OTHERS_CITABLE Factors Influencing Mitochondrial Function as a Key Mediator of Glucose-Induced Insulin Release: Highlighting Nicotinamide Nucleotide Transhydrogenase Pancreatic β-cells recognize blood glucose changes and release insulin that is a peptide hormone responsible for stable glycemia. Diabetes, a chronic disorder of insulin insufficiency, leads to disturbed glucose homeostasis and multi-organ problems. Glucose and insulin are key markers in the follow-up and control of this disease. Mitochondrial metabolism of pancreatic beta cells is a crucial part of glucose-stimulated cascade of insulin secretion. Effective factors on β-cells mitochondrial function in production of compounds such as tricarboxylic acid intermediates, glutamate, nicotinamide adenine dinucleotide phosphate, and reactive oxygen species can have great effects on the secretion of insulin under diabetes. This review enhances our knowledge of factors influencing mitochondrial function as a key mediator of glucose-induced insulin release that accordingly will be helpful to further our understanding of the mechanisms implicated in the progressive beta cell failure that results in diabetes. http://ijmcmed.org/article-1-1227-en.pdf 2020-06-30 107 121 10.22088/IJMCM.BUMS.9.2.107 Mitochondria glucose-sensing insulin release NADPH ROS diabetes Zahra Aghelan padidehbiochemist@yahoo.com 1 Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran. AUTHOR https://orcid.org/0000-0001-8375-7647 Sara Kiani sarah.kiani.mbrc@gmail.com 2 Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. AUTHOR Abolfazl Nasiri Bionasiri69@gmail.com 3 Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. AUTHOR https://orcid.org/0000-0002-2106-5845 Masoud Sadeghi sadeghi_mbrc@yahoo.com 4 Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. AUTHOR https://orcid.org/0000-0001-9733-3300 Alireza Farrokhi alireza.farokhi@kums.ac.ir 5 Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. AUTHOR Reza Khodarahmi rkhodarahmi@mbrc.ac.ir 6 Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. AUTHOR https://orcid.org/0000-0002-2474-5037
ORIGINAL_ARTICLE Increased Expression Level of Long Noncoding RNA H19 in Plasma of Patients with Myocardial Infarction Long noncoding RNAs (lncRNAs) are lengthy noncoding transcripts which are actively involved in crucial cellular pathways. Tissue-specific expression of lncRNAs besides its secretion into the body fluids, has made lncRNAs in attention as biomarkers of the diseases. According to the role of lncRNAs, especially H19 in cardiac regeneration, it is not surprising if their altered expression levels lead to cardiac diseases. In the present study, the relative expression of H19 was compared in the plasma of atherosclerotic myocardial infarction and control individuals by real time- PCR, and data were normalized using GAPDH. The association of plasma level of lipid and homocystine with H19 expression was also considered. The potential of H19 to discriminate the case from control was studied using the ROC analysis. We found that the plasma level of H19 transcript significantly increased in the plasma of patients in comparison with the control group. Additionally, the relative expression level of H19 was directly associated with the plasma homocystine level. The relative expression of H19 at threshold of 0.3 showed 70% sensitivity and 94% specificity to discriminate cases from controls. This study revealed that the expression level of H19 may be considered as a biomarker of myocardial infarction, although further studies are needed to generalize this finding. http://ijmcmed.org/article-1-1266-en.pdf 2020-06-30 122 129 10.22088/IJMCM.BUMS.9.2.122 Atherosclerosis blood-based biomarker homocysteine long noncoding RNA myocardial infarction plasma Shokouh Safaei safaietolou@gmail.com 1 Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. AUTHOR https://orcid.org/0000-0002-0982-0756 Maryam Tahmasebi-Birgani maryam_tahmaseby@yahoo.com 2 Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. AUTHOR https://orcid.org/0000-0002-9624-1903 Mahdi Bijanzadeh mbijanz@yahoo.com 3 Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. AUTHOR https://orcid.org/0000-0002-5650-9450 Masoud Seyedian mseyedian@ajums.ac.ir 4 Cardiovascular Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz; Cardiovascular Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. AUTHOR https://orcid.org/0000-0002-7215-6851
ORIGINAL_ARTICLE Evaluation of miRNAs Related with Nuclear Factor Kappa B Pathway in Lipopolysaccharide Induced Acute Respiratory Distress Syndrome This study aimed to determine the expression of nuclear factor kappa B (NF-κB) pathway related miRNAs in experimental acute respiratory distress syndrome (ARDS) induced by lipopolysaccharide (LPS) in rats, and to elucidate the underlying molecular mechanism. Twenty four sprague dawley rats were randomly divided into two groups; LPS (n = 12) and control (n = 12). Experimental ARDS was induced by intraperitoneal injection of E. coli LPS in LPS group. Intraperitoneal saline was administered in control group. Serum and lung samples were collected from both groups. Immunohistochemistry staining was performed for interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), CD 68, and caspase-3 in lung samples. Intensity of staining was scored as strong, moderate, weak, and no for evaluation of IL-1β and TNF-α. In addition, caspase-3 and CD 68 positive stained cells were counted in sections. Expressions of 9 miRNAs were determined by quantitative real-time PCR in serum samples.  IL-1β and TNF-α staining scores were significantly higher in the LPS group in comparison with the control group (P = 0.04 and P = 0.02, respectively). In addition, caspase-3 and CD 68 positive stained cells were significantly higher in the LPS group (P = 0.02). Expressions of seven miRNAs were significantly changed in the LPS group in comparison with the control group. While six miRNAs (miR-7a-5p, miR-7b, miR-9a-5p, miR-21-5p, miR-29a-3p and miR-138-5p) were up regulated, only miR-124-3p was down-regulated. This study suggests that these miRNAs may have a role in the pathogenesis of ARDS related to NF-κB. However, this relationship needs to be examined in new studies by evaluation of pathways and target genes. http://ijmcmed.org/article-1-1209-en.pdf 2020-06-30 130 139 10.22088/IJMCM.BUMS.9.2.130 Acute respiratory distress syndrome ARDS microRNA nuclear factor kappa B Mustafa Azizoglu dryalamaoglu@hotmail.com 1 Mersin University, Faculty of Medicine, Department of Anesthesiology and Reanimation, Mersin, Turkey. AUTHOR https://orcid.org/0000-0002-8266-5203 Lokman Ayaz lokmanayaz@yahoo.com 2 Trakya University, Faculty of Pharmacy, Department of Biochemistry, Edirne, Turkey. AUTHOR https://orcid.org/0000-0002-2876-055X Gülsen Bayrak gulsenbayrak@mersin.edu.tr 3 Mersin University, Faculty of Medicine, Department of Histology & Embriyology, Mersin, Turkey. AUTHOR https://orcid.org/0000-0002-1397-7203 Banu Çoskun Yılmaz bcoskun@mersin.edu.tr 4 Mersin University, Faculty of Medicine, Department of Histology & Embriyology, Mersin, Turkey. AUTHOR https://orcid.org/0000-0002-7723-9146 Handan Birbiçer handanbirbicer@mersin.edu.tr 5 Mersin University, Faculty of Medicine, Department of Anesthesiology and Reanimation, Mersin, Turkey. AUTHOR https://orcid.org/0000-0003-3510-9279 Nurcan Doruk nurcandoruk@mersin.edu.tr 6 Mersin University, Faculty of Medicine, Department of Anesthesiology and Reanimation, Mersin, Turkey. AUTHOR https://orcid.org/0000-0003-0141-1111
ORIGINAL_ARTICLE Dynamic of miRNA-101a-3p and miRNA-200a during Induction of Osteoblast Differentiation in Adipose-derived Mesenchymal Stem Cells MiRNAs are known as the cellular phenomena regulators that exert their effects in post-transcriptional level. Recent studies highlight the role of miRNAs in mesenchymal stem cells differentiation into osteoblasts. The purpose of this study was to recognize the pattern of miRNA-101a-3p and miRNA-200a expression during osteoblastic differentiation of human adipose tissue-derived mesenchymal stem cells. The cells were incubated in osteoblastic differentiation medium for a period of 21 days. Alizarin red S staining was performed to confirm the successful differentiation of adipose-derived mesenchymal stem cells into osteoblast cells. The expression levels of miRNA-101a-3p and miRNA-200a were analyzed by real-time PCR during 0, 7, 14 and 21 days after differentiation induction. Data exhibited the increase of extracellular red color deposition which was evident at the end of the incubation period. The expression of miRNA-101a-3p and miRNA-200a was upregulated during adipose-derived mesenchymal stem cells trans-differentiation into osteoblast-like cells. These miRNAs could be potential novel biomarkers for monitoring successful differentiation of mesenchymal stem cells toward osteoblasts.   http://ijmcmed.org/article-1-1268-en.pdf 2020-06-30 140 145 10.22088/IJMCM.BUMS.9.2.140 Adipose-derived-mesenchymal stem cells osteoblast-like differentiation miRNA-101a-3p miRNA-200a transcription Somayeh Aslani smh.aslani@gmail 1 Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. AUTHOR https://orcid.org/0000-0001-7174-2181 Reza Rahbarghazi rezarahbardvm@gmail.com 2 Department of Applied Cell Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. AUTHOR https://orcid.org/0000-0003-3864-9166 Sevda Rahimzadeh rahimzadeh.sevda@gmsil.com 3 Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. AUTHOR https://orcid.org/0000-0002-7225-3360 Hadi Rajabi hadirajabi.bio@gmail.com 4 Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. AUTHOR https://orcid.org/0000-0001-6086-591X Alireza Abhari abharial@tbzmed.ac.ir 5 Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. AUTHOR https://orcid.org/0000-0002-3285-5471 Ebrahim Sakhinia esakhinia@yahoo.co.uk 6 Department of Medical Genetics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. AUTHOR https://orcid.org/0000-0001-5480-7414
ORIGINAL_ARTICLE HSV-TK Expressing Mesenchymal Stem Cells Exert Inhibitory Effect on Cervical Cancer Model A growing area of research is focused on cancer therapy, and new therapeutic approaches are welcomed. Mesenchymal stem cell (MSC)-based gene therapy is a promising strategy in oncology. Intrinsic tropism and migration to tumor microenvironment with off lights are attractive features of this type of cell carrier. In this way, suicide genes have also found a good platform for better performance and have shown a stronger anti-tumor mechanism by riding on mesenchymal cells. In this study, we investigated the anti-tumor activity of intratumoral injected MSCs transduced with a lentivector expressing the HSV/TK in a mouse cervical cancer model. Following the injection of MSCs transduced with lentivector carrying TK, MSCs alone or PBS into the mice tumor, ganciclovir was administered intraperitoneally during 14 days, and tumor size, survival time, natural killer (NK) cells and cytotoxic T lymphocyte (CTL) activities were assessed. We demonstrated that combination of suicide therapy and cell therapy leading m,to successful tumor inhibition. Significant reduction in tumor size was detected in test group in comparison with controls. Also, potent antitumor NK and CTL activity was seen in treatment group in comparison with controls. Our data demonstrated that the mesenchymal cells expressing TK had inhibitory effect on cervical cancer model. http://ijmcmed.org/article-1-1154-en.pdf 2020-07-05 146 153 10.22088/IJMCM.BUMS.9.2.146 Cervical cancer mesenchymal stem cell suicide therapy lentivector thymidine kinase cell therapy Azra Kenarkoohi a.Kenarkoohi@gmail.com 1 Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Department of Microbiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran. AUTHOR https://orcid.org/0000-0002-9928-8627 Taravat Bamdad bamdad_t@modares.ac.ir 2 Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. AUTHOR https://orcid.org/0000-0003-3620-0701 Masoud Soleimani soleim_m@modares.ac.ir 3 Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. AUTHOR https://orcid.org/0000-0003-1972-7771 Hoorieh Soleimanjahi soleim_h@modares.ac.ir 4 Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. AUTHOR https://orcid.org/0000-0003-1931-7801 Ali Fallah ali@rnax.co.uk 5 RNAx Ltd., London, UK. AUTHOR Shahab Falahi shahabivan@gmail.com 6 Zoonotic Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran. AUTHOR https://orcid.org/0000-0002-3764-2168
ORIGINAL_ARTICLE Relationship between Single Nucleotide Polymorphisms of GRHL3 and Schizophrenia Susceptibility: A Preliminary Case-Control Study and Bioinformatics Analysis Grainyhead-like (GRHL) transcription factors were recently linked to the etiology of neural tube defects (NTDs). Overlapping patterns in the variation of schizophrenia (SCZ) incidence with that of NTDs suggests the presence of common etiological risk factors. This preliminary study was designed to examine the relationship between two missense variants of GRHL3 gene (rs2486668C/G and rs545809A/T) and SCZ susceptibility among Iranians. Three hundred ninety subjects (192 patients confirmed with SCZ, and 198 healthy controls) were enrolled and genotyped. Statistical and bioinformatics analyzes were performed to determine the effects of the variants. In silico analyzes were performed to determine the effects of the variants on the secondary structure of GRHL3 protein and prediction of silencer motifs for each variation. Statistically significant differences were observed between the studied groups under codominant AA, dominant AT+AA, and recessive AA genetic contrast models for rs545809A/T. The presence of the A allele of rs545809A/T enhanced SCZ risk by 2.33 fold. In contrast, rs2486668C/G was not linked to SCZ susceptibility (P > 0.05). Bioinformatics analysis revealed that both missense SNPs caused substantial changes in the secondary structure of GRHL3-mRNA. Screening of the flanking sequences of rs545809A/T predicted silencer motifs for this SNP. Our results demonstrated that the rs545809A/T of GRHL3 gene could affect the risk of SCZ in Iranian populations. Replication studies are warranted to confirm these results. http://ijmcmed.org/article-1-1317-en.pdf 2020-06-30 154 164 10.22088/IJMCM.BUMS.9.2.154 Bioinformatics grainyhead-like 3 haplotype polymorphism schizophrenia Saman Sargazi sgz.biomed@gmail.com 1 Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran. AUTHOR https://orcid.org/0000-0002-2255-5977 Milad Heidari Nia milad_heidari2003@yahoo.com 2 Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran. AUTHOR https://orcid.org/0000-0002-2954-1009 Roghayeh Sheervalilou r_valiloo@yahoo.com 3 Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran. AUTHOR https://orcid.org/0000-0001-5813-0682 Shekoufeh Mirinejad shokufemn@gmail.com 4 Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran. AUTHOR https://orcid.org/0000-0003-0714-6507 Mahdiyeh Harati-Sadegh m.haratisadegh@yahoo.com 5 Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran. AUTHOR https://orcid.org/0000-0001-9941-2854 Mahdiyeh Moudi mahdiyehmodi@yahoo.com 6 Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran. AUTHOR Ramin Saravani saravaniramin@yahoo.com 7 Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran; Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. AUTHOR https://orcid.org/0000-0003-1941-3617 Mansoor Shakiba mans30817@gmail.com 8 Department of Psychiatry, Zahedan University of Medical Sciences, Zahedan, Iran; Psychosomatic Research Center, Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran. AUTHOR https://orcid.org/0000-0001-7833-7744
ORIGINAL_ARTICLE Comprehensive Analysis of Zinc Derivatives Pro-proliferative, Anti-Apoptotic and Antimicrobial Effect on Human Fibroblasts and Keratinocytes in a Simulated, Nutrient-deficient Environment In Vitro Zinc as therapeutic agent in skin and wound care has been known for centuries, but its role is controversial and comprehensive investigations in nutrient-deficient environments are lacking. We aimed to provide a broad analysis of different zinc derivatives on proliferation, apoptosis and antimicrobial properties in a simulated nutrient-deficient environment in vitro. Human fibroblasts (CRL2522) and keratinocytes (HaCaT) were treated with a broad concentration range (10 – 0.0001 µg/mL) of zinc-sulfate (ZnSO4), -gluconate (ZnGluc) and -histidine (ZnHis) for 1-6 days under nutrient-deficient media conditions. Cell proliferation was investigated by XTT assay. Targeted analyzes in proliferation (E2F1, PCNA) and apoptosis (TP53) associated genes were performed via qRT-PCR and apoptosis was determined via FACS (annexin V/7-AAD staining). Antimicrobial efficacy was investigated using a quantitative suspension method against S. aureus, P. aeruginosa, E. coli, and C. albicans. The results indicated that 0.1 to 0.001 µg/mL Zn increased cell proliferation in both cell lines. Fibroblasts were more susceptible with significant proliferation peaks on days 2 & 6, and days 1 & 4 for keratinocytes. No relevant changes in gene expression were detected for E2F1 and PCNA nor for TP53. Annexin-V/7-AAD-staining of fibroblasts revealed a small, yet insignificant reduction of apoptosis induction for ZnGluc and ZnSO4. ZnGluc and ZnSO4 (0.1%) achieved high microbial reductions (4-5 log10 reductions) against tested pathogens. ZnGluc and ZnSO4 showed relevant pro-proliferative and antimicrobial, as well as tendential anti-apoptotic features in a simulated nutrient-deficient microenvironment in vitro. This further validates a potential benefit of local zinc treatment in deficient wound microenvironments. http://ijmcmed.org/article-1-1277-en.pdf 2020-06-30 165 179 10.22088/IJMCM.BUMS.9.2.165 Wound healing zinc fibroblasts keratinocytes antimicrobial efficacy cell proliferation apoptosis Julian-Dario Rembe julian-dario.rembe@uni-wh.de 1 Department of Vascular and Endovascular Surgery, Heinrich-Heine-University, Düsseldorf, Germany. AUTHOR https://orcid.org/0000-0002-5176-6941 Julia Katharina Boehm julia.boehm@uni-wh.de 2 Institute for Research in Operative Medicine (IFOM), Witten/Herdecke University. AUTHOR Carolin Fromm-Dornieden carolinfromm@gmx.de 3 Institute for Research in Operative Medicine (IFOM), Witten/Herdecke University. AUTHOR https://orcid.org/0000-0002-1894-3942 Nina Hauer nina.hauer@uni-wh.de 4 Chair for Translational Wound Research, Centre for Biomedical Education and Research (ZBAF), Witten/Herdecke University. AUTHOR Ewa Klara Stuermer e.stuermer@uke.de 5 Department of Vascular Medicine, University Heart Center, Translational Wound Research, University Medical Center Hamburg-Eppendorf. AUTHOR https://orcid.org/0000-0003-4193-4857