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The molecule is small enough to cross the epidermal barrier to some degree, but reaching fibroblasts in the mid-to-deep dermis where the structural work happens requires either injection or a delivery mechanism that bypasses the barrier

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J Clin Investig 111(10):14971504 Myers VD, Tomar D, Madesh M, Wang J, Song J, Zhang XQ, Gupta MK, Tahrir FG, Gordon J, McClung JM, Kontos CD, Khalili K, Cheung JY, Feldman AM (2018) Haplo-insufficiency of Bcl2-associated athanogene 3 in mice results in progressive left ventricular dysfunction, -adrenergic insensitivity, and increased apoptosis

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163 Moreover, TNF and IL1 inhibit the circadian rhythm CLOCK:BMAL1 complex