Demethylzeylasteral Exerts Antitumor Effects via Disruptive Autophagic Flux and Apoptotic Cell Death in Human Colorectal Cancer Cells and Increases Cell Chemosensitivity to 5-Fluorouracil.

BACKGROUND: Demethylzeylasteral (ZST93), a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF), has been reported to exert antineoplastic effects in several cancer cell types. However, the anti-tumour effects of ZST93 in human colorectal cancer (CRC) cells are unknown. OBJECTIVE: The aim of the present study was to evaluate the antitumor effects of ZST93 on cell cycle arrest, disruptive autophagic flux, apoptotic cell death and enhanced chemosensitivity to 5-FU in human CRC cells. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, colony formation assay, flow cytometry, immunoblotting, immunofluorescence, 5-ethynyl-20-deoxyuridine (EdU) incorporation assay and autophagy analysis were used to evaluate the effects of ZST93 on cell viability, cell cycle progression, apoptosis and autophagy in two human CRC cell lines. Moreover, ZST93's combined anti-tumour effects with 5-fluorouracil (5-FU) were evaluated. RESULTS: ZST93 inhibited CRC cell proliferation and growth. It was responsible for blocked cell cycle transition by arresting CRC cells in the G0/G1 phase via down-regulation of CDK4, CDK6, Cyclin D1 and c-MYC. Moreover, ZST93 induced suppressive autophagic flux and caspase-3-dependent cell death, which was further strengthened by the blocking of the autophagy process using chloroquine (CQ). Moreover, ZST93 enhanced CRC cells' chemosensitivity to 5-FU via modulation of autophagy and apoptosis. CONCLUSION: ZST93 exerts anti-tumor effects via disruptive autophagic flux and apoptotic cell death in human CRC cells and increases cell chemosensitivity to 5-FU. These results provide insights into the utilisation of ZST93 as an adjuvant or direct autophagy inhibitor and suggest ZST93 as a novel therapeutic strategy for treating CRC.

Papaverine Perfusion via the Aortic Root before Heart Re-beating Alleviates Myocardial Injury after Heart Valve Replacement.

AIM: Myocardial injury is inevitable during cardiac surgical procedures and reducing myocardial injury in patients with CPB surgery is the focus of current research. Papaverine is accepted as an ideal coronary vasodilator. This study was to estimate the effect of papaverine perfusion via the aortic root before heart re-beating on patients undergoing heart valve replacement. METHODS: All the patients enrolled in this study were admitted during 2013-2015. The basic clinical characteristics of the patients preoperative, intraoperative, and postoperative were compared. The immunochemistry assays and enzyme-linked immunosorbent assay (ELISA) were performed to assess the serum biomarkers. Western blot and immunohistochemistry (IHC) were undertaken to detect the expression of associated proteins. RESULTS: Patients receiving papaverine perfusion via the aortic root before heart re-beating during heart valve replacement surgery under CPB showed less extracorporeal circulation time and CPB time, higher automatic heartbeat recovery rate, less mechanical ventilation time, shorter ICU and in-hospital stay, less leak of cTnI and CK-MB, and weaker inflammatory response than the patients in control group. In addition, the protein expression of IL-6/8/10 and TNF-α was reduced by the perfusion of papaverine. The IHC staining for NFκB was depressed in papaverine group. CONCLUSION: Papaverine perfusion presented positive effect during valve replacement; this cardioprotective effect may be associated with inhibition of inflammatory response and NF-κB. These findings provided new clues for reduction of myocardial injury during cardiac surgery.

[Effects of cryopreservation on cellular viability and extracellular matrix of the aortic valves].

Cryopreservation is the best preserving method of the homograft heart valve at present, but at the same time it may damage the valve structural integrity. This study was performed to probe into the effects of cryopreservation on the histology of aortic valve. The viability of the cardiac valves was evaluated by XTT-tetrazolium colorimetric assay and the histologic property was assayed by light microscopy, transmission electron microscopy, and indirect immunofluorescent examination. The results of the experiments showed that the valve cellular viability was markedly decreased (P < 0.05), the cellular ultrastructure was damaged, the soluble extracellular matrix fibronectin and chondroitin sulfate were leached at different degree, and the interstitial collagen fibers were irregularly aligned after cryopreservation, but the damaged degree has no relation to storage within a period of 3 months.