Catechin relieves hypoxia/reoxygenation-induced myocardial cell apoptosis via down-regulating lncRNA MIAT.

BACKGROUND: Catechin protects heart from myocardial ischaemia/reperfusion (MI/R) injury. However, whether catechin inhibits H/R-induced myocardial cell apoptosis is largely unknown. OBJECTIVE: This study aims to investigate the underlying mechanism of catechin in inhibiting the apoptosis of H/R-induced myocardial cells. METHODS: LncRNA MIAT expression was detected by qRT-PCR. Cell viability of H9C2 cells was detected using CCK-8 assay. The apoptosis of H9C2 cells was detected by flow cytometry. The interaction between CREB and MIAT promoter regions was confirmed by dual-luciferase reporter gene assay and ChIP assay. RESULTS: In MI/R rats, catechin improved heart function and down-regulated lncRNA MIAT expression in myocardial tissue. In H/R-induced H9C2 cells, catechin protected against cell apoptosis, and lncRNA MIAT overexpression attenuated this protective effect of catechin. We confirmed that transcription factor CREB could bind to MIAT promoter region, and catechin suppressed lncRNA MIAT expression through up-regulating CREB. Catechin improved mitochondrial function and relieved apoptosis through promoting Akt/Gsk-3ß activation. In addition, MIAT inhibited Akt/Gsk-3ß activation and promoted cell apoptosis in H/R-induced H9C2 cells. Finally, we found catechin promoted Akt/Gsk-3ß activation through inhibiting MIAT expression in H/R-induced H9C2 cells. CONCLUSION: Catechin relieved H/R-induced myocardial cell apoptosis through regulating CREB/lncRNA MIAT/Akt/Gsk-3ß pathway.

Prognostic value of transforming growth factor-beta in patients with colorectal cancer who undergo surgery: a meta-analysis.

BACKGROUND: Transforming growth factor-beta (TGF-ß) is associated with a higher incidence of distant metastasis and decreased survival. Whether TGF-ß can be used as a prognostic indicator of colorectal cancer (CRC) remains controversial. METHODS: The Medline, EMBASE and Cochrane databases were searched from their inception to March 2016. The studies that focused on TGF-ß as a prognostic factor in patients with CRC were included in this analysis. Overall survival (OS) and disease-free survival (DFS) were analysed separately. A meta-analysis was performed, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated. RESULTS: Twelve studies were included in the analysis, of which 8 were used for OS and 7 for DFS. In all, 1622 patients with CRC undergoing surgery were included. Combined HRs suggested that high expression of TGF-ß had a favourable impact on OS (HR = 1.68, 95% CI: 1.10-2.59) and DFS (HR = 1.11, 95% CI: 1.03-1.19) in CRC patients. For OS, the combined HRs of Asian studies and Western studies were 1.50 (95% CI: 0.61-3.68) and 1.80 (95% CI: 1.33-2.45), respectively. For DFS, the combined HRs of Asian studies and Western studies were 1.42 (95% CI: 0.61-3.31) and 1.11 (95% CI: 1.03-1.20), respectively. CONCLUSIONS: This meta-analysis demonstrates that TGF-ß can be used as a prognostic biomarker for CRC patients undergoing surgery, especially for CRC patients from Western countries.

Tiaochang Xiaoyan extract tablets ameliorate chronic inflammation by activating macrophage lysosomes in chronic colitis rats.

BACKGROUND: Tiaochang Xiaoyan tablet (TCXYT) is a traditional Chinese medicine prescription derived from the Xianglian pill, which is a traditional Chinese medicine for treating chronic dysentery recorded in the Taiping Huimin Heji Bureau [1078-1085]. For many years, TCXYT has been used to treat ulcerative colitis, however, its therapeutic mechanism is still unclear. In the present study, we used colonic lamina propria macrophages (LPM) and mouse-derived macrophage cell line RAW264.7 cells as the research objects, with the aim of exploring the therapeutic effects and mechanisms of TCXYT on colitis. METHODS: We used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce a rat model of chronic colitis, and normal rats as the control. The disease activity index (DAI) and colonic histopathological changes of rats were used to evaluate the severity of colitis. Rats were divided into the control group; model group; high, middle-, and low-dose TCXYT group; and the hydroxychloroquine sulfate group. TCXYT was administered by gavage on the 3rd day after model replication and lasted for 7 days. The doses used for the high-, middle-, and low-dose TCXYT groups were 0.8, 0.4 and 0.2 g/kg, respectively. Enzyme-linked immunosorbent assay was used to detect the serum concentration of cytokines. Western blot was used to detect the expressions of Toll-like receptor 9 (TLR9), myeloid differentiation primary response 88 (MyD88), interleukin (IL) receptor-associated kinase (IRAK) 1, and IRAK4 in colonic LPM and RAW264.7 cells. Immunofluorescence was used to detect lysosomal activity. The chemical constituents of TCXYT were separated and identified based on Q-Orbitrap high resolution LC/MS data. RESULTS: TCXYT promoted the repair of colonic mucosal injury, attenuated inflammation, increased lysosome activity in macrophages, and decreased the DAI in rats with colitis compared with those in the model group. TCXYT decreased the serum concentrations of IL-1ß and tumor necrosis factor-α (TNF-α), increased those of IL-4 and IL-10, and decreased the TLR9, MyD88, IRAK1, and IRAK4 protein levels in LPM and RAW264.7 cells compared to the model group. CONCLUSIONS: TCXYT could ameliorate colon inflammation and CD11c+ macrophage infiltration in rats with chronic colitis. This effect may be mediated by activating lysosomes in macrophages by inhibiting the TLR9/MyD88/IRAK signaling pathway.