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Under hypoxic conditions, proline hydroxylase cannot negatively regulate the stability and ubiquitination degradation of HIF-1 through oxygen-dependent hydroxylation modification, resulting in HIF-1 accumulation and translocation to the nucleus and binding to HIF-1 to form a complex, followed by the recruitment of coactivators (CBP/P300) at the hypoxia response element (HRE) to upregulate the transcription of glucose transporters and glycolytic enzymes to promote anaerobic glycolysis [84, 85]

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During the study, female mice were given metformin alone at 500 mg per kg, melatonin at 1mg per kg, or a combination of melatonin at 2mg per kg with testosterone

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