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Mechanism-based research considerations include: Altered methylation: NNMT inhibition affects SAM, a participant in many methylation reactions

Because there were seven randomized trials reporting on more than 500 patients from which to draw evidence (including five trials that compared PPS to placebo, one trial that examined PPS dose-response effects, and one that compared PPS to CyA), the numerous observational studies on PPS were not used

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Neuronal activation mapping using cFos immunostaining in the area postrema (AP), nucleus tractus solitarius (NTS), and lateral parabrachial nucleus (LPBN) provided mechanistic insight

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