Citations

Compared to most of nano-sized particles, core–shell-structured nanoflowers have received great attention as bioactive materials because of their high surface area with the flower-like structures. In this study, core–shell-structured Si-based NiO nanoflowers, Si@NiO, were prepared by a modified chemical bath deposition method followed by thermal reduction. The crystal morphology and basic structure of the composites were characterized by powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), specific surface area (BET) and porosity analysis (BJT), and inductively coupled plasma optical emission spectrometry (ICP-OES). The electrochemical properties of the Si@NiO nanoflowers were examined through the redox reaction of ascorbic acid with the metal ions present on the surface of the core–shell nanoflowers. This reaction favored the formation of reactive oxygen species. The Si@NiO nanoflowers showed excellent anticancer activity and low cytotoxicity toward the human breast cancer cell line (MCF-7) and mouse embryonic fibroblasts (MEFs), respectively, demonstrating that the anticancer activities of the Si@NiO nanoflowers were primarily derived from the oxidative capacity of the metal ions on the surface, rather than from the released metal ions. Thus, this proves that Si-based NiO nanoflowers can act as a promising candidate for therapeutic applications.

Loss of BMP (bone morphogenic protein) signaling induces a phenotype switch of pulmonary arterial smooth muscle cells (PASMCs), which is the pathological basis of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Here, we identified FGF12 (fibroblast growth factor 12) as a novel regulator of the BMP-induced phenotype change in PASMCs and elucidated its role in pulmonary vascular remodeling during PAH development. Using murine models of PAH and lung specimens of patients with PAH, we observed that FGF12 expression was significantly reduced in PASMCs. In human PASMCs, FGF12 expression was increased by canonical BMP signaling. FGF12 knockdown blocked the antiproliferative and prodifferentiation effect of BMP on human PASMCs, suggesting that FGF12 is required for the BMP-mediated acquisition of the quiescent and differentiated PASMC phenotype. Mechanistically, FGF12 regulated the BMP-induced phenotype change by inducing MEF2a (myocyte enhancer factor 2a) phosphorylation via p38MAPK signaling, thereby modulating the expression of MEF2a target genes involved in cell proliferation and differentiation. Furthermore, we observed that TG (transgenic) mice with smooth muscle cell–specific FGF12 overexpression were protected from chronic hypoxia–induced PAH development, pulmonary vascular remodeling, and right ventricular hypertrophy. Consistent with the in vitro data using human PASMCs, FGF12 TG mice showed increased MEF2a phosphorylation and a substantial change in MEF2a target gene expression, compared with the WT (wild type) controls. Overall, our findings demonstrate a novel BMP/FGF12/MEF2a pathway regulating the PASMC phenotype switch and suggest FGF12 as a potential target for the development of therapeutics for ameliorating pulmonary vascular remodeling in PAH.