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Vascular smooth muscle cell (VSMC) phenotypic switching plays a critical role in the formation of abdominal aortic aneurysms (AAAs). FoxO3a is a key suppressor of VSMC homeostasis. We found that in human and animal AAA tissues, FoxO3a was upregulated, SM22α and α-smooth muscle actin (α-SMA) proteins were downregulated and synthetic phenotypic markers were upregulated, indicating that VSMC phenotypic switching occurred in these diseased tissues. In addition, in cultured VSMCs, significant enhancement of FoxO3a expression was found during angiotensin II (Ang II)-induced VSMC phenotypic switching. In vivo, FoxO3a overexpression in C57BL/6J mice treated with Ang II increased the formation of AAAs, whereas FoxO3a knockdown exerted an inhibitory effect on AAA formation in ApoE−/− mice infused with Ang II. Mechanistically, FoxO3a overexpression significantly inhibited the expression of differentiated smooth muscle cell (SMC) markers, activated autophagy, the essential repressor of VSMC homeostasis, and promoted AAA formation. Our study revealed that FoxO3a promotes VSMC phenotypic switching to accelerate AAA formation through the P62/LC3BII autophagy signaling pathway and that therapeutic approaches that decrease FoxO3a expression may prevent AAA formation.

Hydroquinone (HQ) is widely used in food stuffs and is an occupational and environmental pollutant. Although the hepatotoxicity of HQ has been demonstrated both in vitro and in vivo, the prevention of HQ-induced hepatotoxicity has yet to be elucidated. In this study, we focused on the intervention effect of aqueous extracts of Flos lonicerae Japonicae (FLJ) on HQ-induced cytotoxicity. We demonstrated that HQ reduced cell viability in a concentration-dependent manner by administering 160 μmol/L HQ for 12 h as the positive control of cytotoxicity. The aqueous FLJ extracts significantly increased cell viability and decreased LDH release, ALT, and AST in a concentration-dependent manner compared with the corresponding HQ-treated groups in hepatic L02 cells. This result indicated that aqueous FLJ extracts could protect the cytotoxicity induced by HQ. HQ increased intracellular MDA and LPO and decreased the activities of GSH, GSH-Px, and SOD in hepatic L02 cells. In addition, aqueous FLJ extracts significantly suppressed HQ-stimulated oxidative damage. Moreover, HQ promoted DNA double-strand breaks (DSBs) and the level of 8-hydroxy-2′-deoxyguanosine and apoptosis. However, aqueous FLJ extracts reversed HQ-induced DNA damage and apoptosis in a concentration-dependent manner. Overall, our results demonstrated that the toxicity of HQ was mediated by intracellular oxidative stress, which activated DNA damage and apoptosis. The findings also proved that aqueous FLJ extracts exerted protective effects against HQ-induced cytotoxicity in hepatic L02 cells.

BackgroundHuman 8-oguanine glycosylase 1(hOGG1), voltage-dependent anion channel 1(VDAC1), hexokinase 2(HK-2), represented the process of oxidative DNA damage, cell apoptosis and glycolysis, respectively. This study aims to explore the association between expression of hOGG1, VDAC1, HK-2 and cervical carcinoma.MethodsA case-control study was conducted. 65 cervical biopsy samples consist of 20 control and 45 cases. The expression of hOGG1, VDAC1 and HK-2 were examined with immunohistochemistry(IHC), immunolabeling was evaluated with stereological cell counts.ResultsThe data showed that the positive proportion of hOGG1 and HK-2 in the case group was higher than that of the control group (P < 0.05). Further, there was an increasing trend for the positive proportion and expression degree of hOGG1 and HK-2 from Control, Mild cervical carcinoma (MCC), Intermediate cervical carcinoma(ICC) to Severe cervical carcinoma(SCC) in order (P < 0.05). To VDAC1, the significant result was not obtained.ConclusionsThe results suggested that there was a close association between expression of hOGG1, HK-2 and cervical cancer. hOGG1 and HK-2 might play a key role at the early stage of cervical cancer, and the findings of hOGG1 and HK-2 should be considered as a significant biomarker at the early stage of cervical cancer.