Aims: The nephrotoxic side effects of cyclosporine A (CsA) are partly due to induction of the epithelial-to-mesenchymal transition (EMT), possibly through upregulation of connective tissue growth factor (CTGF). Bone morphogenetic protein (BMP-7) has been reported to protect against and reverse renal injury via its renotropic and antifibrotic effects. We therefore designed a method to investigate the mechanism by which BMP-7 inhibits CSA-induced EMT in cultured human renal proximal tubular epithelial (HK-2) cells and whether BMP-7 can antagonize CsA-induced profibrogenic effects. Methods: Cultured HK-2 cells were treated with CsA or a combination of CsA and BMP-7 for 72 h. Morphological changes were assessed by phase-contrast microscopy. The expression of α-smooth muscle actin (α-SMA), E-cadherin, collagen type I and CTGF was analyzed by immunofluorescence, RT-PCR, and Western blot. Additionally, the effect of CTGF silencing on CsA-mediated gene expression was assessed. Results: CsA-induced EMT was associated with decreased expression of E-cadherin, increased expression of α-SMA, collagen type I and CTGF, and loss of epithelial morphology. BMP-7 inhibited these effects in a dose-dependent manner. Using siRNA, CTGF knock-down also attenuated EMT-associated phenotypic changes induced by CsA. Conclusion: These data suggest that BMP-7 can block CsA-induced EMT by downregulating the expression of CTGF, a downstream mediator of EMT.

Calcitriol may be more effective than calcium carbonate in preventing and treating GC-induced osteoporosis in patients with NS.

To recommend one suitable tool material for the cutting of marine steels under special conditions and requirements in emergency rescues of capsized steel ships, the cermet tools, cemented carbide tools and coated carbide tools were evaluated using a fuzzy evaluation method concerning cutting force, cutting temperature, surface roughness and tool wear. Experimental results indicate that the tool cutting performance was diverse and difficult to evaluate with a single evaluation index. The cemented carbide tools presented bad cutting performance with severe wear. Compared with the cemented carbide tools, the cermet tools showed excellent wear resistance with about 60.3% smaller tool flank wear value and good surface quality with about 46.8% smaller surface roughness. The coated carbide tools presented low cutting temperatures about 15.6% smaller than those of the cermet tools. The result of fuzzy evaluation demonstrates that the cermet tools presented the best cutting performance, followed by the coated carbide tools, and then the cemented carbide tools. The cermet tools are recommended to cut marine steels in emergency rescues of capsized steel ships.

No abstract