Disparity of gene expression in coronary artery disease: insights from MEIS1, HIRA, and Myocardin.

INTRODUCTION: Coronary artery disease (CAD) in young adults can have devastating consequences. The cardiac developmental gene MEIS1 plays important roles in vascular networks and heart development. This gene effects on the regeneration capacity of the heart. Considering role of MEIS1 in cardiac tissue development and the progression of myocardial infarction this study investigated the expression levels of the MEIS1, HIRA, and Myocardin genes in premature CAD patients compared to healthy subjects and evaluated the relationships between these genes and possible inflammatory factors. METHODS AND RESULTS: The study conducted a case-control design involving 35 CAD patients and 35 healthy individuals. Peripheral blood mononuclear cells (PBMCs) were collected, and gene expression analysis was performed using real-time PCR. Compared with control group, the number of PBMCs in the CAD group exhibited greater MEIS1 and HIRA gene expression, with fold changes of 2.45 and 3.6. The expression of MEIS1 exhibited a negative correlation with IL-10 (r= -0.312) expression and positive correlation with Interleukin (IL)-6 (r = 0.415) and tumor necrosis factor (TNF)-α (r = 0.534) gene expression. Moreover, there was an inverse correlation between the gene expression of HIRA and that of IL-10 (r= -0.326), and a positive correlation was revealed between the expression of this gene and that of the IL-6 (r = 0.453) and TNF-α (r = 0.572) genes. CONCLUSION: This research demonstrated a disparity in expression levels of MEIS1, HIRA, and Myocardin, between CAD and healthy subjects. The results showed that, MEIS1 and HIRA play significant roles in regulating the synthesis of proinflammatory cytokines, namely, TNF-α and IL-6.

First Iranian guidelines for the diagnosis, management, and treatment of hyperlipidemia in adults.

This guideline is the first Iranian guideline developed for the diagnosis, management, and treatment of hyperlipidemia in adults. The members of the guideline developing group (GDG) selected 9 relevant clinical questions and provided recommendations or suggestions to answer them based on the latest scientific evidence. Recommendations include the low-density lipoprotein cholesterol (LDL-C) threshold for starting drug treatment in adults lacking comorbidities was determined to be over 190 mg/dL and the triglyceride (TG) threshold had to be >500 mg/dl. In addition to perform fasting lipid profile tests at the beginning and continuation of treatment, while it was suggested to perform cardiovascular diseases (CVDs) risk assessment using valid Iranian models. Some recommendations were also provided on lifestyle modification as the first therapeutic intervention. Statins were recommended as the first line of drug treatment to reduce LDL-C, and if its level was high despite the maximum allowed or maximum tolerated drug treatment, combined treatment with ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, or bile acid sequestrants was suggested. In adults with hypertriglyceridemia, pharmacotherapy with statin or fibrate was recommended. The target of drug therapy in adults with increased LDL-C without comorbidities and risk factors was considered an LDL-C level of <130 mg/dl, and in adults with increased TG without comorbidities and risk factors, TG levels of <200 mg/dl. In this guideline, specific recommendations and suggestions were provided for the subgroups of the general population, such as those with CVD, stroke, diabetes, chronic kidney disease, elderly, and women.

Sodium butyrate and voluntary exercise through activating VEGF-A downstream signaling pathway improve heart angiogenesis in type 2 diabetes.

BACKGROUND: Inadequate angiogenesis in patients with type 2 diabetic heart could result in deprived collateral formation. Herein, we aimed to investigate the effects of sodium butyrate (NaB) along with voluntary exercise simultaneously on the mechanisms acting on cardiac angiogenesis. MATERIALS AND METHODS: Animals were divided into the following five groups: control (Con), diabetic rats (Dia), diabetic rats treated with NaB (200 mg/kg, i.p.) (Dia-NaB), diabetic rats receiving voluntary exercise (Dia-Exe), and diabetic rats treated with NaB and exercise simultaneously (Dia-NaB-Exe). After an eight-week duration, NO metabolites levels were measured using Griess method, the VEGF-A and VEGFR2 expressions was examined by PCR, the expressions of VEGF-A and VEGFR2 proteins was investigated by western blot, and ELISA method was used for Akt, ERK1/2 expression. RESULTS: Cardiac VEGF-A and VEGFR2 expressions were higher in the Dia-Exe and Dia-NaB-Exe groups compared to the Dia group. However, a combination of exercise and NaB enhanced the VEGF-A expression in cardiac tissue compared to the Dia-NaB and Dai-Exe groups. Heart NOx concentration was higher in the treated groups compared to the Dia group. The expression of cardiac Akt levels increased in both the Dia-Exe and Dia-NaB-Exe groups compared to the Dia groups. In addition, cardiac ERK1/2 expression was found to be higher in the Dia-NaB-Exe group compared to the Dia group. CONCLUSION: The findings of this study showed the therapeutic potential of a novel combination therapy of sodium butyrate and voluntary exercise in improving cardiac angiogenesis with the enhanced involvement mechanism in high fat/STZ-induced type 2 diabetic rats.

Probiotics act as a potent intervention in improving lipid profile: An umbrella systematic review and meta-analysis.

Several meta-analysis studies have revealed improving effects of probiotics on lipid profile, while some studies have reported controversial findings. The purpose of present study was to evaluate the efficacy of probiotics on blood lipids. Relevant studies were searched in the international databases, including PubMed, Scopus, EMBASE, Web of Science, and Cochrane Central Library up to August 2021. The pooled results were calculated with the use of a random-effects model to assess the effects of probiotics on blood lipids. Overall, 38 meta-analyses were inclueded in the study. The results indicated that the probiotics supplementation was effective on reduction of total cholesterol (TC) (ES= -0.46 mg/dL; 95% CI: -0.61, -0.30, p < 0.001; I2= 83.8%, p < 0.001), triglycerides (TG) (ES= -0.13 mg/dl; 95% CI: -0.23, -0.04, p = 0.006; I2= 74.7%, p < 0.001), and low-density lipoprotein cholesterol (LDL-C)levels (ES= -0.29 mg/dL; 95% CI: -0.40, -0.19, p < 0.001; I2= 77.8%, p < 0.001). There was no significant effect of probiotics on high-density lipoprotein cholesterol (HDL-C) levels (ES= 0.02 mg/dl; 95% CI: -0.04, 0.08, p = 0.519; I2= 72.5%, p= <0.001). The results of present umbrella meta-analysis strongly support supplementation with probiotics as an influential intervention for improving lipid profile.

The roles of quercetin in diabetes mellitus and related metabolic disorders; special focus on the modulation of gut microbiota: A comprehensive review.

Quercetin is a dietary flavonoid that can affect the balance between anti-oxidant defense system and oxidative stress. A number of studies showed the positive effects of quercetin on diabetes mellitus and related metabolic disorders through different pathways such as gut flora. However, findings are conflicting. In addition, it seems no studies have summarized all potential mechanisms of quercetin in diabetes mellitus, so far. Therefore, the aims of the present comprehensive review were to provide an overview on biological and biochemical characteristics of quercetin and investigate the effect of quercetin on diabetes mellitus and related metabolic disorders by focusing on its effects on the modulation of gut microbiota. For this purpose, findings of In vitro, animal studies, clinical trials, and review studies with the English language published until January 2021 were summarized. They were identified through electronic databases (PubMed, Scopus, and Cochrane Library) and Google Scholar. Findings showed that quercetin can be an effective component for improving glycemic status and other metabolic disorders related to diabetes mellitus based on In vitro and animal studies. However, environmental factors, food processing and using nanoformulations can affect its efficacy in human studies. Several potential mechanisms, including the modulation of gut flora are proposed for its actions. However, due to limited clinical trials and contradictory findings, more high-quality clinical trials are needed to make a decision on the efficacy of supplementation with quercetin as a complementary therapy for the management of diabetes mellitus, metabolic disorders, and modulating gut flora.

The expression levels of PPAR-α/γ and UCP1/2 on the slow coronary flow phenomenon; results from a case-control study.

PURPOSE: The slow coronary flow (SCF) phenomenon is considered a coronary artery disorder. Because of the critical function of peroxisome proliferator-activated receptors (PPARs) in regulating the oxidative stress and inflammatory reactions in cardiovascular disease, The aim of the current study was to investigate the expression of the genes for uncoupling proteins 1 and 2 (UCP1 and UCP2), peroxisome proliferator-activated receptors and (PPAR- PPAR-), and PPAR- in SCF patients. METHODS: In this case-control study, coronary angiography examination was used to analyze 35 individuals with SCF and 35 subjects with normal coronary flow (NCF). SCF was diagnosed using the TIMI (thrombolysis in myocardial infarction frame count) method. The SCF phenomenon is thought to be the TIMI > 27. In the peripheral blood mononuclear cells (PBMCs), the messenger ribonucleic acid (mRNA) expression levels of the PPAR-, PPAR-, UCP1, and UCP2 genes were evaluated. RESULTS: UCP1 and UCP2 expression levels were significantly higher in the SCF group compared to the NCF group (P = 0.034 and P0.001, respectively). The PPAR- and PPAR- levels were found to be significantly lower in the SCF group compared to the NCF group (P = 0.015, P0.001, respectively). According to the results of the logistic regression analysis, high UCP1 and UCP2 levels and low PPAR- and PPAR- levels are each independent predictors of the SCF phenomenon. CONCLUSION: This research provided evidence about the potential role of PPAR-α, PPAR-γ, UCP1, and UCP2 as biomarkers in SCF. More investigations are suggested to assess the functions of these factors in SCF patients mechanistically.

The effect of saffron (Crocus sativus L.) on glycemia, lipid profile, and antioxidant status in patients with type-2 diabetes mellitus: A randomized placebo-controlled trial.

In the current study, we aimed to investigate the effect of saffron supplementation on glycemic status, lipid profile, atherogenic indices, and oxidative status in patients with type-2 diabetes (T2DM). In a randomized, double-blind controlled trial, 70 patients were randomly allocated into two groups (n = 35, each) and received 100 mg/day of saffron or placebo for eight weeks. Dietary intake, weight, body mass index (BMI), waist and hip circumferences (WC and HC), waist to hip ratio (WHR), fasting blood sugar (FBS), hemoglobin A1c (HbA1c), insulin, and Homeostatic model assessment for insulin resistance (HOMA-IR), lipid profile, atherogenic indices, oxidative status, and liver enzymes were determined before and after the intervention. At the end of the eighth week, saffron intervention could significantly reduce FBS (7.57%), lipid profile (except high-density lipoprotein cholesterol [HDL-C]), atherogenic indices, and liver enzymes (p < .05). Moreover, saffron could improve oxidative status (nitric oxide [NO] and malondialdehyde [MDA] reduced by 26.29% and 16.35%, respectively). Catalase (CAT) concentration remained unchanged. Saffron supplementation may alleviate T2DM by improving glycemic status, lipid profile, liver enzymes, and oxidative status. Further investigation is necessary to assess possible side effects and confirm the positive effect of saffron as a complementary therapy in clinical recommendations for T2DM.

Curcumin as a novel approach in improving lipid profile: An umbrella meta-analysis.

AIMS: Several meta-analyses exist supporting the beneficial effects of curcumin supplementation on lipid profile parameters; however, some studies' findings are inconsistent. Therefore, the current umbrella of meta-analysis of clinical trials was performed to evaluate the findings of multiple meta-analyses on the efficacy of curcumin on lipid profiles in adults. DATA SYNTHESIS: A comprehensive systematic search of PubMed/Medline, Scopus, Embase, Web of Science and Google Scholar were carried out up to May 2022 (in English only). Random-effects model was employed to conduct meta-analysis. The quality assessment of the selected meta-analyses was measured using a measurement tool to assess multiple systematic reviews (AMSTAR). From 101 articles returned in the literature search, 19 articles were met the qualified for inclusion in the umbrella meta-analysis. The results revealed that the curcumin supplementation was effective on reduction of total cholesterol (TC) (ES = -0.81 mg/dl; 95% CI: 1.39, -0.24, p = 0.006; I2 = 68.8%, p < 0.001), triglycerides (TG) (ES: 0.84 mg/dl, 95% CI: 1.42, -0.27, p = 0.004; I2 = 84.2%, p < 0.001), and low-density lipoprotein cholesterol (LDL-C) levels (ES: 0.49 mg/dl, 95%CI: 0.85, -0.13, p = 0.007; I2 = 51.9%, p = 0.004). Beyond that, Curcumin intake significantly increased high-density lipoprotein cholesterol (HDL-C) levels (ES: 1.34 mg/dl, 95% CI: 0.37, 2.31, p = 0.007; I2 = 97.8%, p < 0.001). CONCLUSION: Curcumin have ameliorating effects on TC, TG, LDL-c, and HDL-c levels. Overall, Curcumin could be recommended as an adjuvant anti-hyperlipidemic agent. REGISTRATION NUMBER: PROSPERO, CRD42021289500.

Sodium selenite and Se-enriched yeast supplementation in atherosclerotic patients: Effects on the expression of pyroptosis-related genes and oxidative stress status.

BACKGROUND AND AIMS: Atherosclerosis as a chronic inflammatory disorder of the arterial wall is the main leading cause of the cardiovascular disease (CVD). Caspase-dependent pyroptosis plays a pivotal role in the pathogenesis of CVD. Selenium (Se) is an important component of the antioxidant defense and plays a crucial role in cardiovascular health. This study aimed to investigate the effects of daily consumption of sodium selenite and Se-enriched yeast on the expression of pyroptosis-related genes, and biomarkers of oxidative stress in patients with atherosclerosis. METHODS AND RESULTS: In this randomized, double-blinded, placebo-controlled clinical trial, 60 patients with atherosclerosis were recruited. Participants received 200 µg/day of sodium selenite, Se-enriched yeast, or placebo for 8 following weeks. The pyroptosis-related genes' mRNA expression in peripheral blood mononuclear cells (PBMCs) was assessed before and after the intervention. Also, the levels of superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and glutathione peroxidases (GPX) were measured at baseline and following the intervention. Following sodium selenite and Se-enriched yeast supplementation, the relative expression levels of TLR4, ASC, NLRP3, and NF-κB1 were significantly downregulated (p < 0.05). Furthermore, the changes in GPX were significantly increased after selenite and yeast supplementation (p < 0.05). Also, selenite and yeast consumption caused a statistically significant decrease in the change of MDA level (p < 0.05). CONCLUSION: In summary, these findings showed that Se supplementation may reduce inflammation through down-regulation of some pro-inflammatory genes, improving antioxidant defenses in atherosclerosis patients. Further research is required to come to a definite conclusion of selenium supplementation on the CVD risk. This study was registered on the Iranian Registry of Clinical Trials website (identifier: RCT20110123005670N28; https://www.irct.ir/).

The therapeutic potential of Crocus sativus Linn.: A comprehensive narrative review of clinical trials.

Crocus sativus Linn. (Saffron) is valued worldwide for its potential use in the management of various degenerative disorders, including cardiovascular diseases (CVDs), diabetes, cancer, metabolic syndrome (MetS), neurodegenerative diseases, immune disorders, and sexual dysfunction. Previous reports, based on clinical trials, suggest that crocetin, crocin, picrocrocin, and safranal are the main bioactive components of saffron with antioxidant, anti-inflammatory, and anti-apoptotic effects. In this comprehensive narrative review, we studied the recent clinical trials, investigating the medicinal applications of saffron and/or its components. The present results can provide important insights into the potential of saffron in preventing and treating different disorders, with a special focus on the underlying cellular and molecular mechanisms. However, further high-quality studies are needed to firmly establish the clinical efficacy of saffron in treating some degenerative diseases.

Expression of NF-κB, IL-6, and IL-10 genes, body composition, and hepatic fibrosis in obese patients with NAFLD-Combined effects of oleoylethanolamide supplementation and calorie restriction: A triple-blind randomized controlled clinical trial.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common noncommunicable diseases worldwide. The present study aimed to investigate the effects of oleoylethanolamide (OEA) supplementation combined with calorie restriction on inflammation, body composition, and hepatic fibrosis among obese patients with NAFLD. In this 12-week randomized clinical trial, 76 obese patients newly diagnosed with NAFLD were randomly allocated into either OEA or placebo group. The weight-loss diet was also designed for both groups. Pre- and postintervention messenger RNA expression levels of the transcription factor nuclear factor-κB (NF-κB), interleukin-6 (IL-6) and IL-10, body composition, and NAFLD fibrosis score were assessed. At the end of the study, the OEA group showed lower NF-κB and IL-6 expression levels compared to the placebo (p < .01). However, IL-10 expression level was approximately twofold higher in the OEA group compared to the placebo group (p = .008). A significant reduction was observed in the fat mass of the OEA group compared to the placebo (p = .044) postintervention. In addition, OEA supplementation led to a significant increase in fat-free mass in the OEA group compared to the placebo (p = .032). A remarkable increase was observed in resting metabolic rate (RMR) in the OEA group (p = .009); however, it was not found in the placebo group. There were no significant between-group differences in RMR postintervention. In addition, no significant within-and between-group differences were observed in the NAFLD fibrosis score at the end of the trial. Treatment with OEA along with weight-loss intervention could significantly improve inflammation and body composition in patients with NAFLD.

A novel inflammatory signaling pathway in patients with slow coronary flow: NF-κB/IL-1ß/nitric oxide.

PURPOSE: The slow coronary flow (SCF) was identified as delayed opacification of epicardial coronary arteries in the absence of stenotic lesion. Metabolic syndrome (MetS), oxidative stress, and inflammation may be possible known insulting factors for the pathogenesis of SCF. This investigation aimed to assess the relationship between some inflammatory markers, oxidative stress parameters and MetS components with SCF phenomenon. METHODS: A total of 35 patients with SCF and 35 subjects with normal coronary flow (NCF) were included in the study. We assessed some inflammatory markers (IL-1ß, IL-18, TNF-α, and NF-κB mRNA expression in peripheral blood mononuclear cells (PBMCs)). Moreover, blood samples of the participants were tested for total antioxidant capacity (TAC), glutathione peroxidase (GPX) and nitric oxide (NO) levels using enzyme-linked immunosorbent assay (ELISA). Diagnosis of MetS was based on the National Cholesterol Education Program's Adult Treatment Panel III report (ATPIII) criteria, 2005. Diagnostic criteria for coronary flow rates of all subjects were documented by thrombolysis in myocardial infarction (TIMI) frame count method. RESULTS: SCF patients had significantly higher prevalence of MetS (46%, p = 0.048).We found that the level of TAC was significantly higher in the NCF group (p = 0.006). Furthermore, the NO concentration was significantly lower in SCF groups (p = 0.001). A significant incremental difference was detected in IL-1ß (fold change 2.82 ± 0.31, p < 0.05) and NF-κB (fold change 4.62 ± 0.32, p < 0.05) mRNA expression in the SCF group when compared with its level in the NCF group. Furthermore, according to logistic regression analysis, there were significant associations between IL-1ß, NF-κB expression levels and the incidence of SCF (p < 0.05). CONCLUSION: Based on the findings of this study, the pathogenesis of the SCF phenomenon may be closely associated with metabolic syndrome and inflammation. The NF-κB/IL-1ß/nitric oxide & MetS signaling pathway might be considered as potential therapeutic targets in the management of SCF patients but further researches is required to guarantee these findings.

Systematic review and meta-analysis of randomised, controlled trials on the effects of garlic supplementation on serum adiponectin and leptin levels.

BACKGROUND: Our aim in this meta-analysis was to determine the effect of garlic supplementation on adiponectin and leptin serum levels. METHOD: A systematic search was conducted using PubMed, Scopus, ISI Web of Science and Cochrane Library for eligible trials up to November 2020. A fixed-effects model was used to pool calculated effect sizes. RESULTS: Five trials were included in the overall analysis. Our analysis showed that garlic supplementation did not significantly affect adiponectin (Hedges's: 0.20; 95% CI: -0.06, 0.47; P-values = .12) and leptin (Hedges's: 0.08; 95% CI: -0.26, 0.41; P-values = .65) concentrations in comparison with placebo. However, in the subgroup analysis, significantly increased serum adiponectin level was seen following garlic supplementation in trials with a mean age of participants ˂30 years (Hedges's: 0.44; 95% CI: 0.01, 0.87; P-values = .04), the doses ˂1.5 g/d (Hedges's: 0.38; 95% CI: 0.02, 0.71; P-values = .04) and trials with duration ≥8 weeks (Hedges's: 0.48; 95% CI: 0.08, 0.89; P-values = .02). CONCLUSION: Overall, garlic supplementation could not change the circulatory adiponectin and leptin levels. Subgroup analyses showed a significant reduction in adiponectin levels in younger participants, longer duration and lower intervention dose. However, further studies are needed to confirm the present results.

Saffron improves life and sleep quality, glycaemic status, lipid profile and liver function in diabetic patients: A double-blind, placebo-controlled, randomised clinical trial.

BACKGROUND: Type 2 diabetes (T2D) is a metabolic disorder that is related to hyperglycaemia, hyperlipidaemia and liver dysfunction and has detrimental effects on a patient's mental health. Hence, the current study investigated the effects of saffron supplementation on dietary intake, anthropometric measures, mood, sleep quality and metabolic biomarkers in overweight/obese patients with T2D. METHODS: In a double-blind, randomised controlled trial, 70 overweight/obese patients with T2D were randomly allocated to two groups and received 100 mg/day saffron or placebo for 8 weeks. Participants completed the Beck depression inventory-II (BDI-II), Hurlbert index of sexual desire (HISD), Pittsburgh Sleep Quality Index (PSQI) and Diabetes-specific Quality-of-Life Brief Clinical Inventory questionnaires (DQOL-BCI). Dietary intake, anthropometric measures, fasting plasma glucose (FPG), haemoglobin A1C (HbA1C), insulin, lipid profile and liver enzymes were determined at baseline and the end of the study. RESULTS: At the end of the eighth week, saffron supplementation significantly decreased FPG, triglyceride (TG), insulin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < .001). Moreover, significant improvements in BDI-II scores and total quality of life were observed in the intervention group (P < .001). The saffron group showed more significant improvements in PSQI scores than the placebo group, such that at the post-intervention analysis, only the saffron group achieved a "good" sleep band. At this relatively high dose, saffron supplementation improved glycaemic status, lipid profile and liver enzyme measures in patients with T2D while also improving sleep and overall quality of life. CONCLUSION: Our results indicate that saffron notably reduced hyperglycaemia and hyperlipidaemia and improved liver function in patients with T2D in an 8-week randomised clinical trial. Saffron also significantly improved depression, sleep quality and overall quality of life in diabetic patients. However, further investigation is necessary to confirm whether saffron is an effective complementary therapy for T2D.

The interplay between fasting, gut microbiota, and lipid profile.

BACKGROUND: This study aimed to investigate the consequence of Ramadan fasting on gut bacterium (Bacteroides and Firmicutes), serum concentration for butyrate, and lipid profile. METHODS: Thirty healthy subjects were enlisted and investigated two times (before and at the end of Ramadan). Fasting blood samples were obtained for measuring fasting blood sugar (FBS) and lipid profile and serum butyrate concentration. Anthropometrics variables were measured before and after Ramadan for all 30 subjects. Quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis, targeting the genome of Bacteroides and Firmicutes was performed to determine its presence in the stool samples. Food intake was assessed by a 3-day food record before and after Ramadan. Statistical analysis was performed by SPSS ver.13 and Minitab ver.17. P < 0.05 considered the level of significance. RESULTS: The study results showed that serum levels of butyrate significantly increase during the month from 0.23 ± 0.02 mM to 0.46 ± 0.03 mM (P < 0.05). The gut Bacteroides and Firmicutes increased by 21 and 13 percent after Ramadan compared to before (P < 0.05). The increment in Bacteroides occurred in both sexes, but Firmicutes significantly increased only in women. Food intake was decreased during Ramadan. Ramadan fasting caused significant reduction in BMI from 25.72 ± 0.58 kg/m2to 25.25 ± 0.55 kg/m2 (P < 0.05). Serum levels of LDL, HDL, LDL/HDL ratio, and total cholesterol significantly decreased during Ramadan (P < 0.05). However, the decrease in FBS and TG level were not statistically significant (P > 0.05). CONCLUSION: It can be stated that the promotion of Bacteroides and Firmicutes in the gut might play a crucial role in health promotion. However, more research is needed to achieve a definite conclusion.

Effects of oral butyrate and inulin supplementation on inflammation-induced pyroptosis pathway in type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

PURPOSE: Pyroptosis, a form of inflammatory programmed cell death, is activated in diabetic patients. This study was conducted to investigate the effects of daily consumption of sodium butyrate (NaBut) and high-performance (HP) inulin supplementation, individually or in combination, on the expression of pyroptosis-related genes, microRNA (miR) 146a-5p, miR-9-5p and biomarkers of oxidative stress in patients with type 2 diabetes (T2DM). METHODS: In this study, we conducted a randomized, double-blinded, placebo-controlled clinical involving sixty patients with type 2 diabetes. Participants received 600 mg/d of NaBut (group A), 10 g/d of HP inulin (group B), 600 mg/d of NaBut + 10 g/d of HP inulin (group C) or placebo (group D) for 45 consecutive days. We assessed the pyroptosis-related genes mRNA expression in peripheral blood mononuclear cells (PBMCs), as well as the plasmatic levels of miR-146a and miR-9 before and after the intervention. Moreover, blood samples of the patients at baseline and following the intervention were tested for total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase levels using enzyme-linked immunosorbent assay (ELISA). This study was registered on the Iranian Registry of Clinical Trials website (identifier: IRCT201605262017N29; https://www.irct.ir/). RESULTS: Following butyrate supplementation, the relative expression levels of TLR2/4, NF-κB1, Caspase-1, NLRP3, IL-1ß & IL-18 were significantly downregulated (p < 0.05). Furthermore, butyrate and concomitant use of butyrate and inulin caused a significant increase in the fold change of miR-146a and miR-9 compared with the placebo group (p < 0.05). Interestingly, the changes in total antioxidant capacity (p = 0.047) and superoxide dismutase (p = 0.006) were significantly increased after butyrate and concomitant use of butyrate and inulin supplement, respectively. CONCLUSION: In summary, the change in expression level of miR-146a-5p and miR-9-5p due to butyrate supplementation may have a pivotal role in alleviating of diabetes via inhibiting pyroptosis by targeting TLR2 and NF-κB1. These microRNAs might be considered as potential therapeutic targets in the treatment of type 2 diabetes but further researches is required to prove the link.

Oleoylethanolamide supplementation in obese patients newly diagnosed with non-alcoholic fatty liver disease: Effects on metabolic parameters, anthropometric indices, and expression of PPAR-α, UCP1, and UCP2 genes.

The effects of oleoylethanolamide (OEA) on NAFLD are yet to be examined in human. The objective of the present study was to examine the effects of OEA supplementation along with weight loss intervention on the expression of PPAR-α, uncoupling proteins 1and 2 (UCP1 and UCP2) genes in the peripheral blood mononuclear cells (PBMCs), metabolic parameters, and anthropometric indices among obese patients with NAFLD. In this triple-blind placebo-controlled randomized clinical trial, 76 obese patients newly diagnosed with NAFLD were randomly allocated into either OEA or placebo group along with calorie-restricted diets for 12 weeks. At pre-and post-intervention phase, mRNA expression levels of PPAR-α, UCP1, and UCP2 genes in the PBMCs, serum levels of metabolic parameters as well as diet and appetite sensations were assessed. There was a significant increase in the expression levels of PPAR-α, UCP1, and UCP2 genes in the PBMCs, compared to the placebo at the endpoint. A significant decrease in the anthropometric indices, energy and carbohydrate intakes, glycemic parameters, except for hemoglobin A1c concentration was also observed in the OEA group, compared to the placebo group. OEA treatment significantly resulted in decreased serum levels of triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, increased serum levels of high-density lipoprotein cholesterol (HDL-C), and improved appetite sensations. Importantly, a significant improvement in TG, ALT, AST, ALT/AST, HDL-C levels as well as appetite sensations by OEA were under the influence of body mass index (BMI). Although liver steatosis severity was significantly reduced in both groups, the between-group differences did not reach statistical significance (P = 0.061). In conclusion, the present study, for the first time, revealed that OEA supplementation significantly improved anthropometric and metabolic risk factors related to NAFLD.

Techniques, perspectives, and challenges of bioactive peptide generation: A comprehensive systematic review.

Due to the digestible refractory and absorbable structures of bioactive peptides (BPs), they could induce notable biological impacts on the living organism. In this regard, the current study was devoted to providing an overview regarding the available methods for BPs generation by the aid of a systematic review conducted on the published articles up to April 2019. In this context, the PubMed and Scopus databases were screened to retrieve the related publications. According to the results, although the characterization of BPs mainly has been performed using enzymatic and microbial in-vitro methods, they cannot be considered as suitable techniques for further stimulation of digestion in the gastrointestinal tract. Therefore, new approaches for both in-vivo and in-silico methods for BPs identification should be developed to overcome the obstacles that belonged to the current methods. The purpose of this review was to compile the recent analytical methods applied for studying various aspects of food-derived biopeptides, and emphasizing generation at in vitro, in vivo, and in silico.

Hypermethylation of IL-10 gene is responsible for its low mRNA expression in Behçet's disease.

Interleukin-10 (IL-10), produced generally by monocyte, T helper type 2 (Th2), and regulatory T cells (Treg), plays a central role in controlling inflammatory responses and regulating the immune response of the IL-10 mRNA expression. It is significantly down-regulated in many autoimmune diseases such as Behçet's disease; this is mostly associated with more aggressive complications. Nevertheless, the essential molecular process for its low expression has not been completely realized. The aim of this project was attempted to estimate the gene expression, promoter methylation, and protein levels to IL-10's down-regulated expression. In this study, blood samples from 51 (4 missed) patients and 63 (2 missed) healthy controls were taken, with the mononuclear cells isolated by the Ficoll Protocol. DNA and RNA were then subsequently extracted. Promoter methylation levels were evaluated by MeDIP-qPCR. Following this, the extracted RNA was converted to cDNA using the RT-PCR method, with the expression of IL-10 later evaluated by Real-time PCR. And then, serum levels of IL-10 were measured using ELISA method. As we expected, the expression level of the IL-10 gene was seen to significantly decline in the patient group in comparison to the control. Also, the rate of promoter methylation was significantly higher in the IL-10 mRNA low expression group (patient group) compared to its high expression group (healthy group) (P < 0.001). We revealed that hypermethylation of promoter region was the principal defect for the IL-10 mRNA low expression in patients with Behçet's disease.