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Age-induced decline in renal function could markedly increase the risk of chronic kidney disease. DL-3-n-butylphthalide (DI-NBP) has notable anti-inflammasome and anti-oxidant effects. However, it’s still unclear whether DI-NBP exerts functions in renal senescence. Thus, the study aims to investigate the effects of DI-NBP on AGE-induced mesangial cells aging and illuminate related pathological process. The cell proliferation levels were detected by CCK8 assay and EDU/DAPI staining, along with the identification of aging-related proteins (β-Gal, p53, p21, p16) by β-Gal staining or Western blot. Intracellular reactive oxygen species (ROS) detection was also performed by ROS kit. In addition, inflammation was evaluated by NLRP3 inflammasome and inflammation-related markers. The results presented increased cell proliferation. Moreover, AGEs-induced cell aging was significantly decreased by DI-NBP, accompanied by decreased ROS levels. Furthermore, DI-NBP reduced NLRP3/caspase1 axis activation and inhibited inflammation in AGEs-induced mesangial cell aging. Thus, DI-NBP might produce significant protective effects on renal aging via decreasing pro-aging-related proteins, oxidative stress and inflammation. DI-NBP could be a potential drug for delaying renal aging.

Background Phenotypic switching of vascular smooth muscle cells (VSMCs) plays a key role in atherosclerosis. Long noncoding RNA ANRIL (lncRNA-ANRIL) is critical in vascular homeostasis. Metformin produces multiple beneficial effects in atherosclerosis. However, the underlying mechanisms need to be elucidated. Methods and results Metformin increased lncRNA-ANRIL expression and AMPK activity in cultured VSMCs, and inhibited the phenotypic switching of VSMCs to the synthetic phenotype induced by platelet-derived growth factor (PDGF). Overexpression of lncRNA-ANRIL inhibited phenotypic switching and reversed the reduction of AMPK activity in PDGF-treated VSMCs. While, gene knockdown of lncRNA-ANRIL by adenovirus or silence of AMPKγ through siRNA abolished AMPK activation induced by metformin in VSMCs. RNA-immunoprecipitation analysis indicated that the affinity of lncRNA-ANRIL to AMPKγ subunit was increased by metformin. In vivo, administration of metformin increased the levels of lncRNA-ANRIL, suppressed VSMC phenotypic switching, and prevented the development of atherosclerotic plaque in Apoe-/- mice fed with western diet. These protective effects of metformin were abolished by infecting Apoe-/- mice with adenovirus expressing lncRNA-ANRIL shRNA. The levels of AMPK phosphorylation, AMPK activity, and lncRNA-ANRIL expression were decreased in human atherosclerotic lesions. Conclusion Metformin activates AMPK to suppress the formation of atherosclerotic plaque through upregulation of lncRNA-ANRIL.

This study was aimed at determining whether late gadolinium enhancement (LGE) in conjunction with Galectin-3 (Gal-3) level offered more precise prognosis of non-ischemic cardiomyopathy (NICM) in comparison to LGE alone. Results of LGE and Gal-3 expression in 192 patients with NICM, including 85 subjects with dilated cardiomyopathy (DCM) and 107 with hypertrophic cardiomyopathy (HCM), were examined. As suggested by the characteristics of LGE and Gal-3 levels, patients were divided into four groups: LGE positive + low Gal-3 (n = 10 for DCM, n = 15 for HCM), LGE positive + high Gal-3 (n = 25 for DCM, n = 51 for HCM), LGE negative + low Gal-3 (n = 32 for DCM, n = 29 for HCM), LGE negative + high Gal-3 (n = 18 for DCM, n = 12 for HCM). Primary endpoints over the follow-up period included major adverse cardiac events (MACEs). Kaplan–Meier survival analysis and univariate Cox proportional hazard models were used to analyze the survival status of patients with NICM. The optimal cut-off value of Gal-3 level for two types of NICM was determined by receiver operating characteristic analysis (13.38 U/L for DCM and 14.40 U/L for HCM). The combination of LGE and Gal-3 levels offered a more significant prognostic value than using LGE alone for both DCM and HCM (DCM P = 0.001

Vascular endothelial dysfunction is the major contributing factor to hypertension. Endothelial progenitor cells (EPCs) are essential for endogenous vascular endothelial renovation. The activity and number of circulating EPCs are preserved in prehypertensive premenopausal females according to our previous research. However, the changes of EPCs in prehypertensive postmenopausal females are poorly understood, and the mechanisms responsible for the loss of the gender protection advantage of cardiovascular disease remain unexplored. In order to determine the effects of EPCs in prehypertensive postmenopausal females, the number and activity of circulating EPCs were tested in the present study. Next, the function of EPCs secreting nitric oxide (NO), vascular endothelial growth factor (VEGF) and granulocyte‑macrophage colony‑stimulating factor (GM‑CSF), as well as their concentration in the plasma, were measured. The association between flow‑mediated dilation (FMD) and EPC secretion was also assessed. Attenuation of proliferation and migration of EPCs was observed in prehypertensive patients in comparison with normotensive subjects. In addition, a reduced NO production secreted by EPCs was detected in prehypertensive patients as compared with that in normotensive patients. There was no significant difference in EPC function between postmenopausal females and age‑matched males. Finally, the association between FMD and NO production was validated. Collectively, these data indicated that impaired EPCs mediated vasodilation dysfunction via decreasing NO production. Therefore, EPC function enhancement and NO level augmentation are emerging as novel therapeutic strategies for prehypertension therapy.

Previous studies have demonstrated that the deleterious effect of diabetes mellitus (DM) on the risk of cardiovascular disease also occurs in premenopausal women, in spite of their relatively high estrogen levels; however, the underlying mechanism remains unclear. The present study aimed to investigate the sex‑related differences in circulating endothelial progenitor cells (EPCs) in a relatively young population with type 2 DM (T2DM) and its underlying mechanism. The number and functional activity of circulating EPCs, and vascular endothelial function assessed using flow‑mediated dilation (FMD), were compared in premenopausal women and age‑matched men with or without T2DM. Nitric oxide (NO) in the plasma or NO secreted by EPCs was also measured. The number and activity of circulating EPCs, and NO levels in the plasma or culture medium, were lower in premenopausal women with T2DM compared with those without T2DM. In addition, the number and activity of circulating EPCs and NO levels were decreased in men with T2DM compared with in age‑matched premenopausal women with T2DM. FMD was positively correlated with the number and activity of circulating EPCs, and NO levels. In conclusion, DM in premenopausal women may significantly impair the repair capability of EPCs and lead to endothelial dysfunction, which may be associated with reduced NO production. In patients with both DM and normal glucose tolerance, sex‑related differences of EPCs are presented in a young population.