{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T20:04:25Z","timestamp":1780689865299,"version":"3.54.1"},"reference-count":76,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST110-2320-B-087-001"],"award-info":[{"award-number":["MOST110-2320-B-087-001"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Cardiovascular disease (CVD) is the leading cause of mortality in diabetes mellitus (DM). Immunomodulatory dysfunction is a primary feature of DM, and the emergence of chronic kidney disease (CKD) in DM abruptly increases CVD mortality compared with DM alone. Endothelial injury and the accumulation of uremic toxins in the blood of DM\/CKD patients are known mechanisms for the pathogenesis of CVD. However, the molecular factors that cause this disproportional increase in CVD in the DM\/CKD population are still unknown. Since long non-protein-coding RNAs (lncRNAs) play an important role in regulating multiple cellular functions, we used human endothelial cells treated with high glucose to mimic DM and with the uremic toxin indoxyl sulfate (IS) to mimic the endothelial injury associated with CKD. Differentially expressed lncRNAs in these conditions were analyzed by RNA sequencing. We discovered that lnc-SLC15A1-1 expression was significantly increased upon IS treatment in comparison with high glucose alone, and then cascaded the signal of chemokines CXCL10 and CXCL8 via sponging miR-27b, miR-297, and miR-150b. This novel pathway might be responsible for the endothelial inflammation implicated in augmenting CVD in DM\/CKD and could be a therapeutic target with future clinical applications.<\/jats:p>","DOI":"10.3390\/toxins13120873","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T20:23:21Z","timestamp":1638908601000},"page":"873","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Indoxyl Sulfate Elevated Lnc-SLC15A1-1 Upregulating CXCL10\/CXCL8 Expression in High-Glucose Endothelial Cells by Sponging MicroRNAs"],"prefix":"10.3390","volume":"13","author":[{"given":"Yu-Chin","family":"Huang","sequence":"first","affiliation":[{"name":"Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"},{"name":"Division of Nephrology, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 33004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Chun","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 33004, Taiwan"},{"name":"Department of Public Health & Medical Humanities, Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Hsin","family":"Chang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Ting","family":"Chang","sequence":"additional","affiliation":[{"name":"Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 33004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin-Hao","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 33004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3913-5338","authenticated-orcid":false,"given":"Liang-Chuan","family":"Lai","sequence":"additional","affiliation":[{"name":"Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"},{"name":"Bioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei 10055, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1056\/NEJMoa1008862","article-title":"Diabetes mellitus, fasting glucose, and risk of cause-specific death","volume":"364","author":"Kondapally","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/biof.1024","article-title":"Inflammatory markers in coronary artery disease","volume":"38","author":"Ikonomidis","year":"2012","journal-title":"BioFactors"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.0022-202X.2004.22711.x","article-title":"Diabetes prolongs the inflammatory response to a bacterial stimulus through cytokine dysregulation","volume":"123","author":"Naguib","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/nri1882","article-title":"The immune response in atherosclerosis: A double-edged sword","volume":"6","author":"Hansson","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.2741\/2757","article-title":"Diabetic complications and dysregulated innate immunity","volume":"13","author":"Graves","year":"2008","journal-title":"Front. Biosci. Landmark"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"178","DOI":"10.3389\/fmed.2020.00178","article-title":"Transcriptome Profiling Reveals Indoxyl Sulfate Should Be Culpable of Impaired T Cell Function in Chronic Kidney Disease","volume":"7","author":"Xiang","year":"2020","journal-title":"Front. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1146\/annurev.pharmtox.42.091901.115838","article-title":"Structure, function, and inhibition of chemokines","volume":"42","author":"Fernandez","year":"2002","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1161\/ATVBAHA.107.161174","article-title":"Chemokines in atherosclerosis: An update","volume":"28","author":"Zernecke","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1161\/01.CIR.101.13.1519","article-title":"IL-8 is an angiogenic factor in human coronary atherectomy tissue","volume":"101","author":"Simonini","year":"2000","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1189\/jlb.1206761","article-title":"Chemokine regulation of atherosclerosis","volume":"82","author":"Barlic","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1159\/000506634","article-title":"Diabetic Kidney Disease: Challenges, Advances, and Opportunities","volume":"6","author":"Chen","year":"2020","journal-title":"Kidney Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Maciel, R.A.P., Cunha, R.S., Busato, V., Franco, C.R.C., Gregorio, P.C., Dolenga, C.J.R., Nakao, L.S., Massy, Z.A., Boullier, A., and Pecoits-Filho, R. (2018). Uremia Impacts VE-Cadherin and ZO-1 Expression in Human Endothelial Cell-to-Cell Junctions. Toxins, 10.","DOI":"10.3390\/toxins10100404"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Leong, S.C., and Sirich, T.L. (2016). Indoxyl Sulfate\u2014Review of Toxicity and Therapeutic Strategies. Toxins, 8.","DOI":"10.3390\/toxins8120358"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/hdi.12483","article-title":"Indoxyl sulfate, a valuable biomarker in chronic kidney disease and dialysis","volume":"21","author":"Tan","year":"2017","journal-title":"Hemodial. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1093\/ndt\/gfm210","article-title":"Review on uraemic toxins III: Recommendations for handling uraemic retention solutes in vitro\u2014Towards a standardized approach for research on uraemia","volume":"22","author":"Cohen","year":"2007","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.arcmed.2014.04.002","article-title":"Protein-bound Uremic Toxins, Inflammation and Oxidative Stress: A Cross-sectional Study in Stage 3\u20134 Chronic Kidney Disease","volume":"45","author":"Rossi","year":"2014","journal-title":"Arch. Med. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.diabres.2008.09.053","article-title":"Serum indoxyl sulfate levels in patients with diabetic nephropathy: Relation to renal function","volume":"83","author":"Atoh","year":"2009","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1900\/RDS.2010.7.275","article-title":"Increased levels of total P-Cresylsulphate and indoxyl sulphate are associated with coronary artery disease in patients with diabetic nephropathy","volume":"7","author":"Chiu","year":"2010","journal-title":"Rev. Diabet. Stud."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12933-020-01057-w","article-title":"Plasma metabolites associated with arterial stiffness in patients with type 2 diabetes","volume":"19","author":"Katakami","year":"2020","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.2337\/db09-1003","article-title":"Epigenetics: A molecular link between environmental factors and type 2 diabetes","volume":"58","author":"Ling","year":"2009","journal-title":"Diabetes"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1161\/CIRCRESAHA.116.303936","article-title":"Epigenetics and metabolism","volume":"116","author":"Keating","year":"2015","journal-title":"Circ. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.hjc.2020.03.003","article-title":"MicroRNAs in cardiovascular disease","volume":"61","author":"Siasos","year":"2020","journal-title":"Hell. J. Cardiol."},{"key":"ref_23","first-page":"3236","article-title":"Long noncoding RNA MANTIS relieved the protein-bound uremic toxin-induced injury on human umbilical vein endothelial cells in chronic kidney disease and end-stage renal disease","volume":"11","author":"Jiang","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1161\/CIRCRESAHA.114.303265","article-title":"Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth","volume":"114","author":"Michalik","year":"2014","journal-title":"Circ. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/414788a","article-title":"Diabetes mellitus and genetically programmed defects in beta-cell function","volume":"414","author":"Bell","year":"2001","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/ng.1035","article-title":"GATA6 haploinsufficiency causes pancreatic agenesis in humans","volume":"44","author":"Allen","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.cmet.2012.08.010","article-title":"Human beta cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes","volume":"16","author":"Moran","year":"2012","journal-title":"Cell Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"24731","DOI":"10.1074\/jbc.M702029200","article-title":"Activation of p53 by MEG3 non-coding RNA","volume":"282","author":"Zhou","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1038\/mt.2016.41","article-title":"A Role for the Long Noncoding RNA SENCR in Commitment and Function of Endothelial Cells","volume":"24","author":"Boulberdaa","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1161\/CIRCULATIONAHA.116.026991","article-title":"Long Noncoding RNA MANTIS Facilitates Endothelial Angiogenic Function","volume":"136","author":"Leisegang","year":"2017","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1093\/cvr\/cvy206","article-title":"Long non-coding RNA H19 regulates endothelial cell aging via inhibition of STAT3 signalling","volume":"115","author":"Hofmann","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1161\/CIRCRESAHA.119.315938","article-title":"Noncoding RNAs in Vascular Diseases","volume":"126","author":"Jae","year":"2020","journal-title":"Circ. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.ymthe.2004.01.010","article-title":"The angiostatic activity of interferon-inducible protein-10\/CXCL10 in human melanoma depends on binding to CXCR3 but not to glycosaminoglycan","volume":"9","author":"Yang","year":"2004","journal-title":"Mol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.atherosclerosis.2004.01.024","article-title":"Aspirin inhibits monocyte chemoattractant protein-1 and interleukin-8 expression in TNF-\u03b1 stimulated human umbilical vein endothelial cells","volume":"174","author":"Yang","year":"2004","journal-title":"Atherosclerosis"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gencer, S., Evans, B.R., van der Vorst, E.P.C., D\u00f6ring, Y., and Weber, C. (2021). Inflammatory Chemokines in Atherosclerosis. Cells, 10.","DOI":"10.3390\/cells10020226"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1093\/cvr\/cvs240","article-title":"Effects of phosphate on vascular function under normal conditions and influence of the uraemic state","volume":"96","author":"Six","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1681\/ASN.2007030308","article-title":"Chronic kidney disease increases risk for venous thromboembolism","volume":"19","author":"Wattanakit","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0002-9394(14)74982-7","article-title":"A morphologic and autoradiographic study of cell death and regeneration in the retinal microvasculature of normal and diabetic rats","volume":"100","author":"Sharma","year":"1985","journal-title":"Am. J. Ophthalmol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1093\/ckj\/sfaa121","article-title":"Serum total indoxyl sulfate and clinical outcomes in hemodialysis patients: Results from the Japan Dialysis Outcomes and Practice Patterns Study","volume":"14","author":"Yamamoto","year":"2020","journal-title":"Clin. Kidney J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"15018","DOI":"10.1038\/nrdp.2015.18","article-title":"Diabetic kidney disease","volume":"1","author":"Thomas","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jdiacomp.2016.06.029","article-title":"Increased levels of inflammatory mediators and proinflammatory monocytes in patients with type I diabetes mellitus and nephropathy","volume":"31","author":"Kolseth","year":"2017","journal-title":"J. Diabetes Complicat."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Espi, M., Koppe, L., Fouque, D., and Thaunat, O. (2020). Chronic Kidney Disease-Associated Immune Dysfunctions: Impact of Protein-Bound Uremic Retention Solutes on Immune Cells. Toxins, 12.","DOI":"10.3390\/toxins12050300"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kami\u0144ski, T.W., Pawlak, K., Karbowska, M., My\u015bliwiec, M., and Pawlak, D. (2017). Indoxyl sulfate\u2014The uremic toxin linking hemostatic system disturbances with the prevalence of cardiovascular disease in patients with chronic kidney disease. BMC Nephrol., 18.","DOI":"10.1186\/s12882-017-0457-1"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1161\/CIRCULATIONAHA.118.034588","article-title":"Uremic Toxin Indoxyl Sulfate Promotes Proinflammatory Macrophage Activation Via the Interplay of OATP2B1 and Dll4-Notch Signaling","volume":"139","author":"Nakano","year":"2019","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Lano, G., Burtey, S., and Sall\u00e9e, M. (2020). Indoxyl Sulfate, a Uremic Endotheliotoxin. Toxins, 12.","DOI":"10.3390\/toxins12040229"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1093\/ckj\/sfx074","article-title":"Sevelamer reduces endothelial inflammatory response to advanced glycation end products","volume":"11","author":"Favretto","year":"2018","journal-title":"Clin. Kidney J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"91","DOI":"10.5500\/wjt.v3.i4.91","article-title":"Role of IL-10 in the progression of kidney disease","volume":"3","author":"Sinuani","year":"2013","journal-title":"World J. Transplant."},{"key":"ref_48","first-page":"223","article-title":"Oxidant stress regulation of IL-8 and ICAM-1 gene expression: Differential activation and binding of the transcription factors AP-1 and NF-kappaB (Review)","volume":"4","author":"Roebuck","year":"1999","journal-title":"Int. J. Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1111\/j.1538-7836.2007.02540.x","article-title":"The uremic solute indoxyl sulfate induces oxidative stress in endothelial cells","volume":"5","author":"Dou","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1159\/000508372","article-title":"Long Non-Coding RNA NEAT1 Regulates Pyroptosis in Diabetic Nephropathy via Mediating the miR-34c\/NLRP3 Axis","volume":"45","author":"Zhan","year":"2020","journal-title":"Kidney Blood Press. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3716","DOI":"10.18632\/aging.102011","article-title":"Long non-coding RNA MEG3 promotes fibrosis and inflammatory response in diabetic nephropathy via miR-181a\/Egr-1\/TLR4 axis","volume":"11","author":"Zha","year":"2019","journal-title":"Aging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4886","DOI":"10.1111\/jcmm.13754","article-title":"Knockdown of lncRNA AK139328 alleviates myocardial ischaemia\/reperfusion injury in diabetic mice via modulating miR-204-3p and inhibiting autophagy","volume":"22","author":"Yu","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_53","first-page":"183","article-title":"Endothelial dysfunction: Cardiovascular risk factors, therapy, and outcome","volume":"1","author":"Hadi","year":"2005","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1161\/CIRCULATIONAHA.106.678342","article-title":"Chronic kidney disease: Effects on the cardiovascular system","volume":"116","author":"Schiffrin","year":"2007","journal-title":"Circulation"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ijcard.2008.04.009","article-title":"Differential expression of cytokines, chemokines and chemokine receptors in patients with coronary artery disease","volume":"136","author":"Mamoni","year":"2009","journal-title":"Int. J. Cardiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/S0167-5699(99)01469-3","article-title":"The chemokine system: Redundancy for robust outputs","volume":"20","author":"Mantovani","year":"1999","journal-title":"Immunol. Today"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.2353\/ajpath.2010.081059","article-title":"CXCR3\/ligands are significantly involved in the tumorigenesis of basal cell carcinomas","volume":"176","author":"Lo","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"133","DOI":"10.7754\/Clin.Lab.2012.120225","article-title":"Plasma levels of CXCL1 (GRO-alpha) and CXCL10 (IP-10) are elevated in type 2 diabetic patients: Evidence for the involvement of inflammation and angiogenesis\/angiostasis in this disease state","volume":"59","author":"Sajadi","year":"2013","journal-title":"Clin. Lab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/j.1365-2249.2006.03229.x","article-title":"Neutrophils and monocytes as potentially important sources of proinflammatory cytokines in diabetes","volume":"146","author":"Hatanaka","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1093\/ndt\/gfs133","article-title":"p-Cresol sulfate and indoxyl sulfate induce similar cellular inflammatory gene expressions in cultured proximal renal tubular cells","volume":"28","author":"Sun","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1161\/ATVBAHA.107.149179","article-title":"Vascular Adhesion Molecules in Atherosclerosis","volume":"27","author":"Galkina","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1161\/01.ATV.0000029781.31325.66","article-title":"Interrelationships among circulating interleukin-6, C-reactive protein, and traditional cardiovascular risk factors in women","volume":"22","author":"Bermudez","year":"2002","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.cyto.2012.02.010","article-title":"Atherogenic effects of TNF-\u03b1 and IL-6 via up-regulation of scavenger receptors","volume":"58","author":"Hashizume","year":"2012","journal-title":"Cytokine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.atherosclerosis.2015.04.783","article-title":"Novel anti-inflammatory therapies for the treatment of atherosclerosis","volume":"240","author":"Khan","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"100130","DOI":"10.1016\/j.ajpc.2020.100130","article-title":"Inflammation and cardiovascular disease: From mechanisms to therapeutics","volume":"4","author":"Alfaddagh","year":"2020","journal-title":"Am. J. Prev. Cardiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/s41419-021-03554-6","article-title":"FoxP3-miR-150-5p\/3p suppresses ovarian tumorigenesis via an IGF1R\/IRS1 pathway feedback loop","volume":"12","author":"Zhang","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1093\/neuonc\/not118","article-title":"A miR-297\/hypoxia\/DGK-axis regulating glioblastoma survival","volume":"15","author":"Kefas","year":"2013","journal-title":"Neuro Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1159\/000492354","article-title":"miR-27b Suppresses Endothelial Cell Proliferation and Migration by Targeting Smad7 in Kawasaki Disease","volume":"48","author":"Rong","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Zeng, X., Huang, C., Senavirathna, L., Wang, P., and Liu, L. (2017). miR-27b inhibits fibroblast activation via targeting TGF\u03b2 signaling pathway. BMC Cell Biol., 18.","DOI":"10.1186\/s12860-016-0123-7"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/s41419-017-0211-4","article-title":"miR-27b-3p inhibits proliferation and potentially reverses multi-chemoresistance by targeting CBLB\/GRB2 in breast cancer cells","volume":"9","author":"Chen","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Jerez-Morales, A., Merino, J.S., D\u00edaz-Castillo, S.T., Smith, C.T., Fuentealba, J., Bernasconi, H., Echeverr\u00eda, G., and Garc\u00eda-Cancino, A. (2021). The Administration of the Synbiotic Lactobacillus bulgaricus 6c3 Strain, Inulin and Fructooligosaccharide Decreases the Concentrations of Indoxyl Sulfate and Kidney Damage in a Rat Model. Toxins, 13.","DOI":"10.3390\/toxins13030192"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Rossi, M., Johnson, D.W., Morrison, M., Pascoe, E., Coombes, J.S., Forbes, J.M., McWhinney, B.C., Ungerer, J.P.J., Dimeski, G., and Campbell, K.L. (2014). SYNbiotics Easing Renal failure by improving Gut microbiologY (SYNERGY): A protocol of placebo-controlled randomised cross-over trial. BMC Nephrol., 15.","DOI":"10.1186\/1471-2369-15-106"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"15571","DOI":"10.1038\/s41598-019-51292-9","article-title":"AST-120, an Oral Carbon Absorbent, Protects against the Progression of Atherosclerosis in a Mouse Chronic Renal Failure Model by Preserving sFlt-1 Expression Levels","volume":"9","author":"Nakada","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4939","DOI":"10.1038\/s41598-017-04949-2","article-title":"Key Role for the Organic Anion Transporters, OAT1 and OAT3, in the in vivo Handling of Uremic Toxins and Solutes","volume":"7","author":"Wu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1186\/gb-2010-11-3-r25","article-title":"A scaling normalization method for differential expression analysis of RNA-seq data","volume":"11","author":"Robinson","year":"2010","journal-title":"Genome Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/12\/873\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:42:18Z","timestamp":1760168538000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/12\/873"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,7]]},"references-count":76,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["toxins13120873"],"URL":"https:\/\/doi.org\/10.3390\/toxins13120873","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,7]]}}}