Publications by authors named "Ramin Saravani"

39 Publications

Convalescent Blood: Current Perspective on the Efficacy of a Legacy Approach in COVID-19 Treatment.

Blood Purif 2021 Mar 31:1-14. Epub 2021 Mar 31.

Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

Since early 2020, COVID-19 has wreaked havoc in many societies around the world. As of the present, the SARS-CoV-2-borne disease is propagating in almost all countries, affecting hundreds of thousands of people in an unprecedented way. As the name suggests, the novel coronavirus, widely known as SARS-CoV-2, is a new emerging human pathogen. A novel disease of relatively unknown origin, COVID-19 does not seem to be amenable to the currently available medicines since there is no specific cure for the disease. In the absence of any vaccine or effective antiviral medication, we have no tools at our disposal, but the method of quarantine, be it domestic or institutional, to hinder any further progression of this outbreak. However, there is a record of physicians in the past who practiced convalescent blood transfusion. To their awe, the method seemed to be useful. It is anticipated that these contemporary methods will outdo any other vaccination process in the time being, as blood transfusion is instead a cost-effective and time-friendly technique. Following a successful trial, this new approach of contemporary nature to a viral disease may serve as an emergency intervention to intercept infectious outbreaks and prevent an impending epidemic/pandemic. In this review, we document the most recent evidence regarding the efficiency of convalescent plasma and serum therapy on SARS, MERS, and particularly COVID-19, while discussing potential advantages and possible risks of such practice.
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http://dx.doi.org/10.1159/000513164DOI Listing
March 2021

Association of a Novel Gene Polymorphism with Susceptibility to Schizophrenia and Breast Cancer: A Case-Control Study.

Iran J Public Health 2021 Feb;50(2):397-406

Department of Biology, Faculty of Science, Isfahan University, Isfahan, Iran.

Background: gene is found to play essential roles in regulating different aspects of cell proliferation and development of the nervous system. We aimed to determine if rs12407427 T/C polymorphism could affect susceptibility to schizophrenia (SZN) and breast cancer (BC), the two genetically correlated diseases.

Methods: The current case-control study was performed from Aug 2018 to Dec 2018. Briefly, 159 female pathologically confirmed BC cases referring to Alzahra Hospital, Isfahan, Iran, and 102 psychologically confirmed SZN patients (60 males and 42 females) admitted to Baharan Hospital, Zahedan, Iran, were enrolled. Using the salting-out method, genomic DNA was extracted, and variants were genotyped using allele-specific amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method.

Results: The results revealed a significant association between the rs12407427 codominant CT (0.001), CC (0.0001), dominant CT+CC, and recessive CC (0.001) genotypes with the risk of developing SZN. Significant correlations were also found regarding rs12407427 and BC susceptibility in different inheritance models, including over-dominant CT (0.026), dominant CT+CC (0.001), recessive CC (0.009), and codominant CT and CC (0.001) genotypes. The over-presence of the C allele was also correlated with an increased risk for SZN (0.0001) and BC (0.0001). Finally, computational analysis predicted that T/C variation in this polymorphism could change the binding sites in proteins involved in splicing.

Conclusion: rs12407427 T/C as a de novo variant might be a novel genetic biomarker for SZN and/or BC susceptibility in a sample of the Iranian population.
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http://dx.doi.org/10.18502/ijph.v50i2.5359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956084PMC
February 2021

SNPs in the 3'-untranslated region of confer risk of type 2 diabetes mellitus in a south-east Iranian population: Evidences from case-control and bioinformatics studies.

J Diabetes Metab Disord 2020 Dec 21;19(2):979-988. Epub 2020 Jul 21.

Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.

Background: Type 2 diabetes mellitus (T2DM) is a heterogenic disease with increasing incidence. The gene encodes an islet zinc transporter (ZnT8), and its variants have been associated with glucose and pro-insulin levels. This study was aimed to examine the effects of a missense variant (rs13266634 C/T), and two 3'UTR variants (rs2466294 C/G and rs2466293 T/C) in gene on T2DM risk in a south-east Iranian population.

Methods: In this experiment, 450 patients diagnosed with T2DM and 453 healthy subjects from the same geographic area were enrolled. Genotypes were amplified using the ARMS-PCR method. analyses were performed to determine the effects of the variants on the local structure of mRNA, splicing patterns, and potential miRNA-gene interactions as well.

Results: Significant differences were noticed between cases and controls regarding the genotypic and allelic distribution of the studied variants. As regards rs2466293 and rs2466294 variants, enhanced risk of T2DM was found under allelic, dominant, recessive, and codominant models (OR > 1). Besides, different genetic models of rs13266634 were associated with decreased risk of T2DM (OR < 1). Bioinformatics analyses indicated that the rs2466293 variant might influence the binding of some miRNAs, while the G-allele of rs2466294 decreased the stability of

Conclusions: In our population, both SNPs in the 3'-untranslated region of increased the risk of T2DM, while the rs13266634 variant showed a protective association against T2DM susceptibility. Investigating the effects of other variants in this gene or other ZnTs can further indicate such associations in subjects from the same ethnicity.
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http://dx.doi.org/10.1007/s40200-020-00590-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843856PMC
December 2020

Functional miR143/145 Cluster Variants and Haplotypes Are Associated with Chronic Kidney Disease: a Preliminary Case-Control Study and Computational Analyses.

Appl Biochem Biotechnol 2021 Jan 23. Epub 2021 Jan 23.

Nephrology Department, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

MiR-143/145 cluster is a novel transcriptional target of many signaling pathways, with variations within this cluster contributed to the risk of multiple diseases. To date, no data regarding the link between miR143/145 cluster polymorphisms and the risk of developing chronic kidney disease (CKD) has been reported. Hence, we aimed to examine such association in a population of Iranian ancestry. In this preliminary study, 276 CKD patients and 300 unrelated age and sex-matched healthy controls were recruited. Genotyping was performed by PCR-RFLP and allele-specific-PCR methods. Computational analyses were performed to predict the potential effects of the variants. Our findings indicated that rs41291957, rs12659504, and rs353292 polymorphisms were positively associated with CKD, while rs4705342 and rs4705343 polymorphisms demonstrated a significant negative association with the disease. Moreover, a significant association was observed between CC + TC and TT genotypes and CKD stages. We found that AACTT, AATTC, AATTT, GATTC, GATTT, and GGCTT haplotypes significantly enhanced the risk of CKD compared with the GACTT haplotype. Computational analysis showed that rs353292, rs4705342, and rs4705343 might alter the binding of the transcription factors in this gene cluster. We found that miR-143/145 cluster polymorphisms were associated with CKD risk in a sample of the Iranian population. Replicated studies on different ethnicities are necessary to investigate the association between these promoter variants and clinical outcomes.
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http://dx.doi.org/10.1007/s12010-021-03489-wDOI Listing
January 2021

Impact of Proliferator-Activated Receptor γ Gene Polymorphisms on Risk of Schizophrenia: A Case-Control Study and Computational Analyses.

Iran J Psychiatry 2020 Oct;15(4):286-296

Department of Psychiatry, Zahedan University of Medical Sciences, Zahedan, Iran.

Schizophrenia (SCZ) is a common psychiatric disorder characterized by a complex mode of inheritance. Peroxisome proliferator-activated receptor-γ (PPARG) mainly regulates lipid and glucose metabolisms while it is constitutively expressed in rat primary microglial cultures. This preliminary study was aimed to investigate the relationship of two polymorphisms in the gene, rs1801282 C/G, and rs3856806 C/T, to the risk of SCZ in the southeast Iranian population. A total of 300 participants (150 patients with SCZ and 150 healthy controls) were enrolled. Genotyping was done using the amplification refractory mutation system polymerase chain reaction (ARMS-PCR) technique. Computational analyses were carried out to predict the potential effects of the studied polymorphisms. A significant link was found between genotypes of rs1801282 and SCZ susceptibility. The G allele of rs1801282 in CG and GG form of the codominant model increased the risk of SCZ by 2.49 and 2.64 folds, respectively. With regards to rs3856806, enhanced risk of SCZ was also observed under different inheritance models except for the overdominant model. Also, the T allele of rs3856806 enhanced the risk of SCZ by 3.19 fold. Computational analyses predicted that rs1801282 polymorphism might alter the secondary structure of -mRNA and protein function. At the same time, the other variant created the binding sites for some enhancer and silencer motifs. Our findings showed that rs1821282 and rs3856806 polymorphisms associate with SCZ susceptibility. Replication studies in different ethnicities with a larger population are needed to validate our findings.
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http://dx.doi.org/10.18502/ijps.v15i4.4294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610076PMC
October 2020

Hydro-alcoholic Extract of C. Koch Reduces the Expression of Cell Death-Associated Genes while Inducing DNA Damage in HeLa Cervical Cancer Cells.

Iran J Med Sci 2020 Sep;45(5):359-367

Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.

Background: C. Koch hydroalcoholic extract (AWHE) is proven to induce cell death. Previous studies suggested that AWHE is an effective inhibitor against the proliferation of prostate cancer cells. The present study aimed to evaluate possible alterations of cell death-associated genes and determine the growth inhibitory activity of AWHE on HeLa cervical cancer cells.

Methods: The antiproliferative activity of AWHE was tested using the tetrazolium dye-based colorimetric assay (MTT assay). The mRNA levels of Vascular endothelial growth factor (), , and Breast Cancer Susceptibility gene 1 () were measured using the real-time Polymerase Chain Reaction method. The in-cell levels of phosphorylated H2AX were determined using the in-cell ELISA method. The data were analyzed using the non-parametric ANOVA and . P<0.05 was considered statistically significant.

Results: Based on the MTT assay, The half-maximal inhibitory concentration and 81.99 µg/mL, respectively. The mRNA levels of increased after 12 and 24 hours of treatment (P<0.001), while the mRNA levels of significantly decreased after 12 hours (P=0.003) and 24 hours (P=0.001). expression was increased in the HeLa cells after 6 and 12 hours (P<0.001) whereas γ-H2AX levels significantly increased after 24 and 48 hours of treatment (P<0.001).

Conclusion: AWHE possesses growth inhibitory activity by altering the expression of cell death-associated genes. Using extracts from herbal plants may provide alternative strategies to be deployed in the fight against cancer.
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http://dx.doi.org/10.30476/ijms.2020.72657.0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519407PMC
September 2020

Relationship between gene polymorphisms and schizophrenia susceptibility: a case-control study and analyses.

Int J Neurosci 2020 Oct 8:1-10. Epub 2020 Oct 8.

Department of Psychiatry, Zahedan University of Medical Sciences, Zahedan, Iran.

Purpose: Converging evidence has recently established the significance of γ-aminobutyric acid neurotransmitter (GABA) system in the development of schizophrenia (SCZ). We aimed to determine the association of two markers of the GABA receptor β subunit gene (), rs12187676 G/C and rs1816072 T/C, with the risk of SCZ in Iranian population.

Materials And Methods: In this case-control study, 190 patients with SCZ and 200 healthy controls were recruited from December 2018 to February 2020. Genotyping was done using the Tetra-ARMS-PCR technique. analyses were performed to determine the potential effects of the variants.

Results: The C allele and genotypes of codominant CC vs.TT and CT vs.TT, dominant TT vs. TC + CC, recessive TT + TC vs. CC of rs1816072 polymorphism, as well as codominant CC vs. GG and recessive GG + GC vs. CC genetic models of rs12187676 polymorphism were significantly associated with SCZ susceptibility. Compared to the TC/GC model, we have found that the TC/CC combination significantly increased the risk of SCZ by 4.32 fold while the TT/GG combination conferred a protective role against SCZ. Haplotypes analysis indicated that polymorphisms are in weak linkage disequilibrium with each other (LD = 0.1). However, bioinformatics analyses predicted that these polymorphisms do not have significant effects on the secondary structure and the splicing of -mRNA.

Conclusions: We found that intronic polymorphisms were associated with SCZ risk in a sample of the Iranian population. These findings provided proof of concept for the involvement of the GABAergic neurotransmission system in SCZ development. These observations should be validated across other ethnicities and clinical subtypes.
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http://dx.doi.org/10.1080/00207454.2020.1830087DOI Listing
October 2020

Relationship between Single Nucleotide Polymorphisms of and Schizophrenia Susceptibility: A Preliminary Case-Control Study and Bioinformatics Analysis.

Int J Mol Cell Med 2020 10;9(2):154-164. Epub 2020 Aug 10.

Department of Psychiatry, Zahedan University of Medical Sciences, Zahedan, Iran.

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 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. analyzes were performed to determine the effects of the variants on the secondary structure of 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 -mRNA. Screening of the flanking sequences of rs545809A/T predicted silencer motifs for this SNP. Our results demonstrated that the rs545809A/T of gene could affect the risk of SCZ in Iranian populations. Replication studies are warranted to confirm these results.
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http://dx.doi.org/10.22088/IJMCM.BUMS.9.2.154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489109PMC
August 2020

Silencing of Nucleostemin by siRNA Induces Apoptosis in MCF-7 and MDA-MB-468 Cell Lines.

Iran J Pharm Res 2020 ;19(1):37-45

Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.

One of the most important modulators involved in controlling apoptosis induction and viability of cancerous cells is nucleostemin (NS). Some studies revealed that NS is also needed to maintain the proliferation of embryonic neural stem cells and early embryogenesis. This study was designed to better elucidate the association between NS depletion status and apoptosis induction of both MCF-7 and MDA-MB-468 cell lines. We examined the effects of NS-targeting siRNAs on the expression of NS in MCF-7 and MDA-MB-468 human breast cancer cell lines by the Real-time polymerase chain reaction method. In addition, we investigated the correlation between knockdown of NS and viability rates and apoptosis induction in MCF-7 and MDA-MB-468 cell lines using the MTT assay and annexin V/PI staining, respectively. The NS-targeting siRNAs inhibited the viability of the cells in a dose- and time-dependent manner and induced apoptosis after 48 h in the cells. Thus, consistent with previous articles, this protein can be one of the regulators related to the inhibition of apoptosis and the increased viability of tumor-initiating cells in human breast cancer cell lines as well as other cancers.
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http://dx.doi.org/10.22037/ijpr.2020.1100950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462512PMC
January 2020

Quantitative Assessment of the Effects of IL-1ß -511 C>T Variant on Breast Cancer Risk: An Updated Meta-Analysis of 3331 Cases and 3609 Controls.

Lab Med 2021 Jan;52(1):36-46

Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.

Objective: Growing evidence suggests that IL-1β -511C>T, as a functional variant, affects the risk of developing breast cancer (BC); however, the results have not been conclusive. This meta-analysis was conducted to estimate the link between this variant and BC risk.

Methods: We retrieved available publications on IL-1β -511C>T polymorphism by conducting a comprehensive literature search on the Web of Science, MEDLINE, PubMed, Scopus, and Google scholar databases (last search on February 25, 2020).

Results: The overall analysis indicates that IL-1β -511C>T polymorphism conferred an increased risk of BC under a recessive TT vs CT+CC model by 1.14-fold and showed protection against BC under an overdominant CT vs TT+CC genetic contrast model (odds ratio = 0.84). Stratified analysis based on ethnicity revealed the protective effect of this single-nucleotide polymorphism against BC risk in Caucasian patients.

Conclusion: Our data results provide a proof of concept for the association of IL-1β -511C>T with BC risk. Larger, well-designed population-based studies are needed to confirm these findings.
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http://dx.doi.org/10.1093/labmed/lmaa055DOI Listing
January 2021

Polymorphism in the 3'-UTR of LIF but Not in the ATF6B Gene Associates with Schizophrenia Susceptibility: a Case-Control Study and In Silico Analyses.

J Mol Neurosci 2020 Dec 5;70(12):2093-2101. Epub 2020 Jun 5.

Department of Psychiatry, Zahedan University of Medical Sciences, Zahedan, Iran.

Schizophrenia (SCZ) is a multifactorial disorder caused by environmental and genetic factors. Studies have shown that various single-nucleotide polymorphisms (SNPs) in the binding sites of microRNAs contribute to the risk of developing SCZ. We aimed to investigate whether the variants located in the 3'-UTR region of LIF (rs929271T>G) and ATF6B (rs8283G>A) were associated with increased susceptibility to SCZ in a population from the south-east of Iran. In this case-control study, a total of 396 subjects were recruited. SNPs were genotyped via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotyping results showed that the G allele of rs929271 significantly increased the risk of SCZ (OR = 1.58 95%CI = 1.19-2.10, p = 0.001). As for rs929271, the GG genotype of co-dominant (OR = 2.54 95%CI = 1.39-4.64, p = 0.002) and recessive (OR = 2.91 95%CI = 1.77-4.80, p < 0.001) models were strongly linked to SCZ. No significant differences were observed between rs8283 polymorphism and predisposition to SCZ. In silico analyses predicted that rs929271 might alter the binding sites of microRNAs, which was believed to have an unclear role in the development of SCZ. Moreover, rs929271 polymorphism changed the LIF-mRNA folding structure. These findings provide fine pieces of evidence regarding the possible effects of LIF polymorphism in the development of SCZ and regulation of the LIF gene targeted by microRNAs.
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http://dx.doi.org/10.1007/s12031-020-01616-6DOI Listing
December 2020

Hydroalcoholic Extract Induces Apoptosis and Alters and Gene Expression in Hela Cervical Cancer Cells.

Rep Biochem Mol Biol 2019 Oct;8(3):318-325

Department of Chemistry, Iran University of Science and Technology; Tehran, Iran.

Background: Inappropriate activation of the proto-oncogene LIN28B and inactivation of the p53 tumor suppressor, have been shown to have a critical role in tumorigenesis. Previous research has shown therapeutic potential for the use of herbal plants as an alternative strategy for cancer treatment. C. Koch is a plant that has been traditionally used for its medicinal properties. The aim of this study was to investigate the cytotoxic and apoptosis-inducing effect of hydroalcoholic extract () on HeLa cervical cancer cells and its effect on and expression.

Methods: The cytotoxic activity of was evaluated on HeLa cells using a trypan blue exclusion assay. The Annexin V/PI double staining assay was used to evaluate the apoptosis-inducing effect of the extract. The expression of and mRNA was measured using the real-time-PCR method.

Results: Treatment with was shown to induce cytotoxicity in both time and concentration-dependent manners (P<0.05). The proposition of HeLa cells undergoing apoptosis increased with increasing concentrations of (P<0.05). The mRNA levels of p53 increased following 12, 24, and 48 hours of AWHE treatment whereas the mRNA levels of were significantly decreased after 4 to 12 hours of treatment (p<0.05).

Conclusion: Our findings confirmed the pro-apoptotic function of on the cervical cancer HeLa cell line. This indicates that targeting the LIN28B signaling cascade may be a promising therapeutic strategy for cervical cancer. Further research is required to understand the therapeutic effects of in primary human cervical cancer cells and a pre-clinical cervical cancer model.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103081PMC
October 2019

Silymarin inhibits Toll-like receptor 8 gene expression and apoptosis in Ramos cancer cell line.

Avicenna J Phytomed 2020 Mar-Apr;10(2):161-169

Department of Laboratory Sciences, Borujerd Branch, Islamic Azad University, Borujerd, Iran.

Objective: Silymarin is a herbal extract containing flavonolignans, and it has inhibitory effects against the growth of different cancer cell lines by inducing apoptosis. Toll-like receptors are suggested as a novel and attractive target to treat cancer. The current study aimed at examining the mechanism of silymarin-induced apoptosis in Ramos cells and investigating its effects on expression.

Materials And Methods: The half maximal inhibitory concentration (IC) of silymarin in Ramos cells was determined via MTT viability test while the type of cell death was tested by annexin V/propidium iodide (PI) double staining method. The activity of caspase-3 and expression of were measured in a time-dependent manner (in IC) by colorimetric assay and real-time polymerase chain reaction (RT-PCR), respectively.

Results: The results of MTT showed that IC of silymarin in Ramos cells was 100 μg/ml after 48 hr treatment (p<0.01). Flow cytometry by annexin V/PI, showed that silymarin induced early/late apoptosis in this cell line (p<0.05 to p<0.01). In addition, the caspase-3 colorimetric method showed that caspase-3 increased in the Ramos cell line after treatment (p<0.01). This treatment led to a reduction in mRNA expression in a time-dependent manner (p<0.01).

Conclusion: The results indicated a new mechanism in the anticancer activity of Toll-like receptor (TLR) signaling after silymarin treatment in Ramos cancer cell line. This plant could be used to develop anticancer agents inhibiting TLRs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103436PMC
April 2020

Association of Two Methylenetetrahydrofolate Reductase Polymorphisms (rs1801133, rs1801131) with the Risk of Type 2 Diabetes in South-East of Iran.

Rep Biochem Mol Biol 2019 Jul;8(2):178-183

Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

Background: DNA methylation has been linked to the development and progression of multiple disorders including T2D. One significant enzyme involved in DNA methylation is methylene tetrahydrofolate reductase (). This study was designed to evaluate the association between rs1801133 and rs1801131 polymorphisms, located in the , and T2D in an Iranian population.

Methods: Blood samples from 151 patients with T2D and 136 healthy individuals were collected and DNA was extracted using the salting out method. Variants were genotyped using amplification tetrarefractory mutation system-polymerase chain reaction analysis. The data were analyzed via independent sample t-test and x tests.

Results: The rs1801131 A/C polymorphism significantly increased the risk of T2D in codominant heterozygous AC (P=0.008), homozygous CC (P=0.01), and recessive CC (P=0.001) genotypes. Significant correlations were found regarding rs1801133 T/C gene polymorphism and the risk of T2D in codominant heterozygous TC (P=0.001), homozygote CC (P=0.001), and recessive CC (P=0.0001) models. The presence of the C allele is a potential risk factor for T2D for rs1801133 T/C (P=0.001) and rs1801131 A/C (P=0.04) polymorphisms.

Conclusion: Both the rs1801133 T/C and rs1801131 A/C polymorphisms significantly increased the risk of T2D in our population. Further studies in other ethnicities are necessary to verify our findings.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844617PMC
July 2019

Extract Triggers Apoptosis and Down-Regulates Gene Expression in Breast Cancer Cell Lines.

Rep Biochem Mol Biol 2019 Jul;8(2):119-125

Cellular and Molecular Research Center, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

Background: Studies have shown that zinc finger protein 703 (ZNF703) is overexpressed in breast cancer. Levisticum (L.) is a herbal plant with proven medical characteristics in traditional medicine. The purpose of the present study was to evaluate the effect of hydroalcoholic extract of (HELO) on both estrogen receptor-positive (ER) and -negative (ER) cell lines (MCF-7 and MDA-MB-468, respectively).

Methods: The anti-proliferative and apoptotic activities of HELO were investigated on both cell lines using MTT and flow-cytometry methods. Real-time PCR was employed to determinate the changes in mRNA expression of the gene.

Results: The 50% maximal inhibitory concentrations (IC) of HELO on ER and ER- cells were 200 and 150 µg/mL after 48 h-treatment. Statistically significant increases in both early and late apoptosis rates were seen in exposed cell lines. expression was less from 4 to 24 h HELO treatment than in untreated cells, and expression was higher in the more invasive MDA-MB-468 cells than in the less invasive MCF-7 cells. Our results demonstrated that HELO induces apoptosis and decreases cell growth in both cell lines.

Conclusion: Our data suggest that HELO alters the mRNA levels of gene while inducing apoptotic cell death in breast cancer-derived cell lines. The use of suppression can be considered as a beneficial target in breast cancer research.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844619PMC
July 2019

Induction of apoptosis and modulation of homologous recombination DNA repair pathway in prostate cancer cells by the combination of AZD2461 and valproic acid.

EXCLI J 2019 8;18:485-498. Epub 2019 Jul 8.

Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Cancer therapies using defects in homologous recombination (HR) DNA repair pathway of tumor cells are not yet approved to be applicable in patients with malignancies other than BRCA1/2-mutated tumors. This study was designed to determine the efficacy of combination therapy of a histone deacetylase inhibitor, valproic acid (VPA) and a novel PARP inhibitor AZD2461 in both PC-3 (PTEN-mutated) and DU145 (PTEN-unmutated) prostate cancer cell lines. The Trypan blue dye exclusion assay and the tetrazolium-based colorimetric (MTT) assay were performed to measure the cytotoxicity while combination effects were assessed based on Chou-Talalay's principles. Flow-cytometric assay determined the type of cell death. The real-time PCR analysis was used to evaluate the alterations in mRNA levels of HR-related genes while their protein levels were measured using the ELISA method. γ-H2AX levels were determined as a marker of DNA damage. We observed a synergistic relationship between VPA and AZD2461 in all affected fractions of PC-3 cells (CI<0.9), but not in DU145 cells (CI>1.1). Annexin-V staining analysis revealed a significant induction of apoptosis when PC-3 cells were treated with VPA+AZD2461 (). Both mRNA and protein levels of and were significantly decreased in PC-3 cells co-treated with VPA+AZD2461 while enhanced H2AX phosphorylation was found in PC-3 cells after 12 and 24 hours of co-treatment (). Our findings established a preclinical rationale for selective targeting of HR repair pathways by a combination of VPA and AZD2461 as a mechanism for reducing the HR pathway sufficiency in -mutated prostate cancer cells.
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http://dx.doi.org/10.17179/excli2019-1098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694702PMC
July 2019

Mild antagonistic effect of Valproic acid in combination with AZD2461 in MCF-7 breast cancer cells.

Med J Islam Repub Iran 2019 10;33:29. Epub 2019 Apr 10.

Student Research committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Breast cancer (BC) is a complex disease, but current treatments are not efficient enough considering increased relapse and decreased survival rate among patients. Poly (ADP-ribose) polymerase inhibitors are recently developed anticancer agents which target cells with defects in homologous recombination (HR) pathway. This study wishes to assess whether the combination of AZD2461 as a newly developed PARP1 inhibitor and valproic acid (VPA), a histone deacetylase inhibitor could effectively reduce the growth of MCF-7 cells with no fundamental DNA repair defect. Both trypan blue dye exclusion assay and MTT viability test were used to evaluate cell death. γ-H2AX levels, as a marker of DNA repair, were measured using in cell ELISA method. The Student's t-test and non-parametric analysis of variance (ANOVA) were applied for our data analyses where p-value <0.05 was considered statistically significant. As calculated by CompuSyn software, IC50 values for VPA and AZD2461 were 4.89 mM and 42.83 µM respectively following 48 hours treatment. Also, the trypan blue exclusion assay results showed a concentration- and time-dependent decrease when MCF-7 cells were treated with both agents (p<0.05). Combination analysis showed a mild antagonism (CI>1.1) while γ-H2AX levels found not to be significantly increased in MCF-7 cells co-treated with VPA+AZD2461 compared to each agent alone (p=0.29). Our findings revealed that the combination of VPA and AZD2461 could decrease cell viability of MCF-7 cells, but it was not able to significantly increase unrepaired DNA damage sites. The mechanism responsible for drugs combination was not of synergism or addition. Determining the type of involved cell death mechanisms might be followed in further studies.
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http://dx.doi.org/10.34171/mjiri.33.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662678PMC
April 2019

HHEX gene polymorphisms and type 2 diabetes mellitus: A case-control report from Iran.

J Cell Biochem 2019 10 25;120(10):16445-16451. Epub 2019 Jun 25.

Department of Laboratory Sciences, School of Allied Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

Genome-wide association studies indicated that hematopoietically-expressed homeobox (HHEX) gene is a remarkable candidate for type 2 diabetes (T2D) mellitus susceptibility in spite of the fact that the results are ambiguous in some cases. So, this study aimed to evaluate the possible correlation between HHEX gene polymorphisms and T2D development in a sample of the Iranian population. The rs1111875G/A, rs7923837A/G, and rs5015480C/T HHEX gene polymorphisms were genotyped in 250 cases and 250 matched (age and sex) healthy controls using tetra-amplification-refractory mutation system-polymerase chain reaction method. The finding revealed the all measured inheritance models of rs1111875G/A and of rs5015480C/T variants dramatically increase the risk of T2D while another polymorphism (rs7923837A/G) was not associated with risk/protective role in T2D. The results indicated that rs1111875G/A and rs5015480C/T may contribute to the enhancement of T2D risk in a sample of the southeast Iranian population.
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http://dx.doi.org/10.1002/jcb.28788DOI Listing
October 2019

Novel Poly(Adenosine Diphosphate-Ribose) Polymerase (PARP) Inhibitor, AZD2461, Down-Regulates VEGF and Induces Apoptosis in Prostate Cancer Cells

Iran Biomed J 2019 09 18;23(5):312-23. Epub 2019 May 18.

International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Background: Prostate cancer (Pca) is a heterogeneous disease, and current treatments are not based on molecular stratification. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors have recently been found to be remarkably toxic to cells with defects in homologous recombination, particularly cells with BRCA-mutated backgrounds. Therefore, this preliminary study was designed to evaluate whether PTEN expression status could have an impact on the sensitivity of invasive Pca cells to the PARP inhibitor, AZD2461.

Methods: MTT viability test, Annexin V‐FITC/propidium iodide double staining, and caspase3 activity assay were used to evaluate the apoptosis and relative expression of PTEN and VEGF in PC-3 and DU145 cell lines using real-time PCR.

Results: MTT results showed that the inhibitory effects of AZD2461 were higher in PC-3 than DU145 cells (with IC50 of 36.48 and 59.03 µM at 48 hours of treatment, respectively). Flow cytometric analysis also showed the same results. When exposed to 40 µM of AZD2461, PC-3 (38.8%) and DU145 (28%) cells underwent apoptosis (p < 0.05). Treatment of cells by AZD2461 also caused a significant increase in apoptosis through caspase3 activation in both cell lines. VEGF mRNA levels in PC-3 cells significantly decreased compared to adjusted untreated cells (p < 0.05) in all measured times while displaying different alteration patterns in DU145 cells (p < 0.05).

Conclusion: AZD2461 suppresses the growth of prostate tumor cells since AZD2461 monotherapy could prove to be efficacious, especially against cells not expressing PTEN besides activating the possible apoptosis-independent cell death pathways.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661129PMC
September 2019

Association of KIF26B and COL4A4 gene polymorphisms with the risk of keratoconus in a sample of Iranian population.

Int Ophthalmol 2019 Nov 10;39(11):2621-2628. Epub 2019 May 10.

Infectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.

Purpose: Keratoconus (KTCN) is a congenital corneal eye disorder which correlates with abnormal distribution of the collagen fiber and causes loss of visual acuity. COLA4A gene has a substantive role in collagen synthesis, whereas KIF26B as a new candidate gene belonging to kinesin superfamily (KIFs) has been suggested to be associated with this disease. So, in this preliminary study, we simultaneously evaluated the effects of two single nucleotide polymorphisms, 222855rs7C/T and rs12407427C/T, on KTCN susceptibility in a sample of Iranian population.

Methods: The present case-control study consists of 144 patients confirmed with KTCN and 153 healthy controls. The variants are genotyped by using amplification refractory mutation system-polymerase chain reaction method.

Results: The findings disclosed that rs2228557C/T and rs12407427C/T polymorphisms significantly increased the risk of KTCN in measured (codominant1; p = 0.0001, codominant2; p = 0.0001, codominant3; p = 0.0006, dominant; p = 0.0001, over-dominant; p = 0.0005) and (codominant1; p = 0.0001, codominant3; p = 0.0005, recessive; p = 0.0001) inheritance patterns, respectively.

Conclusion: Our results did prove a statistical association of both rs2228557 and rs12407427 genotypes (TT and CT + CC) and allele (T) with KTCN susceptibility in Iranian population. Further studies in other ethnicities are required to verify our results.
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http://dx.doi.org/10.1007/s10792-019-01111-xDOI Listing
November 2019

Nitric Oxide Synthase 2 Polymorphisms (rs2779248T/C and rs1137933C/T) and the Risk of Type 2 Diabetes in Zahedan, Southeastern Iran.

Iran J Public Health 2018 Nov;47(11):1734-1741

Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

Background: Nitric oxide (NO) has been associated with insulin resistance and type 2 diabetes (T2D). NO is synthesized enzymatically from l-arginine (l-Arg) by three NO synthase (NOS) isoforms, Neuronal NOS (nNOS or NOS1), Inducible NOS (iNOS or NOS2), and Endothelial NOS (eNOS or NOS3). The impact of NOS2 gene polymorphism was investigated on the susceptibility of T2D in a sample of Iranian population (Southeastern of Iran).

Methods: In 2015, the present case-control study was conducted on 152 T2D patients and 157 healthy control subjects (HCs) referring to Bu-ali Hospital of Zahedan, eastern Iran. Genotyping of NOS2 rs2779248T/C and rs1137933C/T variants were done using the Tetra-Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-ARMS PCR) method.

Results: CT genotype of rs1137933C/T was significantly associated with increased risk of T2D (<0.0001). The T allele of this single nucleotide polymorphism (SNP) was also strongly associated with T2D risk (<0.0001). For rs2779248 T/C, TC genotype of this SNP decreased the risk of T2D (OR=0.25 95%CI= 0.15-0.42, <0.0001); however, CC genotype of this SNP increased the risk of T2D (<0.005). There was no significant association between clinical-demographic characteristics of T2D group with respect to both SNPS in dominant.

Conclusion: CT genotype and C allele of NOS2 rs1137933 C/T polymorphism were associated with a higher risk of T2D, and no association was observed between T allele of NOS2 rs2779248 T/C polymorphism and T2D while TC genotype of this SNP decreased the risk of T2D in the study participants.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294872PMC
November 2018

Genetic Polymorphisms of Catalase and Glutathione Peroxidase-1 in Keratoconus.

Iran J Public Health 2018 Oct;47(10):1567-1574

Dept. of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

Background: Keratoconus (KC) is a degenerative eye disease which results from thinning of the cornea and causes vision distortion. Oxidative stress damage to KC corneas may be because of the failure of corneas to process reactive oxygen species which leads to corneal thinning and loss of vision. Genetic variants in antioxidant defense genes such as catalase (CAT) and glutathione peroxidase (GPX) can decrease antioxidant capacity or increase oxidative stress and alter the risk of KC in patients. We investigated and evaluated the effects of single nucleotide polymorphisms in CAT, GPX-1 on the risk of KC in an Iranian population sample.

Methods: This case-control study was performed on 140 patients with KC and 150 healthy control subjects in a sample of Iranian population from Zahedan, southern Iran in 2015. Genotyping of CAT rs7943316 and GPX-1 rs1050450 polymorphisms was done using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method.

Results: CAT rs7943316 A/T, AA genotype and A allele have a protective role against disease (OR =0.28, 95% CI =0.13-0.61, =0.001 and OR = 0.50, 95% CI =0.35-0.72, =0.0001, respectively) and decreased the risk of KC. Moreover, GPX-1 rs1050450 T allele increased the risk of KC in comparison with C allele (OR = 1.42, 95% CI = 1.01-2.03, =0.03).

Conclusion: CAT rs7943316 A/T, AA genotype, and A allele decreased the risk of KC. Moreover, in GPX-1 rs1050450 C/T polymorphism, T allele was associated with an increased risk of KC in our population.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277734PMC
October 2018

Hydroalcoholic Extract of Levisticum officinale Increases cGMP Signaling Pathway by Down-Regulating PDE5 Expression and Induction of Apoptosis in MCF-7 and MDA-MB-468 Breast Cancer Cell Lines

Iran Biomed J 2019 07 3;23(4):280-6. Epub 2018 Nov 3.

Department of Biology, Faculty of Science, University of Sistan and Baluchestan, Zahedan, Iran.

Background: This study aimed to investigate Levisticum officinale hydroalcoholic extract (LOHE) effect on both cGMP signaling pathway and phosphodiesterase 5 (PDE5) gene expression pattern and to examine the role of LOHE in apoptosis induction of MCF-7 and MDA-MB-468 cell lines.

Methods: The half maximal inhibitory concentration (IC50) of LOHE was examined in both cell lines using the MTT assay. Using IC50 values of LOHE on both cells, the type of cell death was detected by flowcytometric analysis. The values of PDE5 and cGMP were evaluated by real-time PCR and ELISA methods, respectively.

Results: The IC50 values were measured as 150 μg/ml for MDA-MB-468 and 200 μg/ml for MCF-7. At 12 hour of treatment, a significant decrease in the PDE5 expression and maximum increase in the amount of intracellular cGMP were observed (p < 0.05). However, these effects were more noticeable in MDA-MB-468 triple-negative cells.

Conclusion: Our data suggest that LOHE extract could be a potential source for new strategies towards targeting both PDE5 and cGMP signaling pathways.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462291PMC
July 2019

Association study of SREBF-2 gene polymorphisms and the risk of type 2 diabetes in a sample of Iranian population.

Gene 2018 Jun 27;660:145-150. Epub 2018 Mar 27.

Department of Hematology, Faculty of Applied Medicine, Iran University of Medical Sciences, Tehran, Iran.

Type 2 diabetes mellitus (T2D) as an important metabolic disorder is accompanied by dysregulation in lipid metabolism. Sterol regulatory element-binding factor-2 (SREBF-2) gene has a substantive role in lipid metabolism. Recently published report indicated the overexpression of this gene in diabetic patients. So, in this preliminary study we evaluated the effects of three common single nucleotide polymorphisms (SNPs), rs1052717G/A, rs2267439C/T, and rs2267443G/A in risk of T2D in a sample of Iranian population. Present case-control study consists of 250 patients with endocrinologically approved T2D and 250 healthy controls. The variants genotyped by using tetra amplification refractory mutation system polymerase chain reaction (Tetra ARMS-PCR) method. The findings demonstrated that the rs2267439C/T polymorphism increased the risk of T2D in all measured inheritance models (Codominant1; p = 0.003, codominant2; p = 0.014, dominant; p < 0.0001, recessive; p = 0.037, over-dominant; p = 0.0025, and log-additive; p = 0.0048) while our results did not show statistically association between rs1052717G/A and rs2267443G/A SNPs and T2D development. The current investigation indicated that the rs2267439C/T polymorphism in the SREBF-2 gene increased the T2D susceptibility in an Iranian population. Further studies with different ethnicities and more extensive sample sizes are demanded to confirm our finding.
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http://dx.doi.org/10.1016/j.gene.2018.03.080DOI Listing
June 2018

Catechol-O-Methyltransferase (COMT) Gene (Val158Met) and Brain-Derived Neurotropic Factor (BDNF) (Val66Met) Genes Polymorphism in Schizophrenia: A Case-Control Study.

Iran J Psychiatry 2017 Oct;12(4):265-270

Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

Several studies have shown that some polymorphisms of genes encoding catechol-O-methyltransferase (COMT), the key enzyme in degrading dopamine, and norepinephrine and the human brain-derived neurotropic factor (BDNF), a nerve growth factor, are strong candidates for risk of schizophrenia (SCZ). In the present study, we aimed at examining the effects of COMT Val158Met (G>A) and BDNF Val66Met (G>A) polymorphisms on SCZ risk in a sample of Iranian population. This case- control study included 92 SCZ patients and 92 healthy controls (HCs). Genotyping of both variants (COMT Val158Met (G>A) and BDNF Val66Met (G>A)) were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). The findings revealed that the COMT Val158Met (G>A) polymorphism was not associated with the risk/protective of SCZ in all models (OR=0.630, 95%CI=0.299-1.326, P=0.224, GA vs. GG, OR=1.416, 95%CI=0.719-2.793, P=0.314, AA vs. GG, OR=1.00, 95%CI=0.56-1.79, P=1.00 GA+AA vs. GG, OR=1.667, 95%CI=0.885-3.125, P=0.11, AA vs. GG+GA, OR=1.247, 95%CI=0.825-1.885, P=0.343, A vs. G,). However, BDNF Val66Met (G>A) variant increased the risk of SCZ (OR = 2.008 95%CI = 1.008-4.00, P = 0.047, GA vs. GG, OR = 3.876 95%CI = 1.001-14.925, P = 0.049. AA vs. GG, OR = 2.272. 95%CI = 1.204-4.347, P = 0.011, GA+AA vs. GG, OR = 2.22 95%CI = 1.29-3.82. P = 0.005, A vs. G). The results did not support an association between COMT Val158Met (G>A) variant and risk/protective of SCZ. Moreover, it was found that BDNF Val66Met (G>A) polymorphism may increase the risk of SCZ development. Further studies and different ethnicities are recommended to confirm the findings.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816916PMC
October 2017

Common Variations in Perilipin rs1052700 and FTO rs3751812 Gene Variants, and Risk for Obesity and Type-2 Diabetes.

Rep Biochem Mol Biol 2017 Oct;6(1):80-87

Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

Background: Perilipins are proteins that coat lipid globules in adipocytes, which are steroid-generating cells that play a central role in lipid storage and breakdown. The FTO gene is associated with type-2 diabetes (T2D) and increased fat mass. In this work the association of and FTO gene polymorphisms in T2D was investigated.

Methods: One hundred eighty-three Iranian men and women with T2D, and 174 healthy controls with no known metabolic diseases, participated in the study. The subjects were genotyped using tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS-PCR) and their clinical traits were analyzed.

Results: A significant association was found between the rs1052700 polymorphism and T2D, and between the FTO rs3751812 polymorphism and obesity (P = 0.03 and 0.003, respectively); however, no significant relationship was found between rs3751812 and T2D.

Conclusion: The FTO rs3751812 polymorphism is a major genetic determinant of obesity, but not T2D. The rs1052700 polymorphism is related to T2D but not obesity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643444PMC
October 2017

Effect of extract on expression of the human telomerase reverse transcriptase mRNA in the PC3 prostate cancer cell line.

Biomed Rep 2017 Sep 31;7(3):251-256. Epub 2017 Jul 31.

Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan 9816743175, Iran.

Evidence has indicated that human telomerase reverse transcriptase (hTERT) was overexpressed in prostate cancer (PCa). (AW) is a plant that has been traditionally used for its medicinal properties. The aim of current study was to evaluate the effects of AW extract on a PCa cell line. The cytotoxic activity of the hydroalcoholic extract of AW was studied on the PCa PC3 cell line using MTT assay. Flow cytometry was used to evaluate the effects of the extract on the apoptosis. The expression of hTERT mRNA was analyzed by the reverse transcription-quantitative polymerase chain reaction method. The ELISA method was used to measure the levels of telomerase enzyme. The hydroalcoholic AW extract demonstrated the appropriate inhibitory effect in 150 µg/ml concentration (IC) on PC3 cell line following 48 h treatment. Treatment of the PC3 cells with AW resulted in a significant increase in early and late apoptotic cells and a decrease in live cells (P<0.001), in a dose-dependent manner. Moreover, the early apoptotic cells were significantly higher than late apoptotic cells. The hTERT mRNA expression was decreased following 24 h treatment of AW extract, although it was not different between 2, 4, 8 and 12 h treatments or 24, 48 and 72 h treatments. In addition, the hTERT concentration was significantly decreased following 24 h treatment of AW extract with the marginal P-value. There was no significant difference regarding hTERT concentration between 2, 4, 8 and 12 h treatments or 24, 48 and 72 h treatments. The hydroalcoholic extract of AW induced potent antiproliferative and apoptotic effects in PC3 cell line, which could be explainable by its high potency to inhibit expression of the prominent oncogene hTERT in PCa. Therefore, targeting telomerase represents a promising strategy for PCa therapy, and AW may have considerable potential for development as a novel natural anticancer agent.
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http://dx.doi.org/10.3892/br.2017.956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547767PMC
September 2017

The association of the placental MTHFR 3'-UTR polymorphisms, promoter methylation, and MTHFR expression with preeclampsia.

J Cell Biochem 2018 02 27;119(2):1346-1354. Epub 2017 Oct 27.

Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

Preeclampsia (PE) is a pregnancy specific complication arises in presence of the placenta and disappears immediately after delivery. Therefore, the aim of the present study was to investigate the possible effects of the placental 3'-UTR rs1537514C>G and rs4846049C>A polymorphisms and DNA methylation of the MTHFR gene on the MTHFR mRNA expression. The placenta of 74 PE pregnant women and 75 normotensive pregnant women were collected after delivery. The methylation status of the MTHFR promoter was assessed with Methylation Specific PCR (MSP). The rs1537514C>G and rs4846049C>A polymorphisms were genotyped using PCR-RFLP method. The mRNA expression levels were measured by Quantitative Real Time PCR. The results showed the lower MTHFR mRNA expression in the placenta of PE women. There was an association between hypermethylation and lower MTHFR mRNA expression in PE women and entire women but not normotensive pregnant women. The frequency of MTHFR rs1537514CG genotype was significantly lower in PE women; however, there was no association between MTHFR rs4846049C>A polymorphism and PE. The combination effects of MTHFR CG/AC genotypes and G-A haplotype of MTHFR rs1537514/rs4846049 polymorphisms were associated with lower risk of PE. The MTHFR rs1537514G (4869G) allele was associated with higher MTHFR mRNA expression in both groups. However, there was no relation between MTHFR rs4846049C>A polymorphism and MTHFR mRNA expression. Our findings showed lower MTHFR mRNA expression in PE women. The MTHFR rs1537514C>G polymorphism was associated with lower PE risk and MTHFR mRNA expression. Lower expression of MTHFR mRNA was observed in the women with the hypermethylated promoter.
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http://dx.doi.org/10.1002/jcb.26290DOI Listing
February 2018

Association of gene polymorphism with the risk of type 2 diabetes.

Biomed Rep 2017 Jul 22;7(1):85-89. Epub 2017 May 22.

Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan 98167-43463, Iran.

Type-2 diabetes (T2D) is a multifactorial (environmental and genetic factors) and global epidemic disease with an estimated high prevalence worldwide. Studies have indicated that nitric oxide synthase 3 (NOS3) has several important roles in the pathogenesis of T2D. The present study aims to investigate the association between rs1800779(A/G) and T2D in an Iranian sample population. A case-control study was conducted on 250 T2D patients and 250 healthy control subjects (HCs). Genotyping of the rs1800779(A/G) variant was conducted using a Tetra-Amplification Refractory Mutation System polymerase chain reaction. The frequencies of genotypes AA, AG and GG polymorphisms were 56.8, 39.2 and 4% in the T2D group, and 42.8, 56 and 1.2% in the HCs group, respectively. The frequency of the minor (G) allele was 23.6% in the T2D group and 29.2% in the HCs group. The genotype frequencies of the rs1800779(A/G) variant demonstrated statistically significant differences between T2D and controls in a codominant model (AG vs. AA, OR=0.527, 95% CI=0.368-0.756, P<0.001) and dominant model (AG+GG vs. AA, OR=0.569, 95% CI=0.399-0.811, P=0.002). There was no significant association between clinical and demographic characteristics and the rs1800779(A/G) polymorphism in dominant status (P>0.05). The dominant model and AG genotype of rs1800779(A/G) polymorphism may had a protective effect on T2D of Iranian population.
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http://dx.doi.org/10.3892/br.2017.916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492527PMC
July 2017

Inhibition of Phosphodiesterase 5 and Increasing the Level of Cyclic Guanosine 3',5' Monophosphate by Hydroalcoholic C. Koch Extract in Human Breast Cancer Cell Lines MCF-7 and MDA-Mb-468.

Breast Cancer (Auckl) 2017 23;11:1178223417690178. Epub 2017 Feb 23.

Department of Biology, Faculty of Science, University of Sistan and Baluchestan, Zahedan, Iran.

This study aimed to investigate the effect of hydroalcoholic C. Koch extract (HAWE) on phosphodiesterase 5 (PDE5) gene expression and cyclic guanosine 3',5' monophosphate (cGMP) signaling in the MCF-7 and MDA-Mb-468 cell lines. The effective dose (ED50) of HAWE was examined in both cell lines using a 3-(4,5-dimethylhiazol-2-yl)-2,5-diphenyltetrazolium bromide viability test, and the type of cell death was detected by flow cytometry. The expression of PDE5 and the concentration of cGMP were measured in a time-dependent manner in the ED50 by real-time polymerase chain reaction and a colorimetric assay, respectively. Treatment with HAWE showed 25 µg/mL to be the ED50 for both cell lines, and HAWE led to a reduction in the PDE5 messenger RNA expression. The intracellular cGMP increased in a time-dependent manner. The results showed that HAWE has an antiproliferative property in MCF-7 and MDA-Mb-468 cell lines through the cGMP pathway. Therefore, HAWE is a potential source to effectively isolate inhibitory PDE5.
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http://dx.doi.org/10.1177/1178223417690178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391053PMC
February 2017