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Metabolic diseases, especially diabetes mellitus, have become global health issues. The etiology of diabetes mellitus can be attributed to genetic and/or environmental factors. Current evidence suggests the association of gut microbiota with metabolic diseases. However, the effects of glucose-lowering agents on gut microbiota are poorly understood. Several studies revealed that these agents affect the composition and diversity of gut microbiota and consequently improve glucose metabolism and energy balance. Possible underlying mechanisms include affecting gene expression, lowering levels of inflammatory cytokines, and regulating the production of short-chain fatty acids. In addition, gut microbiota may alleviate adverse effects caused by glucose-lowering agents, and this can be especially beneficial in diabetic patients who experience severe gastrointestinal side effects and have to discontinue these agents. In conclusion, gut microbiota may provide a novel viewpoint for the treatment of patients with diabetes mellitus. [ABSTRACT FROM AUTHOR]

PURPOSE: To investigate the effect of lipopolysaccharides (LPS) extracted from Porphyromonas endodontalis (P.e) on the expression of p38 and ERK1/2 in osteoblast. METHODS: MC3T3-E1 cells were stimulated with 10 µg/mL P.e-LPS for 0,5,15,30,60,180 min. The phosphorylation of p38 and ERK1/2 was measured by Western blot. Statistical analysis was performed using one-way ANOVA and Dunnett t test with SPSS 11.0 software package. RESULTS: 10 (µg/mL LPS could significantly activate p38 MAPK. The peak of phosphorylated p38 was detected at 5 to 30 min (P<0.01) and returned to baseline within 60 min; the level of phosphorylated ERK1/2 increased after the stimulation of LPS for 5 min and reached maximum at 15 min (P<0.01) and declined after 30 min. CONCLUSIONS: P.e -LPS can induce the expression of p38 and ERK1/2 in osteoblast MC3T3-E1, which indicates that P.e-LPS may play an important role in osteoblast through p38 and ERK1/2. [ABSTRACT FROM AUTHOR]

• We identified acevaltrate as an inhibitor of hypoxia-inducible factor-1α accumulation from the roots of Valeriana glechomifolia. • Acevaltrate inhibits HIF-1α protein synthesis and promotes degradation of HIF-1α protein. • Acevaltrate inhibits HIF-1α protein expression through suppression of mTOR/p70S6K/4E-BP1 signaling pathway. • Acevaltrate promotes apoptosis and inhibits proliferation by inhibiting HIF-1α. • Acevaltrate could be a valuable candidate for the intervention of hypoxia-inducible factor-1α-dependent anticancer activity. Acevaltrate is a natural product isolated from the roots of Valeriana glechomifolia F.G.Mey. (Valerianaceae) and has been shown to exhibit anti-cancer activity. However, the mechanism by which acevaltrate inhibits tumor growth is not fully understood. We here demonstrated the effect of acevaltrate on hypoxia-inducible factor-1α (HIF-1α) expression. Acevaltrate showed a potent inhibitory activity against HIF-1α induced by hypoxia in various cancer cells. This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently. Further analysis revealed that acevaltrate inhibited HIF-1α protein synthesis and promoted degradation of HIF-1α protein, without affecting the expression level of HIF-1α mRNA. Moreover, the phosphorylation levels of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and eIF4E binding protein-1 (4E-BP1) were significantly suppressed by acevaltrate. In addition, acevaltrate promoted apoptosis and inhibited proliferation, which was potentially mediated by suppression of HIF-1α. We also found that acevaltrate administration inhibited tumor growth in mouse xenograft model. Taken together, these results suggested that acevaltrate was a potent inhibitor of HIF-1α and provided a new insight into the mechanisms of acevaltrate against cancers. [ABSTRACT FROM AUTHOR]