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The triglyceride glucose (TyG) index and triglyceride/high lipoprotein density cholesterol (TG/HDL-C) are two important risk markers to evaluate the insulin resistance and cardiovascular diseases (CVDs). To assess the association between TG/HDL-C and TyG index and CVDs. The Mashhad stroke and heart association disorder cohort study started in 2010 and has been continued until 2020. During 6-year follow-up of 9704 participants, 235 events including 118 acute coronary syndrome (ACS), 83 chronic coronary syndrome, 27 myocardial infarction, and 27 cardiac death were confirmed. SPSS software (version 21) was used for statistical analysis and figures were drawn by GraphPad Prism 6 software. The prevalence of ACS and cardiac death were higher in the fourth quartile of serum TG/HDL-C (>4.43) and higher prevalence of ACS was considered in subjects classified in the fourth quartile of TyG index (>8.98). A high TyG index was associated with an increased risk of ACS and cardiac death [1.362 (95% confidence interval [CI]: [1.013-1.831]) and 2.3 (95% CI: [1.247-4.241])] respectively; based on Cox regression analysis elevated TyG and TG/HDL-C increased the chance of CVD by [1.634 (95% CI: 1.304-2.047) and 1.068 (95% CI: 1.031-1.105)], respectively. Our results strongly showed that TyG index and TG/HDL-C are independent risk factors for incident CVD, suggesting that TyG index and TG/HDL-C may be as an important unique biomarker for predicting CVD outcomes and progression., (© 2022 International Union of Biochemistry and Molecular Biology.)

A randomized clinical trial high-density lipoprotein (HDL) cholesterol uptake capacity (CUC) is reduced in patients with metabolic syndrome (MetS). We have assessed the effect of crocin supplementation on HDL CUC in patients with MetS. Forty-four subjects with MetS were randomly allocated to one of two groups: one group received placebo and the other group received crocin at a dose of 30 mg (two tablets of 15 mg per day) for 8 weeks. Serum biochemical parameters were measured using an AutoAnalyzer BT3000 (BioTechnica). The modified CUC method is a cell free, simple, and high-throughput assay that used to evaluate HDL CUC of serum samples. The decision tree analysis was undertaken using JMP Pro (SAS) version 13. The mean age of the crocin and placebo groups were 38.97 ± 13.33 and 43.46 ± 12.77 years, respectively. There was a significant increase in serum HDL CUC in the crocin group compared to that of the placebo group in patients with MetS (p-value< 0.05). The decision tree analysis showed that serum HDL functionality was more important variable than HDL-C level in predicting patients with hypertension at baseline (p-value < 0.05). Crocin administration (30 mg for a period of 8 weeks) was found to improve serum HDL CUC in patients with MetS. TRIAL REGISTRATION: IRCT2013080514279N1., (© 2021 International Union of Biochemistry and Molecular Biology.)

Vitamin D supplementation has been shown to prevent vitamin D deficiency, but various factors can affect the response to supplementation. Data mining is a statistical method for pulling out information from large databases. We aimed to evaluate the factors influencing serum 25-hydroxyvitamin D levels in response to supplementation of vitamin D using a random forest (RF) model. Data were extracted from the survey of ultraviolet intake by nutritional approach study. Vitamin D levels were measured at baseline and at the end of study to evaluate the responsiveness. We examined the relationship between 76 potential influencing factors on vitamin D response using RF. We found several features that were highly correlated to the serum vitamin D response to supplementation by RF including anthropometric factors (body mass index [BMI], free fat mass [FFM], fat percentage, waist-to-hip ratio [WHR]), liver function tests (serum gamma-glutamyl transferase [GGT], total bilirubin, total protein), hematological parameters (mean corpuscular volume [MCV], mean corpuscular hemoglobin concentration [MCHC], hematocrit), and measurement of insulin sensitivity (homeostatic model assessment of insulin resistance). BMI, total bilirubin, FFM, and GGT were found to have a positive relationship and homeostatic model assessment for insulin resistance, MCV, MCHC, fat percentage, total protein, and WHR were found to have a negative correlation to vitamin D concentration in response to supplementation. The accuracy of RF in predicting the response was 93% compared to logistic regression, for which the accuracy was 40%, in the evaluation of the correlation of the components of the data set to serum vitamin D., (© 2021 International Union of Biochemistry and Molecular Biology.)

Some reports indicated that Vitamin D may improve glycaemia indices in diabetic patients. The aim of this systematic and meta-analysis was to evaluate effects of Vitamin D fortification on indices of glycemic control. Six databases (PubMed/Medline, ISI Web of Knowledge, Cochrane Library, Science Direct, Scopus, and Google Scholar) were searched, for randomized controlled trials that were published up to September 2018 and that compared the effect of Vitamin D-fortified food versus regular diet in relation to glycemic control. Of the 4,379 studies originally found, 11 articles remained to be assessed for meta-analysis. Vitamin D fortification was associated with a significant improvement in fasting serum glucose (mean difference [MD]: -2.772; 95% confidence interval [CI]: -5.435 to -0.109) and fasting serum insulin (MD: -2.937; 95% CI: -4.695 to -1.178) in patients with Type 2 diabetes mellitus. A diet with food enriched with Vitamin D was associated with a significant improvement in homeostatic model assessment of insulin resistance (MD: -1.608; 95% CI: -3.138 to -0.079) but was not associated with a significant reduction in hemoglobin A1C (MD: 0.034; 95% CI: -0.655 to 0.069). This meta-analysis indicates that Vitamin D fortification improves indices of glycemic control. Hence, food fortified with Vitamin D may be of potential therapeutic value in diabetic patients, as an adjuvant therapy., (© 2020 International Union of Biochemistry and Molecular Biology.)

Familial combined hyperlipidemia (FCHL) is a common genetic disorder characterized by increased fasted serum cholesterol, triglycerides, and apolipoprotein B-100. Molecular genetic techniques such as next generation sequencing have been very successful methods for rare variants finding with a moderate-to large effect. In this study, we characterized a large pedigree from MASHAD study in northeast Iran with coinheritance of FCHL and early-onset coronary heart disease. In this family, we used whole-exome sequencing and Sanger sequencing to determine the disease-associated gene. We identified a novel variant in the LPL gene, leading to a substitution of an asparagine for aspartic acid at position 151. The D151N substitution cosegregated with these characters in all affected family members in the pedigree but it was absent in all unaffected members in this family. We speculated that the mutation D151N in LPL gene might be associated with FCHL and early-onset coronary heart disease in this family. However, the substantial mechanism requires further investigation., (© 2019 International Union of Biochemistry and Molecular Biology.)

Cardiovascular disease (CVD), one of the main mortality causes worldwide is considered to be affected by general oxidative stress and inadequacy antioxidant system. Superoxide dismutase 1 (SOD1), a cytosolic antioxidant enzyme has a key role in neutralizing the excessive prooxidant by scavenging the super oxide anions. SOD1 polymorphic variants exhibit the altered activity properties. In the current study, we are aimed to investigate the association between the SOD1 polymorphism and CVD prevalence. A 6-years case control follow up study was designed to genotype the 526 participants (311 controls and 215 cases) for studying the 50 bp INS/DEL polymorphism at SOD1 promoter gene and analyze their blood lipid profile and anthropometric characteristics. Among the two possible alleles of the SOD1 gene (Wild [W] and Mutant [M]) the meaningful association was detected between the Mutants' frequency and the prevalence of CVD patients (p-value <.001). The W and M allele refer to inserted and deleted 50 bp in the polymorphic site of the SOD1 promoter, respectively. The WM and MM genotypes' frequency which indicate the wild heterozygotes and Mutant homozygotes, respectively, were significantly correlated with the prevalence of cardiovascular disease (p-value <.001). The present study has the potential to introduce the 50 bp INS/DEL polymorphism of SOD1 genotyping as a novel unique diagnostic approach for screening the high risk CVD., (© 2019 International Union of Biochemistry and Molecular Biology.)

Vitamin D (VitD) supplementation is an inexpensive and effective approach for improving VitD insufficiency/deficiency. However, the response to supplementation, with respect to the increase in serum 25(OH)D level varies between individuals. In this study, we have assessed the factors associated with the response to VitD supplementation using a decision-tree algorithm. Serum VitD levels, pre- and post-VitD supplementation was used as the determinant of responsiveness. The model was validated by constructing a receiver operating characteristic curve. Serum VitD at baseline levels was at the apex of the tree in our model, followed by serum low-density lipoprotein cholesterol and triglyceride, age, waist-hip ratio, and high-density lipoprotein cholesterol. Our model suggests that these determinants of responsiveness to VitD supplementation had sensitivity, specificity, and accuracy, 59.4, 75.8 and 69.3%, respectively. The decision tree model appears to be a relatively accurate, specific, and sensitive approach for identifying the factors associated with response to VitD supplementation., (© 2019 International Union of Biochemistry and Molecular Biology.)

The red blood cell distribution width (RDW) is an index of the heterogeneity of circulating red blood cell size, which along with other standard complete blood count (CBC) parameters are used to identify hematological system diseases. Besides hematological disorders, several clinical studies have shown that an increased in the RDW may be associated with other diseases including acute pancreatitis, chronic kidney disease, gastrointestinal disorders, cancer, and of special interest in this review, cardiovascular disease (CVD). The diagnostic and prognostic value of RDW in different CVD (acute coronary syndrome, ischemic cerebrovascular disease, peripheral artery disease, atrial fibrillation, heart failure, and acute ischemic stroke) has been reviewed in this article, to provide an understanding how its measurement may be applied to improve the management of these conditions., (© 2019 International Union of Biochemistry and Molecular Biology.)

High-density lipoprotein (HDL) is thought to be protective against cardiovascular disease (CVD), and HDL dysfunction is considered to be a risk factor for CVD. It is unclear whether there is an association between Human T lymphotropic virus type 1 (HTLV1) infection and CVD risk. We have assessed HDL lipid peroxidation (HDLox) as a marker of HDL dysfunction and CVD risk in a subgroup of the MASHAD cohort study. One hundred and sixty two individuals including 50 subjects positive for HTLV1 infection and 112 individuals negative for HTLV1 infection were recruited. Anthropometric and biochemical parameters including serum hs-CRP, fasted lipid profile (HDL-C, LDL, triglycerides, and cholesterol), and fasting blood glucose were determined. Serum HDLox was also measured in the study participants. Multivariate analyses were used to evaluate the association between serum HDLox and HTLV1 infection. None of the traditional CVD risk factors were associated with HTLV1 infection, including serum HDL-C. However, serum HDLox was independently associated with the presence of HTLV1 infection. Logistic regression analysis showed that subjects who were positive for HTLV1 infection were also significantly more likely than uninfected individuals to have higher HDLox (odds ratio 9.35, 95%CI: 3.5-24.7; P < 0.001). HDLox was increased approximately 20% (P < 0.001) in infected subjects compared to the uninfected group. Serum HDLox is a marker of CVD risk factor and increased in individuals affected by HTLV1 infection compared to healthy subjects. © 2019 BioFactors, 45(3):374-380, 2019., (© 2019 International Union of Biochemistry and Molecular Biology.)

Limited studies have examined the effects of vitamin D on liver enzymes in patients with liver disease but none has explored its effects in the healthy subjects. The aim of present study was to evaluate the effects of a high dose vitamin D supplementation on measures of liver function. A total of 988 adolescent girls were recruited; all were assessed for liver function tests (LFTs) including alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (ϒGT), alkaline phosphatase (ALP), total bilirubin, direct bilirubin, albumin, and total protein before and after supplementation with 50,000 IU cholecalciferol perls. Significant reductions were observed for AST, ALT, direct bilirubin, total bilirubin, LDH, and ϒGT at the end of supplementation, only in the group with abnormal reference value. Serum levels of total protein and albumin were higher at the end of follow up in the group with abnormal value. No significant change was obtained for LFTs in the group with normal value. Our findings suggest that vitamin D supplementation may improve markers of liver function in adolescents with abnormal LFTs. More randomized controlled trial with longer follow-up time will be required. © 2019 BioFactors, 45(3):335-342, 2019., (© 2019 International Union of Biochemistry and Molecular Biology.)

Obesity is an important feature of the metabolic syndrome and is associated with an increased risk of type 2 diabetes mellitus, cardiovascular disease, and some cancers. The aim of this study was to determine the relationship between body fat percentage and an imbalance of the prooxidant/antioxidant balance (PAB), serum superoxide dismutase (SOD1) and inflammation (serum hs-CRP) and increase risk of metabolic syndrome and diabetes mellitus. In this study, 9154 individuals were recruited as part of the Mashhad Stroke and Heart Association Disorder (MASHAD) study. Subjects were categorized into two groups according to body fat percentage as defined >25% in male and > 30% in female, according to gender. Biochemical factors, including serum PAB, SOD1, and hs-CRP were measured in all subjects. SPSS version 18 was used for statistical analyses for all. GraphPad Prism 6 for figures was used. Of total number of subjects (9154), 6748 (73.7%) were found to have a high body fat (BF) percentage. Serum hs-CRP and PAB were significantly higher in individuals with a high BF percentage (P < 0.05) but SOD1 was not significantly different between the two groups (P > 0.05). BF percentage, serum PAB and serum hs-CRP were significantly higher in individuals with metabolic syndrome and diabetes versus those without metabolic syndrome and diabetes mellitus (P < 0.05), however serum SOD1 was significantly lower in individuals with metabolic syndrome (P < 0.005). Oxidative stress and inflammation are two factors that may link the presence of high BF percentage with the development of metabolic syndrome, diabetes, and cardiovascular disease. © 2018 BioFactors, 45(1):35-42, 2019., (© 2018 International Union of Biochemistry and Molecular Biology.)

Hematological parameters have emerged as independent determinants of high serum concentrations of uric acid (UA) and predictive factors in the evaluation of the total cardiovascular risk in patients with essential hypertensive. Here, we have investigated the possible relationships between hematological factors and serum uric acid levels in hypertensive patients recruited as part of Mashhad Stroke and Heart Atherosclerotic Disorders cohort study. Two-thousand three-hundred and thirty-four hypertensive individuals were recruited from this cohort and these were divided into two groups; those with either high or low serum UA concentrations. Demographic, biochemical, and hematological characteristics of population were evaluated in all the subjects. Logistic-regression analysis was performed to determine the association of hematological parameters with hypertension (HTN). Of the 2334 hypertensive subjects, 290 cases had low UA, and 2044 had high serum UA concentrations. Compared with the low UA group, the patients with high serum UA, had higher values for several hematological parameters, whilst platelet counts (PLT) were lower. Multiple linear regression analysis showed that PLT and serum high sensitivity-c reactive protein (hs-CRP) were correlated with serum UA level. Stepwise multiple logistic regression model confirmed that platelet distribution width (PDW) and gender were independent determinant of a high serum UA. PDW and PLT appear to be independently associated with serum UA level in patients with HTN. © 2018 BioFactors, 44(6):532-538, 2018., (© 2018 International Union of Biochemistry and Molecular Biology.)

There is persuasive evidence that oxidative stress and inflammation are features of the metabolic syndrome (MetS). We have investigated the relationship between serum pro-oxidant-antioxidant balance (PAB), serum uric acid, and high sensitive C-reactive protein (hs-CRP) in 7,208 participants from the MASHAD study cohort, who were categorized as having MetS, or not, using International Diabetes Foundation (IDF) criteria. Serum hs-CRP was measured by Polyethylene glycol (PEG)-enhanced immunoturbidimetry method using an Alycon analyzer (ABBOTT, Chicago, IL, USA). A colorimetric method was used to determine serum PAB. Serum PAB values were significantly higher in the individuals with MetS compared to those without (P < 0.001). Furthermore, there was a step-wise increase in mean serum PAB concentrations as the number of components of the MetS increased. The combination of features of MetS had different association with serum PAB and hs-CRP. Multiple linear regression analysis showed that body mass index (BMI, B = 2.04, P < 0.001), physical activity level (PAL, B = 18.728, P = 0.001), serum uric acid (B = -1.545, P = 0.003), and serum C-reactive protein (B = 0.663, P < 0.001) were associated with serum PAB in individuals with MetS. Multiple logistic regression analysis showed that serum PAB (B = 0.002, P < 0.001, CI = 1.001-1.003), serum C-reactive protein (B = 0.007, P < 0.015, CI = 1.001-1.013), and serum uric acid (B = 0.207, P < 0.001, CI = 1.186-1.277) were all significantly associated with MetS. Serum PAB was strongly associated with serum uric acid and serum hs-CRP. Moreover, serum PAB as well as serum uric acid and serum hs-CRP were independently associated with MetS. Individual features of MetS were also associated with serum hs-CRP and PAB. © 2018 BioFactors, 44(3):263-271, 2018., (© 2018 International Union of Biochemistry and Molecular Biology.)