{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe provided body of work comprehensively investigates the carrier‐mediated uptake of thiamin (vitamin B1) across several tissues. Several studies characterize how thiamin is absorbed in the intestine, kidney, and pancreatic beta cells by two key transporters—THTR‑1 and THTR‑2, encoded by SLC19A2 and SLC19A3, respectively—detailing elements such as substrate affinity, pH dependency, and adaptive transcriptional regulation in response to vitamin levels. Collectively, these studies underscore the intricate regulation of thiamin homeostasis for normal cellular function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOther investigations highlight the functional significance of these transporters in pancreatic acinar cells and the clinical implications of their disruption. Experiments using gene-silencing and knockout models have demonstrated that deficiencies or mutations—particularly in THTR‑1—lead to markedly reduced thiamin uptake, contributing to cellular dysfunction and neurodegenerative outcomes. These findings also stress the importance of timely, high-dose thiamin administration as a therapeutic intervention in disorders stemming from SLC19A3 deficiency."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA further focus of these studies is the species-specific substrate specificity of thiamin transporters. Comparative analyses reveal that while human SLC19A3 can transport both thiamin and pyridoxine (vitamin B6), its rodent orthologs are restricted to thiamin transport. These differences pinpoint critical amino acid residues responsible for pyridoxine transport and emphasize the need for caution when selecting animal models for vitamin disposition research."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIt is important to note that none of the abstracts provided include any mention or analysis of LINC00396. As a result, while they offer detailed insights into thiamin transporter function and regulation, the role and function of LINC00396 remain undetermined based on the current literature.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jack C Reidling, Svetlana M Nabokina, Krishnaswamy Balamurugan, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Pancreatic beta cells and islets take up thiamin by a regulated carrier-mediated process: studies using mice and human pancreatic preparations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00092.2009"}], "href": "https://doi.org/10.1152/ajpgi.00092.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19423748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19423748"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jack C Reidling, Nils Lambrecht, Mohammad Kassir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impaired intestinal vitamin B1 (thiamin) uptake in thiamin transporter-2-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2009.10.042"}], "href": "https://doi.org/10.1053/j.gastro.2009.10.042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19879271"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19879271"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Veedamali S Subramanian, Sandeep B Subramanya, Hamid M Said "}, {"type": "b", "children": [{"type": "t", "text": "Relative contribution of THTR-1 and THTR-2 in thiamin uptake by pancreatic acinar cells: studies utilizing Slc19a2 and Slc19a3 knockout mouse models."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00484.2011"}], "href": "https://doi.org/10.1152/ajpgi.00484.2011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22194418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22194418"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kaoru Suzuki, Kenichiro Yamada, Yayoi Fukuhara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High-dose thiamine prevents brain lesions and prolongs survival of Slc19a3-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0180279"}], "href": "https://doi.org/10.1371/journal.pone.0180279"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28665968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28665968"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kohei Miyake, Tomoya Yasujima, Syunsuke Takahashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the amino acid residues involved in the species-dependent differences in the pyridoxine transport function of SLC19A3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2022.102161"}], "href": "https://doi.org/10.1016/j.jbc.2022.102161"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35724964"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35724964"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Takahiro Yamashiro, Tomoya Yasujima, Hiroaki Yuasa "}, {"type": "b", "children": [{"type": "t", "text": "Animal species differences in the pyridoxine transport function of SLC19A3: Absence of Slc19a3-mediated pyridoxine uptake in the rat small intestine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Pharmacokinet (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.dmpk.2022.100456"}], "href": "https://doi.org/10.1016/j.dmpk.2022.100456"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35512554"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35512554"}]}]}]}