Comparison of atherogenic indices for predicting the risk of metabolic syndrome in Southwest Iran: results from the Hoveyzeh Cohort Study (HCS).

BACKGROUND: Metabolic syndrome (MetS) is a cluster of risk factors related to diabetes and cardiovascular disease (CVD). Given that early identification of MetS might decrease CVD risk, it is imperative to establish a simple and cost-effective method to identify individuals at risk of MetS. The purpose of this study was to explore the relationships between several atherogenic indices (including AIP, TyG index, non-HDL-C, LDL-c/HDL-c, and TC/HDL-c) and MetS, and to assess the ability of these indices to predict MetS. METHODS: The present cross-sectional study was conducted using baseline data from 9809 participants of the Hoveyzeh Cohort Study (HCS). MetS was defined based on the International Diabetes Federation (IDF). To examine the discriminatory abilities of each atherogenic indices in the identification of MetS, a receiver-operating characteristic curve was conducted. Logistic regression analysis was also performed to evaluate the relationship between atherogenic indices and MetS. RESULTS: All of the atherogenic indices including the TyG index, AIP, non-HDL-C, TC/HDL-c, and LDL-c/HDL-c were significantly higher in participants with MetS than in those without MetS. According to the ROC curve analysis, the TyG index revealed the highest area under the curve (0.79 and 0.85 in men and women, respectively), followed by the AIP (0.76 and 0.83 in men and women, respectively). The best cutoff values for the TyG index and AIP were 8.96 and 0.16 for men and 8.84 and 0.05 for women, respectively. The TyG index and AIP were also strongly associated with MetS. CONCLUSION: Among the 5 atherogenic indices evaluated, the TyG index and AIP were strongly related to MetS. The TyG index also demonstrated superior discriminative ability compared to other atherogenic indices in predicting MetS.

Atorvastatin's Therapeutic Potential in Atherosclerosis: Inhibiting TGF-ß-Induced Proteoglycan Glycosaminoglycan Chain Elongation through ROS-ERK1/2-Smad2L Signaling Pathway Modulation in Vascular Smooth Muscle Cells.

OBJECTIVE: According to the response-to-retention hypothesis, the inception of atherosclerosis is attributed to the deposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongated glycosaminoglycan (GAG) chains. Recent studies have elucidated a signaling pathway whereby transforming growth factor-ß (TGF-ß) promotes the expression of genes linked to proteoglycan GAG chain elongation (CHSY1 and CHST11) via reactive oxygen species (ROS) and the downstream phosphorylation of ERK1/2 and Smad2L. Atorvastatin is known to exhibit pleiotropic effects, including antioxidant and anti-inflammatory. The purpose of the present research was to ascertain the influence of atorvastatin on TGF-ß-stimulated expression of CHSY1 and CHST11 and associated signaling pathways using an in vitro model. MATERIALS AND METHODS: In this experimental study, vascular smooth muscle cells (VSMCs) were pre-incubated with atorvastatin (0.1-10 µM) prior to being stimulated with TGF-ß (2 ng/ml). The experiment aimed to evaluate the phosphorylation levels of Smad2C, Smad2L, ERK1/2, the NOX p47phox subunit, ROS production, and the mRNA expression of CHST11 and CHSY1. RESULTS: Our research results indicated that atorvastatin inhibited TGF-ß-stimulated CHSY1 and CHST11 mRNA expression. Further experiments showed that atorvastatin diminished TGF-ß-stimulated ROS production and weakened TGF-ß-stimulated phosphorylation of p47phox, ERK1/2, and Smad2L; however, we observed no effect on the TGF-ß- Smad2C pathway. CONCLUSION: These data suggest that atorvastatin demonstrates anti-atherogenic properties through the modulation of the ROS-ERK1/2-Smad2L signaling pathway. This provides valuable insight into the potential mechanisms by which atorvastatin exerts its pleiotropic effects against atherosclerosis.

Reducing Proteoglycan Synthesis and NOX Activity by ROCK Inhibitors: Therapeutic Targets in Atherosclerosis.

Atherosclerosis is a chronic inflammatory disease of the arteries characterized by the accumulation of inflammatory cells in the arterial wall. Hypertension, dyslipidemia, and hyperglycemia are major risk factors of atherosclerosis. Rho-associated protein kinase (ROCK), a serine/threonine kinase, is a downstream effector of the small GTPase RhoA. ROCK is involved in different stages of atherosclerosis. Accumulating evidence has demonstrated that ROCK signaling plays vital roles in various cellular functions, such as contraction, migration, and proliferation of smooth muscle cells. Dysregulation of the ROCK pathway is associated with atherosclerosis and hypertension. Experimental studies have shown that ROCK inhibitors may have favorable effects in ameliorating atherosclerosis. ROCK signaling has a role in proteoglycan synthesis through transactivation of the TGF-ß receptor Type I (TßRI) mediated by G-protein-coupled receptor (GPCR) agonists (endothelin-1, angiotensin II and …), and ROCK inhibitors could decrease proteoglycan synthesis and atherosclerotic plaque formation. Based on the hypothesis that targeting ROCK pathway may be effective in ameliorating atherosclerosis, we suggest that ROCK inhibitors may have a potential therapeutic role in inhibition or slowing atherogenesis. However, for this hypothesis more research is needed.

Genetic polymorphisms in DNA repair genes and hepatocellular carcinoma risk.

Hepatocellular carcinoma (HCC) is one of the most frequent types of tumors worldwide. Its occurrence and development have been related to various risk factors, such as chronic infection with hepatitis B or C viruses and alcohol addiction. DNA repair systems play a critical role in maintaining the integrity of the genome. Defects in these systems have been related to increased susceptibility to various types of cancer. Multiple genetic polymorphisms in genes of DNA repair systems have been reported that may affect DNA repair capacity (DRC) and modulate risk to cancer. Several studies have been conducted to assess the role of polymorphisms of DNA repair genes on the HCC risk. Identifying these polymorphisms and their association with HCC risk may help to improve prevention and treatment strategies. In this study, we review investigations that evaluated the association between genetic polymorphisms of DNA repair genes and risk of HCC.

The Effect of Differentially Designed Fusion Proteins to Elicit Efficient Anti-human Thyroid Stimulating Hormone Immune Responses.

The production of human thyroid stimulating hormone (hTSH) immunoassays requires specific antibodies against hTSH which is a cumbersome process. Therefore, producing specific polyclonal antibodies against engineered recombinant fusion hTSH antigens would be of great significance. The best immunogenic region of the hTSH was selected based on in silico analyses and equipped with two different fusions. Standard methods were used for protein expression, purification, verification, structural evaluation, and immunizations of the white New Zealand rabbits. Ultimately, immunized serums were used for antibody titration, purification and characterization (specificity, sensitivity and cross reactivity). The desired antigens were successfully designed, sub-cloned, expressed, confirmed and used for in vivo immunization. Structural analyses indicated that only the bigger antigen has showed changed 2 dimensional (2D) and 3D structural properties in comparison to the smaller antigen. The raised polyclonal antibodies were capable of specific and sensitive hTSH detection, while the cross reactivity with the other members of the glycoprotein hormone family was minimum and negligible. The fusion which was solely composed of the tetanus toxin epitopes led to better protein folding and was capable of immunizing the host animals resulting into high titer antibody. Therefore, the minimal fusion sequences seem to be more effective in eliciting specific antibody responses.

The Distribution of Hepatitis C Virus Genotypes in Middle Eastern Countries: A Systematic Review and Meta-Analysis.

CONTEXT: The hepatitis C virus (HCV) is classified into seven genotypes and more than 100 subtypes. The treatment regimen, duration and efficacy of HCV therapy may vary according to the HCV genotype. Therefore, the HCV genotype should be determined prior to antiviral therapy. The objective of the current study was to review systematically all studies reporting the distribution of HCV genotypes in the countries that make up the Middle East. EVIDENCE ACQUISITION: Articles were identified by searching electronic databases, including Scopus, PubMed and Google scholar, with timeline limits (articles published between 1995 and 2016). We carried out a systematic search regarding the distribution of HCV genotypes in Middle Eastern countries. RESULTS: A total of 579 studies were identified by the electronic search. Of these, a total of 187 were identified as eligible papers including 60,319 patients who were meta-analyzed for pooled distribution of HCV genotypes. In Turkey, Israel, Cyprus, and Iran, genotype 1 was the most prevalent HCV genotype with rates of 82% (95% CI, 82%-83%), 68% (95% CI, 67%-69%), 68% (95% CI, 59%-77%), and 55% (95% CI, 54%-55%), respectively. In Egypt, Iraq, Saudi Arabia, and Syria, HCV genotype 4 was the most common genotype with rates of 86% (95% CI, 85%-88%), 60% (95% CI, 56%-64%), 56% (95% CI, 54%-55%), and 57% (95% CI, 54%-61%), respectively. On the basis of adjusted data, HCV genotype 4 was the most prevalent genotype in the Middle East region, with a rate of 74.7% (95% CI, 73.4%-76%), followed by genotype 1 at 15.1% (95% CI, 14.1%-16%). CONCLUSIONS: Our results showed that HCV genotype 4 is the most prevalent genotype in the Middle East region. However, HCV genotype 1 is the most prevalent among non-Arab countries in the region including Turkey, Iran, Cyprus, and Israel.