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Fatemeh Pourrajab,1,2 Mohamad Reza Zare-Khormizi,3 Mohammad Hasan Sheikhha4 1Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 2Department of Biochemistry and Molecular Biology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 3School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 4Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, IranCorrespondence: Fatemeh PourrajabNutrition and Food Security Research Centre, Shahid Sadoughi University of Medical Sciences, Yazd, IranEmail mina_poorrajab@yahoo.comMohammad Hasan SheikhhaBiotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, IranTel +983538247085Fax +983538247087Email sheikhha@yahoo.comAbstract: Over the past years, several zoonotic viruses have crossed the species barrier into humans and have been causing outbreaks of severe, and often fatal, respiratory illness. The 21st century has seen the worldwide spread of three recognized coronaviruses (CoVs) which can cause pneumonia and severe acute respiratory symptoms (SARSs), SARS, MERS, and recently SARS-CoV-2. Herein, it is raising concerns about the dissemination of another new and highly lethal pandemic outbreak. Preparing for a pandemic outbreak involves a great deal of awareness necessary to stop initial outbreaks, through recognizing the molecular mechanisms underlying virus transmission and pathogenicity. CoV spike protein S is the key determinant of host tropism and viral pathogenicity which can undergo variations and makes the CoV a highly pathogenic and diffusible virus capable of sustained human-to-human transmission and spread easily. The three mentioned CoVs exhibit some similarities in S protein whereby constitute a promising target for the development of prophylactics and therapeutics in the future.Keywords: coronavirus, transmission, receptor binding, spike protein

Background: Women with diminished ovarian reserve (DOR) respond differently to gonadotropin medications., Objective: This study investigates the relationship between effective gene expression in the steroidogenesis pathway and gonadotropin responsiveness in DOR., Materials and Methods: In this case-control study , cumulus cells were obtained from women with DOR after gonadotropin administration (n = 20) and normal ovarian reserve (n = 20). They were divided into the following groups, oocyte number < 3 and oocyte number > 3. After RNA extraction and cDNA synthesis, quantitative polymerase chain reaction was performed to assess the expression levels of cytochrome P450 aromatase ( CYP19A1 ), protein kinase A( PKA ) , and glycogen synthase kinase 3 beta ( GSK3B )genes., Results: The women with DOR had statistically significant lower expression of CYP19A1 and PKA genes in their cumulus cells compared to control group (p = 0.04, and p < 0.001, respectively). There was also lower expression of the GSK3B gene in DOR compared to control group, but it was not significant. Although the expression of the CYP19A1 , PKA , and GSK3B genes was lower in women with < 3 oocytes compared to women with more oocytes, this difference was not statistically significant., Conclusion: In conclusion, DOR may be associated with lower expression of CYP19A1 and PKA genes. Also, considering the decrease in the expression of these genes in people with DOR, the expression of these genes can be used as a tool to predict the treatment., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2024 Ahmadnia et al.)

Background: olycystic ovary syndrome (PCOS) is an endocrine disorder that can lead to major reproductive and metabolic complications. Management of glycemic parameters is an important step to improve the symptoms of PCOS., Objective: This study aims to evaluate the effects of the dietary approaches to stop hypertension (DASH) diet and curcumin (Cur) co-administration on glycemic parameters in normal weight and overweight/obese women with PCOS undergoing in vitro fertilization., Materials and Methods: In this double-blind randomized clinical study, 104 infertile women with PCOS were divided into 4 intervention groups considering treatment conditions and body mass index. They received 500 mg twice daily of Cur or placebo (Pls) along with DASH or a standard diet (St) based on macronutrient composition (52% carbohydrate, 18% protein, and 30% fat) for 12 wk, (DASH + Cur, DASH + Pls, St + Cur, St + Pls). The effect of these interventions on fasting blood sugar and insulin levels, insulin resistance (IR), and insulin sensitivity were determined., Results: Participants adhered to the intervention protocol ( > 80%). Insulin levels in the supplement intervention (Cur + diet) decreased significantly in the crude model. They remained significant even after adjusting for confounding variables in adjusted models (body mass index classification, energy difference, age, and physical activity levels at the baseline) ( β = -45.3, 95% CI [-73.23, -17.46], p = 0.002). Homeostasis model assessment of IR decreased significantly in the supplement intervention even after controlling for confounding factors in adjusted models. Changes in fasting blood sugar and insulin sensitivity were not significant in either the crude or adjusted models., Conclusion: The study results show that adding Cur to the diet can positively reduce insulin levels, improve IR, and lead to faster recovery of hyperinsulinemia. Cur supplementation with a healthy diet has synergistic beneficial effects on glycemic parameters. Larger clinical trials with longer durations are needed to confirm these results., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2024 Zohrabi et al.)

Background: Although several genetic biomarkers have been reported in the tocilizumab (TCZ) response in rheumatoid arthritis, no studies have addressed the pharmacogenomics effect of TCZ in COVID-19., Methods: In this prospective longitudinal study, 95 individuals with severe COVID-19 were selected between 2020-2022. The recovery process was measured at 24 h, 48 h, and 10 days before and after taking TCZ. All participants were genotyped using RFLP-PCR. Different genotypes of FCGR2A rs1801274 and IL-6R rs2228145 were compared in terms of the recovery process., Results: 43.2% of patients were male and 56.8% were female with an average age of 58.20(± 16.214) years. The GA genotype for FCGR2A rs1801274 increased the risk of death (OR = 2.83, P = 0.038) and ventilation (OR = 2.71, P = 0.047) in TCZ-treated individuals. However, there was no risk of death and ventilation with IL-6R rs2228145 (P > 0.05). Additionally, docking analysis showed that not only IL6R but also FCGR2A can be a ligand for TCZ., Conclusion: This study provides valuable insights into the impact of genetic variations on the response rate of TCZ in COVID-19 patients. The GA genotype for FCGR2A rs1801274 was associated with poor treatment outcomes., (© 2024. The Author(s).)

Background: Diminished ovarian reserve (DOR) is a condition that affects fertility by reducing the reproductive potential of the ovary. The altered expression profile of cumulus cells (CCs) can negatively affect the quality and quantity of oocytes in the ovaries. Recent studies suggest that circulating miRNAs play a significant role in the ovary function, and their serum expression changes can be valuable biomarkers for predicting ovarian function., Objective: Investigating the expression levels of circulating miRNA-4463 and its target cytochrome P450 19A1 gene ( CYP19A1 ) in DOR-CCs in order to find a molecular pathway involved in DOR., Materials and Methods: In this case-control study, a total of 20 DOR-women and 20 women with normal ovarian reservation aged between 20-34 yr referred to Yazd Reproductive Science Institute, Yazd, Iran were included in the study. Serum and CCs were collected, and real time-polymerase chain reaction was performed to investigate the expression level of miR-4463 , and its target gene CYP19A1 ., Results: Our results showed an inverse relationship between miR-4463 and CYP19A1 expression levels. Therefore, the increase in the expression of miR-4463 was significantly evident in DOR-women compared to the control group (p = 0.0019), while the expression of its target gene, CYP19A1, has significantly decreased in these women (p = 0.001)., Conclusion: The present study suggests that miR-4463 and CYP19A1 pathways could regulate ovary function. Therefore, examination of this miRNA could be a promising parameter for predicting ovarian reserve and their response to stimulation protocols., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2024 Yazdanian et al.)

The study was designed to assess the association of ACE I/D polymorphism with the severity and prognosis of COVID-19 in the Iranian population. Hence, 186 adult patients were categorized into three clinical groups based on the severity of COVID-19: 1) Outpatients or mildly symptomatic patients as control (n = 71); 2) Hospitalized patients or severe symptomatic cases (n = 53); 3) Inpatients led to ICU/death or critically ill patients needed mechanical ventilation (n = 62). The possible association of ACE I/D polymorphism with the risk of comorbidities and serum level of C-reactive protein was evaluated in two severe cases. The results showed that the frequency of D and I alleles are 69.35% and 30.65%, respectively, in the total population. The analysis of allelic frequencies via Fisher's exact test confirmed significantly higher frequency of D allele in both severe groups than that in the mild one, 78.31% in Hospitalized patients (OR = 2.56; 95% CI 1.46 to 4.46; p-value = 0.0011) and 74.19% in Inpatients led to ICU/death (OR = 2.04; 95% CI = 1.22 to 3.43; p-value = 0.0094) compared to 58.45% in Outpatients. The results of genotype proportions displayed an association between COVID-19 severity and DD genotype. Overall, our findings in Iranian patients supported the undeniable role of the DD genotype in the intensity of the disease, comparable to other populations. Furthermore, there is no definite evidence regarding the protective effect of the I allele in our inquiry., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Polycystic ovary syndrome is a common endocrine disorder in reproductive-age women. Accordingly, abnormal microenvironment may negatively influence oocyte developmental competence as a result of the altered expression profile of cumulus cells (CCs), mainly the key players of oocyte maturation, such as epidermal growth factor receptor (EGFR) and prostaglandin E receptor-2 (PTGER2). This study aimed to examine the expression levels of miR-514, miR-642b, and their candidate target genes (EGFR and PTGER2, respectively) in CCs of immature and mature oocytes in patients with PCOS. A total of 40 oocytes at germinal vesicle (GV) and 40 oocytes at metaphase II (MII) stages were retrieved from 30 PCOS women. Quantitative real-time PCR was performed to analyze the expression level of miR-514, miR-642b, EGFR, and PTGER2 in cumulus cells (CCS) of each oocyte. The expression level of miRNAs and their candidate target genes were compared between CCs of GV and MII oocytes. Our study suggests an inverse relationship exists between the expression levels of miR-514 and EGFR, and miR-642b and PTGER2. Furthermore, we observed that CCs of GV oocytes had higher levels of EGFR and PTGER2 mRNA and lower levels of miR-514 and miR-642b expression compared to those of MII oocytes. The present study demonstrated that miR-514 and miR-642b can regulate oocyte development by targeting EGFR and PTGER2, respectively. Therefore, examination of these miRNAs in CCs could be promising parameters to predict oocyte competence in PCOS patients., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding this article's publication and financial issues., (Copyright © 2024 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Unexpected poor ovarian response (UPOR) occurs when nine or fewer oocytes are retrieved from a young patient with normal ovarian reserve. Bone morphogenetic protein15 (BMP15) and growth differentiation factor 9 (GDF9) are two oocyte-specific factors with pivotal role in folliculogenesis. The aim of this study was to assess the relation between BMP15 and GDF9 variants with UPOR. Hundred women aged ≤ 39 with AMH ≥ 1.27 IU/ml participated as UPOR and normal ovarian responders (NOR) based on their oocyte number. Each group consisted of 50 patients. After genomic DNA extraction, the entire exonic regions of BMP15 and GDF9 were amplified and examined by direct sequencing. Western blotting was performed to determine the expression levels of BMP15 and GDF9 in follicular fluid. Additionally, in silico analysis was applied to predict the effect of discovered mutations. From four novel variants of BMP15 and GDF9 genes, silent mutations (c.744 T > C) and (c.99G > A) occurred in both groups, whereas missense variants: c.967-968insA and c.296A > G were found exclusively in UPORs. The latter variants caused reduction in protein expression. Moreover, the mutant allele (T) in a GDF9 polymorphism (C447T) found to be more in NOR individuals (58% NOR vs. 37% UPOR (OR = 2.3, CI 1.32-4.11, p = 0.004).The novel missense mutations which were predicted as damaging, along with other mutations that happened in UPORs might result in ovarian resistance to stimulation. The mutant allele (T) in C447T polymorphism has a protective effect. It can be concluded that there is an association between BMP15 and GDF9 variants and follicular development and ovarian response., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Several studies have examined the association between CD36 rs1761667 polymorphism with cardiometabolic risk factors and metabolic syndrome (MetS). This study aimed to investigate the interactions between rs1761667 polymorphism and dietary patterns on the cardiometabolic risk factors and the risk of MetS in apparently healthy individuals aged 20-70 years. Food consumption data were acquired using a validated semi-quantitative FFQ. Dietary patterns were identified by factor analysis. CD36 rs1761667 was genotyped by PCR-restriction fragment length polymorphism. The gene-diet interaction was detected by the general linear model or logistic regression. Significant or marginally significant interactions were observed between healthy dietary pattern (HDP) and CD36 rs1761667 on weight ( P = 0·006), BMI ( P = 0·009), waist circumference ( P = 0·005), hip circumference ( P = 0·06), body muscle percentage ( P = 0·02), body fat percentage ( P = 0·09), TAG-glucose index ( P = 0·057), atherogenic index of plasma ( P = 0·07), the risk of MetS ( P = 0·02), risk of abdominal obesity ( P = 0·02) and elevated blood pressure ( P = 0·07). Besides, a gene-diet interaction was detected between the traditional dietary pattern and rs1761667 variants on odds of hypertriglyceridaemia ( P = 0·02). The adherence to HDP was associated with a lower weight, BMI and higher odds of HDL-cholesterol only in A-allele carriers. In conclusion, adherence to HDP (a diet with high fibre, fish and dairy products) can be more effective on some cardiometabolic risk factors and risk of MetS components in the A-allele carrier than the GG genotype of rs1761667 polymorphism. However, future studies are required to shed light on this issue.

The aim of this research is to compare the capabilities of Adipose tissue mesenchymal stem cells (AT-MSCs) and bone marrow mesenchymal stem cells (BM-MSCs) in the treatment of diabetic male mice with CLI model. Supernatants were collected from C57BL/6 mice isolated AT-MSCs and BM-MSCs, afterward their effects on human umbilical vein endothelial (HUVEC) migration potential were evaluated. Diabetes mellitus type 1 was induced by streptozotocin injection. Diabetic mice with CLI model were divided into three groups and injected with AT-MSCs, BM-MSCs, or PBS then the efficacy of them was assessed. Survival of MSCs was analysed by SRY-specific gene. The conditioned medium of AT-MSCs and BM-MSCs stimulated HUVECs migration and the donor cells were detected till 21 day in two groups. BM-MSCs and AT-MSCs improved significantly functional recovery and ischemia damage. Neovascularization in ischemic muscle was significantly higher in mice treated with AT-MSCs and BM-MSCs and they improved muscle regeneration. In vivo and in vitro findings show that AT-MSCs and BM-MSCs transplantation could be proposed as a promising therapy to promote angiogenesis and muscle regeneration through secretion of proangiogenic factors, cytokines and growth factors in diabetic mice with CLI model wherein blood supply is insufficient and disrupted., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Context: In vitro maturation (IVM) of oocytes is an alternative approach for patients with polycystic ovary syndrome (PCOS) predisposing to ovarian hyperstimulation syndrome (OHSS). Transcriptomic analysis of cumulus cells (CC) may help make IVM more efficient. The aim of this study was to examine the impact of miR-144 and miR-224 and their candidate target genes (COX-2 and PTX-3 , respectively) expression on oocyte development in PCOS patients., Methods: Immature oocytes were retrieved from 20 PCOS patients. After IVM, samples were divided into two groups: matured (M) and immatured (I) oocytes. ICSI was performed and the embryo quality was evaluated. qPCR was used to analyse miR-144, miR-224, COX-2 and PTX-3 expression levels in CCs of each group., Key Results: We found that the expression levels of miR-144 and miR-224 were lower and the COX-2 and PTX-3 mRNA levels were higher in CCs of M group than in CCs of I group. The expression level of miR-144 and miR-224 in unfertilised oocytes were higher than fertilised oocytes. The contrary results were observed for COX-2 and PTX-3 . A reduction pattern in the expression level of miR-144 and miR-224 and increasing pattern in the level of COX-2 and PTX-3 expression were observed in high quality compared to low quality embryos., Conclusions: The selected miRNAs were related to oocyte maturation, fertilisation and embryo development. These results support their critical involvement in oocyte development., Implications: Our findings may help reveal the mechanisms of post-transcriptional regulation by miR-144 and miR-224 during IVM procedure.

Purpose: Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease that diabetes mellitus is one of its major risk factors. MiR-126 as an endothelial cells specific miRNA plays a main role in angiogenesis. The objective of this study was to find a promising treatment by increasing therapeutic potential of adipose tissue mesenchymal stem cells (AT-MSCs) with microRNA-126 in diabetic mouse model with critical limb ischemia. AT-MSCs were isolated from male C57BL/6 mouse and characterized., Methods: The cells were infected with miR-126 recombinant lentiviral vectors. Diabetes mellitus type 1 was induced and CLI was created in the animals. Animals were divided in different groups to receive PBS, MSCs, miR-126, and MSC miR-126 and after the experiment, behavioural tests, cell survival, real-time PCR, and histopathological analysis were assessed., Results: The results of function scores, VEGF-A level, and histopathology data demonstrated that the miR-126 treated group was better than PBS and MSCs groups. The expression of PIK3R2 and SPRED1 were decreased in miR-126 group compared to the control group. Our results showed that MSCs miR-126 can live longer than MSCs in the gastrocnemius muscle. We conclude that mice treated with MSCs miR-126 in functional tests showed better results and also the expression of VEGF-A and Microvessel density in them were higher than other groups., Conclusions: This study suggested that AT-MSCs overexpressing miR-126 could be an efficient therapeutic approach for angiogenesis in CLI with diabetes by downregulating SPRED1 and PIK3R2 and increasing secretion of angiogenic cytokines which can prolong the MSC survival., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The cluster of differentiation 36 (CD36) is one of the main receptors implicated in the pathogenesis of the cardiovascular disease. This study aimed to assess the association between CD36 rs1761667 polymorphism and cardiometabolic risk factors including body mass index (BMI), waist circumference (WC), total cholesterol (TC), triglyceride, HDL-C, LDL-C, blood pressure and fasting blood glucose (FBG). PubMed, EMBASE, Scopus, web of science, and Google Scholar were searched up to December 2021. Subgroup and meta-regression analyses were conducted to explore sources of heterogeneity. Eighteen eligible studies (6317 participants) were included in the study. In the overall analysis, a significant association was found between rs1761667 polymorphism of CD36 and TG in allelic (p < 0.001), recessive (p = 0.001) and homozygous (p = 0.006) models. A relationship between this polymorphism and HDL-C and FBG level was observed in the recessive genetic model. In the subgroup analysis, the A allele was associated with impaired lipid profiles (TC, LDL-C and HDL-C) in the Asian population. The influences of health status, design of the study, confounders, and other sources of heterogeneity should be considered when interpreting present findings. Cohort studies with large sample size and in different ethnicities are needed to confirm the relationship between rs1761667 SNP and cardiometabolic risk factors., (© 2022. The Author(s).)

Background: Obesity is associated with many comorbidities including inflammatory bowel disease (IBD). We investigated prophylactic effects of an herbal extract (HE) on the DSS-induced colitis mice challenged with high AGEs-fat diet 60% (HFD)., Methods: Six-week-old C57BL/6 male mice were fed with either HFD (8 groups, 6 mice in each group), or normal diet (ND) (8 groups, 6 mice in each group). After 6 weeks, animals received HE (combination of turmeric, ginger, boswellia and cat's claw extract) for 7 weeks in three doses (high dose (0.6 mg/g); low dose (0.15 mg/g) and mid dose (0.3 mg/g)). Next, mice were subjected to 2.5% DSS in drinking water. Control mice received ND and instead of HE and DSS they received distilled water. Obesity index markers were determined, H&E staining and TUNEL assay evaluated apoptosis. Colonic expressions of IL-6, RAGE, AGER1, Sirt1, Bax, Bcl2, ZO-1 and P53 were determined., Results: HE ameliorated colitis in HFD mice by reducing colonic myeloperoxidase activity (by 2.3-fold), macrophage accumulation (by 2.6-fold) and mRNA expression of IL-6 (by 2.3-fold) in HFD mice. Moreover, HE restored ZO-1 (by 2.7-fold), prevented apoptosis and maintained immune homeostasis. HE reduced activation of NF-κB protein (by 1.3-fold) through decreasing RAGE (by 1.93-fold) and up-regulation of Sirt1 (by 7.71-fold) and prevented down-regulation of DDOST (by 6.6-fold) in HFD mice., Conclusions: HE ameliorated colitis in prophylactic in HFD mice and it was, at least partly, due to the restoration of the gut integrity, suppression of inflammation and apoptosis via modulation of colonic Sirt1, RAGE and DDOST signaling., (© 2021. The Author(s).)

Background: A number of studies were carried out to assess the association of angiotensin I converting enzyme (ACE) I/D and plasminogen activator inhibitor-1 (PAI-1-1) 4G/5G polymorphisms with susceptibility to type 2 diabetes mellitus (T2DM). However, there are a few studies in Iranian patients with T2DM. Here, we tested for an association of ACE I/D and PAI-1 4G/5G polymorphisms with T2DM risk., Methods: One hundred-eighteen patients with T2DM and 125 healthy subjects were participates in this study. The ACE I/D (rs4340) and PAI-1 4G/5G (rs1799889) polymorphisms was genotyped by conventional and PCR-RFLP assays, receptively. The associations was evaluated by calculating the odds ratio (OR) and 95% confidence interval (95% CI)., Results: The genotype distribution of ACE I/D and PAI-1 4G/5G polymorphisms were not deviated from the Hardy-Weinberg equilibrium in healthy controls. The ACE II, ID, and DD genotype frequencies were 18.6%, 48.3%, and 33.1% in the T2DM patients versus 24.0%, 45.6% and 30.4% in healthy subjects, respectively. The PAI-1 4G/4G, 4G/5G, and 5G/5G genotype frequencies were 16.9%, 51.7%, and 31.4% in cases versus 24.8%, 57.6% and 17.6% in controls, respectively. There is a significant distribution in genotype/allele of PAI-1 4G/4G between cases with T2DM and healthy control, but not for ACE I/D. Moreover, the 5G/5G genotype is significantly (OR = 2.139, CI 95% 1.171-3.907, p = 0.013) increased the risk of T2DM by two folds in the cases than healthy controls., Conclusions: Our findings suggest that PAI-1 4G/5G may be likelihood risk factor for the development of T2DM in the Iranian patients. The higher frequency of PAI-1 5G/5G genotype in patients with T2DM revealed that individuals with the 5G allele may be at higher risk of T2DM development than those with 4G. However, there was no significant association between ACE I/D polymorphism and T2DM in our population. Future rigorous, well-designed studies with larger sample should replicate this study to confirm our findings in Iranian T2DM patients., Competing Interests: Conflicts of interestThe authors declare that they have no conflict of interest., (© Springer Nature Switzerland AG 2021.)

The present study sought to evaluate the effect of resveratrol supplementation on mRNA expression levels of peroxisome proliferator-activated receptor alpha (PPARα), p53, p21, p16, and serum levels of cluster of differentiation 163 (CD163) to TNF-like weak inducer of apoptosis (TWEAK) ratio in patients with type 2 diabetes. In this double-blind randomized controlled trial, 71 patients were randomly assigned to receive either 1,000 mg of trans-resveratrol or placebo (methyl cellulose) for 8 weeks. Expression levels of genes of interest, and serum levels of sCD163 and sTWEAK were assessed at baseline and at the end of the study. Resveratrol supplementation significantly increased mRNA expression levels of p53 and p21 genes, compared with the placebo group (fold change of p53 = 1.29, p = .04; fold change of p21 = 1.46, p = .006). However, no significant effect on expression levels of PPARα and p16 genes was observed after supplementation. In addition, resveratrol significantly reduced serum levels of sCD163/sTWEAK ratio compared with the placebo group (p = .003). Resveratrol supplementation resulted in significant changes in p53 and p21 genes expression, while serum levels of sCD163/sTWEAK ratio also improved in the resveratrol group, without any significant change in adjusted sCD163 levels. More research is needed to confirm the beneficial effects of resveratrol for patients with diabetes., (© 2021 John Wiley & Sons, Ltd.)

Introduction: Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment., Methods: For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis., Results: Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups., Conclusions: Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

Object: Immunosuppressive and immunomodulatory activity of mesenchymal stem cells derived from different sources, such as placental membranes, umbilical cord, and amniotic fluid has been proved. The heterogeneous nature of human amniocytes have been confirmed due to different clonal subpopulations found in amniotic fluid. The aim of this study was to investigate a 17-gene panel of immunomodulatory markers in two clonal subpopulations of CD90 + amniocytes, divided based on morphology into epithelioid and fibroblastoid cells., Method: Semi-quantitative RT-PCR was used to study the expression of the chosen genes. Flow cytometry analysis confirmed the non-hematopoietic mesenchymal origin of isolated cells, based on lacking the hematopoietic marker of CD31, and the presence of mesenchymal marker of CD90 (both on more than 90% of cells)., Results: Our results showed that besides growth characteristics, the two cell groups were different in expressional profile, so that, fibroblastoid clones displayed higher level of immunosuppression genes as well as mesenchymal surface marker of CD90 compared to epithelioid ones. Our previous investigation on these clones showed that epithelioid cells have a more potential to express the pluripotency genes. It seems there is an inverse relationship between genes associated with immunosuppression and pluripotency., Conclusion: Although many reports have been published regarding the immunosuppressive properties of fetal stem cells, but few studies to date have explained whether the stemness state of human amniocytes may affect their immunosuppressive potential. Further study on amniocytes, which often has self-renewal ability and high immunomodulatory potential, can help to understand the details of this relationship., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Endometriosis is generally considered as a benign condition; however, there is a possibility for it to become cancerous. miR-125b is upregulated in both endometriotic tissues and serum samples of women with endometriosis but its potential targets in endometriosis are still not fully understood., Objective: The role of miR-125b in the regulation of TP53 expression in endometriosis was tested with a bioinformatics approach. In addition, the expression of miR-125b and TP53 in both eutopic (Eu-p) and ectopic endometrium (Ec-p) in the endometrium tissues of women with endometriosis was compared to those in the normal endometrium tissues of controls (Normal)., Materials and Methods: In this case-control study, the Eu-p and Ec-p samples were collected from 20 women who underwent laparoscopic surgery, and the normal endometrium tissues were collected from 20 controls with no evidence of endometriosis. For bioinformatics approach, a protein-protein interaction network was constructed based on co-expressed potential targets of miR-125b. Quantitative polymerase chain reaction technique was used for the measurement of miR125b and TP53 expression., Results: Our results showed that miR-125b was significantly overexpressed in Ec-p (p-value: 0.021). In addition, there was a significant TP53 under expression in both the Ec-p and Eu-p samples compared with the Normal tissues (p-value: 0.003)., Conclusion: The negative correlation between miR-125b and TP53 as well as a noticeable decreased expression of TP53 in both Ec-p and Eu-p samples may be interpreted as the roles of miR-125b/ TP53 axis in the pathogenesis of endometriosis. In addition, these findings and bioinformatic analyses imply a possible role of miR-125b in cancer-like features of endometriosis., Competing Interests: The authors declare that there is no conflict of interest that could be perceived as prejudicial to the impartiality of the reported research., (Copyright © 2020 Hajimaqsoudi et al.)

Objective: Glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) is a subunit of a ligand-gated ion channel that regulates the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by controlling the release of gonadotropin-releasing hormone. Few studies have investigated the association between the GRIA1 gene and human infertility. This study evaluated the association of the GRIA1 rs548294 C > T and rs2195450 G > A polymorphisms with the ovarian response to human menopausal gonadotropin (HMG) in Iranian women., Methods: One hundred women with histories of at least 1 year of infertility were included. On the second day of menstruation, patients were injected with HMG; on the third day, blood samples were collected. After hormonal analysis, the GRIA1 rs548294 C > T and rs2195450 G > A genotypes of samples were identified via the restriction fragment length polymorphism method, and on day 9, the number of follicles was assessed via ultrasound., Results: For the GRIA1 rs548294 C > T and rs2195450 G > A single nucleotide polymorphisms, the subjects with CT and GG genotypes, respectively, displayed the highest mean FSH level, LH level, and number of follicles on day 9 of the menstrual cycle (p< 0.05). Significant positive correlations were observed between LH and FSH (p< 0.01), LH and follicle count (p< 0.01), FSH and age (p< 0.05), follicle count and age (p= 0.048), and FSH and follicle count (p< 0.01)., Conclusion: This study showed a significant relationship between GRIA1 polymorphisms and ovarian response to the induction of ovulation. Therefore, determining patients' GRIA1 genotype may be useful for improving treatment and prescribing suitable doses of ovulation-stimulating drugs.

According to the WHO, breast cancer is the most common cancer in women worldwide. Identification of underlying mechanisms in breast cancer progression is the main concerns of researches. The mechanical forces within the tumor microenvironment, in addition to biochemical stimuli such as different growth factors and cytokines, activate signaling cascades, resulting in various changes in cancer cell physiology. Cancer cell proliferation, invasiveness, migration, and, even, resistance to cancer therapeutic agents are changed due to activation of mechanotransduction signaling. The mechanotransduction signaling is frequently dysregulated in breast cancer, indicating its important role in cancer cell features. So far, a variety of experimental investigations have been conducted to determine the main regulators of the mechanotransduction signaling. Currently, the role of miRNAs has been well-defined in the cancer process through advances in molecular-based approaches. miRNAs are small groups of RNAs (∼22 nucleotides) that contribute to various biological events in cells. The central role of miRNAs in the regulation of various mediators involved in the mechanotransduction signaling has been well clarified over the last decade. Unbalanced expression of miRNAs is associated with different pathologic conditions. Overexpression and downregulation of certain miRNAs were found to be along with dysregulation of mechanotransduction signaling effectors. This study aimed to critically review the role of miRNAs in the regulation of mediators involved in the mechanosensing pathways and clarify how the cross-talk between miRNAs and their targets affect the cell behavior and physiology of breast cancer cells., (©2020 American Association for Cancer Research.)

Risk factors for ovarian cancer include a number of genetic variants as well as endometriosis. The FAS - FASL system is one of the apoptotic pathways that play an essential role in the apoptotic process within the endometrium. Here, we evaluate the correlation between FAS - FASL polymorphisms with the risk of endometriosis in Iranian patients and healthy controls. We extracted DNA from whole blood samples using a DNA Purification Kit. Using the PCR-RFLP method, three SNPs, including FAS (-670 A/G) and FASL (-844 C/T and &#95;124G/A) genes, were genotyped in 112 patients with endometriosis as well as 110 healthy controls. The frequency of genotypes and the alleles of these SNPs were analyzed by the chi-squared test for the significant association. Haplotype analysis was done by the PLINK software. The frequency distribution of haplotypes was significant between SNPs so that the ACG haplotype was more frequent in the cases than in the controls ( p  = .017). These results indicate that haplotype analysis can be useful for SNP analysis. The ACG haplotypes in FAS -670A/G, FASL -844C/T, and &#95;124G/A genes may be correlated with the progression of endometriosis.

Background: It has been proposed that Noise-induced hearing loss is a complex disease that is combination of environmental and genetic factors. There are inconsistent results concerning the association between variation in glutathione S-transferase ( GST ) genetic polymorphisms ( GSTT1 rs1049055 and GSTM1 rs10712361) and susceptibility to Noise-induced hearing loss., Objective: This study was designed to assess the association between GST gene polymorphism and Noise-induced hearing loss among noise-exposed workers. Methods: In a case-control study, male workers from tile and ceramic factories were selected randomly. Subjects were classified into two groups according to the result of audiometry: 73 subjects showed Noise-induced hearing loss which was considered in the case group and 87 subjects without hearing loss was enrolled in the control group. The GSTT1 and GSTM1 polymorphism of both groups were assessed by multiplex polymerase chain reaction., Results: Null GSTT1 and GSTM1 genotypes were more frequent in case group but no significant statistical difference was seen in case and control groups. No significant link between GSTT1 and GSTM1 genotypes was found., Conclusion: This study suggests that the genetic variability of GSTT1 and GSTM1 has no effect on susceptibility to noise induced hearing loss., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest., (© 2019 the Author(s), licensee AIMS Press.)

The mucosal immune system serves as the first line of defense against Bordetella pertussis . Intranasal vaccination, due to its potential to induce systemic and mucosal immune responses, appears to prevent the initial adherence and colonization of the bacteria at the first point of contact. In the present study, two B. pertussis antigens, pertussis Toxoid (PTd) and Filamentous hemagglutinin (FHA), which play a very significant role in virulence and protection against pertussis, were encapsulate into N-trimethyl chitosan (TMC) nanoparticulate systems. After preparation of TMC nanoparticles (NPs), the NPs were characterized and their ability to induce efficient immune responses against B. pertussis was studied in a mouse model. Our findings showed that PTd + FHA-loaded TMC NPs have strong ability to induce IL-4, IL-17, IFN-γ, IgG, and IgA in the mouse model. Results from this study suggest that nasal administration of the PTd + FHA-loaded TMC NPs induced not only a systemic immune response but also a local mucosal response, which may improve the efficacy of pertussis prevention through respiratory tract transmission.

The aim of the present randomized controlled trial was to evaluate the effect of a micronized resveratrol supplement on glycemic status, lipid profile, and body composition in patients with type 2 diabetes mellitus (T2DM). A total of 71 overweight patients with T2DM (body mass index ranged 25-30) were randomly assigned to receive 1000 mg/day trans-resveratrol or placebo (methyl cellulose) for 8 weeks. Anthropometric indices and biochemical indices including lipid and glycemic profile were measured before and after the intervention. In adjusted model (age, sex, and baseline body mass index), resveratrol decreased fasting blood sugar (-7.97±13.6 mg/dL, p=0.05) and increased high density lipoprotein (3.62±8.75 mg/dL, p=0.01) levels compared with placebo. Moreover, the mean difference in insulin levels reached significance (-0.97±1.91, μIU/mL, p= 0.02). However, no significant differences were observed for anthropometric measures. It was found that 8-week resveratrol supplementation produced useful effects on some cardio-metabolic parameters in patients with T2DM. More studies are needed to confirm these findings., (© 2019 John Wiley & Sons, Ltd.)

Breast cancer (BC), as a heterogeneous disease, is considered as one of the most common malignancies in women worldwide. The resistance of BC cells to therapeutic agents has remained a big challenge in the treatment of BC patients. Some factors such as cytokines, exosomes, and soluble receptors were recognized as crucial agents involved in the development of drug resistance. However, the exact mechanisms underlying the drug resistance is still unknown. There is growing evidence to support the emerging roles of exosomes, especially exosomal miRNAs, in tumor initiation, angiogenesis, proliferation, migration, invasion, metastasis, and drug resistance. Therefore, identification of BC-specific exosomal miRNAs and their underlying mechanisms would be helpful to define sensitivity to therapeutic drugs and establish an appropriate therapeutic strategy. This review focuses mainly on the roles of exosomal miRNAs and their associated mechanisms in the resistance of BC cells to therapeutic agents, as well as critically examines the potential of these macromolecules as a treatment biomarker in BC patients., (© 2019 International Union of Biochemistry and Molecular Biology.)

Background/objectives: Recent studies suggest that, in addition to activation and hypersecretion of matrix components, fibroblasts from patients with systemic sclerosis (SSc) are resistant to apoptosis. Previous studies have shown that survivin, a member of inhibition of apoptosis (IAP) family, plays an important role in apoptosis resistance. Accordingly, we decided to study the expression of the most important members of IAP family in SSc fibroblasts, which can block apoptosis either by binding and inhibiting caspases or through caspase-independent mechanisms., Method: Skin biopsy samples were obtained from 19 patients with diffuse cutaneous SSc (DcSSc) and 16 healthy controls. Dermal fibroblasts were cultured and the total RNA was isolated from cells followed by cDNA synthesis. Real-time PCR was performed using SYBR Green PCR master mix and specific primers for cIAP1, cIAP2, XIAP, and Survivin mRNA quantification., Results: A significantly increased expression level of Survivin was observed in fibroblasts from SSc patients compared to controls (2.26-fold, P = 0.04). However, mRNA expression of cIAP1, cIAP2, and XIAP did not change significantly between cases and controls., Conclusions: Our results showed that survivin is upregulated in SSc skin fibroblast which may lead to resistance to apoptosis. Further studies should be performed to reveal the role of survivin in apoptosis pathway of SSc fibroblasts.

For the first time ever, this paper reports the development of an easily operated and cost-effective electrochemical assay to be used as an appropriate substitute for the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assay. The proposed assay is based on the electrochemical reaction of Saccharomyces cerevisiae (S. cerevisiae) with toxic materials, and it overcomes most of the limitations of MTT such as evaporation of volatile solvents, cytotoxic effects of MTT reagents, high cost, and sensitivity to light. The novel electrochemical assay can be used to detect diazinon in the range of 10 -6 g mL -1 to 10 -2 g mL -1 with the detection limit of 1.5 × 10 -7 g mL -1 .

Background: Genetic factors play a substantial role in acute myeloid leukemia (AML) etiology. Overexpression of the mouse double minute 2 (MDM2) gene has been explored in many tumors. However, the role of MDM2 -309T>G (rs2279744) polymorphism in AML remains unclear. We have performed this study to examine the association of MDM2 -309T>G with AML in an Iranian population., Methods: We have examined the association of N MDM2 -309T>G polymorphism in 73 cases diagnosed with AML and 80 healthy controls by tetra-primer amplification refractory mutation system (ARMS) PCR assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated on the risk genotypes and alleles., Results: The TT, GG and GG genotypes of MDM2 -309T>G polymorphism in patients were 32.9%, 23.2% and 43.9%, while in controls were 86.2%, 7.5% and 6.3%, respectively. Moreover, Frequency of mutant allele (G) was 55.6% in cases with AML and 10.0% in controls. The mutant homozygote genotype (GG) was associated with an increased susceptibility to AML (OR 1.471; 95% CI: 1.062-1.844; p=0.004)., Conclusion: Our results showed that the MDM2 -309T>G polymorphism was significantly associated with increased risk of AML in the Iranian population. Thus, the MDM2 -309T>G polymorphism might be useful genetic susceptibility factors in the pathogenesis of AML.

Introduction: Over the past decades, the number of people with type 2 diabetes (T2D) has increased globally. One of the major complications in these patients is cardiovascular disease; it seems that the cell proliferation inhibition can improve vascular function in these patients. It is proposed that peroxisome proliferator-activated receptor alpha (PPARα) can induce cell cycle arrest via cyclin-dependent kinase inhibitor 2A (p16) activation. Also, it has been shown that phosphorylated tumour suppressor protein p53 is involved in cell senescence by cyclin-dependent kinase inhibitor 1 (p21) upregulation. Resveratrol is a natural polyphenol and appears to improve the vascular function through the mentioned pathways. We will aim to evaluate the effects of resveratrol supplementation on mRNA expression of PPARα, p53, p21 and p16 in patients with T2D. We will also measure serum levels of cluster of differentiation 163 (CD163) and tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) as the indicators of cardiovascular status., Methods and Analysis: Seventy-two subjects suffering from T2D will participate in this double-blind randomised parallel placebo-controlled clinical trial. Participants will be randomly assigned to receive 1000 mg/day trans-resveratrol or placebo (methyl cellulose) for 8 weeks. The mRNA expression levels of PPARα, p53, p21 and p16 genes will be assessed using real-time PCR and serum CD163 and TWEAK levels will be measured using commercially available ELISA kits at baseline and the end of the study. Clinical outcome parameters (glycaemic and lipid profiles and body composition) will also be measured before and after study duration., Ethics and Dissemination: The study is performed in agreement with the Declaration of Helsinki and is approved by the Ethics Committee of the Shahid Sadoughi University of Medical Sciences (no: ir.ssu.sph.rec.1396.120). The results will be published in scientific journals., Trial Registration Number: IRCT20171118037528N1; Pre-results., Competing Interests: Competing interests: The authors declare that they have no competinginterests., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Today, in clinical trials, we suffer from the lack of effective methods with minimal side effects to deliver medication. Thus, efforts to identify better conditions for delivery of biomedical drugs seem necessary. The purpose of this study was to design a new liposomal formula for transportation of microRNA in osteosarcoma., Materials and Methods: In this experimental study, several liposomal formulations were synthesized. Physical and chemical parameters, including size, zeta potential, polydispersity index, long-term stability of the liposomal-microRNA complex and the amount of miR-143 loading in liposome based nano-vesicles were optimized using different techniques. Similarly, the effect of free and encapsulated microRNA toxicity were investigated and compared in a human bone osteosarcoma cell line, named SaOs-2., Results: In this study, we could produce a novel and optimized formulation of cationic PEGylated liposomal microRNA for gene delivery. The present synthesized microRNA lipoplex system was non-agglomerated. The system remained stable after four months and miR-143 leakage was not observed by performing gel electrophoresis. The microRNA lipoplex could enhance conduction of the loaded miR-143 , and it also showed good biocompatibility to the healthy cells., Conclusion: The PEGylated microRNA lipoplex system had a high potential for the systematic migration of miR-143 and it could improve intracellular stability of the released microRNA., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

Research Question: Can a combination of time-lapse morphokinetic parameters and cumulus cell gene expression in polycystic ovary syndrome (PCOS) women be used to predict assisted reproductive treatment outcome?, Design: A total of 547 embryos from 100 intracytoplasmic sperm injection (ICSI) cycles were evaluated. Fifty women with PCOS and 50 women who were categorized as tubal factor infertility were recruited. Time-lapse records were annotated for time to pronuclear fading (tPNf), time to 2 to 8 cells (t2-t8), reverse cleavage, direct cleavage and also for the presence of multinucleation. Expression levels of three genes involved in mitotic divisions, diaphanous-related formin 2 (DIAPH2), nibrin (NBN) and NIMA-related protein kinase (NEK4), were measured in 100 associated cumulus cell samples using quantitative real-time polymerase chain reaction., Results: Expression of DIAPH2 and NBN was significantly higher in the embryos of PCOS patients that resulted in implantation, biochemical and clinical pregnancies as well as live birth compared with embryos that were negative for these outcomes (P <0.01). However, in the tubal factor group, NBN gene expression was significantly higher in embryos resulting in biochemical pregnancy, clinical pregnancy and live birth (P <0.01) only. Multivariate logistic regression analysis showed that tPNf together with DIAPH2 gene expression were independent prognostic factors of clinical pregnancy rate and live birth in both groups., Conclusions: Some time-lapse embryo parameters may be related to cumulus gene expression and clinical outcome. Furthermore, the expressions of cumulus cell genes involved in mitotic divisions are significantly associated with ICSI outcome using Day 3 embryo transfer., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Telomere length (TL) has been suggested to be a surrogate for cellular ageing, and a record of cumulative inflammation and oxidative stress over life. An emerging body of evidence has associated exposure to air pollution to changes in TL. To date there is no available systematic review of literature on this association. We aimed to systematically review and conduct meta-analysis of published studies on the relationship between air pollution and TL in adults. Electronic databases were systematically searched for available English language studies on the association between air pollution and TL published up to 1 July 2018. Meta-analyses were conducted following MOOSE guidelines. The heterogeneity in the reported associations was assessed using Cochran's Q test and quantified as I 2 index. Publication bias was assessed using Egger's regression. Our search identified 19 eligible studies including 11 retrospective and eight prospective studies of which, four had excellent quality, ten had good quality and five had fair quality. Meta-analysis result of two studies on long-term exposure to PM 2.5 showed an inverse association between these exposures and TL (for 5 μg/m 3 PM 2.5 -0.03 95% CI; -0.05, -0.01). Meta-analysis of short-term exposure to PM 2.5 with three studies and Polychlorinated Biphenyls (PCBs) with two studies revealed a direct association between these exposures and TL (0.03 95% CI; 0.02, 0.04 and 0.10 95% CI; 0.06, 0.15 respectively). No statistically significant relationship between exposure to PM 10 and polycyclic aromatic hydrocarbons (PAHs) exposure and TL were observed. We observed suggestive evidence for associations between air pollution and TL with potentially different direction of associations for short- and long-term exposures., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Colorectal cancer (CRC) is one of the most prevalent cancers and microRNAs are involved in colorectal carcinogenesis and progression. The role of our candidate microRNAs (miR-143-3p, -424-5p, -212-3p and -34a-3p) have been investigated in various cancers., Objective: The aim of the current study was to evaluate expression levels of microRNAs (miR-143-3p, -424-5p, -212-3p and -34a-3p) in the sera of patients with CRC in order to identify potential non-invasive biomarker for CRC and investigate the relationship between their expression and clinicopathological features of CRC., Methods: The serological expression of candidate microRNAs were measured in 124 participants, including 62 CRC patients and 62 healthy controls and the serum expression levels of candidate miRNAs were quantified by stemloop reverse transcriptionquantitative polymerase chain reaction., Results: In the present study, results showed a significant upregulation expression level of miR-424-5p (P< 0.001) and decreased expression level of miR143-3p was observed in the sera of patients with CRC (P< 0.001). Receiver operating characteristic (ROC) curve analysis demonstrated the area of miR-424-5p and miR-143-3p under the ROC curve for CRC diagnosis were 0.703 and 0.724 respectively (P< 0.001). In addition, down expression of miR-143-3p was significantly associated with tumor size (P= 0.005) and lymph node metastasis (P= 0.020) in CRC patients., Conclusions: The present investigation suggested that low expression of miR-143-3p and increasing level of miR-424-5p in CRC patients may play an important role in development of CRC and they could function as potential non-invasive biomarkers for CRC.

The aim of this study was to investigate spatial variation and health risk of the exposure to PM 2.5 (particulate matter with a diameter of 2.5 µm or less) and PM 10 (particulate matter with a diameter of 10 µm or less) in Sabzevar, Iran. PM 2.5 and PM 10 were measured during three campaigns from April to November 2017, in 26 sampling points. Spatial analysis was performed using kriging and autocorrelations (Moran's index) model in Arc GIS software. Relationship between exposure to the PM 2.5 and PM 10 and their health impacts were investigated by AirQ 2.2.3 software. The mean concentrations (and standard deviation) of PM 2.5 and PM 10 over the entire study period were 32.54 (37.28) and 42.61 (47.76) μg/m 3 , respectively, which were higher than the guideline of World Health Organization. According to the spatial analysis, the maximum concentrations of PM 2.5 and PM 10 were around the main highway (beltway) which placed all over the south of Sabzevar. According to the Moran's index, the emission patterns for PM 2.5 (Z-score = 2.53; P-value = 0.011) and PM 10 (Z-score = 2.82; P-value = 0.004) were clustered. The attributable percentage (AP) of total mortality related to PM 2.5 and PM 10 were 3.544% (95% confidence interval (CI): 2.623-4.447%) and 2.055% (95% CI: 1.379-2.721%) per increasing each 10 μg/m 3 of these pollutants, respectively. According to observed results, it is suggested that the beltway and other pollution sources, such as industries, should be placed at a greater distance from the city, to reduce PM amounts in residential areas., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Neisseria meningitidis is a facultative pathogen bacterium which is well founded with a number of adhesion molecules to facilitate its colonization in human nasopharynx track. Neisseria meningitidis is a major cause of mortality from severe meningococcal disease and septicemia. Neisseria meningitidis adhesion, NadA, is a trimeric autotransporter adhesion molecule which is involved in cell adhesion, invasion, and antibody induction. It is identified in approximately 50% of N. meningitidis isolates, and is established as a vaccine candidate due to its antigenic effects. In the present study, we exploited bioinformatics tools to better understand and determine the 3D structure of NadA and its functional residues to select B cell epitopes, and provide information for elucidating the biological function and vaccine efficacy of NadA. Therefore, this study provided essential data to close gaps existing in biological areas. The most appropriate model of NadA was designed by SWISS MODEL software and important residues were determined using the subsequent epitope mapping procedures. Locations of important linear and conformational epitopes were determined and conserved residues were identified to broaden our knowledge of efficient vaccine design to reduce meningococcal infectioun in population. These data now provide a theme to design more broadly cross-protective antigens.

Competing Interests: The authors declare that they have no financial or other conflicts of interest.

The aim of this study was to assess the potential health risk of exposure to polycyclic aromatic hydrocarbons (PAHs) at home and kindergarten for pre-school children. The urine samples were taken from 200 pre-school children aged 5-7 years and analyzed for 1-OHP as a biomarker of PAHs. Mixed effect models were applied to investigate the association between effective environmental parameters (mode of transport, distance to major roads, traffic density, greenness, tobacco exposure, home ventilation, and grill foods) and urinary 1-OHP levels. A Monte-Carlo simulation technique was applied to calculate the risk of exposure to PAHs and to check the uncertainty of input variables and the sensitivity of the estimated risk. The median and inter quartile range (IQR) of 1-OHP was 257 (188.5) ng L -1 . There was a positive significant association between distance from the kindergartens to the green space with surface area ≥5000 m 2 and 1-OHP concentration (β = 0.844, 95% CI: 0.223, 1.46, P-value = 0.009). Also, urinary 1-OHP was found to be inversely associated with the time the window was open at the home (β = -12.56, 95% CI: -23.52, -1.596, P-value = 0.025) and normalized difference vegetation index (NDVI) in a 100 m buffer around the homes. The mean (9.76 E-3) and 95th percentile (3.28 E-2) of the hazard quotient (HQ) indicated that the concentration of urinary 1-OHP is at a safe level for the target population (HQ < 1). According to the sensitivity analysis results, the concentration of 1-OHP is the most influential variable in the estimated risk. Our findings indicated that the proximity of homes and kindergartens to green space areas and their remoteness from the main streets and heavy traffic areas are associated with reduced exposure to PAHs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background. Our research was aimed to study p53 protein codon 72 polymorphism, a single base pair change of either arginine (Arg; CGC) or proline (Pro; CCC) that creates 3 distinct genotypes in reticular oral lichen planus (OLP) in comparison to oral SCC which is the most common oral mucosal malignancy as positive control and inflammatory fibrous hyperplasia (IFH) lesion as negative control. Methods. Seventy paraffin-embedded tissue samples (30 OLP, 20 OSCC and 20 IFH) were studied. DNA was purified and amplified using allele-specific polymerase chain reaction to detect polymorphism. The final amplified products were identified using gel electrophoresis. Data were analyzed using chi-squared test and odds ratio. Results. The mean ages in the OLP, OSCC and IFH groups were 43.28, 58.2 and 53.47 years, respectively, with significant differences. There were no significant differences in gender between the three groups (P=0.413); however, the differences in genotypes and alleles were significant between the three groups (P=0.021 and P=0.030, respectively). By considering IFH as a reference, the frequency of proline allele in OLP and OSCC was significantly higher than that of arginine allele (P=0.015 and P=0.028, respectively). In addition, by considering OSCC as a reference and at P=1, there were no significant differences in the frequencies of alleles between OSCC and OLP. Conclusion. The results might indicate the premalignant potential of OLP, and such polymorphism might be a genetic predisposing factor for conversion of OLP to OSCC. In addition, in the subjects evaluated the proline allele was considered a risk factor.

Background: The study of microRNA expression can be effective in the diagnosing and treating different diseases. miR-135a is one of the most important micro-ribonucleic acids involved in endometriosis. Among the genes that become the target of the miR-135a and are subjected to changes in the endometrium of patients with endometriosis is HOXA10 gene which is expressed in the endometrium in response to steroid hormones., Objective: The aim of this study was to evaluate the expression of miR-135a and its relationship with the level of HOXA10 gene expression in both endometrial ectopic and eutopic tissues in patients with endometriosis compared to the control samples., Materials and Methods: In this prospective case-control study, both case-eutopic and case-ectopic tissue samples were obtained from 17 women with endometriosis and the eutopic endometrial tissue was sampled from 17 women with normal endometrium as the control group. The gene's expression of miR-135a and HOXA10 were investigated using quantitative reverse transcription PCR (q-RT PCR)., Results: A significant decrease in the expression of HOXA10 gene was detected in case-eutopic during the luteal phase compared to the control samples (p=0.001), while in the case-ectopic, the expression of this gene was increased (p=0.681) compared to the control samples. In addition, the expression miR-135a in the luteal phase showed a remarkable increase in the case-eutopic endometrial tissue (p=0.026) as well as a significant decrease in the case-ectopic endometrial tissue compared to the control samples (p=0.008)., Conclusion: Considering the inverse relations between the over-expression of miR-135a and the reduction of HOXA10 , it seems that miR-135a may be applied as an endometrial diagnostic and therapeutic biomarker., Competing Interests: The authors declare that they have no competing interests.

Background: Tumor protein p53 ( TP53 ) is a tumor suppressor transcriptional regulator protein which plays a critical role in the spermatogenesis. One of the most important regulators of p53 is Murine double minute 2 ( MDM2 ), which acts as a negative regulator of the p53 pathway. Based on the key role of p53 and MDM2 in germ cell apoptosis, polymorphisms that cause a change in their function might affect germ cell apoptosis and the risk of male infertility., Objective: This study was designed to examine associations of TP53 72 Arg>Pro (rs1042522), and MDM2 309 T>G (rs937283) polymorphisms with spermatogenetic failure in Iranian population., Materials and Methods: A case-control study was conducted with 150 nonobstructive azoospermia or severe oligozoospermia and 150 fertile controls. The two polymorphisms, 72 Arg>Pro in TP53 and 309 T>G in MDM2 , were genotyped using PCR-RFLP and ARMS-PCR respectively., Results: Our analyses revealed that the allele and genotype frequencies of the TP53 R72P polymorphism were not significantly different between the cases and controls (p=0.41, p=0.40 respectively). Also, no significant differences were found in the allelic (p=0.46) and genotypic (p=0.78) distribution of MDM2 309 T>G polymorphism between patients and controls., Conclusion: The results of this study indicate that polymorphisms of TP53 and MDM2 genes are unlikely to contribute to the pathogenesis of male infertility with spermatogenetic failure., Competing Interests: The authors declare no conflicts of interest.

Background: Asthenozoospermia is one of the etiologies for male factor infertility. It was shown that any abnormality in protamines genes, reduction of protamines transcript and protamines deficiency may play a key role in asthenozoospermia., Objective: The aim of the current study was the evaluation of protamine-1 and 2 genes ( PRM1 and PRM2 ) polymorphisms in asthenozoospermic men., Materials and Methods: In this case-control study, the samples were corresponded to asthenozoospermic specimens of infertile men. The normozoospermic samples were considered as the control group. DNA sequence amplification was performed using four PRM1 and PRM2 primers, designed from 5' to 3' flank regions. The human PRM1 and PRM2 gene sequences were screened in search of potential mutations in highly prevalent polymorphism regions in asthenozoospermia versus normozoospermia., Results: Totally, nine highly prevalent polymorphism regions between the forward and reverse primers were screened. Three of them corresponded to PRM1 and six to PRM2 . The most prevalent polymorphism regions in PRM1 were related to 102G>T (rs35576928), 49C>T (rs140477029) and 139C>A (rs737008). In the PRM2 , 6 highly prevalent polymorphisms regions were screened, including 248C>T (rs779337774), 401G>A (rs545828790), 288C>T (rs115686767), 288G>C (rs201933708), 373C>A (rs2070923), and 298G>C (rs1646022). The allele frequencies of three upper mentioned single nucleotide polymorphisms in asthenozoospermic men including 373C>A, 298G>C and 139C>A was higher than the control group., Conclusion: Our findings indicated that the frequency of some altered genotypes in asthenozospermia was slightly higher than control group. We proposed more extensive studies to be sure that; these genotypes can precisely be related to diagnosis of asthenozoospermia, as the molecular markers., Competing Interests: The authors have no conflicts of interest to declare.

In this work we report the synthesis of a stable composite with excellent electrical properties, on the surface of a biosensor. Conductive polymers offer both high electrical conductivity and mechanical strength. Many reports have focused on synthesizing conductive polymers with the aid of high-cost enzymes. In the current work we introduce a novel electrochemical, one-step, facile and cost effective procedure for synthesizing poly (catechol), without using expensive enzymes. The poly (catechol) conductivity was enhanced by modification with graphene sheets and biosynthesized gold nanoparticles. Four different robust methods, DPV, EIS, CV and chronoamperometry, were used to monitor the biosensor modifications. The peak currents of the catechol (an electroactive probe) were linearly related to the logarithm of the concentrations of target DNA in the range 100.0 μM to 10.0 pM, with a detection limit of 1.0 pM for the DNA strand. The current work investigates a new, stable composite consisting of conductive polymers and nanoparticles, which was applied to the detection of acute lymphoblastic leukemia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Problem: The process of industrialization and lifestyle changes have gradually exposed human ‎societies to a larger number of environmental risk factors, which may cause hormonal ‎abnormalities and congenital anomalies., Background: The current study aimed to investigate the relationship ‎between environmental factors and hormonal abnormalities among pregnant women in Yazd, ‎Iran., Methods: A hundred participants were randomly selected from among a group of pregnant women. According to the screening tests (AFP, free β-‎HCG, uE3, PAPP-A, and inhibin-A) performed at the genome clinic in Yazd in 2016, the risk of Down Syndrome (DS) was sufficiently high in this group of pregnant women from which the participants were selected. A ‎questionnaire was used to collect data on the degree of the participants' exposure to pesticides ‎at home, use of canned and fast foods, and consumption of greenhouse fruits. The collected data were ‎analyzed by One-way ANOVA and Kruskal-Wallis Test., Findings: The mean of Multiple of Median (MoM) for inhibin-A was significantly higher among pregnant ‎women who often or always used pesticides at home (p=0.047). The mean MoM ‎for free β-HCG was significantly higher among pregnant women who often or always used canned ‎foods (p=0.024). Finally, the mean MoM for uE3 (1.85±1.30) was significantly higher among ‎pregnant women who never consumed greenhouse fruits (p=0.003)., Conclusion: It can be concluded that it is possible to reduce environmental exposures affecting hormonal abnormalities among pregnant women by improving nutritional patterns, minimizing the use of pesticides at home, and reducing the intake of canned foods and greenhouse fruits., (Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Aneuploidy is of great relevance to embryo selection, as it represents one of the important causes of implantation failure. Furthermore, immature oocytes, retrieved during gonadotrophin-stimulated IVF cycles, are generally discarded in clinics; whereas, there was no detectable comprehensive evidence on higher rates of aneuploidy based on maturity status on the day of oocyte retrieval. As well, the correlation between embryo morphology on aneuploidy remains unclear. The aim was to evaluate the developmental and genetic integrity of human preimplantation embryos from rescue in-vitro matured MII stage oocytes as well as in vivo matured oocytes. 541 rescue in-vitro matured oocytes as case as well as 659 in-vivo matured oocytes as control were used for the developmental assay. Finally, 121 cleaved embryos with good quality were analyzed by FISH technique for the detection of chromosomes X, Y, 13, 15, 16, 18, 21 and 22. The fertilization rates were 61.62% and 61.76% in case and control groups, respectively. Also, embryo formation rates of 89.1% vs. 92.2% were recorded for case and control groups, respectively. Good quality embryos on day 3 were 62.54% in case and 68.36% in control groups. There were insignificant differences in fertilization, embryo formation and quality between the groups. Total abnormality in 35 of the 60 embryos was 58.5% in case and 62.3% in control (p < 0.05). There were significant differences between aneuploidy rates of embryos using only sex chromosome preimplantation genetic screening (PGS) and sex chromosome in combination with autosomal chromosomes PGS in case (58.5% vs 28.3%, p = 0.000) and control groups (62.3% vs 21.3%; p = 0.000). The results demonstrated that a high proportion of good quality embryos were aneuploid in both patient groups with no obvious increase in aneuploidies as a result of rescue IVM application. Furthermore, the morphological characteristics of embryos do not completely consistent with chromosomal content. Despite the Rescue IVM is currently not a routine procedure in association with IVF, our finding suggested a viable option for young infertile women facing cancellation of their IVF treatment due to ovarian over-response or resistance factors as well as patients with low functional ovarian reserve considering good quality of embryos from rescue IVM-MII oocytes., (Copyright © 2017. Published by Elsevier Masson SAS.)

The purpose was to assess the developmental competence of the in vitro or in vivo matured human oocytes as well as the apoptotic genes expression of cumulus cells (CCs) regarding nuclear maturity status of associated oocytes retrieved from stimulated ICSI cycles. A total of 590 oocytes and the associated CCs were retrieved and divided into groups of test and control according to the nuclear maturity status in order to the developmental evaluation as well as expression patterns of apoptosis-related genes using real time PCR. The fertilization and embryo formation rates were 60.3% and 87.5% vs.69.1% and 92.8% in test and control groups, respectively. Good quality embryos on day 3 were 62.2% in test and 69.1% in control groups. There were significant differences in the rates of normal fertilized as well as unfertilized oocytes between the groups. Also, mRNA levels of some apoptotic genes were significantly higher in the CCs obtained from immature oocytes among patients with premature ovarian factors (POF) rather than other infertility etiologies (p < 0.001). The data demonstrated the developmental competence of in vitro matured oocytes -even to good quality cleavage embryos- is not completely consistent with molecular integrity and well-mannered gene expression patterns resulting to ICSI success. It seems that using immature oocytes could be helpful for patients at risk of ovarian hyperstimulation syndrome (OHSS) as the same as patients with diminished ovarian reserve., (Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Background: Familial hypercholesterolemia (FH) is a disorder that is inherited by autosomal dominant pattern. The main cause of FH disease is the occurrence of mutations in low-density lipoprotein receptor (LDLR) gene sequence, as well as apolipoprotein B and proprotein convertase subtilisin/kexin type 9 genes, located in the next ranks, respectively., Materials and Methods: Forty-five unrelated Iranian patients with FH were screened using a high-resolution melting (HRM) method for exon 9 along with intron/exon boundaries of LDLR gene. Samples with shift in resultant HRM curves were compared to normal ones, sequenced, and analyzed., Results: Our findings revealed a missense mutation c. 1246C>T and a known variant IVS9-30C>T (rs1003723) that was recognized in 71% of the patients (22%: homozygous and 49%: heterozygous genotypes). In silico analysis, predicted the pathological effect of the c. 1246C>T mutation in LDLR protein structure, but IVS9-30C>T variant had no predicted effect on splice site and branch point function., Conclusion: FH is a hereditary type of hypercholesterolemia that leads to premature cardiovascular disease and atherosclerosis, and early diagnosis is needed. We detected a rare missense mutation (1246C>T) and a common single nucleotide polymorphism (SNP) in the Iranian population. These reports could help in the genetic diagnosis and counseling of FH patients., Competing Interests: There are no conflicts of interest.

This study focuses on the development of a universal mathematical model for drug release kinetics from liposomes to allow in silico prediction of optimal conditions for fine-tuned controlled drug release. As a prelude for combined siRNA-drug delivery, nanoliposome formulations were optimized using various mole percentages of a cationic lipid (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) in the presence or absence of 3 mol% distearoyl phosphoethanolamine, polyethylene glycol (PEG-2000mDSPE). Outcome parameters were particle size, zeta potential, entrapment efficiency, in vitro drug release, and tumor cell kill efficiency. The optimized formula (containing 20% DOTAP with 3% DSPE-mPEG(2000) was found to be stable for six months, with round-shaped particles without aggregate formation, an average diameter of 71 nm, a suitable positive charge, and 89% drug encapsulation efficiency (EE). The 41% drug release during 6 h confirmed controlled release. Furthermore, the release profiles as functions of pH and temperature were investigated and the kinetics of the drug release could adequately be fitted to Korsmeyer-Peppas' model by multiple regression analysis. The statistical parameters confirmed good conformity of final models. Functionality of the novel cationic liposome formulations (± DOX) was tested on osteosarcoma (OS) cell lines. Increased OS cell toxicity (1.3-fold) was observed by the DOX-loaded vs. the free DOX. A feasibility pilot showed that siRNA could be loaded efficiently as well. In conclusion, we have established a predictive mathematical model for the fine-tuning of controlled drug release from liposomal formulations, while creating functional drug-delivery liposomes with potential for siRNA co-delivery to increase specificity and efficacy.