{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTXNIP is rapidly induced in response to high extracellular glucose and acts as a central negative regulator of cellular energy balance. It directly binds to the glucose transporter GLUT1 to promote its internalization and indirectly reduces GLUT1 mRNA levels, thereby dampening glucose uptake when intracellular glucose is high. In pancreatic β‐cells, elevated TXNIP not only signals glucose excess but also triggers apoptotic pathways that contribute to glucotoxicity and β‐cell loss in diabetes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in metabolism, TXNIP is a pivotal regulator of redox homeostasis. By forming a redox‐sensitive disulfide-linked complex with thioredoxin, TXNIP inhibits the antioxidant function of thioredoxin and thereby enhances reactive oxygen species (ROS) production. This redox imbalance facilitates the activation of stress kinases such as ASK1 and triggers inflammatory cascades—including the NLRP3 inflammasome pathway—in vascular and other cell types. Furthermore, TXNIP protein levels are regulated by ubiquitination, adding a further layer to its control over oxidative stress–driven signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTXNIP also functions as a tumor suppressor in various cancers. Its expression is frequently down‐regulated in tumors, a change often driven by oncogenic signals such as c‐Myc and specific microRNAs (e.g., miR‐373), which in turn enhance glucose uptake and promote cell proliferation, epithelial–mesenchymal transition, and metastasis. Conversely, re-expression of TXNIP—whether induced pharmacologically by histone deacetylase inhibitors or modulated via altered intracellular localization and corepressor interactions—leads to growth arrest, differentiation, and apoptosis of cancer cells. This multifaceted tumor suppressive role is corroborated in different malignancies including breast, thyroid, bladder, and renal cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the settings of diabetes and vascular disease, aberrant up‐regulation of TXNIP exacerbates cellular injury. Hyperglycemia‐induced increases in TXNIP impair thioredoxin activity, thereby fostering ROS accumulation and inflammatory signaling in endothelial cells. This mechanism contributes to pathological processes such as epithelial–mesenchymal transition in renal tubular cells and the progression of diabetic nephropathy, as well as promoting vascular inflammation that can predispose to atherosclerosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "27", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence further implicates TXNIP in the regulation of autophagy and broader metabolic homeostasis. In the liver, TXNIP interacts with key metabolic sensors to influence autophagic and mitophagic processes, thereby promoting fatty acid oxidation and mitigating steatohepatitis. These findings expand TXNIP’s role beyond glucose and redox regulation, suggesting that targeted modulation of TXNIP could offer novel therapeutic avenues for metabolic, neurodegenerative, and inflammatory diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alexandra H Minn, Christian Hafele, Anath Shalev "}, {"type": "b", "children": [{"type": "t", "text": "Thioredoxin-interacting protein is stimulated by glucose through a carbohydrate response element and induces beta-cell apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2004-1378"}], "href": "https://doi.org/10.1210/en.2004-1378"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15705778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15705778"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Z Wang, Y P Rong, M H Malone, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thioredoxin-interacting protein (txnip) is a glucocorticoid-regulated primary response gene involved in mediating glucocorticoid-induced apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1209218"}], "href": "https://doi.org/10.1038/sj.onc.1209218"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16301999"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16301999"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hemang Parikh, Emma Carlsson, William A Chutkow, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TXNIP regulates peripheral glucose metabolism in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Med (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pmed.0040158"}], "href": "https://doi.org/10.1371/journal.pmed.0040158"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17472435"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17472435"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Carrie A Stoltzman, Christopher W Peterson, Kevin T Breen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glucose sensing by MondoA:Mlx complexes: a role for hexokinases and direct regulation of thioredoxin-interacting protein expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0712199105"}], "href": "https://doi.org/10.1073/pnas.0712199105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18458340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18458340"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ning Wu, Bin Zheng, Adam Shaywitz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMPK-dependent degradation of TXNIP upon energy stress leads to enhanced glucose uptake via GLUT1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2013.01.035"}], "href": "https://doi.org/10.1016/j.molcel.2013.01.035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23453806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23453806"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Anath Shalev "}, {"type": "b", "children": [{"type": "t", "text": "Minireview: Thioredoxin-interacting protein: regulation and function in the pancreatic β-cell."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2014-1095"}], "href": "https://doi.org/10.1210/me.2014-1095"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24911120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24911120"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "P Christian Schulze, Jun Yoshioka, Tomosaburo Takahashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hyperglycemia promotes oxidative stress through inhibition of thioredoxin function by thioredoxin-interacting protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M400549200"}], "href": "https://doi.org/10.1074/jbc.M400549200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15128745"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15128745"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hideyuki Yamawaki, Shi Pan, Richard T Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fluid shear stress inhibits vascular inflammation by decreasing thioredoxin-interacting protein in endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI23001"}], "href": "https://doi.org/10.1172/JCI23001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15696199"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15696199"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Parth Patwari, Luke J Higgins, William A Chutkow, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The interaction of thioredoxin with Txnip. Evidence for formation of a mixed disulfide by disulfide exchange."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M600427200"}], "href": "https://doi.org/10.1074/jbc.M600427200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16766796"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16766796"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Pingzhao Zhang, Chenji Wang, Kun Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ubiquitin ligase itch regulates apoptosis by targeting thioredoxin-interacting protein for ubiquitin-dependent degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.063321"}], "href": "https://doi.org/10.1074/jbc.M109.063321"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20068034"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20068034"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Oded N Spindel, Cameron World, Bradford C Berk "}, {"type": "b", "children": [{"type": "t", "text": "Thioredoxin interacting protein: redox dependent and independent regulatory mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Antioxid Redox Signal (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/ars.2011.4137"}], "href": "https://doi.org/10.1089/ars.2011.4137"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21929372"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21929372"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jungwon Hwang, Hyun-Woo Suh, Young Ho Jeon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The structural basis for the negative regulation of thioredoxin by thioredoxin-interacting protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms3958"}], "href": "https://doi.org/10.1038/ncomms3958"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24389582"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24389582"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Xiaolei Sun, Xuefei Jiao, Yarong Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2016.11.017"}], "href": "https://doi.org/10.1016/j.bbrc.2016.11.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27833015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27833015"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Naif Mohammad Alhawiti, Saeed Al Mahri, Mohammad Azhar Aziz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TXNIP in Metabolic Regulation: Physiological Role and Therapeutic Outlook."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Drug Targets (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2174/1389450118666170130145514"}], "href": "https://doi.org/10.2174/1389450118666170130145514"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28137209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28137209"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Lisa M Butler, Xianbo Zhou, Wei-Sheng Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin."}]}, {"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.182372299"}], "href": "https://doi.org/10.1073/pnas.182372299"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12189205"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12189205"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Yumiko Nishinaka, Hiroshi Masutani, Shin-Ichi Oka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Importin alpha1 (Rch1) mediates nuclear translocation of thioredoxin-binding protein-2/vitamin D(3)-up-regulated protein 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M405473200"}], "href": "https://doi.org/10.1074/jbc.M405473200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15234975"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15234975"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Francesco Turturro, Ellen Friday, Tomas Welbourne "}, {"type": "b", "children": [{"type": "t", "text": "Hyperglycemia regulates thioredoxin-ROS activity through induction of thioredoxin-interacting protein (TXNIP) in metastatic breast cancer-derived cells MDA-MB-231."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-7-96"}], "href": "https://doi.org/10.1186/1471-2407-7-96"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17555594"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17555594"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Fuminori Yamaguchi, Maki Takata, Kazuyo Kamitori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rare sugar D-allose induces specific up-regulation of TXNIP and subsequent G1 cell cycle arrest in hepatocellular carcinoma cells by stabilization of p27kip1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2008)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18202760"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18202760"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Parth Patwari, William A Chutkow, Kiersten Cummings, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thioredoxin-independent regulation of metabolism by the alpha-arrestin proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.018093"}], "href": "https://doi.org/10.1074/jbc.M109.018093"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19605364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19605364"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Hyo-Jung Kwon, Young-Suk Won, Hyun-Woo Suh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vitamin D3 upregulated protein 1 suppresses TNF-α-induced NF-κB activation in hepatocarcinogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1000990"}], "href": "https://doi.org/10.4049/jimmunol.1000990"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20826751"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20826751"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Jianbiao Zhou, Wee-Joo Chng "}, {"type": "b", "children": [{"type": "t", "text": "Roles of thioredoxin binding protein (TXNIP) in oxidative stress, apoptosis and cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mitochondrion (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mito.2012.06.004"}], "href": "https://doi.org/10.1016/j.mito.2012.06.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22750447"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22750447"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Jennifer A Morrison, Laura A Pike, Sharon B Sams, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thioredoxin interacting protein (TXNIP) is a novel tumor suppressor in thyroid cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-13-62"}], "href": "https://doi.org/10.1186/1476-4598-13-62"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24645981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24645981"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Liangliang Shen, John M O'Shea, Mohan R Kaadige, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metabolic reprogramming in triple-negative breast cancer through Myc suppression of TXNIP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1501555112"}], "href": "https://doi.org/10.1073/pnas.1501555112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25870263"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25870263"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "D Chen, Bian-Li Dang, Jin-zhou Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-373 drives the epithelial-to-mesenchymal transition and metastasis via the miR-373-TXNIP-HIF1α-TWIST signaling axis in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.4702"}], "href": "https://doi.org/10.18632/oncotarget.4702"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26196741"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26196741"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Qiong Chen, Tao Liu, Yi Bao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CircRNA cRAPGEF5 inhibits the growth and metastasis of renal cell carcinoma via the miR-27a-3p/TXNIP pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2019.10.017"}], "href": "https://doi.org/10.1016/j.canlet.2019.10.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31629934"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31629934"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Shan-Shan Yang, Shuang Ma, He Dou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Breast cancer-derived exosomes regulate cell invasion and metastasis in breast cancer via miR-146a to activate cancer associated fibroblasts in tumor microenvironment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2020.111983"}], "href": "https://doi.org/10.1016/j.yexcr.2020.111983"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32268136"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32268136"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Xiaonan Li, Yuanyuan Rong, Mei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of thioredoxin interacting protein (Txnip) by p38 MAPK and FOXO1 contributes to the impaired thioredoxin activity and increased ROS in glucose-treated endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2009.02.132"}], "href": "https://doi.org/10.1016/j.bbrc.2009.02.132"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19254690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19254690"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Julia Ling-Yu Chen, Daniel Merl, Christopher W Peterson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1001093"}], "href": "https://doi.org/10.1371/journal.pgen.1001093"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20844768"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20844768"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Carolina Soriano-Tárraga, Jordi Jiménez-Conde, Eva Giralt-Steinhauer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenome-wide association study identifies TXNIP gene associated with type 2 diabetes mellitus and sustained hyperglycemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddv493"}], "href": "https://doi.org/10.1093/hmg/ddv493"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26643952"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26643952"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Chunling Huang, Yuan Zhang, Darren J Kelly, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thioredoxin interacting protein (TXNIP) regulates tubular autophagy and mitophagy in diabetic nephropathy through the mTOR signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep29196"}], "href": "https://doi.org/10.1038/srep29196"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27381856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27381856"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Yanlin Yin, Zhihui Zhou, Weiwei Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vascular endothelial cells senescence is associated with NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation via reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP) pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2017.01.001"}], "href": "https://doi.org/10.1016/j.biocel.2017.01.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28064010"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28064010"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Lexiao Li, Saifudeen Ismael, Sanaz Nasoohi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thioredoxin-Interacting Protein (TXNIP) Associated NLRP3 Inflammasome Activation in Human Alzheimer's Disease Brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Alzheimers Dis (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3233/JAD-180814"}], "href": "https://doi.org/10.3233/JAD-180814"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30741672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30741672"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Hee-Seon Park, Ji-Won Song, Jin-Ho Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2020.1834711"}], "href": "https://doi.org/10.1080/15548627.2020.1834711"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33190588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33190588"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Naila Qayyum, Muhammad Haseeb, Moon Suk Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of Thioredoxin-Interacting Protein in Diseases and Its Therapeutic Outlook."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms22052754"}], "href": "https://doi.org/10.3390/ijms22052754"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33803178"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33803178"}]}]}]}