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The initiation of atherosclerosis (AS) induced by dyslipidemia is accompanied by endothelial dysfunction, including decreased healing ability and increased recruitment of monocytes. Studies showed ginsenoside Rg3 has potential to treat diseases associated with endothelial dysfunction which can protects against antineoplastic drugs induced cardiotoxicity by repairing endothelial function, while the effect and mechanism of Rg3 on dyslipidemia induced endothelial dysfunction and AS are not clear. Therefore, we investigated the effects of Rg3 on oxidized low-density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVECs) dysfunction and high-fat diets (HFD) induced atherosclerosis in ApoE −/− mice, as well as the mechanism. For in vitro assay, Rg3 enhanced healing of HUVECs and inhibited human monocytes (THP-1) adhesion to HUVECs disturbed by ox-LDL, down-regulated focal adhesion kinase (FAK)-mediated expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1); restrained the FAK-mediated non-adherent dependent pathway containing matrix metalloproteinase (MMP)-2/9 expression, activation of nuclear factorkappa B (NF-kB), high mRNA levels of monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6), besides Rg3 up-regulated peroxisome proliferators-activated receptor g (PPARg) in ox-LDL-stimulated HUVECs. GW9662, the PPARg-specific inhibitor, can repressed the effects of Rg3 on ox-LDL-stimulated HUVECs. For in vivo assay, Rg3 significantly reduced atherosclerotic pathological changes in ApoE −/− mice fed with HFD, up-regulated PPARg, and inhibited activation FAK in aorta, thus inhibited expression of VCAM-1, ICAM-1 in intima. We conclude that Rg3 may protect endothelial cells and inhibit atherosclerosis by up-regulating PPARg via repressing FAK-mediated pathways, indicating that Rg3 have good potential in preventing dyslipidemia induced atherosclerosis.

The cardioprotective effects of ginsenoside Rb2 on oxidative stress, which is induced by hydrogen peroxide and myocardial ischemia/reperfusion (MI/R) injury, have been studied. The mechanisms were associated with the inhibition of cardiomyocyte apoptosis, a high concentration of antioxidant defense enzymes, and scavenging oxidative stress products. Because of the association with oxidative reaction and cardioprotection, sirtuin‐1 (SIRT1) was selected as a promising target for investigating whether MI/R injury can be alleviated by ginsenoside Rb2 pretreatment through SIRT1 activation. The rats were exposed to ginsenoside Rb2 with or without SIRT1 inhibitor EX527 before ligation of coronary artery. Ginsenoside Rb2 reduced myocardial superoxide generation; downregulated gp91phox expression; and decreased the mRNA expression levels and activities of interleukin‐1β, interleukin‐6, and tumor necrosis factor‐α. The results demonstrated that ginsenoside Rb2 significantly attenuated oxidative stress and inflammation induced by MI/R injury. In addition, ginsenoside Rb2 upregulated SIRT1 expression and downregulated Ac‐p53 expression. However, EX527 blocked the protective effects, indicating that the pharmacological action of ginsenoside Rb2 involves SIRT1. Our results thus revealed that ginsenoside Rb2 alleviated MI/R injury in rats by inhibiting oxidative stress and inflammatory response through SIRT1 activation. Practical Application Ginsenoside Rb2 has a protective effect on MI/R injury by activating SIRT1 expression, reducing myocardium inflammation, and alleviating oxidative stress. Thus, ginsenoside Rb2 is a promising novel agent for ameliorating MI/R injury in ischemic heart diseases and cardiac surgery.

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BackgroundGrowth differentiation factor (GDF) acted as a factor that regulated proliferation, apoptosis and differentiation in several tumors. However, the effects of growth differentiation factor (GDF11) in pancreatic cancer remain unclear.PurposeTo investigate the expression and significance of GDF11 in pancreatic cancer.Patients and methodsPancreatic cancer and corresponding paracancerous tissues (n=28) were collected from the Department of Hepatobiliary and Pancreatic Surgical Oncology of Chinese PLA General Hospital. Tissue microarray was obtained from Outdo Biotech Co., Ltd. (Shanghai, People’s Republic of China). GDF11 mRNA and protein expressions in pancreatic cancer samples and cell lines were detected using qRT-PCR, Western-Blot and immunohistochemistry. Overexpression and knockdown of GDF11 were performed with lentiviral transduction system and siRNA technique in PANC-1 cell line and CFPAC-1 cell line. Proliferation, migration and invasion of pancreatic cancer cell lines were examinated by MTS and transwell assay, respectively. Flow cytometry was used for cell apoptosis analysis.ResultsThe results of this study indicated that GDF11 was significantly down-regulated in pancreatic cancer tissues compared with adjacent tissues of pancreatic cancer. GDF11 was also associated with low expression in pancreatic cancer cell lines when compared with normal pancreatic cell line. In a cohort of 63 pancreatic cancer patients, high GDF11 expression levels was associated with favorable perineural invasion, T classification, N classification and overall survival (OS). Cox proportional hazards model revealed that high GDF11 expression was an independent predictor of favorable prognosis (HR: 0.496; 95% CI: 0.255–0.967; P=0.040). Overexpression of GDF11 in PANC-1 cells repressed the proliferation, migration and invasion abilities in vitro. Inhibition of GDF11 in CFPAC-1 showed inverse results. Furthermore, enhanced GDF11 expression promoted apoptosis and down-regulated GDF11 expression inhibited apoptosis in pancreatic cancer cell lines.ConclusionThese findings suggested that GDF11 acted as a tumor suppressor gene for pancreatic cancer.