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In addition, in the HepG2 cell experiment, some extrahepatic factors, such as erythroid-2-related factor 2 (NRF2) pathway [58], intestinal metabolite sodium butyrate (NaB) [59], Src homology region 2 domain-containing phosphatase-1 (SHP1)/AMPK [60], sirtuin 1 (SIRT1)/heat shock factor 1/heat shock protein (HSP) [61], and other signaling pathways have also been found to be involved in the regulation of liver lipid synthesis

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Any of these can undermine colonization and force a restart

The site affects the absorption curve of each individual dose, not the long-term treatment trajectory