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Once activated, caspase-3 initiates the cleavage of a downstream substrate, such as nuclear poly (ADP-ribose) polymerase (PARP), which facilitates cellular disassembly and serves as a biomarker of cell apoptosis

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To support the connection between drug abuse and constipation, intriguingly, opioid use disorder may lead to the development of primary hypothyroidism (Pezeshki et al., 2023), disease in which constipation is frequently observed (Pustorino et al., 2004)