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References: Acharya Dahal R et al (2014): Computational and biochemical docking of the irreversible cocaine analog RTI 82 directly demonstrates ligand positioning in the dopamine transporter central substrate-binding site

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Mechanistically, metformin enhances the expression and activity of SIRT1 and subsequently downregulates TLR4, p-NF-B, IL-1 and iNOS (the makers of proinflammatory M2 macrophages) and upregulates Arg1 (the maker of anti-inflammatory M1 macrophages) expressions to increase M2 macrophage polarization and inhibit M2 macrophage polarization (Liu H