No abstract

Diabetes mellitus (DM) is one of the primary threats to human health due to its increasing prevalence, chronic course, and disabling complications. Control of postprandial hyperglycemia and inhibition of oxidative stress are suggested to be important in the treatment of diabetes. Many efforts had been made to search for effective and safe alpha-glucosidase inhibitors and antioxidants from natural materials to develop a physiological functional food or lead compounds for curing diabetes. Coarse tea was used to cure diabetics in people in China and Japan. The hypoglycemic activity increased with the contents of polysaccharide in coarse tea. Many studies have focused on the hypoglycemic activities of tea polysaccharides, but little is known about the glycosidase inhibitory effects of tea polysaccharide. The aim of this study was to find a tea polysaccharide with the best potential for exploitation in curing diabetes.

The mechanism of cisplatin resistance in cancer cells is not fully understood. Here, we show that the Akt/mTOR survival pathway plays an important role in cisplatin resistance in human ovarian cancer cells. Specifically, we found that cisplatin treatment activates the Akt/mTOR survival pathway and that inhibition of this pathway by the PI3 K inhibitor LY294002 or knockdown of Akt sensitizes ovarian cancer cells to cisplatin. Furthermore, we generated cisplatin-resistant cells and found that resistant cells express a higher level of activated Akt as compared to their cisplatin sensitive counterparts. Importantly, inhibition of Akt or mTOR sensitized resistant cells to cisplatin-induced apoptosis. Taken together, our data indicate that activation of the Akt/mTOR pathway prevents cisplatin-induced apoptosis, leading to cisplatin resistance. Therefore, our study suggests that cisplatin resistance can be overcome by targeting the Akt/mTOR survival pathway in human ovarian cancer cells.

Earlier, we demonstrated the essential role of Kruppel-like transcription factor, TIEG1, in TGF-β–induced regulatory T cell (Treg) development. In this article, we demonstrate that IL-6, which promotes Th17 development, abrogated TIEG1 nuclear translocation and inhibited TGF-β–induced Treg development. Tyrosine kinase Tyk2-mediated phosphorylation of TIEG1 at Tyr179 promoted noncanonical K-27–linked polyubiquitination, which inhibited TIEG1 nuclear translocation. To test the role of TIEG1-regulated Treg/Th17 development in antitumor immunity, we analyzed TRAMP-C2 tumor growth in TIEG1–/– mice. The defective Treg development and elevated Th17 response resulted in enhanced immune reactivity in the tumor and inhibition of TRAMP-C2 tumor growth in TIEG1–/– mice. Thus, our results uncovered a novel regulatory mechanism that modulates Tregs and may regulate tumor progression.