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Abstract. Lung cancer is the leading cause of cancer-related mortality in humans. The prognosis for advanced lung cancer patients is extremely poor. Current standard care is rather ineffective for prolonging patient life while preserving satisfactory quality of life due to adverse side-effects. Matrine extracted from the traditional Chinese herbal plant Sophora flavescens was shown to induce cancer cell death in vitro. The aim of this study was to investigate the effect of matrine on the proliferation and apoptosis of lung cancer cells and the molecular basis of matrine-induced apoptosis. The results showed that matrine inhibited cell proliferation and induced apoptosis in lung cancer A549 and 95D cells in a dose-and time-dependent manner. The apoptotic effects of matrine on lung cancer cells appeared to act via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathway and downregulation of the expression of the inhibitor of apoptosis protein (IAP) family proteins. Matrine exerts its cancer-killing effect via promoting apoptosis in lung cancer cells and may be a useful adjuvant therapeutic scheme for treating advanced lung cancer patients.

Obstructive sleep apnea (OSA), characterized by recurrent collapse of the upper airway during sleep leading to chronic intermittent hypoxia (CIH), is an independent risk factor for hypertension. Sympathetic excitation has been shown to play a major role in the pathogenesis of OSA-associated hypertension. Accumulating evidence indicates that oxidative stress and inflammation in the hypothalamic paraventricular nucleus (PVN), a critical cardiovascular and autonomic center, mediate sympathetic excitation in many cardiovascular diseases. Here we tested the hypothesis that CIH elevates oxidative stress and inflammation in the PVN, which might be associated with sympathetic excitation and increased blood pressure in a rat model of CIH that mimics the oxygen profile in patients with OSA. Sprague-Dawley rats were pretreated with intracerebroventricular (ICV) infusion of vehicle or superoxide scavenger tempol, and then exposed to control or CIH for 7 days. Compared with control+vehicle rats, CIH+vehicle rats exhibited increased blood pressure, and increased sympathetic drive as indicated by the blood pressure response to ganglionic blockade and plasma norepinephrine levels. Pretreatment with ICV tempol prevented CIH-induced increases in blood pressure and sympathetic drive. Molecular studies revealed that expression of NAD(P)H oxidase subunits, production of reactive oxygen species, expression of proinflammatory cytokines and neuronal excitation in the PVN were elevated in CIH+vehicle rats, compared with control+vehicle rats, but were normalized or reduced in CIH rat pretreated with ICV tempol. Notably, CIH+vehicle rats also had increased systemic oxidative stress and inflammation, which were not altered by ICV tempol. The results suggest that CIH induces elevated oxidative stress and inflammation in the PVN, which lead to PVN neuronal excitation and are associated with sympathetic excitation and increased blood pressure. Central oxidative stress and inflammation may be novel targets for the prevention and treatment of hypertension in patients with OSA.

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The present study aimed to investigate the association between xanthine dehydrogenase (XDH) gene polymorphism and essential hypertension in the rural Han Chinese population of Fuxin, Liaoning. Han Chinese individuals, who had lived in rural areas of Fuxin, were selected as subjects for the present study. A total of 521 unrelated patients with hypertension were selected, along with a further 533 unrelated individuals with normal blood pressure, in order to serve as controls. Five tag single nucleotide polymorphisms (SNP) of the XDH gene were selected. An estimation of SNP allele frequency was determined using DNA pooling and pyrosequencing methods. Prior to Bonferroni correction, T allele frequency for rs206811 was significantly higher in patients with hypertension, as compared with the controls (64.1 vs. 59.4%; P=0.031); C allele frequency for rs1042039 was significantly higher in patients with hypertension, as compared with the controls (66.1 vs. 60.6%; P=0.011), C allele frequency for rs1054889 was significantly lower in patients with hypertension, as compared with the controls (38.8 vs. 44.8%; P=0.007); and A allele frequency for rs2073316 was significantly lower in patients with hypertension, as compared with the controls (29.2 vs. 34.4%; P=0.013). However, once a Bonferroni correction for multiple testing was applied, the XDH gene polymorphisms rs1042039, rs1054889, and rs2073316 were shown to be associated with hypertension (P=0.044, 0.035, and 0.039, respectively). These results suggest that the XDH gene polymorphisms rs1042039, rs1054889, and rs2073316 may be associated with hypertension in the rural Han Chinese population.