[Effect of astragaloside â £ on angiotensin â ¡-induced inflammatory response of vascular endothelial cells and mechanism].

This study was designed to determine the inhibitory effect of astragaloside Ⅳ(AS-Ⅳ), a principal bioactive component extracted from the Chinese medicinal Astragali Radix, on the inflammatory response of vascular endothelial cells induced by angiotensin Ⅱ(Ang Ⅱ), the most major pathogenic factor for cardiovascular diseases, and to clarify the role of calcium(Ca~(2+))/phosphatidylinosi-tol-3-kinase(PI3K)/protein kinase B(Akt)/endothelial nitric oxide synthase(eNOS)/nitric oxide(NO) pathway in the process. To be specific, human umbilical vein endothelial cells(HUVECs) were cultured in the presence of AS-Ⅳ with or without the specific inhibitor of NO synthase(NG-monomethyl-L-arginine, L-NMMA), inhibitor of PI3K/Akt signaling pathway(LY294002), or Ca~(2+)-chelating agent(ethylene glycol tetraacetic acid, EGTA) prior to Ang Ⅱ stimulation. The inhibitory effect of AS-Ⅳ on Ang Ⅱ-induced inflammatory response and the involved mechanism was determined with enzyme-linked immunosorbent assay(ELISA), cell-based ELISA assay, Western blot, and monocyte adhesion assay which determined the fluorescently labeled human monocytic cell line(THP-1) adhered to Ang Ⅱ-stimulated endothelial cells. AS-Ⅳ increased the production of NO by HUVECs in a dose-and time-dependent manner(P<0.05) and raised the level of phosphorylated eNOS(P<0.05). The above AS-Ⅳ-induced changes were abolished by pretreatment with L-NMMA, LY294002, or EGTA. Compared with the control group, Ang Ⅱ obviously enhanced the production and release of cytokines(tumor necrosis factor-α, interleukin-6), chemokines(monocyte chemoattractant protein-1) and adhesion molecules(intercellular adhesion molecule-1, vascular cellular adhesion molecule-1), and the number of monocytes adhered to HUVECs(P<0.05), which were accompanied by the enhanced levels of phosphorylated inhibitor of nuclear factor-κBα protein and activities of nuclear factor-κB(NF-κB)(P<0.05). This study also demonstrated that Ang Ⅱ-induced inflammatory response was inhibited by pretreatment with AS-Ⅳ(P<0.05). In addition, the inhibitory effect of AS-Ⅳ was abrogated by pretreatment with L-NMMA, LY294002, or EGTA(P<0.05). This study provides a direct link between AS-Ⅳ and Ca~(2+)/PI3K/Akt/eNOS/NO pathway in AS-Ⅳ-mediated anti-inflammatory actions in endothelial cells exposed to Ang Ⅱ. The results indicate that AS-Ⅳ attenuates endothelial cell-mediated inflammatory response induced by Ang Ⅱ via the activation of Ca~(2+)/PI3K/Akt/eNOS/NO signaling pathway.

RKIP reduction enhances radioresistance by activating the Shh signaling pathway in non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) is exceptionally deadly because the tumors lack sensitive early-stage diagnostic biomarkers and are resistant to radiation and chemotherapy. Here, we investigated the role and mechanism of Raf kinase inhibitory protein (RKIP) in NSCLC radioresistance. The clinical data showed that the RKIP expression level was generally lower in radioresistant NSCLC tissues than in radiosensitive tissues. Reduced RKIP expression was related to NSCLC radioresistance and poor prognosis. In vitro experiments showed that RKIP knockdown increased radioresistance and metastatic ability in NSCLC cell lines. Mechanistically, RKIP reduction activated the Shh signaling pathway by derepressing Smoothened (Smo) and initiating glioma-associated oncogene-1 (Gli1)-mediated transcription in NSCLC. In addition, the inappropriately activated Shh-Gli1 signaling pathway then enhanced cancer stem cell (CSC) expression in the cell lines. The increasing quantity of CSCs in the tumor ultimately promotes the radiation resistance of NSCLC. Together, these results suggest that RKIP plays a vital role in radiation response and metastasis in NSCLC. RKIP reduction enhances radioresistance by activating the Shh signaling pathway and initiating functional CSCs. This role makes it a promising therapeutic target for improving the efficacy of NSCLC radiation treatment.

Protective effects of Jiashen Prescription () on myocardial infarction in rats.

OBJECTIVE: To evaluate the effects of Jiashen Prescription (, JSP) on myocardial infarction (MI) size and cardiac function at the early stage of MI in rats. METHODS: One hundred male Sprague-Dawley rats were subjected to sham-operation or MI induced by ligating the left anterior descending coronary artery. The rats with MI were treated with vehicle, JSP 3 and 6 g/(kg·d), or losartan 10 mg/(kg·d) for 1 week. RESULTS: Compared with the vehicle-treated MI rats, 6 g/(kg·d) JSP reduced MI size 3 days after MI (P<0.05), and attenuated the MI-induced increases in left ventricular end-diastolic and end-systolic dimension and decreases in fractional shortening and ejection fraction 1 week after MI (P<0.05). In addition, 6 g/(kg·d) JSP and losartan were equally effective in reducing MI size and enhancing cardiac functional recovery. CONCLUSION: JSP reduces MI size and improves cardiac function after MI, suggesting that JSP has potential as a therapy for MI.