Therapeutic Monoclonal Antibodies and Emergence of Their Biosimilars 2 2 Antibodies are proteins of the immune system that are produced by B-lymphocytes. These proteins exert their effects by recognizing and binding to their targets (antigens). A monoclonal antibody (mAb) is originally produced by a single B-cell. Production of mAbs was first introduced in 1975 using cell fusion technique and hybridoma cell production. A Hybridoma is formed by fusion of an antibody producing B-lymphocyte and a myeloma cell line. These cells have two main characteristics, production of uniform, monospecific antibodies (mAbs) that originate from the B-cell and immortality that comes from the myeloma cell line. A hybridoma cell line is thus acting like a biological factory that produces and secretes mAbs into the cell culture medium. Most of the mAbs have been produced in mice and are thus proteins of murine origin. mAbs were later found to be able to bind biological targets like tumor antigens, molecules involved in autoimmune and infectious disease-related molecules, etc. This led to emergence of therapeutic monoclonal antibodies. However, since the first mAbs were murine proteins (OKT3 was injected to kidney transplant patients to prevent graft rejection), their repeated administration raised Human Anti Mouse Antibody (HAMA) in the patients that resulted in neutralization of the injected mAb (OKT3). The solution was to genetically change the murince antibodies to human antibodies. In this regard chimeric (%80 -%90 human), humanized (≥ %90 human) and fully human (%100 human) therapeutic mAbs were produced. At present more than 50 therapeutic mAbs are on the market with more than 120 billion USD global market share. These mAbs have shown very good therapeutic effect in treatment of cancers, autoimmune and infectious diseases. However, these drugs are very expensive and thus their patient accessibility is limited. Although, they are protected by patents, some patents have already expired and some are close to expiration dates. Here, biosimilar versions of these drugs have started to immerge. Biosimilars are defined as biological drugs that are highly similar but not identical to the biological reference (original or originator) drug. The approval of biosimilars to enter the biopharmaceutical market is governed by the regulatory bodies in different countries. This happens under strict and comprehensive comparability exercise. The biosimilarity determination procedure is planned to ensure that the difference between the originator and the biosimilar drug is not clinically significant. The assessment includes immunochemical and physicochemical properties, biological activity, structural similarity, purity, contamination with impurities like host cell protein and DNA. In addition, in vivo pharmacology studies like pharmacokinetic and pharmaco-dynamic characteristics as well as, efficacy, safety and tolerability must be determined and approved. Moreover, after market analyses like pharmaco-epidemiological studies should also be done. These procedures are also necessary to be performed to assure the prescribing physicians to suggest them to their patients. Thus, the biosimilars, due to their lower production costs, are expected to introduce huge amounts of cost savings to healthcare systems and more importantly, increase affordability/accessibility of biological treatment. 61 61 Mahmood Jeddi-Tehrani Department of Hybridoma, Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Department of Hybridoma, Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Iran Editorial 295.pdf ####

Effects of Hypoxia on Biology of Human Leukemia T-cell Line (MOLT-4 cells) Co-cultured with Bone Marrow Mesenchymal Stem Cells 2 2 Background: One of the most significant problems in the treatment of leukemia is the expansion of resistance to chemotherapeutic agents. Therefore, assessing the drug resistance and especially the drug resistance genes of leukemic cells is important in any treatment. The impact of Mesenchymal Stem Cells (MSCs) and hypoxic condition have been observed in the biological performance of majority of leukemic cells. Methods: MOLT-4 cells were co-cultured with MSCs in the hypoxic condition induced by Cobalt Chloride (CoCl2) for 6 and 24 hr. Then, apoptosis of cells was analyzed using annexin-V/PI staining and expression of the drug resistance genes including MDR1, MRP, and BCRP along with apoptotic and anti-apoptotic genes, including BAX and BCL2, was evaluated by real-time PCR. Results: The hypoxic condition for MOLT-4 cells co-cultured with MSCs could significantly increase the expression of MDR1 and BCRP genes (p<0.05) which are involved in drug resistance. Also, the results indicated that this condition significantly increases the expression of BCL2 (p<0.05) and reduces the apoptosis in MOLT- 4 cells co-cultured with MSCs in the hypoxic condition. Conclusions: These effects can demonstrate the important role of hypoxia and MSCs on the biological behavior of Acute Lymphoblastic Leukemia (ALL) cells that may lead to particular treatment outcomes. 62 68 Sina Baharaghdam Immunology Research Center, Tabriz University of Medical SciencesHematology and Oncology Research Center, Tabriz University of Medical Sciences Immunology Research Center, Tabriz University of Medical SciencesHematology and Oncology Research Center, Tabriz University of Medical Sciences IranIran Mehdi Yousefi Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences IranIran Ali Akbar Movasaghpour Hematology and Oncology Research Center, Tabriz University of Medical Sciences Hematology and Oncology Research Center, Tabriz University of Medical Sciences Iran Saeed Solali Hematology and Oncology Research Center, Tabriz University of Medical Sciences Hematology and Oncology Research Center, Tabriz University of Medical Sciences Iran Mehdi Talebi Hematology and Oncology Research Center, Tabriz University of Medical Sciences Hematology and Oncology Research Center, Tabriz University of Medical Sciences Iran Milad Ahani-Nahayati Hematology and Oncology Research Center, Tabriz University of Medical Sciences Hematology and Oncology Research Center, Tabriz University of Medical Sciences Iran Hamid Lotfimehr Hematology and Oncology Research Center, Tabriz University of Medical Sciences Hematology and Oncology Research Center, Tabriz University of Medical Sciences Iran Karim Shamsasanjan Hematology and Oncology Research Center, Tabriz University of Medical Sciences Hematology and Oncology Research Center, Tabriz University of Medical Sciences Iran Acute lymphoblastic leukemiaDrug resistanceHypoxiaMesenchymal stem cell 312.pdf Bozok Cetintas V, Aktug H, Oltulu F, Keskinoglu A, Erer Del Castello B, Taskiran D. 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The Evaluation of Astaxanthin Effects on Differentiation of Human Adipose Derived Stem Cells into Oligodendrocyte Precursor Cells 2 2 Background: Multiple Sclerosis (MS) has been explained as an autoimmune mediated disorder in central nerve system. Since conventional therapies for MS are not able to stop or reverse the destruction of nerve tissue, stem cell-based therapy has been proposed for the treatment of MS. Astaxanthin (AST) is a red fat-soluble xanthophyll with neuroprotection activity. The aim of this study was evaluation of pre-inducer function of AST on differentiation of human Adipose- Derived Stem Cells (hADSCs) into oligodendrocyte precursor cells. Methods: After stem cell isolation, culture and characterization by flow cytometry, hanging drop technique was done for embryoid body formation. In the following, hADSCs were differentiated into oligodendrocyte cells in the presence of AST at various concentrations (1, 5, and 10 ng/ml). Finally, immunocytochemistry and real-time PCR techniques were used for assessment of oligodendrocyte differentiation.  Results: Flow cytometry results indicated that hADSCs were CD44, CD49-positive, but were negative for CD14, CD45 markers. In addition, immunocytochemistry results revealed that, in AST treated groups, the mean percentage of Olig 2 and A2B5 positive cells increased especially in 5 ng/ml AST treated group compared to control group (p<0.001). Moreover, real-time PCR analysis confirmed the results of immunocytochemistry. Conclusion: Since hADSCs have the potential to differentiate into multi lineage cells and due to important functions of AST in regulating various cellular processes, it seems that AST can be used as a promoter for oligodendrocyte differentiation of hADSCs for being used in cell transplantation in multiple sclerosis. 69 74 Nazem Ghasemi Department of Anatomical Science and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences Department of Anatomical Science and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences Iran Adult stem cellsAstaxanthinMultiple sclerosisOligodendroglia 307.pdf Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: pathogenesis, symptoms, diagnoses and cell-based therapy. Cell J 2017;19(1):1-10.##Sadovnick AD, Ebers GC, Dyment DA, Risch NJ. Evidence for genetic basis of multiple sclerosis. The Canadian collaborative study group. Lancet 1996;347(9017):1728-1730.##Fujinami RS, von Herrath MG, Christen U, Whitton JL. 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Ectopic Expression of Human DPPA2 Gene in ESCC Cell Line Using Retroviral System 2 2 Background: Cancer/Testis Antigens (CTAs) are a subgroup of tumor-associated antigens which are expressed normally in germ line cells and trophoblast, and aberrantly in a variety of malignancies. One of the most important CTAs is Developmental Pluripotency Associated-2(DPPA2) with unknown biological function. Considering the importance of DPPA2 in developmental events and cancer, preparing a suitable platform to analyze DPPA2 roles in the cells seems to be necessary. Methods: In this study, the coding sequence of DPPA2 gene was amplified and cloned into the retroviral expression vector to produce recombinant retrovirus. The viral particles were transducted to Esophageal Squamous Cell Carcinoma (ESCC) cell line (KYSE-30 cells) and the stable transducted cells were confirmed for ectopic expression of DPPA2 gene by real-time PCR. Results: According to the critical characteristics of retroviral expression system such as stable and long time expression of interested gene and also being safe due to deletion of retroviral pathogenic genes, this system was used to induce expression of DPPA2 gene and a valuable platform to analyze its biological function was prepared. Transduction results clearly showed efficient overexpression of the gene in target cells in protein level due to high level of GFP expression. Conclusion: Such strategies can be used to produce high levels of desired protein in target cells as a therapeutic target. The produced recombinant cells may present a valuable platform to analyze the effect of DPPA2 ectopic expression in target cells. Moreover, the introduction of its potential capacity into the mouse model to evaluate the tumorigenesis of these cancer cells in vivo leads to an understanding of the biological importance of DPPA2 in tumorigenesis. In addition, our purified protein can be used in a mouse model to produce specific antibody developing a reliable detection of DPPA2 existence in any biological fluid through ELISA system. 75 82 Maryam Khaleghizadeh Department of Microbiology, Damghan Branch, Islamic Azad UniversityHuman Genetic Division, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences Department of Microbiology, Damghan Branch, Islamic Azad UniversityHuman Genetic Division, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences IranIran Mohammad Mahdi Forghanifard Human Genetic Division, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences Human Genetic Division, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences Iran Abolfazl Rad Cellular and Molecular Research Center, Sabzevar University of Medical Sciences Cellular and Molecular Research Center, Sabzevar University of Medical Sciences Iran Moein Farshchian Human Genetic Division, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences Human Genetic Division, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences Iran Zahra Hejazi Department of Microbiology, Damghan Branch, Islamic Azad University Department of Microbiology, Damghan Branch, Islamic Azad University Iran Mehran Gholamin Human Genetic Division, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences Human Genetic Division, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences Iran Bahram Memar Department of Pathology, Imam Reza Hospital, Mashhad University of Medical Sciences Department of Pathology, Imam Reza Hospital, Mashhad University of Medical Sciences Iran Mohammad Reza Abbaszadegan Human Genetic Division, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical SciencesMedical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences Human Genetic Division, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical SciencesMedical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences IranIran CarcinogenesisEsophageal squamous cell carcinomaGerm cellsTestis 305.pdf Evans MJ, Kaufman MH. 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Lavandula angustifolia Effects on Rat Models of Alzheimer’s Disease Through the Investigation of Serum Metabolic Features Using NMR Metabolomics 2 2 Background: Alzheimer’s Disease (AD) is the most prevalent cause of memory impairment in the elderly population, but the diagnosis and treatment of the disease is still challenging. Lavender aqueous extract has recently been shown to have the potential in clearing Amyloid-beta plaques from AD rat hippocampus. To elucidate the therapeutic mechanisms of lavender, serum metabolic fingerprint of Aβ-induced rat Alzheimer’s models was investigated through nuclear magnetic resonance spectrometry. Methods: For the establishment of rat Alzheimer’s models, 10 μg of Amyloid beta 1-42 was injected to male Wistar rats. The lavender aqueous extract was injected 20 days after the establishment of the models, once daily for 20 days. Serum samples were collected and metabolite fingerprints were obtained using 500 MHz 1H-NMR spectrometry, following multivariate statistical analyses. The resulted metabolites were then subjected to pathway analysis tools to reveal metabolic pathways affected by the lavender extract treatment. Results: Levels of 10 metabolite markers including alanine, glutamine, serine, isoleucine, valine, carnitine, isobutyrate, pantothenate, glucose and asparagine were reversed nearly to control values after treatment with lavender extract. The results revealed that the most significantly affected pathways during treatment with lavender extract belonged to carbohydrate and amino acid metabolism, including pantothenate and CoA metabolism, glyoxilate and dicarboxylate metabolism, alanine, aspartate and glutamate metabolism, cysteine and methionine metabolism. Conclusion: As lavender extract reversed the direction of changes of some metabolites involved in AD pathogenesis, it was concluded that the extract might play a role in the disease improvement and serve as a potential therapeutic option for the treatment of AD. Moreover, the metabolites which were found in AD rats could serve as a potential marker panel for the disease; however, much further investigation and validation of the results is needed. 83 92 Afsaneh Arefi Oskouie Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences Iran Reyhaneh Farrokhi Yekta Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical SciencesProteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical SciencesProteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences IranIran Mostafa Rezaie Tavirany Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences Iran Masoud Soheili Kashani Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical SciencesProteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical SciencesProteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences IranIran Fatemeh Goshadrou Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences Iran Alzheimer diseaseLavandulaMetabolomicsSerum 306.pdf Kelley BJ, Petersen RC. 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Isolation and Proliferation of Spermatogonial Cells from Ghezel Sheep 2 2 Background: Sheep industry has taken steps toward transforming itself into a more efficient and competitive field. There are many varieties of sheep breeds in the world that each of them serves a useful purpose in the economies of different civilizations. Ghezel sheep is one of the Iranian important breeds that are raised for meat, milk and wool. Field of spermatogonial cell technologies provides tools for genetic improvement of sheep herd and multiple opportunities for research. Spermatogonial cells are the only stem cells capable of transmitting genetic information to future generations.  Methods: This study was designed to extend the technique of isolation and in vitro proliferation of spermatogonial cells in Ghezel sheep.  Results: Isolated cells were characterized further by using specific markers for type A spermatogonia, including PLZF. Also, sertoli cells were characterized by vimentin which is a specific marker for sertoli cells. After 10 days of co-culture, viability rates of the cells was above 94.7%, but after the freezing process the viability rates were 74 percent. Conclusion: In this study, a standard method for isolation and in vitro proliferation of spermatogonial stem cells in Ghezel sheep was developed. 93 97 Babak Qasemi-Panahi Department of Animal Science, Faculty of Agriculture, University of Tabriz Department of Animal Science, Faculty of Agriculture, University of Tabriz Iran Mansoureh Movahedin Department of Anatomy, Faculty of Medical Science, University of Tarbiat Modares Department of Anatomy, Faculty of Medical Science, University of Tarbiat Modares Iran Gholamali Moghaddam Department of Animal Science, Faculty of Agriculture, University of Tabriz Department of Animal Science, Faculty of Agriculture, University of Tabriz Iran Parviz Tajik Department of Theriogenology, Faculty of Veterinary Medicine, University of Tehran Department of Theriogenology, Faculty of Veterinary Medicine, University of Tehran Iran Mortaza Koruji Department of Anatomy, Faculty of Medical Science, Iran University of Medical Sciences Department of Anatomy, Faculty of Medical Science, Iran University of Medical Sciences Iran Javad Ashrafi-Helan Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz Iran Seyed Abbas Rafat Department of Animal Science, Faculty of Agriculture, University of Tabriz Department of Animal Science, Faculty of Agriculture, University of Tabriz Iran Ghezel sheepIsolationSpermatogonia 308.pdf Baneh H, Hafezian SH, Rashidi A, Gholizadeh M, Rahimi GH. Estimation of genetic parameters of body weight traits in ghezel sheep. Asian Aust J Anim Sci 2010;23(2):149-153.##Aponte PM, de Rooij DG. Biomanipulation of bovine spermatogonial stem cells. Anim Reprod 2008;5(1/2):16-22.##Mulder CL, Zheng Y, Jan SZ, Struijk RB, Repping S, Hamer G, et al. Spermatogonial stem cell autotransplantation and germline genomic editing: a future cure for spermatogenic failure and prevention of transmission of genomic diseases. Hum Reprod Update 2016;22(5):561-573.##Rodriguez-Sosa JR, Dobson H, Hahnel A. Isolation and transplantation of spermatogonia in sheep. Theriogenology 2006;66(9):2091-2103.##Koruji M, Movahedin M, Mowla SJ, Gourabi H. Colony formation ability of frozen thawed spermatogonial stem cell from adult mouse. Int J Reprod BioMed 2007;5(3):109-115.##Avarbock MR, Brinster CJ, Brinster RL. Reconstitution of spermatogenesis from frozen spermatogonial stem cells. Nat Med 1996;2(6):693-696.##Nagano M, Brinster RL. 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Clinically Significant Dysregulation of hsa-miR-30d-5p and hsa-let-7b Expression in Patients with Surgically Resected Non-Small Cell Lung Cancer 2 2 Background: The cyclin E2 (CYCE2) is an important regulator in the progression and development of NSCLC, and its ectopic expression promoted the proliferation, invasion, and migration in several tumors, including Non-Small Cell Lung Cancer (NSCLC). However, the upregulation of CYCE2 in NSCLC cells suggested that it has a key role in tumorigenicity. In addition, the RAS family proteins as oncoproteins were activated in many major tumor types and its suitability as the therapeutic target in NSCLC was proposed. Considering the crucial role of microRNAs, it was hypothesized that altered expression of hsa-miR-30d-5p and hsa-let-7b might provide a reliable diagnostic tumor marker for diagnosis of NSCLC. Method: Real-time RT-PCR approach could evaluate the expression alteration of hsa-miR-30d-5p and hsa-let-7b and it was related to the surgically resected tissue of 24 lung cancer patients and 10 non-cancerous patients. The miRNAs expression was associated with clinicopathological features of the patients. Results: Hsa-miR-30d showed a significant downregulation (p=0.0382) in resected tissue of NSCLC patients compared with control group. Its expression level could differentiate different stages of malignancies from each other. The ROC curve analysis gave it an AUC=0.73 (p=0.037) which was a good score as a reliable biomarker. In contrast, hsa-let-7b was significantly overexpressed in tumor samples (p=0.03). Interestingly, our findings revealed a significant association of hsa-let-7b in adenocarcinoma tumors, compared to Squamous Cell Carcinomas (SCC) (p<0.05). Also, analysis of ROC curve of hsa-let-7b (AUC=0.74, p-value=0.042) suggests that it could be as a suitable biomarker for NSCLC. Conclusion: Together, these results suggest a possible tumor suppressor role for hsa-miR-30d in lung tumor progression and initiation. Moreover, upregulation of hsa-let-7b was associated with the tumor type. 98 104 Sayed Mostafa Hosseini Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University Iran Bahram Mohammad Soltani Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University Iran Mahmoud Tavallaei Human Genetic Research Center, Baqiyatallah University of Medical Sciences Human Genetic Research Center, Baqiyatallah University of Medical Sciences Iran Seyed Javad Mowla Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University Iran Elham Tafsiri Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran Iran Abouzar Bagheri Department of Clinical Biochemistry and Genetics, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences Department of Clinical Biochemistry and Genetics, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences Iran Hamid Reza Khorram Khorshid Genetic Research Centre, University of Social Welfare and Rehabilitation Sciences Genetic Research Centre, University of Social Welfare and Rehabilitation Sciences Iran Lung cancerMicroRNAsTumor markers 311.pdf Hosseini M, Naghan PA, Karimi S, SeyedAlinaghi S, Bahadori M, Khodadad K, et al. 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Quantitative real-time reverse transcription PCR study of the expression of vascular endothelial growth factor (VEGF) splice variants and VEGF receptors (VEGFR-1 and VEGFR-2) in non small cell lung cancer. Clin Chem 2007;53(8):1433-1439.##Cheng HH, Yi HS, Kim Y, Kroh EM, Chien JW, Eaton KD, et al. Plasma processing conditions substantially influence circulating microRNA biomarker levels. PloS One 2013;8(6):e64795.##Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 2004;64(11):3753-3756.##Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 2006;9(3):189-198.##Le HB, Zhu WY, Chen DD, He JY, Huang YY, Liu XG, et al. Evaluation of dynamic change of serum miR-21 and miR-24 in pre- and post-operative lung carcinoma patients. 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Tumor Necrosis Factor-Alpha and Interleukin-6 Gene Polymorphisms in Iranian Patients with Ischemic Heart Failure 2 2 Background: Proinflammatory cytokines have been known to be elevated in patients with Chronic Heart Failure (CHF). Given the importance of proinflammatory cytokines in the context of the failing heart, the prevalence of Tumor Necrosis Factor-α (TNF-α), Interleukin (IL)-6 polymorphisms in patients with CHF was studied due to ischemic heart disease. Methods: Forty three patients with ischemic heart failure were enrolled in this study and compared with 140 healthy individuals. The allele and genotype frequency of four Single Nucleotide Polymorphisms (SNPs) within the IL-6 (-174, nt565) and TNF-α (-308, -238) genes were determined, using Polymerase Chain Reaction with Sequence-Specific Primers (PCR-SSP) assay. Results: The frequency of the TNF-α (-238) A/A genotype was significantly higher in patients comparing to controls (p=0.043), while TNF-α G/A genotype at the same position decreased significantly, in comparison with controls (p=0.018). The most frequent haplotype for TNF-α was A/A in the patient group in comparison with controls (p=0.003). There was no significant difference in allele and genotype frequencies of IL-6 at positions -174 and nt565, and TNF-α at position -308. Conclusion: Certain alleles, genotypes, and haplotypes in TNF-α, but not IL-6, gene were overrepresented in patients with ischemic heart failure, which may, in turn, predispose individuals to this disease. 105 109 Mona Hedayat Division of Immunology, Boston Children's Hospital, Harvard Medical SchoolNetwork of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN) Division of Immunology, Boston Children's Hospital, Harvard Medical SchoolNetwork of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN) USAUSA Mohammad Jafar Mahmoudi Division of Cardiology, Department of Internal Medicine, School of Medicine, Tehran University of Medical Sciences Division of Cardiology, Department of Internal Medicine, School of Medicine, Tehran University of Medical Sciences Iran Mohammad Taghvaei Molecular Immunology Research Center, Tehran University of Medical Sciences Molecular Immunology Research Center, Tehran University of Medical Sciences Iran Ebrahim Nematipour Tehran Heart Center, Tehran University of Medical Sciences Tehran Heart Center, Tehran University of Medical Sciences Iran Elham Farhadi Hematology Department, Faculty of Allied Medical Science, Iran University of Medical Sciences Hematology Department, Faculty of Allied Medical Science, Iran University of Medical Sciences Iran Nilufar Esfahanian Molecular Immunology Research Center, Tehran University of Medical Sciences Molecular Immunology Research Center, Tehran University of Medical Sciences Iran Maryam Mahmoudi School of Nutrition and Dietetics, Tehran University of Medical SciencesDietitian and Nutrition Experts Team (DiNET), Universal Scientific Education and Research Network (USERN) School of Nutrition and Dietetics, Tehran University of Medical SciencesDietitian and Nutrition Experts Team (DiNET), Universal Scientific Education and Research Network (USERN) IranIran Maryam Sadr Molecular Immunology Research Center, Tehran University of Medical Sciences Molecular Immunology Research Center, Tehran University of Medical Sciences Iran Keramat Nourijelyani Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences Iran Ali Akbar Amirzargar Molecular Immunology Research Center, Tehran University of Medical Sciences Molecular Immunology Research Center, Tehran University of Medical Sciences Iran Nima Rezaei Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Tehran University of Medical SciencesMedical Genetics Network (MeGeNe), Universal Scientific Education and Research Network (USERN) Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Tehran University of Medical SciencesMedical Genetics Network (MeGeNe), Universal Scientific Education and Research Network (USERN) IranIranIran GenesHeart failureInterleukin-6Tumor necrosis factor-alpha 309.pdf Lloyd-Jones DM, Larson MG, Leip EP, Beiser A, D'Agostino RB, Kannel WB, et al. Lifetime risk for developing congestive heart failure: the Framingham heart study. Circulation 2002;106(24):3068-3072.##Shioi T, Inuzuka Y. Aging as a substrate of heart failure. J Cardiol 2012;60(6):423-428.##El-Menyar AA. Cytokines and myocardial dysfunction: state of the art. J Card Fail 2008;14(1):61-74.##Hedayat M, Mahmoudi MJ, Rose NR, Rezaei N. Proinflammatory cytokines in heart failure: double-edged swords. Heart Fail Rev 2010;15(6):543-562.##Petersen JW, Felker GM. Inflammatory biomarkers in heart failure. Congest Heart Fail 2006;12(6):324-328.##Kishi T. Heart failure as an autonomic nervous system dysfunction. J Cardiol 2012;59(2):117-122.##Hansson GK, Robertson AK, Söderberg-Nauclér C. Inflammation and atherosclerosis. Annu Rev Pathol 2006;1:297-329.##Kleemann R, Zadelaar S, Kooistra T. Cytokines and atherosclerosis: a comprehensive review of studies in mice. Cardiovasc Res 2008;79(3):360-376.##Grove J, Daly AK, Bassendine MF, Day CP. Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic steatohepatitis. Hepatology 1997;26(1):143-146.##Hoffmann SC, Stanley EM, Darrin Cox E, Craighead N, DiMercurio BS, Koziol DE, et al. Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes. Transplantation 2001;72(8):1444-1450.##Silkov AN, Sennikova NS, Goreva EP, Lopatnikova YA, Sennikov SV. Production of TNF-α and IL-1β by peripheral blood mononuclear cells in carriers of different allele variants of the gene. Bull Exp Biol Med 2012;153(1):68-71.##Amirzargar A, Shahram F, Nikoopour E, Rezaei N, Saeedfar K, Ziaei N, et al. Proinflammatory cytokine gene polymorphisms in Behçet's disease. Eur Cytokine Netw 2010;21(4):292-296.##Amirzargar AA, Bagheri M, Ghavamzadeh A, Alimoghadam K, Khosravi F, Rezaei N, et al. Cytokine gene polymorphism in Iranian patients with chronic myelogenous leukaemia. Int J Immunogenet 2005;32(3):167-171.##Amirzargar AA, Rezaei N, Jabbari H, Danesh AA, Khosravi F, Hajabdolbaghi M, et al. Cytokine single nucleotide polymorphisms in Iranian patients with pulmonary tuberculosis. Eur Cytokine Netw 2006;17(2):84-89.##Barkhordari E, Rezaei N, Ansaripour B, Larki P, Alighardashi M, Ahmadi-Ashtiani HR, et al. Proinflammatory cytokine gene polymorphisms in irritable bowel syndrome. J Clin Immunol 2010;30(1):74-79.##Mahdaviani SA, Rezaei N, Moradi B, Dorkhosh S, Amirzargar AA, Movahedi M. Proinflammatory cytokine gene polymorphisms among Iranian patients with asthma. J Clin Immunol 2009;29(1):57-62.##Rezaei N, Amirzargar AA, Shakiba Y, Mahmoudi M, Moradi B, Aghamohammadi A. Proinflammatory cytokine gene single nucleotide polymorphisms in common variable immunodeficiency. Clin Exp Immunol 2009;155(1):21-27.##Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A, Wadden T. Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab 1998;83(8):2907-2910.##Haddy N, Sass C, Droesch S, Zaiou M, Siest G, Ponthieux A, et al. IL-6, TNF-alpha and atherosclerosis risk indicators in a healthy family population: the STANISLAS cohort. Atherosclerosis 2003;170(2):277-283.##Kubota T, McNamara DM, Wang JJ, Trost M, McTiernan CF, Mann DL, et al. Effects of tumor necrosis factor gene polymorphisms on patients with congestive heart failure. VEST investigators for TNF genotype analysis. vesnarinone survival trial. Circulation 1998;97(25):2499-2501.##Amirzargar AA, Naroueynejad M, Khosravi F, Dianat SS, Rezaei N, Mytilineos J, et al. Cytokine single nucleotide polymorphisms in Iranian populations. Eur Cytokine Netw 2008;19(2):104-112.##Bruggink AH, van Oosterhout MF, De Jonge N, Gmelig-Meyling FH, De Weger RA. TNFalpha in patients with end-stage heart failure on medical therapy or supported by a left ventricular assist device. Transpl Immunol 2008;19(1):64-68.##Kaluza W, Reuss E, Grossmann S, Hug R, Schopf RE, Galle PR, et al. Different transcriptional activity and in vitro TNF-alpha production in psoriasis patients carrying the TNF-alpha 238A promoter polymorphism. J Invest Dermatol 2000;114(6):1180-1183.##Kaijzel EL, van Krugten MV, Brinkman BM, Huizinga TW, van der Straaten T, Hazes JM, et al. Functional analysis of a human tumor necrosis factor alpha (TNF-alpha) promoter polymorphism related to joint damage in rheumatoid arthritis. Mol Med 1998;4(11):724-733.##Pociot F, D'Alfonso S, Compasso S, Scorza R, Richiardi PM. Functional analysis of a new polymorphism in the human TNF alpha gene promoter. Scand J Immunol 1995;42(4):501-504.##Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. 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Association of AIRE Polymorphism and the Susceptibility to Multiple Sclerosis in Iranian Population 2 2 Background: Multiple Sclerosis (MS) is the most common cause of neurologic disability in young adults. Recently, the AIRE gene was identified as a genetic risk factor for several autoimmune diseases in genome wide association studies. The aim of this study was to further investigate the possible role of the AIRE gene in susceptibility to MS in Iranian population. Methods: A total of 112 MS patients and 94 ethnically matched controls were included in the study. The Single-Nucleotide Polymorphism (SNP) (rs1800520, C>G) with a global MAF=0.2282/1143 was selected and genotyped using HRM real-time PCR method. Results: Results showed that AIRE SNP rs1800520 was significantly less common in the MS patients than in healthy controls (17.8 vs. 28.7%, pc=0.032, OR=0.54,95% CI 0.279,1.042). Also, the frequency of allele G was significantly higher among the control group than in the case group (37.77 vs. 25%, pc=0.014). Interestingly, mRNA transcribed on the rs1800520 SNP showed decreased free energy than the wild type suggesting that its increased stability may be responsible for the different activities of the polymorphic AIRE molecule.  Conclusions: This is the first study investigating the relationship between AIRE gene and the susceptibility to MS. These results indicated that the rs1800520 SNP is not a susceptibility gene variant for the development of MS in Iranian population. 110 114 Tahereh Sadeghian-Rizi Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences Iran Fereshteh Alsahebfosoul Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences Iran Mohammad Kazemi Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences Iran Hossein Khanahmad Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences Iran Ali Jahanian Najafabadi Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences Iran AIREIranMultiple sclerosisSingle-nucleotide polymorphism 310.pdf Kidd PM. 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Role of the autoimmune regulator (AIRE) gene in alopecia aureate: strong association of a potentially functional AIRE polymorphism with alopecia universalis. Tissue Antigens 2002;60(6):489-495.##Füchtenbusch M, Vogel A, Achenbach P, Gummer M, Ziegler AG, Albert E, et al. Lupus-like panniculitis in a patient with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Exp Clin Endocrinol Diabetes 2003;111(5):288-293.##Tait KF, Gough SC. The genetics of autoimmune endocrine disease. Clin Endocrinol (Oxf) 2003;59(1):1-11.##Colobran R, Giménez-Barcons M, Marín-Sánchez A, Porta-Pardo E, Pujol-Borrell R. AIRE genetic variants and predisposition to polygenic autoimmune disease: The case of Graves’ disease and a systematic literature review. Hum Immunol 2016;77:643-651.##Zhang X, Ding XJ, Wang Q, Yue YX, Xie Y, Hao HJ, et al. Rs3761389 polymorphism in autoimmune regulator (AIRE) gene is associated with susceptibility of myasthenia gravis in Chinese patients. J Clin Neurosci 2017;40:180-184.##Török HP, Tonenchi L, Glas J, Schiemann U, Folwaczny C. No significant association between mutations in exons 6 and 8 of the autoimmune regulator (AIRE) gene and inflammatory bowel disease. Eur J Immunogenet 2004;31(2):83-86.##De Martino L, Capalbo D, Improda N, D'Elia F, Di Mase R, D'Assante R. APECED: a paradigm of complex interactions between genetic background and susceptibility factors. Front Immunol 2013;4:331. ##Conteduca G, Ferrera F, Pastorino L, Fenoglio D, Negrini S, Sormani MP, et al. The role of AIRE polymorphisms in melanoma. Clin Immunol 2010;136:96-104.##Taniguchi RT, Anderson MS. The role of Aire in clonal selection. Immunol Cell Biol 2011;89(1):40-44.##Waterfield M, Khan IS, Cortez JT, Fan U, Metzger T, Greer A, et al. The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance. Nat Immunol 2014;15:258-265.##Suzuki A, Kochi Y, Okada Y, Yamamoto K. Insight from genome-wide association studies in rheumatoid arthritis and multiple sclerosis. FEBS Lett 2011;585:3627-3632.##Rizzi M, Ferrera F, Filaci G, Indiveri F. Disruption of immunological tolerance: role of AIRE gene in autoimmunity. Autoimmun Rev 2006;5:145-147.##Abramson J, Giraud M, Benoist C, Mathis D. AIRE 's partners in the molecular control of immunological tolerance. Cell 2010;140(1):123-135.##Bruserud Ø,Oftedal BE, Wolff AB, Husebye ES. AIRE-mutations and autoimmune disease. Curr Opin Immunol 2016;43:8-15.##Turunen JA, Wessman M, Forsblom C, Kilpikari R, Parkkonen M, PontynenN, et al. Association analysis of the AIRE and insulin genes in Finnish type 1 diabetic patients. Immunogenetics 2006;58(5-6):331-338.##Faiyaz-Ul-Haque M, Bin-Abbas B, Al-Abdullatif A, Abdullah Abalkhail H, Toulimat M, Al-Gazlan S, et al. Novel and recurrent mutations in the AIRE gene of autoimmune polyendocrinopathy syndrome type 1 (APS1) patients. Clin Genet 2009;76(5):431-440.##

Evaluating the Frequency of aac(6')-IIa, ant(2'')-I, intl1, and intl2 Genes in Aminoglycosides Resistant Klebsiella pneumoniae Isolates Obtained from Hospitalized Patients in Yazd, Iran 2 2 Background: Klebsiella pneumoniae (K. pneumoniae) is an opportunistic pathogen that could be resistant to many antimicrobial agents. Resistance genes can be carried among gram-negative bacteria by integrons. Enzymatic inactivation is the most important mechanism of resistance to aminoglycosides. In this study, the frequencies of two important resistance gene aac(6')-IIa and ant(2'')-I, and genes coding integrase I and II, in K. pneumoniae isolates resistant to aminoglycosides were evaluated. Methods: In this cross-sectional study, an attempt was made to assess the antibiotic susceptibility of 130 K. pneumoniae isolates obtained from different samples of patients hospitalized in training hospitals of Yazd evaluated by disk diffusion method. The frequencies of aac(6')-IIa, ant(2'')-I, intl1, and intl2 genes were determined by PCR method. Data were analyzed by chi-square method using SPSS software (Ver. 16). Results: our results showed that resistance to gentamicin, tobramycin, kanamycin, and amikacin were 34.6, 33.8, 43.8, and 14.6%, respectively. The frequencies of aac(6')-IIa, ant(2'')-I, intl1, and intl2 genes were 44.6, 27.7, 90, and 0%, respectively. Conclusion: This study showed there are high frequencies of genes coding aminoglycosides resistance in K. pneumoniae isolates. Hence, it is very important to monitor and inhibit the spread of antibiotic resistance genes. 115 119 Hesam Mokhtari International Campus, Shahid Sadoughi University of Medical Sciences International Campus, Shahid Sadoughi University of Medical Sciences Iran Gilda Eslami Research Center for Food Hygiene and Safety, Shahid Sadoughi University of Medical SciencesDepartment of Parasitology and Mycology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences Research Center for Food Hygiene and Safety, Shahid Sadoughi University of Medical SciencesDepartment of Parasitology and Mycology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences IranIran Hengameh Zandi Research Center for Food Hygiene and Safety, Shahid Sadoughi University of Medical SciencesDepartment of Microbiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences Research Center for Food Hygiene and Safety, Shahid Sadoughi University of Medical SciencesDepartment of Microbiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences Iran Iran Amin Dehghan-Banadkouki Department of Pathobiology, Faculty of Public Health, Tehran University of Medical Sciences Department of Pathobiology, Faculty of Public Health, Tehran University of Medical Sciences Iran Mahmood Vakili Department of Public Medicine, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences Department of Public Medicine, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences Iran AminoglycosidesDrug resistanceIntegronsKlebsiella pneumoniaeMicrobial 313.pdf Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev 1998;11(4):589-603.##Bbosa GS, Mwebaza N, Odda J, Kyegombe DB, Ntale M. Antibiotics/antibacterial drug use, their marketing and promotion during the post-antibiotic golden age and their role in emergence of bacterial resistance. Health 2014;6(5):410-425.##Maurin M, Raoult D. Use of aminoglycosides in treatment of infections due to intracellular bacteria. Antimicrob Agents Chemother 2001;45(11):2977-2986.##Ramirez MS, Tolmasky ME. Aminoglycoside modifying enzymes. Drug Resist Updates 2010;13(6):151-171.##Cox G, Stogios PJ, Savchenko A, Wright GD. Structural and molecular basis for resistance to aminoglycoside antibiotics by the adenylyltransferase ANT (2″)-Ia. MBio 2015;6(1):e02180-14.##Frasson I, Cavallaro A, Bergo C, Richter SN, Palù G. Prevalence of aac(6')-Ib-cr plasmid-mediated and chromosome-encoded fluoroquinolone resistance in Enterobacteriaceae in Italy. Gut Pathog 2011;3(1):12.##Benveniste R, Davies J. R-factor mediated gentamicin resistance: a new enzyme which modifies aminoglycoside antibiotics. FEBS Lett 1971;14(5):293-296.##Shaw KJ, Rather PN, Hare RS, Miller GH. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol Rev 1993;57(1):138-163.##Shimizu K, Kumada T, Hsieh WC, Chung HY, Chong YU, Hare RS, et al. Comparison of aminoglycoside resistance patterns in Japan, Formosa, and Korea, Chile, and the United States. Antimicrob Agents Chemother 1985;28(2):282-288.##Miller GH, Sabatelli FJ, Hare RS, Glupczynski Y, Mackey P, Shlaes D, et al. The most frequent aminoglycoside resistance mechanisms--changes with time and geographic area: a reflection of aminoglycoside usage patterns? aminoglycoside resistance study groups. Clin Infect Dis 1997;24 Suppl 1):S46-62.##Ramirez MS, Nikolaidis N, Tolmasky M. Rise and dissemination of aminoglycoside resistance: the aac(6′)-Ib paradigm. Front Microbiol 2013;4:121.##Partridge SR. Analysis of antibiotic resistance regions in Gram-negative bacteria. FEMS Microbiol Rev 2011;35(5):820-855.##Zarei-Yazdeli M, Eslami G, Zandi H, Mousavi SM, Kosha H, Akhavan F, et al. Relationship between antimicrobial resistance and class I integron in Pseudomonas aeruginosa isolated from clinical specimens in Yazd during 2012-2013. FEYZ 2014;18(1):60-67.##Patel JB, Tenover FC, Turnidge JD, Jorgensen JH. Susceptibility test methods: dilution and disk diffusion methods. In: Jorgensen JH, Pfaller MA, Carroll KC, Funke G, Landry ML, Richter SS, et al, editors. Manual of clinical microbiology. USA: American Society for Microbiology; 2015.##Citron DM, Ostovari MI, Karlsson A, Goldstein EJ. Evaluation of the E test for susceptibility testing of anaerobic bacteria. 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High frequency of extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Escherichia coli isolates from male patients’ Urine. Arch Clin Infect Dis 2016;11(2):e60127.##Mobarak-Qamsari M, Ashayeri-Panah M, Eftekhar F, Feizabadi MM. Integron mediated multidrug resistance in extended spectrum beta-lactamase producing clinical isolates of Klebsiella pneumoniae. Braz J Microbiol 2013;44(3):849-854.##Liang C, Xing B, Yang X, Fu Y, Feng Y, Zhang Y. Molecular epidemiology of aminoglycosides resistance on Klebsiella pneumonia in a hospital in China. Int J Clin Exp Med 2015;8(1):1381-1385.##Li B, Hu Y, Wang Q, Yi Y, Woo PC, Jing H, et al. Structural diversity of class 1 integrons and their associated gene cassettes in Klebsiella pneumoniae isolates from a hospital in China. PloS One 2013;8(9):e75805.##

Assessment of EGFR Gene Expression Following Vitrification of 2-cell and Blastocyst Mouse Embryos 2 2 Background: Exact mechanisms of fetal harm following vitrification are still unknown. This study was conducted to evaluate the cryopreservation impact on the expression of Epidermal Growth Factor Receptor (EGFR) gene in mouse 2-cell and blastocysts. Methods: To stimulate ovulation in mice, hCG was injected, followed by collecting 2-cells and blastocysts after 44-46 and 88-89 hr, respectively. These embryos were divided into two case and control groups. The fresh case group was cryopreserved using cryotop and warmed after 4 mounts. Normal 2-cells were selected based on their morphology and their RNA was extracted. Quantitative expression of EGFR gene in both groups was investigated by applying real time-PCR. Results: The statistical real-time (RT)-PCR analyses performed using SPSS revealed that the expression level of EGFR gene was diminished in the case group compared to the control group.  Conclusion: The current study indicated the negative effect of cryopreservation on expression amount of EGFR gene in 2-cell and blastocyst mouse embryos. 120 122 Rouhollah Gazor Department of Anatomy and Cell Biology, Faculty of Medicine, Guilan University of Medical Sciences Department of Anatomy and Cell Biology, Faculty of Medicine, Guilan University of Medical Sciences Iran Mozhgan Eskandari Department of Anatomy, Ardabil University of Medical Sciences Department of Anatomy, Ardabil University of Medical Sciences Iran Alireza Sharafshah Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences Iran Mohammad Hadi Bahadori Department of Anatomy and Cell Biology, Faculty of Medicine, Guilan University of Medical Sciences Department of Anatomy and Cell Biology, Faculty of Medicine, Guilan University of Medical Sciences Iran Mohammad Ghasem Golmohammadi Department of Anatomy, Ardabil University of Medical Sciences Department of Anatomy, Ardabil University of Medical Sciences Iran Parvaneh Keshavarz Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences Iran BlastocystCryopreservationEmbryoGene expressionVitrification 334.pdf Roupa Z, Polikandrioti M, Sotiropoulou P, Faros E, Koulouri A, Wozniak G, et al. Causes of infertility in women at reproductive age. Health Sci J 2009;3(2):80-87.##Pera MF, Reubinoff B, Trounson A. Human embryonic stem cells. J Cell Sci 2000;113(1):5-10.##Gardner DK, Weismann A, Howles CM, Shoham Z. Textbook of assisted reproductive technologies: laboratory and clinical perspectives. 3rd ed. UK: Informa Healthcare;2008.##Marshall OJ. PerlPrimer: cross-platform, graphical primer design for standard, bisulphite and real-time PCR. Bioinformatics 2004;20(15):2471-2472.##Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 2002;30(9):e36.##Riesco MF, Robles V. Cryopreservation causes genetic and epigenetic changes in zebrafish genital ridges. PloS One 2013;8(6):e67614.##Qu J, Nisolle M, Donnez J. Expression of transforming growth factor-alpha, epidermal growth factor, and epidermal growth factor receptor in follicles of human ovarian tissue before and after cryopreservation. Fertil Steril 2000;74(1):113-121.##Tachataki M, Winston RM, Taylor DM. Quantitative RT-PCR reveals tuberous sclerosis gene, TSC2, mRNA degradation following cryopreservation in the human preimplantation embryo. Mol Hum Reprod 2003;9(10):593-601.##

Retraction: The Frequency and Importance of Common α-globin Gene Deletions Among β-Thalassemia Carriers in an Iranian Population 2 2 The Editorial Board of Avicenna Journal of Medical Biotechnology (AJMB) has decided to retract the original article entitled “The Frequency and Importance of Common α-globin Gene Deletions Among β-Thalassemia Carriers in an Iranian Population” published in the October-December 2017 issue due to a fact which is contrary to the scientific rules and regulation of AJMB. 123 123 Azam Moosavi Ali M. Ardekani RetractRetraction 10360.pdf ####