The Clinician Scientist Training Program in Iran: Catalyzing Clinical Science Advancements

en 37538238 The Clinician Scientist Training Program in Iran: Catalyzing Clinical Science Advancements 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 https://www.ajmb.org/En/Article.aspx?id=60541 https://www.ajmb.org/PDF/En/FullText/60541.pdf HosseinSanjari Moghaddam Psychiatric Research Center, Roozbeh Hospital Tehran University of Medical Sciences, Tehran, Iran91995ShahinAkhondzadeh739

en 37538241 Effects of Antidepressant Medication on Brain-derived Neurotrophic Factor Concentration and Neuroplasticity in Depression: A Review of Preclinical and Clinical Studies 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. Antidepressant medication, Brain-derived neurotrophic factor, Depression, Neuroplasticity 129 138 https://www.ajmb.org/En/Article.aspx?id=60542 https://www.ajmb.org/PDF/En/FullText/60542.pdf SophiaEsalatmanesh Arash Women Hospital, Tehran University of Medical Sciences, Tehran, Iran92036LadanKashaniArash Women Hospital, Tehran University of Medical Sciences, Tehran, Iran92037ShahinAkhondzadeh739

en 37538236 Application of Menstrual Blood Derived Stromal (stem) Cells Exert Greater Regenerative Potency Than Fibroblasts/Keratinocytes in Chronic Wounds of Diabetic Mice 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. Bilayer scaffold, Diabetic wound, Fibroblasts, Keratinocyte, Menstrual blood stem cells 139 156 https://www.ajmb.org/En/Article.aspx?id=60540 https://www.ajmb.org/PDF/En/FullText/60540.pdf EbrahimMirzadeganNanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran653HannanehGolshahi Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran91933ZahraSaffarianNanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran92032HalehEdalatkhahNanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran1151MaryamDarziNanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran92033SomayehKhorasaniNanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran92034KioomarsSaliminejadReproductive Biotechnology Research Center, Avicenna Research Institute, ACECR,, Tehran, Iran393SomaiehKazemnejad91932

en 37538240 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 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. Conditioned medium, Menstrual blood stem cells, Metaplasia, Mitochondrial transfer, Myocardial infarction 157 166 https://www.ajmb.org/En/Article.aspx?id=60543 https://www.ajmb.org/PDF/En/FullText/60543.pdf MahmoodManshoriNanobiotechnology Research Center, Avicenna Research Institute, ACECR,, Tehran, Iran91931SomaiehKazemnejadNanobiotechnology Research Center, Avicenna Research Institute, ACECR,, Tehran, Iran91932NasimNaderiRajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences,, Tehran, Iran92041AbolfazlShiraziReproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, , Tehran, Iran82MaedehArabianRajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences,, Tehran, Iran92042MarziehEghtedar DoostNanobiotechnology Research Center, Avicenna Research Institute, ACECR,, Tehran, Iran92043MaryamDarziNanobiotechnology Research Center, Avicenna Research Institute, ACECR,, Tehran, Iran92033SamanehMontazeriNanobiotechnology Research Center, Avicenna Research Institute, ACECR,, Tehran, Iran92044Nahid AboutalebDepartment of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran92045HannanehGolshahi 91933

en 37538244 Investigation of Expression Profile of Placenta-specific 1 (PLAC1) in Acute Myeloid and Lymphoid Leukemias 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. Acute lymphoblastic leukemia , Acute myeloid leukemia, Biomarker, Expression profile, Leukemia, PLAC1 167 172 https://www.ajmb.org/En/Article.aspx?id=60544 https://www.ajmb.org/PDF/En/FullText/60544.pdf ParastouGholami Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran91958HosseinAsgarian-OmranDepartment of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran238MarjanYaghmaeiHematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran91961JafarMahmoudianMonoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran114ShirinKianersiHSCT Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran92047SinaSalari HSCT Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran91963EhsanZaboliGastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran92049MahmoodJeddi-TehraniMonoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran15Amir-HassanZarnaniReproductive Biotechnology Research Center, Avicenna Research Institute, ACECR,, Tehran, Iran7MahdiShabani125

en 37538239 Expression of the Hepatitis C Virus core-NS3 Fusion Protein on the Surface of Bacterial Ghosts: Prospects for Vaccine Production 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. Antigen presentation, Epitopes, Flow cytometry, Hepatitic C, Plasmids 173 179 https://www.ajmb.org/En/Article.aspx?id=60545 https://www.ajmb.org/PDF/En/FullText/60545.pdf MinoosadatTayebinia Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran92050SedighehSharifzadeh Division of Medical Biotechnology, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran71787GholamrezaRafiei Dehbidi Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran92052FarahnazZareDiagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran71786RezaRanjbaranDiagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran898AmirRahimiBioinfirmatic and Computational Biology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran92055Mohammad RezaMiriThe Persian Gulf Marine Biotechnology Research Center, the Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran1345MehdiMirzakhani Fars Blood Transfusion Organization, Shiraz, Iran92057AbbasBehzad-BehbahaniDivision of Medical Biotechnology, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran899

en 37538235 Glycation Inhibition of Bovine Serum Albumin by Extracts of Momordica charantia L. using Spectroscopic and Computational Methods 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. Glycation, Molecular docking analysis, Momordica charantia, Phenolic acid 180 187 https://www.ajmb.org/En/Article.aspx?id=60546 https://www.ajmb.org/PDF/En/FullText/60546.pdf BabatundeOsoDepartment of Biochemistry, McPherson University, Seriki Sotayo, Ogun State, Nigeria92060OlubukolaAgboola Department of Biochemistry, McPherson University, Seriki Sotayo, Ogun State, Nigeria92058IgeOlaoye 92059

en 37538242 Anti-proliferative potentials of Aconitum heterophyllum Root Extract in Human Breast cancer (MDA-MB-231) cell lines-Genetic and Antioxidant Enzyme Approach 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. Antioxidants, Apoptotic genes, Enzymatic, Glutathione, Vitamin C, Vitamin E 188 195 https://www.ajmb.org/En/Article.aspx?id=60547 https://www.ajmb.org/PDF/En/FullText/60547.pdf SujathaSaravananDepartment of Biotechnology Dr M.G.R Educational and Research Institute Maduravoyal, Chennai, Tamil Nadu, India92061RajeswaryHari91947KarthikeyanSekarDepartment of Biotechnology Dr M.G.R Educational and Research Institute Maduravoyal, Chennai, Tamil Nadu, India92063

en 37538243 Characterization, Cytotoxicity and Anti-oxidant Studies of Phytoniosome Loaded with Ethanolic Leaf Extract of Tinospora Cordifolia 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.  Antioxidants, Cytotoxicity, Phytoniosomes, Tinospora cordifolia 196 202 https://www.ajmb.org/En/Article.aspx?id=60548 https://www.ajmb.org/PDF/En/FullText/60548.pdf Sri DeviMasilamaniDepartment of Biotechnology, Dr. MGR Educational & Research Institute, Maduravoyal, Chennai, India92064PriyaChokkalingam Department of Biotechnology, Dr. MGR Educational & Research Institute, Maduravoyal, Chennai, India92065RajeswaryHari91947

en 37538237 Transmitted Drug Resistance Against Integrase Strand Transfer Inhibitors in Iranian HIV-Infected Naïve Patients 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. Drug resistance, HIV, Integrase 203 206 https://www.ajmb.org/En/Article.aspx?id=60549 https://www.ajmb.org/PDF/En/FullText/60549.pdf AvaHashempourShiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran92066ZahraMusavi Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran92067JavadMoayediShiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran92068ZahraHasanshahiShiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran92069BehzadDehghani 92070FarzanehGhasabiShiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran92071HassanJoulaei92072