Circulating MicroRNA-30a, Beclin1 and Their Association with Different Variables in Females with Metabolically Healthy /Unhealthy Obesity.

Background: Obesity is associated with metabolic and cardiovascular co-morbidities. It is important to determine the factors associated with metabolic derangement in obesity. Autophagy plays a major role in the pathogenesis of metabolic syndrome. MicroRNA-30a targets beclin1, the main regulator of autophagy. Purpose: We assess circulating microRNA-30a and serum beclin1 in women with metabolically unhealthy obesity (MUO), women with metabolically healthy obesity (MHO) and non-obese healthy control and determine their relationship with different clinical and metabolic variables in women with obesity. Patients and Methods: This cross-sectional study included 34 women with MHO, 34 with MUO, and 20 healthy non-obese women. Blood pressure, body mass index (BMI), and waist circumference were recorded. Glycemic and lipid indices, urinary albumin-to-creatinine ratio, ALT, AST, microRNA-30a expression in serum were measured using real-time polymerase chain reaction and beclin1 by enzyme-linked immunosorbent assay were measured. Results: The expression of microRNA-30a was significantly higher, and beclin1 level was significantly lower in women with MUO compared to those in women with MHO (P<0.001; for both). People with MUO were significantly older (P<0.001) and had higher TSH (P=0.006), HbA1c (P<0.001), triglyceride (P<0.001), and ALT (P<0.001) compared to women with MHO. However, there was no significant difference between the two groups in any anthropometric measurements, HDL-C or LDL-C. In univariate analyses, age, ALT, TSH, microRNA-30a, and beclin1 were significantly correlated with the MUO phenotype (P<0.001; for all). Significance was confirmed in the multivariate analysis for microRNA-30a (95% CI 1.317-28.252; P=0.021). Conclusion: MicroRNA-30a, beclin1, age, and ALT and TSH levels were significantly associated with the MUO phenotype, among which microRNA-30a was the best indicator of metabolic syndrome in women with obesity.

Antioxidant and anti-inflammatory properties of alpha-lipoic acid protect against valproic acid-induced liver injury.

Valproic acid (VPA) is one of the most used antiepileptic drugs despite of its many adverse effects such as anemia, leucopenia, thrombocytopenia, and liver toxicity. The hepatoprotective effect of alpha-lipoic acid (ALA) was confirmed. The aim of this study was to detect the protective effect of ALA against the adverse effects of VPA. To study this, 30 white albino Wistar male rats were divided into four groups. Group I was the control group; Group II included rats that received ALA (100 mg·kg-1·day-1) orally for 14 days; Group III and Group IV included rats that received VPA (500 mg·kg-1·day-1) for 15 days intraperitoneally, but Group IV rats received ALA (100 mg·kg-1·day-1) orally for 14 days prior to VPA. Blood samples were collected and livers were excised from rats for colorimetric analysis and quantitative real-time PCR. The rats that received VPA showed leucopenia, thrombocytopenia, a significant decrease of superoxide dismutase, glutathione, nuclear factor erythroid 2-related factor 2, and sirtuin 1, besides a significant increase of malondialdehyde and tumor necrosis factor α. Prior treatment with ALA prevented all these results; ALA protected against VPA-induced liver damage and hematological disturbance via antioxidant and anti-inflammatory properties.

Contribution of volume overload to progression of cardiovascular disease in a rat model of chronic kidney disease.

Volume overload is a common phenomenon in patients with chronic kidney disease that is associated with cardiovascular risk factors. However, its contribution to the development of adverse cardiovascular outcomes in those patients is not fully understood. Thus, the present work investigated the effect of salt-induced volume overload on cardiac functions and geometry in a rat model of chronic kidney disease. Thirty adult male Sprague-Dawley rats were randomly divided. One set of animals received a sham operation, while another set of animals underwent uninephrectomy. Rats were then fed either a normal-salt (0.4%) or high-salt (8.0%) diet for 6 weeks. The salt-loaded, uninephrectomized rats were treated with indapamide (3 mg·kg-1·day-1, orally) for 6 weeks. We found that uninephrectomized rats subjected to a high-salt diet (8.0%) for 6 weeks presented with hypertension, proteinuria, decreased renal Klotho expression, and deterioration in cardiac hemodynamics and histology. Echocardiography to assess cardiac function showed that ejection fraction and fractional shortening were positively correlated with relative renal Klotho expression. In conclusion, salt-induced volume overload in a rat model of chronic kidney disease has an adverse cardiovascular outcome and is associated with inflammatory activation and decrease in renal Klotho expression.

Combined effect of bone marrow derived mesenchymal stem cells and nitric oxide inducer on injured gastric mucosa in a rat model.

AIM: To study the effect of intravenous injection of bone marrow mesenchymal stem cells (BMMSCs), alone and combined with NO inducer in gastric ulcer healing in a rat model. METHODS: Rats were divided into controls, gastric ulcer, gastric ulcer receiving mesenchymal stem cells (MSCs), gastric ulcer receiving NO inducer (l-Arginine), gastric ulcer receiving MSCs plus NO inducer (l-Arginine) groups. MSCs were given in a dose of (106cells) by intravenous injection. l-Arginine was given 300mg/kg body weight intraperitoneally. 24h and 7days after BMMSCs and NO inducer injection, VEGF, PGE, TNF-α were assessed by ELISA. Gene expression of HGF, caspase-3, eNOS and BAX/Bcl-2 in gastric tissues were studied by real time PCR. Histopathology staining of gastric tissues was performed. RESULTS: Injection of MSCs or NO inducer or both to the gastric ulcer group significantly decreased caspase-3 and BAX genes expression (apoptotic factors) and increased Bcl-2 gene expression (anti-apoptotic factor) compared to that of the gastric ulcer group after both 24h and 7days with more significant results in the gastric group received both MSCs and NO inducer. HGF gene expression was significantly increased in the groups injected with MSCs or NO inducer or both compared with the corresponding gastric ulcer group (p<0.05, p<0.05 & p<0.001 respectively). There was a significant decrease in the mean PGE2 and TNF-α levels in the gastric ulcer group receiving MSCs, the gastric ulcer group receiving NO and the gastric ulcer group receiving both MSCs andNO compared to the gastric ulcer group after both 24h and 7days. Histopathological examination of gastric tissue of groups that received stem cells or NO alone, showed mucosal regenerative changes with increased thickness together with reduced inflammatory cellular infiltrate in the submucosa and decreased congestion. There was complete restoration in gastric mucosa in the group that received both stem cells and NO. CONCLUSION: Administration of MSCs, NO, or MSCs plus NO may exert a therapeutic effect on the mucosal lesion in gastric ulcer through their anti-inflammatory, angiogenic and antiapoptotic actions.