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168 Studies in experimental models have shown an association between AATD and oxidative stress

ROS initiates increase of P2X7 expression on the mitochondrial membrane and activity of Complex I, hence increasing mitochondrial polarization, which leads to an elevation of a cascade of unfavorable processes: depolarization of the mitochondrial membrane, calcium overload, and release of cytochrome c , which ultimately leads to cell death by apoptosis way

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Also, in the late phase of M1 macrophage polarization, lactate-derived lactylation of histone lysine residues as observed in conditions of hypoxia and bacterial challenges served as an epigenetic modification that directly stimulated the expression of homeostatic genes that have been traditionally associated with M2-like macrophages (Zhang et al., 2019)

PI3KAKTmTOR Consistent with their role in apoptosis suppression, cell proliferation, metabolism and anabolic reactions, the interconnected PI3KAKT and mTOR pathways are hyperactivated in almost 40% of all human cancers