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The therapeutic effect of NOS recoupling on endothelial dysfunction in hypertension, diabetes, and myocardial infarction is well recognized ( in vivo tumor models and patient biopsies ( in vivo ( NOS uncoupling and BH4 depletion Biopterins are reductive, enzymatic cofactors required by organisms in all kingdoms of life ( NOS uncoupling is also accompanied by a consequential shift in NO-mediated signaling, which is relevant both to tumor progression as well as the anti-tumor immune response

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Mitochondrial dysfunction, potentially through impaired oxidative phosphorylation, may precipitate ferroptosis by escalating ROS production beyond the cell's antioxidant threshold [41]