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• Expression of CCAT1 and SIRT1 decreased, whereas microRNA-155 was increased in the in vitro model of LPS induced AKI. • CCAT1 restoration and microRNA-155 inhibition exhibited anti-inflammation and pro-survival actions in renal epithelial cells. • SIRT1 knockdown abolished the protective effects of CCAT1 overexpression and microRNA-155 inhibition. • CCAT1 sponged microRNA-155 to regulate the expression of SIRT1. Acute kidney injury (AKI) is characterized by excessive inflammatory response and apoptosis in tubular epithelial cells. Recent studies suggested that long non-coding RNAs colon cancer-associated transcript-1 (CCAT-1) and microRNA-155 (miR-155) might regulate cell death and inflammation. We aimed to explore the role of CCAT-1/miRNA-155 axis in the AKI. LPS was applied to establish in vitro and in vivo models of AKI using HK2 cells and pcDNA-CCAT1 transgenic mice, respectively. Gene overexpression or knockdown were performed through plasmids transfection. Apoptosis were determined by qRT-PCR, western blotting (Fas, FasL, Caspase-3), AnnexinV/PI staining and TUNEL assay. Cytokines were assessed by ELISA. Interaction of CCAT1/miR-155 and miR-155/SIRT1 were detected by dual-luciferase reporter assay. RNA immunoprecipitation (RIP) was also performed to determine CCAT1/miR-155 interaction. Pathological changes of AKI were evaluated using H&E staining, blood urine nitrogen (BUN) and serum creatinine (Cr) detection kits. The degree of renal fibrosis was determined by Masson trichrome stain. LPS administration reduced CCAT1 and SIRT1 expression, but increased miR-155 levels in tubular epithelial cells in vitro. Luciferase assay demonstrated that miR-155 might bind to and regulate CCAT1 and SIRT1. RIP further confirmed the direct interaction of CCAT1 and miR-155. Restoration of CCAT1 attenuated LPS induced inflammation and apoptosis through sequestering miR-155. The anti-inflammation and pro-survival effects of CCAT1 overexpression and miR-155 inhibition were abolished by SIRT1 knockdown, as indicated by the expression of cytokine and apoptotic markers, as well as H&E, BUN and Cr detection. Dysregulated CCAT1/miR-155/SIRT1 pathway regulated disease progression in a murine model of LPS-induced AKI, and NF-κB pathway involved in. CCAT1 restoration sequestered miR-155, leading to upregulation of SIRT1 and alleviated LPS induced renal tubular epithelial cell damage in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Atherosclerosis is an arterial disease associated with inflammation. Hence, the discovery of novel therapeutic agents for suppressing inflammatory responses is urgent and vital for the treatment of atherosclerosis in cardiovascular diseases. The total saponins of Aralia elata (Miq.) Seem. (TAS) are the main components extracted from the Chinese traditional herb Longya Aralia chinensis L., a folk medicine used in Asian countries for treating numerous diseases, enhancing energy and boosting immunity. However, the protective effects of TAS against inflammation-triggered vascular endothelial dysfunction, a critical early event during the course of atherosclerosis, and the potential mechanisms of this protection have been not demonstrated. Accordingly, the aim of this study was to investigate the anti-inflammatory and anti-apoptotic effects and the protective mechanisms of TAS, and show how TAS ameliorates human umbilical vein endothelial cell (HUVEC) damage caused by tumour necrosis factor-α (TNF-α). The results indicated that TAS exerted cytoprotective effects by inhibiting TNF-α-triggered HUVEC apoptosis, mitochondrial membrane potential depolarisation, and the regulation of inflammatory factors (IL-6, MCP-1, and VCAM-1) while suppressing NF-κB transcription. Furthermore, this phenomenon was related to activation of the phosphoinositide 3-kinase (PI3K)/Akt signalling pathway. Blocking the Akt pathway with LY294002, a PI3K inhibitor, reversed the cytoprotective effect of TAS against TNF-α-induced endothelial cell death. Moreover, LY294002 partially abolished the effects of TAS on the upregulation of the Bcl-2 family of proteins and the downregulation of Bax protein expression. In conclusion, the results of our study suggest that TAS suppresses the inflammation and apoptosis of HUVECs induced by TNF-α and that PI3K/Akt signalling plays a key role in promoting cell survival and anti-inflammatory reactions during this process. [ABSTRACT FROM AUTHOR]

Inflammation is a major contributing factor to the progression of atherosclerosis. Ginsenoside Rb1 (Rb1), an active saponin of Panax notoginseng, has been found to exert beneficial effects on inflammation and oxidative stress. This study investigated the ability of Rb1 to inhibit the formation of atherosclerotic plaques and the potential mechanisms. In this study, the effects of Rb1 on the development of atherosclerosis were investigated in ApoE-/- deficient mice fed with a western diet. Mice were intragastrically administrated with Rb1 (10 mg/kg) for 8 weeks. This study is that ginsenoside Rb1 exerted an inhibitory effect on early atherosclerosis in ApoE-/- mice via decreasing body weight and food intake daily, upregulating the lipid levels of serum plasma, including those of TC, TG and LDL-C and HDL-C and reducing the atherosclerotic plaque area, suppressing inflammatory cytokines (levels of IL-1β, IL-6 and TNF-α) in the serum of ApoE-/- mice, changing the expression levels of BCL-2, BAX, cleaved caspase-3 and cleaved caspase-9 and weakening apoptosis associated with anti-inflammatory activity. Hence, all these effects against atherosclerosis were tightly associated with regulation of necrosis or apoptosis associated with anti-inflammatory activity. Additionally, the results found that ginsenoside Rb1 increased autophagy flux to inhibit apoptosis via acceleration of autophagy by promoting transformation of LC3 from type I to type II in high-fat diet-induced atherosclerosis in ApoE-/- mice. This finding, along with those of the previous study, provides evidence that Rb1 promotes the process of autophagy to protect against atherosclerosis via regulating BCL-2 family-related apoptosis. These results indicate that Rb1 exhibits therapeutic effects in atherosclerosis by reversing the imbalance between apoptosis and autophagy. [ABSTRACT FROM AUTHOR]

Ischemia/reperfusion (IR) injury causes damage in aerobically metabolizing organs or tissues, which is an essential injury mechanism in various clinical settings. SRY-related high mobility group-Box gene 9 (SOX9) is a transcription factor of the SRY family, modulating various cellular processes, including fibrosis formation and tumor growth. However, the effects of SOX9 on hepatic IR injury have not been explored. In the present study, a hepatic IR injury model was established, supported by a significant histological alteration with high Suzuki scores, and a remarkable up-regulation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Importantly, we found that SOX9 was over-expressed in liver of mice after IR operation. Suppressing SOX9 markedly reduced inflammatory response, as evidenced by the reduced mRNA expressions of tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-1β and inactivation of inhibitor of κBα (IκBα)/nuclear factor (NF)-κB pathway. In addition, SOX9 suppression alleviated apoptosis in liver of mice after IR injury, as supported by the reduced number of terminal deoxyribonucleotidyl transferse (TdT)-mediated biotin-16-dUTP nick-end labelling (TUNEL)-staining cells and decreased expression of Caspase-3 in liver tissue sections. The role of SOX9 in accelerating hepatic IR injury was further confirmed in primary hepatocytes under hypoxiaand reoxygenation (HR) treatment by enhancing inflammatory response and apoptosis. Of note, we found that transforming growth factor (TGF)-β1 was highly induced in liver of mice after IR injury. HR treatment also stimulated TGF-β1 expressions in vitro. Significantly, SOX9 over-expression-induced inflammation and apoptosis were obviously reduced by pirfenidone (Pirf), TGF-β1 inhibitor. In contrast, TGF-β1 exposure to cells further enhanced inflammation and apoptosis in HR-operated cells either with SOX9 knockdown or over-expression. Therefore, we identified a novel SOX9-dependent pathway that contributed to hepatic IR injury through enhancing inflammation and apoptosis by activating TGF-β1. [ABSTRACT FROM AUTHOR]