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It should be added that aberrations in the paracellular route of the gut barrier are associated with an increased bacterial or LPS translocation (leaky gut) and, thus, activation of the IO&NS pathways (9)

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Importantly, the circadian interplay between PER2 and p53 forms a regulatory feedback loop in which p53 suppresses PER2 expression, while PER2 stabilizes p53 by inhibiting MDM2-dependent ubiquitination, linking circadian rhythm to cellular stress responses and tumor suppression (Gotoh et al., 2015