Publications by authors named "Shaban Alizadeh"

50 Publications

Expression and methylation status of vascular endothelial growth factor and thrombospondin-1 genes in congenital factor XIII-deficient patients with intracranial hemorrhage.

Blood Coagul Fibrinolysis 2021 Jul;32(5):317-322

Hematology Department, Allied Medical School, Tehran University of Medical Sciences, Tehran, Iran.

Congenital factor XIII (FXIII) deficiency is one of the rarest bleeding disorders, with an incidence of one per 2 million persons. Intracranial hemorrhage (ICH), a major cause of mortality in FXIII deficiency, is reported to be associated with vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1). Therefore, we investigated the association of VEGF and TSP-1 expression and methylation patterns with ICH in congenital FXIII deficiency patients. This study was conducted on 40 participants with FXIII, 20 of whom experienced ICH (cases), and 20 who did not (controls). Methylation pattern, gene expression, and plasma protein level were assessed using bisulfite sequencing PCR, quantitative real-time PCR, and ELISA. We found a partially methylated pattern for both VEGF and TSP-1 (P > 0.05). VEGF mRNA levels of the case group were significantly higher than those of the control group (P < 0.05), whereas TSP-1 mRNA levels did not show significant upregulation (P > 0.05). Plasma VEGF and TSP-1 concentrations in the case group were higher, but not statistically significant (P > 0.05). Our findings showed no obvious correlation between VEGF or TSP-1 methylation patterns and expression, suggesting that their expression in FXIII deficiency may not solely be controlled by gene methylation.
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http://dx.doi.org/10.1097/MBC.0000000000001039DOI Listing
July 2021

Promoter Methylation Status and Expression Levels of RASSF1A Gene in Different Phases of Acute Lymphoblastic Leukemia (ALL).

Int J Hematol Oncol Stem Cell Res 2021 Jan;15(1):7-14

Department of Hematology and Blood Banking, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.

: Although the precise pathogenesis of acute lymphoblastic leukemia (ALL) remains unclear, studying gene-regulating mechanisms during ALL pathogeneses may shed light on the underlying mechanisms driving malignant behavior. There is some evidence showing the promoter hypermethylation and silencing of RASSF1A tumor suppressor gene in ALL cells; however, there is a lack of evidence for whether the gene indeed alters during different phases of ALL or in response to therapy. Thus, the current study aimed to clarify this issue using groups of adult ALL patients who have been scarcely investigated regarding expression levels and promoter methylation status. : In this case/control study, the expression levels and methylation status of the gene promoter was evaluated using quantitative real-time PCR and methylation-specific PCR (MSP), respectively in adults with ALL. The study included peripheral blood of patients with newly diagnosed ALL (n=10), complete remission (CR) (n=10), or relapse (n=10), and 10 control samples from healthy individuals. : MSP results revealed an unmethylated status for almost all patients and control samples, except a case with relapsing ALL, which showed a hemimethylated pattern. RASSF1A also showed no difference in terms of gene expression in the patients compared with the control group (>0.05). : The results revealed an up-regulation of RASSF1A tumor suppressor in adult ALL patients experiencing CR, suggesting this to be a marker of therapy response. However, further investigations using more sensitive methylation detecting tools with larger sample sizes may better clarify the involvement of the promoter methylation of RASSF1A in these patients.
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http://dx.doi.org/10.18502/ijhoscr.v15i1.5245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885129PMC
January 2021

Validity of a Serological Diagnostic Kit for SARS-CoV-2 Available in Iran.

Arch Iran Med 2020 09 1;23(9):629-632. Epub 2020 Sep 1.

Department of Environmental Health Engineering, Tehran University of Medical Sciences, Tehran, Iran.

Background: The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic broke out in December 2019 and is now characterized as a pandemic. Effective control of this infectious disease requires access to diagnostic techniques, for both case finding and epidemic size estimation. The molecular technique is routinely used worldwide. Although it is the "standard" case detection and management method, it has its own shortcomings. Thus, some easy-to-use rapid serological tests have been developed.

Methods: One hundred and fourteen positive RT-PCR-diagnosed patients were tested by VivaDiag Kit, a brand of rapid serological kits available in hospitals affiliated to Tehran University of Medical Sciences (TUMS), Tehran, Iran. Frozen serum specimens taken from healthy people in summer and fall 2019 were also tested as negative controls.

Results: Test sensitivity was 47.9% (95% confidence interval [CI]: 38.8-56.9) for IgM and 47.0% (95% CI: 38.0-56.0) for IgG. There was no difference between IgG and IgM seropositivity except in one case. Specificity was calculated as 99.0% (95% CI: 96.4-99.9) for IgM and of 100.0% (95% CI: 0.98.2-100.0) for IgG. Sensitivity was higher in men and older participants.

Conclusion: This test can be used for epidemiological investigations, especially for the estimation of the level of infection in the community, after it is properly corrected for sensitivity and specificity. The low sensitivity could be attributed to the technical limitations of the kit or low levels of antibodies after infection. The different sensitivity in age and sex groups supports the hypothesis that different people show different immune responses to this virus.
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http://dx.doi.org/10.34172/aim.2020.75DOI Listing
September 2020

Comparison of Patient-collected and Lab Technician-collected Nasopharyngeal and Oropharyngeal Swabs for Detection of COVID-19 by RT-PCR.

Iran J Pathol 2020 16;15(4):313-319. Epub 2020 Jul 16.

Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background & Objective: A simple approach to prevent close contact in healthcare settings during the COVID-19 outbreak is to train patients to collect their own nasopharyngeal and oropharyngeal swabs and deliver them to medical laboratories to have them processed. The aim of our study was to compare lab technician- with patient- collected oropharyngeal and nasopharyngeal samples for detection of the coronavirus disease 2019 (COVID 19) using rapid real-time polymerase chain reaction (rRT-PCR).

Methods: Fifty adult patients with flu-like symptoms and radiologic findings compatible with atypical pneumonia who were admitted to the infectious diseases ward of Imam Khomeini Hospital Complex, Tehran, Iran, with a clinical diagnosis of COVID-19 from February 28 to April 27 of 2020 were randomly selected and entered in our study. Two sets of naso- and oropharyngeal swabs were collected, one set by a lab technician and the other by the patients, and the COVID-19 rRT-PCR test was performed.

Results: Of 50 selected cases, in seven patients all collected naso- and oropharyngeal swabs tested positive, and in 22 patients all samples tested negative for COVID-19 in rRT-PCR. Discrepancies between rRT-PCR results of lab technician- and patient-collected swabs were observed in 12 nasopharyngeal and 13 oropharyngeal specimens. Positive lab technician-collected and negative patient-collected samples were observed in 10 and 5 nasopharyngeal and oropharyngeal specimens, respectively. Negative lab technician-collected and positive patient-collected samples were observed in two and seven nasopharyngeal and oropharyngeal specimens, respectively. The overall percentage of agreement among both nasopharyngeal and oropharyngeal swabs taken by a lab technician and patients was 76% with a kappa value of 0.49 (=0.001).

Conclusion: Based on our findings, lab technician-collected naso- and oropharyngeal swabs cannot be replaced by patient-collected ones with regard to COVID-19 rRT-PCR.
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http://dx.doi.org/10.30699/ijp.2020.127312.2387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477688PMC
July 2020

Determining the association of thrombophilic gene polymorphisms with recurrent pregnancy loss in Iranian women.

Gynecol Endocrinol 2020 Dec 4;36(12):1082-1085. Epub 2020 Jun 4.

Hematology and Blood Banking Department, Allied School of Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.

Objective: Thrombophilia is known to be associated with poor pregnancy outcomes. In this study, three thrombophilic gene polymorphisms, including EPCR (Ser219Gly), F11 (rs4253417) and F7 (323 Ins10) were investigated in an Iranian population of women in order to determine the correlation between thrombophilia and recurrent pregnancy loss (RPL).

Methods: Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to evaluate the frequency of three candidate thrombophilic risk factors for recurrent pregnancy loss. The frequencies of the polymorphisms were compared between the case (144 patients with a history of at least two miscarriages) and the control (150 healthy women with no abortion) group.

Results: Our results show that EPCR and FVII polymorphisms of the patient and control group have the same genotype frequency, and the difference is not statistically significant (-value > .05). Regarding FXI polymorphism, TT genotype frequency was higher in the patient group than the control group (-value < .05); however, CT heterozygote form was higher in the control group compared to the patient group (-value < .05).

Conclusion: In FXI polymorphism, T allele is possibly an RPL risk factor and C allele has a protective role. Thus, wild type FXI could be related to RPL, but EPCR and FVII polymorphism have no such correlation.
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http://dx.doi.org/10.1080/09513590.2020.1769060DOI Listing
December 2020

Residual methylation of tumor suppressor gene promoters, RASSF6 and RASSF10, as novel biomarkers for minimal residual disease detection in adult acute lymphoblastic leukemia.

Ann Hematol 2019 Dec 5;98(12):2719-2727. Epub 2019 Sep 5.

Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Aberrant promoter methylation of RASSF6 and RASSF10 occurs at a high frequency in acute lymphoblastic leukemia (ALL). Because of the complexity of the current minimal residual disease (MRD) detecting-methods, the DNA methylation status of the RASSF6 and RASSF10 genes could potentially become biomarkers for the assessment of MRD levels in ALL patients. The promoter methylation status of RASSF6 and RASSF10 was assessed by using methylation-specific PCR (MSP) in the DNA isolated from 280 peripheral blood (PB) samples taken at the time of diagnosis, day 14, 28, and from the subsequent 30-month follow-ups of 45 adult ALL patients. The relative methylation level obtained during the follow-ups by MSP was compared to the MRD results obtained by the amplification of IG/TCR clonal rearrangements using the allele-specific quantitative-PCR (ASO-PCR) assay. Frequently, RASSF6 was methylated in B-ALL, and RASSF10 was methylated in T-ALL. The applicability and accuracy of the assays were increased when these markers were combined (91.1% and 93.8%, respectively). When a cutoff was defined for the PCR-MRD level, results of the 30 months of MRD detection showed a significant correlation between the PCR and MSP techniques (r = 0.848; p < 0.001). Due to the high applicability, the non-invasiveness, and promising prospect of longitudinal assessment, the DNA methylation status of the RASSF6 and RASSF10 genes could be potential biomarkers for the assessment of residual disease in PB of patients with ALL.
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http://dx.doi.org/10.1007/s00277-019-03775-yDOI Listing
December 2019

Expression and CpG island methylation pattern of MMP-2 and MMP-9 genes in patients with congenital factor XIII deficiency and intracranial hemorrhage.

Hematology 2019 Dec;24(1):601-605

Hematology Department, Allied Medical School, Tehran University of Medical Sciences , Tehran , Iran.

Objectives: Congenital factor XIII (FXIII) deficiency is a rare severe bleeding disorder. Intracranial hemorrhage (ICH) is the leading cause of mortality and morbidity in FXIII deficiency. However, its pathogenesis is not well understood yet. In this study, we investigated the expression and CpG island methylation status of matrix metalloproteinase-2 (MMP-2) and MMP-9 in patients with FXIII deficiency and ICH.

Methods: Forty patients with FXIII deficiency including twenty patients with ICH, and twenty without ICH were recruited as case and control groups, respectively. Methylation status was determined by bisulfite sequencing polymerase chain reaction (PCR), and gene expression was assessed by quantitative real-time PCR.

Results And Discussion: We found an unmethylated pattern for both and genes in the case group. Both genes were partially methylated in the control group, while the percentage of methylated CpGs was significantly higher in than ( = 0.001). Furthermore, higher expression of (in both the mRNA and protein levels) was found in the case than control group ( = 0.008 and  = 0.009, respectively). On the other hand, there was no significant difference in expression level (neither mRNA nor protein) between the two groups ( = 0.12 and  = 0.25, respectively).

Conclusion: Our findings indicated that over-expression might be related to ICH in FXIII deficiency, and gene methylation effectively regulates its expression. Future researches will expand our understanding of the pathogenesis of ICH in congenital FXIII deficiency.
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http://dx.doi.org/10.1080/16078454.2019.1654181DOI Listing
December 2019

Effect of a high-intensity interval training on serum microRNA levels in women with breast cancer undergoing hormone therapy. A single-blind randomized trial.

Ann Phys Rehabil Med 2019 Sep 7;62(5):329-335. Epub 2019 Aug 7.

Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran; Breast Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: The role of microRNAs (miRs) in hormone therapy (HT) is of keen interest in developing biomarkers and treatments for individuals with breast cancer. Although miRs are often moderate regulators under homeostatic conditions, their function is changed more in response to physical activity.

Objective: This single-blind randomized trial aimed to explore the effect of high-intensity interval training (HIIT) on serum levels of miRs in individuals with early-stage breast cancer undergoing HT.

Methods: Hormone receptor-positive women with breast cancer and healthy women were randomly assigned to a healthy control group (n=15), healthy group with HIIT (n=15), breast cancer group with HT (HT, n=26), and breast cancer group with HT and HIIT (HT+HIIT, n=26). The exercise groups underwent interval uphill walking training on a treadmill 3 times a week for 12weeks. At the end of the study, we analyzed changes in levels of cancer-related miRs (oncomiRs) and tumour suppressor miRs (TSmiRs) in response to the HT and HIIT.

Results: In women with breast cancer versus healthy controls, the expression of some oncomiRs was significantly increased - miR-21 (P<0.001), miR-155 (P=0.001), miR-221 (P=0.008), miR-27a (P<0.001), and miR-10b (P=0.007) - and that of some TSmiRs was significantly decreased - miR-206 (P=0.048), miR-145 (P=0.011), miR-143 (P=0.008), miR-9 (P=0.020), and let-7a (P=0.005). Moreover, HT considerably downregulated oncomiRs and upregulated TSmiRs. HIIT for 12weeks with HT significantly decreased the expression of the oncomiRs and significantly increased that of the TSmiRs as compared with HT alone.

Conclusions: HITT could amplify the decrease and/or increase in expression of miRs associated with HT in women with breast cancer. A prospective trial could determine whether the use of circulating miRs for monitoring treatment can be useful in therapy decisions.

Trial Registration: Iranian Registry of Clinical Trials (No.: IRCT201202289171N1).
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http://dx.doi.org/10.1016/j.rehab.2019.07.001DOI Listing
September 2019

Generation of Induced Pluripotent Cancer Cells from Glioblastoma Multiform Cell Lines.

Cell Reprogram 2019 10 1;21(5):238-248. Epub 2019 Aug 1.

Department Hematology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.

Generation of induced pluripotent stem cells (iPSCs) has been described as a powerful method to dedifferentiate the specialized cells to pluripotency. However, obtaining cancer-specific iPS cells (iPCs) encounters several barriers. The generation of iPCs provides valuable experimental platforms to mimic oncogenesis and offers potentials regarding drug screening. To overcome the difficulties regarding the iPC generation, we aimed at optimizing the generation of iPCs from glioblastoma multiform (GBM) cell lines and at understanding the potential barriers ahead of this process. The T731, T653, and mouse embryonic fibroblast cells were transduced by using retroviral plasmids encoding , , and . The cells were cultured on a layer of feeder cells for 14 days in iPS media and the obtained colonies were then picked and expanded to be evaluated for pluripotency markers by alkaline phosphatase staining, qRT-PCR, and Western blotting. Our findings confirmed resistance in cancer cells to achieve the pluripotency markers. In addition to designing technical tricks to obviate the barriers ahead of iPC generation, we suggested the small molecule PD98059 to enhance the efficiency of iPC generation from GBM cell lines. The resulting iPCs can further be used as a platform to study the mechanism of cancer formation and as a tool for drug screening for the treatment of patients with GBM.
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http://dx.doi.org/10.1089/cell.2019.0046DOI Listing
October 2019

Autologous Platelet-rich Plasma Eye Drops Accelerate Re-epithelialization of Post-keratoplasty Persistent Corneal Epithelial Defects.

J Ophthalmic Vis Res 2019 Apr-Jun;14(2):131-135

Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Purpose: To investigate whether autologous platelet-rich plasma (PRP) eye drops accelerate re-epithelialization of post-keratoplasty persistent corneal epithelial defects (PEDs).

Methods: A total of 34 eyes with PEDs after keratoplasty (24 penetrating keratoplasty and 10 deep anterior lamellar keratoplasty) that were refractory to conventional medical treatments were treated with PRP eye drops every 3 hours. PRP eye drops were prepared with a low- and high-speed centrifugation method and final platelet counts were 700,000-800,000 plt/μl. The mean treatment duration for complete re-epithelialization was compared with the mean treatment duration of conventionally treated corneal defects before the PRP treatment by paired -test. The mean treatment duration was also statistically analyzed between age groups, gender, indications for keratoplasty, and types of keratoplasty using analysis of variance (ANOVA).

Results: Treatment with autologous PRP eye drops led to rapid re-epithelialization in all eyes. The mean treatment duration for complete re-epithelialization was 2.47 ± 1.21 weeks, which was significantly shorter than the mean treatment duration of conventionally treated corneal defects before PRP treatment (6.82 ± 1.24 weeks) ( = 0.0001). There was no significant correlation between re-epithelialization time and patients' age, sex, indications for keratoplasty, and techniques of corneal transplantation.

Conclusion: Treatment with autologous PRP eye drops is an effective and reliable approach that accelerates re-epithelialization of post-transplantation PEDs.
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http://dx.doi.org/10.4103/jovr.jovr_279_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504730PMC
May 2019

Relationship Between Single-Nucleotide Polymorphisms of Tumor Necrosis Factor Alpha, Interleukin-10, Factor II and Factor V with Risk of Inhibitor Development in Patients with Severe Hemophilia A.

Cardiovasc Hematol Disord Drug Targets 2019 ;19(3):228-232

Department of Hematology and Blood Transfusion, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: About one-fourth of patients with hemophilia A (HA) develop alloantibodies against factor (F) VIII, as the main treatment challenge. Here, we assessed the relationship between interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), FII and FV polymorphisms and risk of inhibitor formation in patients with severe HA.

Methods: We divided 39 patients with severe HA in two groups of case (n: 19) and control (n: 20). Genotyping was performed by multiplex amplification tetra arms refractory mutation systempolymerase chain reaction (ARMS-PCR) and PCR-restriction fragment-length polymorphism (PCR-RFLP).

Results: TNFα rs1800629 G>A polymorphism decreased the risk of inhibitor development in codominant and dominant inheritance pattern. Moreover, TNFα rs1800629 A allele, decrease the risk of inhibitor formation, while IL10 rs1800896 A>G, FV rs6025 G>A, and FII rs1799963 G>A polymorphisms were not associated with risk of inhibitor development.

Conclusion: It seems that TNFα rs1800629 G>A polymorphism decreased the risk of inhibitor formation in Iranian patients with HA.
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http://dx.doi.org/10.2174/1871529X19666190206152315DOI Listing
August 2020

Effects of fibrin glue as a three-dimensional scaffold in cultivated adult human retinal pigment epithelial cells.

J Biomater Appl 2018 10 13;33(4):514-526. Epub 2018 Sep 13.

4 Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

This study was conducted to examine morphological, genotypic, and phenotypic alterations occurring in cultured adult human retinal pigment epithelial cells when encapsulated with different concentrations of fibrin glue. Cultivated adult human retinal pigment epithelial cells were encapsulated with different concentrations of fibrin glue, namely FG1 (42 mg/dl), FG2 (84 mg/dl), FG3 (124 mg/dl), FG4 (210 mg/dl), followed by the evaluation of genetic and cytomorphological changes and protein expression. Cultured adult human retinal pigment epithelial cells showed dendritiform morphology during the early days of encapsulation with fibrin glue. Moreover, an increasing inhibitory effect on cell growth was observed with increasing concentrations of fibrin glue. At the transcriptional level, the expression of MMP2, PAX6, and ITGB1 in FG1-encapsulated cells was significantly higher than that in other treated groups; however, the expression of ACTA2 was lower in all fibrin glue-encapsulated groups compared to that in the controls. Immunocytochemistry showed that FG2-encapsulated cells expressed cytokeratin 8/18, RPE65, and ZO-1 proteins, but not PAX6. In conclusion, fibrin glue at a concentration of 84 mg/dl allows proper encapsulation of adult human retinal pigment epithelial cells, while preserving the morphometric, genotypic, and phenotypic features of the cells. This three-dimensional biopolymer can be considered a reliable vehicle for retinal pigment epithelium cell transplantation in cell-based therapies.
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http://dx.doi.org/10.1177/0885328218799506DOI Listing
October 2018

Upregulation of miR-210 promotes differentiation of mesenchymal stem cells (MSCs) into osteoblasts.

Bosn J Basic Med Sci 2018 Nov 7;18(4):328-335. Epub 2018 Nov 7.

Department of Hematology, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.

Numerous studies indicated that microRNAs are critical in the regulation of cellular differentiation, by controlling the expression of underlying genes. The aim of this study was to investigate the effect of miR-210 upregulation on differentiation of human umbilical cord blood (HUCB)-derived mesenchymal stem cells (MSCs) into osteoblasts. MSCs were isolated from HUCB and confirmed by their adipogenic/osteogenic differentiation and flow cytometric analysis of surface markers. Pre-miR-210 was amplified from human DNA, digested and ligated with plenti-III-mir-green fluorescent protein (GFP) vector, and cloned in STBL4 bacteria. After confirmation with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), the plenti-III-GFP segment bearing pre-miR-210 was transfected into MSCs by electroporation. Two control vectors, pmaxGFP and Scramble, were transfected separately into MSCs. The expression of miR-210 and genes related to osteoblast differentiation, i.e., runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin gene, in the three groups of transfected MSCs was analyzed 0, 7, 14, and 21 days of transfection by quantitative reverse transcription PCR (qRT-PCR). Overexpression of miR-210 was observed in MSCs transfected with miR-210-bearing plasmid, and this was significantly different compared to Scramble group (p < 0.05). Significantly increased expression of Runx2 (at day 7 and 14), ALP and osteocalcin genes (at all time points for both genes) was observed in MSCs with miR-210-bearing plasmid compared to controls. Overall, the overexpression of miR-210 in MSCs led to MSC differentiation into osteoblasts, most probably by upregulating the Runx2, ALP, and osteocalcin genes at different stages of cell differentiation. Our study confirms the potential of miRNAs in developing novel therapeutic strategies that could target regulatory mechanisms of cellular differentiation in various disease states.
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http://dx.doi.org/10.17305/bjbms.2018.2633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252095PMC
November 2018

Study of the Relationship between HPA-1 and HPA-5 Gene Polymorphisms and Refractory to Platelet Therapy and Recombinant Factor VII in Glanzmann Thrombasthenia Patients in Southeast of Iran.

Int J Hematol Oncol Stem Cell Res 2018 Jan;12(1):43-48

Department of Hematology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.

Glanzmann Thrombasthenia (GT) is a rare autosomal disease. HPA (Human Platelet Alloantigen) is a surface polymorphic alloantigen of platelets. This study was intended to investigate and compare the polymorphism of HPA-1 and HPA-5 genes in two groups of GT patients, with and without resistance to platelet and recombinant factor VII therapy. This case control study was performed on GT patients (n=16) with resistance to platelet therapy and recombinant factor VII and control group of GT patients (n=16) without resistance to platelet therapy and recombinant factor VII. The consent form was completed by each patient. Gene polymorphisms of HPA-1 and HPA-5 were investigated using SSP-PCR, and the obtained data were analyzed using statistical software SPSS16.0. The results indicated no significant relationship between the studied genes and their resistance to platelet therapy and recombinant factor VII. The frequencies of HPA-1 genotype a/a were 98% and 94% in patient and control groups, respectively. The frequency of allele b was found to be less than allele a. The value of this allele was 4% in patient group and 1% in control group. In addition, the HPA-5a/a (98%) was the most frequent alloantigen?? (check it) in both groups. Seven percent (7%) of the patients had the HPA-5a/b genotype, and the HPA-5b/b was found to be absent in these individuals. According to the results obtained, it could be concluded that these genes play no role in resistance to platelet therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018251PMC
January 2018

Disulfiram/copper causes ROS levels alteration, cell cycle inhibition, and apoptosis in acute myeloid leukaemia cell lines with modulation in the expression of related genes.

Biomed Pharmacother 2018 Mar 20;99:561-569. Epub 2018 Feb 20.

Hematologic Malignancies Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

The majority of acute myeloid leukaemia (AML) patients will die from their disease or therapy-related complications. There is an inevitable need to improve the survival of AML patients. Previous studies show that disulfiram (DSF), an anti-alcoholism drug with a low toxicity profile, demonstrates anticancer behaviors. Here, we evaluated the cytotoxicity and mechanistic action of DSF on the AML cell lines KG-1, NB4, and U937. The microculture tetrazolium test revealed that DSF alone or in combination with copper (Cu) is highly toxic to the AML cells at concentrations lower than those achievable in the clinical setting, with Cu increasing the DSF-induced inhibition of metabolic activity. Flow cytometric analysis and QRT-PCR indicated that in the two cell lines, NB4 and U-937, DSF/Cu increased reactive oxygen species (ROS) levels in association with the induction of superoxide dismutase 2 (SOD2) expression and suppression of catalase (CAT). In the KG-1 cell line, DSF/Cu reduced the ROS levels in agreement with the induction of CAT expression. The cell cycle and apoptosis assessment by flow cytometry demonstrated that DSF/Cu induced G0/G1 cell cycle arrest and apoptosis. These were associated with the increased expression of FOXO tumor suppressors, decreased expression of the MYC oncogene and the modulation of their known target genes related to the cell cycle and apoptosis. Therefore, DSF/Cu caused the disturbance of the ROS balance, cell cycle arrest and apoptosis in AML cells in coordination with the modulation in expression of their related genes. These results propose the possible use of DSF in AML therapies.
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http://dx.doi.org/10.1016/j.biopha.2018.01.109DOI Listing
March 2018

The impact of Mir-9 regulation in normal and malignant hematopoiesis.

Oncol Rev 2018 Jan 27;12(1):348. Epub 2018 Mar 27.

Thalassemia & Hemoglobinopathy Research Center, Research Institute of Health, Ahvaz Jun-dishapur University of Medical Sciences, Ahvaz, Iran.

MicroRNA-9 (MiR-9) dysregulation has been observed in various cancers. Recently, MiR-9 is considered to have a part in hematopoiesis and hematologic malignancies. However, its importance in blood neoplasms is not yet well defined. Thus, this study was conducted in order to assess the significance of MiR-9 role in the development of hematologic neoplasia, prognosis, and treatment approaches. We have shown that a large number of MiR-9 targets (such as FOXOs, SIRT1, CCND1, ID2, CCNG1, Ets, and NFkB) play essential roles in leukemogenesis and that it is overexpressed in different leukemias. Our findings indicated MiR-9 downregulation in a majority of leukemias. However, its overexpression was reported in patients with dysregulated MiR-9 controlling factors (such as MLLr). Additionally, prognostic value of MiR-9 has been reported in some types of leukemia. This study generally emphasizes on the critical role of MiR-9 in hematologic malignancies as a prognostic factor and a therapeutic target.
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http://dx.doi.org/10.4081/oncol.2018.348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939831PMC
January 2018

TNF-α and TGF-ß level after intraoperative allogeneic red blood cell transfusion in orthopedic operation patients

Turk J Med Sci 2017 Dec 19;47(6):1813-1818. Epub 2017 Dec 19.

Background/aim: Blood transfusion is associated with immunosuppression, referred to as transfusion-related immunomodulation (TRIM). In this study, for the first time, changes in the concentration of TGF-ß and TNF-α were measured postoperatively in orthopedic patients with intraoperational allogeneic red blood cell transfusion. Considering the use of packed cell units with different ages, it is possible to suggest the more appropriate product for clinical applications.Materials and methods: Two groups of 35 orthopedic surgery patients (with or without transfusion as case and control groups, respectively) were involved. Serum levels of TNF-α and TGF-ß were measured by ELISA.Results: The data suggested significant differences in age (P = 0.0001), lowered hemoglobin (P = 0.003), and hematocrit (P = 0.003) between the control and case groups. Pre- and postoperation levels of TNF-α and TGF- ßwere not significantly different, but the results showed significant increases in levels of both cytokines after the operation (P = 0.0001) in both groups.Conclusion: Increased levels of TNF-α and TGF-ß are probably related to surgery and packed cell transfusion, respectively. Further studies using more packed cell units or other blood products and assessment of more cytokines are needed to have better understanding about this issue.
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http://dx.doi.org/10.3906/sag-1508-36DOI Listing
December 2017

Redistribution of cell cycle by arsenic trioxide is associated with demethylation and expression changes of cell cycle related genes in acute promyelocytic leukemia cell line (NB4).

Ann Hematol 2018 Jan 20;97(1):83-93. Epub 2017 Nov 20.

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation in acute promyelocytic leukemia (APL). Transcription induction and recruitment of DNA methyltransferases (DNMTs) by PML-RARα and subsequent hypermethylation are components of this perturbation. Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARα induces cell cycle change and apoptosis. How ATO causes cell cycle alteration has remained largely unexplained. Here, we investigated DNA methylation patterns of cell cycle regulatory genes promoters, the effects of ATO on the methylated genes and cell cycle distribution in an APL cell line, NB4. Analysis of promoter methylation status of 22 cell cycle related genes in NB4 revealed that CCND1, CCNE1, CCNF, CDKN1A, GADD45α, and RBL1 genes were methylated 60.7, 84.6, 58.6, 8.7, 33.4, and 73.7%, respectively, that after treatment with 2 μM ATO for 48 h, turn into 0.6, 13.8, 0.1, 6.6, 10.7, and 54.5% methylated. ATO significantly reduced the expression of DNMT1, 3A, and 3B. ATO induced the expression of CCND1, CCNE1, and GADD45α genes, suppressed the expression of CCNF and CDKN1A genes, which were consistent with decreased number of cells in G1 and S phases and increased number of cells in G2/M phase. In conclusion, demethylation and alteration in the expression level of the cell cycle related genes may be possible mechanisms in ATO-induced cell cycle arrest in APL cells. It may suggest that ATO by demethylation of CCND1 and CCNE1 and their transcriptional activation accelerates G1 and S transition into the G2/M cell cycle arrest.
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http://dx.doi.org/10.1007/s00277-017-3163-yDOI Listing
January 2018

DNA hypermethylation of tumor suppressor genes RASSF6 and RASSF10 as independent prognostic factors in adult acute lymphoblastic leukemia.

Leuk Res 2017 10 30;61:33-38. Epub 2017 Aug 30.

Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: The Hypermethylation of Ras association domain family (RASSF) often plays a key role in malignant progression of solid tumors; however, their impact on the prognosis and survival of adult ALL patients remain elusive.

Methods: The frequency of the promoter methylation pattern of RASSF6 and RASSF10 were analyzed in the peripheral blood (PB) samples taken at the time of diagnosis of 45 ALL patients. The methylation-specific PCR (MSP) assay was used to detect the DNA methylation patterns.

Results: RASSF6 was frequently hypermethylated in patients diagnosed with pre-B-ALL (90.9%) and B-ALL (87.5%), followed by T-ALL (66.7%); whereas, RASSF10 methylation was more confined to T-ALL (80%) as compared to B-ALL (25%) and pre-B ALL (9.1%) patients. Moreover, hypermethylation of RASSF6 was significantly associated with a poor prognosis and shorter overall survival (OS) in patients with pre-B-ALL (log-rank test; P=0.041).

Conclusion: RASSF6 and RASSF10 were frequently hypermethylated in the samples at the time of diagnosis of adult ALL patients. Our study represents the first report of methylation of RASSF6 at a high frequency in patients with pre-B ALL. Furthermore, hypermethylation of RASSF6 was significantly associated with inferior overall survival in pre-B ALL patients. It may suggest that the frequent epigenetic inactivation of RASSF6 plays an important role in the pathogenesis and progression of pre-B-ALL.
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http://dx.doi.org/10.1016/j.leukres.2017.08.016DOI Listing
October 2017

The enhancement of differentiating adipose derived mesenchymal stem cells toward hepatocyte like cells using gelatin cryogel scaffold.

Biochem Biophys Res Commun 2017 09 1;491(4):1000-1006. Epub 2017 Aug 1.

Hematology department, Allied medical school, Tehran University of Medical Sciences, Tehran, Iran.

Liver tissue engineering creates a promising methodology for developing functional tissue to restore or improve the function of lost or damaged liver by using appropriate cells and biologically compatible scaffolds. The present paper aims to study the hepatogenic potential of human adipose derived mesenchymal stem cells (hADSCs) on a 3D gelatin scaffold in vitro. For this purpose, mesenchymal stem cells were isolated from human adipose tissue and characterized by flowcytometry analysis and mesodermal lineage differentiation capacity. Then, porous cryogel scaffolds were fabricated by cryogelating the gelatin using glutaraldehyde as the crosslinking agent. The structure of the scaffolds as well as the adhesion and proliferation of the cells were then determined by Scanning Electron Microscopy (SEM) analysis and MTT assay, respectively. The efficiency of hepatic differentiation of hADSCs on 2D and 3D culture systems has been assessed by means of morphological, cytological, molecular and biochemical approaches. Based on the results of flowcytometry, the isolated cells were positive for hMSC specific markers and negative for hematopoietic markers. Further, the multipotency of these cells was confirmed by adipogenic and osteogenic differentiation and the highly porous structure of scaffolds was characterized by SEM images. Biocompatibility was observed in the fabricated gelatin scaffolds and the adhesion and proliferation of hADSCs were promoted without any cytotoxicity effects. In addition, compared to 2D TCPS, the fabricated scaffolds provided more appropriate microenvironment resulting in promoting the differentiation of hADSCs toward hepatocyte-like cells with higher expression of hepatocyte-specific markers and appropriate functional characteristics such as increased levels of urea biosynthesis and glycogen storage. Finally, the created 3D gelatin scaffold could provide an appropriate matrix for hepatogenic differentiation of hADSCs, which could be considered for liver tissue engineering applications.
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http://dx.doi.org/10.1016/j.bbrc.2017.07.167DOI Listing
September 2017

miR-155 effectively induces apoptosis in K562 Philadelphia positive cell line through upregulation of p27kip1.

Bioimpacts 2017 26;7(2):109-114. Epub 2017 Apr 26.

Cancer Prevention Research Center, Shahroud University of Medical Sciences, Shahroud, Iran.

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder caused by the Philadelphia chromosome translocation, at (9; 22), which results in BCR-ABL fusion tyrosine kinase oncoprotein. This fusion induces down-regulation of miR-155. Upregulation of miR-155 can influence cell fate via the effect on p27kip1 and apoptosis. The aim of this study was to induce apoptosis in K562 CML cell line by overexpression of miR-155. The K562 cell line was transfected with pLenti-III-pre mir155-GFP constructs through electroporation. Then, overexpression of miR-155 as well as the expression level of p27kip1 and c-Myc was analyzed by quantitative PCR (qPCR). The level of p27 (Kip1) protein expression was measured by Western blot and the Annexin V method was carried out to investigate apoptosis. Flow cytometric analysis results of K562 cells transfected with pLenti-III-pre mir155-GFP construct showed a significant increase in cell apoptosis. Gene expression and protein level of p27kip1 were upregulated. However, there was no change in c-Myc expression profile. miR-155 could be a promising approach to aid in the treatment of CML. However, further studies are required in this respect.
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http://dx.doi.org/10.15171/bi.2017.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524985PMC
April 2017

The effects of platelet gel on cultured human retinal pigment epithelial (hRPE) cells.

Bosn J Basic Med Sci 2017 Nov 20;17(4):315-322. Epub 2017 Nov 20.

Department of Hematology, School of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran.

The positive role of platelet gel (PG) in tissue regeneration is well known, however, other characteristics of PG still remain to be determined. We investigated cellular and molecular changes in cultured human retinal pigment epithelial (hRPE) cells when treated with different concentrations of PG named PG1, PG2, and PG3. hRPE cells were isolated from donor eyes of two newborn children, within 24 hours after their death. The cells were treated with three concentrations of PG for 7 days: 3 × 104/ml (PG1), 6 × 104/ml (PG2), and 9 × 104/ml (PG3). Fetal bovine serum was used as a control. Immunocytochemistry was performed with anti-RPE65 (H-85), anti-Cytokeratin 8/18 (NCL-5D3), and anti-PAX6 antibody. We used MTT assay to determine cell viability. Gene expressions of PAX6, MMP2, RPE65, ACTA2, MKI67, MMP9, and KDR were analyzed using real-time PCR. A significant increase in viability was observed for PG3-treated cells compared to control (p = 0.044) and compared to PG1 group (p = 0.027), on day 7. Cellular elongation together with dendritiform extensions were observed in PG-treated cells on days 1 and 3, while epithelioid morphology was observed on day 7. All cells were immunoreactive for RPE65, cytokeratin 8/18, and PAX6. No significant change was observed in the expression of MKI67 and PAX6, but the expressions of MMP2, MMP9, ACTA2, and KDR were significantly higher in PG2-treated cells compared to controls (p < 0.05). Our results indicate that increased concentration of PG and extended exposure time have positive effects on viability of hRPE cells. PG may be useful for hRPE cell encapsulation in retinal cell replacement therapy.
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http://dx.doi.org/10.17305/bjbms.2017.2103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708902PMC
November 2017

Childhood acute lymphoblastic leukemia: refusal and abandonmentof treatment in the southeast of Iran.

Turk J Med Sci 2016 Apr 19;46(3):706-11. Epub 2016 Apr 19.

School of Nursing and Midwifery, Shahroud University of Medical Sciences, Shahroud, Iran.

Background/aim: Acute lymphoblastic leukemia (ALL) accounts for 25% of all malignancies in children. ALL treatment has standard protocols, and treatment abandonment is a main cause of treatment failure. Therefore, this study aimed to assess the relationship between socioeconomic status and rate as well as cause of abandoned treatment in children with ALL in the southeast of Iran.

Materials And Methods: This retrospective, descriptive cohort study was conducted with ALL patients at the Ali Asghar Hospital in the city of Zahedan. The study population included 22 children with different subtypes of ALL who had abandoned their treatment. A structural questionnaire was filled out by patients or their parents. Results were assessed using descriptive and analytical tests.

Results: The rate of treatment abandonment was 24.4% (22 patients).We had 18 ALL-L1 (78.3%) and four ALL-L2 (17.4%) patients. Reasons for treatment abandonment were low family income, transportation difficulties, the father's education status, conviction about ALL's incurability, and reference to spiritual means, respectively.

Conclusion: Low family income, transportation difficulties, the father's education status, belief about ALL's incurability, and reference to spiritual means were the most common associations with ALL treatment abandonment in that order. Financial problems in this part of the country can impose high costs to the healthcare system.
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http://dx.doi.org/10.3906/sag-1412-42DOI Listing
April 2016

The Role of MicroRNAs in Myeloproliferative Neoplasia.

Int J Hematol Oncol Stem Cell Res 2016 Jul;10(3):172-85

Hematology Department, School of Medicine, Tarbiat Modares University, Tehran, Iran.

MiRs are 17-25 nucleotide non-coding RNAs. These RNAs target approximately 80% of protein coding mRNAs. MiRs control gene expression and altered expression of them affects the development of cancer. MiRs can function as tumor suppressor via down-regulation of proto-oncogenes and may function as oncogenes by suppressing tumor suppressors. Myeloproliferative neoplasias (formerly known as chronic myeloproliferative disorders) form a class of hematologic malignancies demonstrating the expansion of stem cells in one or more hematopoietic cell lines. CML results from an acquired translocation known as BCR-ABL (Philadelphia chromosome). JAK2V617F mutation is present in over 95% of PV, 55% of ET and 65% of PMF cases. Aberrant expression of miR is associated with myeloproliferative neoplasias, pathogenesis, disease progress and response to treatment. MiRs can also be potential therapeutic targets. CML is mainly treated by tyrosine kinase inhibitors such as Imatinib. In addition, altered function of miRs may be used as a prognostic factor in treatment. Resistance to Imatinib is currently a major clinical problem. The role of a number of miRs has been demonstrated in this resistance. Changing expression pattern of miRs can be effective in response to treatment and inhibition of drug resistance. In this paper, we set out to evaluate the effect of miRs in pathogenesis and treatment of MPN.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969562PMC
July 2016

Spectrum of factor X gene mutations in Iranian patients with congenital factor X deficiency.

Blood Coagul Fibrinolysis 2016 Apr;27(3):324-7

aDepartment of Hematology and Blood Transfusion, School of Allied Medical Sciences bCellular and Molecular Research Center, Iran University of Medical Sciences, Tehran cDepartment of Laboratory Medicine, Zabol University of Medical Sciences, Zabol dSchool of Nursing and Midwifery, Shahroud University of Medical Sciences, Shahroud eDepartment of Hematology and Blood Transfusion, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.

Congenital factor X deficiency is one of the most severe forms of rare bleeding disorders transmitted in autosomal recessive manner. According to the World Federation of Hemophilia survey, 153 patients with factor X deficiency (FXD) live in Iran, but a few studies have been performed to determine the precise distribution of FXD in different parts of the country and to assess molecular basis of this disorder in Iranian patients. This study was conducted to assess the spectrum of factor X gene mutation in Iranian patients with congenital FXD. All relevant English and Persian-language publications were searched (until 2015). Clinical presentations or molecular basis of nearly 90 Iranian patients were reported in different studies. Most of these studies focused on clinical presentations of patients, whereas molecular analyses were rarely performed. Most molecular studies found a diversity in factor X disease causing mutations in Iranian patients. Like other parts of the world, the majority of mutations in Iranian patients were missense mutations, but splice-site mutations were relatively common. Three extremely rare cases of combined factor X and factor VII deficiencies were observed in two cases of which this disorder resulted from different missense mutations in respective factor genes. A wide spectrum of factor X gene mutations was observed in Iranian patients with congenital FXD that revealed diversity in FXD gene mutations.
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http://dx.doi.org/10.1097/MBC.0000000000000435DOI Listing
April 2016

Modulation of microRNAs expression in hematopoietic stem cells treated with sodium butyrate in inducing fetal hemoglobin expression.

Artif Cells Nanomed Biotechnol 2017 Feb 2;45(1):146-156. Epub 2016 Feb 2.

e Department of Hematology, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran.

Context Inherited hemoglobin diseases are the most common single-gene disorders. Induction of fetal hemoglobin in beta hemoglobin disorders compensate for abnormal chain and ameliorate the clinical complications. Sodium butyrate is used conventionally for fetal hemoglobin induction; it can be replaced by safer therapeutic tools like microRNAs, small non-coding RNAs that control number of epigenetic mechanisms. Objective In this study, we compared the changes in the microRNAs of differentiated erythroid cells between control and sodium butyrate treated groups. The objective is to find significant association between these changes and gamma chain up regulation. Materials and methods First, CD133 hematopoietic stem cells were isolated from cord blood by magnetic cell sorting (MACS) technique. After proliferation, the cells were differentiated to erythroid lineage in culture medium by EPO, SCF, and IL3. Meanwhile, the test group was treated with sodium butyrate. Then, gamma chain upregulation was verified by qPCR technique. Finally, microRNA profiling was performed through microarray assay and some of them confirmed by qPCR. Result Results demonstrated that gamma chain was 5.9-fold upregulated in the treated group. Significant changes were observed at 76 microRNAs, in which 20 were up-regulated and 56 were down-regulated. Discussion Five of these microRNAs including U101, hsa-miR-4726-5p, hsa-miR7109 5p, hsa-miR3663, and hsa-miR940 had significant changes in expression and volume. Conclusion In conclusion, it can be assumed that sodium butyrate can up-regulate gamma chain gene, and change miRNAs expression. These results can be profitable in future studies to find therapeutic goal suitable for such disorders.
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http://dx.doi.org/10.3109/21691401.2016.1138487DOI Listing
February 2017

Establishment of a prenatal diagnosis schedule as part of a prophylaxis program of factor XIII deficiency in the southeast of Iran.

Blood Coagul Fibrinolysis 2016 Jan;27(1):97-100

aDepartment of Pediatrics Hematology & Oncology, Ali Ebn-e Abitaleb Hospital Research Center for Children and Adolescents Health [RCCAH], Zahedan University of Medical Sciences, Zahedan bDepartment of Hematology, Allied Medical School, Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran cDepartment of Hematology and Blood Transfusion, School of Allied Medicine, Iran University of Medical Sciences dDepartment of Hematology and Blood Transfusion, School of Allied Medicine, Tehran University of Medical Sciences eDepartment of Biochemistry, School of Allied Medicine, Tehran University of Medical Sciences, Tehran fGenetic of Non-Communicable Disease Researcher Center, Zahedan University of Medical Sciences, Zahedan, Iran.

Factor XIII deficiency (FXIIID) is an extremely rare bleeding disorder with a prevalence of 1 in 3 million in the general population. Compared to its global incidence, it has the greatest prevalence in Sistan and Baluchistan Province in the southeast of Iran. The high incidence of FXIIID in this region causes a high rate of morbidity and mortality among the affected individuals because of life-threatening episodes such as central nervous system (CNS) bleeding, umbilical cord bleeding, as well as miscarriage. CNS bleeding leads to a considerable number of neurological and behavioral complications. Therefore, we have designed an established prenatal diagnosis (PND) program to prevent the increasing incidence of life-threatening bleeding episodes and related complications among neonates with congenital FXIIID. This study was conducted from September 2013 to August 2014. A consent form was signed by the parents. Fetal sampling was done via abdominal chorionic villus sampling passage under local anesthesia and ultrasonic guidance within the first trimester of pregnancy. Fetal DNA was extracted, and PCR-restriction fragment length polymorphism was performed for the only reported mutation of FXIII (Trp187Arg) in the southeast of Iran. During the period of study, PND was performed on eight fetuses. Six fetuses were offspring of parental consanguineous marriages, and all of them had a positive family history of FXIIID. Seven out of the eight fetuses had a family member with CNS bleeding due to FXIIID. Four fetuses had a FXIIID-related death. One of the fetuses bore homozygous Trp187Arg mutation, whereas six were heterozygous, and one of the mothers gave birth to an unaffected fetus. To the best of our knowledge, PND is a possible solution to control high incidence of life-threatening episodes of FXIIID in southeast Iran.
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http://dx.doi.org/10.1097/MBC.0000000000000374DOI Listing
January 2016

Effects of exercise training together with tamoxifen in reducing mammary tumor burden in mice: Possible underlying pathway of miR-21.

Eur J Pharmacol 2015 Oct 20;765:179-87. Epub 2015 Aug 20.

Colon Cancer Center, South Carolina University, United States of America.

Exercise training has an anti-tumor effect and can reduce tumor growth; however, the exact underlying mechanisms of its protective effects are still obscure. MicroRNA (miR)-21 is a predictor in cancer survival, and has a potential use as an indicator of therapeutic outcome in breast malignancies. Forty-eight female BALB/c mice were equally divided into six groups to investigate the effects of interval exercise training with tamoxifen on miR-21 expression and its possible assumed mechanisms in an estrogen receptor-positive breast cancer model. ELISA, immunohistochemistry, western blot, qRT-PCR assays were performed at the end of the study. Tumor size was significantly declined in exercise training and tamoxifen groups compared to tumor group (P<0.05). Expression of miR-21 was significantly down-regulated in trained and tamoxifen treated mice in comparison with tumor group (P<0.05). Exercise training was as effective as tamoxifen treatment in decreasing serum estradiol and ER-α expression (P<0.05). Exercise training and tamoxifen reduced tumor IL-6 levels, NF-kB and STAT3 expressions, and up-regulated TPM1 and PDCD4 expressions (P<0.05). Both exercise and tamoxifen had synergistic effects in reducing miR-21 and Bcl-2, and up-regulating PDCD4 expression. Results showed that interval exercise training may reduce mammary tumor burden in mice through possible underlying pathway of miR-21.
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http://dx.doi.org/10.1016/j.ejphar.2015.08.031DOI Listing
October 2015

First cases of severe congenital factor XIII deficiency in Southwestern Afghanistan in the vicinity of southeast of Iran.

Blood Coagul Fibrinolysis 2015 Dec;26(8):908-11

aDepartment of Hematology and Blood Transfusion, School of Allied Medical, Iran University of Medical Sciences bDepartment of Hematology and Blood Transfusion, School of Allied Medical, Tehran University of Medical Sciences, Tehran cGenetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences dDepartment of Pediatrics Hematology & Oncology, Ali Ebn-e Abitaleb Hospital Research Center for Children and Adolescents Health (RCCAH), Zahedan University of Medical Sciences, Zahedan, Iran eCivil Hospital Nimrooz, Zaranj, Nimrooz, Afghanistan fSchool of Nursing and Midwifery, Shahroud University of Medical Sciences, Shahroud gHormozgan Institute of Health, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

Factor XIII deficiency (FXIIID) is an extremely rare bleeding disorder with the highest global incidence in southeast of Iran. Southwestern Afghanistan (Nimruz Province) is located near the border with Iran in the vicinity of Sistan and Baluchestan Province in southeast Iran, and there seems to be a high prevalence of FXIIID in Nimruz. Thus, this cross-sectional study was designed to assess the prevalence of FXIIID, molecular basis as well as clinical manifestations of FXIIID in Southwestern Afghanistan. During the course of the study, all patients suspected of FXIIID were clinically examined and assessed by routine coagulation tests, including bleeding time, activated partial thromboplastin time, prothrombin time, as well as platelet count and clot solubility test. Patients with normal routine coagulation tests, but abnormal clot solubility test, underwent further investigations by FXIII activity, as well as molecular analysis for FXIII-A gene mutation (Trp187Arg) by PCR-restriction fragment length polymorphism that confirmed by sequencing. Patients with confirmed FXIIID deficiency were registered to receive prophylaxis treatment. All data including demographic information, clinical manifestations, as well as therapeutic response and type and duration of treatment, were recorded, and the data were analyzed by SPSS software. In this cross-sectional study, we found five patients with abnormal clot solubility test, among whom two patients abandoned the study, whereas three patients remained for a more precise study. All the patients were residents of Zaranj city, the capital of Nimruz Province. All these patients had undetectable activity of FXIII, which indicates a severe deficiency. Molecular analysis of patients showed mutation of Trp187Arg in all of them. Hematoma was the most common clinical presentation leading to diagnosis of FXIIID in these patients (100%). Epistaxis (67%), gum bleeding (33%), and hematuria (33%) were other recurrent clinical presentations of the patients. Three cases of death due to FXIIID were detected in the family of these patients. There was a high prevalence of FXIIID in Zaranj city with a population of 50 000, which was appropriately equal to the prevalence of the disorder in southeast of Iran, which seemed to have the highest global prevalence of FXIIID, and underlines that the same mutation (Trp187Arg) in both regions is same.
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http://dx.doi.org/10.1097/MBC.0000000000000358DOI Listing
December 2015
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