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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

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Endogenous and exogenous antioxidants neutralize harmful free radicals

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However, our earlier observations in the same species (unpublished data) did not reveal any significant differences in renal morphology or urinary protein excretion between SHR and WKY rats aged 416 weeks, except after 48 weeks of age when significant decreases in glomerular filtration rate and glomerular necrosis was evident in SHR

8), thus providing further evidence to support the in silico predictions (Supplementary Fig