA structure.

Four-stranded structure,Doxorubicin,Guanine oxidation,c-Myc gene

سودابه شکرالهی صورتی, سودابه شکرالهی صورتی

A Study on the Interaction between Human Serum Albumin (HSA) and Fibroblast Activation Protein Inhibitor (FAPi): Experimental and Theoretical Perspectives

Fibroblast activation protein (FAP) is a membrane-bound protease that has limited expression in normal adult tissues but is highly expressed in the tumor microenvironment of many solid cancers. Among them, a class of FAP inhibitors (FAPi) with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold displayed nanomolar affinity and high selectivity against other interfering dipeptidyl peptidases and prolyl oligopeptidase [4]. FAP-2286 is a FAP-binding peptide coupled to a radionuclide chelator that is currently being investigated in patients as an imaging and therapeutic agent. FAPI-46 is a quinoline-based fibroblast activation protein (FAP)-targeted radiotracer. FAPI-46 has higher tumor uptake and prolonged tumor accumulation. FAPI-46 can be used for tumor imaging of a multitude of different cancers. In this study, FAPi-46 and FAP-2286, as well-known FAP inhibitor, were selected and prepared. Furthermore, the binding affinity between the above-mentioned inhibitors and human serum albumin (HSA) were studied under simulated physiological conditions (using molecular docking (MD)) and experimental analyses (using fluorescence and CD spectroscopies and cyclic voltametry). The obtained results revealed that the formation of a complex between HSA and drugs were responsible for quenching the native fluorescence of protein at 343 nm and can be illustrated by the static mechanism. The binding constant and number of binding sites were considered and proposed that the combination of hydrophobic and electrostatic forces were the principal intermolecular forces stabilizing the complex. Also, theoretical results show that the both of drugs have high affinity for binding to HSA.

FAP, human serum albumin, anticancer potential, molecular properties, molecular docking,

آی سودا محمدزاده

Encapsulation of Phytase Using Freeze-Drying Method to Enhance Performance and Stability

Phytase is a critical enzyme in the feed industry for livestock, poultry, and aquaculture, as it facilitates phosphorus absorption and improves the digestibility of other nutrients. Given its essential role, extensive research has been conducted on encapsulation techniques to preserve and stabilize phytase activity under harsh environmental and gastrointestinal conditions. We investigated a novel phytase enzyme that demonstrates optimal activity for reducing phosphorus-related pollution. By analyzing soil samples with an enhanced selective culture medium, we successfully isolated bacterial phytase producers. We extracted enzymes from these bacterial isolates and measured their phytase activity. Our characterization of the phytase included optimal pH, temperature, and substrate specificity. In the current study, we used chitosan, gum Arabic, and gelatin as encapsulation materials. Freeze-drying, a widely recognized and industrially practical method, was employed to dry the encapsulated enzyme samples. This encapsulation strategy aims to enhance the enzyme`s resistance to temperature and pH fluctuations, ensuring its functionality throughout the storage and digestive processes. To confirm the encapsulation of phytase, the enzyme was labeled with FITC, and fluorescence microscopy images validated the successful encapsulation. The encapsulated phytase demonstrated superior activity and stability compared to the free enzyme, showing better performance in terms of enzyme activity retention and prolonged shelf life. The results of this study have significant implications for the development of more efficient and stable phytase supplements, potentially enhancing nutrient absorption and reducing environmental phosphorus pollution from animal waste.

Enzyme Encapsulation, Freeze-drying, FITC, enhancing nutrient absorption and environmental phosphorus pollution, Phytase

فاطمه بهرامی, رقیه حلقومی, اباصلت حسین زاده ی کلاگر

From Functionalization to Characterization: Investigating Tryptophan-Functionalized Carbon Nanotubes and Unveiling its Properties

Nanobiotechnology is a combination of nanotechnology and biotechnology that suggests new methods to produce lighter and stronger materials widely used in biology and medicine. Carbon-based nanomaterials are one of the tools of nanobiotechnology, and we can mention carbon nanotubes (CNTs) as one of the most important of them. They are classified into multi-walled (MWCNTs) and single-walled (SWCNTs) CNTs categories. As CNTs are insoluble in water and are toxic for cells, we can functionalize them with various agents to improve their performance. In this study we functionalized MWCNTs with tryptophan an essential amino acid with unique properties and potential applications in biomedicine and nanotechnology. Then we use scanning electron microscope (SEM) and FT-IR analyses to ensure in functionalization of MWCNTs. Results from these analyses show that functionalization of MWCNTs have be done correctly. Functionalization of MWCNTs makes lower their insolubility and toxicity and improve their performance in cell environment. Now they can be used in biological and medical applications like drug delivery, biosensing, tissue engineering and so on.

carbon nanotubes, functionalization, nanobiotechnoiogy, multi-walled carbon nanotubes

امیررضا محمدی, فاطمه خاتمی, وهب جعفریان

bioinformatics studies on the F87D mutation in the photoprotein Mnemiopsin 2

Calcium-regulated photoproteins are a type of non-enzymatic proteins capable of emitting light, with a wide range of applications in biological and agricultural studies. Mnemiopsin 2, a member of this group, consists of two primary parts: an apoprotein (apomnemiopsin) and a chromophore containing coelenterazine and oxygen, bound non-covalently. These photoproteins are extensively utilized in fields such as protein-protein interactions, calcium signal tracking, gene expression analysis, and drug discovery. Mnemiopsin 2 contains three active EF-hand motifs (I, III, and IV), which can bind calcium ions, while EF-hand II cannot. Each EF-hand has a conserved helix-loop-helix structure essential for calcium binding. This study employs bioinformatics tools and physico-chemical measurements to analyze the structural and functional changes in Mnemiopsin2 mutated at position 87, comparing it with the wild-type protein. Using Medeller (v10.4) and Chimera (v1.13.1) software, along with parameters like RMSD, ERRAT, and Ramachandran score, we identified the most optimal model. Additional analysis, including hydrophobicity and accessible surface calculations, were conducted using resources like ProtParam, VADAR, and Protscale on Expasy. This comprehensive analysis offers insights into the potential applications of mutated Mnemiopsin 2 in biological fields. It was found in this instance that the protein`s hydrophobicity was not significantly changed by the F87D mutation. Furthermore, the instability was furthered by the F87D mutation. The mutation did not lead to any remarkable alterations in the protein`s structure when compared to the wild-type protein.

Bioinformatics, EF-hand, Mnemiopsin2, Molecular modeling, Photoprotein.

زهرا کریمی

Investigation of Glycin 96 roles in EF-handII photoprotein Mnemiopsin 2: bioinformatics Studies

Bioluminescence is the process of light emission by some living organisms. Mnemiopsin 2, a Ca2+ regulated photoprotein isolated from Mnemiopsis leidyi, having a blue flash type emission and belongs to family of ctenophore photoproteins. Photoprotein mnemiopsin 2 is a single subunit protein consisting of 207 amino acid residues. These photoproteins have been exploited as markers or reporters for biochemical processes in biological and biomedical researches. They are precharged bioluminescent proteins that are triggered to emit light by binding Ca2+ or certain other inorganic ions. They contain three EF-hand domains to bind Ca2+, and accommodate a peroxidized coelenterazine in the central cavity of the protein. Ctenophore photoproteins also contain three canonical sequence loop regions, each of 12 contiguous residues, which supply the oxygen ligands needed for calcium ion coordination. The residue of Glycin 96 is the twelfth residue in the EF-hand II loop of mnemiopsin 2, EF-hand II has lost its function during evolutionary stages. For this purpose, Glycin 96 was replaced with Glutamate residue (G96E). The three-dimensional structure of mutant was made with MODELLER program V. 10.4 and the best structure was evaluated using ModEval, SAVES. VADAR and ProtParam servers were used to calculate the interactions, Structural stability and physico-chemical properties of protein. ProtScale server showed Kyte & Doolittle hydropathy plot.Then, the graphical form of the desirable model was drawn using the UCSF Chimera software Finally, the optimized models were compared with the native model, The results indicate that the mutated model is slightly unstable than the native model, And it also increases the polarity in its structure. However, the free energy of G96E mutant has increased compared to native, and indicates the sturactural stability of the mutant.

Keywords: Molecular Modeling, Photoprotein, Site-directed mutagenesis, Stability.

کوثر ذبیح پور شاره, احمد امیری, سودابه شکراللهی صورتی

Synthesis, Characterization, and Drug-Like Interaction Evaluation of Copper Schiff Base Complex with Human Serum Albumin: A Study on Structural Attributes and Therapeutic Applications

In this research, a novel Copper Schiff Base Complex was designed and synthesized, evaluated for its unique properties as a drug-like compound. Its molecular structure was confirmed using advanced techniques such as 1H-NMR, IR, UV-Vis, and X-Ray, which collectively verified the integrity and accuracy of the molecular configuration. Understanding the interaction of potential drug candidates with target proteins in the body is critical in pharmaceutical development. Therefore, we focused on assessing the interaction of this complex with human serum albumin (HSA) using fluorescence spectroscopy and circular dichroism (CD) techniques. The results revealed a specific interaction between the complex and HSA, highlighting its potential therapeutic efficacy and safety profile. Furthermore, to gain deeper insights into the type and mechanism of molecular interactions, molecular docking simulations were employed. These simulations provided valuable information regarding the binding sites and interaction mechanisms of the complex with biological machinery, paving the way for further development of this complex as a potential therapeutic agent.

Copper Schiff Base Complex, human serum albumin, molecular docking circular dichroism, fluorescence spectroscopy

نگین ساعتی

مشخصه یابی اتصال نانوذره طلا به توالی الیگونوکلئوتیدی جهت ایجاد نانوپروب به منظور استفاده در بیوسنسور تشخیصی سرطان

بیوسنسور ها در طراحی تست های تشخیصی سریع که امکان سنجش سریع، آسان و غیر تهاجمی را فراهم می کنند، کاربرد وسیعی دارند. حساسیت تشخیصی بیوسنسور با استفاده از نانوذرات طلا و خواص اپتوالکترونیکی آنها افزایش می یابد. هدف از این مطالعه بررسی اتصال نانوذره به توالی انتخاب شده از جنس الیگونوکلئوتید، به منظور استفاده در بیوسنسور تشخیصی سرطان است. در این راستا ابتدا انتخاب توالی الیگونوکلئوتیدی مورد نظر و طراحی پروب صورت گرفت. سپس فانکشنال کردن نانو ذره طلا با استفاده از نوعی فسفین به عنوان یک کاهنده یونی پس از انکوباسیون های متعدد در 72 ساعت صورت گرفت. بدین ترتیب، پس از ایجاد نانوپروب، برای بررسی اتصال نانوذره و توالی مورد نظر تست های تحمل نمک (پایداری نانوذرات)، FTIR، زتا پتانسیل و DLS صورت گرفت. در تست پایداری ، نانوذره در مجاورت غلظتی از نمک رسوب پیدا کرده و محلول به رنگ خاکستری در می آید ولی نانوپروب به همان رنگ قرمز باقی می ماند. طیف سنجی 300-800 نانومتر نشان داد که نانوپروب در محدوده طول موج قرمز (حدود 500 نانومتر) پیک جذب دارد در حالیکه نانوذره فاقد پیک در این محدوده طول موج بود. در روش پراش پرتو مادون قرمز پیک ایجاد شده در بازه عددی موج 1950 تا 1050 〖cm〗^(-1) نشانگر باند های قند فسفات ایجاد شده در نانوپروب می باشد. نتایج DLS نشان داد که پس از فانکشنال کردن، اندازه و فاصله بین نانوذرات از حدود 30 نانومتر افزایش داشت. همچنین در تست پتانسیل زتا بار نانوذره ا به -10 میلی ولت کاهش یافت که می تواند نشان دهنده اتصال موفق و تولید نانوپروب ها برای هدف تشخیص سرطان باشد. این مطالعه میتواند تحولی در طراحی بیوسنسورهای تشخیصی ساده و سریع سرطان با قدرت تشخیص فوق العاده حساس و انتخابی در مولکولهای زیستی ایجاد نماید.

miRNA، AuNPs، مشخصه یابی ، FTIR، زتاپتانسیل، DLS

نسرین ملانیا, فریبا ملانیا, حانیه نزهتی, فاطمه زهرا باقری نژاد, فاطمه ملایجردی

Effects of organic solvent and ionic liquids on the kinetic behavior of chromate reductase

Organic solvent and ionic liquids have received increasing attention as attractive solvents in medical and biotechnological usages. The present study has been carried out to study the comparative influence of 1-butyl-3-methylimidazolium, 1-methylimidazolium and some organic solvent on the kinetic parameters of the chromate reductase. Km and Vmax values for enzyme were calculated 1.39 mM and 0.26 μ mol.min-1.mg-1, respectively. As the concentration of ionic liquids increased, Km increased and kcat decreased. The inhibition profile indicated mixed inhibition and the Ki (affinity of IL for the enzyme) and KI (affinity of IL for enzyme-substrate complex) values were calculated. In addition, the associated tertiary structures changes of enzyme caused by ILs (100 mM) were studied by fluorescence method. The enzyme activity in the presence of 0.5 mM [MIm][Cl] and 0.4 mM [MIm][BF4] reduced to 35./. of the initial reaction rate whereas this enzyme demonstrated 76./. of its initial activity in the presence of organic solvent such as Tween 20, indicating that the chromate reductase is more sensitive to these ILs compared to Tween 20.

Organic solvent, Ionic liquids, Chromate reductase,

حانیه رمضانی, فاطمه خاتمی, وهب جعفریان

اثر تغییر بار در بازیابی EF-hand Ⅱ نمیوپسین 2 با اعمال جهش H95D

بیولومینسانس به پدیده انتشار نور مرئی توسط موجودات زنده گفته می شود که در آن انرژی شیمیایی به انرژی نوری تبدیل می شود. این فوتوپروتئین کروی از 207 آمینواسید با وزن مولکولی 24 کیلو دالتون تشکیل شده است. این فوتوپروتئین دارای چهار موتیف EF-hand با ساختار مارپیچ- حلقه- مارپیچ است که جایگاه اتصال یون کلسیم هستند. سه باقی مانده آسپارتیک اسید در موقعیت 1، گلایسین در موقعیت 6 و گلوتامیک اسید در موقعیت 12 حفاظت شده می باشند. شایان ذکر است که Ⅱ EF-hand قابلیت اتصال به کلسیم خود را از دست داده است. همچنین نموپسین2 دارای یک حفره آبگریز است که جایگاه اتصال کلنترازین می باشد. هدف از این پروژه بررسی خواص ساختاری و عملکردی پروتئین جهش یافته H95D به منظور بازیابی فعالیت موتیف EF-hand Ⅱ است. بدین ترتیب ابتدا، توالی آمینواسیدی نموپسین 2 از پایگاه داده NCBI بدست آمد و مدل های جهش یافته طراحی شدند. در نهایت، تطبیق توالی پروتئین نمیوپسین 2 طبیعی و جهش یافته، اوبلین، برووین و آکورین با نرم افزار Clastal W تطبیق شد و از طریق سرور ESPript3 بررسی شد. با استفاده از نرم افزار Modeller 9.20، ساختارهای سه بعدی پروتئین های طبیعی و جهش یافته ایجاد شدند. با استفاده از سرورهای VADAR، SAVES و ModEval بهترین مدل براساس پارامترهایی مانند ERRAT، WHATCHECK، PROCHECK، z-DOP و RMSD تایید شد. سرور ProtScale برای ترسیم نمودار هیدروپاتی استفاده شد، در حالی که چندین پارامتر بیوشیمیایی با استفاده از ProtParam محاسبه گردید. بررسی نتایج نشان می دهد اعمال جهش باعث افزایش پایداری ساختاری پروتئین شده است .

جهش هدفمند، فوتوپروتئین، مدل سازی مولکولی، موتیف EF-hand II.

Tooba Abdizadeh

β-site amyloid precursor protein cleaving enzyme-1 molecular docking with ferulic acid and p-coumaric acid in Alzheimer`s disease

Alzheimer`s disease (AD) is a brain disorder that affecting a large population worldwide is characterized. This disease has no definitive treatment and imposes a great economic burden on the patients` families, and therefore, improvement of treatment methods is needed. β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) acts as a rate-limiting step in the production of amyloid beta (Aβ) that alters the course of Alzheimer`s disease. Abnormal activity of BACE1 in the brains of people with AD leads to the formation of beta-amyloid proteins. Receptor-ligand binding studies were performed using Autodock software. The ligands of ferulic acid, p-coumaric acid, and donepezil, were taken from Pubchem and converted into PDB format by AutoDock software for docking analysis. Afterward, the BACE1 protein was received from the Protein Data Bank, and after the preparation of this protein, molecular docking was done with these ligands by using the Autodock software. Finally, the obtained results were analyzed. Molecular docking shown high binding affinity for selective ligands to BACE1 enzyme. The ligands interacted with residues Asp228, Lys224, and Asp32 of BACE1, all of which fall within the active site of the enzyme, which may be critical for BACE1 inhibitory activity. This study provided evidence to consider these ligands as a valuable small molecule in the treatment and prevention of AD-related diseases, and further research in vitro and in vivo may show their therapeutic potential.

Alzheimer`s disease, Ferulic acid, p-Coumaric acid, Molecular docking

نسرین ملانیا, فریبا ملانیا, فاطمه ملایجردی, فاطمه زهرا باقری نژاد, حانیه نزهتی

Evaluation of folate-conjugated green synthetized gold nanoparticle potential for Human Colorectal Adenocarcinoma and gastric cancer therapy

One of the important applications of green biosynthesized gold nanoparticles by medical plants is their use as a carrier in drug delivery for cancerous cell treatment. In cancer, a group of body cells undergoes irregular proliferation that can subsequently invade other tissues and adjacent organs and ultimately cause metastasis and spread throughout the body. Many anticancer drugs need to be released at the appropriate concentration and in a suitable place to have the best effect: hence, this work has tried to develop beneficial nanomaterials by medicinal plants such as Salvia rosmarinus extract in the biomedical field. This work considered the development of a new biological system with the least side effects and the most impact, and the gold nanoparticles as carriers were biosynthesized. On the other hand, for more impact, the non-covalent nanoparticle and folate interaction was done. Human Colorectal Adenocarcinoma and gastric cancer are two foremost among many carcinoma cases globally and most of the enhanced treatments could not significantly decrease the mortality range of these cancers. The current work is planned to develop a folate-conjugated green synthesized gold nanoparticle that are effective drug against these diseases. Therefore, for the cytotoxicity assay by MTT assay, the HT-29 and gastric carcinoma (AGS) cell lines were selected, respectively. In the results, the nanoparticles in the presence of folic acid have the best effect on these cancer treatments.

green synthetized nanoparticle, gold nanoparticle, cancer therapy, colorectal and gastric cancer.

فاطمه زارع

Kinetics of Caspase7 Thermal Inactivation

Caspase 7 is a cysteine protease that induces programmed cell death in the internal pathway of apoptosis. The active enzyme consists of a homodimer of a hetero dimer. Thus, we sought to determine the mechanism of inactivation, i.e. aggregation versus the loss of the qurternary structure. For this purposee, recombinant caspase7 protein was expressed and purified by affinity chromatography method. The purified enzyme was subjected to elevated temperatures for a period of 0 to 16 hours. Then the enzymatic activities of aliquates withdrawn at certin time points were measure by the hdrolysis of the chromogenic substrate DEVD-pNA monitored at 405 nm. The enzyme was completely inactive following 10 hours incubation at 37 degrees. SDS-PAGE analysis of the samples revealed no hydrolysis of the proteins due to self celavage or by proteases that migh be presnt as minor impurities. Analysis of the kinetics of enzyme inactivation by fitting to 1st and 2st degree equations showed that that enzyme inactivation follows the 1st degree equation. This indicates that either the hetero dimer is being dissociated or homodimer is falling apart leading to loss of activity.

Caspase7, Inactivation, Denaturation

سودابه شفیعی

In Silico Evaluation of Anti-Cancer Ligands Targeting LGR4 Receptor

Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4/GPR48) has recently emerged as a critical player in various malignancies, including breast cancer, participating in tumor progression, invasion, and metastasis [1,2]. LGR4 inhibitors are currently being explored for a variety of medical applications, with cancer therapy being the most promising application. The extracellular domain of LGR4 (LGR4-ECD) has shown potential as a new therapeutic for cancer [3]. In this study, a molecular docking-based screening approach was used to identify the natural compounds with anti-breast cancer activities. The 3D structure of LGR4 protein (PDB ID: 4QXE) was retrieved from PDB, RCSB. Several natural compounds including Myricetin, Quercetin, Apigenin, Luteolin and Baicalein were chosen to be investigated as LGR4 binders. Ligands were acquired in their 3D conformer forms from the PubChem database (https://pubchem.ncbi.nlm.nih.gov/). The structures of both the protein and ligands were subsequently prepared for molecular docking using Molegro Virtual Docker (MVD). From protein-ligand interaction analysis and binding energies determined following docking, we found that the Baicalein had the highest binding affinity to the target protein (MolDock Score of −118.95). These findings may provide important information for developing anti-breast cancer therapeutics targeting LGR4.

Key words: LGR4, Breast cancer, molecular docking simulations, 3D structure

ملیکا نیک سرشت, احمد امیری

Study of the interaction between Schiff base complex and human serum albumin by fluorescence spectroscopy

new Schiff-base has been synthesized from the 1:1 M condensation of 2,2`-((1E,1`E)-(1,2-phenylenebis(azaneylylidene))bis(methaneylylidene))bis(4-bromophenol) (H2L) with Co(OAC).4H2O. The present study aims to investigate and identify the modes in the binding of the Schiff base complex to HSA. Hence, [ Co(H2L)(Py)2]ClO4 complex has been characterized by spectroscopic methods such as infrared and 1H-NMR as well as chemical analysis. studies on the interactions between metallodrugs and Human Serum Albumin (HSA), as carriers for drugs and biological molecules, are extremely important to design new drugs[1]. In this study, the interaction between HSA and newly designed anti-cancer compounds has been investigated[2]. Circular dichroism and fluorescence quenching studies revealed one molecule of our Schiff base to bind to HSA. The number of binding sites, the Stern-Volmer quenching constant and the association constant of the complex was calculated on the HSA protein[3]. According to the results, these complex can bind to the main blood carrier protein (HSA) and change the secondary structure of the protein Schiff base complex is shown. The in vitro cytotoxicity of the metal complex on the SW-480 cancer cell line was evaluated using the MTT test. The complex exhibited more activity against SW-480 than fluorouracil (FU), with an IC50 value of 0.107μM.

HSA, Schiff base, Anti cancer

رومینا عشایر, رومینا عشار

تولید نانو ذرات مگنتیت (Fe3O4) از بازیافت باطله های صنعت شکل دهی فولاد

رادار به عنوان یک سیستم مهم برای تشخیص و ردیابی مورد استفاده قرار می گیرد. استفاده از مواد جاذب امواج، یکی از روش های مرسوم در برابر حسگر راداری می باشد. این مواد، امواج رادار را جذب میکند، امواج برگشت داده شده را کاهش داده و در نتیجه از شناسایی جلوگیری می&#172:کنند. امروزه مواد جاذب رادار در صنایع مختلف دارای جایگاه خاصی هستند، این مواد می تواند شامل یک پوشش نازک از مواد مغناطیسی و مواد دی الکتریکی &#172:باشند. مگنتیت(Fe3O4) یکی از مهمترین مواد مغناطیسی است که به طور گسترده ای به عنوان یک ماده جاذب امواج مایکروویو بکار رفته است. این نانوذرات در کاربردهای مهمی همچون بیوشیمی، می تواندحامل داروهای مغناطیسی باشد. رنگ&#172:های ضدرادار، که به عنوان رنگ های استتاری یا رنگ های کم دید نیز شناخته می شوند، به منظور کاهش قابلیت شناسایی و ردیابی اشیاء توسط رادارها طراحی شده&#172:اند که معمولا در این رنگ ها از این پودر در کنار مواد دی الکتریک مانند گرافیت استفاده می شود. در این پژوهش پودر (Fe3O4) که از بازیافت صنایع شکل دهی فولاد بدست آمده، با هدف تولید نانوذرات اکسید آهن استفاده شده است. این رنگدانه می&#172:تواند در داخل رنگ ها برای ماده جاذب رادار مورد استفاده قرار گیرد. همچنین خواص فیزیکی و شیمیایی برای تعیین مورفولوژی و آنالیز عناصر، توسط آنالیزهای SEM و EDX مورد بررسی قرار گرفته است. در نتیجه پودر اکسید آهن با اندازه ذرات کمتر از 20 نانومتر به روش شیمیایی و از طریق فرآیند همرسوبی تولید گردید. از جمله ویژگی دیگر پودر حاصل شده، حضور ذرات کربن در کنار این پودر می باشد که می تواند گزینه مناسبی جهت تولید رنگ های ضد رادار باشد.

اکسید آهن، رنگ ضدرادار، گرافیت، مگنتیت، نانوذرات

فائضه ثمری, فائضه ثمری, سعیده مجنون پور

Controllable fabrication and characterization of green synthesized ZnO nanoparticles

Zinc oxide nanoparticles (ZnO NPs) are regarded as highly attractive multifunctional nano-semiconductors owing to their exceptional photostability, wide bandgap, non-toxic nature, thermal stability, cost-effectiveness, corrosion resistance, biocompatibility, wide absorption spectrum, and notable antioxidant, antimicrobial, antibacterial, and anticancer properties [1]. Also, the Food and Drug Administration has recognized it as a safe substance for human use [2]. With these regards, the green synthesis of ZnO NPs using plant extracts has driven tremendous interest in recent years [3]. This research aimed to facilitate the phyto-fabrication of ZnO NPs using the aqueous leaf extract of Manilkara zapota (M. zapota, commonly known as Chikoo) as a renewable and non-toxic reducing agent and effective capping agent in the synthesis process. The study investigated the effects of varying leaf extract quantities and calcination temperatures to determine the optimal conditions for synthesis. The physicochemical characteristics of the synthesized ZnO NPs were evaluated using ultraviolet-visible spectroscopy (UV-Vis), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and energy-dispersive X-ray spectroscopy (EDS). The ZnO NPs derived from the leaf extract of M. zapota displayed a broad absorption band in the range of 356–369 nm, indicative of the intrinsic band-gap absorption of ZnO, thereby confirming the formation of ZnO NPs. FE-SEM imaging revealed that the majority of the nanoparticles are spherical, with diameters ranging from 35 to 75 nm. EDX analysis validated the presence of zinc and oxygen, confirming the successful production of ZnO NPs. Finally, the XRD pattern corroborated their crystalline nature with a hexagonal wurtzite structure.

Green synthesis, ZnO nanoparticles, Manilkara zapota leaf extract, Characterization.

مهدی صفایی زاده, مهدی صفایی زاده, معصومه فلاح زیارانی

آنالیز بیوانفورماتیکی BRI1-ASSOCIATED RECEPTOR KINASE (BAK1) در Arabidopsis thaliana و مقایسه آن با ارتولوگ&#172:های Homo sapiens

ژن BAK1 در آپوپتوزیز و همچنین در بیماری&#172:های خود ایمنی نقش دارد. شاخص ناپایداری برای پروتئین BAK1 در آرابیدوپسیس بالاتر از 40 (59/43) و در انسان (86/46) می&#172:باشد. بنابراین پروتئین BAK1 جزو پروتئین&#172:های پایدار نمی&#172:باشد .چون شاخص آلیفاتیک پروتئین مورد مطالعه کمتر از 100 (93/97) در آرابیدوپسیس و در انسان (69/89) می&#172:باشد، در نتیجه این پروتئین در برابر حرارت پایداری بالایی ندارد و در دمای بالا قادر به حفظ ساختار سوم خود نمی&#172:باشد.به دلیل اهمیت این ژن، پایداری این ژن در آرابید.وپسیس و انسان بررسی شد و نتایج نشان داد که این ژن چه در انسان و چه در آرابیدوپسیس جزو ژن&#172:های ناپایدار است.

BAK1، آپوپتوزیز، آرابیدوپسیس، خود ایمنی

فاطمه هنرآسا

Nanozyme, a new horizon in artificial enzymes

Nanozymes are nanomaterials with intrinsic enzyme-like properties. As an artificial enzyme, nanozymes take advantage of good stability, easy modification, designability, ease of preparation, and low cost. Nanozymes have been booming over the past decade because of their capability to address the limitations of natural enzymes such as low stability, high cost, and difficult storage. Along with the rapid development and ever-deepening understanding of nanoscience and nanotechnology, nanozymes hold promise to serve as direct surrogates of traditional enzymes by mimicking and further engineering the active centers of natural enzymes. In recent years, a great number of nanozymes have been fabricated. Nanozymes were synthesized in different spatial dimensions (0D, 1D, 2D, 3D). Moreover, over the past decade, multi-functional nanozymes have been developed for various applications. The nanozymes were applied for disease diagnosis, tumor microenvironment sensing, pathogen detection, drug detection, food detection, and environmental sensing. In this work, a short review on nanozymes, their mechanism and applications was provided.

Nanozyme, Artificial enzyme, Enzyme-mimetic, Catalyst.

زهرا زارعی, زهرازارعی

Reltecimod sodium synthesis optimization

Reltecimod Sodium Acetate is a salt of the synthetic peptide (H-D-Ala-Ser-Pro-Met-Leu-Val-Ala-Tyr-Asp-D-Ala-OH) binds and modulate CD28 co-stimulatory receptor that provides protection from bacterial super antigen toxins and from lethal bacterial infections in experimental models of a wide range of bacterial pathogens (both Gram positive and Gram negative. The sequences were synthesized at room temperature on 2-CTC resin with HATU activation using an orbital shaker. Amide bond formation was performed in 60 minute, and Fmoc group were removed in 30 minute with 25./. (v/v) piperidine in DMF, after completion of synthesis, the resin-peptide were washed with DMF (3×), The peptide is separated by performing the following steps: first of all adding dichloromethane and MeOH and then dried by Filtration system, after that we use cleavage solution including: TFA, TES, Me OH, the solution under the filter is separated and most of it is removed by rotary evaporator and the remaining solution is added to the cold diethyl ether and the white precipitate was collected. We did purification by Preparative HPLC (c18 column). The synthesis of the final material was confirmed with high yield by HPLC, mass spectrometry.

Optimization , peptide synthesis, Reltecimod Sodium, chemical synthesis

نسیم فرقانی, Matia Sadat Borhani, Zhoheir Heshmatipour, Mahmoud Salehi, Mohadeseh Piri

Investigation of Genetic, Structural, and Physicochemical Diversity of AHL-Lactonase in Bacillus Species Isolated from Soil

The quorum sensing (QS) system is a key communication mechanism in microorganisms, playing a role in regulating processes such as biofilm formation, virulence factor expression, and antibiotic resistance. Bacteria communicate via autoinducer (AI) molecules, and when the concentration of these molecules reaches a specific threshold, certain genes are activated, causing physiological changes in the microbial community. One of the most important autoinducers is N-acyl homoserine lactone (AHL), which is degraded by lactonase and acylase enzymes, disrupting QS and pathogenicity. Bacillus species are among those that produce AHL-lactonase, which breaks down these molecules. The aim of this study is to investigate the diversity of the gene encoding AHL-lactonase in Bacillus and its impact on the enzyme`s structure, physicochemical properties, and interactions with QS ligands. In this research, 130 Bacillus isolates were collected from soil in various regions of Iran. Among the nine isolates containing the gene, isolate ELMX2Bwas selected for further studies. The genes were amplified via PCR and sequenced, the enzyme`s 3D structure was predicted using Swiss-Model, and molecular docking studies were conducted. The results indicated a high similarity in sequences and genetic relatedness of these enzymes to GenBank data, and the ELMX2Blactonase showed the highest binding affinity to C12-HSL (ΔG = -6.7 kcal/mol) compared to the reference lactonase. Additionally, it was found that variations in the ligand`s carbon chain length did not affect the enzyme`s binding affinity. Physicochemical studies demonstrated that the stability of the target lactonase is higher than that of the reference enzyme. Overall, this study provides new insights into the structure and function of AHL-lactonases in Bacillus species and their potential to disrupt bacterial communications.

Quorum sensing, Molecular docking, Homology modeling, Acyl-homoserine lactones

شادی نصرتی, maryam gheisari

The impact of diabetic glucose concentration on viability and cardiac differentiation of mesenchymal stem cells

Introduction: Hyperglycemia may be a stumbling block for delivery of regenerative benefits of mesenchymal stem cells (MSCs) to diabetic patients with cardiovascular diseases. Our study aims to assess the viability and cardiac differentiation potential of MSCs after being exposed to diabetic glucose concentration. Methods: MSCs were extracted from rat bone marrow. Cells were characterized based on morphology, differentiation potential, and expression of mesenchymal specific markers. MTT assay was done to evaluate the viability of MSCs after treatment with different glucose concentrations. Case group was MSCs treated with diabetic concentration of glucose versus cells treated with PBS as the control group. Growth curve and population doubling time were calculated in both groups. Expression of GATA4 and troponin, as the early and late markers during cardiac differentiation, were measured following 5-azacytidine exposure. Results: Proliferated cells at passage three had fibroblastic-shape, was able to differentiate into adipocytes or osteocytes, and expressed CD73 and CD90. MSCs viability was gradually decreased by increasing glucose concentration. Irrespective of nicotine concentration, three-day exposure imposed more severe detrimental effects on viability compared with one-day treatment. Proliferation rate of the MSCs was lower in the case group, and they need more time for population doubling. Expression of both cardiac markers were downregulated in the case group at day three. However, their expression became higher at day seven. Conclusion: Diabetic glucose concentration inhibits normal proliferation and cardiac differentiation of MSCs. This effect should be considered in stem cell therapy of cardiovascular patients who are concurrently affected by hyperglycemia, a common comorbidity in such individuals.

Glucose: Diabetes: Cardiovascular disease: Mesenchymal stem cells: Proliferation: Differentiation

ساره ارجمند, فاطمه کرمی زرندی, ساره ارجمند, یحیی سفیدبخت, پردیس میرسید

Investigating the Factors Influencing Human Serum Albumin Fibrillation Using Thioflavin T

Protein fibrillation, a process implicated in various neurodegenerative diseases, is a critical area of study for understanding amyloid-related pathologies and developing therapeutic strategies. This study utilized human serum albumin (HSA), a well-characterized model protein, to explore how temperature, pH, and protein concentration affect fibrillation. A Central Composite Design (CCD) experimental framework was implemented, assessing three levels for each factor: temperature (37°C, 47°C, and 57°C), pH (3, 5, and 7), and concentration (1, 1.5, and 2 mg/mL). Fibrillation was induced over a 48-hour period at a stirring speed of 300 rpm, with aggregation monitored using thioflavin T (ThT), a fluorescent dye that selectively binds to amyloid fibrils, allowing real-time observation of the fibrillation dynamics. Fluorescence intensity was recorded at an excitation wavelength of 440 nm and emission wavelengths of 450 nm and 600 nm. Results indicated that the combined effects of temperature, pH, and concentration significantly influenced HSA fibrillation, with aggregation observed. The quadratic model accounted for 92./. of the variance in yield, highlighting significant contributions from concentration. Normalization was performed using a power transformation of -1.24. The model demonstrated significance with a p-value of 0.0013 and an F-value of 10.85. The optimal conditions identified were a concentration of 2 mg/mL at 57°C and pH 3. This research enhances our understanding of the conditions that facilitate fibrillation.

Protein Fibrillation, Human Serum Albumin, Thioflavin T, amyloid-related diseases

فاطمه کرمی, مونس رحماندوست, ساره ارجمند

Novel technique for detection of Tryptophan using carbon quantum dots synthesized from plastic waste

Tryptophan, an essential amino acid, plays a unique and critical role in biology due to its distinctive structure and functions. Its indole side chain, featuring an aromatic, binuclear ring, sets it apart among amino acids, and it exists in cells at notably low levels. As humans cannot synthesize tryptophan, it must be obtained from dietary sources. In the body, tryptophan supports protein synthesis, growth, and overall health and acts as a precursor to several important biomolecules, including the neurotransmitter serotonin, the hormone melatonin, and niacin. Deficiencies in tryptophan are linked to a range of metabolic and neurological disorders, underscoring the importance of accurate detection in both food and biological samples. Variations in tryptophan levels are associated with numerous health conditions, including depression, cancer, and cardiovascular disease. For example, reduced tryptophan levels can serve as a biomarker for diabetic nephropathy, colorectal cancer, and Alzheimer’s disease. In the fields of food safety, clinical diagnostics, and biochemical research, monitoring tryptophan and its metabolites is essential to understanding metabolic processes and assessing nutritional quality. Fluorescent nanoparticles, especially carbon quantum dots (CQDs), have garnered significant attention for their applications in bioimaging and sensing. Synthesizing CQDs from plastic waste, such as polyethylene terephthalate (PET), offers an environmentally friendly approach to repurposing waste materials for scientific applications. In this study, CQDs synthesized from PET via a hydrothermal method were used for the detection of tryptophan. The addition of tryptophan effectively quenched the fluorescence of the CQDs, demonstrating a novel approach for tryptophan detection.

tryptophan, optical sensor, graphene quantum dots (GQDs), circular economy, waste upcyclying, bioimaging

مهدیس احمدی, Azadeh Hekmat, Aghdas Bani

Synthesis, characterization and biocompatibility evaluation of bone cement composite reinforced with squid bone (Sepia Officinalis)

Calcium phosphate ceramics have limited mechanical properties and are brittle and fragile, with a very low degradation rate in the body. On the other hand, the brittle nature of calcium phosphate ceramics limits their use alone. The bone of the common cuttlefish (Sepia officinalis) is primarily composed of a mineral compound known as calcium carbonate. Calcium carbonate, by itself, does not possess desirable mechanical strength and cannot be directly used to enhance the mechanical properties of cement. Additionally, the main mineral components of bone are derived from calcium phosphate compounds. In this project, the conversion of calcium carbonate obtained from the bone tissue of fish into calcium phosphate, the main mineral component of body bone, was carried out using a hydrothermal method. Finally, the compressive strength and biocompatibility of the cement were evaluated using MTT toxicity testing. Based on the results of XRD, SEM, and FTIR, it was shown that natural aragonite from squid bone was hydrothermally converted into hydroxyapatite. SEM images of composite samples showed that hydroxyapatite was well mixed with poly-caprolactone. The results obtained from the biocompatibility test showed that the bone cement composite reinforced with squid bone did not have toxic properties. Besides, the results of compressive strength tests showed that adding hydroxyapatite powder to bone cement could improve the mechanical properties of the composite. The results showed that increasing the percentage of hydroxyapatite powder improves the compressive strength and decreases the injectability of bone cement. Accordingly, this composite can serve as an appropriate alternative for use in the repair and reinforcement of weak and damaged bones.

Hydroxyapatite, Hydrothermal treatment, Bone cement, Compressive strength, Sepia Officinalis

مهدی صفایی زاده, مهدی صفایی زاده, معصومه فلاح زیارانی

آنالیز بیوانفورماتیکی پایداری پذیرنده EF-TU در آرابیدوپسیس

چکیده EF-TU فاکتورهای مرحله افزایش طول است و در بیان پروتئین¬ها نقش مهمی دارد. به دلیل اهمیت این پروتئین در فرایند ترجمه پایداری این پروتئین مورد بررسی قرار گرفت. نتایج نشان داد که این پروتئین جزو پروتئین¬های ناپایدار می¬باشد.

EF-TU، پایداری، ترجمه

منصوره شمیلی, Razie Esfandiari Ghalati

Enzyme kinetics in Ficus carica.L, cv. ‘Sabzʼ

There is a growing request for enzymes in the universal market. Proteases are among the most industrial commanded enzyme, included animal proteases (trypsin and pepsin), microbial proteases (bacterial, fungal and viral proteases) and plant proteases (papain and ficin). The upward requirement for biologic-based enzymes, in the food industry, made them an interesting subject for biochemists. But, their sensitivity to extreme conditions causes some restrictions. We examined the fig leaf protease stability at a range of pH (2, 3, 4, 5, 6, 7, 8) and temperature (30, 40, 50, 60, 70, 80 and 90 °C). According to our result, the optimal temperature for fig leaf proteases activity was 30 °C. The optimal pH for the leaf extract protease activity was 4. The findings revealed protease obtained from fig is a probable candidate to be used as a natural food stabilizer.

Enzyme stability: Fig: pH stability: Protease activity: Thermal stability

منصوره شمیلی, Razie Esfandiari Ghalati

Anthocyanin stability kinetics in Ficus carica.L, cv. ‘Shah anjirʼ

Anthocyanins are water-soluble pigments bringing a distinct color, from pink, red, violet, to dark blue (by pH rises). Anthocyanins are present at high concentrations in various plant derived products. Anthocyanins noticed for their potential anti-oxidant and anti-inflammatory activities to improve human health and reduce risks of diseases. One of the main limit the industrial application of anthocyanins is their instability during storage and processing. The degradation of anthocyanins during thermal process and storage can be enhanced by light conditions. In the present research, fig leaf extract was studied to examinate the thermal stability of anthocyanins. To extract leaf anthocyanin leaves were ground with acidic methanol and the absorption was read at 530 and 670 nm. Extract containing anthocyanins was heated (10, 20, 30, 40, 50, 60, 70, 80, 90 and 100ºC) under different pH (2, 3, 4, 5 and 6) and light conditions (light and dark). Fig anthocyanin extracts were more stable under pH 4 and 5, temperature 20 and 30° C, both dark and light conditions. The findings revealed fig anthocyanin is a probable candidate to be used as a natural food colorant.

anthocyanin, temperature, light, pH

داریوش مینایی تهرانی, فاطمه سید مراد

تاثیر دترژانت غیر یونی بر آنزیم لیپاز باکتری سودوموناس ، مطالعه کینتیکی و دینامیک مولکولی

چکیده: لیپازها در واقع آنزیم های ارزشمندی در صنعت هستند، به ویژه در تولید پودر لباسشویی که در آن نقش مهمی دارند. لیپاز باکتریایی، به ویژه از سودوموناس، به دلیل فعالیت زیاد و پتانسیل اصلاح ژنتیکی، مورد توجه خاص است. تعامل بین لیپاز و مواد شوینده موضوع تحقیق بوده است که منجر به یک مطالعه تحقیقاتی در مورد اثر Triton X-100 بر سودوموناس لیپاز شد. در این تحقیق از هر دو روش سیلیکونی و آزمایشگاهی استفاده شد. نتایج in silico نشان داد که Triton X-100 می تواند به یک منطقه خاص خارج از محل فعال آنزیم متصل شود و منجر به برهمکنش های آبگریز با فنیل آلانین ها در آنزیم شود. در آزمایشگاه (در شرایط آزمایشگاهی)، مشاهده شد که آنزیم بالاترین فعالیت خود را در حضور دترژانت، به ویژه در غلظت مرز بین مونومر و حالت میسلی دترژانت نشان داد. علاوه بر این، وجود دترژانت باعث تغییر در pH و دمای بهینه برای آنزیم شد. تجزیه و تحلیل طیف فلورسانس از یافته‌های in silico پشتیبانی کرد، که نشان‌دهنده تغییر در طیف انتشار آنزیم در حضور دترژانت است، که نشان‌دهنده انتقال آمینو اسیدهای آروماتیک به یک محیط آبدوست‌تر در حضور دترژانت است (Hyochromicity). به طور کلی، یافته‌های تحقیق تأیید کرد که لیپاز در حضور دترژانت غیر یونی ترایتون X-100 کاملاً فعال باقی می‌ماند، در حالی که پتانسیل دترژانت را برای تغییر خواص فیزیکی و شیمیایی آنزیم برجسته می‌کند. این بینش‌ به درک ما از رفتار لیپاز در حضور مواد دترژانت برای استفاده در صنعت کمک می‌کند.

آنزیم، یاکتری، دترژانت، فعالیتّ ، دینامیک مولکولی

سید حسین خالقی نژاد, سیدحسین خالقی نژاد, داریوش غلامی

Principles of Droplet-based digital PCR (ddPCR) and its applications

As an innovative advancement in the realm of absolute quantitative polymerase chain reaction methodologies, the droplet-based digital PCR (ddPCR) technique offers a multitude of advantages including exceptionally high sensitivity, remarkable precision and outstanding reproducibility, which are critical parameters in the realm of molecular diagnostics. in light of the burgeoning demand for point-of-care (POC) detection and clinical diagnostics, a low-cost, portable, and user-friendly droplet-based digital PCR device has emerged as an intriguing focal point of research, attracting significant attention from the scientific community. Given its extraordinary potential for seamless integration and advanced miniaturization, microfluidic technology has been proficiently utilized across a diverse range of digital droplet polymerase chain reaction (ddPCR) methodologies, significantly augmenting both their operational efficiency and overall practicality in various applications.

PCR, Droplet-based digital PCR, qPCR, applications.

زهرا جعفری, سمیه قره قومی

Optimizing ZIF-8 nanocomposite for Quercetin loading efficiency

Cancer is the second most common cause of mortality worldwide. Advanced drug delivery systems offer a targeted and efficient approach for improving cancer therapy outcomes while minimizing side effects. Zeolitic imidazolate frameworks (ZIFs) constitute a category of metal-organic frameworks (MOFs) distinguished by a zeolite-like architecture and the incorporation of imidazolate linkers. Zn2+-based ZIF (ZIF-8) has garnered considerable attention within the biomedical domain owing to its minimal toxicity and favorable biocompatibility profile. Quercetin (Que) stands out as the most prevalent flavonoid, exhibiting potent antioxidant properties and a multitude of biological functions, including antimicrobial, antidiabetic, anticancer, and anti-inflammatory activities within the biomedical sphere. By conducting research, the Mechanochemical method was used for ZIF-8 nanocomposite at different times (8, 16, 24 h), while the amount of initial materials was the same in all three times. Proceeded the Que loading as a pharmacological agent at ratios of 1:1 and 2:1 (ZIF-8: Que). Based on the obtained results, the efficiency of ZIF-8 synthesis is directly dependent on the time of synthesis. Also, drug loading at lower ratios of quercetin, yielded superior outcomes.

Antioxidant, Drug delivery, Optimization, Quercetin, Zeolitic imidazolate frameworks (ZIFs)

ساجده باهنر, ساجده باهنر

Clustering the Generalized Binding Region of Beta-Secretase for Alzheimer`s Drug Design

Introduction Beta-secretase-1 (BACE-1), a type I transmembrane aspartic protease, is a critical enzyme involved in the pathology of Alzheimer’s disease, making it a prime target for therapeutic intervention. The identification and characterization of its Generalized Binding Region (GBR) provide crucial insights into ligand-protein interactions, aiding in drug design. By leveraging structural data and computational approaches, this study aims to define the GBR of BACE-1, analyze its structural conformations, and cluster these conformations for efficient ligand-binding studies [1,2]. Methods and Materials Thirteen BACE-1 protein-ligand complexes were obtained from the Protein Data Bank (PDB) and processed using VMD software to clean and extract relevant structural data. The GBR was defined as residues within 4.5 Å: of the ligands, and structural superposition was performed to minimize RMSD between equivalent residues. An RMSD-based dissimilarity matrix was calculated, and k-means clustering was applied to group the conformations into structurally homogeneous clusters. Representative complexes for each cluster were identified, and hydrogen atoms were added using Reduce software. All analyses were conducted using TCL scripts in VMD and statistical tools in R. Results and Discussion The GBR analysis identified seven key residues (GLY11, GLN12, GLY13, LEU30, ASP32, GLY34, SER35) frequently interacting with ligands, predominantly located in beta-sheet and turn secondary structures. Clustering the complexes based on the RMSD matrix resulted in three distinct clusters, each represented by a conformationally unique structure. These representative structures provide a comprehensive view of the GBR, facilitating the reduction of docking experiments and offering a robust framework for targeted drug design. Further exploration of alternate conformations and contact thresholds could enhance the accuracy of GBR characterization, contributing to more effective inhibitor development for Alzheimer’s treatment.

Key words: Beta-secretase-1, Alzheimer’s disease, Generalized Binding Region, structural clustering, RMSD, drug design.

فاطمه صداقتی جهرمی, طیبه کمالی, فائضه ثمری

Synthesis of Magnetic Nanocomposites from Shrimp Shells

Shrimp shell waste, a significant byproduct of the seafood industry, presents a substantial environmental challenge [1]. This study explores the valorization of this waste material into value-added products through the development of magnetic nanocomposites. Chitosan, a biodegradable and biocompatible polymer, was extracted from shrimp shells and subsequently was used as bio-based material for the synthesis of magnetic nanocomposite. The influence of various factors on the synthesis of magnetic nanocomposites was studied. The structural, morphological, and chemical properties of chitosan and the magnetic nanocomposite were investigated using FTIR, XRD, SEM-EDX, BET and VSM. The resulting nanocomposites exhibited excellent magnetic properties and high surface area. The potential applications of this nanocomposites include wastewater treatment, drug delivery, and biosensing. This research provides a sustainable solution for shrimp shell waste management while offering promising opportunities for the development of advanced materials with diverse applications.

Shrimp shells, Chitosan, Waste material, Magnetic nanocomposite, Characterization

فریبا ملانیا, نسرین ملانیا, فاطمه تکتاز

A novel NADPH-dependent nitrate reductase with tellurite reductase activity from heavy metal resistance bacteria, Bacillus licheniformis strain ZT1

The tellurium and tellurium-containing compounds have been used extensively in several fields such as electronics, optics and biosensor creation. Some reductase enzymes could reduce tellurite or tellurate to generate tellurium nanoparticles. In this work, the NADPH-dependent nitrate reductase enzyme with tellurite reductase activity was purified from Bacillus licheniformis strain ZT1 that resistant to some heavy metals. The Km and Vmax values of purified enzyme were 1.5 mM and 0.3 µmol/min, respectively. The enzyme exhibited its optimum activity at pH 9 and 45°C. Divalent cations, such as Mn2+, Ca2+ and Mg2+, had no effect on the activity, while similar concentrations of Cu2+ abolished the activity. N-ethylmalemide furthermore could completely inhibit the enzyme activity due to changes in enzyme conformation. In order to investigate correctly the effects of water-miscible organic solvents on the behavior of the enzyme, some organic solvents were selected for the investigation. The enzyme revealed 65./. of its initial activity in the presence of Tween 80.

NADPH-dependent nitrate reductase, Tellurite reductase activity, Heavy metal resistance strain

پرتو طراح

Establishment of an orthotopic xenograft retinoblastoma nude mouse model by intravitreal injection of human RB Y-79 cells and histological follow up

Retinoblastoma (RB), is the most frequent primary intraocular tumor in children which if left untreated, can cause death. Preclinical animal models that mimic molecular, genetic and cellular features of cancers are essential for studying cancer and searching for promising diagnosis and treatment modalities and can also help to understand tumor biology, screening of new drugs and studying new ways of drug administration. To develop animal models of retinoblastoma that accurately resembles metastatic and non-metastatic form of the human disease, we injected human retinoblastoma Y79 cells intravitreally in both eyes of 6 BALB/c nude mice (male,5 weeks old), The incidences of retinoblastoma were analyzed by hematoxylin/eosin (HE) staining. Additionally, one injected nude mouse was kept for a longer period of time in order to study histological examination for potential metastases. Eyes were monitored morphologically every week for five weeks, tumor growth resulted in swelling of the eyes in individual animals. 8 weeks after injection histological analysis was performed and showed that Y79 retinoblastoma cells formed intraocular tumors that were initially confined to the vitreous cavity. Tumors progressively invaded the retina, subretinal space and anterior chamber of the eyes. The model described here has several advantages. It is readily available, easily established, and easy to work with. The existence of an in vivo model may offer new opportunities for the further cellular and molecular analysis of a human intraocular tumor.

Retinoblastoma, Xenograft, Mouse model, Histology

الهه طویلی

دمین I اینتگرین آلفا 11 نوترکیب: بستری برای تحقیقات ساختاری، عملکردی و درمانی

اینتگرین‌ها گیرنده‌های چسبندگی هستند که نقش مهمی در تعاملات سلول-ماتریکس و سلول-سلول ایفا می‌کنند. تحقیقات اخیر اینتگرین α11β1 را با پیشرفت تومور و متاستاز، رگ‌زایی، پیشرفت بیماری‌های فیبروتیک و ترمیم زخم مرتبط کرده است. دمین I اینتگرین α11 یک جزء ساختاری و عملکردی حیاتی است که مسئول اتصال اولیه لیگاند و تنظیم فعال‌سازی اینتگرین و آغاز مسیر سیگنالینگ درون سلول است. از آنجا که اینتگرین آلفا 11 یک گیرنده بزرگ است، بیان دمین I فعال اینتگرین α11 می‌تواند مزایای متعددی برای تحقیقات بیشتر و کاربردهای درمانی بالقوه فراهم کند. در این مطالعه، با توجه به مزایای بیان پروتئین‌ها در سیستم‌های بیان پروکاریوتی، دمین I اینتگرین α11 در اشریشیاکلی بیان شد و با استفاده از سارکوزیل در بافر لیز پروتئین محلول بدست آمد وسرانجام توسط کروماتوگرافی تمایلی نیکل خالص سازی شد. سپس برای افزایش پایداری پروتئین در طول ذخیره‌سازی، تأثیر اسمولیت‌های مختلف بررسی شد. نتایج نشان داد که 40 میلی‌مولار مانیتول می‌تواند با افزایش انرژی آزاد حالت باز شده، پایداری پروتئین را افزایش دهد. برای بررسی فعالیت پروتئین بیان شده، از روش الایزا فاز جامد استفاده شد و نتایج نشان داد که دمین I نوترکیب به صورت وابسته به غلظت به کلاژن نوع I متصل می‌شود و . به طور کلی، این مطالعه روشی برای بیان، خالص‌سازی و افزایش پایداری دمین I محلول نوترکیب اینتگرین α11 ارائه کرد که می‌تواند برای تحقیقات بیشتر در شرایط آزمایشگاهی روی اینتگرین α11 و بیان سایر پروتئین‌های مشابه مفید باشد.

اینتگرین α11β1، سیستم بیان پروکاریوتی، سارکوزیل، اسمولیت ها.

معروف زارعی

Synthesis of new β-lactams contain anthraquinone and their molecular docking

β-Lactam antibiotics are the most important antibacterial agents for human health and it began with the discovery of penicillin by Alexander Fleming in 1928. In addition, β-lactams are an important class of heterocyclic compounds due to their wide range of applications in other biological activities. With the alarming trends in bacterial resistance to many β-lactam antibiotics it has become necessary to synthesize novel β-lactams for bioassay of antibacterial activity and the need for drugs with more specific antibacterial activity. Therefore, the synthesis of the new β-lactams is the subject of extensive study. The anthraquinone and related compounds have been represented as a broad and growing family of bioactive molecules. Novel β-lactams contain anthraquinone on C-3 position were synthesized by ketene-imine cycloaddition and characterized by spectral data. Molecular docking studies were carried out by Autodoc software. Penicillin-binding protein 2a (PDB ID: 1VQQ) from methicillin-resistant Staphylococcus aureus strain used as a target which good binding interactions were observed. In silico molecular docking studies of novel β-lactam-anthraquinone hybrids showed moderate to excellent interactions. Some of the synthesized β-lactams have lower binding energy than penicillin G. The overall interaction may be attributed to the presence of β-lactam ring and anthraquinone moiety.

β-lactam, anthraquinone, antibacterial, bacterial resistance, molecular docking

معروف زارعی

The use of copper nanoparticles stabilized by C. Tinctorius plant extract in the Kinugasa reaction for the synthesis of β-lactams as potential antibacterial agents

Besides the extensive medical application with high importance of the β-lactam antibiotics, β-lactams (2-azetidinones) have also represented other biological activities. Due to biological application of 2-azetidinones and their utility as synthetic intermediates, several methods for the preparation of 2-azetidinones have been presented. One of the applicable methodologies for the synthesis of 2-azetidinones is the Kinugasa reaction. The Kinugasa reaction is the direct synthesis of β-lactams from copper acetylides and nitrones which provides some advantages including its optimal atom economy and its employment of readily accessible starting materials. Recently, nanoparticles have been widely used in various biological applications and organic reactions because of low toxicity, easy preparation without the need for filtration step, large surface area ratio and increase the efficiency of catalytic activity. Today, a considerable number of reports have shown that the addition of rhus and safflower in food or water can have valuable effects on human and animal health. Safflower has been used for a long time as a basis for dietary fat, food coloring, and Chinese medicines. The goal of our work is to produce Cu nanoparticles by Carthamus tinctorius extract through green synthetic pathways which has been used in the synthesis of β-lactams from nitrones and alkynes using Kinugasa reaction. Due to the presence of β-lactam ring and various substitutions, the products can exhibit antibacterial properties and other biological activities.

β-lactam, 2-azetidinone, antibacterial, Cu nanoparticles, Kinugasa reaction

fatemeh vaghefi, Teymoor Khosravi, Farzaneh Motallebi, Yahya Sefidbakht, Morteza Oladnabi

Investigating a Novel Bi-allelic Mutation in HPD-Like Protein: Docking Simulation Insights and Literature Overview

Background: Hereditary Spastic Paraplegia (HSP) is a rare neurodegenerative disorder characterized by progressive weakness and spasticity in the lower limbs. Mutations in the HPDL gene are associated with Spastic Paraplegia 83 (SPG83), an autosomal recessive form of HSP. Although HPDL mutations are known to contribute to SPG83, the molecular mechanisms underlying their role remain poorly understood, primarily due to the rarity of the condition. This study aims to investigate the genetic basis of HSP in two consanguineous families from Iran. Methods: Whole-exome sequencing (WES) was utilized to identify genetic variants in the probands. To assess the pathogenic potential of the identified variants in the HPDL gene, various computational tools such as SIFT, CADD, Mutation Taster, Polyphen-2, and PANTHER were employed. Conservation analysis of the HPDL protein sequence was conducted using Clustal Omega and ConSurf tools, while the 3D structure of HPDL variants was predicted using the I-TASSER server. Protein-protein interactions involving HPDL were explored through the STRING database. Additionally, the DynaMut web server was used to evaluate the impact of the identified mutations on protein dynamics and stability. The effects of the variants on protein stability were further assessed using the I-Mutant and MUpro web servers. Finally, protein-ligand docking simulations were performed using Molegro Virtual Docker (MVD), a state-of-the-art integrated platform. Results: WES identified two biallelic missense mutations: c.3G>C (p.Met1Ile) and c.128G>A (p.Arg43Pro) in the HPDL gene. The c.128G>A mutation is novel and is reported here for the first time in a patient with SPG83. Trio-based co-segregation analysis confirmed the inheritance of these variants. A thorough literature review indicated a significant consanguinity rate (49.55./.) among families with HPDL mutations. Additionally, based on ΔΔG predictions and protein flexibility analysis, it was found that the p.Arg43Pro variant led to a reduction in molecular flexibility. Conclusion: This study reinforces the association between HPDL mutations and HSP, specifically SPG83. Moreover, our bioinformatics findings represent an initial step toward validating the identified variant as a pathogenic mutation, paving the way for future functional studies

Hereditary spastic paraplegia, Spastic paraplegia 83, HPDL gene, Whole Exome Sequencing, Iran

farzaneh motallebi, Fatemeh Vaghefi, Teymoor Khosravi, Yahya Sefidbakht, Morteza Oladnabi

In Silico Investigation of PAH Gene Mutations in Iran: Identification and Docking Simulation of Potential Pathogenic Variants

Abstract Background: Phenylketonuria (PKU) is the most prevalent inherited metabolic disorder resulting from a malfunction in the phenylalanine hydroxylase (PAH) enzyme. The diverse and consanguineous nature of the Iranian population offers a valuable opportunity to investigate autosomal recessive disorders. Methods: We investigated 159 mutations in the PAH gene reported in Iran using various computational approaches. Pathogenicity and stability of genetic variants were assessed using tools like ACMG, Fathmm, CADD, SIFT, PolyPhen-2, Mutation Taster, MUpro, and I-Mutant 2.0. Amino acid conservation was analyzed with Clustal Omega and Consurf web servers. Secondary and tertiary modeling of wild-type and mutant PAH enzymes was performed using PSIPRED and I-TASSER, respectively, and 3D structures were visualized with PyMOL. Protein-protein interactions were explored using the STRING database, and potential pathogenic variants were identified through the Iranome Genomic Database. Additionally, we conducted protein-ligand docking simulations with Molegro Virtual Docker (MVD) to evaluate the structural and functional consequences of the putative pathogenic mutation (c.688G>A). Results: Our analysis revealed that 80.8./. of mutations occur in conserved regions, especially within the catalytic domain, with nearly half being missense mutations. The c.688G>A variant was identified as a putative pathogenic mutation according to the Iranome Genomic Database. The cohort had a consanguinity rate of 31.67./.. Docking studies indicated that this variant results in a significant loss of a catalytic site residue in the catalytic domain. PCR sequencing was the most common genetic testing method, accounting for 71.5./. of cases. Conclusion: This study provides insights for future functional research, genetic counseling, and the development of diagnostic tools, including a strip assay kit

PAH Gene, Phenylketonuria, Iran, Spectrum of Mutation.

فرشته رمضانی خرسند, بهاره دبیرمنش, خسرو خواجه

فلاوونوئیدها به عنوان مهارکننده‌های فیبریلاسیون پروتئین‌های آمیلوئیدوژنیک: شناسایی و ارزیابی کاندیداها

در سال‌های اخیر، درمان‌های گیاهی به دلیل هزینه پایین و عوارض جانبی کمتر، توجه بیشتری را به خود جلب کرده‌اند. فلاونویدها، به عنوان یکی از این ترکیبات، توانایی کاهش تجمع پروتئین‌های آمیلوئیدوژنیک را دارند. هدف این مطالعه شناسایی فلاوونوئیدهایی با بیشترین میزان تأثیر در مهار فیبریلاسیون پروتئین‌های آمیلوئیدوژنیک مرتبط با بیماری‌های عصبی مانند پارکینسون و آلزایمر است. در فاز اول، ۹۸ فلاوونوئید از پایگاه‌های داده مختلف انتخاب و بررسی شدند که در نهایت ۴۶ مورد از آن‌ها به عنوان کاندیدهای اولیه انتخاب شدند. این انتخاب بر اساس اثرگذاری فلاوونوئیدها بر مهار تجمع پروتئین‌های آمیلوئیدوژنیک در تحقیقات پیشین انجام شد. در مرحله بعد، با استفاده از وب‌سرورهای OSIRIS و Swiss ADME، سمیت، جهش‌زایی، شباهت دارویی و توانایی آن‌ها در عبور از سد خونی مغزی مورد بررسی قرار گرفت و برخی از آن‌ها به دلیل عدم تطابق با این معیارها از چرخه بررسی خارج شدند. داکینگ Vina نیز برای بررسی تعامل میان فلاوونوئیدها و پروتئین‌های آمیلوئیدوژنیک در نواحی اتصال محتمل شناسایی شده توسط وب‌سرورهای DoGSiteScorer وCASTp انجام شد و آمینواسیدهای درگیر در اتصال با استفاده از Ligplot و PLIP مشخص شدند. در نهایت، فلاوونویدهایی که کمترین انرژی اتصال را داشته و با آمینواسیدهای نقاط داغ آمیلوئیدی شناسایی شده توسط وب‌سرورهای FoldAmyloid،TANGO و Waltz تعامل داشتند، به عنوان کاندیدهای بررسی‌های آزمایشگاهی انتخاب شدند. در این مرحله، آلفاسینوکلئین تحت شرایط فیبریلاسیون در حضور و عدم حضور تیمارهای فلاوونوئیدی انکوبه شد. نتایج آزمون فلورسانس تیوفلاوین-T، میکروسکوپی نیروی اتمی و آزمون هضم آنزیمی پروتئیناز K نشان داد که برخی از فلاوونوئیدها می توانند به طور قابل توجهی تشکیل فیبریل‌های آلفاسینوکلئین را مهار کنند. طیف‌سنجی مادون قرمز تبدیل فوریه نیز کاهش محتوای β-sheet را نشان داد و اثر مهاری این فلاوونوئیدها را تأیید کرد. بررسی‌های کشت سلولی نیز نشان داد که این فلاوونوئیدها زنده‌مانی سلول‌های عصبی که در معرض فیبریل‌های آلفاسینوکلئین قرار داشتند، افزایش می‌دهند.

فلاوونوئید، آمیلوئید بتا، آلفا سینوکلئین، بیماری های نورودژنراتیو

زینب رضائی

A bioluminescent molecular switch for Label-Free Detection of SARS-CoV-2

Bioluminescent proteins, especially photoproteins like aequorin, have gained significant attention for their ability to emit light upon binding with specific ions, such as calcium. This unique property makes photoproteins highly effective in biosensor applications, enabling precise and sensitive detection of biological targets [1-3]. Amid the ongoing global challenge of SARS-CoV-2 in 2024, the need for advanced diagnostic tools is critical. Aequorin-based biosensors stand out due to their rapid response, real-time detection capabilities, and exceptional sensitivity, offering a powerful approach for detecting viral components and managing the spread of COVID-19[4,5]. This study focuses on the design of AeqACE2, a fusion protein combining aequorin, with an ACE2-driven peptide for the detection of SARS-CoV-2, which is known to bind to the spike protein of SARS-CoV-2. The protein construct was expressed in E. coli BL21(DE3) cells as inclusion bodies. After the refolding process, the protein was successfully recovered in a soluble form suitable for further characterization. Circular dichroism spectroscopy was employed to assess the secondary structure of the refolded protein. We evaluated the bioluminescent emission of the AeqACE2 in the presence and absence of SARS-CoV-2. The results showed a significant increase in bioluminescent intensity in the presence of the virus, confirming that the construct acts as a molecular switch. Control experiments with non-specific proteins and virus-free conditions demonstrated minimal or no change in luminescence, highlighting the specificity of AeqACE2 for SARS-CoV-2. Quantitative analysis revealed a dose-dependent increase in bioluminescent emission with increasing concentrations of SARS-CoV-2, demonstrating the sensitivity of the biosensor. Additionally, the protein`s rapid response to the presence of the virus supports its potential for real-time detection. In conclusion, the successful design and expression of this switch demonstrate its potential for use in a highly sensitive biosensor for the detection of COVID-19, providing a promising diagnostic tool in the ongoing fight against it.

Bioluminescent proteins, Photoprotein, COVID-19 detection, Protein switch, Aequorin, SARS-CoV-2

حمید ساعدی, دکتر خسرو خواجه، دکتر بهاره دبیرمنش، حمید ساعدی

بررسی اثر سومو (SUMO) در ممانعت از میزان فیبریلاسیون پروتئین های آلفا سینوکلئین، آمیلوئید بتا

مطالعه ی فیبریلاسیون پروتئین ها و پیدا کردن راهکاری جهت ممانعت از این کار، باعث شده است که میزان زیادی از پژوهش ها در سال های اخیر روی این موضوع متمرکز شود. نقش پروتئین سومو بعنوان یک چاپرون در حلالیت آمیلوئید فیبریل ها و ممانعت از فیبریلاسیون پروتئین ها در مطالعات قبلی به اثبات رسیده است. در این مطالعه میزان فیبریلاسیون پروتئین های آلفا سینوکلئین، آمیلوئید بتا در حضور و عدم حضور سومو، مورد بررسی و مقایسه قرار گرفت. میزان تشکیل آمیلوئید فیبریل ها با استفاده از بررسی میزان نشر فلورسانس تیوفلاوین T (ThT) در طول موج 485 نانومتر، بررسی شد. نتایج حاصل از آن با کمک تکنیک های دیگری مثل عکسبرداری AFM، اسپکتروسکوپی دو رنگ نمایی دایره ای (CD)، اسپکتروسکوپی FT-IR و بررسی طیف جذبی Congo Red مورد تایید قرار گرفت. در تمامی نمونه ها و تحت شرایط فیبریلاسیون، در عدم حضور سومو، میزان تشکیل صفحات آمیلوئیدی بطور قابل توجهی بالا بود در حالیکه در حضور سومو، میزان تشکیل این صفحات بطور چشمگیری کاهش پیدا کرد. نتایج حاصل از این مطالعه نقش سومو را به عنوان یک چاپرون در حل کردن آمیلوئید های فیبریلی را تایید می کند.

سومو، فیبریلاسیون، آمیلوئید بتا، آلفاسینوکلئین

سپیده جهاندار, فائزه موسوی موحدی, لیلا رضایی, علی اکبر صبوری, رضا یوسفی

مطالعه‌ی اثر یون آهن(II) بر ساختار و فعالیت چاپرونی آلفا-Bکریستالین انسانی

آلفاB-کریستالین یک پروتئین شوک حرارتی کوچک است که در اندام‌های مختلفی مثل لنز چشم، قلب و مغز حضور داشته و وظایف مختلفی از جمله عملکرد چاپرونی برعهده دارد. آب مروارید، از شایع‌ترین دلایل نابینایی است که در آن آلفاB-کریستالین عملکرد خود را از دست می‌دهد. بعلاوه، در بیماری پارکینسون اختلال در عملکرد آلفاB-کریستالین رخ می‌دهد. یون آهن برای انجام فعالیت‌های طبیعی سلول‌ها ضروری است و در آب مروارید و پارکینسون غلظت آن افزایش می‌یابد. از این‌رو بررسی اثر یون آهن بر ساختار و عملکرد آلفاB-کریستالین دارای اهمیت می‌باشد که در این پژوهش با روش‌های طیف سنجی فلوئورسانس ذاتی و عارضی، مطالعات پیوندی، طیف سنجی دورنگ‌نمایی دورانی فرابنفش دور، اسکن گرماسنجی افتراقی، میکروسکوپ نیروی اتمی، پراکنش پویای نور و مطالعه فعالیت چاپرونی، بررسی شد. یون آهن با برهم‌کنش با آلفاB-کریستالین موجب خاموشی نشر فلورسانس می‌شود. یون آهن تنها به نیمی از جایگاه‌های فلوئورسانس پروتئین آلفاB-کریستالین دسترسی دارد و به ازای هر مولکول پروتئین یک جایگاه اتصال برای یون آهن وجود دارد. در غلظت‌های بالای یون آهن، برهم‌کنش بین یون آهن و آلفاB-کریستالین غیراختصاصی است. در اثر پیوند یون آهن به پروتئین، دمای انتقال فاز حرارتی (Tm) آن اندکی نسبت به حالت کنترل (غیاب یون آهن) افزایش داشته که می‌تواند به مفهوم افزایش مقاومت الیگومرها برای بازشدن در اثر افزایش دما و در نتیجه فشردگی آن‌ها باشد. بعلاوه، پیوند شدن یون آهن باعث افزایش چشمگیر تغییرات آنتالپی غیرطبیعی شدن خرارتی می‌شود که دلالت بر افزایش پایداری حرارتی پروتئین از طریق ایجاد پیوندهای مستحکمتر در درون ساختار پروتئین است. دیگر بررسی‌ها نشان داد که یون آهن باعث کاهش فعالیت چاپرونی، کاهش اندازه الیگومرهای آلفاB-کریستالین درغلظت پایین و افزایش اندازه در غلظت بالا، فشرده شدن ساختار و افزایش پایداری دمایی آلفاB-کریستالین می‌شود.

آلفاB-کریستالین، یون آهن، پروتئین شوک حرارتی، فلورسانس، دورنگ نمایی دورانی

حانیه نزهتی, نسرین ملانیا, رسول اسمعیلی نیسیانی

Evaluation of α-amylase enzyme immobilization upon chitosan polymer for the evaluation of biosensors synthesis

The application of enzymes in various fields such as medicine, the food industry, the environment, and biotechnology is very common. One of the important applications of enzymes is in enzymatic biosensors which can play a significant role in processes such as drug tracking and disease treatment. Enzyme immobilization is a method to increase their efficiency and facilitate their recovery. The aim of this study was to immobilized the α-amylase enzyme on a polymeric chitosan through covalent bonding using glutaraldehyde cross-linking agent. The results of this study showed that the enzyme activity in the immobilized state on the polymeric substrate was still within the normal range of enzyme activity, which was confirmed by XRD test.

Immobilization, Enzyme activity, α-amylase, Chitosan

اوین آسیابانی

Antiglycation Potential of Oregano (Origanum vulgare) Leaf Extract: A Natural Approach to Combat Diabetes-Related Complications

Diabetes mellitus is a chronic disorder of glucose metabolism with serious clinical consequences. The multi-system complications of diabetes include microvascular and macrovascular endpoints. Persistent hyperglycemic state in type 2 diabetes mellitus leads to the initiation and progression of non-enzymatic glycation reaction with proteins, lipids, and nucleic acids, leading to the formation of advanced glycation end-products (AGEs). These compounds are associated with various chronic conditions, including cardiovascular and neurological diseases, as well as aging. The inhibition of glycation has become a significant focus in biomedical research, with natural compounds from medicinal plants showing great potential as therapeutic agents. Oregano (Origanum vulgare), a well-known medicinal plant with anti-inflammatory, antimicrobial, and antioxidant properties. This study aimed to evaluate the inhibitory effects of oregano leaf extract on the production of fluorescent end-products in glycated human serum albumin (HSA). HSA was incubated with a high glucose concentration in the presence or absence of oregano leaf extract for 35 days. The obtained results from spectroscopic techniques indicated that oregano extract significantly reduced the formation of AGEs. Furthermore, circular dichroism (CD) analysis demonstrated that the extract modulates the structural alterations of glycated HSA. These findings highlight the critical role of plant-based interventions in mitigating complications associated with diabetes and glycation.

Advanced glycation end-products (AGEs), Diabetes, Glycation, Herbal plants, Human serum albumin (HSA), Oregano.

زهرا بوربور حسین بکی

The Effect of Deep Eutectic Solvent on the Stability of LCD-TDP-43 Protein Liquid Droplets

The distinctive characteristics of deep eutectic solvents (DESs) offer the potential to stabilize proteins. They can prevent the aggregation of proteins, such as LCD-TDP-43, which serves as a model for prion-like protein [1]. Essentially, DESs impede denaturation caused by external stressors by encapsulating proteins within a protective barrier [2]. DESs fulfill their function by enhancing solvation around proteins, reducing hydrophobic interactions, and maintaining protein structure during phase separation [3.4]. This study aims to develop and refine DES formulations to enhance protein stability during the phase separation pathway [5]. In this study, the pJ-411 vector was used to express the recombinant LCD-TDP-43 protein in E. coli BL21 (DE3). Affinity chromatography with Ni-NTA was employed to purify the protein. Dialysis was used to study phase transitions from liquid droplets to amyloid fibrils. After 72 hours of dialysis, the LC domain transitioned from liquid droplets to amyloid fibrils. Liquid-liquid phase transitions occurred first, followed by liquid-solid phase transitions, with a white precipitate indicating amorphous mature droplets and amyloid fibrils. Five DESs were prepared to investigate their effect as chemical chaperones on the aggregation process of LCD-TDP-43 protein. These DESs included betaine: glycerol (1:2), betaine: sorbitol (1:2), betaine: citric acid (1:1), betaine: tartaric acid (1:1), and betaine: xylose (1:2). Protein aggregation in the phase separation pathway was examined, and amyloid fibrils were identified using turbidity measurements and ThT fluorescence. Turbidity measurements revealed a decrease in UV-visible absorption in the presence of several DESs, indicating their potential role in inhibiting amyloid growth in LCD-TDP-43 proteins. This finding suggests that DESs may play a crucial role in improving protein stability during liquid-phase separation. Consequently, DESs may be considered as promising candidates in the search for new therapeutic agents to treat diseases associated with protein aggregation.

DESs, LCD-TDP-43, LLPS, Protein aggregation, Neurodegeneration, ALS

شیدا ضرغامی

Exploring Anti-cancer Drugs Membrane Permeation: A Molecular Dynamics Study Using Umbrella Sampling

This study investigates the permeation of various anti-cancer drugs through lipid bilayers using molecular dynamics (MD) simulations enhanced by umbrella sampling techniques. The focus is on understanding how different lipid compositions affect the membrane interaction and transport properties of these therapeutics, which is crucial for optimising drug delivery systems. In our approach, we systematically analyse multiple anti-cancer agents, including both hydrophilic and hydrophobic compounds, to elucidate their permeation mechanisms across lipid membranes with varying compositions, such as phosphatidylcholine, sphingomyelin, and cholesterol. The umbrella sampling method is employed to calculate the potential of mean force (PMF) associated with drug insertion into the lipid bilayer, providing insights into the free energy landscape governing drug-membrane interactions. By defining a reaction coordinate based on the distance between the drug molecule and the center of mass of the lipid bilayer, we create multiple overlapping windows to enhance sampling efficiency. This allows us to capture critical conformational changes and energy barriers during the permeation process. Our findings reveal that lipid composition significantly influences drug permeability, with certain lipid environments facilitating or hindering drug translocation, and our simulations revealed distinct variations in the free energy landscape based on the physicochemical properties of the drugs, including lipophilicity and molecular size. Notably, smaller and more hydrophobic drugs exhibited lower energy barriers, facilitating their permeation compared to larger, more polar compounds. The results underscore the importance of employing umbrella sampling in molecular dynamics studies to accurately characterise the complex interactions between anti-cancer drugs and lipid membranes. This research contributes to a deeper understanding of drug delivery mechanisms and may inform the design of more effective anti-cancer therapies by optimising their membrane permeation properties.

Molecular Dynamics, Lipid Bilayers, Anti-cancer Drugs, Umbrella Sampling, Permeation, Drug Delivery

محمد ترکاشوند

Fabrication of an optical sensor for the detection of iron(II) ions using the green synthesized CQDs extracted from Urtica dioica

Carbon Quantum Dots (CQDs), due to their wide range of sources and their features such as fluorescence emission, have shown many different incredible applications in the past years. In this study, hydrothermal method, as a reliable and low cost method, was used for green synthesis of CQDs from Urtica dioica. For the hydrothermal process, 1.5 g of the plant was powdered and mixed with 30 ml of water. After that, the solution was sonicated for 30 min at the room temperature (25 °C). The solution was then transferred into a hydrothermal reactor and was placed and heated in an oven at 250 °C for 6 h. The resulting solution was then allowed to cool down to room temperature. The synthesized CQDs were purified in 3 steps, first by Whatman filter paper, after that, they were centrifuged at 20000 rpm for 20 min, and at last, by 0.22µm syringe filter. The synthesized CQDs were then used as a probe for metal detection against 10 mM of Cu(II), Hg(II), Pb(II), Fe(II), and Fe(III). Fluorescence quenching studies revealed that these CQDs can be used as an optical sensor for detecting trace amounts of iron(II) ions.

Graphene quantum dots, Optical sensor, Photoluminescence, Hydrothermal

شیدا ضرغامی

Probing Electroporation in Lipid Bilayers: Insights from Molecular Dynamics Simulations

Electroporation is a critical phenomenon in cellular processes, where applied electric fields induce transient pores in lipid bilayers, facilitating molecular transport. This study aims to elucidate the underlying mechanisms of electroporation at the molecular level, using advanced molecular dynamics simulations to model the effects of specific electric field strengths ranging from 10 to 100 MV/m on various lipid bilayer compositions. By systematically varying the electric field intensity and lipid types, we investigated the dynamics of lipid rearrangements, pore formation, and stabilization. Our simulations revealed that fields exceeding 50 MV/m significantly enhanced pore formation, with distinct differences observed based on lipid saturation and headgroup structure. Furthermore, we characterized the critical transition points for pore emergence, highlighting the role of lipid packing and hydrophobic mismatches in modulating electroporation susceptibility. These findings provide a comprehensive understanding of how electric fields interact with lipid membranes, offering insights that could enhance applications in drug delivery and gene therapy. The results underscore the importance of optimizing electric field parameters for efficient electroporation, paving the way for future experimental validations and practical applications in biotechnology and membrane biophysics.

Electroporation, Molecular Dynamics, Lipid Bilayers, Electric fields, Pore Formation, Membrane Permeability

هانیه حقیقی, دکتر مریم مهرابی, دکتر بهاره دبیرمنش, دکتر خسرو خواجه

بررسی نقش دنباله سومو((SUMO در فیبریلاسیون لیپاز باکتریایی

علاقه به موضوع تشکیل &quot:آمیلوئید&quot: توسط پپتیدها و پروتئین‌ها در سال‌های اخیر به طور چشمگیری افزایش یافته و به سبب کاربرد در شیمی پروتئين، زيست فناوری، زيست شناسی و پزشكی توجه بسياری را جلب نموده است. این فرآیند از سه مرحله آهسته، رشد و اشباع تشکیل شده است. در این مطالعه تشکیل فیبریل های آمیلوئیدی از لیپاز میکروبی سویه سودوموناسی تحت شرایطی که نزدیک به حالت فیزیولوژیک می باشد ، در حضور و عدم حضور دنباله سومو انجام گرفت. از آنجایی که دنباله سومو به عنوان توالی چسبنده برای افزایش بیان و حلالیت پروتئین نوترکیب استفاده می شود، بدین منظور در این مطالعه دو سازه ژنی با دنباله سومو و بدون دنباله سومو طراحی شد.. کلونینیگ ، بیان و تخلیص این دو سازه ژنی انجام شد. سپس تشکیل فیبریل های آمیلوئیدی پس از رقيق سازی اوره با روش های فلورسانس تیوفلاوینT ThT))، اتصال قرمز كنگو، پراكنش نوری پويا، طيف سنجی دو رنگ نمايی دورانی و مادون قرمز تبديل فوريه، پراكنش پرتو X و تصويربرداری با ميكروسكوپ نیروی اتمی (AFM) بررسی شد. نتایج حاصل از این بررسی نشان می دهد تجمعات شکل گرفته در ساختار بدون سومو در مقایسه با سازه ی دارای دنباله سومو افزایش تعداد صفحات یتا را نشان می دهد و تشکیل فیبریل لیپاز بلافاصله بعد از رقیق سازی در چند ثانیه ابتدایی در ساختار بدون سومو انجام می گیرد، ولی در سازه ی دارای دنباله سومو فیبریل آمیلوئیدی تشکیل نشد که این موضوع بیانگر این است احتمالا دنباله سومو بر عدم تشکیل فیبریل های آمیلوئیدی نقش دارد.

واژگان کلیدی: فیبریل آمیلوئیدی، لیپاز، دنباله سومو، تجمعات سریع

طاهره ساوئی

Inducing Robust Humoral and Mucosal Immunity against SARS-CoV-2 using Yeast Surface Display System

The SARS-CoV-2 virus, the causative agent of the COVID-19 pandemic, has become a serious global health threat. The receptor-binding domain (RBD) of the spike protein is a critical component of the virus, essential for its entry into human cells, and a prime target for vaccine development. In this study, we aimed to enhance humoral and mucosal immunity by developing recombinant P. pastoris yeast displaying the RBD on its surface using the SEDI anchor. The RBD gene was synthesized and electroporated into competent P. pastoris cells. After screening positive clones on PAD plates, P. pastoris/pPink-αHC-RBD-SEDI was cultivated in BMGY medium and subsequently induced in BMMY medium. The surface expression of the RBD protein was confirmed using ELISA, flow cytometry, and immunofluorescence assays. Oral immunization was administered to mice on days 1 and 2 for primary immunization and on days 14 and 15 for booster immunization. Blood and fecal samples were collected on day 28. ELISA results indicated that the absorbance at 450 nm for yeast expressing RBD was twice as high as that of the control yeast. Mice administered with RBD-expressing yeast exhibited higher serum IgG levels compared to those receiving control yeast. Fecal IgA levels were also elevated in mice treated with RBD yeast compared to the control group, indicating enhanced mucosal immunity. Our findings underscore the significance of the RBD as a key target for SARS-CoV-2 vaccine design and provide evidence for the efficacy of an orally administered yeast based SARS-CoV-2 vaccine in inducing robust immune responses. Importantly, the yeast surface display system could serve as a universal technological platform for the development of other oral vaccines.

p. pastoris, SARS-CoV-2, receptor-binding domain (RBD), Immune response, yeast surface display.

هلیا واحدی

Structural adaptation of late embryogenesis abundant protein from Artemia under molecular crowding conditions

Late embryogenesis abundant (LEA) proteins are crucial for protecting organisms like Artemia against abiotic stresses, such as high salinity and drought [1,2]. Although their protective roles are well-documented, the underlying molecular mechanisms, particularly regarding their structural adaptations under stress, remain poorly understood. This study investigates the structural behavior of LEA proteins in response to molecular crowding agents and membrane mimetics, which replicate conditions similar to those encountered during environmental stress. LEA protein from Artemia urmiana was expressed in E. coli BL21(DE3) and purified. To mimic the molecular crowding and stress conditions, we selected compounds such as polyethylene glycol (PEG), glycerol, trifluoroethanol (TFE), and sodium dodecyl sulfate (SDS). PEG and glycerol simulate molecular crowding, while TFE induces the formation of helical structures, and SDS serves as a membrane mimic, as LEA proteins are known to protect cell membranes under stress [3,4,5]. We used spectroscopic techniques-UV absorption, circular dichroism (CD), and fluorescence spectroscopy-to examine the structural transitions of LEA proteins in the presence of these compounds. Our results show that in its native, hydrated state, the LEA protein predominantly adopts a random coil conformation. However, in the presence of PEG, glycerol, and TFE, the protein underwent a structural shift toward increased helicity, indicating a transition to a more compact conformation. This helical formation was most pronounced in the presence of TFE, suggesting that LEA proteins may utilize such structural changes to stabilize cellular structures under stress. Additionally, in the presence of SDS, which mimics a membrane environment, LEA proteins showed enhanced folding, supporting their known membrane-protective role.

LEA proteins, Molecular Crowding, Trifluoroethanol, Sodium dodecyl sulfate, Artemia

فرناز مقامی

Effect of exosomes on retinoblastoma cancer cells in drug delivery

Exosomes are extracellular vesicles secreted by almost all cell types, playing a significant role in cell-to-cell communication and in transporting therapeutic agents and biomolecules such as proteins and RNA. Mesenchymal stem cell-derived exosomes have attracted attention due to their unique characteristics, including low toxicity, biocompatibility, and minimal immune response. On the other hand, doxorubicin is a chemotherapy drug widely used to treat various cancers, including retinoblastoma—a common intraocular cancer in children caused by mutations in the RB1 gene. In this research, exosomes derived from mesenchymal stem cells were employed to deliver doxorubicin to retinoblastoma cancer cells in order to investigate their effects. Exosomes were isolated from Wharton jelly mesenchymal stem cells using size-exclusion chromatography. They were then loaded with doxorubicin by sonication, and the effect of exosomes, drugs, and doxorubicin-loaded exosomes on Y-79 cells was examined through an apoptosis assay. The results indicate that the exosomes alone exhibited no toxicity toward the cancer cells, while the combination of exosomes and the drug showed enhanced induced apoptosis compared to the drug alone.

Exosome, Retinoblastoma, Drug delivery

سارا عسگری

Investigation of the interaction of human α-1-acid glycoprotein (AGP) with copper oxide nanoparticles (CuO NPs)

Nanoparticles in the diameter range of 1-100 nm show physical properties that can be completely different from the bulk. The parameters such as the size of the particles, the distance between the particles, the nature of the protective organic layer on the nanoparticles surface, and the shape of the nanoparticles affect the nanoparticles properties. It is now well accepted that when nanoparticles come into contact with a biological environment, their surface is covered by many different biomolecules such as enzymes, proteins, peptides, and amino acids. The adsorbed protein layer on the surface of nanoparticles is called protein corona. Alpha-1-acid-glycoprotein, AGP, is one of the positive acute-phase proteins of all mammals. AGP is a plasma protein with a molecular weight of 37-54 kDa, a very low isoelectric point of 2.8-3.8, and with a plasma concentration of about 0.4-1.2 mg/l. Copper oxide nanoparticles (CuO NPs) are one of the most important intermediate metal oxides nanoparticles, which have unique physicochemical properties due to their large size and effective surface area (high surface to volume ratio). Copper oxide nanoparticles have attractive properties such as high stability, reactivity, high critical temperature, availability, non-toxic nature, biocompatibility, and high absorption of visible light. Also, CuO NPs have antioxidant and antibacterial activities that protects against cell damage. In this study, we have synthesized and characterized the CuO NPs and further their cytotoxicity against the normal cells were investigated. The formation of protein corona upon interaction of AGP protein with CuO NPs have been studied using cyclic voltammetry method. According to the results obtained from this method, the redox peak currents decreased considerably and the redox peak potentials shifted which indicating the adsorption of the AGP molecules on the surface of CuO NPs. The binding constant as a parameter reflecting the strength of the formed protein corona of AGP estimated from the cyclic voltamogram showed the high affinity of AGP to adsorb on the surface of CuO NPs.

Copper oxide Nanoparticles, Human α-1-acid glycoprotein (AGP), Protein corona, Cyclic voltammetry.

داریوش غلامی, سید حسین خالقی نژاد

بررسی دستیابی به داروی کنترل کننده اختلالات افسردگی با مهار آنزیم مونوآمین اکسیداز A

افسردگی یکی از اختلات عصبی حاد است که سالانه افراد زیادی را در ایران و سرتاسر جهان درگیر خود می¬کند. میزان سطح فعالیت آنزیم مونوآمین اکسیداز A در ایجاد اختلالات ناشی از افسردگی از جمله انواع ناهنجاری های روان¬شناختی نقش دارد. در این مطالعه تعدادی از لیگاندهای مستعد برای مهار آنزیم مونو آمین اکسیداز A مورد ارزیابی قرار گرفت. ابتدا این لیگاندهای آنزیمی انتخاب و ساختار سه بعدی آنها از پایگاه اطلاعات ساختاری PubChem تهیه شد. همچنین ساختار سه بعدی آنزیم منوآمین اکسیداز A از پایگاه اطلاعات پروتئینی PDBتهیه شد. سپس فرآیند داکینگ مولکولی پس از آماده سازی لیگاند و گیرنده، برای بررسی میانکنش بین آنها اجرا شد. نتایج این تحقیق نشان دادند که این مشتقات متناسب با ویژگی های ساختاری خود اثربخشی های متنوعی در مهار آنزیم مونوآمین اکسیداز A اعمال می¬کنند. بنابراین از بررسی تغییرات در ساختار شیمیایی مورد نظر میان مشتقات بررسی شده، دکستروآمفتامین (L5) در مهار منوآمین اکسیداز A از مهمترین مشتقات سلژیلین معرفی می شود.

مونوآمین اکسیداز A، بیماری¬های عصبی، داکینگ مولکولی، دکستروآمفتامین

عسل بانو فامیلی, عسل بانو فامیلی

افزایش پایداری حرارتی آنزیم اوریکاز آسپرژیلوس فلاووس با استفاده از جهش زایی هدفمند

اوریکاز یک اکسیدوردوکتاز پروکسیزومی است که باعث اکسیداسیون اسید اوریک به پراکسید هیدروژن و آلانتوئین می شود. عدم وجود آن در انسان، سبب افزایش سطح اسیداوریک (هایپراوریسمی)با مصرف غذاهای پر پروتئین ونهایتا ایجاد بیماریهایی نظیر نقرس می شود. بنابراین از اوریکاز به عنوان آنزیمی دارویی جهت درمان بیماریهای مرتبط با هایپراوریسمی در انسان استفاده می شود. هدف از این مطالعه پایداری حرارتی آنزیم اوریکاز به روش مهندسی ژنتیک با ایجاد جهش زایی هدفمند در آن است. ابتدا برای انتخاب جهشی مناسب، شبیه سازی دینامیک مولکولی به منظور بررسی بازشدگی پروتئین انجام شد. با مقایسه نتایج پارامترهایی نظیر انرژی، شعاع ژیراسیون ، RMSD ، RMSF بین جهش های کاندید و تایپ وحشی آنزیم، جهش مطلوب انتخاب شد. ایجاد جهش با استفاده از جهش زایی هدفمند صورت گرفت. سپس ترانسفورم و بیان آنزیم در باکتری E.coli بهینه سازی و تخلیص آن با استفاده از ستون کروماتوگرافی نیکل سفارز صورت گرفت. جهت تایید بیان و خلوص آنزیم از SDS-PAGE ، با جرم مولکولی 34 کیلو دالتون برای آنزیم اوریکاز در الکتروفورز عمودی، استفاده شد. در این مطالعه به فعالیت آنزیم جهش یافته و وحشی و مقایسه این دو واریانت در ارزیابی پایداری حرارتی آنزیم پرداخته خواهد شد.

شبیه سازی دینامیک مولکولی، شعاع ژیراسیون، جهش زایی هدفمند، الکتروفورز عمودی،

علی رکن رابعی, علی رکن رابعی

طراحی و ساخت هیدروژل نانوکمپوزیتی بر پایه پلی اکریلیک اسید دارای نانوذرات زینک سولفید و کریستال نانوسلولز برای استفاده به عنوان زخم‌پوش

هیدروژل‌ها موادی هستند که مشابه ماتریکس خارج سلولی بافت‌های نرم بیولوژیک رفتار می‌کنند. به همین دلیل، استفاده از هیدروژل‌ها به یکی از حوزه‌های پژوهشی رو به رشد در زمینه پزشکی تبدیل شده است. ساخت زخم‌پوشی که به‌طور همزمان دارای خواص زیستی و مکانیکی مطلوب باشد، چالشی مهم به شمار می‌رود. هدف از این پژوهش، بهره‌گیری از نانومواد برای ایجاد خواص مکانیکی و زیستی مناسب در هیدروژل بر پایه پلی‌اکریلیک اسید برای کاربرد زخم‌پوش است. به این منظور هیدروژل بر پایه پلی اکریلیک اسید (PAA) حاوی نانوذرات سلولز و نانوذرات سولفید روی سنتز شد. نانوذرات سلولز برای بهبود خواص مکانیکی و نانوذرات سولفید روی برای ایجاد خواص ضد باکتریایی به پانسمان زخم در نظر گرفته شدند. آنالیزهایی مانند SEM، FTIR و TGA برای مشخصه یابی هیدروژل انجام شد. آزمون MTT تایید کرد که زخمپوش سنتز شده زیست سازگار است. مطالعات حیوانی نشان دادند که هیدروژل به طور قابل توجهی به بهبود زخم‌های پوستی تمام‌ضخامت در مدل موش کمک می‌کند. علاوه بر این، تحلیل‌های میکروبیولوژیکی نشان داد که پانسمان زخم دارای فعالیت ضد میکروبی قابل توجهی در برابر Staphylococcus aureus و Escherichia coli است. حاصل این پژوهش معرفی یک هیدروژل زیست‌سازگار و آنتی باکتریال است که می‌تواند کاربردهای بالینی امیدوارکننده‌ای به عنوان زخم‌پوش داشته باشد.

زخم‌پوش ، هیدروژل ، پلی اکریلیک اسید ، سلولز نانوکریستال ، نانوذرات زینک سولفید

زینب امیری

(بیان و تخلیص فاکتور رشد فیبروبلاستی پایه (bFGF) و بررسی اثر آن بر افزایش میزان رشد و تکثیر سلول¬های فیبروبلاست)

پروتئین bFGF یک گلیکوپروتئین 18 کیلودالتونی است که باعث افزایش میزان مهاجرت فیبروبلاست¬ها در محل زخم می¬شود. مطالعاتی كه در مورد میزان بیان mRNA انجام شده است نشان می¬دهد كه با افزایش سن میزان FGF كاهش می¬یابد و رابطه مستقیم با اختلال در تکثیر فیبروبلاست¬ها، كراتینوسیت¬ها، سلول¬های پیش ساز آدیپوسیت وجود دارد. پروتئین bFGF به-صورت گسترده برای ترمیم زخم¬های بالینی كاربرد دارد. با توجه به کاربرد bFGF در ترمیم زخم، هدف از این پژوهش ساخت این فاکتور رشد به صورت محلول و بررسی اثر آن بر سلول¬های فیبروبلاستی می¬باشد. از باکتری E.coli سویه DH5α به جهت كلونینگ، تکثیر، حفظ و نگهداری وكتور استفاده شد. همچنین در این پژوهش سویه BL21به عنوان میزبان اختصاصی برای بیان ژن كلون شده استفاده شد. توالی پروتتئین مذکور در انتهای آمینی به دنباله سومو به جهت افزایش حلالیت و 6 آمینواسید هیستیدین به منظور تخلیص پروتئین نوتركیب متصل شده است. به همین دلیل از روش كروماتوگرافی تمایلی ستون نیکل-آگارز استفاده گردید. نمونه¬های تخلیص شده با استفاده از كیسه دیالیز 5 كیلودالتون در بافر با حجم 1 لیتر و در 4 درجه سانتیگراد تعویض بافر شد. پروتئین آماده شده توسط روش¬های کشت سلولی بر روی سلول L-929 اثر داده شد و توسط روش MTT میزان زنده¬مانی و میزان سمیت آن سنجیده شد که نتیجه تست بیانگر این است که میزان زنده¬مانی سلول¬ها نسبت به گروه کنترل افزایش یافته است. همچنین برای بررسی میزان تکثیر و مهاجرت سلول¬ها تست ترمیم زخم انجام شد که نتایج آن نشان دهنده افزایش میزان تکثیر و مهاجرت سلولی است. پژوهش حاضر نشان داد که امکان بیان محلول فاکتور bFGF با استفاده از دنباله سومو وجود دارد. همچنین نتیجه آزمون MTT و ترمیم زخم فعالیت پروتئین مذکور را تائید کرد. پروتئین bFGF تولید شده در پژوهش پیش رو می¬تواند کاربردهای متعددی در کشت سلول، طراحی زخم پوش¬ها و تحقیقات دانشگاهی داشته باشد.

واژه‌هاي كليدي:فاکتور رشد، bFGF،بیان،تکثیر فیبروبلاستی

سارا جمشیدی زاده

Biomolecules-incorporated marine bioceramic-based nanomaterials for drug localized delivery

The use of both manmade and natural materials for repairing and reconstructing bodily organs and tissues has a long history dating back to prehistoric times. However, in recent decades, there has been a significant acceleration in their utilization in scientific research and clinical applications. The advanced processing methods and new chemical strategies allow the incorporation of drugs within them or on their functionalized surfaces. In this regard, bioceramics act as local drug delivery systems to treat large bone defects, osteoporotic fractures, bone infections and bone tumours.The importance of understanding implant-tissue interactions on a nanoscale level has led to the widespread use of nanotechnology in the field of biomedical science and engineering. This is supported by the idea that nanostructured materials can be customized and integrated into various biomedical implants and devices. Additionally, natural nanostructured patterns can be observed in biological systems like membranes, viruses, and protein complexes, while intricate architectural designs with interconnected open pores can be found in marine environments. Utilizing naturally-occurring marine skeletons offers promising solutions for advancing research and development in regenerative medicine for dentistry and orthopedics. These materials provide abundant supplies of osteopromotive analogues, biomineralization proteins, and a variety of framework designs and devices. Marine organisms, whether used in their original form or transformed into materials suitable for human implantation, possess unique characteristics such as chemical composition and strong mechanical properties that make them ideal for applications in dentistry and orthopedics.

Biomulecules, Bioceramic, Drug delivery, Nanomaterial

پگاه حاجی کرمی

Comparison of the effects of aspirin and salicylic acid on the structural changes and fibrillation of hemoglobin

Hemoglobin is one of the vital proteins in the body, playing a critical role in oxygen transport. Aspirin is a widely used medication. Salicylic acid is a natural compound found in various plants, particularly in willow bark extract. On the other hand, aspirin is a synthetic derivative of salicylic acid. Current research investigates and compares the effects of aspirin and salicylic acid on the structural changes and fibrillation of human hemoglobin. The methodology employed in this experimental study was investigated using spectroscopic techniques, including circular dichroism (CD), intrinsic fluorescence spectroscopy, and scanning electron microscopy (SEM). The results obtained from the intrinsic fluorescence emission through the incubation method indicate that the position of heme prosthetic group in hemoglobin-aspirin has changed or caused heme degradation more than hemoglobin-salicylic acid compared to the initial state. Findings from the circular dichroism spectroscopy, which was examined via the incubation approach, revealed a more significant alteration in the secondary structure of hemoglobin incubated with different concentrations of aspirin compared to salicylic acid. Additionally, the results from scanning electron microscopy (SEM) demonstrated that the sample incubated with aspirin exhibited a greater number and larger size of fibrils compared to the sample incubated with salicylic acid.

salicylic acid, Aspirin, human hemoglobin, heme degradation, fibrillation

یاسمین جنتی

The impact of various organic solvents on the solubility of polyester compounds

Plastics are organic polymers created through the polymerization of long hydrocarbon chains. Because of their high durability, plastics persist in the environment for a long time. One effective method to break them down and convert them into simpler materials is to use a suitable solvent that alters their structure. Some solvents can break down the structure of a plastic, while others may soften or distort it. The type of plastic and contact time with the solvent also matter. In this study Dimethylformamide (DMF), Dimethylsulfoxide (DMSO), Phenol, Trifluoroacetic acid (TFA), Dichloromethane, Chloroform, and Toluene were utilized in quantities of 2 ml to assess dissolution rate of small pieces obtained from plastic bottles, which are considered as a source of polyester plastics. Furthermore, constant stirring, boiling the solvent, and the application of heat and time were found to be able to enhance solubility. Results showed that polyester polymers can be transformed from solid to liquid when they’re exposed to suitable solvents. Trifluoroacetic acid (TFA) is the most effective one, able to depolymerize bottles by 50./. and dissolve films due to its acidic nature, particularly at high temperatures. Chloroform has 40./. solubility, while Toluene has a lower solubility. Phenol and Dimethyl sulfoxide (DMSO) each have 20./. solubility, Dichloromethane and Dimethylformamide (DMF) have 10./.. Based on our results, Trifluoroacetic acid can be used as the best solvent for polyester degradation.

Organic Solvents, Solubility, Polyester, Plastics

سیده فائزه ناصری

Investigation of the interaction of a new ruthenium complex with DNA and human serum albumin

The transition metal-based compounds are extensively used in chemotherapy, and the ruthenium complexes have been introduced as promising options in the treatment of cancer. Regarding the chemical properties such as high ligand transfer rate, different oxidation numbers, and the ability of ruthenium to mimic iron in binding to biological molecules, these compounds have been used for pharmaceutical aims as anticancer drugs to replace platinum compounds in cisplatin-resistant cancers. In this research, the interaction of a new ruthenium complex, complex [(p-cymene) RuCl (ppy)] (1) with calf thymus DNA and human serum albumin (HSA) were investigated using fluorescence spectroscopy and ultraviolet-visible absorption spectroscopy. The competitive diffusion experiments were performed to investigate the mode of interaction of the complex 1 with DNA using several markers including ethidium bromide, thiazole orange, DAPI, methylene blue and Hoechst 33258. The results of the competitive experiments indicated that this complex bind to DNA through the intercalation mode. The values of the thermodynamic functions, Stern-Volmer constant, binding constant and the number of binding sites for the interaction of the complex 1 with DNA and HSA were calculated from the results of fluorescence quenching experiments at different temperatures using the van’t Hoff method. According to the obtained results, the quenching mechanism for the interaction of complex 1 with DNA and HSA is of the static type and the effective forces in the interaction of this complex with both DNA and HSA are van der Waals type or hydrogen bond formation.

Ruthenium complexes, DNA binding, Human Serum Albumin (HSA), and ligand-binding.

Tooba Abdizadeh

Investigation of chrysin as interleukin 6 potential inhibitor by in silico method

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease distinguished by painful inflammation of the joints (1). Cytokines such as IL-6 have a crucial role in the initiation and development of rheumatoid inflammation. IL (interleukin)-6 is a multi-functional cytokine essential for hematopoiesis, immunology, bone metabolism, and inflammation (2, 3). This study aimed to investigate the molecular mechanism of chrysin in the treatment of rheumatoid arthritis (RA) using molecular docking approach. Molecular docking studies were performed using Autodock software. The 3D structure of the chrysin was obtained from Pubchem and converted into PDB format by AutoDock software for docking analysis. Afterward, the IL6 protein was taken from the Protein Data Bank (PDB), molecular docking was done with chrysin by using the Autodock software. Then, the obtained results were analyzed by Chimera software. Molecular docking shown high binding affinity for the chrysin to IL6 protein. The ligands interacted with IL6 residues in the active site of the protein, which may be important for IL6 inhibitory activity. This study can provided evidence to consider the chrysin as natural product with further research in vitro and in vivo in the treatment of the rheumatoid arthritis.

Rheumatoid arthritis, Chrysin, Molecular docking

وحیده عبدی, وحیده عبدی, زهرا قاسمی, ایمان سوری نژاد

سنتز سبز نانو ذرات مگنتیت Fe3O4 و کاربردهای زیست پزشکی در سیستم دارو رسانی هوشمند

نانو فناوری به دلیل کاربرد بالقوه آن در علم پزشکی توجه زیادی را به خود جلب کرده است. یکی از تکنیک¬های تحویل هوشمند دارو که در سال¬های اخیر شهرت یافته است، استفاده از نانوذرات مغناطیسی است. نانوذرات Fe3O4 به دلیل خواص فوق پارامغناطیس، زیست سازگاری بالا، غیرسمی بودن، تولید در مقیاس بزرگ، قابلیت بازیابی، پایداری شیمیایی، بی ضرر بودن به طور گسترده مورد استفاده قرار می¬گیرند. نانو ذرات مغناطیسی در کاربردهای مختلف زیست‌ پزشکی مانند دارو رسانی، تصویر برداری رزونانس مغناطیسی (MRI)، ردیابی سلولی، ژن درمانی، مهندسی بافت و ردیابی سلول‌های بنیادی مورد استفاده قرار می¬گیرند. عوامل مختلفی مانند شکل، اندازه، ساختار کریستالی و توزیع اندازه ذرات، خواص مغناطیسی نانو ذرات آهن را کنترل می‌کنند. معمولا داروها به سطح نانو ذرات مغناطیسی متصل می¬شوند یا درون یک نانو کامپوزیت از پلیمر و نانو ذرات مغناطیسی کپسوله می¬شوند. رهایش هدفمند دارو به بافت آسیب دیده بدن، یکی از مهم¬ترین جنبه¬های سیستم دارو رسانی می¬باشد. در سیستم دارو رسانی هوشمند، داروهای بارگذاری شده در نانو ذرات Fe3O4 می¬توانند با کمک میدان مغناطیسی خارجی در محل مورد نظر تجمع پیدا کنند. نانو ذرات حاوی دارو، باید دارو را در محل مورد نظر با سرعت مناسب و بدون آسیب رساندن به سلول¬های سالم آزاد کنند. به منظور اعمال نانو ذرات آهن در بدن انسان، نانو ذرات باید زیست سازگار و زیست تخریب پذیر باشند تا سمیت را به حداقل برسانند. بنابراین، سنتز سبز نقش مهمی ایفا می¬کند. بسیاری از مطالعات نتایج امیدوارکننده نانو ذرات Fe3O4 را در درمان سلول¬های آسیب دیده از طریق مطالعه آزمایشگاهی نشان دادند. از این رو، نانو ذرات Fe3O4 از لحاظ دارا بودن شرایط مناسب برای دارو رسانی هوشمند مناسب هستند.

نانو ذرات مغناطیسی، دارو رسانی، نانو حامل، زیست پزشکی

رقیه حیران

Computational Approaches to Accelerate Drug Discovery

Protein-ligand interactions are fundamental to numerous biological processes. These interactions are indispensable for cellular communication, metabolic pathways, immune responses, and numerous other vital functions. A comprehensive understanding of protein-ligand interactions is crucial for drug discovery and development. This study examines the intricate mechanisms underlying these interactions, with a focus on the role of non-covalent forces such as hydrogen bonding, electrostatic interactions, van der Waals forces, and hydrophobic effects. By elucidating the molecular determinants of binding affinity and specificity, various drug design strategies have been explored to target specific proteins implicated in disease pathogenesis. This involves understanding the intricate interplay of non-covalent interactions, including hydrogen bonding, electrostatic interactions, van der Waals forces, and hydrophobic effects, that govern the formation of protein-ligand complexes. Computational approaches, such as molecular docking and dynamics simulations, have become indispensable tools in drug discovery, enabling the identification of novel protein targets, pharmacophore mapping, molecular docking, virtual screening of lead compounds, prediction of bioactivity, simulation of protein-ligand complex dynamics, affinity prediction, and the design of optimized ligands. These techniques enable researchers to virtually screen vast chemical libraries, identify potential drug candidates, and refine their structures to enhance binding affinity and selectivity. By simulating the dynamic behavior of protein-ligand complexes, these computational methods provide valuable insights into the molecular mechanisms underlying drug action, ultimately accelerating the drug discovery process.[1][2]

Protein-ligand interaction, molecular docking, dynamics simulations, drug discovery.

فاطمه زهرا باقری نژاد

Preparation of exfoliated MoS2 nanosheets with catalytic active edges

Two-dimensional MoS2 nanosheets have been widely studied in diverse application fields (1). MoS2 nanosheets can be prepared via different synthesis methods such as hydrothermal/solvothermal and liquid-phase-exfoliation method (2). In this study, MoS2 nanosheets have been prepared through exfoliation of bulk MoS2 powder in NMP via combination of bath and then tip sonication. In order to activate the MoS2 nanosheets edges, appropriate amount of highly oxidant H2O2 was added to NMP solution. The best results was obtained where the volume ration of 3:17 was chosen for H2O2:NMP. Obtaining catalytic active MoS2 nanosheets via such a facile and straightforward procedure is an important achievement for various applications such as water splitting and pollutants degradation (3).

MoS2 , H2O2 , NMP , exfoliation

زهره قلندری, دکترنرگس امراللهی بیوکی

پتانسیل ضایعات شیلاتی در سنتز نانو کیتوسان

در سال های اخیر، بهره برداری از ضایعات زیستی به عنوان یک راهکار نوین در راستای توسعه پایدار و کاهش اثرات زیست محیطی، به طور چشمگیری مورد توجه قرار گرفته است. ضایعات شیلاتی، از جمله پوسته سخت پوستان و سایر بقایای آبزیان، به عنوان منبعی غنی و مقرون به صرفه از کیتین، فرصتی بی بدیل برای تولید مواد پیشرفته همچون نانوکیتوسان ارائه میدهند. کیتوسان یک پلی ساکارید با ساختار منحصر به فرد و ویژگی های استثنائی نظیر خاصیت آنتی باکتریال، زیست سازگاری، زیست تخریب پذیری و قابلیت جذب بالا ، به طور گسترده در صنایع پزشکی، داروسازی، کشاورزی و بسته بندی زیستی کاربرد دارد. برای استخراج کیتین و تبدیل آن به نانو کیتوسان روشهای متعددی وجود دارد که از این میان میتوان به روش زیستی( بیولوژیکی) که در این روش از تخمیر میکروبی و آنریم های زیستی استفاده میشود و همچنین به استخراج شیمیایی که شامل مراحل دمینرالیراسیون، پروتئین زدایی و استیل زدایی اشاره کرد. تولید نانو کیتوسان از ضایعات شیلاتی نه تنها بهره وری این منابع تجدید پذیر را افزایش میدهد، بلکه به طور موثری، آلودگی های زیست محیطی ناشی از این ضایعات را نیز کاهش میدهد. نانوکیتوسان، با سطح ویژه بالا و خواص فیزیکی و شیمیایی بهبود یافته، در مقایسه با کیتوسان معمولی عملکردی به مراتب برتر دارد و در حوزه هایی مانند دارو رسانی هدفمند، بهبود زخم ها، حذف آلاینده ها و فناوری های زیستی نوین، افق های تازه ای می گشاید. نتایج این مطالعه نشان میدهند که استفاده از ضایعات شیلاتی به عنوان منبع اولیه برای تولید نانو کیتوسان علاوه بر اینکه راه حل پایدار برای کاهش ضایعات و آلودگی های محیطی است میتواند به عنوان یک روش اقتصادی و زیست محیطی برای تولید مواد نانو ساختار با خواص برتر مطرح شود.

ضایعات شیلاتی،سنتز زیستی،نانوفناوری، پلیمرهای زیستی

داریوش غلامی, سید حسین خالقی نژاد

بررسی اثر ترامادول بر فراسنجه های بیوشیمیایی سرم خون در موش های صحرایی نر نژاد ویستار

امروزه استفاده از داروهای کنترل کننده درد در انواع جراحی ها مرسوم است. یکی از این داروها ترامادول می باشد. ترامادول نوعی مخدر مصنوعی با فعالیت مرکزی است. در این مطالعه اثرات این دارو بر روی فعالیت آنزیم های کبدی، نیتروژن اوره خون (BUN) و کراتینین در موش ها مورد بررسی قرار گرفت. برای این منظور 15 موش نر نژاد ویستار مورد استفاده قرار گرفتند که در سه گروه مساوی (گروه کنترل، گروه دریافت کننده ترامادول هیدروکلراید با دوز 2 میلی گرم/کیلوگرم، گروه دریافت کننده ترامادول هیدروکلراید با دوز 5 میلی گرم بر کیلوگرم) تقسیم شدند. مطالعه حاضر نشان داد که تجویز حاد و مزمن ترامادول تاثیر معنی داری بر فراسنجه های بیوشیمیایی سرم و همچنین هماتولوژیکی خون در موش های نر نژاد ویستار داشت. بنابراین پیشنهاد می شود در استفاده از این دارو برای تسکین درد افراد تحت درمان و عمل جراحی با احتیاط بیشتری رفتار شود.

ترامادول، فراسنجه های خونی، فراسنجه های بیوشیمیایی، موش صحرایی نر

امیرحسین رضائی لطیفی, علی رضائی لطیفی

شبیه سازی یک سنسور اپتیکی پایش ضربان قلب انسان در مد انعکاسی با کمک مدل سه لایه ای پوست

سنسورهای اپتیکی پایش ضربان قلب پوشیدنی بر روی سطح پوست قرار می گیرند و با اندازه گیری های فیزیولوژیکی از سطح پوست نظارت راحت و مداوم ضربان قلب را فراهم میکنند. این سنسورها در دو مد انعکاسی و عبوری ساخته میشوند و هر دو شامل یک منبع نور برای گسیل نور به بافت پوست و یک آشکارساز برای اندازه گیری تغییرات نور پراکنده شده توسط بافت پوست می باشند. در این کار یک سنسور اپتیکی پایش ضربان قلب در مد انعکاسی که در آن منبع نور و آشکارساز هر دو در یک طرف بافت پوست قرار داده میشوند مدل سازی میشود. برای این هدف، در ابتدا بوسیله یک مدل سه لایه ای پوست و با کمک نرم افزار اپتیکی زیمکس، انتقال نور در پوست انسان در طول موج 600 نانومتر شبیه سازی میشود. سپس تغیییرات حجم خون شریانی پوست بین فاز سیستولیک و دیاستولیک چرخه قلبی به مدل اعمال شده و تغییرات توان سیگنال دریافت شده در آشکارساز مورد محاسبه قرار می گیرند. خروجی شبیه سازی نشان می دهد که در فاز سیستولیک که حجم خون افزایش می یابد توان سیگنال و تعداد فوتون های رسیده شده به آشکارساز کاهش ولی در فاز دیاستولیک با کاهش حجم خون افزایش می یابند. سیگنال خروجی سنسور با سیگنال های اندازه گیری شده بر روی افراد سالم در شرایط استاندارد مقایسه می شوند. مقایسه نشان می دهد که توافق خوبی بین شکل سیگنال خروجی سنسور شبیه سازی شده و نمونه های اندازه گیری شده بر روی افراد سالم در رده های سنی مختلف وجود دارد.

سنسور اپتیکی پایش قلب ، پوست سه لایه ای، اندازه گیری فیزیولوژیکی، زیمکس، سیستولیک، دیاستولیک

فاطمه صداقتی جهرمی, مهدیه خیری, فائضه ثمری

Eco-friendly synthesis of zinc oxide nanoparticles using Ficus religiosa leaves

Green synthesis represents an innovative approach to nanomaterial production, leveraging biological entities such as plants, fungi, bacteria, and algae as reducing and capping agents. This sustainable methodology offers a compelling alternative to conventional chemical methods, which often rely on toxic chemicals and generate harmful byproducts [1]. Ficus religiosa, commonly known as the sacred fig or peepal tree, has emerged as a promising natural resource for the green synthesis of nanoparticles. This ancient tree, revered in many cultures, contains a wealth of bioactive compounds that can act as reducing and capping agents in the synthesis process. This study presents a novel and green method for synthesizing zinc oxide nanoparticles (ZnO NPs) utilizing Ficus religiosa leaf extract as a renewable, non-toxic, and effective stabilizer. Optimizing the synthesis process to achieve specific nanoparticle properties, including size, shape, and crystallinity, is of significant importance. The amount of leaf extract, reaction temperature, and reaction time are crucial parameters that significantly influence the synthesis process and subsequent properties of the nanoparticles. The quantity of leaf extract and calcination temperature in the synthesis of ZnO NPs were optimized and the volume of leaf extract=60 ml and T=400 ⸰C were considered. Along with the synthesis and fabrication processes, it is necessary to characterize nanoparticles to assess their properties, so, information on the size, morphology, chemical composition, crystal structure, surface composition, optical band-gap value, and thermal stability were concluded using some of the most common characterization techniques, namely, UV–Visible spectroscopy, X-ray diffraction, field-emission scanning electron microscopy with energy dispersive X-ray spectroscopy, transmission electron microscopy, Fourier transform infrared spectroscopy and thermal gravimetric analysis. The results confirmed the successful synthesis of ZnO nanoparticles, which exhibited a spherical morphology with an average size of 50 nm and a band gap energy of 3.14 eV.

Green synthesis, ZnO nanoparticles, Ficus religiosa. Leaf extract

آیدا داوری

An Investigation Towards MIL-101 (Fe-Cu) Structures to Achieve Optimal Activity Across a pH Range

Metal-organic frameworks (MOFs) are compounds consisting of metal and organic linkers with properties such as high porosity, chemical and thermal stability, and structure tunability that have diverse applications including catalysis, biosensors, and drug delivery in the fields of industry, therapy, and medicine. Due to combination of nanozyme and enzyme in biosensing fields to measure metabolites, pH is one of the most effective factors related to functional performance of both nanozyme and enzyme, so it should be optimized. In this study, the bimetallic structure MIL-101 (Fe/Cu) was prepared with different Iron to Copper ratios (5:1, 2:1, 1:1, 1:2, and 1:5) and its Peroxidase-like activity was investigated in the pH range of 4 to 6.5. The results showed that the optimal pH is about 4.5, but the ratio of metals plays a key role in increasing the catalytic activity at other pHs. The compounds (Fe:Cu 1:2) and (Fe:Cu 1:5) compounds had a relatively rapid decrease in activity with increasing pH, like compound (Fe:Cu 5:1), although their absorption level at pH 4 was more than 2 times the value reported for (Fe:Cu 5:1). These findings indicate that designing and tuning the metal ratio in bimetallic MOFs can improve their catalytic efficiency in biosensing applications.

MOF, Nanozyme, Peroxidase, Fe-Cu, Activity

فاطمه ملایجردی

Simulating the release of metformin as anti-diabetic drug from carbon nanotubes

Diabetes mellitus (DM) and its complications constitute a serious public health issue facing modern societies (1). Metformin is currently the most widely used hypoglycemic drug for diabetes mellitus (2). Furthermore, in recent years, it has been determined that, this drug has direct effects on cancer cells. Fig. 1: Structure of N`N-Dimethylimidodicarbonimidicdiamide (Metformin Based on previous research, it was demonstrated that metformin loaded on carbon nanotubes under near-infrared (NIR) irradiation led to a significantly increased response to cancerous cells. Molecular dynamics simulations are a very powerful method to Study the drug delivery process and improve its efficacy and safety by controlling the rate, time, and place of release of drugs. in this study the dynamic release of metformin from the interior of carbon nanotube in the aquatic environment using the dl-poly software.

Diabetes, Diabetes mellitus, Metformin, Molecular dynamics simulation

امیرحسین رضائی لطیفی, علی رضائی لطیفی

مدلسازی اپتیکی پوست نه لایه ای انسان و بررسی تاثیر غلظت هموگلوبین و تغییرحجم شریانی خون بر روی سیگنال فوتوپلتیسموگرافی

در این کار ابتدا با تقسیم پوست به نه لایه و با کمک خوص اپتیکی مولفه های تشکیل دهنده خون و بافت پوست مانند غلطت ملانین و غلظت هموگلوبین و استفاده از روابط مربوطه کمیت های ضریب جذب، ضریب پراکندگی و پارامتر ناهمسانگردی هر کدام از نه لایه پوست در طول موج 575 نانومتر محاسبه می شوند. سپس با در نظرگرفتن تغییرات حجم خون شریانی در هر سیکل قلبی و انتقال نور از این مدل نه لایه ای پوست و دریافت فوتون های پراکنده شده توسط ردیاب نوری و محاسبه توان دریافت شده، سیگنال فوتوپلتیسموگرافی در شرایط استاندارد بر حسب وات شبیه سازی میشود.سیگنال های خروجی نرمالیزه شده، با نمونه های اندازه گیری شده بر روی افراد سالم در شرایط استاندارد مقایسه میشوند. این مقایسه نشان می دهد که سیگنال های&#160: شبیه &#173:سازی شده توافق خوبی با نمونه های اندازه گیری شده دارند. در آخر با تغییر غلظت هموگلوبین و تغییر حجم خون پمپ شده در هر سیکل قلبی تاثیر این دو کمیت بر روی شکل سیگنال فوتوپلتیسموگرافی بررسی می شوند. نتایج شبیه سازی نشان میدهد که با افزایش یا کاهش غلظت هموگلوبین، مولفه DC توان سیگنال نیز کاهش یا افزایش می یابد و تغییرات حجم خون پمپ شده از طرف قلب بیشترین تاثیر بر روی شکل سیگنال توان فوتوپلتیسموگرافی دارد. مدلسازی پوست و استخراج سیگنال خروجی با کمک نرم افزار اپتیکی زیمکس و برنامه نویسی در محیط پایتون انجام می شوند.

مدلسازی اپتیکی پوست نه لایه ای، غلظت خون، هموگلوبین، ضریب جذب، ضریب پراکندگی،‌ سیگنال فوتوپلتیسموگرافی

رقیه حیران, Elham Riazimontazer

Antibacterial Agents: Design and in silico Studies

The emergence of antibiotic resistance poses a severe threat to global health. β-lactams, a class of antimicrobial agents renowned for their broad-spectrum activity, favorable pharmacokinetic properties, low toxicity, oral bioavailability, and bactericidal action, have been a cornerstone of antimicrobial therapy.[1] These agents exert their antibacterial effect by inhibiting the catalytic activity of bacterial transpeptidases, also known as penicillin-binding proteins (PBPs), which are essential enzymes in the cross-linking of peptidoglycan chains during cell wall synthesis.[2] In this study, we designed a series of monocyclic β-lactams incorporating diverse substituents. These compounds were subsequently evaluated for their inhibitory potential against PBP, a crucial target in bacterial cell wall biosynthesis, using molecular docking simulations with the validated PDB structure 1MWT. Visual analysis of the docking results revealed favorable interactions between the designed compounds and the active site residues of PBP. Notably, several compounds exhibited promising binding affinities and could potentially serve as lead candidates for the development of novel antimicrobial agents to combat infectious diseases.

2-Azetidinone, molecular docking, antibacterial, drug design.

فهیمه ملانیا, فریبا ملانیا, نسرین ملانیا

Biosynthesis of iron oxide nanoparticles by Bacillus sp. GFCr-1

Nanostructured materials, including iron oxide nanoparticles (IONPs), have important application in nanotechnology due to their unique properties (1). Various studies have been conducted to biosynthesize this nanoparticles using extremophile bacteria (2, 3). The aim of this study was to optimize iron oxide nanoparticle biosynthesis by Bacillus sp. GFCr-1 in the invitro condition. The biosynthesized IONP was characterized by UV-vis spectrophotometry at 370 nm, X-ray Diffraction (XRD), and scanning electron microscope (SEM). In the first, changing the medium reaction color to dark brown indicated the biosynthesis of iron oxide nanoparticles.

biosynthesis, iron oxide nanoparticles, Bacillus sp.

بهاره فراهانی محرابی

پایداری گلوکز اکسیداز کپسوله شده در ژل پلی اکریل آمید

گلوکز اکسیداز یک آنزیم مهم است که به طور گسترده در صنعت و پزشکی مورد استفاده قرار می‌گیرد. بنابراین پایدارسازی این آنزیم در بیوتکنولوژی یک دستاورد بزرگ محسوب می‌شود. برخی شرایط محیطی شبیه دما، نمک‌های آلی و اسیدیته بر روی پایداری آنزیم موثرند. چندین راهکار شبیه تثبیت پروتئین و مهندسی حلال و پروتئین برای افزایش پایداری آنزیم و حفظ ساختار آن در طول مدت ذخیره سازی و به کارگیری آن وجود دارد. در این پژوهش آنزیم گلوکز اکسیداز در ژل پل ‌اکریل ‌آمید به عنوان یک روش تثبیت، کپسول شده و پایداری آن به وسیله روش طیف‌سنجی جذبی ارزیابی شد. برای کپسول کردن آنزیم ان اکریل ‌اکسی‌ سوکسینیمید به عنوان لینکری که به باقیمانده لایزین متصل می‌شود به محلول آنزیم اضافه شده و سپس آنزیم توسط ژل حاصل از اکریل آمید و بیس اکریل آمید کپسوله شد. نمونه‌های متنوعی از آنزیم کپسوله شده در غلظت‌های مختلفی از لینکر و آکریل آمید تهیه شدند. فعالیت باقیمانده آنزیم در دمای ۵۰ درجه سانتیگراد اندازه‌گیری شد و نتایج نشان دادند که نسبت پایین لینکر و مواد ژل برای کپسوله کردن آنزیم، اثر قابل توجهی بر ساختار پروتئین ندارد؛ اما در نسبت بالا، پایداری آنزیم تا حدی کاهش پیدا می کند. پایداری آنزیم در ۴۰ و ۵۰ درصد حلال آلی دی متیل سولفوکساید نشان داد کپسوله کردن نه تنها در غلظت‌های پایین، بلکه در غلظت‌های بالا نیز تغییر معنی داری بر پایداری آنزیم نداشته ‌است. بنابراین شرایط کپسوله کردن که منجر به کپسوله شدن محکم و شل می‌شود برای پایداری آنزیم اثر می‌گذارد و یافتن شرایط بهینه برای کپسول کردن عامل مهمی در تثبیت آنزیم است.

پایدارسازی، گلوکز اکسیداز، کپسوله کردن، پلی اکریل آمید

مریم ناصری, مریم ناصری, علیرضا لطف آبادی, ژیلا ایزدی

Protein Replacement Therapies for Recessive Dystrophic Epidermolysis Bullosa (RDEB)

Recessive dystrophic epidermolysis bullosa (RDEB) is a debilitating genetic disorder caused by mutations in the COL7A1 gene encoding type VII collagen (C7), an essential component of the dermal-epidermal junction (DEJ). This deficiency results in extreme skin fragility, blistering, and chronic wounds, significantly impairing patients’ quality of life and increasing the risk of skin cancer (1, 2). Recent advancements in protein replacement therapy have shown promise in addressing the underlying cause of RDEB by restoring C7 function. Studies in murine models lacking C7 have demonstrated that intravenous and topical administration of recombinant human C7 (rhC7) can effectively incorporate into the DEJ, leading to the reformation of anchoring fibrils and improved skin integrity (3). This approach reduces skin fragility and blistering, ultimately extending the survival of affected animals. The potential of rhC7 to serve as a therapeutic agent for RDEB is further bolstered by its ability to evade significant immune responses, particularly when mechanisms like the CD40-CD40L pathway are inhibited to prevent antibody generation (2, 4). The half-life of C7 in the DEJ is approximately 30 days, necessitating considerations for dosage and frequency to maintain therapeutic levels in human applications (5). Innovations in recombinant technologies have facilitated the production of stable, disulfide-bonded C7 trimers that form effective dermal-epidermal anchors, even in pathogenic mutations (6). Such mutations, while posing challenges due to the potential for protein misfolding or increased proteolytic sensitivity, underscore the importance of tailoring protein therapy to individual genetic profiles (6). Furthermore, topical applications of recombinant C7 in mouse models have demonstrated efficacy in promoting wound closure and minimizing scar formation by modulating transforming growth factors, suggesting additional therapeutic pathways for chronic wound management beyond genetic correction (7). This indicates a dual potential for C7 therapies to restore structural integrity and enhance regenerative healing processes, emphasizing the need for comprehensive approaches that integrate gene, protein, and immune modulation strategies in treating RDEB (8, 9). Complementing direct protein therapies, biomaterial advancements such as RHC-conjugated chitosan hydrogels offer innovative solutions for wound management. These hydrogels, incorporating recombinant human collagen-peptide (RHC), support enhanced mechanical properties and bioactivity, addressing the typical limitations of traditional chitosan hydrogels (10). The thermosensitive properties of such hydrogels enable better handling and application flexibility, which is critical for treating complex wounds like burns. In vitro and in vivo studies reveal that RHC-chitosan hydrogels significantly promote cell viability, infiltration, and vascularization, which are crucial for tissue regeneration and repair (10). The hydrogel matrix provides a supportive environment that facilitates cell migration and integration, which, paired with increased mechanical stiffness and optimized water vapor transmission, accelerates the healing process and improves clinical outcomes (10). This dual focus on structural and therapeutic attributes highlights the promising future of combined cell-based, protein, and biomaterial therapies for RDEB and other conditions characterized by structural protein defects. Continued research and clinical evaluation will be vital to refine these techniques and verify efficacy and safety in human populations, potentially transforming treatment paradigms for genetic skin disorders (1, 10). In summary, the convergence of protein replacement therapies and advanced biomaterials like RHC-conjugated hydrogels represents a significant leap forward in treating severe dermatological conditions. These emerging strategies provide a foundation for innovative, personalized therapeutic interventions that may soon extend beyond the scope of RDEB to tackle a range of complex wound healing challenges (2, 9, 11).

Recessive Dystrophic Epidermolysis Bullosa (RDEB), Protein Replacement Therapy , Recombinant Biomaterials , Chitosan Hydrogels

یحیی سفیدبخت

بررسی دینامیک مولکولی و بیوانفورماتیک جهش‌های پروتئین اسپایک SARS-CoV-2 از سویه ووهان تا سویه XEC&quot:

از زمان ظهور SARS-CoV-2، این ویروس تغییرات تکاملی قابل توجهی به ویژه در پروتئین اسپایک تجربه کرده است که منجر به ظهور سویه‌های نگران‌کننده مانند آلفا، بتا، گاما، دلتا و امیکرون شده است. جهش‌های این پروتئین باعث افزایش انتقال‌پذیری ویروس، تمایل به اتصال به گیرنده ACE2، فرار از ایمنی و بیماری‌زایی شده و انتشار جهانی سویه‌های جدید را تسهیل کرده‌اند. این مطالعه به بررسی تأثیرات جهش‌های اخیر بر ساختار و دینامیک پروتئین اسپایک SARS-CoV-2 با استفاده از شبیه‌سازی‌های دینامیک مولکولی می‌پردازد. همچنین، تأثیر این جهش‌ها بر تعاملات پروتئین اسپایک با گیرنده ACE2 و ویژگی‌های آنتی‌ژنی آن مورد بررسی قرار گرفته است. شبیه‌سازی‌های دینامیک مولکولی برای پروتئین‌های اسپایک نسخه اول و جهش‌یافته در ترکیب با گیرنده ACE2 با استفاده از GROMACS (نسخه 2020.6) انجام شد. برای پارامتری‌سازی سیستم، میدان نیروی CHARMM36 استفاده شد و هر سیستم برای 100 نانوثانیه شبیه‌سازی شد. ثبات ساختاری، انرژی آزاد اتصال و تغییرات ساختمانی برای ارزیابی تأثیر جهش‌ها تحلیل شد. بررسی&#172:های بیوانفورماتیکی و مقدماتی نشان می‌دهند که برخی از جهش‌ها با تثبیت نواحی اتصال در برهمکنش پروتئین ها، تمایل پروتئین اسپایک به اتصال به ACE2 را افزایش می‌دهند، در حالی که برخی دیگر از طریق تغییرات در اپیتوپ‌های سطحی به فرار ایمنی کمک می‌کنند. تجزیه و تحلیل‌های دینامیکی تغییراتی در انعطاف‌پذیری، ثبات و دینامیک ساختاری نشان می‌دهند که این تغییرات ممکن است به بیماری‌زایی بیشتر ویروس کمک کنند. به طور خاص، سویه XEC که یک ترکیب از زیرسویه‌های KS.1.1 و KP.3.3 است، از جهش نادر T22N (از KS.1.1) به همراه Q493E (از KP.3.3) بهره می‌برد که به افزایش فرار ایمنی و اتصال به گیرنده کمک می‌کند. یافته‌های این مطالعه درک مولکولی دقیقی از نحوه تأثیر جهش‌های پروتئین اسپایک در ظهور و گسترش سویه‌های جدید SARS-CoV-2 ارائه می‌دهد و می‌تواند طراحی واکسن‌ها و استراتژی‌های درمانی برای مقابله با سویه‌های آینده را بهبود بخشد

-2 ِ، پروتئین اسپایک، جهش‌ها، دینامیک مولکولی، گیرنده ACE2 ، فرار ایمنی

زهرا نوا

Stabilization of photoprotein aequorin through mutagenesis and Deep Eutectic Solvents

Aequorin, a calcium-regulated photoprotein, has diverse applications in biosensing and imaging [1-2]. However, its stability limits its broader usage, particularly under harsh conditions [3]. This study investigates the impact of two types of deep eutectic solvents (DES), choline chloride-glycerol (ChCl-Gly) and choline chloride-urea (ChCl-Urea), on enhancing of structural and thermal stability of G14A mutant of aequorin. so far, there has been a steady increase in utilization of these solvents on protein stabilization [4]. The G14A mutation, because of local increase in the number of van der Waals interactions, is hypothesized to influence its stability and folding properties [5]. The G14A variant of aequorin was expressed in E. coli BL21(DE3) cells and purified using affinity chromatography. Structural analysis was performed using Far-UV circular dichroism (CD) spectroscopy, while intrinsic fluorescence measurements and thermal stability assays were employed to assess the protein`s structural integrity and heat tolerance in the presence of DESs. The stability of G14A aequorin was evaluated by monitoring changes in secondary structure and fluorescence intensity after exposure to DES solutions at different time intervals (5, 10, 15, 30, and 60 minutes) at 70 °:C. Far-UV CD spectra revealed that both ChCl-Gly and ChCl-Urea significantly increased the secondary structure content of G14A aequorin compared to the control. The intrinsic fluorescence intensity of this mutant in the presence of ChCl-Gly was significantly decreased compared to the control, while ChCl-Urea caused a minor increase in emission. Thermal stability assays showed that G14A in the presence of both ChCl-Gly and ChCl-Urea buffers exhibited improved stability over time at 70 °:C. Both DES buffers facilitated increased protein stability compared to the control, indicating a protective effect on the protein’s conformation. The G14A mutation, in combination with DES buffers, enhances the stability of aequorin, making it more robust and applicable for a broader range of biotechnological and analytical applications.

Aequorin, deep eutectic solvents, choline chloride-glycerol, choline chloride-urea

مهدیه پورسرگل, Fatemeh Rigi

Evaluation the origin of conformational and tautomeric preferences in N-acetylacetamide- a quantum chemical study

Quantum chemical study of N-acetylacetamide was carried out at various theoretical levels such as HF, B3LYP and MP2 methods with the most popular basis set, 6-311++G (d, p). The computational results reveal that the amide resonance and intramolecular hydrogen bonding are two superior factors in determining the most stable conformation of diamide and amide–imidic acid tautomers, respectively. The evaluation of hydrogen bond energies predicts that the hydrogen bond strength of N-acetylacetamide is weaker than acetylacetamide. But the results of atoms in molecules, natural bond orbital, and geometrical parameters are given a different order, EHB (N-acetylacetamide) > EHB (acetylacetamide). Although the bond average energies of tautomerization process emphasized on more stability of amide–imidic acid tautomer, but our theoretical calculations reveal that the diamide conformers are more stable than the amide–imidic ones. The population analyses of equilibrium conformations by natural bond orbital method also predict that the origin of tautomeric preference is mainly because of the electron delocalization of amide functional group, especially LP(N)→ π*C=O charge transfer.

N-acetylacetamide: Intramolecular hydrogen bond: Amide resonance: AIM and NBO

مهدیه پورسرگل, حکیمه میر

مطالعه نظری جذب داروی ضدسرطان ایبروتینیب بر روی نانولوله های تک دیواره نیترید بور

دارورسانی نوین در درمان سرطان تدبیری برای کاسته شدن عوارض شیمی درمانی است. حامل¬هایی از جنس¬های مختلف برای دارورسانی کاربرد دارند. از جمله این حامل¬ها نانولوله¬های نیترید بور هستند. در این تحقیق نانولوله¬های تک دیواره نیترید بور به عنوان حامل داروی ضدسرطان ایبروتینیب مورد بررسی قرار گرفت. جذب این دارو در دو موقعیت درون و بیرون نانولوله¬های نیترید بور با قطرهای مختلف بررسی شد. براساس مقادیر انرژی لنارد-جونز مابین دارو و نانولوله و منحنی¬های RDF جذب دارو در هر دو موقعیت از لحاظ ترمودینامیکی مطلوب است. نتایج شبیه¬سازی نشان داد که برهمکنش بین دارو و نانولوله در موقعیت درونی قوی¬تر از موقعیت بیرونی است. قطر نانولوله¬ها بر انرژی برهمکنش بین نانولوله¬ها و دارو تأثیر داشت. قوی¬ترین برهمکنش ایبروتینیب مربوط به موقعیت درونی نانولوله (9, 9) با قطر 20/12 آنگسترم بود. همچنین مشاهده شد که قدرت برهمکنش¬ها بین نانولوله¬ها و دارو در موقعیت درونی با افزایش قطر نانولوله¬ها کاهش می¬یابد، اما قدرت برهمکنش¬ها بین نانولوله¬ها و دارو در موقعیت بیرونی با افزایش قطر نانولوله-ها تغییر چندانی نمی¬کند. برهمکنش قوی داروی جذب شده برروی سطح بیرونی نانولوله¬ها با ملکول¬های آب سبب بهبود حلالیت نانولوله¬ها می¬شود.

داروی ضدسرطان، ایبروتینیب، جذب، نانولوله¬های تک دیواره نیترید بور

شهره رحیمی

Enhanced D-HPG Synthesis Using Surface-Displayed Enzymes in E. coli

D-p-Hydroxyphenylglycine (D-HPG) is an essential building block for the synthesis of semisynthetic antibiotics, such as amoxicillin and cefadroxil. Traditionally, D-HPG is produced through chemical synthesis, which involves harsh reaction conditions, high energy consumption, and generates significant environmental waste . While enzymatic production offers a greener alternative, conventional approaches require the purification of the two key enzymes involved, D-hydantoinase (D-Hase) and D-carbamoylase (D-Case), before use. This purification step is labor-intensive, costly, and time-consuming, limiting the practicality of enzymatic methods. The surface display system, which anchors enzymes directly to the surface of the cell, addresses this limitation by bypassing the need for enzyme purification. In this study, we employed a surface display system on E. coli BL21(DE3) to produce D-HPG efficiently. D-Hase hydrolyzes hydantoin derivatives to N-carbamoyl-D-amino acids, which are further converted to D-amino acids by D-Case. We constructed recombinant E. coli BL21(DE3) strains with surface-displayed D-Hase and D-Case by designing fusion constructs for efficient enzyme localization. Expression conditions were optimized to enhance enzyme activity. Semi-quantitative enzymatic activity analysis using Ehrlich’s reagent confirmed the functionality of the surface-displayed enzymes. D-HPG production was analyzed using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). Quantitative HPLC measurements demonstrated a high production yield of approximately 95./.. This method offers significant advantages over traditional approaches, including mild reaction conditions, reduced environmental impact, and cost-effectiveness. In conclusion, this study highlights the successful application of a surface display system on E. coli for whole-cell biocatalysis of D-HPG. This innovative method provides a sustainable and efficient alternative to traditional chemical synthesis, offering great potential for industrial-scale production of D-HPG.

Bacterial surface display, D-p-hydroxyphenylglycine, D-hydantoinase: D decarbamoylase

مهسا تیرمومنین

Investigating the expression of recombinant protein (survivin) in BL21 expressing bacteria in the presence of 2 inducers and comparing the expression of 2 bacterial strains from Escherichia coli BL21 and C41

Mahsa Tirmomenin, Farangis Ataei*, Saman Hosseinkhani Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran Ataei_f@modares.ac.ir ABSTRACT One of the precise methods for producing recombinant proteins is by expressing bacteria. In the last decade, producing these types of proteins has made significant progress in treating many diseases as clinical applications. So far, many proteins have been expressed due to the rapid progress in genetic engineering technology. At present, various hosts, such as mammals, insects, yeast, etc., are used for protein production. However, the gram-negative bacteria Escherichia coli is known due to factors such as having an easy and cheap culture medium, short life cycle, and rapid growth and genetic expression. Furthermore, easy manipulation is known as a suitable host for recombinant protein production. In addition, it is used as the most widespread host for producing heterologous proteins. On the other hand, the main problem of this expression system is the production of non-functional proteins in the form of inclusion bodies, which, unlike mammals, do not have organizations to achieve folding and post-translational motifs. As a result, to solve this problem, scientists often use methods such as changing the vector / changing the parameters of the culture medium from the recombinant host strain / changing the host, etc., to express and produce proteins at high levels. This research is of utmost importance as it contributes to optimizing our parameters. Our study focuses explicitly on survivin, the smallest protein member of the apoptosis inhibitor family. Survivin has been found in both the cytosol and mitochondria, which is why it is called a nuclear export signal, and it is also known as a tumor marker. Its expression is enormously increased in most malignant and benign tumors, but they are found in mature and differentiated cells other than embryonic and undifferentiated tissues. Our study investigates the expression of recombinant protein (survivin) in BL21-expressing bacteria. We are particularly interested in the presence of 2 inducers and comparing the expression of 2 bacterial strains from Escherichia coli BL21 and C41. This comparison is crucial to our research and provides valuable insights into survivin expression. Method: The Pet 28E vector containing the wild-type survivin gene was transferred to Escherichia coli BL21 expression. The expression of the recombinant protein was induced with the inducers of the final concentration of 0.5 mM IPTG and 4 mM lactose and then at different times and temperatures that were contained the temperatures of 37, 30, 22, and 18 °:C, respectively, in a shaker incubator. Their expression levels were checked by 17.5./. SDS PAGE gel. Finally, its expression was compared in 2 different sides of The Escherichia coli family, i.e., BL21 and C41, which was done before, were compared, reported, and investigated. Results: Under all conditions, BL21-expressing bacteria express serovar protein in a significant amount of soluble form. Also, the expression of recombinant protein in the presence of an IPTG inducer was greater than that of lactose in the insoluble sediment residues. Also, the results prove that the expression in C41 bacteria at 30 degrees Celsius is much less than in BL21 bacteria, but more protein is observed in the form of soluble in soup.

Keywords: Survivin, Expression, BL21&:C41 Escherichia coli bacteria, IPTG, Lactose.

فاطمه ایزدپناه, Ahmad Homaei

Cloning, expression, and characterization of a novel marine L-asparaginase from Pseudomonas aeruginosa HR03

The present study focused on the cloning, expression, and characterization of marine L-asparaginase of Pseudomonas aeruginosa HR03 isolated from fish intestine (L.klunzingeri). Marine Pseudomonas aeruginosa HR03 was used for retrieving the l-asparaginase encoding gene (HR03Asnase) of size 936 bp. The gene was successfully cloned into the pET21a vector and expressed into Escherichia coli BL21 (DE3) for characterization of the protein. The recombinant HR03Asnase enzyme was purified by affinity chromatography using nickel affinity chromatography, and the enzymatic properties of HR03Asnase, including the effects of pH and temperature on HR03Asnase activity and kinetic parameters, were determined. The recombinant enzyme HR03Asnase showed the highest similarity to type I bacterial L-asparaginase from Pseudomonas aeruginosa. The three-dimensional (3D) modeling results indicate that HR03Asnase exists as a homotetramer. Also, The Molecular weight analysis using SDS-PAGE revealed  ~ 35 kDa. The HR03Asnase showed optimum pH and temperature of 8.0 and 40 °:C, respectively. The maximum activity of HR03Asnase was reduced by 50./. at 90 °:C after 10-min incubation: though, the enzyme preserved more than 20./. of its activity after 30-min incubation. This enzyme also preserved almost 50./. of its activity at pH 12 after 40-min incubation. The km and Vmax of the enzyme obtained with l-asparagine as substrate were 10.904 mM and 3.44 ×: 10−2 mM/min, respectively. The recombinant HR03Asnase of marine P. aeruginosa may also be explored as a potential agent in pharmaceutical and food applications. The assessment of pH and temperature stability of HR03Asnase showed that the enzyme has a wide range of activity, which is a suitable characteristic for its application in different industries. Overall, the results of the present study show that marine sources are promising biological reservoirs for enzymes to be used for biotechnological purposes, and marine thermostable HR03Asnase is likely a potential candidate for its future usage in the pharmaceutical and food industries.

Purification , Cloning, E. coli, Enzyme activity, Acrylamide

محمد حسین حقیر ابراهیم آبادی

Advancing Alzheimer`s disease research and drug discovery through the use of artificial intelligence

Artificial intelligence (AI) and machine learning (ML) have revolutionized Alzheimer`s disease (AD) research, driving advancements in both diagnosis and drug discovery. AI-based models, such as convolutional neural networks (CNNs) and support vector regression (SVR), have demonstrated high precision in differentiating between AD, mild cognitive impairment (MCI), and healthy individuals through neuroimaging techniques like MRI and PET. These technologies have enhanced the detection of early AD biomarkers, aiding in more accurate diagnosis. In drug discovery, AI-driven methods like machine learning and deep learning are transforming key processes such as virtual screening, de novo drug design, and pharmacokinetic/pharmacodynamic (PK/PD) modeling. AI plays a crucial role in predicting drug properties related to absorption, distribution, metabolism, excretion, and toxicity (ADMET), particularly in evaluating blood-brain barrier (BBB) penetration. Models like support vector machines (SVM) and light gradient boosting machine (LightGBM) have achieved high accuracy in predicting BBB permeability, accelerating the development of therapeutic candidates. Furthermore, AI integration in multiomic data analysis, utilizing public datasets like ADNI and NIAGADS, has enabled the identification of key genes and pathways involved in AD, which serve as potential drug targets. Advanced machine learning techniques, including logistic ridge regression, random forest, and support vector machines, have identified critical pathways like mitochondrial dysfunction and NF-kappa B signaling in AD pathogenesis. Overall, AI has been pivotal in AD research, improving early diagnosis and expediting drug discovery, offering promising avenues for future treatments and precision medicine.

artificial intelligence, Alzheimer`s disease, drug discovery, multi-omics analyses, machine learning

سید فرزاد حسینی, احمد امیری

سنتز، شناسایی و مطالعات برهم‌کنش یک لیگاند شیف-باز جدید با سرم آلبومین انسانی (HSA): بررسی طیف‌سنجی و داکینگ مولکولی

شیف‌بازها و کمپلکس‌های فلزی آنها از ترکیبات قابل توجهی در زمینه های پزشکی و دارویی هست. کاربردهای بیولوژیکی آنها به دلیل خواص ضد میکروبی، ضد قارچی، ضد باکتریایی، ضد ویروسی، تب بر، ضد دیابتی و ضد توموری می‌باشد. با توجه به پتانسیل آنها به عنوان عوامل ضد سرطان، درک نحوه‌ی برهم‌کنش شیف‌بازها با سرم آلبومین انسانی (HSA)، رایج ترین پروتئین حامل پلاسما، بسیار جالب است. این موضوع را می توان از طریق تکنیک‌های مختلف طیف‌سنجی و مدل‌سازی مولکولی کشف کرد. به دلیل ظرفیت سرم آلبومین انسانی در اتصال به طیف گسترده‌ای از متابولیت‌ها و داروها که می تواند عمیقاً بر ویژگی‌های فارماکوکینتیک این داروها تأثیر بگذارد، توجه صنعت داروسازی را به خود جلب کرده است. در این تحقیق، یک لیگاند شیف‌باز (L2) ‌ جدید سنتز با استفاده از طیف‌سنجی UV-Vis و FT-IR شناسایی شده است. برهم‌کنش بین این لیگاند و HSA از طریق طیف‌سنجی فلورسانس و ولتامتری چرخه‌ای بررسی شد. تمایل اتصال لیگاند به HSA تحت شرایطی که محیط فیزیولوژیکی را شبیه‌سازی می‌کند، با استفاده از هر دو روش اتصال مولکولی (MD) و تجربی ارزیابی شد. یافته‌ها نشان داد که تشکیل کمپلکس بین HSA و لیگاند منجر به خاموش شدن فلورسانس ذاتی پروتئین در 343 نانومتر شد، که نشان‌دهنده‌ی مکانیسم اتصال استاتیک است.

شیف‌باز، سرم آلبومین انسانی، پتانسیل ضد سرطان، ولتامتری چرخه‎‌ای، داکینگ مولکولی

کاوه کاوسی, کاوه کاوسی

The Power of Microbial Proteins in Clinical Diagnostics: A Metaproteomic Approach

Metaproteomics, the study of all proteins expressed by a microbial community, is revolutionizing clinical diagnostics by providing a deeper understanding of host-microbiome interactions. Microbial proteins serve as critical indicators of disease, offering insights into complex pathologies that traditional biomarkers often miss. This study explores the potential of gut microbiome metaproteomics for diagnosing pediatric Inflammatory Bowel Disease (IBD), specifically Crohn`s Disease (CD) and Ulcerative Colitis (UC). We demonstrate that microbial protein profiles provide superior diagnostic accuracy compared to conventional methods. By applying machine learning algorithms to metaproteomic data, we developed a diagnostic panel capable of distinguishing between CD and UC with high precision. This non-invasive approach offers a promising alternative for diagnosing IBD, particularly in children where current procedures can be challenging. Our findings highlight the broader significance of omics data, particularly microbiome metaproteome, in modern medicine. Metaproteomic analysis not only aids in accurate diagnosis but also paves the way for personalized medicine. By understanding the functional changes within the microbiome, clinicians can tailor treatments and improve patient outcomes. This study underscores the transformative power of metaproteomics in clinical settings, with potential applications extending beyond IBD to various complex diseases.

Metaproteomics, Complex Diseases, Diagnostic Biomarkers, Gut Microbiome, Machine Learning

آزاده حکمت, امیر حکمت, آزاده حکمت

Fibrillar proteins and their role in the removal of heavy metal contamination from water sources: A study of the β-Lactoglobulin-Lactic acid complex

Currently, water pollution caused by heavy metals is an important global phenomenon. Lead and cadmium are among the most important heavy elements that enter water sources through various ways such as industrial and agricultural effluents unsanitary burial places and urban and industrial water materials and cause serious harm to human health. Recently the use of economic absorbents has received much attention. This research aims to evaluate the beta-lactoglobulin (BLG)-lactic acid hybrid protein as a membrane filter in removing heavy metals such as lead and cadmium. Beta-lactoglobulin Protein fibers were prepared by incubation of the protein in pH 2 and lactic acid. Then the BLG-lactic-acid hybrid was studied by ultraviolet-visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). After performing dialysis, the absorption capacity of the hybrid was evaluated by atomic absorption spectroscopy (AAS) using standard solution samples of lead and cadmium heavy metals. The structure of the fibers was observed by SEM. UV-visible absorption and FTIR spectra showed the formation of a fiber-lactic acid hybrid. The results of mass spectrometry showed that the percentage of hybrid efficiency for lead and cadmium metal were 31./. and 25./., respectively. According to the results obtained from this research, the beta-lactoglobulin-lactic acid hybrid is a suitable substrate for the absorption of lead and cadmium heavy metals in polluted waters.

Beta-Lactoglobulin, Water refinery, Lead, Cadmium, Lactic acid, Membrane filter

شهره آریائی نژاد

Discovering Enzybiotics in Metagenomes: Innovative Enzymes as Sustainable Alternatives to Antibiotics

Abstract: The global rise in antibiotic resistance has necessitated the exploration of innovative and sustainable alternatives to traditional antibiotics. This study introduces ":enzybiotics,": enzymes derived from metagenomic datasets that target and degrade bacterial cell components such as DNA, polysaccharides, and proteins, as a promising solution. Enzybiotics disrupt bacterial growth and biofilm formation through various mechanisms, such as degradation of cell walls, disruption of DNA replication, and interference with essential metabolic processes. Leveraging metagenomics, the study of genetic material from environmental samples allows access to diverse microbial communities. These include those from extreme habitats and plant/animal microbiomes, which offer a source of novel enzymes with unique functionalities. Advanced bioinformatics pipelines and machine learning techniques enable the efficient mining of metagenomic data, prediction of enzymatic activities, and prioritization of high-potential candidates. Unlike conventional antibiotics, enzybiotics offer versatility and function independently or synergistically to prevent or degrade biofilms. This dual-action capability positions enzymes as robust biocatalysts for applications in food safety, healthcare, agriculture, and environmental sustainability. State-of-the-art biotechnological tools, including protein engineering, domain swapping, and high-throughput DNA sequencing, have enhanced the discovery and optimization of these enzymes. This research not only highlights the immense potential of enzybiotics to revolutionize biotechnological processes but also underscores their critical role in addressing pressing global challenges, such as antibiotic resistance and microbial spoilage. This research demonstrates the potential of enzybiotics as sustainable alternatives to traditional antibiotics. By integrating metagenomics and advanced biotechnological tools, this study paves the way for novel solutions to combat antibiotic resistance and to promote environmental and human health.

metagenomic, enzybiotics, biotechnological tools, antibiotic resistance.

محمدرضا صادقیان

Construction and Characterization of Epidermal Growth Factor-Loaded Nanosystem for the skin topical application

Skin is the largest organ in the body that plays a role in the body`s immunity, sensation, and protection. Skin can age and damage for a variety of reasons, and there are several ways to slow it down or prevent it. Different cosmetics are used for this purpose in cosmetics. Human growth factors are one of the most effective uses for this purpose. These factors have low absorption through the skin due to their high molecular weight. With the help of nanoparticles, effective drug delivery systems can be designed to increase the absorption and effectiveness of these growth factors. Liposomes are one of the most widely used materials in the healthcare industry and have shown significant benefits. Flexible liposomes that have a surface activator (Edge Activator) in their structure can perform dermal drug delivery in large quantities and with good biocompatibility. The human epidermal growth factor, which is used as an effective factor in skin rejuvenation, was recombinantly expressed in E. coli and then purified by affinity chromatography. Flexible liposomes were synthesized as growth factor nanocarriers by the thin-layer extrusion method. The lipid composition used in this project was egg yolk phosphatidylcholine (EPC) and tween 80 (TW80) with a ratio of 1:31 (EPC: TW80). Synthesized particle size 130 nm, dispersion index less than 0.2, zeta potential -25 mV, spherical morphology, trapping efficiency 72.12./., loading capacity 1.47./., controlled release of the 7-day drug, and good stability in 10 days were reported for these particles. Liposomal nanocarriers containing recombinant human epidermal growth factor were evaluated for function on fibroblast cells and were completely filled in the scratch test after 72 hours. In the MTT test, no toxicity was observed for liposomes in the studied concentrations of liposomes, and liposomes containing growth factor showed a positive effect on the effect of growth factor.

growth factor- epidermal growth factor – nanosystems – liposome – drug delivery

حامد نوید, فرناز جعفرپور

Exploring Indole Ligand Interactions with Human Serum Albumin (HSA) via Spectroscopy and Molecular Docking Techniques

Indoles represent one of the most promising heterocyclic structures, noted for their distinctive properties attributed to the presence of an electron-rich pyrrole component. Heteroannulated indole derivatives have garnered significant interest due to their diverse biological and pharmacological activities [1,2]. This study reports the synthesis and characterization of an Indole ligand using UV–Vis and FT-IR spectroscopy. The interaction between this ligand and human serum albumin (HSA) was explored through fluorescence spectroscopy and cyclic voltammetry. Human serum albumin (HSA) has attracted considerable interest from the pharmaceutical industry owing to its capacity to bind a broad spectrum of metabolites and pharmaceuticals, which can significantly impact the pharmacokinetic profiles of these compounds [3]. Molecular docking and experimental techniques were employed to evaluate the binding affinity of the ligand to HSA under physiologically relevant conditions. The results demonstrated that the formation of a complex between HSA and the ligand resulted in the quenching of the protein`s native fluorescence at 358 nm, which can be attributed to a static binding mechanism.

Indole, HSA, Anticancer, Interaction, Molecular docking.

اباذر ابوذرخانی فرد, زهره زهرایی

A review of AlphaFold, a method for protein structure prediction

Abstract Introduction: Proteins are regarded as one of the most important biological macromolecules. Identifying their structure will help researchers understand protein’s function and practical applications. In the past, experimental and classical methods such as X-ray crystallography or NMR were used, with advantages and disadvantages. Today, new methods based on artificial intelligence have made a big change in predicting the structure of proteins, an example of which is the method called AlphaFold. Methodology: Articles related to the present topic were reviewed from databases such as Google Scholar and Pubmed from 2019 to 2024. Results: AlphaFold, a method for predicting the structure of proteins in three versions has been introduced to the world. This method, based on deep learning based on convolutional neural networks, processes input data that are often collected from PDB and accurately and quickly predicts the structure of proteins. This method can be widely used in medical, biological, education, industrial and production cases. Discussion and conclusion: Different methods are used in protein structure prediction. New methods that are based on artificial intelligence have attracted the attention of researchers because they have high accuracy and speed. However in order to gain confidence, they need to be measured.

Protein, Protein structure prediction, Artificial intelligence, Deep neural network, AlphaFold

سیده فاطمه ابوترابی, حسن فریدنوری

Development of an Electrochemical Tyrosinase Biosensor Using Sulfonic Acid-Modified Magnetic Nanoparticles for Dopamine and Phenolic Compound Detection

An electrochemical biosensor based on tyrosinase (Tyr) was developed for the detection of dopamine and phenolic compounds across medical, environmental, and industrial applications. The biosensor utilized sulfonic acid (SO₃H)-modified magnetic nanoparticles (MNPs) prepared via a hydrothermal synthesis method followed by in-situ surface functionalization. The MNPs enhanced the electrical conductivity and enzyme adsorption on the electrode surface, significantly improving sensor performance. A magnetic carbon paste electrode was fabricated with an optimal graphite-to-paraffin weight ratio. Subsequently, MNP suspension was deposited on the electrode surface, followed by the addition of 15 µ:L of 4 mg/mL Tyr solution. The biosensor was allowed to stabilize for 24 hours before undergoing electrochemical characterization. Cyclic voltammetry (CV) revealed an apparent electron transfer rate constant (kₛ) of 0.008 s⁻¹: and a formal potential (E˚ʹ) of 0.21 V. Differential pulse voltammetry (DPV) demonstrated the biosensor`s performance for catecholamine detection. For cafeic acid, the limit of detection (LOD) was 45.4 µ:M within a linear range of 1–74 µ:M, with a sensitivity of 1.68 µ:A·:µ:M⁻¹:·:cm⁻²: and a Michaelis-Menten constant (Km) of 30 µ:M. For catechol, the LOD was 68 µ:M in a linear range of 1–107 µ:M, with a sensitivity of 1.8 µ:A·:µ:M⁻¹:·:cm⁻²: and Km of 55.3 µ:M. For L-DOPA, the LOD was 50.6 µ:M in a linear range of 1–137 µ:M, with a sensitivity of 0.9 µ:A·:µ:M⁻¹:·:cm⁻²: and Km of 68.92 µ:M. The results suggest that incorporating cross-linking agents such as glutaraldehyde to covalently stabilize the enzyme on the nanoparticles could further enhance the biosensor`s kinetic and electrochemical properties, offering improved reliability and sensitivity.

Magnetic nanoparticles, sulfonic acid modification, polyphenols, L-DOPA, and carbon paste electrode

اوین آسیابانی

Antiglycation Potential of Oregano (Origanum vulgare) Leaf Extract: A Natural Approach to Combat Diabetes-Related Complications

Diabetes mellitus is a chronic disorder of glucose metabolism with serious clinical consequences. The multi-system complications of diabetes include microvascular and macrovascular endpoints. Persistent hyperglycemic state in type 2 diabetes mellitus leads to the initiation and progression of non-enzymatic glycation reaction with proteins, lipids, and nucleic acids, leading to the formation of advanced glycation end-products (AGEs). These compounds are associated with various chronic conditions, including cardiovascular and neurological diseases, as well as aging. The inhibition of glycation has become a significant focus in biomedical research, with natural compounds from medicinal plants showing great potential as therapeutic agents. Oregano (Origanum vulgare), a well-known medicinal plant with anti-inflammatory, antimicrobial, and antioxidant properties. This study aimed to evaluate the inhibitory effects of oregano leaf extract on the production of fluorescent end-products in glycated human serum albumin (HSA). HSA was incubated with a high glucose concentration in the presence or absence of oregano leaf extract for 35 days. The obtained results from spectroscopic techniques indicated that oregano extract significantly reduced the formation of AGEs. Furthermore, circular dichroism (CD) analysis demonstrated that the extract modulates the structural alterations of glycated HSA. These findings highlight the critical role of plant-based interventions in mitigating complications associated with diabetes and glycation.

Advanced glycation end-products (AGEs), Diabetes, Glycation, Herbal plants, Human serum albumin (HSA), Oregano.

فاطمه گشتاسبی

Novel approach for the High-yield expression and Purification of Bio- Active LL-37: Implications for Biomedical Research

LL-37, the sole human cathelicidin, is a multifunctional antimicrobial peptide with potential applications in wound healing due to its chemotactic, endotoxin-neutralizing, and angiogenic properties. Previous recombinant production approaches have typically involved the addition of N-terminal fusion proteins to enhance peptide expression, requiring complex purification processes that diminish yield and increase costs. This study presents the first successful recombinant production of LL-37 in its active form without N-terminal fusions. The LL-37 gene sequence was cloned with a G4S linker and hydroxyapatite binding domain into the pET21a(+) vector and expressed in E. coli Shuffle. The recombinant peptide was purified in a single step via affinity chromatography, achieving a yield of 1.02 mg of LL-37 per liter of culture. To evaluate any effects of C-terminal fused sequences on LL-37 activity, a series of assays were conducted. Antimicrobial assays demonstrated reduced activity of the recombinant LL-37 against E. coli and S. aureus compared to its native counterpart. Enzyme-linked immunosorbent assay (ELISA) revealed that the recombinant peptide binds to lipopolysaccharides (LPS) in a dose-dependent manner (p < 0.05), confirming its endotoxin-neutralizing capabilities. Wound healing potential was assessed using cell scratch assays on human umbilical vein endothelial cells (HuVEC) and human dermal fibroblasts (HDF), showing that recombinant LL-37 (100 ng/mL) significantly enhanced cell migration, achieving an 86./. wound repair rate in contrast to 14./. in controls after 12 hours (p < 0.05). Additionally, a cell-based ELISA confirmed the binding of recombinant LL-37 to endothelial cell surface receptors in a dose-dependent manner. Importantly, the recombinant LL-37 displayed no cytotoxic effects on HuVEC and fibroblast cells, even at concentrations up to 25 µg/mL. These findings suggest that the recombinant LL-37 can be produced efficiently without fusion tags, retaining its biological activities, and have significant implications for its use in therapeutic applications for wound healing.

LL-37 peptide, antimicrobial peptide, wound healing, cost benefit expression and purification

روشنک امیریان, حسین درخشان خواه, ژیلا ایزدی

Targeted Protein Modification: A Revolutionary Approach in Neurodegenerative Disease Therapy

TPM heralds a paradigm shift in the definition of therapeutic strategies against complex diseases, such as neurodegenerative disorders, particularly Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. Unlike conventional small-molecule inhibitors, TPM uses bifunctional agents to control protein activity or degradation pathways against previously undruggable targets. Novel approaches, including proteolysis-targeting chimeras and autophagy-tethering compounds, represent new modalities for reducing the levels of pathological proteins, such as misfolded or aggregated alpha-synuclein and tau, which are believed to play a central role in the pathogenesis of these disorders. Neurodegenerative diseases are characterized by toxic protein aggregates disrupting cellular homeostasis and contributing to synaptic and neuronal loss(1). TPM strategies exploit either the UPS or autophagy-lysosome pathway for aggregate degradation and, thus, afford a particular and effective therapeutic intervention. Recent advances have emphasized the potential of bifunctional molecules that selectively bind pathological proteins, thereby tethering them to the cellular degradation machinery and stimulating their removal with minimal impact on normal proteins. Such specificity minimizes off-target effects—a critical limitation of conventional therapies. This review represents recent progress in TPM technologies, highlighting the design of small-molecule ligands capable of inducing protein degradation and stabilization. We review various applications related to the modulation of neurotoxic protein aggregates, attenuation of oxidative stress, and restoration of cellular homeostasis pertaining to neurodegenerative diseases. Modern tools of TPM, integrating ATTECs targeting autophagy pathways with PROTACs inducing ubiquitination of pathogenic proteins, highlight a strong potential for halting disease progression and promoting neuronal function and survival recovery. These results point to the role of TPM as a transformative intervention in the field of neurodegenerative disease treatment, filling critical gaps in current therapies. The development of this area opens unparalleled opportunities for drug discovery and points toward the possibility of personalized and disease-modifying interventions, marking a significant leap in combating such destructive disorders(2).

targeted protein modification, neurodegenerative diseases, autophagy, protein aggregation, therapeutic innovation

مصطفی شوریان

Using Gold Nanoparticles for Combination Therapy of Gemcitabine

The most of chemo drugs have short half-life. The inadequate sustained release can lead to severe side effects, including myelosuppression and nephrotoxicity. In our studies were used the properties of gold nanoparticles (AuNPs). For example, one of them presents a novel nano-drug delivery system utilizing AuNPs optimized with ascorbyl palmitate (AsP) to enhance gemcitabine hydrochloride (GEM) stability and therapeutic efficacy. AuNPs were modified using a single-phase emulsification technique to create a nanoemulsion coated with a hydrophobic AsP layer, resulting in improved tumor targeting through the enhanced permeability and retention (EPR) effect. Besides that, in another study AuNPs was synthesized by PEG. The modified AuNPs was immobilized by GEM and Paclitaxel (PAX). The formulations demonstrated a sustained release profile, and enhanced cytotoxicity in the 4T1 and MIA-PACA-2/ PACA-1 cell lines, respectively. Significantly outperforming free GEM/PAX and modified Au-GEM/Au-PEG-GEM/PAX formulations. Notably, for AuNPs-GEM/AsP and Au-PEG-GEM/PAX, those exhibited several months of accelerated stability, attributed to amide bond formation in the functionalized AuNP matrix. The study highlights the synergistic effects of AsP or PAX in enhancing the therapeutic efficacy of Au-GEM-based formulations, supporting its role as a key component in combination therapy. These researches lay the foundations for future developments AuNPs devices that combine chemo drugs for therapeutic and diagnostic applications in nanomedicine.

Gold Nanoparticles, Combination Therapy, Gemcitabine, Paclitaxel

ستاره فرهمند عراقی, دکتر ملیحه السادات عطری (نویسنده مسئول)

بررسی بیوانفورماتیکی تشکیل کمپلکس الئوروپین زیتون و چند پروتئین گیاهی به منظور غنی سازی مواد خوراکی

معمولاً استفاده مستقیم از ترکیبات فنلی طبیعی در صنایع غذایی به دلیل ناپایداری و طعم ناخوشایندشان محدود است. اصلی&#172:ترین ترکیب فنلی موجود در برگ زیتون، اولئوروپین است که اثرات آنتی&#172:اکسیدانی و ضدسرطانی دارد. کپسوله&#172:سازی مواد زیست&#172:فعال می&#172:تواند از آن&#172:هادر حین فرآوری محافظت کند و یا سبب پوشاندن عطر و طعم نامطلوب آن&#172:ها شود. در میان بیوپلیمرهای طبیعی، پروتئین&#172:های گیاهی، مزایای زیادی دارند و می&#172:توانند برای کاربردهای مختلف از جمله کپسوله&#172:سازی در صنایع غذایی استفاده شوند. از آ&#172:ن جایی که گندم، سویا و نخود منابع مهم پروتئین گیاهی در غذای انسان هستند؛ سه پروتئین لگومین نخود، گلیسینین سویا و آگلوتینین گندم جهت بررسی تشکیل کمپلکس با الئوروپین انتخاب شدند. در این مطالعه ابتدا الئوروپین از نظر خصوصیات بیوفیزیکوشیمیایی توسط سرور SwissADME بررسی شد. سپس ساختار سه بعدی پروتئین&#172:ها از بانک اطلاعاتی پروتئین دانلود شد و پس از آماده&#172:سازی، جایگاه&#172:های احتمالی اتصال اولئوروپین به پروتئین&#172:ها توسط داکینگ&#172:مولکولی با استفاده از نرم&#172:افزار اتوداک 6.2.4 مورد بررسی قرار گرفت. نتایج نشان داد که اولئوروپین می&#172:تواند توسط برهمکنش&#172:های هیدروژنی و آبگریز به لگومین، گلیسینین و آگلوتینین پیوند شود. لگومین چهار جایگاه اتصال برای الئوروپین نشان داد که انرژی آزاد اتصال بر روی بهترین جایگاه 92/4- کیلوکالری بر مول به دست آمد. الئوروپین بر روی گلیسینین پنج و بر روی آگلوتینین سه جایگاه اتصال دارد که انرژی آزاد اتصال بهترین جایگاه به ترتیب 14/4- و ۵6/۵- کیلوکالری بر مول بدست آمد. بنظر می&#172:رسد از بین این سه پروتئین آگلوتینین کاندید بهتری برای تشکیل کمپلکس با اولئوروپین است و با پیوند این پروتئین گیاهی به اولئوروپین می&#172:توان کمپلکس پایداری ایجاد کرد و از این کمپلکس به منظور غنی&#172:سازی موادغذایی استفاده کرد.

مواد زیست&#172:فعال، داکینگ مولکولی، پروتئین&#172:های گیاهی، کپسوله&#172:سازی، اولئوروپین

محبوبه افرند

Harnessing the Power of Amino-graphene and Chitosan: Novel Nanohybrid Supports for Enzyme Applications

Composite materials and hybrid organic-inorganic systems have surfaced as advantageous platforms for the immobilization of industrial enzymes. The hybrid supports utilize the beneficial characteristics inherent in both inorganic nanoparticles and biopolymeric materials. Nanomaterials are particularly well-suited for use as enzyme supports owing to their extensive surface area. Graphene, characterized by its two-dimensional arrangement of sp² hybridized carbon atoms, exhibits distinctive properties, such as exceptional mechanical, electrical, and chemical attributes, while also being cost-effective. Nevertheless, numerous intriguing properties may be augmented via functionalization. The incorporation of bioactive compounds, including amines, onto materials offers numerous benefits. These advantages encompass enhanced stability of the active compound, improved dispersibility, increased surface area, protection from specific environmental factors, and the potential for controlled release, among others. Chitosan, the most abundant natural biopolymer, is derived from chitin, a major component of the exoskeletons of crustaceans, such as crab and shrimp shells. Chitosan is associated with excellent biological, physicochemical, antimicrobial, and nontoxic properties, making it a superior eco-friendly material. In this study, we synthesized novel nanohybrid supports by combining amino-functionalized graphene nanoplatelets and chitosan nanoparticles. AG was dispersed in water and mixed with a CS solution, and then the mixture was dripped into NaOH to form AG/CS beads. These beads were cross-linked with glutaraldehyde and washed to obtain stable AG/CS nanohybrids. Characterization with FTIR, XRD, DLS, and FE-SEM showed nanohybrid production. The synthesized AG/CS nanohybrids exhibit considerable promise as adaptable platforms for enzyme immobilization, integrating the advantageous characteristics of both inorganic and organic nanomaterials. This study demonstrates the potential for developing enzyme-based biotechnologies through the use of logically constructed inorganic-bio hybrid systems. On these nanohybrid supports, more research is necessary to fully understand enzyme loading, activity, and operational stability.

Amino-graphene, Chitosan, Nanohybrids, Enzyme Immobilization

فاطمه میری

The Inhibitory Effect of Synthesized Porphyrins on Lysozyme Protein Aggregation

Amyloid aggregation is recognized as a key pathological feature in many neurodegenerative diseases, including Alzheimer`s disease, Parkinson`s disease, and Huntington`s disease. These conditions are characterized by the gradual loss of neurons and glial cells in the brain and spinal cord, leading to significant neurological impairments. The aggregation of specific proteins in these diseases results in neuronal toxicity and causes serious damage to the functionality of nerve cells. Amyloid beta (Aβ) protein is one of the most important proteins associated with Alzheimer`s disease, where the aggregation of amyloid beta peptides leads to neuronal toxicity and serious damage to the functionality of nerve cells in the brain due to an imbalance, disrupting neuronal function. Additionally, the tau protein, which aggregates inside neurons, appears in the form of neurofibrillary tangles and plays a significant role in disease progression. Targeting the aggregation of proteins and peptides presents a promising avenue for therapeutic intervention in neurodegenerative diseases. Small molecules and compounds, such as tetrapyrroles, have been identified as potential inhibitors of amyloid formation. These compounds interact with the aromatic residues of proteins and peptides, thereby stabilizing non-toxic oligomeric forms and preventing the formation of harmful aggregates. The aggregation of lysozyme in the presence and absence of MCTPP and TCPP was initially investigated using thioflavin T fluorescence assays. The results indicated that various concentrations of these compounds could inhibit lysozyme fibrillation by approximately 89./. through an increase in the lag phase and a decrease in emission intensity. These findings demonstrate that MCTPP and TCPP effectively influence lysozyme fibrillation, showing a dose-dependent effect of the porphyrin compounds. To confirm the results obtained from thioflavin T fluorescence, Congo red assays, and atomic force microscopy imaging were also conducted, which verified the presence of fibrils in both the presence and absence of porphyrin compounds. The results obtained from UV spectroscopy confirmed the structure of the porphyrin compounds and lysozyme protein, as well as potential interactions between MCTPP, TCPP, and lysozyme protein.

Degenerative diseases of the nervous system, Lysozyme, Porphyrin, Porphyrin derivatives, Amyloid aggregation

سیده سارا قرشی

Investigation of the effect of melatonin on the aggregation of proteins

Alzheimer`s disease is one of the most common degenerative diseases of the nervous system that disrupts the cognitive and behavioral abilities of its sufferers. Alzheimer`s has pathological symptoms including extracellular senile plaques mainly consist of aggregated amyloid beta fibrils, intracellular neurofibrillary tangles consisting of hyperphosphorylated tau protein, oxidative stress, and neuroinflammation. In most people with Alzheimer`s, circadian rhythm disorders that are the basis of sleep-wake cycle disorders have also been seen, and there is a two-way relationship between Alzheimer`s and sleep disorders. Melatonin is a hormone that regulates the sleep-wake cycle, circadian rhythm, and sleep homeostasis, it also acts as a scavenger of free radicals and an antioxidant and causes the differentiation and proliferation of nerve cells. The level of melatonin gradually decreases with age, and elderly people secrete the least amount of melatonin, which is considered as an important factor in the development of Alzheimer`s. Since melatonin has anti-aggregation properties, in this study, using fluorescence and absorption spectrometry methods, fluorescence imaging, and atomic force microscopy, investigating possible interactions with the molecular docking method, and its comparative effect on the aggregation of proteins was investigated. Also, the antioxidant effects of melatonin on the treated SH-SY5Y cell line with protein aggregated were studied using cell viability, reactive oxygen species, and mitochondrial membrane potential. The results showed that melatonin, with its anti-amyloid properties, can reduce the formation of protein aggregates in proteins and considering the docking findings, it seems that there is a molecular interaction between melatonin and the above proteins. Also, the results of this research showed that due to its antioxidant properties, melatonin was able to increase survival, reduce reactive oxygen species, and reduce mitochondrial membrane damage in cells treated with aggregates.

Alzheimer`s disease, protein aggregation, melatonin, sleep

پویا علیمحمدی

Statistical Investigation on the Occurrence of Liquid-Liquid Phase Separation in Proteins Involved in Neurodegenerative Proteins

Neurodegenerative diseases are among the most prevalent health issues worldwide. Among them, Alzheimer’s is known to rank as the 6th leading cause of death and exhibits heterogeneous mechanisms. According to research, neurodegenerative diseases are more common among older people. Protein aggregation is a common feature among them, forming in the brains of affected patients. Liquid-liquid phase separation is an important pathway that plays a crucial role in the formation of membraneless organelles and fibrils. Molecular studies suggest that non-covalent interactions are crucial for the creation of these organelles. The amino acid sequence or content can shed light on the interactions leading to the formation of membraneless organelles. Therefore, bioinformatics methods (e.g., data mining) can reveal amino acid content and sequence-mediated phase separation in neurodegenerative diseases. In this work, we have investigated the effects of occurrence of specific amino acids (content) or specific nearest neighbor (sequence) in neurodegenerative peptides and proteins. We have analyzed sequence-based statistics investigating the occurrence of LLPS in the LLPSv2 database, and on neurodegenerative peptides and proteins. The calculations were based on statistical methodologie (e.g., Paired T-test). Our results indicated that specific AACs (amino acid compositions) such as A, L, F, and Y, and PCs (peptide compositions) such as KK, VG, GV, and YY were important in the occurrence of LLPS. We concluded that hydrophobic, hydrophilic, and electrostatic interactions were the most important physicochemical properties and were frequently involved in the interactions that play crucial roles in the occurrence of LLPS.

Bioinformatics, phase separation, aggregation, amino acid content and sequence

سحر میرصالحی

Investigation of the interaction of a new platinum complex with DNA

Platinum-based compounds such as cisplatin and carboplatin which can stop the growth of cancer cells and are approved by the FDA, have limited use due to the side effects and drug resistance. In order to develop this class of platinum drugs, cyclometalated compounds have been designed and synthesized. They are stable under physiological conditions and reach the target cells. The incorporation of phosphine ligands increases the lipophilicity of cycloplatinum complexes and their high cytotoxicity, which is more active than cisplatin against a variety of cancer cell lines. Replacing fluorine with phosphine ligands in the synthesis of the new complex is an excellent choice to modify the electronic and hydrophobic properties. In this study, the interaction of a new platinum complex, [Pt(dfppy)Cl (Pph2 Me)] (complex 1) with calf thymus DNA was investigated using fluorescence spectroscopy and ultraviolet-visible absorption spectroscopy. To reveal the mode of interaction between complex 1 and DNA, the competitive experiments have been carried out using several markers including ethidium bromide, thiazole orange, DAPI, methylene blue and Hoechst 33258. The main mode of the interaction of this complex with DNA was intercalation according to the competitive experiments. The fluorescence quenching data at different temperatures have been analyzed to estimate the values of the binding parameters including binding constant, Stern-Volmer constant, thermodynamic functions, and the number of binding sites for the interaction of the complex 1 with DNA. According to the values of thermodynamic functions, it was inferred that the effective forces in the interaction of this new cylcloplatinated compound with DNA are van der Waals type or hydrogen bond formation.

Platinum complexes, Cycloplatinated Compounds, DNA binding, ligand-binding.

شیوا اکبری بیرگانی

فراتر از آپوپتوز: نقش های متنوع کاسپاز-9 در تعیین سرنوشت سلول های سرطانی

آپوپتوز فرآیندی بسیار پیچیده و تنظیم شده است که شامل مسیرهای سیگنالینگ و مکانیسم های مولکولی متعدد است. چندین مرحله و اجزای کلیدی، از جمله فعال سازی کاسپازها، خانواده ای از پروتئازها، نقش مهمی در پیشبرد آپوپتوز دارند. فعال شدن کاسپازها مجموعه‌ای از رویدادها را آغاز می‌کند که منجر به مرگ سلولی می‌شود. مطالعات اخیرنشان داده اند، کاسپاز-9، یک کاسپاز آغازگر در مسیر آپوپتوز ذاتی، نقش‌های غیر آپوپتوزی را در فرآیندهای سلولی مانند تمایز و مهاجرت بازی می‌کند. مطالعه حاضر، به بررسی عملکردهای غیر آپوپتوتیک کاسپاز-9 و سهم احتمالی آن در مکانیسم‌های مولکولی در سلول‌های سرطانی میپردازد. فعال‌سازی کاسپاز-9 و اثرات آن در رده‌های سلولی گلیوبلاستوما، نوروبلاستوما، لوسمی، و سرطان پستان و ارگانوئیدهای مربوطه آن‌ها مورد بررسی قرار گرفته و تأثیر آن بر ویژگی های مولکولی و پاتولوژیک نیز ارزیابی شده است. این مطالعه اثرات متنوعی از فعال‌سازی کاسپاز-9 را در رده‌های سلولی سرطانی و ارگانوئیدهای مختلف نشان میدهد. به گونه ای که در سرطان پستان نوع لومینال، باعث آپوپتوز شده، در حالی که در انواع سلول های مقاوم به تاموکسیفن منجر به مرگ نمیشود. در سرطان پستان سه گانه منفی، خواص ضد متاستاتیکی از خود نشان میدهد. در گلیوبلاستوما، پیری سلولی را القا کرده و در سلول‌های لوکمیک و نوروبلاستوما، علائم تمایز را ارتقا میدهد. جالب توجه است، همه مدل‌های ارگانوئیدی ویژگی‌های پاتولوژیک مرتبط با تغییرات اپیتلیال مزانشیمی (EMT) را بصورت کاهش یافته نشان دادند. علاوه بر این، مطالعه داده کاوی ما بر روی داده‌های ترنسکریپتومی سرطان پستان، ارتباط بین کاهش بیان کاسپاز-9 و ویژگی‌های تهاجمی سرطان پستان را نشان داد. یافته های این مطالعه در مجموع، نشان می دهند که فعال کردن کاسپاز 9 می تواند سرنوشت سلولی را در سرطان های مختلف تغییر دهد، ضمن اینکه پتانسیل فعال سازی هدفمند کاسپاز-9 را به عنوان یک استراتژی درمانی جدید برای درمان سرطان، به ویژه برای سرطان های تهاجمی با ویژگی های EMT را برجسته می کند. البته همچنان مطالعات بیشتری برای درک مکانیسم‌ عملکرد غیر آپوپتوز کاسپاز-9 در سلول‌های سرطانی و ارزیابی پتانسیل درمانی این رویکرد مورد نیاز است.

کاسپاز-9, سرنوشت سلولی، آپوپتوز، پیری، تمایز، سلول سرطانی، مدلهای ارگانوئیدی

شیوا اکبری بیرگانی, فائزه ریاحی, علی صالح زاده یزدی

p53: A Molecular Switch Determining Cell Fate Between Apoptosis and Differentiation

Apoptosis and differentiation are two critical cellular processes that share common molecular features, including, cytochrome c release and caspase activation. Despite these shared characteristics, the factors determining whether a cell undergoes apoptosis or differentiation remain poorly understood. In this study, we sought to identify the key genes and pathways that regulate cell fate decisions between these two processes. We first curated gene sets related to apoptosis and differentiation from the GSEA database, narrowing our focus to genes with high occurrence frequencies within each set. This led to the creation of refined gene sets that were analyzed using Enrichr. To validate these gene sets, we utilized 80 microarray samples from the GEO database and performed enrichment analysis with hallmark gene sets for apoptosis and differentiation. Remarkably, over 70./. correlation was observed between our refined gene sets and hallmark gene sets, with substantial overlap in gene expression changes between apoptosis and differentiation samples. Further analysis revealed 16 common genes between the apoptosis and differentiation networks, with p53 exhibiting the highest betweenness centrality. Apoptosis and differentiation protein-protein interaction (PPI) networks were constructed using Cytoscape and then merged. Network analysis identified p53 as the most critical node in the final PPI network. To explore the functional role of p53, we analyzed its activity during differentiation using ISMARA and GEO datasets. We observed transient p53 activity during the differentiation of mesenchymal stem cells, consistent with reports that p53 dynamic regulates cell fate. Our findings highlight the pivotal role of p53 in balancing apoptosis and differentiation, providing insights into its function as a critical determinant of cell fate. Further research is needed to elucidate the precise mechanism by which p53 and other key regulators control the balance between apoptosis and differentiation.

Apoptosis: Differentiation: Cell fate: Cell signaling: p53

شیوا اکبری بیرگانی, پریسا مقدم, علی صالح زاده یزدی, شیوا اکبری بیرگانی

TP53: A Key Regulator in the Decision Between Cellular Senescence and Apoptosis

Senescence and apoptosis are distinct cellular fates with interconnected regulatory mechanisms. While apoptosis results in rapid cell death, senescence is characterized by stable cell cycle arrest and a distinct secretory phenotype. Studies suggest that cells exposed to apoptotic stimuli can undergo senescence under certain conditions. This study aimed to identify critical regulators determining cell fate choice between senescence and apoptosis. We collected the curated gene sets from the GSEA and utilized STRING database to construct and analyze the protein-protein interaction (PPI) networks for apoptosis and senescence in cells. Functional enrichment analysis using Enrichr validated the identified networks, and then PPI network analysis using Cytoscape revealed TP53 as a protein with the highest degree of interactions and a pivotal regulator influencing cell fate. Our findings consistent with other scientific reports suggest that TP53 modulates cell cycle control mechanisms, thereby impacting the decision between senescence and apoptosis. However, further investigation is warranted to elucidate the precise role of TP53 and other regulators in this cellular fate choice.

Apoptosis - Senescence - TP53 - Cell cycle

الهه کاشانی امین, الهه کاشانی امین, هما فرجی, سارا نوری ینگجه, آزاده ابراهیم حبیبی

Enhancing Publication Retrieval in Basic Sciences: Insights from a Systematic Review on Structure-Sweetness Relationship of Sweet Molecules

To investigate the structure-sweetness relationship of sweet molecules, four scientific databases Web of Science, SCOPUS, PubMed, and FlavorDB were systematically searched for related studies on sweet proteins and small sweet molecules on the SweetenersDB database. No comprehensive study on this topic was retrieved. Then, the same search was performed with very general keywords such as sweetener, sweet molecules, and sweetening agents. A total of 8231 studies were retrieved, but only 122 studies for small molecules and 38 studies for sweet proteins met the inclusion criteria for the structure-function relationship investigations. Analyses showed that the studies on small sweet molecules used more diverse names than those common names used in the SweetenersDB. For example, instead of using saccharin, acesulfame, and cyclamate, they used sulfamate, sulfonyl, or even the chemical formula RNHSO3-M+. So, few and scattered studies were retrieved in the primary search. Including these new keywords yielded so many related studies that practically no new studies were demanded. Also, we found many eligible studies that had either not been retrieved at all or were excluded during the initial screening of the title and abstract. This happened because, in the title/abstract/keywords of these articles, there was either no informative keyword such as “sweetener”, or no sufficient and accurate information about the purpose of the study (structure-function relationship). Therefore, they were missed in the primary search or further screening steps. In conclusion, the diversity of expertise in basic sciences results in a diversity in terms and points of view on a topic. So, it is suggested that the keywords and purpose of a study be clearly and accurately included in the title, abstract, and keywords. These are the first, and probably the only sections to have a chance to be retrieved and caught by the readers.

systematic review, basic sciences, title, abstract, keyword, skills

حمید شیخ, فاطمه بابایی, عادله دیو سالار

Structural changes in Insulin via binding of anticancer drug of Pomalidomide

Insulin is a peptide hormone produced by the beta cells of the pancreas that plays a critical role in regulating blood glucose levels. By binding to its specific receptors on cell surfaces, insulin can facilitate the uptake of glucose from the bloodstream into cells. It is commonly used in the treatment of type 1 and type 2 diabetes, particularly in patients experiencing elevated blood sugar levels due to deficiencies in insulin production or function. Pomalidomide is an anti-cancer drug primarily used in the treatment of multiple myeloma, a type of blood cancer. This drug suppresses the growth of cancer cells by inhibiting certain immune processes and activating caspases. In this study, the interaction of pomalidomide with insulin protein was examined to assess potential changes in the structure and function of this hormone. Fluorescence spectroscopy and ultraviolet-visible (UV-Vis) spectroscopy were employed for this purpose. Intrinsic fluorescence results indicated that the addition of pomalidomide to insulin solution can led to a significant decreasing and quenching in the fluorescence intensity of insulin, which could be attributed to structural or conformational changes in the protein. Fluorescence emission data analysis using the Stern-Volmer and the logarithmic Hill equations revealed that approximately one binding site exists for pomalidomide on insulin at different temperatures of 27 and 37 C. This binding occurs through a static mechanism, which may indicate a specific type of interaction between the drug and the protein.

Insulin, Pomalidomide, Fluorescence Spectroscopy, UV-Visible Spectroscopy

فاطمه بابائی, حمید شیخ, دکتر عادله دیوسالار

Investigation of interaction and structural changes of insulin in the presence of Lenalidomide

Insulin, a globular peptide hormone (MW 5808 Da), comprises two polypeptide chains: the A-chain (21 amino acids) and the B-chain (30 amino acids), linked by disulfide bonds. Lenalidomide as a potent immunomodulatory drug, is a less toxic analog of thalidomide and was developed to reduce side effects like peripheral neuropathy. Our main aim in the present study is to investigate the interaction and structural alterations in Insulin due to presence of different concentrations of Lenalidomide. For this purpose, we execute two different spectroscopy methods, Fluorescence and UV-Visible, to examine the interactions, structural changes and related parameters. The intrinsic fluorescence data show systematic quenching of insulin`s natural emission spectrum in the presence of various concentrations of lenalidomide at both of the temperatures of 25 and 37 C. The number of binding sites and binding constants were analyzed by using quenching data. Hill equation analysis identifies that there is one binding site on insulin for binding of lenalidomide at both of the temperatures. Also, according to Stern-Volmer equation and plots which confirm the static quenching mechanism. These results suggest lenalidomide can interact and bind with insulin protein through static quenching, offering insights into their molecular interactions and potential effects.

Insulin, Lenalidomide, Hill equation, Stern-Volmer equation

محبوبه افرند

Application of Genetic Engineering in Commercial Enzyme Production: Expression of Recombinant Serine Protease from Virgibacillus natechei

Hydrolysis of fish waste protein is an effective and economical strategy for obtaining valuable products with diverse applications. Fish waste, often considered a byproduct, is rich in proteins and bioactive compounds that can be transformed into high-value products such as peptides and amino acids. In recent years, researchers have prioritized green and sustainable technologies for the hydrolysis of fish-derived proteins. These approaches aim to replace traditional chemical methods, which may pose environmental and health risks, with safer and more environmentally friendly alternatives. Among these, proteolytic enzymes have emerged as a promising solution, offering high specificity, efficiency, and mild operational conditions. However, natural enzymes face significant challenges, including high production costs, limiting their large-scale industrial application. To address this limitation, modern biotechnology tools, particularly genetic engineering, are being employed to produce recombinant enzymes with enhanced properties. In the present study, the synthetic gene encoding serine protease, an enzyme with considerable potential for protein hydrolysis, was inserted into the PET28a expression vector. This recombinant construct was then successfully introduced into the E. coli BL21(DE3) strain. The accuracy of the gene transfer was confirmed using Colony PCR, while the expression of the recombinant enzyme was evaluated through Real-Time PCR analysis. The successful production of serine protease from Virgibacillus natechei highlights its potential as a cost-effective alternative for various applications. If the purified enzyme demonstrates suitable biochemical properties, including high activity and stability, further studies may establish its viability for commercial use in industries like fisheries, waste management, and protein recovery.

Gene Synthesis, Recombinant Protease, E. coli BL21(DE3), Real-Time PCR

علی رکن رابعی

طراحی و ساخت هیدروژل نانوکمپوزیتی بر پایه پلی اکریلیک اسید دارای نانوذرات زینک سولفید و کریستال نانوسلولز برای استفاده به عنوان زخم‌پوش

هیدروژل‌ها موادی هستند که مشابه ماتریکس خارج سلولی بافت‌های نرم بیولوژیک رفتار می‌کنند. به همین دلیل، استفاده از هیدروژل‌ها به یکی از حوزه‌های پژوهشی رو به رشد در زمینه پزشکی تبدیل شده است. ساخت زخم‌پوشی که به‌طور همزمان دارای خواص زیستی و مکانیکی مطلوب باشد، چالشی مهم به شمار می‌رود. هدف از این پژوهش، بهره‌گیری از نانومواد برای ایجاد خواص مکانیکی و زیستی مناسب در هیدروژل بر پایه پلی‌اکریلیک اسید برای کاربرد زخم‌پوش است. به این منظور هیدروژل بر پایه پلی اکریلیک اسید (PAA) حاوی نانوذرات سلولز و نانوذرات سولفید روی سنتز شد. نانوذرات سلولز برای بهبود خواص مکانیکی و نانوذرات سولفید روی برای ایجاد خواص ضد باکتریایی به پانسمان زخم در نظر گرفته شدند. آنالیزهایی مانند SEM، FTIR و TGA برای مشخصه یابی هیدروژل انجام شد. آزمون MTT تایید کرد که زخمپوش سنتز شده زیست سازگار است. علاوه بر این، تحلیل‌های میکروبیولوژیکی نشان داد که این هیدروژل نانوکمپوسیتی دارای فعالیت ضد میکروبی قابل توجهی در برابر Staphylococcus aureus و Escherichia coli است. حاصل این پژوهش معرفی یک هیدروژل نانوکمپوسیتی زیست‌سازگار و آنتی باکتریال است که می‌تواند کاربردهای بالینی امیدوارکننده‌ای به عنوان زخم‌پوش داشته باشد.

زخم‌پوش ، هیدروژل ، پلی اکریلیک اسید ، سلولز نانوکریستال ، نانوذرات زینک سولفید