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As GPX4 serves as the master regulator of lipid hydroperoxide reduction, its suppression triggers irreversible lipid peroxide accumulation that culminates in ferroptotic cell death ( Complementing this primary mechanism, emerging evidence indicates that SFN modulates iron metabolism through upregulation of ferritin heavy chain (FTH1), potentially altering intracellular iron homeostasis to promote iron-mediated lipid peroxidation via Fenton chemistry ( 4.3 Targeting CSCs through coordinated pathway disruption SFN demonstrates remarkable efficacy against CSCs through its ability to simultaneously disrupt multiple signaling pathways that maintain stemness and self-renewal capacity

Funding This paper was supported by San Matteo Hospital Foundation, Internal Medicine research fundings, PRIN2017. Publishers note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers

Bull Cancer (2020) 107:88195

GSH levels in macrophages, directly affect the Th1/Th2 cytokine response, and more specifically, GSH depletion inhibits Th1-associated cytokine production and/or promotes Th2 associated responses (Fraternale et al., 2006)

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In CriglerNajjar syndrome patients, orlistat cotreatment resulted in up to a 21% reduction in serum bilirubin by diverting bilirubin from enterohepatic circulation into the intestinal lumen [60]