Melatonin Protects Against Hyperoxia-Induced Apoptosis in Alveolar Epithelial type II Cells by Activating the MT2/PI3K/AKT/ETS1 Signaling Pathway.

PURPOSE: Hyperoxia-induced apoptosis in alveolar epithelial type II cells (AECIIs) plays a critical role in the development of bronchopulmonary dysplasia (BPD). Melatonin has been shown to improve BPD. However, the protective effect of melatonin on hyperoxia-induced apoptosis in AECIIs and the precise mechanisms involved remain unclear. METHODS: Human alveolar epithelial type II A549 cells were treated with hyperoxia as an in vitro model to investigate the antiapoptotic mechanism of melatonin. CCK-8 assays were performed to investigate the viability of A549 cells. Hoechst 33,258 staining was carried out to quantify apoptosis in A549 cells. The protein expression levels of E26 oncogene homolog 1 (ETS1), Bcl-2, Bax, Bim, Wnt, ß-catenin, AKT and phosphorylated AKT were measured by western blotting. LY294002, SC79 and the downregulation of ETS1, melatonin receptor 1 (MT1) and MT2 with specific siRNAs were used to investigate the role of the PI3K/AKT pathway, ETS1, MT1 and MT2 in hyperoxia-induced apoptosis in A549 cells. RESULTS: Melatonin prevented hyperoxia-induced apoptosis in A549 cells, and the upregulation of E26 oncogene homolog 1 (ETS1) contributed to the antiapoptotic effect of melatonin. Melatonin activated the PI3K/AKT axis, which led to ETS1 upregulation and inhibited apoptosis in hyperoxia-exposed A549 cells. Furthermore, melatonin-induced activation of the PI3K/AKT axis, upregulation of ETS1 and inhibition of apoptosis were reversed by melatonin receptor 2 (MT2) siRNA in hyperoxia-exposed A549 cells. CONCLUSION: Melatonin prevents hyperoxia-induced apoptosis by activating the MT2/PI3K/AKT/ETS1 axis in alveolar epithelial cells.

Novel Core-Shell Hybrid Nanosphere towards the Mechanical Enhancement and Fire Retardance of Polycarbonate.

It is a huge challenge to achieve highly efficient fire retardance with no mechanical damage to polymers. In our current research, a novel core-shell titanium dioxide@diphenylphosphinic (TiO2@DPP) nanosphere was first synthesized through a hydrothermal reacting process, and applied in simultaneously enhancing the fire retardance and mechanical properties of polycarbonate (PC). The well-designed TiO2@DPP exhibited a significant effect on combustion performance and mechanical reinforcement of PC. At only 0.10 wt % of TiO2@DPP, PC/TiO2@DPP passed the UL-94 V-0 rating, and its oxygen index value rose to 29.3%. Moreover, the peak value of the heat release rate was remarkably decreased by 34.1% in the combustion test, accompanied by the formation of more compacted char layer and the release of more incombustible gas. Equally important another aspect is that the PC containing only 0.10 wt % of TiO2@DPP possessed higher elongation at break and higher tensile strength than pure PC, correspondingly increased by 27.7 and 14.7%. The analysis of the flame-retardant mechanism revealed that the improved fire retardance of PC is primarily ascribed to the barrier action of a cross-linking network containing phosphorus and titanium, the dilution of nonflammable gases such as H2O, and the quenching effect of free radicals which are from the phosphorous group in the gas phase. All these experimental results demonstrate that the core-shell hybrid TiO2@DPP may achieve a simultaneous significant improvement in fire retardance and mechanical properties of PC.