NFE2L2 and Sepsis: In the early stage of sepsis, HO-1, transcriptionally activated by nuclear factor erythroid 2-related factor 2 (NRF2), exerts antioxidant and cytoprotective effects by degrading labile heme into biliverdin, carbon monoxide, and Fe2+, thereby alleviating oxidative stress and preserving microcirculatory integrity [83, 165].