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Additionally, nicotine can increase the risk of thrombosis through the increased cellular expression of the pro-inflammatory cytokine TNF- and plasminogen activator inhibitor-1, as well as the downregulation of NrF2, which regulates the antioxidative response system, and thrombomodulin, responsible for the crucial anticoagulant properties of thrombin (Lau et al., 2006

[7] The kiseru would be the main way to smoke tobacco until after the Meiji Restoration of 1868, when cigarettes were introduced and rapidly became popular

David SP, Munaf MR, Johansen-Berg H, Smith SM, Rogers RD, Matthews PM et al (2005)