Hepatocellular carcinoma (HCC) cells rapidly switch their energy source from oxidative phosphorylation to glycolytic metabolism in order to efficiently proliferate. However, the molecular mechanisms responsible for this switch remain unclear. In this study, we found that miR-592 was frequently downregulated in human HCC tissues and cell lines, and its downregulation was closely correlated with aggressive clinicopathological features and poor prognosis of HCC patients. Overexpression of miR-592 inhibited aerobic glycolysis and proliferation in HCC cells in vitro. Conversely, knockdown of miR-592 promoted HCC growth in both subcutaneous injection and orthotopic liver tumor implantation models in vivo. Mechanistically, miR-592 downregulation in human HCCs was correlated with an upregulation of WD repeat and SOCS box containing 1 (WSB1). We further showed that miR-592 directly binds to the 3'-UTR of the WSB1 gene, thus disrupting hypoxia inducible factor-1α (HIF-1α) protein stabilization. In turn, overexpression of WSB1 in HCC cells rescued decreased HIF-1α expression, glucose uptake, and HCC growth induced by miR-592. Collectively, our clinical data and functional studies suggest that miR-592 is a new robust inhibitor of the Warburg effect and a promising therapeutic target for HCC treatment.

Renal ischemia-reperfusion (I/R) injury is associated with high morbidity and mortality as there is currently no available effective therapeutic strategy with which to treat this injury. Thus, the aim of this study was to investigate the potential protective effects of brazilin, a major active component of the Chinese medicine Caesalpinia sappan L., against renal I/R injury in vitro and in vivo. Rats were subjected to removal of the right kidney and I/R injury to the left kidney (ischemia for 45 min followed by reperfusion for 24 h). Treatment with brazilin (30 mg/kg, administered intravenously at 30 min prior to ischemia) led to the reversal of I/R-induced changes in serum creatinine (Scr) and blood urea nitrogen (BUN) levels, and also attenuated the histopathological damage induced by I/R. Furthermore, TUNEL assay revealed that brazilin reduced cell necrosis, and significantly decreased the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in renal tissue. Moreover, HK-2 cells were used in order to elucidate the mechanisms responsible for the protective effects of brazilin. The levels of phosphorylated IκBα and the nuclear translocation of nuclear factor-κB (NF-κB) were all evidently decreased by brazilin. These findings suggested that pre-treatment with brazilin protects against I/R-induced renal damage and suppresses the inflammatory response by inhibiting the activation of the NF-κB signaling pathway.

Abstract:Oxidative stress plays an important role in Parkinson's disease and other neurodegenerative disorders. Lycium barbarum polysaccharides (LBP), the main active ingredients extracted from the fruits of Lycium barbarum L., have been shown to be a potent antioxidant. In the present study, we investigated the protective effects, and the possible mechanism of action of LBP against 6-hydroxydopamine (6-OHDA)-induced apoptosis in PC12 cells. Our data demonstrated that LBP significantly reversed the 6-OHDA-induced decrease in cell viability, prevented 6-OHDA-induced changes in condensed nuclei and decreased the percentage of apoptotic cells in a dose-dependent manner. Furthermore, LBP also slowed the accumulation of reactive oxygen species (ROS) and nitric oxide (NO), decreased the level of protein-bound 3-nitrotyrosine (3-NT) and intracellular free Ca 2+ , and inhibiting the overexpression of nuclear factor κB (NF-κB), neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS). These results demonstrate that OPEN ACCESSMolecules 2015, 20 294 LBP prevents 6-OHDA-induced apoptosis in PC12 cells, at least in part through the ROS-NO pathway.