The Need to Continue the Education of Medical Doctors in Medical Basic Science: Existing Obstacles

en 39606682 The Need to Continue the Education of Medical Doctors in Medical Basic Science: Existing Obstacles In recent years, many prominent professors of basic sciences in Iranian medical schools had entered basic sciences from the field of medicine. This would facilitate the connection between basic and clinical sciences, providing a more attractive educational field for medical students in basic sciences 1,2. Of course, this does not mean that all professors of basic sciences must have a medical background. Maybe during my studies in the pharmacy field of Tehran University, Dr. Adibfar, Dr. Maleknia, Dr. Jahanghiri, Dr. Abdulwahabi and Dr. Shadan were all examples of that period. Also, many professors of basic sciences came from pharmacy, the best examples of which were Dr. Zarrindast and Dr. Dehpour. In those years, there was no empty place for Dr. Dehapour’ classes even to sit on the corridors of the salon. In the past two decades, when the salary of an assistant professor with a medicine or pharmacy background became half the average salary of a general practitioner or pharmacist, only the love of the principle of science was no longer enough to attract doctors and pharmacists in basic sciences. Maybe if a student of medicine saw Dr. Farrokh Shadan's old age and retirement period and never be interested in continuing his/her education in basic sciences. I hope that the new Minister of Health and Medical Education, Dr. Zafarqandi, who is a graduate of Tehran Medical School and has seen all these professors, and most importantly, was a biology teacher in high school, will urgently think about reviving basic medical sciences. In the scientific and career history of Dr. Zafarghandi, especially in 8 year-imposed war, the term of triage is very repeated. Mr. Minister, based on the triage, one of the first problems that your Excellency and the vice minister of education should urgently address, are the revival of basic medical science, the maintenance of the living conditions of basic science professors, and the renovation of teaching and research laboratories of basic science departments.   136 136 https://www.ajmb.org/En/Article.aspx?id=60587 https://www.ajmb.org/PDF/En/FullText/60587.pdf ShahinAkhondzadeh739

en 39606680 Overview on Immunopathology of Chronic Lymphocytic Leukemia and Tumor-Associated Antigens with Therapeutic Applications Chronic Lymphocytic Leukemia (CLL) is a clinically and biologically heterogeneous disease with a variable clinical course. The induction of a generalized state of immunosuppression, leading to susceptibility to infections and the failure of anti-tumor immune responses, is a key feature of the clinical course of CLL. In addition to B-cell receptor (BCR) signaling in CLL, several receptor tyrosine kinases (RTKs) have been reported to be constitutively active in leukemic B cells, resulting in promoted survival and resistance to apoptosis induced by chemotherapy. Several treatment options are available for CLL, including a watch-and-wait strategy, chemotherapy, targeted therapies, immunotherapies such as adoptive cellular therapy (CAR T-Cell Therapy), stem cell transplantation (allogeneic transplantation), radiation therapy and surgery. The identification of Tumor-Associated Antigens (TAAs) is the bottleneck of tumor immunology and immunotherapy, serving as promising targets for precise diagnosis, monitoring, or therapeutic approaches. Numerous TAAs have been identified, and their application in immunotherapy holds promise for the treatment of CLL. Furthermore, extensive ongoing research aims to identify new cancer TAAs. In this review, our objective is to provide a comprehensive overview of CLL immunology and recent findings regarding advances in TAAs with therapeutic applications in CLL. Cell therapy, Chronic lymphocytic leukemia, Hematologic malignancies, Immunotherapy, Tumor antigens 201 222 https://www.ajmb.org/En/Article.aspx?id=60588 https://www.ajmb.org/PDF/En/FullText/60588.pdf MahdiShabani125DavoudRostamzadehMedicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran92235MansoureMansouriDepartment of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran92236MahmoodJeddi-TehraniMonoclonal Antibody Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR) , Tehran, Iran15

en 39606684 The Importance of Biosecurity in Emerging Biotechnologies and Synthetic Biology The age of synthetic biology is ushering in new technologies for the advancement of society, human health, and agriculture. It appears that synthetic biology has integrated engineering paradigms into biological contexts. The combined use of new biotechnology and synthetic biology raises concerns about biosafety, biosecurity, and even cyberbiosecurity. For example, synthetic biology increases the possibility of designing, developing, and deploying pathogenic bioweapons in new and different ways than natural pathogens, as well as manipulating the genome. Evaluation of new technologies and platforms that enable creative or destructive manipulation of biological materials, systems, and organisms is important to identify potential security opportunities and vulnerabilities. This issue poses challenges to the medical community and civilian populations worldwide, creating a growing need to implement and enforce standardized biosafety and biosecurity regulations to protect humans, animals, plants, and the environment. It is critical to establish rules and management guidelines, provide strong leadership at the individual and institutional levels, and utilize established biosafety and biosecurity tools to mitigate the risks associated with synthetic biology. This review addresses the current state of synthetic biology, focusing on the concepts of biosafety, biosecurity, and cyber-biosecurity, as well as enhancing the standardization, regulation, and management of biosecurity in synthetic biology. In this review, the current situation in the Middle East region has been discussed and the challenges and opportunities encountered by synthetic biology researchers in this area is explored. The Middle East region is vulnerable to bioterrorism due to various factors. However, some countries in this strategically important region face challenges as they lack the necessary resources to effectively combat this significant global threat. These attacks are not limited to a specific border or area; they can affect multiple countries or have a global impact. Biosecurity, Biotechnology, Bioterrorism, Synthetic biology 223 232 https://www.ajmb.org/En/Article.aspx?id=60589 https://www.ajmb.org/PDF/En/FullText/60589.pdf MahboubehSoleimani SasaniChemical, Biological, Radiological & Nuclear (CBRN) Instructor, Iran's Passive Defense Organization, Tehran, Iran92195

en 39606678 The Potential of Human Wharton’s Jelly Mesenchymal Stem Cells Secretome Based Topical Gel for Therapeutic Application Background: Diabetic Foot Ulcer (DFU) might be worsened by neuropathy and vascular issues. This condition can cause 14.3% fatality, stressing the need for effective wound healing therapy. Wound healing is a complex biological process, and human Wharton's Jelly Mesenchymal Stem Cells (hWJMSCs) may help manage DFU treatment issues. This research focuses on utilizing a gel carrier to deliver bioactive substances from Wharton's Jelly Mesenchymal Stem Cells secretome (hWJ-MSCs-Sec) as a possible treatment for DFU. Methods: To maintain quality, hWJMSCs-Sec is thoroughly mixed with carbomer gel and freeze-dried. ELISA test is performed to determine the characterization of the gel of hWJMSCs-Sec such as Keratinocyte Growth Factor (KGF), Platelet-Derived Growth Factor (PDGF), Hepatocyte Growth Factor (HGF), Epidermal Growth Factor (EGF), and Heparin-Binding EGF-Like Growth Factor (HB-EGF). The antioxidant activity was also measured with Hydrogen peroxide (H2O2), Nitric oxide (NO), and Ferric Reducing Antioxidant Power (FRAP) assay. Proliferation assay was utilized using WST-8 and the wound healing potential was assessed via the migration cell ability of scratched-human skin fibroblast (BJ cells). Results: The freeze-dried hWJ-MSCs-Sec showed higher levels of KGF, HGF, PDGF, EGF, HB-EGF, and the antioxidant activities compared to fresh hWJ-MSCs-Sec. Additionally, the gel of freeze-dried hWJ-MSCs-Sec exhibited higher levels compared to the gel of fresh hWJMSCs-Sec. This was evidenced by faster closure of scratched wounds on BJ cells treated with hWJMSCs-Sec and freeze-dried hWJ-MSCs-Sec gel. Conclusion: The freeze-dried hWJ-MSCs-Sec gel exhibits superior quality compared to the non-freeze-dried hWJ-MSCs-Sec gel. This demonstrates that the freeze-drying procedure can maintain the bioactive chemicals found in hWJMSCs-Sec, potentially enhancing the efficacy of this gel in promoting cell regeneration for wound healing. Antioxidants, Carbomer gel, Freeze dried secretome gel, hWJ-MSCs, Wound healing 233 243 https://www.ajmb.org/En/Article.aspx?id=60590 https://www.ajmb.org/PDF/En/FullText/60590.pdf WahyuWidowati41601AhmadFariedDr. Hasan Sadikin Hospital, Bandung 40163, Indonesia92239RimontaFebby GunanegaraFaculty of Medicine, Maranatha Christian University, Bandung 40163, Indonesia92240FannyRahardjaFaculty of Medicine, Maranatha Christian University, Bandung 40163, Indonesia92241FadhilahHaifa ZahirohBiomolecular and Biomedical Research Center Bandung, Aretha Medika Utama, Bandung 40163, Indonesia92247AnnisaFirdaus Sutendi Biomolecular and Biomedical Research Center Bandung, Aretha Medika Utama, Bandung 40163, Indonesia92243RizalAzisDepartment of Translational Medical Science, Division of Cancer and Stem Cell, Biodiscovery Institute 3, The University of Nottingham, University Park, United Kingdom NG72RD, Nottingham, United Kingdom NG72RD92245RenandyKristianlie Ekajaya Biology Study Program, Faculty of Mathematics and Science Education, Universitas Pendidikan Indonesia, Bandung 40163, Indonesia92246

en 39606677 5-Fluorouracil Effectively Depletes Tumor Induced Myeloid Derived Suppressor Cells in 4T1 Mammary Carcinoma Model Background: Myeloid Derived Suppressor Cells (MDSCs) are capable of inhibiting both innate and adaptive immune responses and accumulate in the microenvironment of breast tumors. Hence, MDSC depletion by chemotherapeutic agents can improve clinical efficacy of cancer immunotherapy. The effects of 5-FU and doxorubicin agents on MDSC reduction in 4T1 breast cancer murine model were evaluated. Methods: 5×105 of 4T1 tumor cells were injected into mammary fat pad of BALB/c female mice. Tumor bearing mice were randomly divided into 4 groups: PBS receiving control group, doxorubicin receiving groups at doses of 2.5 and 5 mg/kg, and 5-FU receiving group at dose of 50 mg/kg. Doxorubicin and 5-FU agents were intraperitoneally administrated at three doses with 5-day intervals and five doses for three times a week, respectively. Then, on day 20 post tumor cells injection, spleens and tumors were isolated to determine frequency of CD11b+ Gr1+ MDSCs by flow cytometry analysis. Results: 5-FU was able to reduce significantly both splenic and interatumoral MDSCs comparing to control group (p=0.0276 and p=0.0067, respectively). Also, Doxorubicin treatment at dose of 50 mg/kg was associated to a significant reduction of splenic MDSCs in comparison to untreated group (p=0.0382). However, only 5-FU injection led to inhibit notably tumor growth in comparison to control group (p=0.0139). Conclusion: Findings show that 5-FU has inhibitory effects on MDSCs and tumor growth in 4T1 tumor model. So, more investigations are needed to study combination of 5-FU with immune based approaches to enhance the efficacy of cancer therapies. Breast cancer, Fluorouracil, Immunotherapy, Mammary neoplasm, Tumor microenvironment, Treatment outcome 244 250 https://www.ajmb.org/En/Article.aspx?id=60591 https://www.ajmb.org/PDF/En/FullText/60591.pdf KhadijehRamezani-AliakbariDepartment of Pathobiology, Faculty of Veterinary Science, Bu-Ali Sina University, Hamadan, Iran92248Seyed AmirJalali Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran92084MaedehAlinejadDepartment of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran92251MahmoodJeddi-TehraniMonoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran15MahdiShabani125

en 39606679 Immunogenic Consideration of a Designed Polypeptide Against Brucellosis Compared to RB51: An In Vivo Study Background: Brucellosis in livestock and its transmission to humans through the consumption of contaminated dairy products is an important issue. The introduction of new approaches using immunogenic proteins against and diagnosing brucellosis is a serious issue in human health. Methods: Brucella abortus contains five proteins including: MOXR family ATPase-α2, T9SS C-terminal target domain-containing protein, Cobyric acid synthase, Hypothetical protein, and VirB11 type IV Secretion protein, which were considered and the designed recombinant polypeptide was produced and evaluated. The pure recombinant protein ABOR with 549aa in combination with chitin as an adjuvant was injected subcutaneously into guinea pigs to evaluate their immunity responses. Results: The results indicated that the ABOR recombinant protein induced Th1 immunity with high levels of specific IgG (IgG2a) as well as Interferon-γ (IFN-γ), Interleukin-2 (IL-2), IL-12, and Tumor Necrosis Factor-alpha (TNF-α), compared to the control group. Th1/Th2 ratio analysis demonstrated the efficacy of ABOR protein combined with chitin in stimulating cellular immunity in the animals. Conclusion: Designed recombinant polypeptide combined with chitin showed ability for induction of cellular and humoral immunity an guinea pigs compared to RB51 vaccine. Brucella abortus, Guinea pigs, Immunity, Recombinant proteins 251 259 https://www.ajmb.org/En/Article.aspx?id=60592 https://www.ajmb.org/PDF/En/FullText/60592.pdf MinaSaadatDepartment of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran92253MojganBandehpourDepartment of Embryology and Andrology, Avicenna Research Institute, ACECR, Tehran, Iran390BahramKazemiCellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran388NarimanMosaffaDepartment of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran92255

en 39606683 The Effect of Simulated Physiological Oocyte Maturation (SPOM) and L-Carnitine on Bovine Oocyte Developmental Competence Background: Simulated Physiological Oocyte Maturation (SPOM) mimics in vitro the physiological events of oocyte maturation in the presence of cAMP modulators. These modulators increase the intracellular concentrations of cAMP, which inhibits the immediate resumption of meiosis and gives the oocyte more time to gain optimal developmental competence. In addition, L-carnitine helps to increase the energy supply of cells through the β-oxidation of fatty acids. This study aimed to investigate the effect of SPOM and L-carnitine supplementation during In Vitro Maturation (IVM) and In Vitro Culture (IVC) on the developmental competence of bovine oocytes. Methods: Ovarian Cumulus Complexes (COCs) were cultured in the presence or absence of forskolin+IBMX during the first 2 hr of IVM (pre-IVM) with or without L-carnitine (LC) during IVM or IVC in six experimental groups as follows: I) pre-IVM (pre-IVM group), II) pre-IVM with L-carnitine supplementation during IVM (pre-IVM/LC group), III) L-carnitine supplementation during IVM (IVM/LC group), IV) L-carnitine supplementation during in vitro culture (IVC/LC group), V) pre-IVM+ IVC/LC group, and VI) no treatment during IVM and IVC (Control group). The cleavage and blastocyst rates, the blastocysts’ total cells number, and the expression of Nanog, Bax, Oct4, Cdx2, and Ifnt genes in resulting blastocysts were assessed. To assess differences among experimental groups, a one-way analysis of variance was initially employed, followed by post hoc Fisher LSD. The difference between groups was considered statistically significant when p<0.05. Results: The cleavage and blastocyst rates in the Pre-IVM and Pre-IVM/LC groups was higher than control group and other groups (p≤0.05) except for IVC/LC and IVM/LC groups, respectively. The number of blastocyst’s Inner Cell Mass (ICM) in pre-IVM and Pre-IVM/LC groups as well as the ratio of ICM/TE were higher than control group (p<0.05). The expression of OCT4, CDX2, and IFNT increased in both the pre-IVM and pre-IVM/LC groups compared to the control group (p<0.05). Conclusion: In conclusion, the application of SPOM-adapted IVM and L-carnitine during IVM of bovine oocyte improves the quantity and quality of the resulting embryos. 3-Isobutyl-l-methylxanthine, bcl-2-associated X protein, Blastocyst, Carnitine, Cattle, Meiosis, Oocytes, Pre-IVM 260 267 https://www.ajmb.org/En/Article.aspx?id=60593 https://www.ajmb.org/PDF/En/FullText/60593.pdf AliMalekpourSina Fanavaran Mandegar Company, Alborz Science and Technology Park, Kamalshahr, Iran92256AbolfazlShiraziSina Fanavaran Mandegar Company, Alborz Science and Technology Park, Kamalshahr, Iran82SaraBorjian BoroujeniSina Fanavaran Mandegar Company, Alborz Science and Technology Park, Kamalshahr, Iran337AliSarvariSina Fanavaran Mandegar Company, Alborz Science and Technology Park, Kamalshahr, Iran335Mohammad MehdiNaderiSina Fanavaran Mandegar Company, Alborz Science and Technology Park, Kamalshahr, Iran334MostafaPournourali Sina Fanavaran Mandegar Company, Alborz Science and Technology Park, Kamalshahr, Iran91924BaharehBehzadiDepartment of Embryology and Andrology, Avicenna Research Institute, ACECR, Tehran, Iran506Mohammad MehdiMehrazarDepartment of Embryology and Andrology, Avicenna Research Institute, ACECR, Tehran, Iran11473

en 39606685 Generation of Optimized Consensus Sequences for Hepatitis C virus (HCV) Envelope 2 Gly-coprotein (E2) by a Modified Algorithm: Implication for a Pan-genomic HCV Vaccine Background: Despite the success of "direct-acting antivirals" in treating Hepatitis C Virus (HCV) infection, invention of a preventive HCV vaccine is crucial for global elimination of the virus. Recent data indicated the importance of the induction of Pan-genomic neutralizing Antibodies (PnAbs) against heterogenic HCV Envelope 2(E2), the cellular receptor binding antigen, by any HCV vaccine candidate. To overcome HCVE2 heterogeneity, "generation of consensus HCVE2 sequences" is proposed. However, Consensus Sequence (CS) generating algorithms such as "Threshold" and "Majority" have certain limitations including "Threshold-rigidity" which leads to induction of undefined residues and insensitivity of the "Majority" towards the "evolutionary cost of residual substitutions". Methods: Herein, first a modification to the "Majority" algorithm was introduced by incorporating BLOSUM matrices. Secondly, the HCVE2 sequences generated by the "Fitness" algorithm (using 1698 sequences from genotypes 1, 2, and 3) was compared with those generated by the "Majority" and "Threshold" algorithms using several in silico tools. Results: Results indicated that only "Fitness" provided completely defined, gapless HCVE2s for all genotypes/subtypes, while considered the evolutionary cost of amino acid replacements (main "Majority/Threshold" limitations) by substitution of several residues within the generated consensuses. Moreover, "Fitness-generated HCVE2 CSs" were superior for antigenic/immunogenic characteristics as an antigen, while their positions within the phylogenetic trees were still preserved. Conclusion: "Fitness" algorithm is capable of generating superior/optimum HCVE2 CSs for inclusion in a pan-genomic HCV vaccine and can be similarly used in CS generation for other highly variable antigens from other heterogenic pathogens. Amino acids, Antibodies, Antiviral Agents, Consensus sequence, Genomics, Genotype, Hepacivirus, Hepatitic C, Inventions, Phylogeny, Vaccines, Virus diseases 268 278 https://www.ajmb.org/En/Article.aspx?id=60594 https://www.ajmb.org/PDF/En/FullText/60594.pdf ReyhanehMohabatiDepartment of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran92259RezaRezaeiSchool of Biology, College of Science, University of Tehran, Tehran, Iran92260NasirMohajelDepartment of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran92261Mohammad MehdiRanjbarDepartment of FMD Vaccine Production, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Tehran, Iran92262KatayounSamimi-RadDepartment of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran92263KayhanAzadmanesh483FarzinRoohvand160

en 39606681 Optimization of the Production of Soluble Recombinant TEV Protease in Two E. coli Strains Background: The low solubility of Tobacco Etch Virus (TEV) protease, a functional enzyme that cleaves protein tags without significant modification in its sequence, is one of the most important limitations of this enzyme. In this study, the aim was to increase the solubility of TEV by changing the expression conditions and designing lysis buffer with various solubilizing agents to improve its solubility. Methods: Escherichia coli (E. coli) BL21 (DE3) and E. coli origami harboring wild type TEV-pKR793 and mutant N23F TEV-pKR793 plasmids were used for the expression. Response surface methodology was used to determine the best culture conditions (IPTG concentration, incubation time and incubation temperature) of soluble expression. Furthermore, eight different solubilizing agents were added separately to the lysis buffer to check their effect on the protein solubility. Results: The production of soluble N23F in E. coli BL21 (DE3) was two-folds more than the wild type and the inclusion body formation in the mentioned form was diminished as about 25% in comparison to the wild type. Finally, betaine had the most effects for enhancing the soluble expression of N23F in both host cells. For the wild type, sodium selenite, xylitol, and glycine showed the most effects on soluble production. Conclusion: The solubility of the mutant form of TEV protease increased in E. coli BL21 (DE3) compared to its wild form. Also, using additives such as betaine to the lysis buffer, increased the solubility of N23F in E. coli BL21 (DE3) and origami strains. Escherichia coli (E. coli), Solubility, Solubilizing agents, TEV protease 279 283 https://www.ajmb.org/En/Article.aspx?id=60595 https://www.ajmb.org/PDF/En/FullText/60595.pdf MatinehShahriari Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Tehran, Iran92264FatemehShafieeBioinformatics Research Center, School of pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran92265FatemehMoazenDepartment of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Tehran, Iran92266HamidMir Mohammad SadeghiDepartment of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran302