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Furthermore, the mechanistic understanding of metabolite-mediated epigenetic reprogramming continues to expand, with evidence showing that lactate-induced histone lactylation and itaconate-driven Nrf2 activation can establish and sustain an anti-inflammatory macrophage phenotype, opening avenues for durable immunomodulation (78, 82, 84)

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Taken together, these findings suggest that the downstream effects of the PI3K/AKT/GSK3 pathway may involve FoxK1 or other coexisting transcription factors that facilitate HIF-1 transcription [51], and further investigations are needed to explore these signaling pathways in cancer cells

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10.1038/180326a0 47 IngramV