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Activation of the UPR generally serves as a readout for ER stress, but it is not clear what diminished UPR signaling implies in terms of actual accumulation of unfolded proteins, particularly because some stressors, such as palmitate loading, activate the UPR apparently independent of the protein folding process (Volmer et al., 2013)

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This is part of why B12 has a strong safety record, and it is also why levels sometimes need regular replenishment during active treatment

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Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication