Magnesium Supplementation Affects the Expression of Sirtuin1, Tumor Protein P53 and Endothelial Nitric Oxide Synthase Genes in Patients with Atherosclerosis: A Double-Blind, Randomized, Placebo-Controlled Trial.

Magnesium seems to play a role in improving cardiovascular function, but its exact mechanism is unknown. In this study, we hypothesized that magnesium could modulate the expression of genes involved in atherosclerosis. The aim of the present investigation was to evaluate the effect of magnesium sulfate on the expression of sirtuin1 (SIRT1), tumor protein p53 (TP53), and endothelial nitric oxide synthase (eNOS) genes in patients with atherosclerosis. This study was a placebo-controlled double-blind randomized clinical trial on 56 patients with angiographically proven atherosclerosis. Participants were randomly divided into two groups receiving 300 mg/day magnesium sulfate (n = 29) and placebo (n = 27) for three months (following up every month). Fasting blood samples were taken before and after the intervention and total RNA was extracted and used to evaluate the expression level of SIRT1, TP53, and eNOS genes by Real-Time PCR. The expression of eNOS gene was significantly increased (P < 0.0001) and the expression of TP53 gene was decreased (P = 0.02) in the magnesium sulfate group compared to the placebo group. But SIRT1 gene expression was not significantly different between the two groups. Our findings demonstrate that magnesium sulfate supplementation may have a protective role against the progression of atherosclerosis through upregulation of eNOS and downregulation of TP53 gene. Trial registration: This present clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT) with the registration code of "IRCT20151028024756N3", https://www.irct.ir/trial/29097?revision=114102. Registered on 16 December 2019.

The association of sleep duration and metabolic syndrome in the Bandare-Kong cohort study, a cross-sectional survey (finding from PERSIAN cohort study).

BACKGROUND: A variety of health problems, such as metabolic syndrome (MetS), have been linked to sleep disorders. While numerous epidemiological studies have shown a U-shaped relationship between sleep duration and poor health outcomes, the results were limited and inconsistent. This study was designed to evaluate the relationship between sleep duration and MetS. METHODS: This population-based study was conducted on the participants aged 35-70 of Bandare-Kong Non-Communicable Diseases (BKNCD) Cohort Study, a part of Prospective Epidemiological Research Studies in IrAN (PERSIAN). MetS was diagnosed according to the National Cholesterol Education Program (NCEP) criteria and the Iranian-specific cut-off for waist circumference (≥ 95 cm). Sleep information was extracted through a standard questionnaire based on self-reported information. Data were analyzed by R software using generalized additive models (GAMs). A statistically significant level was considered as P < 0.05. RESULTS: A total of 3695 participants were included in the analyses. The mean age was 48.05 years (SD 9.36), and 2067 (55.9%) were female. The estimated Prevalence of MetS was 35.9%, and women appeared to be more likely to have MetS than men (P < 0.001). There was a non-linear and linear association between sleep duration and the risk of MetS in women and men, respectively. The lowest risk was observed among those with 7-7.5 h of sleep duration per night. CONCLUSION: Long sleep duration was associated with increased risk of MetS and higher MetS severity score in both genders, while the short sleep duration increased the risk of Mets as well as MetS severity score just in women. The longitudinal studies would be suggested to assess the relationship between sleep quality and quantity components and MetS.

Influance of regular swimming on serum levels of CRP, IL-6, TNF-α in high-fat diet-induced type 2 diabetic rats.

Due to key role of inflammation in pathogenesis of type 2 diabetes mellitus (T2DM), aim of this study was evaluating the influance of regular swimming on serum levels of C-reactive protein (CRP), interlukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in high-fat diet-induced diabetic rats. Fourty male Wistar rats were randomly divided into control, diabetic, exercise and diabetic-exercise groups (n = 10). Diabetes was induced by high-fat diet and streptozotocin (35 mg/kg, i.p.). In exercise groups, after induction of diabetes, animals were subjected to swimming (60 min/5 days a week) for 10 weeks. At the end of training, rats were anestatized and blood samples and pancreatic tissues were collected and used for evaluation of CRP, IL-6, TNF-α and pancreatic histopatholology. Our results showed significantly increase in lymphocytes, monocytes and decrease in neutrophils in diabetic rats (p < 0.01), which these parameters significantly reversed to control levels by induction of swimming (p < 0.01). In diabetic group, the levels of CRP, IL-6 and TNF-α increased (p < 0.01), and swimming decreased these factors significantly. Histopathological results of this study also showed that swimming can prevent damage induced by diabetes. The present study indicates that swim training is associated with improved inflammation and inflammatory mediators and pancreatic damage.

Alteration in Inflammation-related miR-146a Expression in NF-KB Signaling Pathway in Diabetic Rat Hippocampus.

PURPOSE: The purpose of the present study is to evaluate the expression of miR-146a gene, its adaptor genes (TRAF6, NF-KB, and IRAK1), and possible changes in the cellular signaling pathway in diabetic hippocampus tissue. METHODS: Male Sprague-Dawley rats are randomly selected and divided into control and diabetic (n=6) groups. Diabetes induced by the single-dose injection of nicotinamide [110 mg/kg, (i.p.)], 15 min before streptozotocin (50 mg/kg; i.p.) in 12-h fasted rats. The rats are kept at the laboratory for two months. After anaesthetization, hippocampus of the rats was removed in order to measure the expression of miR-146a, NFK-B, IRAK1, and TRAF6 genes using real-time PCR and activity of NF-KB as well as amount of apoptosis rate using ELISA. RESULTS: The results indicated a reduction in expression of miR-146a and an increase in expression of IRAK1, NF-KB, and TRAF6 genes in the hippocampus of diabetic rats compared to control. Also it reveals an increase in the activity of NF-KB and apoptosis rate in the hippocampus of diabetic rats. CONCLUSION: Our results report the probability that reduction of miR-146a expression in the negative feedback loop between miR-146a and NF-KB increases NF-kB expression and thus intensifies inflammation and apoptosis in hippocampus.

Swim Training Improves HOMA-IR in Type 2 Diabetes Induced by High Fat Diet and Low Dose of Streptozotocin in Male Rats.

PURPOSE: Insulin resistance plays a key role in the onset and development of type 2 diabetes mellitus (T2DM) and its complications. In this study, we evaluated the effect of swim training on insulin resistance in diabetic rats. METHODS: Forty male Wistar rats were randomly divided into four groups (n=10): sedentary control (Con), sedentary diabetic (Dia), swim trained control (Exe) and swim trained diabetic (Dia+Exe) rats. Diabetes was induced by high fat diet (HFD) and a low dose of streptozotocin (35 mg/kg, i.p). In trained groups, one week after the induction of diabetes, animals were subjected to swimming (60 min/5 days a week) for 10 weeks. At the end of training, fasting blood sugar (FBS), oral glucose tolerance test (OGTT), fasting/basal insulin, glycosylated hemoglobin (HbA1c) levels, insulin resistance index, homeostasis model assessment method (HOMA-IR), triglycerides (TG,) total cholesterol (TCh), and high density lipoprotein (HDL) levels in blood were measured. RESULTS: Swimming significantly improved OGTT (P<0.01) and HOMA-IR (P<0.01). Swim training also significantly decreased FBS (p<0.01), fasting/basal insulin (P<0.01), HbA1C (p<0.01), TG (P<0.05), and TCh (P<0.05) levels. It also significantly increased HDL (p<0.05) level. CONCLUSION: Our findings indicate that swim training improved glycemic control and insulin sensitivity in type 2 diabetes caused by high fat diet in male rats.

A signature of microRNA-155 in the pathogenesis of diabetic complications

The current study was designed to explore the potential involvement of miR-155 in the pathogenesis of diabetes complications. Male rats were divided into control and diabetic groups (n = 6). Type 2 diabetes was induced by a single-dose injection of nicotinamide (110 mg/kg; intraperitoneal (i.p.)), 15 min before injection of streptozotocin (STZ; 50 mg/kg; i.p.) in 12-h fasted rats. Two months after induction of diabetes, the rats were sacrificed for subsequent measurements. The nuclear factor kappa B (NF-κB) activity was higher in diabetic peripheral blood mononuclear cells (PBMCs), aorta, heart, kidney, liver, and sciatic nerve, than the control counterparts. Also, apoptosis rate was increased in these tissues, except the aorta. NF-κB messenger RNA (mRNA) expression level was higher in the kidney, heart, PBMCs, and sciatic nerve of diabetic rats than their control counterparts. Except the liver, the miR-155 expression level was significantly decreased in diabetic kidney, heart, aorta, PBMCs, and sciatic nerve versus the controls. Moreover, the expression of miR-155 was negatively correlated with NF-κB activity and apoptosis rate. These results suggest that changes in the expression of miR-155 may participate in the pathogenesis of diabetes-related complications, but causal relationship between miR-155 dysregulation and diabetic complications is unknown

A signature of microRNA-155 in the pathogenesis of diabetic complications.

The current study was designed to explore the potential involvement of miR-155 in the pathogenesis of diabetes complications. Male rats were divided into control and diabetic groups (n = 6). Type 2 diabetes was induced by a single-dose injection of nicotinamide (110 mg/kg; intraperitoneal (i.p.)), 15 min before injection of streptozotocin (STZ; 50 mg/kg; i.p.) in 12-h fasted rats. Two months after induction of diabetes, the rats were sacrificed for subsequent measurements. The nuclear factor kappa B (NF-κB) activity was higher in diabetic peripheral blood mononuclear cells (PBMCs), aorta, heart, kidney, liver, and sciatic nerve, than the control counterparts. Also, apoptosis rate was increased in these tissues, except the aorta. NF-κB messenger RNA (mRNA) expression level was higher in the kidney, heart, PBMCs, and sciatic nerve of diabetic rats than their control counterparts. Except the liver, the miR-155 expression level was significantly decreased in diabetic kidney, heart, aorta, PBMCs, and sciatic nerve versus the controls. Moreover, the expression of miR-155 was negatively correlated with NF-κB activity and apoptosis rate. These results suggest that changes in the expression of miR-155 may participate in the pathogenesis of diabetes-related complications, but causal relationship between miR-155 dysregulation and diabetic complications is unknown.

Deregulation of NF-kB–miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy

The current study was designed to explore whether microRNA-146a and its adapter proteins (tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1)) are involved in the pathogenesis of diabetes neuropathy. Twelve male Sprague Dawley rats were randomized into control and diabetic groups (n = 6). Diabetes was induced by a single-dose injection of nicotinamide (110 mg/kg; i.p.), 15 min before injection of streptozotocin (50 mg/kg; i.p.) in 12-h-fasted rats. Diabetic neuropathy was evaluated by hot plate and tail emersion tests, 2 months after the injection of streptozotocin. The gene expression level of microRNA-146a (miR-146a), IRAK1, TRAF6, and nuclear factor kappa B (NF-κB) was measured in the sciatic nerve of rats using the real time-PCR method. Moreover, the activity of NF-κB and the concentration of pro-inflammatory cytokines were determined by the ELISA method. In comparison with the control group, a threefold increase in the expression of miR-146a and NF-κB, and a twofold decrease in the expression of TRAF6 were observed in the sciatic nerve of diabetic rats. Furthermore, the NF-κB activity and the concentration of TNF-α, interleukin 6 (IL-6), and interleukin 1β (IL-1β) in the sciatic nerve of diabetic rats were higher than in those of control counterparts. These results suggest that a defect in the NF-кB–miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy

Anti-inflammatory properties of resveratrol in the retinas of type 2 diabetic rats.

Resveratrol (trans-3,5,4'-trihydroxystilbene) is a nutritional supplement with anti-inflammatory properties. The present study investigated the long-term anti-inflammatory property of resveratrol in the retinas of type 2 diabetic rats. Male Wistar rats were divided into four groups: normal control, diabetic control, resveratrol-treated normal rats and resveratrol-treated diabetic rats. Type 2 diabetes was induced by a single dose injection of streptozotocin (50 mg/kg; i.p.) 15 min after the administration of nicotinamide (110 mg/kg; i.p.) in 12-h fasted rats (the streptozotocin-nicotinamide type 2 diabetic model). Oral resveratrol administration (5 mg/kg per day for 4 months) significantly improved glucose tolerance, and alleviated hyperglycemia and weight loss in diabetic rats. Furthermore, resveratrol administration significantly decreased the elevated levels of nuclear factor-κB activity, and mRNA expression, tumour necrosis factor alpha level and apoptotic cells in the retinas of the diabetic rats. Furthermore, resveratrol did not significantly affect plasma insulin levels. Long-term resveratrol administration has beneficial anti-inflammatory properties in a rat model of diabetes. However, whether resveratrol exerts its effects directly or through reducing blood glucose levels requires further investigation.