Ursolic acid derivative ameliorates streptozotocin-induced diabestic bone deleterious effects in mice.

OBJECTIVE: This study was performed to investigate bone deteriorations of diabetic mice in response to the treatment of ursolic acid derivative (UAD). METHODS: The biomarkers in serum and urine were measured, tibias were taken for the measurement on gene and protein expression and histomorphology analysis, and femurs were taken for the measurement on bone Ca and three-dimensional architecture of trabecular bone. RESULTS: UAD showed a greater increase in bone Ca, BMD and significantly increased FGF-23 and OCN, reduced PTH and CTX in diabetic mice. UAD reversed STZ-induced trabecular deleterious effects and stimulated bone remodeling. The treatment of STZ group with UAD significantly elevated the ratio of OPG/RANKL. Moreover, insulin and IGF-1 showed a negative correlation with both FBG and Hb1Ac in STZ group. We attributed down-regulating the level of Hb1Ac in diabetic mice to that ursolic acid derivative could primely control blood sugar levels. After analyzing of two adipocyte markers, PPARγ and aP2, increased expression in the tibias of diabetic mice, and UAD could improve STZ-induced adipocyte dysfunction. CONCLUSIONS: These results demonstrated that UAD could ameliorate STZ-induced bone deterioration through improving adipocyte dysfunction and enhancing new bone formation and inhibiting absorptive function of osteoclast in the bone of diabetic mice.

Bisulfite sequencing reveals that Aspergillus flavus holds a hollow in DNA methylation.

Aspergillus flavus first gained scientific attention for its production of aflatoxin. The underlying regulation of aflatoxin biosynthesis has been serving as a theoretical model for biosynthesis of other microbial secondary metabolites. Nevertheless, for several decades, the DNA methylation status, one of the important epigenomic modifications involved in gene regulation, in A. flavus remains to be controversial. Here, we applied bisulfite sequencing in conjunction with a biological replicate strategy to investigate the DNA methylation profiling of A. flavus genome. Both the bisulfite sequencing data and the methylome comparisons with other fungi confirm that the DNA methylation level of this fungus is negligible. Further investigation into the DNA methyltransferase of Aspergillus uncovers its close relationship with RID-like enzymes as well as its divergence with the methyltransferase of species with validated DNA methylation. The lack of repeat contents of the A. flavus' genome and the high RIP-index of the small amount of remanent repeat potentially support our speculation that DNA methylation may be absent in A. flavus or that it may possess de novo DNA methylation which occurs very transiently during the obscure sexual stage of this fungal species. This work contributes to our understanding on the DNA methylation status of A. flavus, as well as reinforces our views on the DNA methylation in fungal species. In addition, our strategy of applying bisulfite sequencing to DNA methylation detection in species with low DNA methylation may serve as a reference for later scientific investigations in other hypomethylated species.

Mechanisms of diabetes mellitus induced with FK506 in SD rats models.

BACKGROUND: Tacrolimus causes post-transplant diabetes mellitus, however the pathogenetic mechanisms remain controversial. In this study we probed into the mechanisms of tacrolimus-induced diabetes mellitus in rats. METHODS: Glucose levels were determined on whole blood samples using a glucose oxidase method. Levels of serum insulin and C-peptide were measured with ELISA. Histological damage of ultra-structure and apoptosis of beta cells of the pancreas were assayed with electric microscope and tunnel methods respectively.--Ultra-structure were assayed with electric microscope and apoptosis of beta cells of the pancreas were assayed with tunnel methods. Immunohistochemistry was utilized to detect the sum of insulin receptors of hepatic cells. RESULTS: Compared to control group, insulin and C peptide levels in serum decreased in rats of diabetes mellitus models induced with FK506(P<0.05). Compared to the control group, the sum of apoptosis body in pancreatic islets increased in rats of diabetes mellitus models induced with FK506 (P<0.05). Compared to the control group, electron microscopy showed cytoplasm swelling and vacuolization, and marked decrease or absence of dense-core secretory granules in beta cells in rats with diabetes mellitus induced with FK506.Compared to the control group, expression of insulin receptor of hepatic cell decreased in rats of diabetes mellitus models induced with FK506 (P<0.05). CONCLUSION: Pathogenetic mechanisms of rats of diabetes mellitus models induced with FK506 including reduction of secretion of insulin in beta cells of pancreatic islets, damages of ultra-structure of beta cells of pancreatic islets, increasing of apoptosis of beta cells of pancreatic islets and decreasing of expression of insulin receptors in hepatic cells.