Influence of microcurrent on the modulation of remodelling genes in a wound healing assay.

The literature has shown the beneficial effects of microcurrent (MC) therapy on tissue repair. We investigated if the application of MC at 10 µA/90 s could modulate the expression of remodeling genes transforming growth factor beta (Tgfb), connective tissue growth factor (Ctgf), insulin-like growth factor 1 (Igf1), tenascin C (Tnc), Fibronectin (Fn1), Scleraxis (Scx), Fibromodulin (Fmod) and tenomodulin in NIH/3T3 fibroblasts in a wound healing assay. The cell migration was analyzed between days 0 and 4 in both fibroblasts (F) and fibroblasts + MC (F+MC) groups. On the 4th day, cell viability and gene expression were also analyzed after daily MC application. Higher expression of Ctgf and lower expression of Tnc and Fmod, respectively, were observed in the F+MC group in relation to F group (p < 0.05), and no difference was observed between the groups for the genes Tgfb, Fn1 and Scx. In cell migration, a higher number of cells in the scratch region was observed in group F+MC (p < 0.05) compared to group F on the 4th day, and the cell viability assay showed no difference between the groups. In conclusion, MC therapy at an intensity/time of 10 µA/90 s with 4 daily applications did not affect cell viability, stimulated fibroblasts migration with the involvement of Ctgf, and reduced the Tnc and Fmod expression.

Short-term effects induced by nicotinamide in ovariectomized females.

Nicotinamide adenine dinucleotide (NAD)+ precursors such as nicotinamide activate sirtuins and enhance energy metabolism. The aim of this study was to evaluate the metabolic effects of nicotinamide in ovariectomized (OVX) female rats to establish molecular targets against obesity, which support the safe therapeutic application of nicotinamide. The OVX animals were divided into groups: SHAM (simulated surgery), SHAMn (two weeks of 35 mg·kg-1 nicotinamide per day, by gavage), OVX, and OVXn (two weeks of 35 mg·kg-1 nicotinamide per day, by gavage). The results indicated that nicotinamide favored lipolysis, as evidenced by an increase in free fatty acid and hepatic triglyceride levels, which were not fully normalized during the treatment period. The lipolysis appeared to be due to increased SIRT1 and mitochondrial oxidative phosphorylation in muscle and adipose tissue. There were decreases in muscle and fat nicotinamide N-methyltransferase (NNMT), which were associated with decreases in mass and triglyceride, low-density lipoprotein cholesterol (LDLc), and total cholesterol content. Nicotinamide appeared to be beneficial for the glycemic profile, with normal hepatic glycogen storage and a tendency towards insulin sensitivity in the OVXn. In the SHAMn group, nicotinamide led to glucose intolerance, together with reduced muscle expressions of nicotinamide phosphoribosyltransferase (NAMPT) and SIRT3, suggesting that there were no short-term benefits. Supplementation with nicotinamide led to tissue-specific adaptive lipid and molecular changes in OVX rats.

Vitamin E supplementation and caloric restriction promotes regulation of insulin secretion and glycemic homeostasis by different mechanisms in rats.

Vitamin E and caloric restriction have antioxidant effects in mammals. The aim of this study was to evaluate effects of vitamin E supplementation and caloric restriction upon insulin secretion and glucose homeostasis in rats. Male Wistar rats were distributed among the following groups: C, control group fed ad libitum; R, food quantity reduction of 40%; CV, control group supplemented with vitamin E [30 mg·kg-1·day-1]; and RV, food-restricted group supplemented with vitamin E. The experiments ran for 21 days. Glucose tolerance and insulin sensitivity was higher in the CV, R, and RV groups. Insulin secretion stimulated with different glucose concentrations was lower in the R and RV groups, compared with C and CV. In the presence of glucose and secretagogues, insulin secretion was higher in the CV group and was lower in the R and RV groups. An increase in insulin receptor occurred in the fat pad and muscle tissue of groups CV, R, and RV. Levels of hepatic insulin receptor and phospho-Akt protein were higher in groups R and RV, compared with C and CV, while muscle phospho-Akt was increased in the CV group. There was a reduction in hepatic RNA levels of the hepatocyte growth factor gene and insulin degrading enzyme in the R group, and increased levels of insulin degrading enzyme in the CV and RV groups. Thus, vitamin E supplementation and caloric restriction modulate insulin secretion by different mechanisms to maintain glucose homeostasis.

Vitamin E and caloric restriction promote hepatic homeostasis through expression of connexin 26, N-cad, E-cad and cholesterol metabolism genes.

Connexins (Cx) and cadherins are responsible for cell homeostasis. The Cx activity is directly related to cholesterol. The present work investigates whether vitamin E, with or without caloric restriction (CR), alters the mRNA expression of Cx26, Cx32, Cx43, N-cadherins (N-cads), E-cadherins (E-cads) and alpha-smooth muscle actin (α-SMA), and evaluates their relation to cholesterol metabolism in rat liver. Animals were divided into different groups: control with ad libitum diet (C), control+vitamin E (CV), aloric restriction with intake to 60% of group C (CR), and the intake of group CR+vitamin E (RV). There were increases of manganese superoxide dismutase (Mn-SOD) and glutathione S-transferase mu 1, indicating antioxidant effects of CR and vitamin E. An increase of nitric oxide in the CR group was in agreement with the Mn-SOD data. Supplementation with vitamin E, with or without CR, upregulated the expression of Cx26 mRNA and increased low-density lipoprotein cholesterol (LDL-c) in the CV group. Reductions of Cx32 and Cx43 were associated with lower LDL-c. Increases in Hmgcr and low-density lipoprotein receptor (LDLr) in the CV and RV groups could be explained by the effect of vitamin E. A reduction of LDLr in the CR group was due to the reduced dietary intake. Increases in cadherins in the CV, CR and RV groups were indicative of tissue maintenance, which was also supported by increases of α-SMA in groups CV and RV. Finally, vitamin E, with or without CR, increased Cx26, probably modulated by expression of the Hmgcr and LDLr genes. This suggests important relationship of Cxs and cholesterol metabolism genes.