Association of Functional Genetic Variations in Uric Acid Transporters with the Risk of Idiopathic Male Infertility: A Genetic Association Study and Bioinformatic Analysis.

Uric acid plays an important role in sustaining and improving sperm morphology, viability, and motility. It is known that SLC2A9 and ABCG2 protein are the main urate transporter and genetic variations in these genes could be associated with the levels of serum uric acid. This study aimed to investigate the association between single-nucleotide polymorphisms (SNPs) SLC2A9-rs16890979, SLC2A9-rs3733591, ABCG2-rs2231142, and ABCG2-rs2231137 with male infertility. Additionally, the correlation of these SNPs with the uric acid level in seminal plasma of infertile men was examined. Subsequently, an in silico analysis was performed. In a case-control study, 193 infertile and 154 healthy controls were recruited. After semen sample collection, the uric acid level of seminal plasma was measured by a commercial kit. After genomic DNA extraction from sperm samples, SNPs genotyping was performed by PCR-RFLP method. Lastly, the effects of SNPs on the SLC2A9 and ABCG2 gene function were evaluated by bioinformatics tools. The genetic association study revealed that there are significant associations between rs16890979, rs3733591, rs2231142, and rs2231137 genetic variations and increased risk of male infertility. Also, these variations were associated with oligozoospermia and teratozoospermia, and sometimes with asthenozoospermia. Also, we found that four studied SNPs could be associated with a decreased level of uric acid of seminal plasma in teratozoospermia and asthenozoospermia. Bioinformatic analysis revealed that the mentioned polymorphisms could affect molecular aspects of SLC2A9 and ABCG2 genes. In this preliminary study, the rs16890979, rs3733591, rs2231142, and rs2231137 genetic variations could be considered as genetic risk factors for male infertility by interfering with the uric acid level of seminal plasma.

The influence of propolis plus Hyoscyamus niger L. against COVID-19: A phase II, multicenter, placebo-controlled, randomized trial.

The incubation period of COVID-19 symptoms, along with the proliferation and high transmission rate of the SARS-CoV-2 virus, is the cause of an uncontrolled epidemic worldwide. Vaccination is the front line of prevention, and antiinflammatory and antiviral drugs are the treatment of this disease. In addition, some herbal therapy approaches can be a good way to deal with this disease. The aim of this study was to evaluate the effect of propolis syrup with Hyoscyamus niger L. extract in hospitalized patients with COVID-19 with acute disease conditions in a double-blinded approach. The study was performed on 140 patients with COVID-19 in a double-blind, randomized, and multicentral approach. The main inclusion criterion was the presence of a severe type of COVID-19 disease. The duration of treatment with syrup was 6 days and 30 CC per day in the form of three meals. On Days 0, 2, 4, and 6, arterial blood oxygen levels, C-reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell, as well as the patient's clinical symptoms such as fever and chills, cough and shortness of breath, chest pain, and other symptoms, were recorded and analyzed. Propolis syrup with H. niger L. significantly reduces cough from the second day, relieving shortness of breath on the fourth day, and significantly reduces CRP, weakness, and lethargy, as well as significantly increased arterial blood oxygen pressure on the sixth day compared to the placebo group (p < 0.05). The results in patients are such that in the most severe conditions of the disease 80% < SpO2 (oxygen saturation), the healing process of the syrup on reducing CRP and increasing arterial blood oxygen pressure from the fourth day is significantly different compared with the placebo group (p < 0.05). The use of syrup is associated with a reduction of 3.6 days in the hospitalization period compared with the placebo group. Propolis syrup with H. niger L. has effectiveness in the viral and inflammatory phases on clinical symptoms and blood parameters and arterial blood oxygen levels of patients with COVID-19. Also, it reduces referrals to the intensive care unit and mortality in hospitalized patients with COVID-19. So, this syrup promises to be an effective treatment in the great challenge of COVID-19.

The eNOS-G894T genetic polymorphism and risk of preeclampsia: A case-control study, an updated meta-analysis, and a bioinformatic assay.

OBJECTIVES: Preeclampsia (PE) is a leading cause of maternal death worldwide and involves vascular endothelial dysfunction. The aim of this study was to investigate the association of the G894T polymorphism in the endothelial nitric oxide synthase (eNOS) gene and the risk of preeclampsia in a case-control design in an Iranian population, which was followed by a meta-analysis and an in silico approach. METHODS: In the case-control study, 300 people including 135 pregnant women with preeclampsia and 165 healthy pregnant women were included. The genotype of G894T polymorphism was determined by the PCR-RFLP method. We searched authoritative scientific databases to find eligible studies for meta-analysis. The odds ratio with a 95% confidence interval was estimated to find the strength of the association of the mentioned polymorphism with the risk of preeclampsia. In addition, the effect of G894T transversion on eNOS gene function was evaluated by some bioinformatics tools. RESULTS: Our case-control data showed that the G894T polymorphism is associated with an increased risk of preeclampsia. In the meta-analysis, 33 eligible studies were included, and the results showed that the G894T polymorphism is associated with an increased risk of preeclampsia in the overall analysis and some stratified analyses. In addition, the structural analysis showed that the G894T variant can affect the splicing process as well as the protein stability. CONCLUSIONS: Based on the results, the aforementioned polymorphism may be a risk factor for preeclampsia and could be considered a potential molecular biomarker for screening susceptible individuals.

Molecular mechanisms involved in anosmia induced by SARS-CoV-2, with a focus on the transmembrane serine protease TMPRSS2.

Since 2020, SARS-CoV-2 has caused a pandemic virus that has posed many challenges worldwide. Infection with this virus can result in a number of symptoms, one of which is anosmia. Olfactory dysfunction can be a temporary or long-term viral complication caused by a disorder of the olfactory neuroepithelium. Processes such as inflammation, apoptosis, and neuronal damage are involved in the development of SARS-CoV-2-induced anosmia. One of the receptors that play a key role in the entry of SARS-CoV-2 into the host cell is the transmembrane serine protease TMPRSS2, which facilitates this process by cleaving the viral S protein. The gene encoding TMPRSS2 is located on chromosome 21. It contains 15 exons and has many genetic variations, some of which increase the risk of disease. Delta strains have been shown to be more dependent on TMPRSS2 for cell entry than Omicron strains. Blockade of this receptor by serine protease inhibitors such as camostat and nafamostat can be helpful for treating SARS-CoV-2 symptoms, including anosmia. Proper understanding of the different functional aspects of this serine protease can help to overcome the therapeutic challenges of SARS-CoV-2 symptoms, including anosmia. In this review, we describe the cellular and molecular events involved in anosmia induced by SARS-CoV-2 with a focus on the function of the TMPRSS2 receptor.

Influence of FOXP3 gene polymorphisms on the risk of preeclampsia: a meta-analysis and a bioinformatic approach.

BACKGROUND AND AIM: Preeclampsia (PE), a multifactorial disorder, is the main cause of maternal mortality and morbidity. Genetic polymorphisms in key proteins involved in the immune system may change the risk of PE risk. In this study, we examined the association of two rs2232365 and rs3761548 common polymorphisms of the FOXP3 immune response gene with PE susceptibility by a meta-analysis which was followed by an in-silico analysis. MATERIALS AND METHODS: Through a systematic search in databases including PubMed, MEDLINE, Google Scholar, and Science Direct, we find eligible studies for meta-analysis. Some bioinformatics tools were used to detect the impact of rs2232365 and rs3761548 polymorphisms on the FOXP3 gene function. RESULTS: Our data revealed that there is a significant association between rs3761548 polymorphism and decreased risk of PE. In addition, we observed a significant association between rs2232365 and increased risk of mild preeclampsia. Also, our bioinformatic analysis showed that both rs2232365 and rs3761548 polymorphisms could affect FOXP3 gene function. CONCLUSION: Based on our findings, the rs3761548 genetic variation could be a protective factor against PE risk. While the rs2232365 polymorphism may be a genetic risk factor for mild preeclampsia. Therefore, as a preliminary study, these genetic variations could be considered molecular biomarkers for PE disorder.

Calcitriol Ameliorates Brain Injury in the Rat Model of Cerebral Ischemia-Reperfusion Through Nrf2/HO-1 Signalling Axis: An in Silico and in Vivo Study.

OBJECTIVES: Calcitriol has been revealed to exert neuroprotective effects in ischemic stroke; however, its role and the underlying mechanisms in brain injury induced by ischemia are not well known. The purpose of this study was to determine the neuroprotective effects of calcitriol pretreatment and to assess the possible neuroprotective function of nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) signalling pathway against brain ischemia/reperfusion (I/R) injury in the rat models which was followed by a bioinformatics approach. METHODS: The experimental I/R model induction was performed in male Wistar rats for 1 h followed by 23 h reperfusion. Calcitriol was administered intraperitoneally for 7 days prior to stroke. Following ischemia induction 24 h later, neurobehavioral deficits and infarction volume were examined. Oxidative stress was assessed by measurement of malondialdehyde (MDA), nitric oxide (NO) and total antioxidant capacity (TAC). The protein and mRNA expression of HO-1 and Nrf2 were determined by western blot and reverse transcription polymerase chain reaction (RT-PCR), respectively. A molecular docking approach was applied to identify the interaction value of Keap1 with calcitriol. RESULTS: Our data demonstrated that calcitriol significantly decreased infarction volume and ameliorated neurological deficits in brain I/R. MDA and NO levels were decreased and TAC level was elevated significantly after calcitriol pretreatment. Furthermore, calcitriol upregulated the expression of HO-1 and Nrf2 protein and mRNA in ischemic brain. Molecular modelling demonstrated that calcitriol could interact with the pocket of Keap1 by an appropriate binding energy. CONCLUSIONS: The results indicate that calcitriol protects the brain against I/R injury. This effect may pass through inhibition of oxidative stress and Nrf2/HO-1 pathway activation and this may arise by interaction of Keap1 and calcitriol.

Herbal therapy as a promising approach for regulation on lipid profiles: A review of molecular aspects.

Impaired lipid profile is defined as abnormal plasma levels of low-density lipoprotein, triglycerides, and total cholesterol. This disease state is associated with the development and progression of various disorders, such as diabetes mellitus, cardiovascular diseases, and acute myocardial infarction. Globally, all of these disorders are related to a significant rate of death. Therefore, finding a suitable approach for the prevention and treatment of lipid profile-related disorders is in the spotlight. Recently, herbal therapy has been considered a promising therapeutic approach for the treatment of hyperlipidemia or its related disorders due to its safety and efficacy. Hereby, we address the potential benefits of some of these herbal compounds on different aspects of lipid profile and its abnormalities with a special focus on their underlying mechanisms. Using herbal products, such as teas and mushrooms, or their derivatives, Rosmarinus officinalis Linn, Curcuma longa, Green tea, Lippia triphylla, Lippia citriodora, Plantago asiatica L, Vine tea, and Grifola frondosa have been proved to exert several therapeutic impacts on lipid profile and its related disorders, and we would provide a brief review on them in this literature.

Serum Vitamins and Homocysteine Levels in Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis.

Vitamin and homocysteine (Hcy) alternations have been associated with psychiatric disorders. The aim of this meta-analysis was to assess the association of serum vitamin and Hcy levels with obsessive-compulsive disorder (OCD). Following PRISMA protocol, we used the databases including Scopus, PubMed, Google Scholar, and Web of Science with no time restriction. Data were pooled using a random-effects model and/or fixed-effects model to estimate the standard mean difference (SMD) for evaluation of the strength of association analyses. Our data showed a significant reduction in vitamin B12 (SMD = -0.58, 95% CI = -1.08 to -0.08, p = 0.02, I2 = 65%; pheterogeneity = 0.06), vitamin E (SMD = -0.89, 95% CI = -1.23 to -0.56, p < 0.00001, I2 = 23%; pheterogeneity = 0.26), and vitamin C (SMD = -1.40, 95% CI = -2.44 to -0.36, p = 0.008, I2 = 92%; pheterogeneity < 0.0001) in OCD patients. In addition, the findings showed significantly higher levels of Hcy (SMD = 1.11, 95% CI = [0.48, 1.75], p = 0.0006, I2 = 73%; ph = 0.02) in patients compared to controls. Also, our data showed that vitamin B9 and D levels are not associated with OCD (vitamin B9: SMD = -0.23, 95% CI = -1.01 to 0.55, p = 0.56, I2 = 88%; pheterogeneity < 0.0001; vitamin D: SMD = -0.63, 95% CI = -1.41 to 0.15, p = 0.11, I2 = 88%; pheterogeneity = 0.0002). Our findings support significant impacts of Hcy and vitamin B12, E, and C levels in OCD pathogenesis. This will be important for prevention and treatment of OCD. However, further studies are recommended to elucidate more accurate conclusions.

Neutrophil-to-Lymphocyte Ratio as a Poor Prognostic Factor in Iranian COVID-19 Patients.

BACKGROUND: We aimed to accumulate evidence that suggests the potential role of neutrophil-to-lymphocyte ratio (NLR) in determining the prognostic factor for COVID-19 patients. METHODS: A cohort of COVID-19 hospitalized patients at the Ilam University of Medical Sciences was analyzed. Logistic regression models were performed to identify the potential role of NLR in determining the prognostic factor for COVID-19 patients. RESULTS: The total number of in-hospital mortality was 43/328 (13.1%). Multivariate analysis identified that there was a 26% higher risk of in-hospital death for each unit increase in NLR (Odds ratio [OR] = 1.08; 95% confidence interval [95% CI], 1.01 to 1.14; p = 0.0147). Multivariate analysis identified that there was an 8% higher risk of in-hospital death for each unit increase in NLR (Odds ratio [OR] = 1.08; 95% confidence interval [95% CI], 1.01 to 1.14; p = 0.0147). Compared with patients in the NLR < 5 group, the NLR of patients in the NLR ≥ 5 group had a 16-fold higher risk of mortality (OR = 16.04; 95% CI, 1.14 to 224.95; p = 0.0395) after adjustment for potential confounders. CONCLUSIONS: NLR is an independent risk factor of mortality COVID-19 patients.

Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management.

Infertility is a global health problem involving about 15% of couples. Approximately half of the infertility cases are related to male factors. The oxidative stress, which refers to an imbalance in levels of reactive oxygen species (ROS) and antioxidants, is one of the main causes of infertility in men. A small amount of ROS is necessary for the physiological function of sperm including the capacitation, hyperactivation and acrosomal reaction. However, high levels of ROS can cause infertility through not only by lipid peroxidation or DNA damage but inactivation of enzymes and oxidation of proteins in spermatozoa. Oxidative stress (OS) is mainly caused by factors associated with lifestyle. Besides, immature spermatozoa, inflammatory factors, genetic mutations and altering levels of sex hormones are other main source of ROS. Since OS occurs due to the lack of antioxidants and its side effects in semen, lifestyle changes and antioxidant regimens can be helpful therapeutic approaches to overcome this problem. The present study aimed to describe physiological ROS production, roles of genetic and epigenetic factors on the OS and male infertility with various mechanisms such as lipid peroxidation, DNA damage, and disorder of male hormone profile, inflammation, and varicocele. Finally, the roles of oral antioxidants and herbs were explained in coping with OS in male infertility.

Oxytocin improves ischemic stroke by reducing expression of excitatory amino acid transporter 3 in rat MCAO model.

Various molecular mechanisms are activated in neurons during ischemic stroke. Extracellular glutamate secretion into brain tissue causes neurotoxicity and brain damage. Excitatory amino acid transporter 3 (EAAT3) could remove the extracellular glutamate. Neuroprotective activity of oxytocin (OT) in ischemia of various tissues has been reported. This study investigates the neuroprotective effect of OT in an animal model of middle cerebral artery occlusion (MCAO) and the possible role of EAAT3. Transient MCAO was performed as a model of ischemic stroke in male rats and then OT was administrated intra-nasally. Infarct volume was measured by 2, 3, 5-triphenyl tetrazolium chloride staining. Nissl staining method was performed for the evaluation of neuronal cell morphology. Immunohistochemistry assay was performed to analyze the EAAT3 expression in the ischemic region. OT significantly reduced the infarct volume in the cerebral cortex and striatum after ischemia (P< .05). In addition, OT reduces the number of neurons with pyknotic nuclei that are significantly increased in the ischemic region (P< .01) Immunohistochemistry results showed that although EAAT3 expression increased after ischemia, OT therapy increased EAAT3 expression further (P< .05). Therefore, increased EAAT3 expression could be one of the neuroprotective mechanisms of OT after MCAO.

Chest computed tomography scan findings of coronavirus disease 2019 (COVID-19) patients: a comprehensive systematic review and meta-analysis.

INTRODUCTION: Numerous cases of pneumonia caused by coronavirus disease 2019 (COVID-19) were reported in Wuhan, China. Chest computed tomography (CT) scan is highly important in the diagnosis and follow-up of lung disease treatment. The present meta-analysis was performed to evaluate chest CT scan findings in COVID-19 patients. MATERIAL AND METHODS: All research steps were taken according to the Meta-Analysis of Observational Studies In Epidemiology (MOOSE) protocol and the final report was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We registered this review at the International Prospective Register of Systematic Reviews (PROSPERO, CRD42019127858). RESULTS: Forty eligible studies including 4598 patients with COVID-19 were used for meta-analysis. The rate of positive chest CT scan in patients with COVID-19 was 94.5% (95% CI: 91.7-96.3). Bilateral lung involvement, pure ground-glass opacity (GGO), mixed (GGO pulse consolidation or reticular), consolidation, reticular, and presence of nodule findings in chest CT scan of COVID-19 pneumonia patients were respectively estimated to be 79.1% (95% CI: 70.8-85.5), 64.9% (95% CI: 54.1-74.4), 49.2% (95% CI: 35.7-62.8), 30.3% (95% CI: 19.6-43.6), 17.0% (95% CI: 3.9-50.9) and 16.6% (95% CI: 13.6-20.2). The distribution of lung lesions in patients with COVID-19 pneumonia was peripheral (70.0% [95% CI: 57.8-79.9]), central (3.9% [95% CI: 1.4-10.6]), and peripheral and central (31.1% [95% CI: 19.5-45.8]). The pulmonary lobes most commonly involved were the right lower lobe (86.5% [95% CI:57.7-96.8]) and left lower lobe (81.0% [95% CI: 50.5-94.7]). CONCLUSIONS: The most important outcomes in chest CT scan of patients with COVID-19 pneumonia were bilateral lung involvement, GGO or mixed (GGO pulse consolidation or reticular) patterns, thickened interlobular septa, vascular enlargement, air bronchogram sign, peripheral distribution, and left and right lower lobes involvement. Our study showed that chest CT scan has high sensitivity in the diagnosis of COVID-19, and may therefore serve as a standard method for diagnosis of COVID-19.

The survivin molecule as a double-edged sword in cellular physiologic and pathologic conditions and its role as a potential biomarker and therapeutic target in cancer.

Survivin is a member of the family of apoptosis inhibitory proteins with increased expression level in most cancerous tissues. Evidence shows that survivin plays regulatory roles in proliferation or survival of normal adult cells, principally vascular endothelial cells, T lymphocytes, primitive hematopoietic cells, and polymorphonuclear neutrophils. Survivin antiapoptotic role is, directly and indirectly, related to caspase proteins and shows its role in cell division through the chromosomal passenger complex. Survivin contains many genetic polymorphisms that the role of some variations has been proven in several cancers. The -31G/C polymorphism is one of the most important survivin mutations which is located in the promoter region on a CDE/CHR motif. This polymorphism can upregulate the survivin messenger RNA. In addition, its allele C can increase the risk of cancers in 1.27-fold than allele G. Considering the fundamental role of survivin in different cancers, this protein could be considered as a new therapeutic target in cancer treatment. For this purpose, various strategies have been designed including the prevention of survivin expression through inhibition of mRNA translation using antagonistic molecules, inhibition of survivin gene function through small inhibitory molecules, gene therapy, and immunotherapy. In this study, we describe the structure, played roles in physiological and pathological states and genetic polymorphisms of survivin. Finally, the role of survivin as a potential target in cancer therapy given challenges ahead has been discussed.

Common gene polymorphism in ATP-binding cassette transporter A1 and coronary artery disease: A genetic association study and a structural analysis.

ATP-binding cassette transporter A1 (ABCA1) has a crucial role in removing intracellular cholesterol and plays a protective role against atherosclerosis. Therefore, genetic polymorphisms in this gene may alter the susceptibility to coronary artery disease (CAD). This study was aimed to examine the association of rs2230806 (c.1051 G > A; p.R219K) variation in the ABCA1 gene with CAD in a case-control design which was followed by a meta-analysis and in silico approach. In the case-control study, 300 subjects including 150 individuals with CAD and 150 healthy controls were recruited. The c.1051 G > A genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method. In the meta-analysis, eligible studies were collected from PubMed, Google Scholar, and ScienceDirect databases and pooled odds ratio, heterogeneity, publication bias, and sensitivity analyses were carried. Finally, some bioinformatics tools were employed to assess the impacts of p.R219K variation on ABCA1 protein structure. Our case-control examination showed a statistically significant association between c.1051 G > A genetic polymorphism and CAD risk. In addition, the meta-analysis showed reliable significant associations between c.1051 G > A transition and risk of CAD in the Caucasian population. In silico analysis showed that the p.R219K substitution could alter the secondary structure, hydrophobicity pattern, and Ramachandran plot of ABCA1. These findings elucidate that the c.1051 G > A variation could be a genetic risk factor for CAD and it could be considered as a prognostic and predictive biomarker for susceptible individuals.

Retinoic acid and/or progesterone differentiate mouse induced pluripotent stem cells into male germ cells in vitro.

Numerous reagents were employed for differentiating induced pluripotent stem cells (iPSCs) into male germ cells; however, the induction procedure was ineffective. The aim of this study was to improve the in vitro differentiation of mice iPSCs (miPSCs) into male germ cells with retinoic acid (RA) and progesterone (P). miPSCs were differentiated to embryoid bodies (EBs) in suspension with RA with or without progesterone for 0, 4, and 7 days. Then, the expression of certain genes at different stages of male germ cell development including Ddx4 (pre meiosis), Stra8 (meiosis), AKAP3 (post meiosis), and Mvh protein was examined in RNA and/or protein levels by real-time polymerase chain reaction or flow cytometry, respectively. The Stra8 gene expression increased in the RA groups on all days. But, expression of this gene declined in RA + P groups. In addition, an increased expression of Ddx4 gene was observed on day 0 in the P group. Also, a significant upregulation was observed in the expression of AKAP3 gene in the RA + P group on days 0 and 4. However, gene expression decreased in P and RA groups on day 7. The expression of Mvh protein significantly increased in the RA group on day 7. The Mvh expression was also enhanced in the P group on day 4, but it decreased on day 7, while this protein upregulated on day 0 and 7 in the RA + P group. The miPSCs have the capacity for in vitro differentiation into male germ cells by RA and/or progesterone. However, the effects of these inducers depend on the type of combination and an effective time.

Neurosteroids and their receptors in ischemic stroke: From molecular mechanisms to therapeutic opportunities.

Extensive progress has been made to understand the pathophysiology of stroke but it is still a major cause of mortality and disability worldwide. There are few strategies for the treatment of this disease and the use of thrombolytic tissue plasminogen activator is limited due to the narrow time window. However, the administration of neuroactive steroids could be considered as a potential treatment approach to decrease ischemia-induced lesions. Neurosteroids receptors play important roles in neuroprotection mediated by these hormones. Membrane and intracellular receptors are both involved in the protective effects of estrogen and progesterone on ischemic brain injury. The intracellular receptors often regulate the gene transcription while the membrane receptors act through modulation of signal transduction pathways. Besides, allopregnanolone acts as a potent positive modulator of the GABA receptor. Moreover, the neuroprotective effects of vitamin D and dehydroepiandrosterone (DHEA) are mediated through the binding to vitamin D receptor (VDR) and several intracellular and membrane receptors, respectively. Activation of VDR could affect various processes including apoptosis, calcium metabolism, oxidative stress, immune modulation, inflammation and detoxification, and DHEA can modulate neurogenesis, neuronal function, and mitochondrial oxidative capacity. The present study aimed to describe the neuroprotective roles of the aforementioned neurosteroids with a focus on their receptors against ischemic stroke.

Heat shock protein 27 as a neuroprotective biomarker and a suitable target for stem cell therapy and pharmacotherapy in ischemic stroke.

Ischemic stroke is a major common cause of death and long-term disability worldwide. Several pathophysiological events including excitotoxicity, oxidative/nitrative stress, inflammation, and apoptosis are involved in ischemic injuries. Recently, the molecular mechanisms involved in cerebral ischemia through a focus on a member of small heat shock proteins family, Hsp27, has been developed. Notably, following exposure to ischemia, Hsp27 expression in the brain could be increased rather than the normal condition and it may play an important role in neuroprotection after ischemic stroke. The neuroprotection effects of Hsp27 may arise from its anti-oxidant, anti-inflammatory, anti-apoptotic, and chaperonic properties. Moreover, some therapeutic strategies such as stem cell therapy and pharmacotherapy have been developed with Hsp27 targeting. In this review, we describe the function and structure of Hsp27 and its possible role in neuroprotection after ischemic stroke. Finally, we present current studies in stroke therapy, which focused on Hsp27 targeting.

The relationship between metabolic syndrome and increased risk of Barrett's esophagus: an updated systematic review and meta-analysis.

BACKGROUND: The relationship between metabolic syndrome (MetS) and Barrett's esophagus (BE) is still a challenging issue, and inconsistent results have been reported in different studies. Therefore, this study was conducted to determine the relationship between MetS and BE. METHODS: In this study, we followed the MOOSE protocol and results were reported according to the PRISMA guidelines. All study steps were performed independently by two authors. If necessary, the dispute was resolved by consultation with a third author. The search strategy is designed to find published studies. Comprehensive search was done in the following databases until July 2019: Cochrane Library, PubMed/Medline, Web of Science, Science Direct, EMBASE, Scopus, CINAHL, EBSCO, and Google Scholar search engine. All analyses were performed using Comprehensive Meta-Analysis Software Ver.2, while p-value lower than 0.05 was considered significant. RESULTS: In 14 studies with a sample size of 108,416, MetS significantly increased the risk of BE (OR = 1.354; 95% CI: 1.145-1.600; P < 0.001; Heterogeneity: I2 = 81.95%; P < 0.001). Sensitivity analysis by omitting one study showed that overall estimates are still robust. Subgroup analysis was significant for continent (P < 0.001) and MetS diagnostic criteria (P = 0.043), but was not significant for variables of study type (P = 0.899), study setting (P = 0.115), control groups (P = 0.671) and quality of studies (P = 0.603). The Begg (P = 0.912) and Egger's (P = 0.094) tests were not significant; therefore, the publication bias did not play a role in the results. CONCLUSION: MetS increases the risk of BE compared to control groups. The results of this study can help health practitioners by identifying a treatable risk factor for the most important risk factor for esophageal carcinoma (ie, BE). Future studies should examine whether treatment for MetS reduces the risk of BE.

Epidemiology of gastroesophageal reflux disease in Iran: a systematic review and meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD), which leads to acid reflux into the esophagus, is a common gastrointestinal disorder. Several studies have shown the prevalence of GERD in Iranian population, but their evidence is contradictory. Therefore, the present study was conducted to investigate the epidemiology of GERD in Iran. METHODS: The entire steps of this systematic review and meta-analysis were based on the MOOSE protocol, and the results were reported accordance with the PRISMA guideline. This review is registered on PROSPERO (registration number: CRD42020142861). To find potentially relevant published articles, comprehensive search was done on international online databases Scopus, Science Direct, EMBASE, PubMed/Medline, CINAHL, EBSCO, Cochrane Library, Web of Science, Iranian online databases and the Google Scholar search engine in June 2019. Cochran test and I2 index were used to assess the heterogeneity of the studies. Data were analyzed using Comprehensive Meta-Analysis software ver. 2. The significance level of the test was considered to be P <  0.05. RESULTS: The daily, weekly, monthly, and overall prevalence of GERD symptoms in Iranian population was 5.64% (95%CI [confidence interval]: 3.77-8.35%; N = 66,398), 12.50% (95%CI: 9.63-16.08%; N = 110,388), 18.62% (95%CI: 12.90-26.12%; N = 70,749) and 43.07% (95%CI: 35.00-51.53%; N = 73,189), respectively. The daily, weekly, monthly, and overall prevalence of heartburn in Iranian population was 2.46% (95%CI: 0.93-6.39%; N = 18,774), 9.52% (95%CI: 6.16-14.41%; N = 54,125), 8.19% (95%CI: 2.42-24.30%; N = 19,363) and 23.20% (95%CI: 13.56-36.79%; N = 26,543), respectively. The daily, weekly, monthly, and overall prevalence of regurgitation in Iranian population was 4.00% (95%CI: 1.88-8.32%; N = 18,774), 9.79% (95%CI: 5.99-15.60%; N = 41,140), 13.76% (95%CI: 6.18-44.31%; N = 19,363) and 36.53% (95%CI: 19.30-58.08%; N = 21,174), respectively. The sensitivity analysis for prevalence of all types GERD, heartburn and regurgitation symptoms by removing a study showed that the overall estimate is still robust. CONCLUSION: The present meta-analysis provides comprehensive and useful information on the epidemiology of GERD in Iran for policy-makers and health care providers. This study showed a high prevalence of GERD in Iran. Therefore, effective measures on GERD-related factors such as lifestyle can be among the health policies of Iran.

The regulatory role of Toll-like receptors after ischemic stroke: neurosteroids as TLR modulators with the focus on TLR2/4.

Ischemic stroke is the most common cerebrovascular disease and considered as a worldwide leading cause of death. After cerebral ischemia, different pathophysiological processes including neuroinflammation, invasion and aggregation of inflammatory cells and up-regulation of cytokines occur simultaneously. In this respect, Toll-like receptors (TLRs) are the first identified important mediators for the activation of the innate immune system and are widely expressed in glial cells and neurons following brain trauma. TLRs are also able to interact with endogenous and exogenous molecules released during ischemia and can increase tissue damage. Particularly, TLR2 and TLR4 activate different downstream inflammatory signaling pathways. In addition, TLR signaling can alternatively play a role for endogenous neuroprotection. In this review, the gene and protein structures, common genetic polymorphisms of TLR2 and TLR4, TLR-related molecular pathways and their putative role after ischemic stroke are delineated. Furthermore, the relationship between neurosteroids and TLRs as neuroprotective mechanism is highlighted in the context of brain ischemia.