{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T10:40:48Z","timestamp":1777891248050,"version":"3.51.4"},"reference-count":37,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["THC"],"published-print":{"date-parts":[[2024,3,14]]},"abstract":"<jats:p>BACKGROUND: Anemia associated with heart failure is frequent and can exacerbate the symptoms of heart failure. Dapagliflozin is the first SGLT-2 inhibitor with significant cardiovascular protection. However, the effect of dapagliflozin on anemia in elderly patients with heart failure is unknown. OBJECTIVE: We aimed to study the effect of dapagliflozin on anemia in elderly patients with heart failure by bioinformatics analysis. METHODS: The target genes were determined, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network and modules were constructed. The dapagliflozin-targets network in anemia and heart failure was constructed. Molecular docking experiments between dapagliflozin and its key target AKT1 were performed. RESULTS: We found 1 dapagliflozin related target gene and 2 disease related genes. Totally, 134 target genes of dapagliflozin on anemia in elderly patients with heart failure were determined. The pathways may involve lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, hepatitis B, insulin signaling pathway, fluid shear stress and atherosclerosis, neurotrophin signaling pathway, insulin resistance, toxoplasmosis, colorectal cancer, and EGFR tyrosine kinase inhibitor resistance. The hub genes in network were AKT1, TP53, GAPDH, TNF, CASP3, EGFR, and MAPK3. The structure of dapagliflozin and AKT1 molecular docking was exhibited. CONCLUSIONS: The hub genes in network were AKT1, TP53, GAPDH, TNF, CASP3, EGFR, and MAPK3. The structure of dapagliflozin and AKT1 molecular docking was exhibited.<\/jats:p>","DOI":"10.3233\/thc-230563","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T13:52:14Z","timestamp":1695736334000},"page":"1079-1089","source":"Crossref","is-referenced-by-count":3,"title":["The effect of dapagliflozin on anemia in elderly patients with heart failure by bioinformatics analysis"],"prefix":"10.1177","volume":"32","author":[{"given":"Feixing","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huixian","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangjiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobo","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ai\u2019ai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianying","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Binyu","family":"Niu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiqing","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"issue":"6","key":"10.3233\/THC-230563_ref2","doi-asserted-by":"publisher","first-page":"e137","DOI":"10.1161\/CIR.0000000000000509","article-title":"2017 ACC\/AHA\/HFSA Focused Update of the 2013 ACCF\/AHA Guideline for the Management of Heart Failure: A report of the american college of cardiology\/american heart association task force on clinical practice guidelines and the heart failure society of america","volume":"136","author":"Yancy","year":"2017","journal-title":"Circulation."},{"issue":"1","key":"10.3233\/THC-230563_ref3","doi-asserted-by":"publisher","first-page":"52","DOI":"10.14744\/AnatolJCardiol.2018.08634","article-title":"Anemia in heart failure \u2013 from guidelines to controversies and challenges","volume":"20","author":"S\u00eerbu","year":"2018","journal-title":"Anatol J Cardiol."},{"issue":"5","key":"10.3233\/THC-230563_ref4","doi-asserted-by":"publisher","first-page":"383","DOI":"10.2169\/internalmedicine.42.383","article-title":"Heart failure in the elderly","volume":"42","author":"Yamasaki","year":"2003","journal-title":"Intern Med."},{"issue":"4","key":"10.3233\/THC-230563_ref5","first-page":"47","article-title":"Chronic heart failure in the elderly: Still a current medical problem","volume":"58","author":"Skrzypek","year":"2018","journal-title":"Folia Med Cracov."},{"issue":"5","key":"10.3233\/THC-230563_ref6","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1161\/CIRCHEARTFAILURE.114.001100","article-title":"Heart failure with anemia: Novel findings on the roles of renal disease, interleukins, and specific left ventricular remodeling processes","volume":"7","author":"O\u2019Meara","year":"2014","journal-title":"Circ Heart Fail."},{"issue":"4","key":"10.3233\/THC-230563_ref7","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/s10741-008-9085-y","article-title":"Approaches to the treatment of anaemia in patients with chronic heart failure","volume":"13","author":"Murphy","year":"2008","journal-title":"Heart Fail Rev."},{"issue":"10","key":"10.3233\/THC-230563_ref8","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1002\/ajh.24820","article-title":"Iron deficiency across chronic inflammatory conditions: International expert opinion on definition, diagnosis, and management","volume":"92","author":"Cappellini","year":"2017","journal-title":"Am J Hematol."},{"issue":"1","key":"10.3233\/THC-230563_ref9","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1161\/CIRCULATIONAHA.118.030099","article-title":"Anemia and iron deficiency in heart failure: Current concepts and emerging therapies","volume":"138","author":"Anand","year":"2018","journal-title":"Circulation."},{"issue":"5","key":"10.3233\/THC-230563_ref10","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.jacc.2007.07.094","article-title":"Evaluation and long-term prognosis of new-onset, transient, and persistent anemia in ambulatory patients with chronic heart failure","volume":"51","author":"Tang","year":"2008","journal-title":"J Am Coll Cardiol."},{"issue":"8","key":"10.3233\/THC-230563_ref11","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1161\/CIRCULATIONAHA.104.512988","article-title":"Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: Results from Val-HeFT","volume":"112","author":"Anand","year":"2005","journal-title":"Circulation."},{"key":"10.3233\/THC-230563_ref12","doi-asserted-by":"publisher","first-page":"237","DOI":"10.2147\/vhrm.s4619","article-title":"Managing anemia in patients with chronic heart failure: What do we know","volume":"6","author":"Sandhu","year":"2010","journal-title":"Vasc Health Risk Manag."},{"issue":"3","key":"10.3233\/THC-230563_ref13","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.hfc.","article-title":"Pathophysiology of anemia in heart failure","volume":"6","author":"Anand","year":"2010","journal-title":"Heart Fail Clin."},{"issue":"1","key":"10.3233\/THC-230563_ref15","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s12933-020-01197-z","article-title":"Cardiovascular and renal outcomes with SGLT-2 inhibitors versus GLP-1 receptor agonists in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and network meta-analysis","volume":"20","author":"Yamada","year":"2021","journal-title":"Cardiovasc Diabetol."},{"issue":"3","key":"10.3233\/THC-230563_ref16","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1161\/CIRCULATIONAHA.117.029190","article-title":"Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors)","volume":"136","author":"Kosiborod","year":"2017","journal-title":"Circulation."},{"issue":"1","key":"10.3233\/THC-230563_ref17","doi-asserted-by":"publisher","first-page":"13714","DOI":"10.1038\/s41598-019-50214-z","article-title":"Low CYP24A1 mRNA expression and its role in prognosis of breast cancer","volume":"9","author":"Cai","year":"2019","journal-title":"Sci Rep."},{"key":"10.3233\/THC-230563_ref18","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.actbio.2021.03.051","article-title":"Ataxia telangiectasia mutated inhibitor-loaded copper sulfide nanoparticles for low-temperature photothermal therapy of hepatocellular carcinoma","volume":"127","author":"Cai","year":"2021","journal-title":"Acta Biomater."},{"issue":"7","key":"10.3233\/THC-230563_ref19","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.1021\/acs.molpharmaceut.0c01225","article-title":"Combining gemcitabine-loaded macrophage-like nanoparticles and erlotinib for pancreatic cancer therapy","volume":"18","author":"Cai","year":"2021","journal-title":"Mol Pharm."},{"issue":"10","key":"10.3233\/THC-230563_ref20","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1007\/s00125-018-4656-5","article-title":"Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2","volume":"61","author":"Ghezzi","year":"2018","journal-title":"Diabetologia."},{"issue":"5","key":"10.3233\/THC-230563_ref21","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1038\/ki.2013.199","article-title":"Targeting of sodium-glucose cotransporters with phlorizin inhibits polycystic kidney disease progression in Han: SPRD rats","volume":"84","author":"Wang","year":"2013","journal-title":"Kidney Int."},{"issue":"2","key":"10.3233\/THC-230563_ref23","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1111\/dom.13077","article-title":"Dapagliflozin is associated with lower risk of cardiovascular events and all-cause mortality in people with type 2 diabetes (CVD-REAL Nordic) when compared with dipeptidyl peptidase-4 inhibitor therapy: A multinational observational study","volume":"20","author":"Persson","year":"2018","journal-title":"Diabetes Obes Metab."},{"key":"10.3233\/THC-230563_ref24","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s12933-016-0419-0","article-title":"Research into the effect of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus (REFORM) trial rationale and design","volume":"15","author":"Singh","year":"2016","journal-title":"Cardiovasc Diabetol."},{"issue":"3","key":"10.3233\/THC-230563_ref25","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1177\/2042018814544153","article-title":"Renal effects of dapagliflozin in patients with type 2 diabetes","volume":"5","author":"Thomas","year":"2014","journal-title":"Ther Adv Endocrinol Metab."},{"issue":"12","key":"10.3233\/THC-230563_ref26","doi-asserted-by":"publisher","first-page":"844","DOI":"10.14740\/jocmr2760w","article-title":"Increased hematocrit during sodium-glucose cotransporter 2 inhibitor therapy indicates recovery of tubulointerstitial function in diabetic kidneys","volume":"8","author":"Sano","year":"2016","journal-title":"J Clin Med Res."},{"issue":"2","key":"10.3233\/THC-230563_ref27","doi-asserted-by":"publisher","first-page":"41","DOI":"10.31083\/j.rcm.2018.02.907","article-title":"Cardiorenal Outcomes in the CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME Trials: A systematic review","volume":"19","author":"Kluger","year":"2018","journal-title":"Rev Cardiovasc Med."},{"issue":"5","key":"10.3233\/THC-230563_ref28","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1177\/1479164115585298","article-title":"Dapagliflozin lowers blood pressure in hypertensive and non-hypertensive patients with type 2 diabetes","volume":"12","author":"Sj\u00f6str\u00f6m","year":"2015","journal-title":"Diab Vasc Dis Res."},{"key":"10.3233\/THC-230563_ref29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-7133.2008.07394.x"},{"issue":"3","key":"10.3233\/THC-230563_ref30","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.hfc.2010.03.008","article-title":"Mediators of anemia in chronic heart failure","volume":"6","author":"Le Jemtel","year":"2010","journal-title":"Heart Fail Clin."},{"issue":"20","key":"10.3233\/THC-230563_ref31","doi-asserted-by":"publisher","first-page":"2454","DOI":"10.1161\/CIRCULATIONAHA.105.583666","article-title":"Anemia in chronic heart failure: Prevalence, etiology, clinical correlates, and treatment options","volume":"113","author":"Tang","year":"2006","journal-title":"Circulation."},{"issue":"6","key":"10.3233\/THC-230563_ref32","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1111\/j.1445-5994.2011.02566.x","article-title":"Anaemia is highly prevalent among unselected internal medicine inpatients and is associated with increased mortality, earlier readmission and more prolonged hospital stay: An observational retrospective cohort study","volume":"42","author":"Nathavitharana","year":"2012","journal-title":"Intern Med J."},{"issue":"11","key":"10.3233\/THC-230563_ref33","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1016\/s0735-1097(02)01854-5","article-title":"Anemia is associated with worse symptoms, greater impairment in functional capacity and a significant increase in mortality in patients with advanced heart failure","volume":"39","author":"Horwich","year":"2002","journal-title":"J Am Coll Cardiol."},{"issue":"10","key":"10.3233\/THC-230563_ref34","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1016\/j.jacc.2008.04.061","article-title":"Anemia and mortality in heart failure patients a systematic review and meta-analysis","volume":"52","author":"Groenveld","year":"2008","journal-title":"J Am Coll Cardiol."},{"issue":"6","key":"10.3233\/THC-230563_ref35","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1016\/j.ahj.2009.10.015","article-title":"Prospective evaluation of the association between hemoglobin concentration and quality of life in patients with heart failure","volume":"158","author":"Adams","year":"2009","journal-title":"Am Heart J."},{"issue":"3","key":"10.3233\/THC-230563_ref36","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1007\/s10557-021-07176-0","article-title":"Rationale and design of the ADIDAS study: Association between dapagliflozin-induced improvement and anemia in heart failure patients","volume":"36","author":"Zeng","year":"2022","journal-title":"Cardiovasc Drugs Ther."},{"issue":"4","key":"10.3233\/THC-230563_ref37","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1002\/ejhf.2132","article-title":"Effect of dapagliflozin on anaemia in DAPA-HF","volume":"23","author":"Docherty","year":"2021","journal-title":"Eur J Heart Fail."},{"key":"10.3233\/THC-230563_ref38","unstructured":"Begic E, Gurbeta Pokvic L, Begic Z, Begic N, Dedic M, Mrsic D, Jamakovic M, Vila N, Badnjevic A. From heart murmur to echocardiography \u2013 congenital heart defects diagnostics using machine-learning algorithms. Psychiatr Danub. 2021 Dec; 33(Suppl 13): 236-246. PMID: 35150491."},{"key":"10.3233\/THC-230563_ref39","doi-asserted-by":"publisher","DOI":"10.1109\/MECO.2017.7977152"},{"key":"10.3233\/THC-230563_ref40","doi-asserted-by":"publisher","DOI":"10.1109\/MECO49872.2020.9134333"}],"container-title":["Technology and Health Care"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/THC-230563","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:58:14Z","timestamp":1777615094000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/THC-230563"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,14]]},"references-count":37,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3233\/thc-230563","relation":{},"ISSN":["0928-7329","1878-7401"],"issn-type":[{"value":"0928-7329","type":"print"},{"value":"1878-7401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,14]]}}}