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Rationale: Neointimal hyperplasia is characterized by excessive accumulation of vascular smooth muscle cells (SMCs) leading to occlusive disorders, such as atherosclerosis and stenosis. Blood vessel injury increases growth factor secretion and matrix synthesis, which promotes SMC proliferation and neointimal hyperplasia via FAK (focal adhesion kinase). Objective: To understand the mechanism of FAK action in SMC proliferation and neointimal hyperplasia. Methods and Results: Using combined pharmacological FAK catalytic inhibition (VS-4718) and SMC-specific FAK kinase-dead (Myh11-Cre-ER T2 ) mouse models, we report that FAK regulates SMC proliferation and neointimal hyperplasia in part by governing GATA4- (GATA-binding protein 4) cyclin D1 signaling. Inhibition of FAK catalytic activity facilitates FAK nuclear localization, which is required for proteasome-mediated GATA4 degradation in the cytoplasm. Chromatin immunoprecipitation identified GATA4 binding to the mouse cyclin D1 promoter, and loss of GATA4-mediated cyclin D1 transcription diminished SMC proliferation. Stimulation with platelet-derived growth factor or serum activated FAK and redistributed FAK from the nucleus to cytoplasm, leading to concomitant increase in GATA4 protein and cyclin D1 expression. In a femoral artery wire injury model, increased neointimal hyperplasia was observed in parallel with elevated FAK activity, GATA4 and cyclin D1 expression following injury in control mice, but not in VS-4718-treated and SMC-specific FAK kinase-dead mice. Finally, lentiviral shGATA4 knockdown in the wire injury significantly reduced cyclin D1 expression, SMC proliferation, and neointimal hyperplasia compared with control mice. Conclusions: Nuclear enrichment of FAK by inhibition of FAK catalytic activity during vessel injury blocks SMC proliferation and neointimal hyperplasia through regulation of GATA4-mediated cyclin D1 transcription.

Morin, a flavonoid found in figs and other Moraceae, displays a variety of biological actions, such as anti-oxidant, anti-inflammatory and anti-carcinogenic. However, the anticancer effects of morin and in particular its anti-metastatic effects are not well known. Therefore, in the present study, we investigated the anticancer effects of morin on highly metastatic human breast cancer cells. Our results showed that morin significantly inhibited the colony forming ability of highly metastatic MDA-MB‑231 breast cancer cells from low doses (50 µM) without cytotoxicity. In addition, morin changed MDA-MB‑231 cell morphology from mesenchymal shape to epithelial shape and inhibited the invasion of MDA-MB‑231 cells in a dose-dependent manner. Morin decreased matrix metalloproteinase-9 (MMP-9) secretion and expression of the mesenchymal marker N-cadherin of MDA-MB‑231 cells, suggesting that morin might suppress the EMT process. Furthermore, morin significantly decreased the phosphorylation of Akt, and inhibition of the Akt pathway significantly reduced MDA-MB‑231 invasion. In an in vivo xenograft mouse model, morin suppressed MDA-MB‑231 cancer cell progression. Taken together, our findings suggest that morin exhibits an inhibitory effect on the cancer progression and EMT process of highly metastatic breast cancer cells at least in part through inhibiting Akt activation. This study provides evidence that morin may have anticancer effects against metastatic breast cancer.

A novel method to launch finite power Airy beams based on a metasurface is presented. By tailoring the amplitude and phase of the transmitted fields from a metallic C‐aperture array, launching Airy beams is achieved in free space. The amplitude and phase of the Airy beam profile can be mapped and tailored by tuning only the tilt angles of the aperture. This structure has multifrequency characteristics, which facilitates Airy beam steering because the trajectory of Airy beams is dependent on the wavelength. In addition, the design method can generate Airy beams which have a very compact main lobe (≈2 µm). Computational and experimental results show that proposed metasurface can overcome some limitations of the traditional methods to generate Airy beams. The results can be used for potential applications in integrated optics, beam shaping, biosensing, and next‐generation holography.

Naringin, one of the major bioflavonoid of Citrus, has been demonstrated as potential anticancer agent. However, the underlying anticancer mechanism still needs to be explored further. This study investigated the inhibitory effect of Naringin on human AGS cancer cells. AGS cell proliferation was inhibited by Naringin in a dose- and time-dependent manner. Naringin did not induce apoptotic cell death, determined by no DNA fragmentation and the reduced Bax/Bcl-xL ratio. Growth inhibitory role of Naringin was observed by western blot analysis demonstrating downregulation of PI3K/Akt/mTOR cascade with an upregulated p21CIPI/WAFI. Formation of cytoplasmic vacuoles and autophagosomes were observed in Naringin-treated AGS cells, further confirmed by the activation of autophagic proteins Beclin 1 and LC3B with a significant phosphorylation of mitogen activated protein kinases (MAPKs). Collectively, our observed results determined that anti-proliferative activity of Naringin in AGS cancer cells is due to suppression of PI3K/Akt/mTOR cascade via induction of autophagy with activated MAPKs. Thus, the present finding suggests that Naringin induced autophagy- mediated growth inhibition shows potential as an alternative therapeutic agent for human gastric carcinoma.