EW-7197, a potent oral ALK5 inhibitor, was assessed for its impact on transforming growth factor beta 1 (TGF-β1)–induced fibrosis in a three-dimensional (3D) renal fibrosis-on-a-chip and a mouse model. The evaluation included tubular epithelial- mesenchymal transition, angiogenesis, and inflammatory cytokine expression. Methods: In a 3D renal fibrosis-on-a-chip model, three cell types(kidney fibroblasts, human proximal tubular cells, and human umbilical vein endothelial cells) were cultured and treated with TGF-β1 and EW-7197. Alpha smooth muscle actin (α-SMA) and keratin 8 (KRT-8) was assessed, angiogenesis observed via confocal microscopy, and cytokine levels measured by polymerase chain reaction, immunoassay, and enzyme-linked immunosorbent assay. In a cisplatin-induced renal fibrosis mouse model, blood urea nitrogen levels, TGF-β, and Smad 2/3 were determined, and fibrosis was assessed with Masson’s trichrome stain. Results: The α-SMA expression was significantly lower in the EW-7197 group than in the TGF-β fibrosis group. TGF-β decreased the expression of the epithelial marker KRT-8, an effect that was reversed by EW-7197 and SB431542. In the TGF-β–induced fibrosis model, the length of the thick vessels was reduced, and the diameter of both thick and thin vessels was decreased, but EW-7197 reversed these effects. EW-7197 significantly reduced the messenger RNA expression of TGF-β and increased the levels of vascular endothelial growth factor receptor 2, interleukin (IL)-10, and IL-6. EW-7197 reduced the levels of secretory cytokines TGF-β1, TGF-β3, IL- 1β. In the cisplatin-induced renal fibrosis mouse model, EW-7197 reduced renal fibrosis by down-regulating TGF-β signaling. Conclusion: EW-7197 attenuated the TGF-β1–induced fibrotic cellular response in the 3D chip model and animal model. These findings indicate the potential effect of EW-7197 in attenuating renal fibrosis.

Although the frequency of composite resin restoration in children is gradually increasing, there are insufficient researches about the rate of composite resin repair in children. The purpose of this study was to evaluate the repair rate of composite resin restorations in the permanent first molar in children under 12 years old. This study retrospectively analyzed 169 children treated with composite resin restoration in the permanent first molar from May 2014 to April 2015.According to the location of the tooth, the repair rate was higher in the mandible than maxilla and in the left than right. In the classification of restoration, the repair rate was the highest in the class II cavity, and the repair rate was the lowest in the restoration of the occlusal surface only. Repair rate in two years was 14.8%, and repair hazard ratio decreased with age. The most common reason of composite resin restoration replacement was the secondary caries (74.1%).Within the limits of study, the repair rate of children was higher than that of adult due to the characteristics of children. Therefore, dentists should understand these characteristics and try to reduce the repair rate of composite resin composite restorations.
Adult ; Child ; Classification ; Dentists ; Humans ; Mandible ; Maxilla ; Molar ; Retrospective Studies ; Tooth