In in vitro macrophage polarization models, exogenous -KG significantly increases Arg1 expression and suppresses iNOS expression, and changes in the -KG/succinate ratio are closely associated with the expression of M2-related genes ( in vitro cultured macrophage models, high concentrations of leucine can enhance anti-inflammatory gene expression through mechanistic target of mTORC1 signaling, which is inconsistent with other theoretical views and suggests that its effects are condition-dependent ( In addition to energy supply and metabolic flux remodeling, amino acid-derived metabolites can also directly participate in signaling regulation
Low GSH levels could also increase viral replication, pro-inflammatory cytokine release, endothelial damage, and immune-thrombosis, which is a hyper-coagulative clinical condition that could exacerbate morbidity and mortality in COVID-19 and PASC 598
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Conclusions Up to the 1980s, cell death caused by drugs, chemicals, and other pathophysiologies was primarily considered necrosis
