OBJECTIVETo investigate the effect of metformin in protecting against advanced glycation end products (AGEs)-induced apoptosis in human primary dermal fibroblasts.

METHODSFibroblasts were exposed to 100, 200, or 300 µg/mL AGEs, 300 µg/mL bovine serum albumin (BSA), or 300 µg/mL AGEs and 1 mmol/L metformin for 24, 48, or 72 h. The exposed cells were examined for cell apoptosis using a cell counting kit. The expressions of caspase-3, Bax and Bcl-2 protein in the fibroblasts treated for 72 h were detected with Western blotting.

RESULTSAGEs exposures caused significant dose- and time-dependent apoptosis in the fibroblasts. A 72-h exposure to 300 µg/mL AGEs resulted in obviously increased apoptosis of the fibroblasts compared to the control group (0.72 ± 0.02 vs 1 ± 0.04, P<0.05), and metformin significantly decreased AGEs-induced apoptosis (0.98 ± 0.02 vs 0.72 ± 0.02, P<0.05). The expressions of caspase-3 and Bax protein were significantly increased (P<0.05) and Bcl-2 protein expression was decreased (P<0.05) with a lowered Bcl-2/Bax ratio in AGEs-treated fibroblasts (P<0.05), and such changes were significantly reversed by metformin treatment (P<0.05).

CONCLUSIONMetformin can antagonize AGEs-induced apoptosis in human dermal fibroblasts by regulating the expressions of caspase-3, Bax and Bcl-2.

Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cells, Cultured ; Dermis ; cytology ; Fibroblasts ; cytology ; drug effects ; Glycation End Products, Advanced ; adverse effects ; Humans ; Metformin ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; bcl-2-Associated X Protein ; metabolism

Objective To explore the influence of preoperative transarterial chemoembolization on short-term prognosis in patients with hepatocellular carcinoma after liver transplantation Methods From Jan 2006 to Sep 2016 in Ruijin Hospital 21 patients received preoperative hepatic transarterial chemoembolization (TACE) before liver transplantation,the other 30 patients undergoing upfront liver transplantation served as control group.Results No statistical difference was found in the total operation time (401 ± 72) min vs.(377 ± 100) min,blood loss (2 785 ± 25 56) ml vs.(4 199 ± 3 748) ml and length of hospital stay (32-± 16) d vs.(28 ± 17) d between two groups,and the occurrence rate of vascular complications (14.3％ vs.0) or biliary complications (9.5％ vs.6.7％) also showed no difference (P ＞ 0.05).Although more patients were diagnosed with postoperative infection in the observation group (81％ vs.40％) (P ＜ 0.05),there was no statistically significant difference in complication grade and perioperative mortality between two groups (P ＞ 0.05).There's no remarkable difference in the liver function recovery level between two groups in terms of postoperative indexs of liver function such as TBL,ALT,AST,and there was also no statistical difference between two groups in 1-year,2-year and 3-year overall survival (P ＞ 0.05).The waiting time in the study group was significantly longer than that in the control group (P ＜ 0.05),and the incidence of postoperative immune dysfunction was lower than that of the control group (P ＜ 0.05).Conclusion Preoperative TACE does not affect liver function recovery and perioperative safety after liver transplantation.