When Classrooms Become Battlegrounds: The Assault on Iranian Science 2 2 When Classrooms Become Battlegrounds: The Assault on Iranian Science In a shocking escalation, Iran was recently targeted by the Israeli regime in a military operation that, among its many atrocities, aimed to undermine the nation's scientific and intellectual infrastructure. Alarming reports indicate that key figures in Iran’s academic community, especially in fields like physics and medical sciences were directly attacked. Universities and classrooms were struck by missiles and drones. Several academics were assassinated along with their families, including women and children. During the brutal 12-day attack by the Zionist regime on Iran, Shahid Beheshti University and many of its professors, especially in the physics department, were directly attacked with missiles and drones in the classroom and at home, which is a rare incident in the current world. Tragically, six medical doctors and eighteen healthcare workers were martyred, including two pediatricians and gynecologists who lost their lives alongside their young children. Beyond the irreparable human loss, these attacks caused severe psychological trauma. Students preparing for national and final exams experienced acute distress, and many along with their families are now dealing with Post-Traumatic Stress Disorder (PTSD) (1,2). In light of this devastating assault, we must reflect on the broader implications for scientific progress, particularly in the realm of basic sciences (3). Two opposing perspectives emerge: <ol> <li style="text-align:justify">Support for Basic Sciences is Crucial: Fundamental research, especially when translatable into clinical or applied outcomes, is the backbone of innovation. It fuels optimism, confidence, and problem-solving within academic communities. Supporting basic sciences fosters resilience in both students and faculty, helping societies confront and overcome crises.</li> <li style="text-align:justify">Neglecting Science is Self-Sabotage: A narrow, short-sighted approach to funding where research budgets are cut due to economic pressures risks compounding the damage inflicted by external attacks. When scientific development is deprioritized, the consequences for national resilience and innovation are even more severe than the physical destruction wrought by missiles.</li> </ol> Unfortunately, the challenges Iranian scientists face extend beyond the battlefield. As an editor, I am increasingly concerned by the unscientific treatment of Iranian researchers by international publishers. In recent months, many submissions have been rejected on non-academic grounds, reflecting a troubling politicization of global science. This practice, which echoes earlier directives by U.S. authorities to restrict Iranian authors, is a clear departure from the ideals of impartial and collaborative scientific inquiry (4). Indeed, science should never be a casualty of politics. Yet, despite these adversities, Iran’s scientific community endures. As affirmed in the Holy Qur’an, “Indeed, Allah is with those who are patient.” In the face of oppression, our scientists continue to pursue knowledge, serve humanity, and inspire hope. 158 158 Shahin Akhondzadeh Editorial 70623.pdf Jafari P, Ghanizadeh A, Akhondzadeh S, Mohammadi MR. Health-related quality of life of Iranian children with attention deficit/hyperactivity disorder. Qual Life Res 2011;20(1):31-6. ##Amiri S, Mohammadi MR, Mohammadi M, Nouroozinejad GH, Kahbazi M, Akhondzadeh S. Modafinil as a treatment for Attention-Deficit/Hyperactivity Disorder in children and adolescents: a double blind, randomized clinical trial. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32(1):145-9. ##Akhondzadeh S. The Need for Serious Support for Basic Medical Science in Iran. Avicenna J Med Biotechnol 2024;16(3):136. ##Akhondzadeh S. US Editors and Reviewers can no Longer Handle Submissions by Authors Employed by the Government of Iran: Is it Fair and Logical? Avicenna J Med Biotechnol 2013 Oct;5(4):203.##

Production and Characterization of IgY Polyclonal Antibodies Specific to Human Interleukin-6 and Their Neutralization Potential for Anti-inflammatory Responses 2 2 Background: Interleukin-6 plays an essential role in cytokine storm and cytokine release syndrome, which occur in response to pathogen infection or tissue injury and are associated with severe symptoms. Neutralizing IL-6 can help reduce symptom severity. Chicken eggs serve as an excellent alternative antibody source compared to mammalian serum. The immunoglobulin Y (IgY) in the chicken’s blood is transferred to and deposited within the egg yolk in large amounts. Several IgY products have been developed for therapeutic applications in various diseases. This study focuses on producing anti-human IL-6 (IL-6) IgY antibodies to support therapeutic advancements. Methods: Anti-IL-6 IgY was generated by immunizing three hens with recombinant IL-6 protein mixed with alum adjuvant, immunized four times at three-week intervals. Then, IgY was extracted from egg yolks. The specificity of IgY was determined by Western blot. The neutralizing activity against secreted IL-6 was demonstrated by Human Coronavirus OC43 (HCoV-OC43)-infected cells and Lipopolysaccharide (LPS)-stimulated human lung fibroblast MRC-5 cells. Results: The specific anti-IL-6 was detected starting from day 10 to day 90 after immunization. The average yield of total IgY was 17.97±15.66 mg per egg. The extracted anti-IL6 IgY antibody exhibited efficient neutralizing effects against secreted IL-6 in the HCoV-OC43-infected or LPS-stimulated cells in a dose-dependent manner. Conclusion: This study highlights the ease of production and the satisfactory yield of anti-IL-6 IgY derived from chicken eggs. The antibody demonstrates an in vitro inhibitory effect on IL-6, with potential applications in therapeutic development. 159 166 Pacharaporn Khumpim Institute of Molecular Biosciences, Mahidol University, Salaya, PhutthamonthonFaculty of Veterinary Science, Mahidol University, Salaya, Phutthamonthon Institute of Molecular Biosciences, Mahidol University, Salaya, PhutthamonthonFaculty of Veterinary Science, Mahidol University, Salaya, Phutthamonthon ThailandThailand Charin Thawornkuno Faculty of Tropical Medicine, Mahidol University, Ratchathewi Faculty of Tropical Medicine, Mahidol University, Ratchathewi Thailand Surapon Piboonpocanun Institute of Molecular Biosciences, Mahidol University, Salaya, Phutthamonthon Institute of Molecular Biosciences, Mahidol University, Salaya, Phutthamonthon Thailand Wongsakorn Wongwadhunyoo Faculty of Veterinary Science, Mahidol University, Salaya, Phutthamonthon Faculty of Veterinary Science, Mahidol University, Salaya, Phutthamonthon Thailand Promsin Masrinoul ChickensCoronavirusEgg yolksIgYInterleukin-6Lipopolysaccharides 70615.pdf Khong WX, Foo DGW, Trasti SL, Tan EL, Alonso S. Sustained high levels of interleukin-6 contribute to the pathogenesis of Enterovirus 71 in a neonate mouse model. J Virol 2011;85(7):3067-76.##Zhang SY, Xu MY, Xu HM, Li XJ, Ding SJ, Wang XJ, et al. Immunologic Characterization of Cytokine Responses to Enterovirus 71 and Coxsackievirus A16 Infection in Children. Medicine (Baltimore) 2015;94(27):e1137. ##Talwar D, Kumar S, Acharya S, Raisinghani N, Madaan S, Hulkoti V, et al. Interleukin 6 and Its Correlation with COVID-19 in Terms of Outcomes in an Intensive Care Unit of a Rural Hospital: A Cross-sectional Study. Indian J Crit Care Med 2022;26(1):39-42.##Hack CE, De Groot ER, Felt-Bersma RJ, Nuijens JH, Strack Van Schijndel RJ, Eerenberg-Belmer AJ, et al. Increased plasma levels of interleukin-6 in sepsis. Blood 1989;74(5):1704-10.##Molano Franco D, Arevalo-Rodriguez I, Roqué I Figuls M, Montero Oleas NG, Nuvials X, Zamora J. Plasma interleukin-6 concentration for the diagnosis of sepsis in critically ill adults. Cochrane Database Syst Rev 2019;4(4):CD011811. ##Kishimoto T. IL-6: from its discovery to clinical applications. Inter Immnol 2010;22(5):347-52. ##Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 2014;6:a016295. ##Schaper F, Rose-John S. Interleukin-6: Biology, signaling and strategies of blockade. Cytokine Growth Factor Rev 2015;26(5):475-87. ##Velazquez-Salinas L, Verdugo-Rodriguez A, Rodriguez LL, Borca MV. The role of Interleukin 6 during viral infections. Front Microbiol 2019;10:1057.##Reza Elahi R, Karami P, Heidary AH, Esmaeilzadeh A. An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19). Int Immunopharmacol 2022;105:108536.##Barati B, Ebrahimi F, Nazarian S. Egg yolk antibodies for disease prevention. J Bacteriol Mycol Open Access 2016;3(2):219-22.##Suthaus J, Adam N, Grötzinger J, Scheller J, Rose-John S. Viral Interleukin-6: Structure, pathophysiology and strategies of neutralization. Eur J Cell Biol 2011;90:495-504. ##Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents 2020;55:105954. ##Aletaha D, Kerschbaumer A, Kastrati K, Dejaco C, Dougados M, McInnes IB, et al. Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update. Ann Rheum Dis 2023;82(6):773-87. ##Yao X, Huang J, Zhong H, Shen N, Faggioni R, Fung M, et al. Targeting interleukin-6 in inflammatory autoimmune diseases and cancers. Pharmacol Ther 2014;141(2):125-39. ##Pelletier JP, Mukhtar F. Passive monoclonal and polyclonal antibody therapies. InImmunologic Concepts in Transfusion Medicine 2020 Jan 1 (pp. 251-348). Elsevier.##Kumaran T. Production of IgY antibodies from egg yolk of immunized chickens. Advancements Bioequiv Avilab 2018;1(1):3-4.##da Silva WD, Tambourgi DV. IgY: A promising antibody for use in immunodiagnostic and in immunotherapy. Vet Immunol Immunopathol 2010;135(3-4):173-80. ##Amro WA, Al-Qaisi W, Al-Razem F. Production and purification of IgY antibodies from chicken egg yolk. J Genet Eng Biotechnol 2018;16:99-103.##Bizanov G. IgY extraction and purification from chicken egg yolk. Journal of the Hellenic Veterinary Medical Society 2017;68(3):265-72.##Karachaliou C, Vassilakopoulou V, Livaniou E. IgY technology: methods for developing and evaluating avian immunoglobulins for in vitro detection of biomolecules. World J Methodol 2021;11(5):243-62. ##Nilsson E, Stålberg J, Larsson A. IgY stability in eggs stored at room temperature or at + 4 ̊C. Br Poult Sci 2012;53:42-6. ##Zhang WW. The use of gene specific IgY antibodies for drug target discovery. Drug Discov Today 2003;8(8):364-71. ##Michael A, Meenatchisundaram S, Parameswari G, Subbraj T, Selvakumaran R, Ramalingam S. Chicken egg yolk antibodies (IgY) as an alternative to mammalian antibodies. Indian J Sci Technol 2010 Apr;3(4):468-74.##Ramakrishnan MA. Determination of 50% endpoint titer using a simple formula. World J Virol 2016;5(2):85-6. ##Woolley JA, Landon J. Comparison of antibody production to human interleukin-6 (IL-6) by sheep and chickens. J Immunol Methods 1995;178(2):253-65. ##Redwan EM, Aljadawi AA, Uversky VN. Simple and efficient protocol for immunoglobulin Y purification from chicken egg yolk. Poult Sci 2021;100(3):100956. ##Idar I, Yusuf M, Al Anshori J, Subroto T. Purification of IgY Anti-SARS-CoV-2-Chicken Nucleocapsid and Elimination of Its Low-temperature Storage-induced Aggregates. Trends in Sciences. 2024 Mar 20;21(5):7649.##Rose-John S. Interleukin-6 Family Cytokines. Cold Spring Harb Perspect Biol 2018;10(2):a028415. ##McElvaney OJ, McEvoy NL, McElvaney OF, Carroll TP, Murphy MP, Dunlea DM, et al. Characterization of the Inflammatory Response to Severe COVID-19 Illness. Am J Respir Crit Care Med 2020;202(6):812-21. ##Tasoudis PT, Arvaniti CK, Adamou AT, Belios I, Stone JH, Horick N, et al. Interleukin-6 inhibitors reduce mortality in coronavirus disease-2019: An individual patient data meta-analysis from randomized controlled trials. Eur J Intern Med 2022;101:41-48. ##Hsu HY, Yang CW, Lee YZ, Lin YL, Chang SY, Yang RB, et al. Remdesivir and Cyclosporine Synergistically Inhibit the Human Coronaviruses OC43 and SARS-CoV-2. Front Pharmacol 2021;12:706901. ##Beurel E, Jope RS. Lipopolysaccharide-induced interleukin-6 production is controlled by glycogen synthase kinase-3 and STAT3 in the brain. J Neuroinflammation 2009;6:9. ##Ma L, Zhang H, Yin YL, Guo WZ, Ma YQ, Wang YB, et al. Role of interleukin-6 to differentiate sepsis from non-infectious systemic inflammatory response syndrome. Cytokine 2016;88:126-35. ##Hamilton FW, Thomas M, Arnold D, Palmer T, Moran E, Mentzer AJ, et al. Therapeutic potential of IL6R blockade for the treatment of sepsis and sepsis-related death: A Mendelian randomisation study. PLoS Med 2023;20(1):e1004174. ##

Characterization and Evaluation of the Anti-proliferative Activity and Hypersensitivity of L-Asparaginase from Trichosporon asahii Isolate ChL11 and Candida palmioleophila Isolate JK12 2 2 Background: L-Asparaginase is a crucial enzyme to treat Acute Lymphoblastic Leukemia (ALL), as it depletes L-asparagine, an essential amino acid for cancer cell survival. However, its clinical use is often restricted due to hypersensitivity reactions. This study examined the anti-proliferative effects and hypersensitivity of fungal L-asparaginases (L-ASNases) from Trichosporon asahii isolate ChL11 (TaIChL11 L-ASNase) and Candida palmioleophila isolate JK12 (CpIJK12 L-ASNase). Methods: The enzymes were produced and purified through ammonium sulfate precipitation, dialysis, and Sephadex G-100 chromatography, and tested on leukemia cells and BALB/c female mice to assess immune responses. Results: TaIChL11 L-ASNase had a molecular weight of 40 kDa, Michaelis constant (KM) of 1.66×10⁻² mM, and Vmax of 37.23 mM/min, while CpIJK12 L-ASNase had a molecular weight of 135 kDa, KM of 2.3×10⁻² mM, and Vmax of 14.03 mM/min. Both enzymes exhibited significant anti-proliferative effects against CCRF-CEM cancer cells, with half-maximal inhibitory concentration (IC50) values of 2.74 U/ml for TaIChL11 L-ASNase and 3.30 U/ml for CpIJK12 L-ASNase after 48 hr, improving further after 72 hr. They also showed low cytotoxicity toward normal Vero E6 cells. in vivo studies demonstrated that TaIChL11 ASNase-treated mice had significantly lower Immunoglobulin (Ig) G levels than those treated with commercial L-ASNase from Erwinia chrysanthemi (Owenism) (p<0.005), with no detectable IgE response. Conclusion: These findings indicate that fungal L-ASNases, particularly TaIChL11 ASNase, with lower L-glutaminase activity and a favorable safety profile, could be promising alternatives to bacterial L-ASNases, potentially enhancing ALL treatment with fewer side effects. 167 179 Tekeba Sisay Department of Medical Biotechnology, Institute of Biotechnology, University of Gondar Department of Medical Biotechnology, Institute of Biotechnology, University of Gondar Ethiopia Naomi Maina Department of Molecular Biology and Biotechnology, Pan African University Institute for Basic Sciences, Technology and Innovations (PAUSTI)Biochemistry Department, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Department of Molecular Biology and Biotechnology, Pan African University Institute for Basic Sciences, Technology and Innovations (PAUSTI)Biochemistry Department, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Kenya Kenya Victor Mobegi Department of Biochemistry, Faculty of Science and Technology, University of Nairobi Department of Biochemistry, Faculty of Science and Technology, University of Nairobi Kenya Sabina Wachira Kenya Medical Research Institute, Center for Traditional Medicine and Drug Research Kenya Medical Research Institute, Center for Traditional Medicine and Drug Research Kenya Ammonium sulfateAsparaginaseAsparagineDickeya chrysanthemiGlutaminaseSephadexTrichosporon asahii 70616.pdf Brumano LP, da Silva FVS, Costa-Silva TA, Apolinário AC, Santos JHPM, Kleingesinds EK, et al. 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Synthesis of a Unique Dextran Polymer-Conjugated Antibody and Horseradish Peroxidase Complex 2 2 Background: Immunohistochemistry (IHC) is a practical technique that utilizes the specific binding between an antigen and antibody to detect and localize specific antigens in tissue and cells. The optimal sensitivity in IHC is of utmost importance to achieve reliable results even when antigens are present at low abundance on the samples. Here, a dextran polymer labeled with Horseradish Peroxidase (HRP) and an anti-body to improve the sensitivity of the IHC technique was synthesized. Methods: To this end, free thiol groups were introduced on sodium periodate-activated 30 kDa dextran using cystamine, followed by attachment of sulfo-MBS-activated goat anti-mouse antibody and sulfo-MBS-activated HRP to the activated dextran. Results: The production of Poly-HRP Antibody (PHA) was confirmed by the appearance of a new protein band exceeding 150 kDa on Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE). Additionally, Enzyme-Linked Immunosorbent Assay (ELISA) and IHC techniques were employed to characterize PHA’s functionality. The data demonstrated that PHA effectively detected target antigens in these assays. Conclusion: The newly synthesized PHA has the potential to provide a more sensitive platform for early detection of biomarkers in IHC. Further research is needed to evaluate its cost-effectiveness. 180 185 Bahareh Zamani Monoclonal Antibody Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR) Monoclonal Antibody Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR) Iran Niloofar Agharezaee Monoclonal Antibody Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR) Iran Farshid Moosavi Monoclonal Antibody Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR) Iran Saeideh Zamani Koukhaloo Monoclonal Antibody Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR) Iran Parisa Yousefi Monoclonal Antibody Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR) Iran Jafar Mahmoudian AntibodiesDextransHorseradish peroxidaseImmunohistochemistry 70617.pdf Su F, Luo X, Du Z, Chen Z, Liu Y, Jin X, Guo Z, Lu J, Jin D. 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The Quality and Quantity of Nanoparticles Extracted from Human Adipose Tissue Derived-Mesenchymal Stem Cells 2 2 Background: Nanoparticles, as small extracellular vesicles, are considered promising tools in tissue engineering and regenerative medicine. This study aimed to investigate the effects of different processing and culture condition on the quality and quantity of extracts derived from human Adipose-Mesenchymal Stem Cells (AD-MSCs). Methods: AD-MSCs were proliferated in both the experimental and control groups. Nanoparticles were extracted from AD-MSCs-extracts and analyzed using SEM, TEM, DLS, Zeta potential, FTIR and BCA analyses. The morphological characteristics (shape, size, distribution, surface topography, and  agglomeration/aggregation), structural appearance (poly-disperse intensity, colloidal particle behavior, surface charge, and stability), chemical properties (functional groups and ionic interactions) and total protein concentration were detected in the extracted nanoparticles. Additionally, the morphological characteristics, apoptosis, mitochondrial oxidoreductase activity, and migration potential of AD-MSCs in both groups were evaluated using acridine orange staining, MTT, and scratch assays. Results: In the experimental group, 100% of the nanoparticles had a diameter of 112.8±25 nm, with the most frequency of 111.4 nm. However, in the control group, 72% of nanoparticles had a diameter of 350.2±43.6 nm with the highest frequency of 339.8 nm (p≤0.05). The Z-average, Poly-disperse intensity, and electrostatic stability of nanoparticles in the control and experimental groups were 171.9 nm, 0.727 and -0.000011 cm2/Vs vs. 103.7 nm, 0.205 and 0.000481 cm2/Vs, respectively (p≤0.05). In the experimental group, Zeta potential was -61.8 mV, which is in the range of ζ >-30mV. Although, Zeta potential in the control group was -1.5 mV, which is in the range of -30 mV <ζ <30 mV (p≤0.05). Total protein concentrations in the control and experimental groups were 11 and 41%, respectively (p≤0.05). Conclusion: Nanoparticles derived from AD-MSCs have high therapeutic applications in tissue engineering and regenerative medicine. 186 195 Mobina Karimi Department of Biology, SR.C, Islamic Azad University Department of Biology, SR.C, Islamic Azad University Banafsheh Heidari Hanieh Jafary Department of Biology, SR.C, Islamic Azad University Department of Biology, SR.C, Islamic Azad University Iran Kavosh Zandsalimi Department of Medical Laser (MLRC), Medical Laser Research Center, Yara Institute, ACECR Iran Acridine orangeControl groupsFourier transform infraredImmunologic factorsNanoparticlesObesityRegenerative medicineRegenerative medicineSpectroscopyStatic electricityTissue engineering 70618.pdf Cai Y, Li J, Jia C, He Y, Deng, C. Therapeutic applications of adipose cell-free derivatives: a review. Stem Cell Res Ther 2020;11(1):312. ##Barreca MM, Cancemi P, Geraci F. Mesenchymal and induced pluripotent stem cells-derived extracellular vesicles: the new frontier for regenerative medicine? Cells 2020;9(5):1163. ##Chen B, Li Q, Zhao B, Wang Y. Stem cell-derived extracellular vesicles as a novel potential therapeutic tool for tissue repair. Stem Cells Transl Med 2017;6(9):1753-8. ##Baglio SR, Rooijers K, Koppers-Lalic D, Verweij FJ, Pérez Lanzón M, Zini N, et al. Human bone marrow-and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species. Stem Cell Res Ther 2015;6(1):127. ##Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science 2020;367(6478):eaau6977. ##Kiyota T, Machhi J, Lu Y, Dyavarshetty B, Nemati M, Yokoyama I, et al. Granulocyte-macrophage colony-stimulating factor neuroprotective activities in Alzheimer’s disease mice. J Neuroimmunol 2018;319:80-92. ##Dittmer J, Leyh B. Paracrine effects of stem cells in wound healing and cancer progression. Int J Oncol 2017;44(6):1789-98. ##Gao Y, Yuan Z, Yuan X, Wan Z, Yu Y, Zhan Q, et al. Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration. Bioact Mater 2022;14:377-88.##Gurunathan S, Kang MH, Jeyaraj M, Qasim M, Kim JH. Review of the isolation, characterization, biological function, and multifarious therapeutic approaches of exosomes. Cells 2019;8(4):307. ##Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA, Easton J, et al. Germline mutations in predisposition genes in pediatric cancer. N Engl J Med 2015;373(24):2336-46. ##Nam G-H, Choi Y, Kim GB, Kim S, Kim SA, Kim I-S. Emerging prospects of exosomes for cancer treatment: from conventional therapy to immunotherapy. Adv Mater 2020;32(51):2002440. ##Vu NB, Nguyen HT, Palumbo R, Pellicano R, Fagoonee S, Pham PV. Stem cell-derived exosomes for wound healing: current status and promising directions. Minerva Med 2021;112(3):384-400. ##Zhang Y, Jiayao B, Huang J, Tang Y, Du Sh, Pengyue L. Exosome: A review of its classification, isolation, storage, diagnostic and targeted therapy applications. Int J Nanomedicine 2020;15:6917-34. ##Heidari B, Jaffary H, Golshahi H, Soltanghoraei H, Shams S, Soltani A, et al. Efficient procedure for human adipose tissue cryopreservation without specialized freezing equipment. Cryoletters 2025;46(3):197-206. ##Heidari B, Eidi N, Mortazavi P, Saffarian Z, Soltani A, Mansouri P, et al. Morphological characteristics, mitochondrial oxidoreductase activity, and vascularization of human adipose tissues pre-and post-xenotransplantation into BALB/c female nude mice. Cryobiology 2025; 2025 May 6;119:105248. ##Safwani WKZW, Wong CW, Yong KW, Choi JR, Adenan NAM, Omar S, et al. The effects of hypoxia and serum-free conditions on the stemness properties of human adipose-derived stem cells. Cytotechnology 2016;68(5):1859. ##Kim JY, Rhim WK, Seo HJ, Lee JY, Park CG, Han DK. Comparative analysis of MSC-derived exosomes depending on cell culture media for regenerative bioactivity. Tissue Eng Regen Med 2021;18(3):355-67. ##Wei Q, Wei L, Zhang J, Li Z, Feng H, Ren L. EphA2 enriched exosomes promote cell migration and are a potential diagnostic serum marker in pancreatic cancer. Mol Med Rep 2020;22(4):2941-7. ##Misaghian A, Ghadiri AA, Asadirad A, Amirzadeh S, Amari A. The Effect of Exosomes Isolated from Poly (I:C) Treated Human Wharton's Jelly Mesenchymal Stem Cells on CD4+CD25+Foxp3+ Regulatory T Cells. Iran J Allergy Asthma Immunol 2024;23(3):288-98. ##Dong B, Wang C, Zhang J, Zhang J, Gu Y, Guo X, Zuo X, Pan H, Hsu ACY, Wang G, Wang F. Exosomes from human umbilical cord mesenchymal stem cells attenuate the inflammation of severe steroid-resistant asthma by reshaping macrophage polarization. Stem Cell Res Ther 2021;12(1):204. ##

Resorbable Bone-Fixation Materials: Synthesis, Physical-Chemical and Biological Properties 2 2 Artificial bone materials were synthesized using the "solvent casting method" using polylactide/hydroxyapatite and various organic-inorganic modifiers. The physicochemical properties of the materials were studied using modern methods. IR spectroscopy showed that interactions between polymer macromolecules and hydroxyapatite occurred. When the powder was studied by the X-ray diffraction method, it was found to have an average crystallinity of 50-60%. When the textural properties were examined using SEM analysis, it was found that the introduction of magnesium phosphate into the samples resulted in the formation of porous particles with dimensions of 100-250 µm. This in turn, leads to the improvement of metabolic processes when the samples are introduced into living tissues. When the microhardness was determined by the Vickers method, it was found to be close to the hardness of natural bone, i.e. 27-34 HV. In vitro resorption was also performed in Simulated Body Fluids (SBF). Non-toxicity was observed when cytotoxic properties were studied. When the resorption process was studied in vivo in the upper third of the femur of rabbits, it was found that the ossification process of the samples was satisfactory after 28 days 196 207 Bakhtiniso Muzaffarova Department of Organic synthesis and Bioorganic chemistry, Samarkand State University named after Sharof Rashidov Department of Organic synthesis and Bioorganic chemistry, Samarkand State University named after Sharof Rashidov Uzbekistan Sherzod Eranov Department of Traumatology and Orthopedics, Samarkand State Medical University Department of Traumatology and Orthopedics, Samarkand State Medical University Uzbekistan Sanjar Tillayev DurapatiteFemurHydroxyapatite-polylactideLagomorphaPorosityPowders 70619.pdf Campana V, Milano G, Pagano E, Barba M, Cicione C, Salonna G, et al. Bone substitutes in orthopaedic surgery: from basic science to clinical practice. J Mater Sci Mater Med 2014 Oct;25(10):2445-61. ##Chai Y, Okuda M, Otsuka Y, Ohnuma K, Tagaya M. Comparison of two fabrication processes for biomimetic collagen/hydroxyapatite hybrids. Advanced Powder Technology 2019 Jul 1;30(7):1419-23.##Irawan V, Kajiwara D, Nakagawa Y, Ikoma T. Fabrication of mechanically robust bilayer membranes of hydroxyapatite/collagen composites. Materials Letters 2021 May 15;291:129514.##Çelik T, Saraçoğlu B, Özkan A, İlhan Y. Biodegradable Pla/Ha Composite Material Production and Mechanical Characterization for Temporary Implant Applications. International Journal of Pioneering Technology and Engineering 2023 Dec 15;2(02):188-92.##Aihemaiti P, Jiang H, Aiyiti W, Wang J, Dong L, Shuai C. Mechanical properties enhancement of 3D-printed HA-PLA composites using ultrasonic vibration assistance. Virtual and Physical Prototyping 2024 Dec 31;19(1):e2346271.##Li M, Jia W, Zhang X, Weng H, Gu G, Chen Z. Hyaluronic acid oligosaccharides modified mineralized collagen and chitosan with enhanced osteoinductive properties for bone tissue engineering. 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Short-Term Inflammatory Exposure Affects Umbilical Cord-derived Mesenchymal Stem Cells Migration and Differentiation Through Modulation of NLRP3 Inflammasome Expression 2 2 Background: An innovative approach for tissue restoration using Umbilical Cord-derived Mesenchymal Stem Cells (UC-MSCs) is hindered by their poor survival rate due to the detrimental effects of the injured tissue microenvironment. Activation of NLRP3 inflammasome in an inflammatory environment which is followed by cellular impairment, has been reported. However, the expression of NLRP3 inflammasome in UC-MSCs in response to the inflammatory environment is not well understood. This study aims to investigate the impact of short-term exposure to an inflammatory environment induced by Lipopolysaccharide (LPS) on hUC-MSCs, focusing on cell viability, migration, differentiation, and the expression of NLRP3 inflammasome-related genes. Methods: hUC-MSC were exposed to LPS at concentration of 10 and 50 μg/ml for 3 and 6 hr. Cell viability was assessed using CCK-8 assay, migration capacity was evaluated using a scratch test, and differentiation capacity and the expression of NLRP3 inflammasome-related genes were measured using qRT-PCR.  Results: Short-term LPS induction did not affect the viability of hUC-MSCs but reduced their migration and differentiation capacity, particularly at 50 μg/ml for both time points (p<0.05). The induction caused an increase in the mRNA levels of NLRP3, TLR-4, and RelA/p65, which correlated with elevated expression of caspase-1 and IL-1β.  Conclusion: Short-term exposure to LPS influences hUC-MSCs by upregulating NLRP3, TLR4/ReIA (p65), IL-1β, and caspase-1 mRNA levels, leading to impaired migration and differentiation ability. This study underscores the significant impact of short-term exposure to an inflammatory microenvironment on hUC-MSC, potentially compromising their migration and differentiation capacity through the NLRP3 pathway. 208 215 Helsy Junaidi Faculty of Medicine, Universitas Indonesia Faculty of Medicine, Universitas Indonesia Indonesia Dewi Sukmawati Faculty of Medicine, Universitas Indonesia Faculty of Medicine, Universitas Indonesia Indonesia Anoop Narayanan V Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Pharmaceutics, Mangaluru Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Pharmaceutics, Mangaluru India Jeanne A. Pawitan Faculty of Medicine, Universitas IndonesiaDepartment of Histology, Faculty of Medicine, Universitas IndonesiaStem Cell and Tissue Engineering (SCTE) Research Cluster, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas IndonesiaIntegrated Service Unit of Stem Cell Medical Technology (IPT TK Sel Punca), Dr. Cipto Mangunkusumo General Hospital (RSCM) Faculty of Medicine, Universitas IndonesiaDepartment of Histology, Faculty of Medicine, Universitas IndonesiaStem Cell and Tissue Engineering (SCTE) Research Cluster, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas IndonesiaIntegrated Service Unit of Stem Cell Medical Technology (IPT TK Sel Punca), Dr. Cipto Mangunkusumo General Hospital (RSCM) IndonesiaIndonesiaIndonesiaIndonesia Sri Widia Jusman Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia Indonesia InflammationUC-MSCCell migrationDifferentiationLipopolysaccharideNLRP3 inflammasome 70620.pdf Song N, Scholtemeijer M, Shah K. 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Ameliorating Potential of Quercetin and Curcumin on Glucose-6-Phosphate Dehydrogenase Expression via miRNAs in Rats with Type 2 Diabetes Mellitus 2 2 Background: Type 2 diabetes mellitus (T2DM) is accompanied by a significant risk of oxidative stress. While a link between T2DM and G6PD deficiency has been suggested, their interaction is not precisely understood. Furthermore, emerging evidence suggests an expression association between G6PD and miR-1, miR-122, and miR-206. Given the antioxidant and anti-inflammatory properties of Curcumin (Cur) and Quercetin (Q), This study aimed to assess the effects of curcumin and quercetin on G6PD expression and its correlation with the mentioned microRNA expression in liver, renal, heart, and muscle in rats with T2DM. Methods: RT-qPCR was employed to determine miR-1, miR-122, miR-206, and G6PD expression. Results: The findings revealed that curcumin and quercetin treatment elevated G6PD gene expression. Also, the treated groups exhibited down-regulation of miR-1, miR-122, and miR-206 (p<0.05). Furthermore, there was a significant inverse correlation between G6PD and miR-1 in heart, miR-122 in all tissues except renal and miR-206 expression in skeletal muscle and heart (p<0.05). Conclusion: This study suggests that curcumin and quercetin may prevent the development of T2DM by effectively increasing G6PD expression and reducing miR-1, miR-122, and miR-206 expression. 216 224 Mahsima Bagheri International Campus of Shahid Sadoughi University of Medical Sciences International Campus of Shahid Sadoughi University of Medical Sciences Iran Ameneh Khodarahmi Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services Iran Fatemeh Zare Mehrjardi Department of Physiology, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services Department of Physiology, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services Iran Ali Moradi CurcuminG6PDmiRNAQuercetinType 2 diabetes mellitus 70621.pdf Krentz NAJ, Gloyn AL. 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Swimming Exercise Attenuates DOX-Induced Cardiotoxicity by Modulating Apoptosis and DRP1/PGC1α/ miR-23a Dependent Pathway in Rat Heart Tissue 2 2 Background: Doxorubicin (DOX) is a widely used drug in cancer chemotherapy, but its cardiotoxicity limits its clinical applications. Combining exercise with chemotherapy offers a promising approach to mitigate the side effects of chemotherapy drugs. Limited information is available on the effects of swimming exercise on the molecular mechanisms related to Dox cardiotoxicity. This study aims to investigate the modulatory effect of swimming exercise on the apoptosis and miR-23a-dependent mitochondrial biogenesis and dynamics pathways in rat heart tissue treated with dox. Methods: In this experimental study, thirty-two adult male Wistar desert rats (200-220 g) were randomly divided into four groups, including control, doxorubicin (DOX; intraperitoneal injection of 5 mg/kg of Dox, once a week, for five weeks), swimming exercise (SE; water exercise for 60 min/day, five days a week, for six weeks) and Dox group along with Swimming Exercise (DOX-SE). At the end of the study, the cardiac expression of proteins related to apoptosis and mitochondrial biogenesis and mir23-a were analyzed using western blot and real-time PCR methods, respectively. One-way analysis of variance (ANOVA)with Tukey's post hoc test was used to analyze the data. Results: These findings revealed that DOX administration led to a significant decrease in the cardiac expression of PGC-1α and DRP-1 proteins and an increase in apoptotic proteins (caspase 3 and cytochrome C) compared to the control group (p<0.0001). Swimming exercise resulted in a significant increase expression in cardiac tissue of PGC-1α and DRP-1 proteins and a decrease in the expression of apoptotic proteins in the DOX-treated group (p<0.0001, p<0.01). Compared to the control group, the protein levels in the heart of the miR-23a were significantly increased in the DOX-treated group (p<0.001). However, exercise training attenuated the DOX-induced reduction in miR-23a expression gene in the cardiac muscle of DOX-treated mice (p<0.05). Conclusion: These findings suggest that swimming exercise may protect against DOX-induced cardiotoxicity by regulating apoptosis and DRP1/PGC1α/ miR-23a pathway. This highlights exercise as a potential non-pharmacological strategy to mitigate chemotherapy-related heart damage. 225 232 Hassan Darvakh Shohadayehoveizeh Campus of Technology, Shahid Chamran University of Ahvaz Shohadayehoveizeh Campus of Technology, Shahid Chamran University of Ahvaz Iran Saied Shakerian Rohollah Ranjbar Department of Sport Physiology, Faculty of Sport Science, Shahid Chamran University of Ahvaz Department of Sport Physiology, Faculty of Sport Science, Shahid Chamran University of Ahvaz Iran Mohammad reza Tabandeh Department of Basic, Science, Division of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz Department of Basic, Science, Division of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz Iran ApoptosisCardiotoxicityDoxorubicinSwimming 70622.pdf Lee Y, Kwon I, Jang Y, Cosio-Lima L, Barrington P. 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