{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough none of the provided abstracts directly mention or investigate MIR4720, the collection of studies offers important insights into the metabolic pathways and enzymatic functions related to retinol metabolism that may serve as a contextual backdrop for understanding potential microRNA regulation. In particular, these studies elucidate how alcohol dehydrogenases—especially ADH3—mediate the oxidation of retinol to retinal, a critical first step in the synthesis of retinoic acid which is essential for tissue development and cellular growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe research also shows that ADH3, being a ubiquitously expressed enzyme, plays a central, though secondary, role in retinol utilization and clearance compared to other ADH isoforms. Its activity influences not only normal development via retinoid signaling but also impacts pathological conditions such as vitamin A toxicity, where a deficiency in ADH1 predominantly causes toxicity issues, while ADH3’s involvement is moderate yet important in metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, ADH3 expression in non-hepatic tissues is linked with broader physiological roles including the modulation of liver fibrosis. Specifically, its expression in hepatic stellate cells and natural killer cells regulates fibrogenesis by affecting collagen production and immune responses; inhibition or genetic depletion of ADH3 attenuates fibrosis and enhances NK cell activity. Moreover, low-level expression of ADH3 along the gastrointestinal tract suggests a role in the defense against toxic aldehydes and alcohols."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andrei Molotkov, Xiaohong Fan, Louise Deltour, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stimulation of retinoic acid production and growth by ubiquitously expressed alcohol dehydrogenase Adh3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.082093299"}], "href": "https://doi.org/10.1073/pnas.082093299"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11959987"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11959987"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Andrei Molotkov, Xiaohong Fan, Gregg Duester "}, {"type": "b", "children": [{"type": "t", "text": "Excessive vitamin A toxicity in mice genetically deficient in either alcohol dehydrogenase Adh1 or Adh3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Biochem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1432-1033.2002.02935.x"}], "href": "https://doi.org/10.1046/j.1432-1033.2002.02935.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12027900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12027900"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hyon-Seung Yi, Young-Sun Lee, Jin-Seok Byun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alcohol dehydrogenase III exacerbates liver fibrosis by enhancing stellate cell activation and suppressing natural killer cells in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.27137"}], "href": "https://doi.org/10.1002/hep.27137"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24668648"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24668648"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Marie Westerlund, Andrea Carmine Belin, Michael R Felder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High and complementary expression patterns of alcohol and aldehyde dehydrogenases in the gastrointestinal tract: implications for Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1742-4658.2007.05665.x"}], "href": "https://doi.org/10.1111/j.1742-4658.2007.05665.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17257171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17257171"}]}]}]}