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In in vitro macrophage polarization models, exogenous α-KG significantly increases Arg1 expression and suppresses iNOS expression, and changes in the α-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

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Remarkably, increasing evidence also points toward GPX4 protein degradation as a means to incite cancer cell ferroptosis and apoptosis in hepatocellular carcinoma and breast cancer cells [221,222,223]

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