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BackgroundWe investigated the association of cumulative smoking exposure and duration of smoking cessation with peripheral arterial disease (PAD).MethodsThe study population consisted of 2517 community-dwelling Korean men aged 50 years and older. Information on smoking characteristics such as smoking status, pack-years of smoking, and years since quitting smoking was collected using a standardized questionnaire. PAD was defined as an ankle-brachial index (ABI) less than 0.90 in either leg.ResultsThe odds ratio (OR, 95% confidence interval) of PAD was 2.31 (1.20-4.42) for former smokers and 4.30 (2.13-8.66) for current smokers, after adjusting for other cardiovascular risk factors. There was a significant dose-response relationship between pack-years of smoking and PAD. Compared with those who had never smoked, the multivariate-adjusted ORs of PAD for smokers of 0.1-20.0, 20.1-40.0, and >40.0 pack-years were 2.15 (1.06-4.38), 2.24 (1.08-4.65), and 2.93 (1.41-6.09), respectively. There was a significant decrease in PAD risk as the years since quitting smoking increased. The multivariate-adjusted ORs of PAD for 11-20 and ≥21 years smoking cessation were 0.41 (0.19-0.86) and 0.49 (0.24-0.98), compared with current smokers.ConclusionsCumulative smoking exposure and duration of smoking cessation were significantly associated with PAD in middle aged and older Korean men.

These two cohorts were designed to examine the increasing burden of chronic diseases among Korean populations. The studies investigated determinants for stroke, osteoporosis, dementia and cancer among middle-aged and elderly Korean populations. The Namwon Study baseline survey was performed between 2004 and 2007 (n = 10 667), and followed up 4 years later (n = 8157, follow-up rate = 76.5%). The baseline survey of the Dong-gu Study was administered over 2007-2010 (n = 9260), and will be followed up between 2014 and 2015. Questionnaires included assessment of cognitive function, psychiatric health and lifestyle factors. Clinical examinations, biochemical tests and genotyping focused on evaluating the determinants of target diseases and their intermediate phenotypes. Potential collaborators will be invited to contact the chief investigators.

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Abstract. In the present study, we investigated berberine-induced apoptosis and the signaling pathways underlying its activity in FaDu head and neck squamous cell carcinoma cells. Berberine did not affect the viability of primary human normal oral keratinocytes. In contrast, the cytotoxicity of berberine was significantly increased in FaDu cells stimulated with berberine for 24 h. Furthermore, berberine increased nuclear condensation and apoptosis rates in FaDu cells than those in untreated control cells. Berberine also induced the upregulation of apoptotic ligands, such as FasL and TNF-related apoptosis-inducing ligand, and triggered the activation of caspase-8, -7 and -3, and poly(ADP ribose) polymerase, characteristic of death receptor-dependent extrinsic apoptosis. Moreover, berberine activated the mitochondria-dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bax, Bad, Apaf-1, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. In addition, berberine increased the expression of the tumor suppressor p53 in FaDu cells. The pan-caspase inhibitor Z-VAD-fmk suppressed the activation of caspase-3 and prevented cytotoxicity in FaDu cells treated with berberine. Interestingly, berberine suppressed cell migration through downregulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and p38, components of the mitogen-activated protein kinase pathway that are associated with the expression of MMP and VEGF, was suppressed in FaDu cells treated with berberine for 24 h. Therefore, these data suggested that berberine exerted anticancer effects in FaDu cells through induction of apoptosis and suppression of migration. Berberine may have potential applications as a chemotherapeutic agent for the management of head and neck squamous carcinoma.