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Statins are inhibitors of β-hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase (HMGCR). They are used in patients with cardiovascular risk and/or suffering with cardiovascular disease. In addition to their efficient lipid-lowering effects, statins exhibit independent so called pleiotropic effects potentially affecting several immune response properties including immune cell activation, migration, cytokine generation, immune metabolism, and survival. Statins also regulate innate and acquired immunity. The focus of this review is to highlight the role of statins in modulating the function and differentiation of various blood cells. Given the proposed wider application of these medicines and their potentially important advantages in treatment of inflammatory and autoimmune disorders, more studies are needed with special focus on the molecular targets of statins included in regulating the immune response. [ABSTRACT FROM AUTHOR]

Introduction: Serum vitamin D levels are related to a wide spectrum of factors including low sunlight exposure, high oxidative stress, low physical activity and sleep disorders. In this paper we are going to investigate the most crucial parameters associated with serum vitamin D levels in survey of ultraviolet intake by nutritional approach (SUVINA) study with a data mining approach. Material and Methods: Data including demographic, anthropometric, clinical and laboratory information were extracted from the SUVINA dataset comprising 289 subjects who were enrolled into our study. The XGBoost algorithm was used to define the most important features related to vitamin D level in our population. Results: Applying XGBoost modeling for vitamin D level showed that the presented scheme can determine the most important determinants of serum vitamin D level with an accuracy of 91%. Pro-oxidant anti-oxidant balance (PAB), body fat percentage, physical activity level (PAL), age, restless leg syndrome (RLS), and dietary inflammatory index (DII) density were the most important variables correlated with vitamin D deficiency. Conclusion: Using XGBoost and with an accuracy of more than 90%, we showed that the six most important risk factors for vitamin D deficiency are PAB, PAL, age, body fat percentage, RLS and DII density, respectively. [ABSTRACT FROM AUTHOR]

Introduction: The development of type 2 diabetes mellitus (T2DM) is associated with lifestyle factors, including dietary patterns. A diet rich in macro- and micronutrients has been reported to reduce the risk of T2DM. Therefore, this study aimed to identify the dietary factors most closely associated with T2DM in subjects within the MASHAD cohort using a decision tree algorithm. Methods: This cross-sectional study was conducted on 9704 individuals from the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD), of whom 5936 participants completed a 24h dietary recall questionnaire. Macronutrients and micronutrients were estimated using Diet Plan 6 software. A decision tree algorithm was utilized to evaluate the most crucial dietary nutrient intakes concerning T2DM. Results: The algorithm showed a high specificity (81.34%) but low sensitivity (34.21%), which could predict T2DM with a low-to-moderate diagnostic ability (AUC=0.58). Based on the decision tree, eight features, including dietary potassium, total sugar, sucrose, riboflavin, thiamin, sodium, total nitrogen, and magnesium, were T2DM’s most critical dietary components. Conclusion: Based on the results, consuming sugar, salt, and vitamin B was the most critical related dietary intake to T2DM. Dietary interventions may be a cost-effective strategy for preventing T2DM. [ABSTRACT FROM AUTHOR]

Introduction: It has been shown that angioplasty and endovascular stent deployment, used after coronary revascularization, are associated with an inflammatory response. Inflammation has a key role in the complications of atherosclerotic plaque, coronary artery disease (CAD) and in-stent restenosis (ISR). The objectives of the present study was to investigate serum levels of 12 pro/anti-cytokines and growth factors and their relationship with restenosis. Methods: A total of 244 subjects were recruited in current study including unrelated patients who previously underwent coronary stent implantation (between 2014 and 2017) and were subsequently indicated for coronary angiography. According to angiography results patients were allocated into two groups: cases with stenosis more than 50% within the stent (N=79) and controls with stenosis less than 50% within the stent (N=165). Serum was separated by centrifuging the blood for 15 min at 1000 rpm. Serum cytokines levels including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, MCP-1, EGF, and VEGF were measured using an EV 3513 cytokine biochip array (Randox Laboratories, Crumlin, UK). Results: The mean age of the NISR and ISR groups were 62.47±9.2 and 59.49±8.48 years, respectively. The diabetes frequency was significantly higher in the ISR group (55.1%) compared with NISR group (30.9%) (p<0.001). There was no significant difference in levels of cytokines between the two groups (p>0.05). Conclusions: The results showed that serum levels of pro/anti-inflammatory cytokines and growth factors did not have a significant difference between NISR and ISR study groups. [ABSTRACT FROM AUTHOR]

Introduction: Depression, anxiety, and stress have been shown to be associated with quality of life and sleep quality. This association did not examine separately in men and women. In the present study, we aim to examine the association between depression, anxiety and stress with RLS, Epworth, insomnia, apnea, PSIQ and QoL by gender in Mashhad-study data. Methods: A total of 289 individuals (143 male and 146 female) aged 50-30 years old who completed the SUVINA study. They completed the Epworth sleepiness scale (ESS), Pittsburg sleep quality index (PSQI) and quality of life (QoL). For statistical analysis, SPSS software was used for data analysis and p value 0.05<0 was considered significant. Results: Depression scores were correlated with higher scores for RLS, ESS, insomnia, and PSQI in men but inversely related to QoL (P < 0.05). RLS and PSQI was positively correlated with anxiety in women, and subjects without anxiety had lower mean of RLS and PSQI scores than the other anxiety groups (P < 0.05 for both). QoL was conversely associated with anxiety in women. Stress was related with higher scores of RLS, ESS, insomnia and PSQI in men (all P <0.05). Conclusion: OlderAlthough scores for depression, anxiety and stress were higher in women compared to men, the association of depression, anxiety and stress with RLS, quality of life and sleep quality varies between genders and unlike our expectation these disorders were more highly correlated with RLS, QoL and sleep quality in men. [ABSTRACT FROM AUTHOR]

Introduction: Metabolic syndrome (MetS) is comprised of a clustering of various cardiovascular risk factors that can also affect bone health. We aimed the associations between MetS and bone mineral density (BMD) and trabecular bone score (TBS) in subjects with abdominal adiposity. Methods: Individuals with body mass index less than 25 kg/m2 were enrolled from the SUVINA study and allocated into two groups according criteria of IDF for metabolic syndrome. TBS T-score and Z/T score of fore skeletal region were measured using dual-energy X-ray absorptiometry (DXA). SPSS software was used for statistical analysis and p value 0.05<0 was considered significant. Results: DXA measurements were made in 201 participants, of whom 75 had MetS and 126 did not. Scores related to the neck of femur and total femur, radius Z-score and TBST-score were lower in subjects with MetS (all P<0.05). Subjects with FBG=100 had lower TBST-score (p < 0.05). SBP=130 and DBP=85 in subjects, led to the lower TBST-score, and lumbar T-score (both P < 0.05). Subjects with (LDL-C=160 mg/dl) had lower TBST-score, neck of femur Z score, and total femur T/Z scores (all P < 0.05). TBST-score and scores related to neck of femur, and total femur were lower in participants with serum cholesterol=200 mg/dl (P < 0.05). Conclusion: MetS is negatively associated with TBS and BMD scores. Higher levels of LDL-C and cholesterol were the most associated factors related to TBST-score decrease. The neck of femur was the most vulnerable skeletal against the MetS components increment. [ABSTRACT FROM AUTHOR]

Introduction: The Coronavirus Disease 2019 (COVID-19) outbreak is still an ongoing problem affecting people's well-being globally. It is known that malnutrition is an important determinant of immune function, leading to an increased risk of infection and severity of diseases. The aim of this study was to characterize the relationship between macronutrients and micronutrients and this viral infection. Methods: This study was a historical cohort including 6539 subjects (57.2% females, 42.8% males) from the Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study. Dietary intakes were assessed using a 65-item validated food frequency questionnaire (FFQ). Data on COVID-19 diagnosis was collected from online health records of patients available in the Sina health information system from the onset of the disease to the end of July 2020. COVID-19 diagnosis has been confirmed using a lung spiral CT scan or PCR laboratory test. SPSS software (Version 20) was used for the analysis of data. Results: A total of 154 subjects including 85 men (55.2%) and women (44.8%) were infected with COVID-19. Body mass index (p=0.03) and waist circumference (p=0.01) of the patients along with the protein (p=0.02), total N2 (p=0.02), calcium (p=0.02) and thiamin (p=0.04) content of their diet was significantly associated with COVID-19. After multivariate analysis, dietary calcium remained the only dietary factor that predicted COVID-19 infection (OR=0.94, 95%CI [0.87-0.99], p value=0.04). Conclusion: Our findings indicated that prevalence of COVID-19 may be affected by dietary macronutrients and micronutrients. According to our data, increased calcium intake can reduce the prevalence of COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: In-stent restenosis (ISR) is an unfavorable outcome that occurs in patients after coronary stenting. Use of drugs such as statins as well as drug-eluting stents has only been partially effective in reducing the rate of ISR. Since low high-density lipoprotein cholesterol (HDL-C) concentration is a pivotal cardiovascular disease risk factor, this study aimed to evaluate the compositional and functional alterations of HDL in individuals with ISR. Material and methods: This case-control study included 21 ISR, 26 non-ISR (NISR), 16 angiography-negative, and 18 healthy subjects. Serum HDL2 (d: 1.063-1.125 g/ml) and HDL3 (d: 1.125-1.210 g/ml) subfractions were extracted from each subject using sequential ultracentrifugation. The capacity of HDL to efflux cellular cholesterol from lipid-loaded macrophages as well as to take up free cholesterol (FC) from triglyceride-rich lipoproteins (TGRLs) during lipolysis was assessed. Results: No difference was found in the HDL2 and HDL3 content of free cholesterol and total protein among the groups. The NISR group showed lower triglyceride content in HDL2 and higher phospholipid content in HDL3 relative to healthy subjects. Strong positive correlations were found between the cholesterol efflux capacity (CEC) of HDL2 and its phospholipid content in the healthy (r = 0.50), angiography-negative (r = 0.55) and ISR (r = 0.52) groups. The capacity of apolipoprotein B (apoB)-depleted serum to take up free cholesterol was not different among the groups. Conclusions: Despite some compositional alterations, the capacity of HDL to efflux cholesterol from lipid-loaded macrophages as well as to take up free cholesterol from TGRLs during lipolysis was not associated with ISR in this study. [ABSTRACT FROM AUTHOR]

Background: Heat shock protein 27 (HSP27) is found in several cell types of adults, such as cardiomyocytes, and endothelial cells. It is expressed in response to different cellular stress conditions. HSP27 decreases the levels of reactive oxygen species (ROS) and dyslipidemia is closely associated with increased endothelial production of reactive oxygen species (ROS). Objective: Higher serum HSP27 antigen and anti-HSP27 antibodies have been reported in patients with unstable angina and myocardial infarction Methods: This population-based case-control study was conducted in 2018. We investigated serum anti-HSP27 antibody titers in all participants with dyslipidemia from the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study (n=8141) and those who were healthy in terms of dyslipidemia (n=1637) using an in-house enzymelinked immune sorbent assay (ELISA) in individuals with dyslipidemia. Findings: Anti-HSP27 titers were significantly lower in individuals with dyslipidemia compared to people without dyslipidemia (P=0.036). Conclusion: Our results revealed that the anti-HSP27 antibody titer was lower in the participants with dyslipidemia than in the negative group. However, there may be a confounding effect of drug therapy. In a subgroup of dyslipidemic subjects, we observed lower anti-HSP27 antibody titers in patients treated with some drugs (statins or corticosteroids, non-steroidal anti-inflammatory drugs [NSAIDs], or anti-diabetic and antihypertensive) compared to subjects untreated with these drugs. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes (DM) is a type of metabolic disorder that its types are generated by collectingof genetic and environmental risk agents. Here, the association between HSPB1 polymorphism as a genetic risk factor and DM was investigated. Methods: Total 690 participants from MASHAD cohort study population were recruited into the study. Anti-HSP-27level was assessed followed by genotyping using Taqman®-probes-based assay. Anthropometric, demographic and hematological/biochemical characteristics were evaluated. Kaplan-Meier curves were utilized, while logistic regression models were used to assess the association of the genetic variant with clinical characteristics of population. Results: Finds was shown there are meaningful differences among groups of age, height, waist circumference, systolic blood pressure, FBG,TG, HDL-C, and hs-CRP, and was no big -significant difference between theexists in different HSP27 SNP in the two studied groups (with and without DM), also was no remarkable relation between genetic forms of HSPB1and T2DM. This investigation was the first research that analyzed the relationship between the genetic type of the HSPB1 gene (rs2868371) and Type 2 diabetes (DM2). In our population, the CC genotype (%68.1) had a higher prevalence versus GC (%26.6) and GG (%5.3) genotypes and the data shown that no genetic difference of HSPB1 gene polymorphism (rs2868371) was related with DM2. Conclusion: HSPB1 polymorphism, rs2868371, was not associated with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

This study investigates the effect of the nanostructure of squalene in the form of microemulsion on COVID-19 patients. In this blinded clinical trial, a comparison was made between the efficacy of squalene treatment and controls. A total of 30 COVID-19 patients admitted to the emergency department, and the infection ward was equally allocated to case (n = 15) and control (n = 15) groups according to their age and underlying diseases. The baseline characteristics of subjects, including age, gender, time of treatment onset, underlying condition, white blood cells count, and lymphocyte count were similar (p < 0.05). Baseline laboratory tests and computed tomography (CT) scans were performed for the study groups. The treatment group received 5 mg of intravenous squalene twice a day and standard treatment for 6 days, while controls received only standard treatment. After 6 days of treatment, clinical and CT scan changes were evaluated and compared in intervention and control groups. The need for oxygen therapy (p = 0.020), 2 days of no fever (p = 0.025), cough alleviation (p = 0.010), and lung high-resolution computed tomography improvement (p = 0.033) were significantly different between cases and controls within 7 days of admission. No adverse effects were observed in the treatment group. Our data suggest that squalene could be considered as a potential treatment for COVID-19, and further studies are required to confirm the results. [ABSTRACT FROM AUTHOR]

Curcumin is a safe and dietary phytochemical that can improve different pathophysiologic features of non-alcoholic fatty liver disease (NAFLD). Here, we investigated the efficacy of phospholipidated curcumin supplementation in NAFLD patients. In this single-arm study, 36 patients were recruited. Each patient received three capsules a day (each containing 500 mg of phospholipidated curcumin [overall content of curcuminoids per capsule: 100 mg]) for a period of 8 weeks. The results indicated that phospholipidated curcumin supplementation reduced NAFLD severity and ameliorated ultrasonographic and biochemical measures (including liver transaminases and lipid profile) associated with disease progression. [ABSTRACT FROM AUTHOR]

Background: Advances in the technology for percutaneous coronary angioplasty, such as coated stents, have reduced its complications, but restenosis remains an important clinical problem. The factors associated with an increased risk of restenosis include diabetes mellitus and multiple coronary artery disease. It is also possible that genetic factors play a role in restenosis although there are little data on this. We have investigated the association of three genetic markers of genes involved in inflammation leading to restenosis. Materials and Methods: In this case--control study, 306 unrelated Iranian patients who were thought to have restenosis on clinical grounds were investigated. Based on the results of angiography, 104 patients were found to have >50% stenosis within an implanted stent, and these were allocated to the in stent restenosis (ISR) group; 202 patients with no in stent stenosis or stenosis ≤50% were allocated to the non ISR (NISR) group. Demographic data were collected from medical records. Biochemical parameters were measured using routine methods. Genotypes of the interleukin 10 (IL 10), annexin A5 (AnxA5), and tumor necrosis factor alpha (TNFα) loci were determined using real time polymerase chain reaction and a high resolution melting assay. Results: Fasting blood glucose, serum triglycerides, and serum high sensitivity C reactive protein (hs CRP) concentrations were higher in the ISR group than in the NISR group (P < 0.05), and a history of diabetes mellitus was significantly related to the presence of restenosis (P < 0.001). There were no significant differences in the frequency of the genetic polymorphisms of IL 10, AnxA5, and TNFα genes and the presence of ISR. Conclusion: After adjustment for clinical variables, the genetic polymorphisms at the IL 10, TNFα, and ANXA5 gene loci do not appear to be risk factors for >50% ISR in our population. However, our data suggested a significant association between diabetes mellitus, serum hs CRP, stent type, and restenosis. [ABSTRACT FROM AUTHOR]

Background: Anemia is a serious public health problem which may be associated with cardiovascular diseases (CVDs) and brain damage. This survey aims to determine the prevalence of anemia and its association with demographic and biochemical factors and metabolic syndrome in a human sample derived from the MASHAD cohort study. Methods: This survey was conducted on a sub-sample of 9847 individuals aged 35 to 65 as part of the MASHAD cohort study. Demographic characteristics and biochemical and anthropometrics indices were recorded. Data were analyzed using SPSS version 20. Results: Anemia was seen in 11.5% of the population. Anemia was significantly more prevalent in younger subject (P < 0.001), females (P < 0.001) and those with elevated body mass index (BMI) (P < 0.001). Mean high-density lipoprotein (HDL) was higher in anemic participant (P = 0.032). The incidence of anemia was significantly lower in smokers (P < 0.001) and also participant with hypertension (HTN) (P < 0.001), diabetes mellitus (DM) (P < 0.001) and metabolic syndrome (MetS) (P < 0.001). Mean FBG (P < 0.001), TG (P < 0.001), total cholesterol (P < 0.001), LDL (P < 0.001) and uric acid (P < 0.001) were significantly lower in anemic subjects. Cholesterol, MetS, low-density lipoprotein (LDL), BMI, uric acid, diabetes mellitus and also TG remained significantly different after multivariate analysis between anemic and healthy participants. Conclusion: The studied population had a lower prevalence of anemia compared to the previous WHO report for Iranians. Iron deficiency is recognized as the most important cause of anemia in Iran; however, further investigations will be need to confirm this pattern. We demonstrated that anemia is adversely associated with MetS and DM. [ABSTRACT FROM AUTHOR]

Background: Development of generic drugs has numerous benefits in terms of cost-efficiency and availability. Slow-release nitroglycerin is a vasodilator drug commonly prescribed for patients with angina pectoris. Objective: The objective of this study was to compare the efficacy and safety of generic slow-release nitroglycerin (Dorocontin®) with that of the innovator brand (Sustac®) in patients with stable angina pectoris. Methods: In this randomized, double-blind comparative trial, 110 patients were allocated to Dorocontin® (n=67) or Sustac® (n=43) at a dose of 6.4 mg TID, for a total period of two months. Maximum endurable MET (metabolic equivalent of task), MPI (myocardial perfusion imaging), along with changes in the ECG and biomarkers of renal (serum creatinine, BUN) and hepatic (AST, ALT, and ALP) function, lipid profile (total cholesterol, LDL-C, HDL-C, VLDL-C, and triglycerides), electrolytes (Na+ and K+), CBC-diff (RBC, WBC, Plt, Hb, Hct, MCV, MCH, MCHC, and RDW), and FBS were assessed at the baseline and at the end of the trial. The frequency of adverse events during the course of the trial was also recorded. Results: Apart from a significantly greater reduction in maximum ST depression in the Sustac® versus the Dorocontin® group (p=0.03), none of the functional (MET, MPI, and ECG) and paraclinical (renal function, hepatic function, lipid profile, electrolytes, and FBS) parameters significantly differed between the study groups. The mean Hb (p=0.035), Hct (p=0.045), and MCH (p=0.032) were decreased by the end of the trial in the Sustac®, but not in the Dorocontin® group, whilst there was no change in other CBC-diff parameters. Reported adverse events were not serious and included headache, vertigo, gastrointestinal upset, and orthostatic hypotension. The frequency of these adverse events was comparable between the study groups. Conclusion: The findings of the present trial showed comparable efficacy and safety of the generic and innovator products of slowrelease nitroglycerin in the management of stable angina pectoris. [ABSTRACT FROM AUTHOR]

Statins are inhibitors of β-hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase (HMGCR). They are used in patients with cardiovascular risk and/or suffering with cardiovascular disease. In addition to their efficient lipid-lowering effects, statins exhibit independent so called pleiotropic effects potentially affecting several immune response properties including immune cell activation, migration, cytokine generation, immune metabolism, and survival. Statins also regulate innate and acquired immunity. The focus of this review is to highlight the role of statins in modulating the function and differentiation of various blood cells. Given the proposed wider application of these medicines and their potentially important advantages in treatment of inflammatory and autoimmune disorders, more studies are needed with special focus on the molecular targets of statins included in regulating the immune response., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Termedia & Banach.)

Background: It has been shown that increased serum PON1 levels are protective against several disorders. Several single nucleotide polymorphisms (SNPs) of the PON1 gene have been reported to be associated with serum enzyme protein levels and activity., Objective: To investigate the association of SNPs of PON1 and serum paraoxonase activity with coronary artery disease (CAD)., Methods: A total of 601 unrelated patients who underwent coronary angiography including those who had &gt;50% stenosis (N=266) and those with &lt;30% stenosis (N=335) were studied. The Paraoxonase gene rs662 and rs840560 SNPs were determined using the ARMS-PCR method and the rs705379 SNP was genotyped using PCR-RFLP analysis. Serum paraoxonase activity was measured using paraoxon as a substrate. A p value of p&lt;0.05 was considered as significant., Results: Serum paraoxonase activity was not significantly different between the study groups. After adjustment for age, sex, hypertension, diabetes mellitus and dyslipidemia, the GG genotype and co-dominant model of rs662 was positively associated with a positive angiogram (respectively, OR=2.424, 95%CI [1.123-5.233], p&lt;0.05, OR=1.663, 95%CI [1.086-2.547]). Serum paraoxonase activity was significantly higher in the G allele and GG variant of rs662, A allele and AA variant of rs854560 and C allele and CC variant of rs705379. The haplotype analysis has shown that the ATC haplotype was significantly more prevalent among the angiogram negative group. The analysis between groups indicated that the A allele of rs662 was significantly associated with lower paraoxonase activity in the positive angiogram group (p=0.019)., Conclusions: The presence of the G allele of the rs662 single nucleotide polymorphism is independently associated to increased risk of CAD.

Introduction: In-stent restenosis (ISR) is an unfavorable outcome that occurs in patients after coronary stenting. Use of drugs such as statins as well as drug-eluting stents has only been partially effective in reducing the rate of ISR. Since low high-density lipoprotein cholesterol (HDL-C) concentration is a pivotal cardiovascular disease risk factor, this study aimed to evaluate the compositional and functional alterations of HDL in individuals with ISR., Material and Methods: This case-control study included 21 ISR, 26 non-ISR (NISR), 16 angiography-negative, and 18 healthy subjects. Serum HDL2 (d: 1.063-1.125 g/ml) and HDL3 (d: 1.125-1.210 g/ml) subfractions were extracted from each subject using sequential ultracentrifugation. The capacity of HDL to efflux cellular cholesterol from lipid-loaded macrophages as well as to take up free cholesterol (FC) from triglyceride-rich lipoproteins (TGRLs) during lipolysis was assessed., Results: No difference was found in the HDL2 and HDL3 content of free cholesterol and total protein among the groups. The NISR group showed lower triglyceride content in HDL2 and higher phospholipid content in HDL3 relative to healthy subjects. Strong positive correlations were found between the cholesterol efflux capacity (CEC) of HDL2 and its phospholipid content in the healthy ( r = 0.50), angiography-negative ( r = 0.55) and ISR ( r = 0.52) groups. The capacity of apolipoprotein B (apoB)-depleted serum to take up free cholesterol was not different among the groups., Conclusions: Despite some compositional alterations, the capacity of HDL to efflux cholesterol from lipid-loaded macrophages as well as to take up free cholesterol from TGRLs during lipolysis was not associated with ISR in this study., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Termedia & Banach.)