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It was shown in vitro using ZF cell lines that constant ACTH treatment led to larger increase in pCREB and steroidogenic gene transcription at the start of treatment but the cells became unresponsive to the stimuli over time (158)

Oxidative Stress and Diabetic Retinopathy: Molecular Mechanisms, Pathogenetic Role and Therapeutic Implications

Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis
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PLoS ONE 13 (12), 119 (2018)

In fact, since B12 deficiencies can lead to mood changes, proper supplementation often helps improve mood-related issues
