Large artery atherosclerosis (LAA) is known as an important cause of ischemic stroke (IS), which is a multifactorial disorder. Many candidate genes have been proposed for IS like (TBXAS1) that plays a significant role in LAA stroke pathogenesis. This is the first study on the evaluation of the association of the five single‐nucleotide polymorphisms (SNPs) in TBXAS1 promoter region and the level of TBXAS1 transcript with large‐artery atherosclerosis stroke. Five SNPs in TBXAS1 genes were investigated in 248 patients with large‐artery atherosclerosis stroke and 199 healthy controls in Iranian population in this case‐control study through using the high‐resolution melting assay. In addition, the relationships between the selected SNPs with alteration of TBXAS1 gene expressions were investigated in terms of blood platelets through the reverse transcription‐quantitative polymerase chain reaction. Multivariate logistic analysis with adjustments indicated that rs10256282CC, rs10237429CC, and rs4590360GG genotypes were associated with large‐artery atherosclerosis stroke (adjusted odds ratio = 2.804, 2.872, and 2.432, respectively; P < 0.05, q < 0.05). Furthermore, the frequency of CACCG haplotype in the patients was greatly higher than that in the controls (OR = 1.424, 95% CI: 1.071‐1.893, P = 0.014738). In addition, TBXAS1 expression was higher in patients compared to the controls (P = 0.021), and individuals with the homozygous mutated genotypes of these SNPs showed a higher expression level compared to other genotype (P < 0.05). In total, our findings indicate a significant association of TBXAS1 gene rs10256282CC, rs10237429CC, and rs4590360GG polymorphisms with large‐artery atherosclerosis stroke susceptibility and the level of TBXAS1 expression, which was not previously reported in any population.
ObjectivesAflatoxin M1 (AFM1)-contaminated dairy products pose serious human health risks, causing liver and renal failure if consumed. They are also related to decreased milk and egg production in infected animals. This study investigated the AFM1 contamination levels in cheeses sold in Isfahan province, Iran, by enzyme-linked immunosorbent assay (ELISA).MethodsA total of 100 white cheese samples were randomly collected from supermarkets in Isfahan province and after extraction using dichloromethane were prepared for the ELISA.ResultsOf the 100 samples, 52 (52%) were contaminated by AFM1, at levels ranging from 50.2 to 424.4 ng/kg. The remaining 48% of the samples had undetectable AFM1 levels (< 50 ng/kg). Based on the standard limit set by the European Commission and Iran, 8% (8/100) of the AFM1-positive samples (with concentrations between 250.2 and 424.4 ng/kg) had levels higher than the permissible value of 250 ng/kg.ConclusionAlthough the percentage of cheese samples in Isfahan province with AFM1 levels exceeding the national permissible limit was low, the examination of cheeses and the milk used for their production is nevertheless important for ensuring public health. Furthermore, optimum storage conditions of animal feed should be ensured, and livestock nutrition must be monitored for the presence of AFM1 and other aflatoxins.
Background: Lymphotoxin-alpha (LTA), a proinflammatory cytokine, is significantly associated with the progression of atherosclerosis as an independent hazard factor for stroke. According to new genetic studies, polymorphisms in the LTA gene that influence its expression or biological function may play a role in the progress of stroke; thus, the present case-control study investigated LTA gene polymorphisms (rs909253, rs1800683 and rs2229094) and the risk of large artery atherosclerosis stroke (LAA) in an Iranian population. Methods: For 211 large artery atherosclerosis patients and 186 ischemic strokefree controls, genotypes were determined using the tetra-primer amplificationrefractory mutation system polymerase chain reaction method. Linkage disequilibrium and estimated haplotypes were analyzed using SNP Analyzer 2 software. The strength of the link between LTA gene polymorphisms (rs1800683, rs909253, and rs2229094) and the risk of stroke was determined using conditional logistic regression. Results: Analysis revealed that the patterns of the rs1800683, rs909253 and rs2229094 genotypes showed no significant difference between the LAA and control group, although the distribution of the GAT (rs1800683G, rs909253A and rs2229094T) haplotype was significantly higher in the control group (odds ratio = 0.707, 95% confidence interval = 0.53-0.942, p = 0.0355). Conclusions: Our results indicate that the GAT haplotype in LTA gene is associated with a decreased risk of LAA incidence in a northeastern Iranian population.
Recent studies have shed light on the involvement of long non-coding RNAs (lncRNAs) in the initiation and development of stroke. However, the regulatory function of many lncRNAs in large artery atherosclerosis (LAA) has not been fully elucidated. Based on the competing endogenous RNA (ceRNA) hypothesis recently proposed by Pandolfi, the present study was conducted using experimental techniques and bioinformatics to investigate the expression and regulatory function of a lncRNA involved in the development of LAA. The lncRNAs differentially expressed in stroke were obtained using meta-analysis, and one lncRNA was selected for experimental studies on patients with LAA (n = 100) and healthy controls (n = 100) using quantitative real-time polymerase chain reaction (qRT-PCR). The patients were also evaluated through meta-analysis to identify the function of the selected lncRNA, miRNAs, and mRNAs with altered expression in stroke. Finally, the experimental results and meta-analysis findings were integrated, and different functional groups were assigned. The results indicated that the level of lncRNA-RUNX1-IT1 was significantly lower in the patients with LAA compared to the healthy control subjects (p > 0.05). Logistic regression analyses revealed that the expression of lncRNA-RUNX1-IT1 was inversely correlated with LAA (P = 009, OR = 0.871, 95% CI: 0.786-0.965). In addition, a network of differentially expressed genes (DE genes) was created for miRNAs and mRNAs based on their association with lncRNA-RUNX1-IT1. Functional analysis showed that the DE genes in the network are involved in the apoptosis and alternative splicing of RNAs. The findings of the present study suggest that the downregulation of lncRNA-RUNX1-IT1 is associated with LAA development by interrupting the regulatory network of cells. The results of network analysis demonstrated that the lncRNA-RUNX1-IT1 could influence the expression of mRNAs and miRNAs involved in the apoptosis and alternative splicing of RNAs.
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