Epigenetic Control of Hypertension by DNA Methylation: A Real Possibility.

Hypertension is a common chronic disease that particularly affects the elderly and can trigger several cardiovascular conditions. Although the treatment of hypertension has evolved in recent decades, many hypertensive patients still do not have properly controlled blood pressure. Accumulating evidence supports the hypothesis that DNA methylation plays an important role in regulating gene expression, altering the phenotype and function of the cardiovascular system. The present review highlights recent advances in research on DNA methylation in the development of hypertension. Several preclinical and clinical evidence show that methylation of different targets appears to be involved in hypertension. Studies of the involvement of DNA methylation have greatly improved our understanding of hypertension, but its use as a valid therapeutic target is still unknown. Further studies could help to bring to light the truth about gene therapy in hypertension.

Predictive Value of Sirtuins in Acute Myocardial Infarction - Bridging the Bench to the Clinical Practice.

Acute myocardial infarction (AMI) is a non-transmissible condition with high prevalence, morbidity, and mortality. Different strategies for the management of AMI are employed worldwide, but its early diagnosis remains a major challenge. Many molecules have been proposed in recent years as predictive agents in the early detection of AMI, including troponin (C, T, and I), creatine kinase MB isoenzyme, myoglobin, heart-type fatty acid-binding protein, and a family of histone deacetylases with enzymatic activities named sirtuins. Sirtuins may be used as predictive or complementary treatment strategies and the results of recent preclinical studies are promising. However, human clinical trials and data are scarce, and many issues have been raised regarding the predictive values of sirtuins. The present review summarizes research on the predictive value of sirtuins in AMI. We also briefly summarize relevant clinical trials and discuss future perspectives and possible clinical applications.

Effects of acute and chronic quercetin administration on methylphenidate-induced hyperlocomotion and oxidative stress.

AIMS: Increases in protein kinase C (PKC) and oxidative stress have been related to mania. Drugs with antioxidant effects or inhibitory actions on PKC may have antimanic effects. The flavonoid quercetin has antioxidant and PKC-inhibiting effects that resemble those of lithium, the first-line treatment for mania in bipolar disorder. We hypothesized that quercetin may have antimanic-like effects in an animal model. MAIN METHODS: In the present study, we investigated the effects of acute and chronic treatment with quercetin (2.5, 5, 10, and 40mg/kg, i.p.) in male Swiss mice that were subjected to methylphenidate (5mg/kg, i.p.)-induced hyperlocomotion, an animal model of mania. Lithium (100mg/kg, i.p.) and diazepam (5mg/kg, i.p.) were used as positive and negative controls, respectively. We also evaluated the effects of these treatments on methylphenidate-induced oxidative stress in the brain by measuring reduced glutathione (GSH) and lipid peroxidation (LPO) levels in the prefrontal cortex, hippocampus, and striatum. KEY FINDINGS: Acute and chronic (21-day) treatment with lithium and diazepam reduced methylphenidate-induced hyperlocomotion. Chronic but not acute treatment with quercetin (10 and 40mg/kg) blocked methylphenidate-induced hyperlocomotion. These effects of lithium and quercetin occurred at doses that did not alter spontaneous locomotor activity, whereas diazepam reduced spontaneous locomotor activity. Chronic treatment with lithium and quercetin blocked the methylphenidate-induced increase in LPO levels in the striatum. SIGNIFICANCE: These results suggest that chronic quercetin treatment has antimanic-like and antioxidant effects, thus encouraging further studies of quercetin as a putative new antimanic drug.

Necroptosis mediates the antineoplastic effects of the soluble fraction of polysaccharide from red wine in Walker-256 tumor-bearing rats.

Polysaccharides are substances that modify the biological response to several stressors. The present study investigated the antitumor activity of the soluble fraction of polysaccharides (SFP), extracted from cabernet franc red wine, in Walker-256 tumor-bearing rats. The monosaccharide composition had a complex mixture, suggesting the presence of arabinoglactans, mannans, and pectins. Treatment with SFP (30 and 60mg/kg, oral) for 14days significantly reduced the tumor weight and volume compared with controls. Treatment with 60mg/kg SFP reduced blood monocytes and neutrophils, reduced the tumor activity of N-acetylglucosaminidase, myeloperoxidase, and nitric oxide, increased blood lymphocytes, and increased the levels of tumor necrosis factor α (TNF-α) in tumor tissue. Treatment with SFP also induced the expression of the cell necroptosis-related genes Rip1 and Rip3. The antineoplastic effect of SFP appears to be attributable to its action on the immune system by controlling the tumor microenvironment and stimulating TNF-α production, which may trigger the necroptosis pathway.

Quercetin reduces manic-like behavior and brain oxidative stress induced by paradoxical sleep deprivation in mice.

Quercetin is a known antioxidant and protein kinase C (PKC) inhibitor. Previous studies have shown that mania involves oxidative stress and an increase in PKC activity. We hypothesized that quercetin affects manic symptoms. In the present study, manic-like behavior (hyperlocomotion) and oxidative stress were induced by 24h paradoxical sleep deprivation (PSD) in male Swiss mice. Both 10 and 40mg/kg quercetin prevented PSD-induced hyperlocomotion. Quercetin reversed the PSD-induced decrease in glutathione (GSH) levels in the prefrontal cortex (PFC) and striatum. Quercetin also reversed the PSD-induced increase in lipid peroxidation (LPO) in the PFC, hippocampus, and striatum. Pearson's correlation analysis revealed a negative correlation between locomotor activity and GSH in the PFC in sleep-deprived mice and a positive correlation between locomotor activity and LPO in the PFC and striatum in sleep-deprived mice. These results suggest that quercetin exerts an antimanic-like effect at doses that do not impair spontaneous locomotor activity, and the antioxidant action of quercetin might contribute to its antimanic-like effects.