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In some embodiments, the invention encompasses a method of providing muscular therapy by contacting a cell expressing NNMT with a NNMT inhibitor (such as a cation of Formula I or IA, or otherwise disclosed herein) and one or more chemical entities (e.g., nicotinamide riboside, nicotinamide mononucleotide) that increases intracellular NAD+ levels to provide muscular therapy

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Since ZO-1directly binds to F-actin [20] and the actin binding region of ZO-1 is required for barrier regulation by MLCK [21], ZO-1 downregulation or knockdown increases leak pathway permeability [22]