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Oxidative stress decreases BH4 levels in the endothelium, driving the uncoupling of nitric oxide synthase and the production of more oxidative stress

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GAPDH (glyceraldehyde 3-phosphate dehydrogenase) served as a loading control for total protein, while Histone-H3 was used for nuclear extracts

To bridge the preclinicalclinical gap, three concrete translational pathways are proposed: (1) Biomarker validation: Conduct prospective human cohort studies to verify preclinical biomarkers (e.g., GSDMD-NT for pyroptosis, HMGB1 for inflammation, MDA for lipid peroxidation, ferritin for ferroptosis) in serum and liver biopsies of EHS/CHS patients, establishing their diagnostic (early liver injury detection) and prognostic (MODS progression prediction) utility [59, 89]