SIRT5 belongs to a family of NAD + -dependent lysine deacetylases called sirtuins. Although accumulating evidence indicates SIRT5 upregulation in cancers, including liver cancer, the detailed roles and mechanisms remain to be revealed. Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths among men worldwide, and finding effective targets for HCC treatment and prevention is urgently needed. In the present study, we confirmed that mitochondrial sirtuins, particularly SIRT5, are more highly expressed in HCC cell lines than in normal liver cell lines. Moreover, SIRT5 knockdown suppresses HCC cell proliferation and SIRT5 overexpression promotes HCC cell proliferation. Furthermore, we verified that SIRT5 knockdown increases HCC cell apoptosis via the mitochondrial pathway. By co-IP and western blotting, we illustrated that SIRT5 deacetylates cytochrome c thus regulating HCC cell apoptosis. Taken together, our findings suggest that SIRT5 may function as a prognostic factor and drug target for HCC treatment.

Several studies have shown the safety and feasibility of laparoscopic common bile duct exploration (LCBDE) as a minimally invasive treatment options for choledocholithiasis. Use of T-tube or biliary stent drainage tube placement after laparoscopic choledochotomy for common bile duct (CBD) stones is still under debate. This study tried to confirm the safety of spontaneously removable biliary stent in the distal CBD after LCBDE to allow choledochus primary closure. A total of 47 patients with choledocholithiasis underwent LCBDE with primary closure and internal drainage using a spontaneously removable biliary stent drainage tube (stent group, N = 22) or T-tube (T-tube group, N = 25). Operative parameters and outcomes are compared. Surgical time, intraoperative blood loss, length of hospital stay, drainage tube removal time, postoperative intestinal function recovery, and cost of treatment were all significantly lower in the stent group as compared to that in the T-tube group (P < 0.05 for all). Otherwise, Bile leakage between the two groups had no significant difference (P > 0.05). The biliary stent drainage tube was excreted spontaneously 4 to 14 days after surgery with the exception of one case, where endoscopic removal of biliary tube was required due to failure of its spontaneous discharge. LCBDE with primary closure and use of spontaneously removable biliary stent drainage showed advantage over the use of traditional T-tube drainage in patients with choledocholithiasis.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, often diagnosed in late stages when most therapeutic methods are not very effective. The introduction of the multikinase inhibitor sorafenib as the standard of care has opened a window of hope for patients with advanced HCC, patients with very poor prognosis; however, patients usually develop acquired resistance to sorafenib limiting its therapeutic benefits. Melatonin (MT), an indoleamine compound produced in the pineal gland, has shown a substantial beneficial effect in increasing the efficacy of common anticancer drugs and decreasing their toxic effects. Here we demonstrate that MT potentiated the sorafenib-mediated inhibition of cell viability and colony formation in HCC cell lines. Moreover, combined treatment of MT and sorafenib enhanced the cell cycle arrest of HCC cells at the G0/G1 phase. Co-treatment of sorafenib and MT was found to upregulate p27, an inhibitor of several cyclin-dependent kinases (CDK), and downregulate p-AKT, c-myc, cyclin D1 and CDK4/6 protein expression. Furthermore, overexpression of p-AKT using SC79 reversed the effect of sorafenib and MT combination on cell viability and growth of HCC cells. These results suggest that the AKT pathway might be critical for the enhanced anticancer effect observed after co-treatment with MT and sorafenib. Taken together, our findings demonstrated that AKT/p27-mediated cell growth arrest induced by MT increased the sensitivity of HCC cells to the effect of sorafenib.

The advances in microfluidic technology have recently generated various microfluidic-based biomimetic models as novel 3D models for life science research, offering some great advantages over conventional models.

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