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Pharmacologic activation of this pathway by metformin amplifies Treg populations (104), while glycolysis inhibition with 2-deoxyglucose (2-DG) shifts metabolism toward FAO, thereby promoting a phenotypic switch from Th17 to Treg cells ( FAO-driven OXPHOS is necessary for Treg cells to continue their suppressive role (105)

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In certain embodiments, the pharmacokinetics of the otic formulations or compositions described herein are determined by injecting the formulation on or near the round window membrane of a test animal (including by way of example, a guinea pig, a chinchilla, or a rat)