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NNMT influences this regulatory landscape via: Reducing SAM availability for DNA and histone methylation Causing altered chromatin states that can activate oncogenes or silence tumor suppressors Facilitating oncogenic reprogramming in both tumor cells and stromal microenvironment 9

Based on the increase in cardiolipin biosynthesis, we hypothesize that luseogliflozin facilitates the maintenance of mitochondrial ATP production in response to I/R injury-induced tissue damage and oxidative stress