The Clinician Scientist Training Program in Iran: Catalyzing Clinical Science Advancements 2 2 The Clinician Scientist Training Program (CSTP) is a transformative educational initiative that combines clinical training with scientific research, producing a unique cohort of physician-scientists. In Iran, the CSTP has emerged as a catalyst for propelling clinical science forward 1. By equipping medical professionals with the skills to bridge the gap between research and clinical practice, this program is revolutionizing healthcare, fostering innovation, and contributing to significant advancements in clinical sciences. CSTP represents a paradigm shift in medical education in Iran by emphasizing the integration of clinical practice and scientific inquiry. It recognizes the intrinsic value of research in enhancing patient care, and, thus, cultivates a cohort of physician-scientists capable of seamlessly navigating both domains. By blending clinical training with rigorous research experience, the program nurtures a new generation of medical professionals who can effectively address complex healthcare challenges through a comprehensive understanding of clinical practice and cutting-edge scientific knowledge. Impact of CSTP on clinical science in Iran is remarkable. Although there are no reports on outcomes of CSTP or views from program directors, physician-scientists trained through this program play a pivotal role in advancing medical knowledge, exploring disease mechanisms, and developing innovative therapeutic interventions. The ability to straddle the two worlds of clinical practice and scientific research facilitates uncovering novel insights, contributing to breakthrough discoveries in fields such as molecular biology, genomics, pharmacology, and epidemiology. These advancements translate into tangible benefits for patients, improving diagnosis, treatment options, and overall healthcare outcomes. One of the core strengths of the CSTP lies in its emphasis on translational research. By facilitating collaborations between basic scientists, clinical practitioners, and industry partners, this program accelerates the translation of scientific discoveries into clinical applications Clinician-scientists trained through the CSTP act as crucial mediators, ensuring that research findings are effectively implemented at the bedside. This synergy between research and clinical practice leads to development of innovative diagnostics, therapies, and preventive strategies, ultimately transforming patient care in Iran. Furthermore, CSTP has played a pivotal role in bolstering research infrastructure in Iran. By producing a cohort of highly skilled physician-scientists, the program promotes research excellence, fosters collaborations, and establishes multidisciplinary research teams. This investment in research infrastructure enhances the capacity of research institutions, attracts funding opportunities, and positions Iran as a hub for cutting-edge clinical research. The long-term effects of this strengthened research ecosystem are far-reaching, fueling continuous advancements in clinical science and contributing to the overall development of the healthcare sector. CSTP nurtures a culture of inquiry and scientific curiosity among medical professionals in Iran. By integrating research training into medical education, the program inspires aspiring physicians to embrace evidence-based practice and pursue scientific careers. The exposure to rigorous research methodologies and critical thinking instills a lifelong commitment to advancing medical knowledge and continually improving patient care. This cultural shift fosters a vibrant community of medical professionals dedicated to pushing the boundaries of clinical science, promoting collaboration, and inspiring future generations of clinician-scientists. The Clinician Scientist Training Program in Iran is revolutionizing clinical science by empowering clinician-scientists with a unique blend of clinical expertise and research acumen. This integration is driving advancements in medical knowledge, fostering translational research, strengthening research infrastructure, and cultivating a culture of scientific inquiry. As Iran continues to invest in CSTP, it positions itself at the forefront of clinical science, poised to make significant contributions to global healthcare advancements while addressing the unique healthcare challenges of the nation. 128 128 Hossein Sanjari Moghaddam Psychiatric Research Center, Roozbeh Hospital Tehran University of Medical Sciences Psychiatric Research Center, Roozbeh Hospital Tehran University of Medical Sciences Iran Shahin Akhondzadeh Editorial 60541.pdf Haspel RL, Orlinick JR. Physician-scientist training. JAMA 2006;295(6):623; author reply -4.##

Effects of Antidepressant Medication on Brain-derived Neurotrophic Factor Concentration and Neuroplasticity in Depression: A Review of Preclinical and Clinical Studies 2 2 Depression is the most prevalent and debilitating disease with great impact on societies. Evidence suggests Brain-Derived Neurotrophic Factor (BDNF) plays an important role in pathophysiology of depression. Depression is associated with altered synaptic plasticity and neurogenesis. BDNF is the main regulatory protein that affects neuronal plasticity in the hippocampus. A wealth of evidence shows decreased levels of BDNF in depressed patients. Important literature demonstrated that BDNF-TrkB signaling plays a key role in therapeutic action of antidepressants. Numerous studies have reported antidepressant effects on serum/ plasma levels of BDNF and neuroplasticity which may be related to improvement of depressive symptoms. Most of the evidence suggested increased levels of BDNF after antidepressant treatment. This review will summarize recent findings on the association between BDNF, neuroplasticity, and antidepressant response in depression. Also, we will review recent studies that evaluate the association between postpartum depression as a subtype of depression and BDNF levels in postpartum women. 129 138 Sophia Esalatmanesh Arash Women Hospital, Tehran University of Medical Sciences Arash Women Hospital, Tehran University of Medical Sciences Iran Ladan Kashani Arash Women Hospital, Tehran University of Medical Sciences Arash Women Hospital, Tehran University of Medical Sciences Iran Shahin Akhondzadeh Antidepressant medicationBrain-derived neurotrophic factorDepressionNeuroplasticity 60542.pdf Abdoli N, Salari N, Darvishi N, Jafarpour S, Solaymani M, Mohammadi M, et al. The global prevalence of major depressive disorder (MDD) among the elderly: A systematic review and meta-analysis. Neurosci Biobehav Rev 2022;132:1067-73.##Reddy MS. Depression: the disorder and the burden. 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Application of Menstrual Blood Derived Stromal (stem) Cells Exert Greater Regenerative Potency Than Fibroblasts/Keratinocytes in Chronic Wounds of Diabetic Mice 2 2 Background: In this study we differentially showed the effects of cell-seeded bilayer scaffold wound dressing in accelerating healing process in diabetic ulcers that still remains as a major clinical challenge. The aim of the study was to compare immunomodulatory and angiogenic activity, and regenerative effect differences between Menstrual blood-derived Stem Cells (MenSCs) and foreskin-derived keratinocytes/fibroblasts. Methods: The streptozotocin-induced diabetic mice model was developed in male C57/BL6 mice. A bilayer scaffold was fabricated by electrospining silk fibroin nanofibers on human Amniotic Membrane (AM). Dermal fibroblasts and keratinocyte isolated from neonatal foreskin and MenSCs were isolated from the menstrual blood of healthy women. The diabetic mice were randomly divided into three groups including no treatment group, fibroblast/keratinocyte-seeded bilayer scaffold group (bSC+FK), and MenSCs-seeded bilayer scaffold group. The healing of full-thickness excisional wounds evaluations in the diabetic mice model in each group were evaluated at 3, 7, and 14 days after treatment. Results: The gross and histological data sets significantly showed wound healing promotion via re-epithelialization and wound contraction along with enhanced regeneration in MenSCs-seeded bilayer scaffold group with the most similarity to adjacent intact tissue. Immunofluorescence staining of mouse skin depicted a descending trend of type III collagen along with the higher expression of involucrin as keratinocyte marker in the MenSCs-seeded bilayer nanofibrous scaffold group in comparison with other treatment groups from day 7 to day 14. Moreover, higher levels of CD31 and von Willebrand factor (VWF), and also a higher ratio of M2/M1 macrophages in association with higher levels of the neural marker were observed in the bSC+MenSCs group in comparison with bSC+FK and no treatment groups. Conclusion: Healing symptoms in wounds dressed with keratinocyte/fibroblast-seeded bilayer scaffold was significantly lower than MenSCs-seeded bilayer scaffold done on impaired diabetic wound chronicity. 139 156 Ebrahim Mirzadegan Nanobiotechnology Research Center, Avicenna Research Institute, ACECR Iran Hannaneh Golshahi Nanobiotechnology Research Center, Avicenna Research Institute, ACECR Iran Zahra Saffarian Nanobiotechnology Research Center, Avicenna Research Institute, ACECR Iran Haleh Edalatkhah Nanobiotechnology Research Center, Avicenna Research Institute, ACECR Nanobiotechnology Research Center, Avicenna Research Institute, ACECR Iran Maryam Darzi Nanobiotechnology Research Center, Avicenna Research Institute, ACECR Iran Somayeh Khorasani Nanobiotechnology Research Center, Avicenna Research Institute, ACECR Iran Kioomars Saliminejad Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Iran Somaieh Kazemnejad Bilayer scaffoldDiabetic woundFibroblastsKeratinocyteMenstrual blood stem cells 60540.pdf Hart T, Milner R, Cifu A. 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Higher Improvement of Cardiac Function Following Myocardial Infarction using Menstrual Blood Stromal/Stem Cells (MenSCs) Suspended in Conditioned Medium versus Conditioned Medium Alone in Rat Model 2 2 Background: To evaluate the efficiency of Menstrual blood Stromal/Stem Cells (MenSCs) administration in Myocardial Infarction (MI), the effects of MenSCs and their derived conditioned Medium (CM) on cardiac function in MI rat model was assessed. Methods: Animals were divided into four groups including sham group, MI group, MenSCs derived CM group (CM group), and MenSCs suspended in CM (MenSCs+ CM) group. The injection of different groups was carried out 30 min after ligation of left anterior descending coronary artery into the infarct border zone. Results: The results showed a significant reduction in scar size after injection of MenSCs+CM compared to MI group. Ejection fraction and fractional shortening of MenSCs+CM group were higher than CM and MI group at day 28. Administration of MenSCs+CM led to much more survival of cardiomyocytes, and prevention of metaplastic development. Moreover, human mitochondrial transfer from MenSCs to cardiomyocytes was seen in group treated by MenSCs+CM. Indeed, MenSCs+CM treatment evoked nuclear factor-κB (NF-κB) down-regulation more than other treatments. Conclusion: MenSCs+CM treatment could significantly ameliorate cardiac function by different mechanisms including inhibition of cartilaginous metaplasia, inhibition of NF-κB and mitochondrial transfer. 157 166 Mahmood Manshori Faculty of Veterinary Medicine, Shahrekord University,Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Faculty of Veterinary Medicine, Shahrekord University,Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, IranIran Somaieh Kazemnejad Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Iran Nasim Naderi Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Iran Abolfazl Shirazi Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Iran Maedeh Arabian Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Iran Marzieh Eghtedar Doost Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Iran Maryam Darzi Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Iran Samaneh Montazeri Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Iran Nahid Aboutaleb Physiology Research Center, Iran University of Medical ScienceDepartment of Physiology, Faculty of Medicine, Iran University of Medical Sciences Physiology Research Center, Iran University of Medical ScienceDepartment of Physiology, Faculty of Medicine, Iran University of Medical Sciences IranIran Hannaneh Golshahi Conditioned mediumMenstrual blood stem cellsMetaplasiaMitochondrial transferMyocardial infarction 60543.pdf Petersen PE, Bourgeois D, Ogawa H, Estupinan-Day S, Ndiaye C. 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Human mesenchymal stem cells reprogram adult cardiomyocytes toward a progenitor‐like state through partial cell fusion and mitochondria transfer. Stem Cells. 2011;29(5):812-24.##Feng Y, Zhu R, Shen J, Wu J, Lu W, Zhang J, et al. Human bone marrow mesenchymal stem cells rescue endothelial cells experiencing chemotherapy stress by mitochondrial transfer via tunneling nanotubes. Stem Cells Dev 2019;28(10):674-82.##Paliwal S, Chaudhuri R, Agrawal A, Mohanty S. Regenerative abilities of mesenchymal stem cells through mitochondrial transfer. J Biomed Sci 2018;25(1):31.##Xing L, Cui R, Peng L, Ma J, Chen X, Xie R-J, et al. Mesenchymal stem cells, not conditioned medium, contribute to kidney repair after ischemia-reperfusion injury. Stem Cell Res Ther 2014;5(4):101.##Dai W, Hale SL, Kloner RA. Role of a paracrine action of mesenchymal stem cells in the improvement of left ventricular function after coronary artery occlusion in rats. 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Investigation of Expression Profile of Placenta-specific 1 (PLAC1) in Acute Myeloid and Lymphoid Leukemias 2 2 Background: Placenta-specific 1 (PLAC1) is one of the cancer-testis-placenta antigens that has no expression in normal tissue except placenta trophoblast and testicular germ cells, but is overexpressed in a variety of solid tumors. There is a lack of studies on the expression of PLAC1 in leukemia. We investigated expression of PLAC1 in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL). Methods: In this study, we investigated expression pattern of PLAC1 gene in peripheral blood and bone marrow mononuclear cells of newly-diagnosed patients with AML (n=31) and ALL (n=31) using quantitative real-time PCR. Normal subjects (n=17) were considered as control. The PLAC1 protein expression in the samples were also detected using western blotting. Results: Our data demonstrated that PLAC1 transcripts had 2.7 and 2.9 fold-change increase in AML and ALL, respectively, compared to normal samples. PLAC1 transcript expression was totally negative in all studied normal subjects. Level of PLAC1 mRNA expression in ALL statistically increased compared to normal samples (p=0.038). However, relative mRNA expression of PLAC1 in AML was not significant in comparison to normal subjects (p=0.848). Furthermore, relative mRNA expression of PLAC1 in AML subtypes was not statistically significant (p=0.756). PLAC1 gene expression showed no difference in demographical clinical and para-clinical parameters. Western blotting confirmed expression of PLAC1 in the ALL and AML samples. Conclusion: Considering PLAC1 expression profile in acute leukemia, PLAC1 could be a potential marker in leukemia which needs complementary studies in the future. 167 172 Parastou Gholami Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences Iran Hossein Asgarian-Omran Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences Iran Marjan Yaghmaei Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences Iran Jafar Mahmoudian Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Iran Shirin Kianersi HSCT Research Center, Shahid Beheshti University of Medical Sciences HSCT Research Center, Shahid Beheshti University of Medical Sciences Iran Sina Salari HSCT Research Center, Shahid Beheshti University of Medical Sciences HSCT Research Center, Shahid Beheshti University of Medical Sciences Iran Ehsan Zaboli Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences Iran Mahmood Jeddi-Tehrani Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Iran Amir-Hassan Zarnani Department of Immunology, School of Public Health, Tehran University of Medical Sciences,Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Department of Immunology, School of Public Health, Tehran University of Medical Sciences, IranIran Mahdi Shabani Acute lymphoblastic leukemia Acute myeloid leukemiaBiomarkerExpression profileLeukemiaPLAC1 60544.pdf Sharma P, Pollyea DA. Shutting Down Acute Myeloid Leukemia and Myelodysplastic Syndrome with BCL-2 Family Protein Inhibition. Curr Hematol Malig Rep 2018;13(4):256-64.##De Kouchkovsky I, Abdul-Hay M. 'Acute myeloid leukemia: a comprehensive review and 2016 update'. Blood Cancer J 2016 1;6(7):e441.##Cobaleda C, Sanchez-Garcia I. B-cell acute lymphoblastic leukaemia: towards understanding its cellular origin. Bioessays 2009;31(6):600-9.##Hunger SP, Mullighan CG. Acute Lymphoblastic Leukemia in Children. N Engl J Med 2015;373(16):1541-52.##Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000 Jan 7;100(1):57-70.##Cocchia M, Huber R, Pantano S, Chen EY, Ma P, Forabosco A, et al. PLAC1, an Xq26 gene with placenta-specific expression. Genomics 2000 ;68(3):305-12.##Fant M, Barerra-Saldana H, Dubinsky W, Poindexter B, Bick R. The PLAC1 protein localizes to membranous compartments in the apical region of the syncytiotrophoblast. Mol Reprod Dev 2007;74(7):922-9.##Chen Y, Moradin A, Schlessinger D, Nagaraja R. RXRalpha and LXR activate two promoters in placenta- and tumor-specific expression of PLAC1. Placenta 2011;32(11):877-84.##Fant M, Weisoly DL, Cocchia M, Huber R, Khan S, Lunt T, et al. PLAC1, a trophoblast-specific gene, is expressed throughout pregnancy in the human placenta and modulated by keratinocyte growth factor. Mol Reprod Dev 2002;63(4):430-6.##Silva WA, Jr., Gnjatic S, Ritter E, Chua R, Cohen T, Hsu M, et al. PLAC1, a trophoblast-specific cell surface protein, is expressed in a range of human tumors and elicits spontaneous antibody responses. Cancer Immun 2007;7:18.##Fant M, Farina A, Nagaraja R, Schlessinger D. PLAC1 (Placenta-specific 1): a novel, X-linked gene with roles in reproductive and cancer biology. Prenat Diagn 2010 ;30(6):497-502.##Wang X, Baddoo MC, Yin Q. The placental specific gene, PLAC1, is induced by the Epstein-Barr virus and is expressed in human tumor cells. Virol J 2014;11:107.##Massabbal E, Parveen S, Weisoly DL, Nelson DM, Smith SD, Fant M. PLAC1 expression increases during trophoblast differentiation: evidence for regulatory interactions with the fibroblast growth factor-7 (FGF-7) axis. Mol Reprod Dev 2005;71(3):299-304.##Koslowski M, Sahin U, Mitnacht-Kraus R, Seitz G, Huber C, Tureci O. A placenta-specific gene ectopically activated in many human cancers is essentially involved in malignant cell processes. Cancer Res 2007;67(19):9528-34.##Dong XY, Peng JR, Ye YJ, Chen HS, Zhang LJ, Pang XW, et al. Plac1 is a tumor-specific antigen capable of eliciting spontaneous antibody responses in human cancer patients. Int J Cancer 2008;122(9):2038-43.##Tchabo NE, Mhawech-Fauceglia P, Caballero OL, Villella J, Beck AF, Miliotto AJ, et al. Expression and serum immunoreactivity of developmentally restricted differentiation antigens in epithelial ovarian cancer. Cancer Immun 2009;9:6.##Ghods R, Ghahremani MH, Madjd Z, Asgari M, Abolhasani M, Tavasoli S, et al. High placenta-specific 1/low prostate-specific antigen expression pattern in high-grade prostate adenocarcinoma. Cancer Immunol Immunother 2014;63(12):1319-27.##Ghods R, Ghahremani MH, Darzi M, Mahmoudi AR, Yeganeh O, Bayat AA, et al. Immunohistochemical characterization of novel murine monoclonal antibodies against human placenta-specific 1. Biotechnol Appl Biochem 2014;61(3):363-9.##Mahmoudi AR, Ghods R, Rakhshan A, Madjd Z, Bolouri MR, Mahmoudian J, et al. Discovery of a potential biomarker for immunotherapy of melanoma: PLAC1 as an emerging target. Immunopharmacology Immunotoxicol 2020;42(6):604-13.##Liu F, Shen D, Kang X, Zhang C, Song Q. New tumour antigen PLAC1/CP1, a potentially useful prognostic marker and immunotherapy target for gastric adenocarcinoma. J Clin Pathol 2015;68(11):913-6.##Yuan H, Chen V, Boisvert M, Isaacs C, Glazer RI. PLAC1 as a serum biomarker for breast cancer. PLoS One 2018;13(2):e0192106.##Li Y, Chu J, Li J, Feng W, Yang F, Wang Y, et al. Cancer/testis antigen-Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway. Mol Oncol 2018 ;12(8):1233-48.##Li Q, Liu M, Wu M, Zhou X, Wang S, Hu Y, et al. PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer. Oncol Lett 2018 ;15(4):5924-32.##

Expression of the Hepatitis C Virus core-NS3 Fusion Protein on the Surface of Bacterial Ghosts: Prospects for Vaccine Production 2 2 Background: Antigen presentation using bacterial surface display systems, on one hand, has the benefits of bacterial carriers, including low-cost production and ease of manipulation. On the other hand, the bacteria can help in stimulating the immune system as an adjuvant. For example, using bacterial surface display technology, we developed a hepatitis C virus (HCV) multiple antigens displaying bacteria's surface and then turned it into a bacterial ghost. Methods: The HCV core and NS3 proteins' conserved epitopes were cloned into the AIDA gene plasmid as an auto transporter. The recombinant plasmid was then transformed into Escherichia coli (E. coli) Bl21 (DE3). Recombinant bacteria were then turned into a bacterial ghost, an empty cell envelope. Whole-cell ELISA, flow cytometry, and Western blot techniques were used for monitoring the expression of proteins on the surface of bacteria. Results: A fusion protein of HCV core-NS3-AIDA was successfully expressed on the E. coli Bl21 (DE3) surface and confirmed by western blotting, Enzyme-Linked Immunosorbent Assay (ELISA), and flow cytometry detection techniques. Conclusion: The presence of HCV antigens on non-pathogen bacteria surfaces holds promise for developing safe and cost-benefit-accessible vaccines with optimal intrinsic adjuvant effects and exposure of heterologous antigens to the immune system. 173 179 Minoosadat Tayebinia Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences Iran Sedigheh Sharifzadeh Division of Medical Biotechnology, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences Division of Medical Biotechnology, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences Iran Gholamreza Rafiei Dehbidi Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences Iran Farahnaz Zare Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences Iran Reza Ranjbaran Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences Iran Amir Rahimi Bioinfirmatic and Computational Biology Research Center, Shiraz University of Medical Sciences Bioinfirmatic and Computational Biology Research Center, Shiraz University of Medical Sciences Iran Mohammad Reza Miri The Persian Gulf Marine Biotechnology Research Center, the Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences The Persian Gulf Marine Biotechnology Research Center, the Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences Iran Mehdi Mirzakhani Fars Blood Transfusion Organization Fars Blood Transfusion Organization Iran Abbas Behzad-Behbahani Division of Medical Biotechnology, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences Division of Medical Biotechnology, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences Iran Antigen presentationEpitopesFlow cytometryHepatitic CPlasmids 60545.pdf Hedskog C, Parhy B, Chang S, Zeuzem S, Moreno C, Shafran SD, et al., editors. Identification of 19 novel hepatitis C virus subtypes—further expanding HCV classification. Open forum infectious diseases; 2019: Oxford University Press US.##Kouka Saadeldin Abdelwahab ZNAS. Status of hepatitis C virus vaccination: Recent update. World J Gastroenterol 2016;22(2):862-73.##Walker CM, Grakoui A. Hepatitis C virus: why do we need a vaccine to prevent a curable persistent infection? Curr Opin Immunol 2015;35:137-43.##Chigbu DI, Loonawat R, Sehgal M, Patel D, Jain P. Hepatitis C virus infection: host–virus interaction and mechanisms of viral persistence. Cells 2019;8(4):376.##Bailey JR, Barnes E, Cox AL. Approaches, progress, and challenges to hepatitis C vaccine development. Gastroenterology 2019;156(2):418-30.##Stuart JD, Salinas E, Grakoui A. Immune system control of hepatitis C virus infection. Curr Opin Virol 2021;46:36-44.##Schlotthauer F, McGregor J, Drummer HE. To include or occlude: rational engineering of HCV vaccines for humoral immunity. 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Glycation Inhibition of Bovine Serum Albumin by Extracts of Momordica charantia L. using Spectroscopic and Computational Methods 2 2 Background: Momordica charantia (M. charantia) has been used in traditional medicine for the management of complications associated with diabetes mellitus. Several phytochemicals with different pharmacological properties have been previously identified from the botanical; however, the mechanisms of actions of this plant vis-à-vis inhibition of non-enzymatic protein glycation are not known. This study aimed at understanding the putative mechanisms underlying the antiglycation properties of M. charantia extracts experimental and theoretical approaches. Methods: The antiglycation properties of the plant were evaluated by studying the inhibitory actions of methanol and aqueous extracts on glucose-induced glycation of Bovine Serum Albumin (BSA) and protein aggregation. The mode of binding of identified phenolics of the botanical with BSA, amyloid beta-peptide (1-42) and 3D amyloid beta (1-42) fibrils were also investigated. Results: The in vitro experimental properties of the extracts showed that the extracts could prevent inductions of protein glycation and protein folding. The molecular docking analyses revealed that phenolics had better binding affinities with chlorogenic acid showing the highest binding score (-7.13±0.04 kcal/mol) towards BSA than glucose and their respective interactions with BSA could prevent glucose-induced protein aggregation. Conclusion: Consequently, the results of this study provide insight into the probable mechanisms of actions of the extracts of M. charantia against the inhibition of advanced glycation end products formation. 180 187 Babatunde Oso Department of Biochemistry, McPherson University, Seriki Sotayo Department of Biochemistry, McPherson University, Seriki Sotayo Nigeria Olubukola Agboola Department of Biochemistry, McPherson University, Seriki Sotayo Department of Biochemistry, McPherson University, Seriki Sotayo Nigeria Ige Olaoye GlycationMolecular docking analysisMomordica charantiaPhenolic acid 60546.pdf Li WL, Zheng HC, Bukuru J, De Kimpe N. Natural medicines used in the traditional Chinese medical system for therapy of diabetes mellitus. J Ethnopharmacol 2004 May 1;92(1):1-21.##Cho SJ, Roman G, Yeboah F, Konishi Y. The road to advanced glycation end products: a mechanistic perspective. Curr Med Chem 2007 Jun 1;14(15):1653-71.##Ulrich P, Cerami A. Protein glycation, diabetes, and aging. Recent Prog Horm Res 2001 Jan 1;56(1):1-22.##Finlayson C, Zimmerman D. Hyperglycemia not due to diabetes mellitus. Clinical Pediatric Emergency Medicine 2009 Dec 1;10(4):252-5.##Rondeau P, Bourdon E. The glycation of albumin: structural and functional impacts. Biochimie 2011 Apr 1;93(4):645-58.##Kooti W, Moradi M, Ali-Akbari S, Sharafi-Ahvazi N, Asadi-Samani M, Ashtary-Larky D. Therapeutic and pharmacological potential of Foeniculum vulgare Mill: a review. J HerbMed Pharmacology 2015 May 26;4(1):1-9.##Ahmed N, Babaei-Jadidi R, Howell SK, Beisswenger PJ, Thornalley PJ. Degradation products of proteins damaged by glycation, oxidation and nitration in clinical type 1 diabetes. Diabetologia 2005 Aug;48:1590-603.##Ahmed N, Thornalley PJ. Advanced glycation endproducts: what is their relevance to diabetic complications?. 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Anti-proliferative potentials of Aconitum heterophyllum Root Extract in Human Breast cancer (MDA-MB-231) cell lines-Genetic and Antioxidant Enzyme Approach 2 2 Background: One of the most important research activities around the world is the screening of various plant components for novel anticancer medicines. The anticancer activities of Aconitum heterophyllum were studied in human breast cancer MDA-MB- 231 cells in this study. Since tumorigenesis is thought to be the result of a series of pro- gressive gene alterations, including oncogene activation and tumour suppressor gene in- activation, the expression of genes like p53, p21, STAT, and Bcl-2, which are thought to be important in tumorigenesis and cell death, was determined. In the present study there was an upregulation in the level expression of p53and p21 and down regulation in the expression of BCL2 and STAT. However, there is increase and decrease level of gene expression in Aconitum heterophyllum roots loaded Phyto-Niosomes (nEEAH), when compared to ethanolic root extract of Aconitum heterophyllum EEAH extract treated MDA-MB-231 cell lines. Methods: The enzymatic antioxidants such as CAT, SOD, GR, GST, and GPX as well as non-enzymatic antioxidants such as glutathione, Vitamin E and Vitamin C were esti- mated in the treated MDA-MB-231 cells at the end of incubation. The RT-PCR tech- nique was performed to study the expression patterns of apoptotic genes such as p53 and p21 and anti-apoptotic genes BCL2 and STAT in the drug treated MDA-MB-231 cells Results: In the present study there was a significant (p<0.05) increase in CAT and glutathione levels and a decrease in Vit C, Vit E and SOD, GR, GST, GPX levels in the untreated MDA-MB-231 cells. Increased apoptotic gene expression and decreased anti-apoptotic gene expression suggest the anti-proliferative nature of the drug extract was comparable to the doxorubicin the positive drug used in the present study. Conclusion: It can be concluded that the ethanolic extract of Aconitum heterophyllum roots loaded Phyto-Niosomes (nEEAH), when compared to ethanolic root extract of Aconitum heterophyllum EEAH extract treated MDA-MB-231 cell lines exert its anticancer activity by activating the apoptotic genes, suppressing anti-apoptotic genes as well as modulating the antioxidant enzymes. 188 195 Sujatha Saravanan Department of Biotechnology Dr M.G.R Educational and Research Institute Maduravoyal, Chennai Department of Biotechnology Dr M.G.R Educational and Research Institute Maduravoyal, Chennai India Rajeswary Hari Karthikeyan Sekar Department of Biotechnology Dr M.G.R Educational and Research Institute Maduravoyal, Chennai Department of Biotechnology Dr M.G.R Educational and Research Institute Maduravoyal, Chennai India AntioxidantsApoptotic genesEnzymaticGlutathioneVitamin CVitamin E 60547.pdf Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A, et al. 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Characterization, Cytotoxicity and Anti-oxidant Studies of Phytoniosome Loaded with Ethanolic Leaf Extract of Tinospora Cordifolia 2 2 Background: From time immemorial herbal preparations are been employed for the treatment of several ailments. In recent years due to poor bioavailability the conventional herbal preparations are replaced by phytoniosomes, an advanced novel drug delivery system in which the herbal extracts are incorporated into a non-ionic surfactant to yield higher absorption and remarkable desired pharmacological activity. The present study is aimed to prepare and characterize the ethanolic leaf extract of Tinospora cordifolia (nELETC) loaded phytoniosome and to compare its antioxidant properties with ethanolic leaf extract of Tinospora cordifolia (ELETC). Methods: The ethanolic leaf extract and ethanolic leaf extract of Tinospora cordifolia loaded phytoniosome (ELETC and nELETC) were prepared. The characterization of the prepared phytoniosomes were performed by UV-Visible spectroscopy, FTIR, XRD, SEM, TEM, DLS and zeta potential. The nontoxic nature of the prepared phytoniosomes was analyzed using MTT assay in vero cell line. The antioxidant potential of ELETC and nELETC were compared by the scavenging activity of DPPH, Hydrogen peroxide and Superoxide radicals. Results: The formation of ethanolic leaf extract of Tinospora cordifolia loaded phytoniosome (nELETC) was confirmed with UV-Vis spectroscopy. The SEM and TEM images confirmed the spherical shape of the nELETC with average size ranging from 600 to 1800 nm. The zeta potential showed magnitude of -65.55 to -77.83 mV and its crystalline structure was confirmed by XRD analysis. Through the FTIR spectrum presence of alcohols, alkanes, phenols, esters, aliphatic and aromatic compounds as well as alkenes and carbolic acids were identified. MTT assay establishes the non-toxic nature of the synthesized nELETC and excellent antioxidant potential was observed for nELETC than ELETC. Conclusion: In conclusion, the ethanolic leaf extract of Tinospora cordifolia loaded phytoniosome (nELETC) will serve as a promising drug carrier in scavenging the free radicals and can be used in various biological applications.  196 202 Sri Devi Masilamani Department of Biotechnology, Dr. MGR Educational & Research Institute, Maduravoyal Department of Biotechnology, Dr. MGR Educational & Research Institute, Maduravoyal India Priya Chokkalingam Department of Biotechnology, Dr. MGR Educational & Research Institute, Maduravoyal Department of Biotechnology, Dr. MGR Educational & Research Institute, Maduravoyal India Rajeswary Hari AntioxidantsCytotoxicityPhytoniosomesTinospora cordifolia 60548.pdf Mishra N, Yadav NP, Meher JG, Sinha P. Phyto-vesicles: conduit between conventional and novel drug delivery system. 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Transmitted Drug Resistance Against Integrase Strand Transfer Inhibitors in Iranian HIV-Infected Naïve Patients 2 2 Background: Human Immunodeficiency Virus (HIV) has claimed the lives of millions of people during the past decades. While several antiretroviral drugs like Integrase Strand Transfer Inhibitors (INSTIs) have been introduced to control HIV, Transmitted Drug Resistance (TDR) in HIV genome caused failure in treatment. This study aimed to investigate TDR and natural occurring mutations (NOPs) in HIV integrase gene in Irani-an HIV patients. Methods: In this cross-sectional study, blood samples of 30 HIV-positive patients who had never taken integrase inhibitors were considered for CD4 T cell count, RT real-time PCR, and, Nested PCR. The sequencing results were analyzed by CLC sequence viewer software and Stanford University HIV Drug Resistance Database. Results: In all samples, nine NOPs with a high prevalence were found; however, we did not find any drug resistance mutations, except for a mutation in one sample, which showed a low resistance level. Subtype A1 was dominant in all samples. Conclusion: Based on the findings and compared to our previous study, all patients were sustainable to main integrase inhibitors, including bictegravir, raltegravir, bicte-gravir, elvitegravir and dolutegravir. It seems the resistant mutation pattern attributed to integrase inhibitors was not diffent among studied patients; hence, the prescription of such inhibitors helps physicians to control HIV infection in Iranian HIV-infected pa-tients. 203 206 Ava Hashempour Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences Iran Zahra Musavi Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences Iran Javad Moayedi Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences Iran Zahra Hasanshahi Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences Iran Behzad Dehghani Farzaneh Ghasabi Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences Iran Hassan Joulaei Drug resistanceHIVIntegrase 60549.pdf Ghassabi F, Hashempour T, Moghadami M, Davarpanah M, Kalani M, Chatrabnous N, et al. 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Infect Agent Cancer 2006;1(1):4.##Baesi K, Moallemi S, Farrokhi M, Alinaghi SAS, Truong HHM. Subtype classification of Iranian HIV-1 sequences registered in the HIV databases, 2006-2013. PloS One 2014;9(9):e105098.##Baesi K, Moradbeigi M, Ravanshad M, Baghban A. Phylogeny and drug resistance of HIV PR gene among HIV patients receiving RT inhibitors in Iran. Asian Pacific J Tropical Biomedicine 2016;6(5):451-4.##Baesi K, Ravanshad M, Hosseini Y, HAJI AM. Drug resistance profile and subtyping of HIV-1 RT gene in Iranian patients under treatment. Iranian J Biotechnol 2012;10(1):1-7.##