ORIGINAL_ARTICLE A Bioinformatics Approach to Prioritize Single Nucleotide Polymorphisms in TLRs Signaling Pathway Genes It has been suggested that single nucleotide polymorphisms (SNPs) in genes involved in Toll-like receptors (TLRs) pathway may exhibit broad effects on function of this network and might contribute to a range of human diseases. However, the extent to which these variations affect TLR signaling is not well understood. In this study, we adopted a bioinformatics approach to predict the consequences of SNPs in TLRs network. The consequences of non-synonymous coding SNPs (nsSNPs) were predicted by SIFT, PolyPhen, PANTHER, SNPs&GO, I-Mutant, ConSurf and NetSurf tools. Structural visualization of wild type and mutant protein was performed using the project HOPE and Swiss PDB viewer. The influence of 5′-UTR and 3′- UTR SNPs were analyzed by appropriate computational approaches. Nineteen nsSNPs in TLRs pathway genes were found to have deleterious consequences as predicted by the combination of different algorithms. Moreover, our results suggested that SNPs located at UTRs of TLRs pathway genes may potentially influence binding of transcription factors or microRNAs. By applying a pathway-based bioinformatics analysis of genetic variations, we provided a prioritized list of potentially deleterious variants. These findings may facilitate the selection of proper variants for future functional and/or association studies. http://ijmcmed.org/article-1-451-en.pdf 2016-05-01 65 79 10.22088/acadpub.BUMS.5.2.65 Bioinformatics in-silico analysis single nucleotide polymorphisms toll- like receptors Behnam Alipoor Behnaalipoor@gmail.com 1 Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AUTHOR Hamid Ghaedi ghaedi.65@gmail.com 2 Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. AUTHOR Mir Davood Omrani davood_omrani@yahoo.co.uk 3 Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. AUTHOR Milad Bastami m.bastami@live.com 4 Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. AUTHOR Reza Meshkani rmeshkani@tums.ac.ir 5 Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AUTHOR Taghi Golmohammadi taghigolmohammadi@yahoo.com 6 Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AUTHOR
ORIGINAL_ARTICLE Carcinoembryonic Antigen Expression and Resistance to Radiation-and 5-Fluorouracil-Induced Apoptosis and Autophagy Understanding the mechanism of tumor resistance is critical for cancer therapy. In this study, we investigated the effect of carcinoembryonic antigen (CEA) overexpression on UV-and 5-fluorouracil (5-FU)-induced apoptosis and autophagy in colorectal cancer cells. We used histone deacetylase (HDAC) inhibitor, NaB and DNA demethylating agent, 5- azacytidine (5-AZA) to induce CEA expression in HT29/219 and SW742 colorectal cancer cell lines. MTT assay was used to measure IC50 value of the cells exposed to graded concentrations of 5- FU with either 0.1 mM NaB or 1 μM 5-AZA for 72 h . Using CHO- and SW742-CEA transfectants, we also investigated the effect of CEA expression on UV- and 5-FU-induced apoptosis and autophagy. Treatment of HT29/219 cell line with NaB and 5-AZA increased CEA expression by 29% and 31%, respectively. Compared with control cells, the IC50 value for 5-FU of NaB and 5-AZA-treated cells increased by 40% and 57%, respectively. Treatment of SW742 cells with NaB or 5-AZA increased neither CEA expression nor the IC50 value for 5-FU. In comparison to parental cells, CEA expression also significantly protected transfected cells against UV-induced apoptosis. Decreased proportions of autophagy and apoptosis were also observed in 5-FU treated SW742- and CHO-CEA transfectants. We conclude that CEA expression can effectively protect colorectal cancer cells against radiation and drug-induced apoptosis and autophagy. http://ijmcmed.org/article-1-460-en.pdf 2016-05-17 80 89 10.22088/acadpub.BUMS.5.2.80 Carcinoembryonic antigen (CEA) colorectal cancer 5-fluorouracil apoptosis autophagy Ebrahim Eftekhar eftekhar_msc@yahoo.com 1 Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran. AUTHOR Hajar Jaberi jaberiehajar@yahoo.com 2 Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran. AUTHOR Fakhraddin Naghibalhossaini fakhraddin.naghibalhossaini@mail.mcgill.ca 3 Autoimmune Research Center, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran. AUTHOR
ORIGINAL_ARTICLE Gene Expression and Methylation Pattern in HRK Apoptotic Gene in Myelodysplastic Syndrome Myelodysplastic syndromes (MDSs) are a clonal bone marrow (BM) disease characterized by ineffective hematopoiesis, dysplastic maturation and progression to acute myeloid leukemia (AML). Methylation silencing of HRK has been found in several human malignancies. In this study, we explored the association of HRK methylation status with its expression, clinical parameters and MDS subtypes in MDS patients. To study the methylation status of HRK gene, we applied Methylation Sensitive-High Resolution Melting Curve Analysis (MS-HRM) in MDS patients, as well as healthy controls and EpiTect®PCR Control DNA. Real time RT-PCR was used for gene expression analysis. Methylation frequency in promoter region of HRK in patient samples was 20.37%. Methylation of HRK was significantly related to transcriptional downregulation (P=0.023). The difference in frequency of hypermethylated HRK gene was significant between good (10%) and poor (71.42%) cytogenetic risk groups (P= 0.001), advanced stage MDS patients (66.66%) in comparison with early stage MDS patients (2.56%) (P= 0.00), higher- risk MDS group (61.53%) and lower- risk MDS group (7.31%) (P= 0.00). HRK hypermethylation was associated with advanced- stage MDS and downregulation of HRK gene may play a role in the progression of MDS. http://ijmcmed.org/article-1-497-en.pdf 2016-06-19 90 99 10.22088/acadpub.BUMS.5.2.90 High Resolution Melting (HRM) methylation myelodysplastic syndrome HRK Farhad Zaker farhadz20@yahoo.co.uk 1 Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. AUTHOR Naser Amirizadeh amiri_na@yahoo.com 2 Blood transfusion research center, High institute for Education and Research in Transfusion Medicine, Tehran, Iran. AUTHOR Nahid Nasiri nahid.nasiri64@yahoo.com 3 Department of Hematology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran. AUTHOR Seyed Mohsen Razavi s_m_raz@yahoo.com 4 Hematology and Oncology Department, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran. AUTHOR Ladan Teimoori-Toolabi lateimoori@gmail.com 5 Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. AUTHOR Marjan Yaghmaie marjan_yaghmaie@yahoo.com 6 Hematology, Oncology and Stem cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran. AUTHOR Roya Mehrasa mehrasa.roya@yahoo.com 7 Blood transfusion research center, High institute for Education and Research in Transfusion Medicine, Tehran, Iran. AUTHOR
ORIGINAL_ARTICLE The Relation between GABA and L-Arginine Levels with some Stroke Risk Factors in Acute Ischemic Stroke Patients Changes in extra and intracellular neurotransmitter amino acids concentration in the early stage of acute cerebral ischemia have been reported. In this the study, serum level of gamma aminobutyric acid (GABA) and L-Arginine in acute ischemic stroke patients was assessed. 60 patients with acute ischemic stroke and sixthy healthy volunteers as a control group were assessed. Serum GABA was measured with modified enzymatic method and serum L- Arginine was measured by modified Sakaguchi method. Serum GABA level in stroke cases was lower than that of the control group. There was no relationship between GABA level and age or gender. Also, no significant correlation was observed between GABA levels with ischemic stroke risk factors such as smoking, diabetes mellitus, and hypertension. Serum L- Arginine level in patients was slightly increased in comparison with control group. There was a positive relationship between serum L- Arginine level and acute ischemic stroke risk factors. Serum GABA level was reduced in patients and had no correlation with acute ischemic stroke risk factors. http://ijmcmed.org/article-1-452-en.pdf 2016-06-19 100 105 10.22088/acadpub.BUMS.5.2.100 Gamma aminobutyric acid (GABA) arginine acute ischemic stroke Mohsen Hosinian 1 Student Research Committee, Babol University of Medical Sciences, Babol, Iran. AUTHOR Durdi Qujeq dqujeq@hotmail.com 2 Cellular and Molecular Biology Research Center (CMBRC), Health Reasearch Institute, Babol University of Medical Sciences, Babol, Iran. AUTHOR Alijan Ahmadi Ahangar ahmadiahangaralijan@yahoo.com 3 Mobility Impairment Research Center, Babol University of Medical Sciences, Babol, Iran. AUTHOR
ORIGINAL_ARTICLE Expression of HCA2 Receptors in Femoral Epiphysis and Metaphysis of Rats with Dexamethasone-Induced Osteoporosis The present study describes the changes in expression of hydroxy- carboxylic acid receptor 2 (HCA2 receptor) in femoral epiphysis and metaphysis of rats with glucocorticoid-induced osteoporosis (GIO). 16 growing male Sprauge dawley rats were randomly divided into two equal groups consisting of normal control and rats that were rendered osteoporotic by receiving 0.1 mg/kg/day dexamethasone through injected subcutaneously. After 4 weeks, all rats were sacrificed and immediately right and left femoral bones were removed for RT-qPCR and histological examination, respectively. Immunohistochemical parameters using a primary rabbit polyclonal GPR109A antibody in hematoxylin and eosin- counter stained slides were determined. HCA2 receptor expression was evaluated using RT- qPCR. Qualitative and histomorphometric evaluation of slides revealed the establishment of glucocorticoid- induced osteoporosis (GIO) in rats treated with dexamethasone. In immunohistochemical study, dexamethasone administration appreciably reduced receptor density in all evaluated cell types and in total slides as compared to control. mRNA level of HCA2 receptor gene was reduced in dexamethasone- treated group. GIO may be associated with down regulation of HCA2 receptors in proximal femoral bone of rats at mRNA as well as protein level in no- cell type-specific manner, although reduction in protein expression needs to be further confirmed by western blotting. http://ijmcmed.org/article-1-500-en.pdf 2016-06-19 106 113 10.22088/acadpub.BUMS.5.2.106 Glucocorticoid-induced osteoporosis hydroxyl-carboxylic acid receptor 2 RT-qPCR immunohistochemistry rat Tahoora Shomali tshomali@shirazu.ac.ir 1 Division of Pharmacology and Toxicology, Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran. AUTHOR Mohammad Kamalpour mk.vet82@gmail.com 2 Division of Pharmacology and Toxicology, Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran. AUTHOR Mehdi Fazeli fazelim@shirazu.ac.ir 3 Division of Pharmacology and Toxicology, Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran. AUTHOR Alireza Rafati arafati@yahoo.com 4 Division of Pharmacology and Toxicology, Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran. AUTHOR
ORIGINAL_ARTICLE Mutation Screening of BRCA Genes in 10 Iranian Males with Breast Cancer Male breast cancer is a rare disease with an increasing trend. Due to limited information especially about the genetic basis of the disease in Iran and the lower age of its onset, the disease requires more attention. The aim of this study was to screen the male patients with breast cancer for BRCA mutations as well as tissue markers of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER-2) and cytokeratin 5/6 (CK5/6). Ten Iranian males with breast cancer were selected regardless of their histologic subtypes, age and family history from patients referred to Mehrad, Day and Parsian hospitals in Tehran, Iran, during a two-year period. Paraffin blocks of the tumoral regions were tested for ER, PR, HER-2 and CK5/6 immunostaining. DNA extraction was carried out on the EDTA blood samples followed by Sanger sequencing. Immunohistochemistry results for ER, and PR were negative in 2 out of 10 patients, while the results of HER-2 and CK5/6 were negative in all the cases. A missense mutation in exon 18 of BRCA1 and a nonsense mutation in exon 25 of in BRCA2 were detected in one patient each. Both patients belonged to luminal A subtype. Despite the low number of patients in this study, it could be concluded that mutations in BRCA1 and BRCA2 occur in male breast cancer patients of luminal A subtype. The negative status of the tissue markers could not be used for the prediction of BRCA mutations. http://ijmcmed.org/article-1-407-en.pdf 2016-05-09 114 122 10.22088/acadpub.BUMS.5.2.114 Male breast cancer BRCA genes human epidermal growth factor receptor cytokeratin 5/6 estrogen receptor progesterone receptor Atieh Zorrieh Zahra 1 Genetics Research Center-University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. AUTHOR Sepideh Kadkhoda 2 Genetics Research Center-University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. AUTHOR Behjati Farkhondeh 3 Genetics Research Center-University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. AUTHOR Fatemeh Aghakhani Moghaddam 4 Genetics Research Center-University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. AUTHOR Azadeh Badiei 5 Genetics Research Center-University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. AUTHOR Fereidoon Sirati 6 Cancer Institute- Department of surgery- Tehran University of Medical Sciences, Tehran, Iran. AUTHOR Hossein Afshin Alavi 7 Pathology Ward-Day hospital,Tehran, Iran. AUTHOR Morteza Atri 8 Cancer Institute- Department of surgery- Tehran University of Medical Sciences, Tehran, Iran. AUTHOR Ramesh Omranipour 9 Cancer Institute- Department of surgery- Tehran University of Medical Sciences, Tehran, Iran. AUTHOR Elahe Keyhani 10 Genetics Research Center-University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. AUTHOR
OTHERS_CITABLE A Novel PKD1 Mutation in a Patient with Autosomal Dominant Polycystic Kidney Disease                   http://ijmcmed.org/article-1-483-en.pdf 2016-06-08 123 124 10.22088/acadpub.BUMS.5.2.123 PKD1 Mutation Polycystic Kidney disease Javad Jamshidi j.jamshidi@fums.ac.ir 1 Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran. AUTHOR Hamed Naderi hamnaderi1@tums.ac.ir 2 Department of Neurology, School of Medicine, Imam Khomeini Hospital AND Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran. AUTHOR Shaghayegh Taghavi shaghtaghvh@sbmu.ac.ir 3 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. AUTHOR Babak Emamalizadeh babemamia@sbmu.ac.ir 4 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. AUTHOR Hossein Darvish darvish_mg@yahoo.com 5 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. AUTHOR