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Wei H, Zhang WJ, McMillen TS, Leboeuf RC, Frei B

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In addition to inhibiting proliferation, carotenoids affect the cellular DNA damage response pathway, enhancing p53-mediated gene monitoring and repair

Trials should co-primary mechanistic change (e.g., Prx cycling, 2-OH-E by DHE-HPLC, LIP de-quench) and clinical improvement, with biomarker gates for entry and adaptive dosing to respect where, when, how much. Pre-specified normalization (per protein/cell, oxygenation, m for mito-probes) and orthogonal controls (SOD/catalase, chelators, genetics) should be mandatory (Katerji et al