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Oxytocin (OT) is a nonapeptide hormone that can improve cardiomyocyte proliferation, suggesting a potential heart regeneration function. Here, we investigated the role of oxytocin and the c-Myc pathway in cardiac remodeling in neonatal rats undergoing cardiac apical resection. We have utilized a knockout of oxytocin receptor (OTR) with OTR-shRNA. A neonatal rat model of cardiac resection (≈10%-15%) was first established. The protein levels of OTR and c-Myc and the expression of cyclin d1 and c-Myc genes were then evaluated in the cardiac tissues at 1, 7, and 21 days after cardiac resection. We also analyzed the proliferation of cardiomyocytes through α-actinin, BrdU, and ki-67 markers. At last, the hemodynamic and electrophysiologic functions were evaluated eight weeks after cardiac resection. At 21 days, the regeneration of cardiomyocytes was repaired among rats in the control and resection groups, while OTR-shRNA groups were failed to improve. Inhibition of OTR failed cardiac regeneration and reduced the number of proliferating cardiomyocytes. The c-Myc protein was significantly reduced in the OTR-shRNA injection hearts. Moreover, we have severely found a depressed heart function in the OTR-shRNA injection animals. These observations revealed that the OT must improve cardiac remodeling in neonatal rat hearts by regulating the c-Myc pathway.Pulmonary fibrosis (PF) is a progressive respiratory disease. Phycocyanin derived eicosapeptide (PP20) is a novel peptide derived from active protein C-phycocyanin in Cyanobacteria. The aim of our study was to explore the anti-fibrotic activity of the PP20 and its underlying mechanism. Characteristic features of pulmonary fibrosis in oleic acid (OA)-induced mice and epithelial-mesenchymal transition (EMT) in TGF-β1-exposed A549 and HFL-1 cells with or without PP20 and the change of TGF-β/Smad and MAPK signaling pathways were examined. Smad and MAPK agonists were used to explore the role of TGF-β/Smad and MAPK signaling in TGF-β1- induced collagen I expression in A549 cells and α-SMA expression in HFL-1 cells when treated with PP20. Our results showed that PP20 significantly alleviated the inflammatory response and tissue destruction, inhibited EMT, restored the imbalance of TIMP-1/MMP-9 and reduced collagen fiber deposition. Moreover, PP20 inhibited TGF-β1-induced EMT and collagen I expression in A549 cells. PP20 could also inhibit the proliferation, and decrease TGF-β1-induced the expression of collagen I and transformation of fibroblasts into myofibroblasts in HFL-1 cells. Additionally, animal experiments and cell experiments combined with pathway agonists have shown that PP20 can negatively regulate TGF-β/Smad and MAPK pathways and show anti-fibrotic properties. Selleckchem K03861 PP20 may be a promising drug candidate for protection against pulmonary fibrosis.Thymosin beta 4 (Tβ4) can improve the liver fibrosis and reduce inflammation, while the role of Tβ4 in non-alcoholic fatty liver disease (NAFLD) whether mediated by ferroptosis remains unclear. A rat model of NAFLD was established on a high-fat diet (HFD), and rats were assigned ferroptosis inducer erastin and inhibitor Ferrostatin 1 (Fer-1). Subsequently, histopathology of the liver and the expression of ferroptosis-related genes in rat liver were detected. The steatosis of LO2 cells was induced by palmitic acid (PA) to reproduce the results of the rat experiment. The small interfering RNA (siRNA) was used to interfere with GPX4 expression to explore the influence on Tβ4 function. Tβ4 improved the inflammation, biochemical and lipid metabolism indexes, increased the antioxidant level, and inhibited abnormal accumulation of intracellular reactive oxygen species in HFD-induced NAFLD rats. Also, Tβ4 improved PA-induced LO2 damage and inhibited apoptosis of PA-induced LO2 cells. Both in vivo and in vitro, Tβ4 regulated expression of genes associated with ferroptosis, and Fer-1 treatment exaggerated the above effects of Tβ4, while erastin attenuated the protective effect of Tβ4. Moreover, siRNA GPX4 attenuated the protective effect of Tβ4 on the rat liver and on the mitochondrial membrane integrity of LO2 cells. Interfered expression of GPX4 with siRNA also regulated the expression of Bcl-2, Bax, Caspase-3 and SOD1, which attenuated therapeutic effect of Tβ4 on rat liver and LO2 cells. This study revealed that Tβ4 protects hepatocytes by inhibiting the GPX4-mediated ferroptosis pathway, which provides a new strategy and target for the treatment of NAFLD.A new adipocytokine, visfatin is expressed in perivascular adipose tissue (PVAT) and exerts effects on vascular system in addition to its relationship with various pathological conditions. The present study aimed to investigate the functional effects of visfatin and the possible underlying mechanism(s) of the effects of visfatin in isolated rat mesenteric small resistance arteries. The study was conducted in small resistance arterial rings isolated from rat mesenteric vascular beds. While visfatin incubation did not produce significant alterations in contractile responses of mesenteric arterial rings to noradrenaline, relaxation responses to acetylcholine but not to sodium nitroprusside (SNP) were significantly reduced in endothelium-intact rings. The inhibitory effect of visfatin on responses to acetylcholine was not observed in endothelium-denuded preparations. Incubation of tissues with nicotinamide phosphoribosyl transferase (NAMPT) inhibitor FK866 or superoxide dismutase (SOD) reversed the inhibitory effects of visfatin on relaxation responses to acetylcholine. Co-incubation of visfatin with Nω-nitro-L-arginine methylester (L-NAME) did not produce a significant alteration in vascular responses to acetylcholine compared to L-NAME incubation alone. Mesenteric PVAT visfatin levels were significantly higher than and correlated positively with plasma visfatin levels. The results of our study indicated that visfatin-induced reductions in endothelium-dependent relaxations of rat isolated small resistance arteries are mediated by oxygen free radicals and a reduction in nitric oxide (NO) bioavailability. It was suggested that increment in systemic and/or local visfatin levels due to various pathologies including obesity and excessive weight gain may play a substantial role in initiation and/or propagation of vascular dysfunctions.
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