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9.1 Integrated discussion on mechanistic evidence strength, gaps, and confounding factors (1) Strength ranking of core mechanistic evidence and prioritization for clinical translation Based on a systematic analysis of each nutrient's regulatory pathway, the mechanisms with the strongest evidence for clinical translation are prioritized as follows: Omega-3 polyunsaturated fatty acids (EPA/DHA) anti-inflammatory pathway: Supported by human RCTs (65, 69), which show that EPA/DHA supplementation reduces the levels of pro-inflammatory cytokines (IL-1, IL-6) and improves depressive symptoms

Oncotarget 8:103931103951 Kumamoto S, Nishiyama A, Chiba Y, Miyashita R, Konishi C, Azuma Y, Nakanishi M (2021) HPF1-dependent PARP activation promotes LIG3-XRCC1-mediated backup pathway of Okazaki fragment ligation

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In addition, excessive iron could be exported through the iron efflux pump, FPN, thereby reducing intracellular iron overload (Geng et al., 2018)

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