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Altered circadian rhythm leads to increased oxidative stress resulting in the nuclear translocation of Nrf2, where it binds to the ARE initiating the transcription of several cytoprotective genes

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proposed two mechanisms by which (i) melatonin pretreatment represents an interfering mechanism for Ripk3/PGAM5/CypD axis execution, desensitizing cells to necroptosis triggered by RipK3 activation, PGAM upregulation, and CypD phosphorylation 50 in endothelial cells

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