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Finally, peroxynitrite inactivates prostacyclin synthase by activating NF-B and increasing nitric oxide synthase expression in endothelial cells in vitro , which also leads to endothelial dysfunction ( in vitro studies of human gingival epithelial cells (Semlali et al., 2012) and macrophages (Yang et al., 2006), smoking leads to dysregulation of TLRs and NF-B, which contribute to atherogenesis by promoting OxS, inflammation, and endothelial dysfunction (Hovland et al., 2015
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In the Kaplan-Meier estimates in Supplementary file Figure 1, significant differences in incidence rates of T2DM were observed only among males, which contributed to the overall population effect
