{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:08:47Z","timestamp":1785431327489,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009110","name":"Natural Science Foundation of Xinjiang Uygur Autonomous Region","doi-asserted-by":"crossref","award":["2022D01A299"],"award-info":[{"award-number":["2022D01A299"]}],"id":[{"id":"10.13039\/100009110","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009110","name":"Natural Science Foundation of Xinjiang Uygur Autonomous Region","doi-asserted-by":"crossref","award":["2025D01B101"],"award-info":[{"award-number":["2025D01B101"]}],"id":[{"id":"10.13039\/100009110","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009110","name":"Natural Science Foundation of Xinjiang Uygur Autonomous Region","doi-asserted-by":"crossref","award":["2023D01B46"],"award-info":[{"award-number":["2023D01B46"]}],"id":[{"id":"10.13039\/100009110","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82460848"],"award-info":[{"award-number":["82460848"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82260845"],"award-info":[{"award-number":["82260845"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82460848"],"award-info":[{"award-number":["82460848"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82260845"],"award-info":[{"award-number":["82260845"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Technological Innovation Leading Talent Special Fund of Tianshan Talents Program in Xinjiang Uygur Autonomous Region","award":["2023TSYCLJ0042"],"award-info":[{"award-number":["2023TSYCLJ0042"]}]},{"name":"Second Batch of Tianshan Talent Young Talent Support Project of Xinjiang Uygur Autonomous Region","award":["2023TSYCQNTJ0010"],"award-info":[{"award-number":["2023TSYCQNTJ0010"]}]},{"name":"Xinjiang Uygur Autonomous Region of the major science and technology projects in China","award":["2022A03007-3"],"award-info":[{"award-number":["2022A03007-3"]}]},{"name":"Scientific Research Business Expenses of Xinjiang Uygur Autonomous Region","award":["KY2024121"],"award-info":[{"award-number":["KY2024121"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Early identification of ischemic heart failure (IHF) is critical for improving patient prognosis and clinical outcomes. However, effective diagnostic biomarkers and targeted therapeutic strategies for IHF remain limited. Total flavonoids from Dracocephalum moldavica L. (TFDM) exert potential cardioprotective effects; however, the molecular mechanisms by which TFDM acts against IHF have not been fully elucidated. Therefore, this study aims to identify diagnostic biomarkers for IHF and explore the potential therapeutic mechanism of TFDM targeting these key genes. Given the small sample size (n = 17) of the clinical dataset, LASSO regression and Random Forest were employed due to their superior performance in feature selection, noise reduction, and stability in small-sample scenarios. In this study, we screened key characteristic genes of IHF through bioinformatics analysis and further investigated the binding potential between these key genes and active components of TFDM using molecular docking, thus providing new targets for the early diagnosis of IHF and new evidence for the intervention mechanism of TFDM in IHF.<\/jats:p>","DOI":"10.3390\/cimb48040406","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T15:56:56Z","timestamp":1776268616000},"page":"406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Precision Intervention of Isorhamnetin Total Flavonoids in Ischemic Heart Failure: Mechanistic Exploration Based on Signature Gene Targets"],"prefix":"10.3390","volume":"48","author":[{"given":"Li-Juan","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Xinjiang Medical University, Urumqi 830017, China"},{"name":"Xinjiang Key Laboratory of Uyghur Medical Research, Xinjiang Institute of Materia Medica, Urumqi 830004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Hu","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Uyghur Medical Research, Xinjiang Institute of Materia Medica, Urumqi 830004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kader","family":"Kaderyea","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xinjiang Medical University, Urumqi 830017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Ling","family":"Su","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xinjiang Medical University, Urumqi 830017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6122-9963","authenticated-orcid":false,"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xinjiang Medical University, Urumqi 830017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di-Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Uyghur Medical Research, Xinjiang Institute of Materia Medica, Urumqi 830004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Fang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Uyghur Medical Research, Xinjiang Institute of Materia Medica, Urumqi 830004, China"},{"name":"Department of Clinical Pharmacy, School of Preclinical Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Guo","family":"Xing","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Uyghur Medical Research, Xinjiang Institute of Materia Medica, Urumqi 830004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gallo, G., and Savoia, C. (2024). Hypertension and Heart Failure: From Pathophysiology to Treatment. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126661"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1053\/j.ajkd.2024.12.006","article-title":"Kidney Dysfunction in Heart Failure: Core Curriculum 2025","volume":"86","author":"Lo","year":"2025","journal-title":"Am. J. Kidney Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1056\/NEJMoa051530","article-title":"Outcome of heart failure with preserved ejection fraction in a population-based study","volume":"355","author":"Bhatia","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1001\/jama.1995.03520420066040","article-title":"Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials","volume":"273","author":"Garg","year":"1995","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.jacc.2023.05.043","article-title":"A Global Challenge and a Global Opportunity for the Heart Failure Community","volume":"82","author":"DeVore","year":"2023","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.jacc.2023.05.040","article-title":"Global Comparison of Readmission Rates for Patients With Heart Failure","volume":"82","author":"Foroutan","year":"2023","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1016\/j.jacc.2013.05.019","article-title":"2013 ACCF\/AHA guideline for the management of heart failure: A report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines","volume":"62","author":"Yancy","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ejhf.592","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"18","author":"Ponikowski","year":"2016","journal-title":"Eur. J. Heart Fail."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Xu, M., Zhou, H., Hu, P., Pan, Y., Wang, S., Liu, L., and Liu, X. (2023). Identification and validation of immune and oxidative stress-related diagnostic markers for diabetic nephropathy by WGCNA and machine learning. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1084531"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2008). WGCNA: An R package for weighted correlation network analysis. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-559"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6241","DOI":"10.2147\/JIR.S442388","article-title":"Identifying and Validating GSTM5 as an Immunogenic Gene in Diabetic Foot Ulcer Using Bioinformatics and Machine Learning","volume":"16","author":"Shi","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1196\/annals.1310.015","article-title":"Application of the random forest classification algorithm to a SELDI-TOF proteomics study in the setting of a cancer prevention trial","volume":"1020","author":"Izmirlian","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s12967-023-04840-x","article-title":"Integrating network pharmacology and animal experimental validation to investigate the action mechanism of oleanolic acid in obesity","volume":"22","author":"Liu","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1161\/CIRCRESAHA.116.309398","article-title":"C1q-TNF-Related Protein-9 Promotes Cardiac Hypertrophy and Failure","volume":"120","author":"Appari","year":"2017","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1161\/01.ATV.0000142812.03840.6f","article-title":"Chemokines: Key regulators of mononuclear cell recruitment in atherosclerotic vascular disease","volume":"24","author":"Weber","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1161\/CIRCRESAHA.125.325496","article-title":"Metabolic and Immune Crosstalk in Cardiovascular Disease","volume":"136","author":"Mohanta","year":"2025","journal-title":"Circ. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/j.1582-4934.2007.00194.x","article-title":"Ccr1 deficiency reduces inflammatory remodelling and preserves left ventricular function after myocardial infarction","volume":"12","author":"Liehn","year":"2008","journal-title":"J. Cell. Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s42255-022-00715-5","article-title":"TREM2hi resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis","volume":"5","author":"Zhang","year":"2023","journal-title":"Nat. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s13075-024-03364-z","article-title":"Expression of CD163 and major histocompatibility complex class I as diagnostic markers for idiopathic inflammatory myopathies","volume":"26","author":"Ghang","year":"2024","journal-title":"Arthritis Res. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"18834","DOI":"10.1074\/jbc.M113.471060","article-title":"CD163 binding to haptoglobin-hemoglobin complexes involves a dual-point electrostatic receptor-ligand pairing","volume":"288","author":"Nielsen","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.5301\/jn.5000245","article-title":"Soluble TWEAK is associated with atherosclerotic burden in patients with chronic kidney disease","volume":"26","author":"Valdivielso","year":"2013","journal-title":"J. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1089\/ars.2012.4834","article-title":"CD163 and inflammation: Biological, diagnostic, and therapeutic aspects","volume":"18","author":"Etzerodt","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/cyto.b.20031","article-title":"Human monocyte CD163 expression inversely correlates with soluble CD163 plasma levels","volume":"63","author":"Davis","year":"2005","journal-title":"Cytom. B Clin. Cytom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6024","DOI":"10.1002\/jsfa.11955","article-title":"The impact of probiotic yogurt versus ordinary yogurt on serum sTWEAK, sCD163, ADMA, LCAT and BUN in patients with chronic heart failure: A randomized, triple-blind, controlled trial","volume":"102","author":"Pourrajab","year":"2022","journal-title":"J. Sci. Food Agric."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/5584_2017_91","article-title":"An Update on P2Y13 Receptor Signalling and Function","volume":"1051","author":"Ortega","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.2147\/IJN.S131893","article-title":"Development of solid lipid nanoparticles containing total flavonoid extract from Dracocephalum moldavica L. and their therapeutic effect against myocardial ischemia-reperfusion injury in rats","volume":"12","author":"Tan","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_30","first-page":"2744","article-title":"Effect of Dracocephalum moldavica total flavones on expression of TGF-\u03b21\/Smad signaling pathway and matrix metalloproteinase of atherosclerosis ApoE-\/- mice","volume":"42","author":"Liu","year":"2017","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17491","DOI":"10.1038\/s41598-018-35726-4","article-title":"Pretreatment with Total Flavonoid Extract from Dracocephalum moldavica L. Attenuates Ischemia Reperfusion-induced Apoptosis","volume":"8","author":"Zeng","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zheng, R.F., Du, Y.W., Zeng, C., Wang, H.F., Xing, J.G., and Xu, M. (2020). Total flavones of Dracocephalum moldavica L. protect astrocytes against H2O2-induced apoptosis through a mitochondria-dependent pathway. BMC Complement. Med. Ther., 20.","DOI":"10.1186\/s12906-020-2846-4"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Liu, M., Shan, G., Jiang, H., Zeng, L., Zhao, K., Li, Y., Ashraf, G.M., Li, Z., and Liu, R. (2021). Identification of miRNA and Their Regulatory Effects Induced by Total Flavonoids from Dracocephalum moldavica in the Treatment of Vascular Dementia. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.796628"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Dawuti, A., Sun, S., Wang, R., Gong, D., Yuan, T., Zhang, L., Yang, S., Xing, J., Zheng, R., and Lu, Y. (2022). Systems Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Total Flavonoids in Dracocephalum moldavica on Chronic Heart Failure. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158409"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zheng, R.F., Kader, K., Liu, D.W., Su, W.L., Xu, L., Jin, Y.Y., and Xing, J.G. (2024). A network pharmacology approach to decipher the mechanism of total flavonoids from Dracocephalum moldavica L. in the treatment of cardiovascular diseases. BMC Complement. Med. Ther., 24.","DOI":"10.1186\/s12906-023-04316-x"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Hu, X., Mola, Y., Su, W.L., Wang, Y., Zheng, R.F., and Xing, J.G. (2023). A network pharmacology approach to decipher the total flavonoid extract of Dracocephalum moldavica L. in the treatment of cerebral ischemia-reperfusion injury. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0289118"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/4\/406\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:12:13Z","timestamp":1776399133000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/4\/406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":36,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["cimb48040406"],"URL":"https:\/\/doi.org\/10.3390\/cimb48040406","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]}}}