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Furthermore, AS-IVs cardioprotective effects in heart failure appear to be dose-dependent, as demonstrated by increased expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE)-dependent genes, such as heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO-1), and sulfiredoxin-1 (Srxn-1), with rising AS-IV concentrations in the oxygen-glucose deprivation model (Yu et al., 2007)