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SUMOylation regulates the transcriptional activity of NRF2, affects its interaction with other proteins and intracellular localization, and protects NRF2 from ubiquitination-mediated degradation [129]

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Thus, determining whether metabolic changes observed in vivo are the either the cause or the result of a toxicity event, represents a significant challenge in metabolomics ( On the other hand, in vitro metabolomics can overcome the limitations of in vivo studies and reveal early events following drug exposure

During the resolution of inflammation, SPMs produced by polymorphonuclear cells and macrophages act to limit local tissue damage caused by inflammatory responses, including signaling cessation of polymorphonuclear cell infiltration, macrophage switching to an anti-inflammatory phenotype, apoptotic cell clearance, and reducing pain caused by nociceptor sensitization (61)

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