{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:56:58Z","timestamp":1782917818802,"version":"3.54.5"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019725","name":"Deanship of Scientific Research, Prince Sattam bin Abdulaziz University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus (SLE) remains difficult to control despite current therapies, highlighting the need for more selective, mechanism-based treatments targeting key innate immune components such as Toll-like receptor 7 (TLR7).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To identify natural flavonoid compounds with favorable stability and drug-like properties as hypothesis-generating TLR7 inhibitors for SLE using an integrated\n                      <jats:italic>in silico<\/jats:italic>\n                      workflow.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Six flavonoids (bavachinin, baicalein, apigenin, wogonin, eupalitin, and oroxylin A) were screened against TLR7 using molecular docking and 100-ns molecular dynamics simulations of the two top-scoring complexes. Drug likeness and ADME-toxicity were assessed using\n                      <jats:italic>in silico<\/jats:italic>\n                      toxicity models. KEGG pathway enrichment of predicted flavonoid targets was performed, and two independent SLE GEO datasets (GSE65391 and GSE61635) were analyzed to define upregulated genes and identify overlap with predicted targets retrieved from SwissTargetPrediction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Docking identified bavachinin and oroxylin A as the strongest initial binders to TLR7, while molecular dynamics showed that the oroxylin A\u2013TLR7 complex exhibited greater conformational stability and more persistent interactions than bavachinin. Both ligands met drug-likeness criteria, but oroxylin A displayed a more balanced ADME\u2013toxicity profile and less toxicity than the more lipophilic, immunotoxic bavachinin. KEGG enrichment of predicted oroxylin A targets highlighted inflammatory and immune-related pathways, and 12 predicted oroxylin A targets were consistently upregulated across both SLE datasets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Oroxylin A showed the most favorable combination of TLR7 complex stability, ADME\u2013toxicity properties, immune-related pathway enrichment, and overlap with SLE-upregulated genes, supporting its prioritization as a potential TLR7-directed, hypothesis-generating candidate for SLE that warrants rigorous\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fchem.2026.1863132","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:34:46Z","timestamp":1782916486000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated docking\u2013molecular dynamics, ADME\u2013toxicity profiling, and transcriptomic validation identify oroxylin a as a TLR7-targeting flavonoid candidate in systemic lupus erythematosus"],"prefix":"10.3389","volume":"14","author":[{"given":"Nourah","family":"Albarrak","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University","place":["Al-Kharj, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanadi","family":"Albjeedi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University","place":["Al-Kharj, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebtihal","family":"Kamal","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University","place":["Al Kharj, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed F.","family":"Aldawsari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University","place":["Al-Kharj, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisham N.","family":"Altayb","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehssan","family":"Moglad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University","place":["Al-Kharj, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100787","DOI":"10.1016\/j.imu.2021.100787","article-title":"Discovery of new TLR7 agonists by a combination of statistical learning-based QSAR, virtual screening, and molecular dynamics","volume":"27","author":"Abiri","year":"2021","journal-title":"Inf. Med. Unlocked"},{"key":"B2","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.mam.2015.09.002","article-title":"Role of glycogen phosphorylase in liver glycogen metabolism","volume":"46","author":"Agius","year":"2015","journal-title":"Mol. Asp. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"12321","DOI":"10.1021\/bi0353124","article-title":"Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium\/bicarbonate co-transporter","volume":"42","author":"Alvarez","year":"2003","journal-title":"Biochemistry"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e30330","DOI":"10.7759\/cureus.30330","article-title":"An overview of systemic lupus erythematosus (SLE) pathogenesis, classification, and management","volume":"14","author":"Ameer","year":"2022","journal-title":"Cureus"},{"key":"B5","doi-asserted-by":"publisher","first-page":"102886","DOI":"10.1016\/j.tice.2025.102886","article-title":"Bavachinin attenuates cerebral ischemia\/reperfusion injury in rats via its anti-inflammatory and antioxidant effects","volume":"95","author":"Atlasbaf","year":"2025","journal-title":"Tissue Cell"},{"key":"B6","doi-asserted-by":"publisher","first-page":"740","DOI":"10.2174\/1570159X15666171016163510","article-title":"Computer aided drug design and its application to the development of potential drugs for neurodegenerative disorders","volume":"16","author":"Baig","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"W257","DOI":"10.1093\/nar\/gky318","article-title":"ProTox-II: a webserver for the prediction of toxicity of chemicals","volume":"46","author":"Banerjee","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"W513","DOI":"10.1093\/nar\/gkae303","article-title":"ProTox 3.0: a webserver for the prediction of toxicity of chemicals","volume":"52","author":"Banerjee","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1089\/jir.2008.0125","article-title":"Production of cytokines and stimulation of resistance to viral infection in human leukocytes by Scutellaria baicalensis flavones","volume":"28","author":"B\u0142ach-Olszewska","year":"2008","journal-title":"J. Interferon Cytokine Res."},{"key":"B10","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1109\/SC.2006.54","article-title":"Scalable algorithms for molecular dynamics simulations on commodity clusters","volume-title":"ACM\/IEEE SC 2006 Conference (SC\u201906)","author":"Bowers","year":"2006"},{"key":"B11","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/s41586-022-04642-z","article-title":"TLR7 gain-of-function genetic variation causes human lupus","volume":"605","author":"Brown","year":"2022","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1038\/cdd.2017.30","article-title":"Anti-apoptotic proteins BCL-2, MCL-1 and A1 summate collectively to maintain survival of immune cell populations both in vitro and in vivo","volume":"24","author":"Carrington","year":"2017","journal-title":"Cell Death Differ."},{"key":"B13","doi-asserted-by":"publisher","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":"B14","doi-asserted-by":"publisher","first-page":"W357","DOI":"10.1093\/nar\/gkz382","article-title":"SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules","volume":"47","author":"Daina","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1007\/s10875-024-01660-6","article-title":"Interface gain-of-function mutations in TLR7 cause systemic and neuro-Inflammatory disease","volume":"44","author":"David","year":"2024","journal-title":"J. Clin. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"107","DOI":"10.34172\/bi.2021.22143","article-title":"Molecular docking, molecular dynamics simulation, and ADMET analysis of levamisole derivatives against the SARS-CoV-2 main protease (MPro)","volume":"12","author":"El Khatabi","year":"2022","journal-title":"Bioimpacts"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.2337\/db12-1139","article-title":"Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome","volume":"62","author":"Escande","year":"2013","journal-title":"Diabetes"},{"key":"B18","doi-asserted-by":"publisher","first-page":"8316","DOI":"10.3390\/molecules20058316","article-title":"Structure based modeling of small molecules binding to the TLR7 by atomistic level simulations","volume":"20","author":"Gentile","year":"2015","journal-title":"Molecules"},{"key":"B19","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1124\/mol.65.3.711","article-title":"Expression of A3 adenosine receptors in human lymphocytes: up-regulation in T cell activation","volume":"65","author":"Gessi","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1146791","DOI":"10.3389\/fimmu.2023.1146791","article-title":"CD38: an ecto-enzyme with functional diversity in T cells","volume":"14","author":"Ghosh","year":"2023","journal-title":"Front. Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"228","DOI":"10.3390\/cells9010228","article-title":"Roles of CD38 in the immune response to infection","volume":"9","author":"Glar\u00eda","year":"2020","journal-title":"Cells"},{"key":"B22","doi-asserted-by":"publisher","first-page":"5090","DOI":"10.1021\/acs.jcim.4c00578","article-title":"Discovery of novel small molecule dual inhibitor targeting toll-like receptors 7 and 9","volume":"64","author":"Haseeb","year":"2024","journal-title":"J. Chem. Inf. Model"},{"key":"B23","doi-asserted-by":"publisher","first-page":"384","DOI":"10.3390\/nano11020384","article-title":"Green synthesis of silver nanoparticles using Annona muricata extract as an inducer of apoptosis in cancer cells and inhibitor for NLRP3 inflammasome via enhanced autophagy","volume":"11","author":"Jabir","year":"2021","journal-title":"Nanomater. (Basel)"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1002\/med.21456","article-title":"A3 adenosine receptors as modulators of inflammation: from medicinal chemistry to therapy","volume":"38","author":"Jacobson","year":"2018","journal-title":"Med. Res. Rev."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1001\/jama.2022.13591","article-title":"Hydroxychloroquine dose per ophthalmology guidelines and the risk of systemic lupus erythematosus flares","volume":"328","author":"Jorge","year":"2022","journal-title":"JAMA"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3947","DOI":"10.1093\/nar\/gkt078","article-title":"Design, synthesis and biological evaluation of novel antagonist compounds of toll-like receptors 7, 8 and 9","volume":"41","author":"Kandimalla","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3939","DOI":"10.1016\/j.bmcl.2011.05.022","article-title":"Flavonoids as inhibitors of human CD38","volume":"21","author":"Kellenberger","year":"2011","journal-title":"Bioorg Med. Chem. Lett."},{"key":"B28","doi-asserted-by":"publisher","first-page":"966","DOI":"10.6026\/973206300200966","article-title":"Molecular docking and dynamics analysis of flavonoids from Retama monosperma with drug-resistant GIST mutations","volume":"20","author":"Khattabi","year":"2024","journal-title":"Bioinformation"},{"key":"B29","doi-asserted-by":"publisher","first-page":"D1516","DOI":"10.1093\/nar\/gkae1059","article-title":"PubChem 2025 update","volume":"53","author":"Kim","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.ajhg.2009.06.014","article-title":"Mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum of metaphyseal anadysplasia","volume":"85","author":"Lausch","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"B31","doi-asserted-by":"publisher","first-page":"338","DOI":"10.3390\/ijms27010338","article-title":"In silico prediction of potential pTLR7\/pSTING dual-targeting ligands via virtual screening and molecular dynamics simulation","volume":"27","author":"Liu","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"107466","DOI":"10.1016\/j.intimp.2021.107466","article-title":"Patients with systemic lupus erythematosus face a high risk of cardiovascular disease: a systematic review and Meta-analysis","volume":"94","author":"Lu","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"4157","DOI":"10.7150\/ijbs.86492","article-title":"The PTGS2\/COX2-PGE2 signaling Cascade in inflammation: pro or anti? A case study with type 1 diabetes mellitus","volume":"19","author":"Mart\u00edn-V\u00e1zquez","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"38553","DOI":"10.1038\/srep38553","article-title":"GSK-3\u03b2 controls NF-kappaB activity via IKK\u03b3\/NEMO","volume":"6","author":"Medunjanin","year":"2016","journal-title":"Sci. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"B36","doi-asserted-by":"publisher","first-page":"41959","DOI":"10.18632\/oncotarget.9747","article-title":"Comparative evaluation of three proliferation markers, Ki-67, TOP2A, and RacGAP1, in bronchopulmonary neuroendocrine neoplasms: issues and prospects","volume":"7","author":"Neubauer","year":"2016","journal-title":"Oncotarget"},{"key":"B37","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural products as sources of new drugs over the nearly four decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"B38","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1758-2946-3-33","article-title":"Open babel: an open chemical toolbox","volume":"3","author":"O\u2019Boyle","year":"2011","journal-title":"J. Cheminform"},{"key":"B39","doi-asserted-by":"publisher","first-page":"10221","DOI":"10.1021\/acs.jmedchem.9b01201","article-title":"Discovery of novel small molecule dual inhibitors targeting toll-like receptors 7 and 8","volume":"62","author":"Padilla-Salinas","year":"2019","journal-title":"J. Med. Chem."},{"key":"B40","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nrm2125","article-title":"Matrix metalloproteinases and the regulation of tissue remodelling","volume":"8","author":"Page-McCaw","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e20250196","DOI":"10.70962\/jhi.20250196","article-title":"TLR7 F507S gain-of-function mutation presenting with early-onset SLE and hypertriglyceridemia: response to JAK inhibition","volume":"2","author":"Parvaneh","year":"2026","journal-title":"J. Hum. Immun."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.3390\/biom12091185","article-title":"Oroxylin A: a promising flavonoid for prevention and treatment of chronic diseases","volume":"12","author":"Sajeev","year":"2022","journal-title":"Biomolecules"},{"key":"B43","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1007\/s11926-021-01047-1","article-title":"TLR7 signaling in lupus B cells: new insights into synergizing factors and downstream signals","volume":"23","author":"Satterthwaite","year":"2021","journal-title":"Curr. Rheumatol. Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.numecd.2006.06.002","article-title":"Orange flavonoid hesperetin modulates cardiac hERG potassium channel via binding to amino acid F656","volume":"17","author":"Scholz","year":"2007","journal-title":"Nutr. Metab. Cardiovasc Dis."},{"key":"B45","doi-asserted-by":"publisher","first-page":"e46","DOI":"10.1111\/j.1755-5922.2010.00212.x","article-title":"Cardiovascular ion channels as a molecular target of flavonoids","volume":"28","author":"Scholz","year":"2010","journal-title":"Cardiovasc Ther."},{"key":"B46","doi-asserted-by":"publisher","first-page":"71","DOI":"10.5487\/TR.2011.27.2.071","article-title":"Inhibition of p65 nuclear translocation by baicalein","volume":"27","author":"Seo","year":"2011","journal-title":"Toxicol. Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e20250194","DOI":"10.70962\/jhi.20250194","article-title":"Identification of a novel TLR7 gain-of-function variant that underlies systemic lupus erythematosus","volume":"2","author":"Sethumadhavan","year":"2026","journal-title":"J. Hum. Immun."},{"key":"B48","doi-asserted-by":"publisher","first-page":"113983","DOI":"10.1016\/j.lwt.2022.113983","article-title":"A comprehensive spectral and in silico analysis on the interactions between quercetin, isoquercitrin, rutin and HMGB1","volume":"169","author":"Shen","year":"2022","journal-title":"LWT"},{"key":"B49","doi-asserted-by":"publisher","first-page":"107457","DOI":"10.1016\/j.phrs.2024.107457","article-title":"Flavonoids and their derivatives as DNA topoisomerase inhibitors with anti-cancer activity in various cell models: exploring a novel mode of action","volume":"209","author":"Sitarek","year":"2024","journal-title":"Pharmacol. Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1089\/ten.2005.11.267","article-title":"Matrix metalloproteinase 9 facilitates collagen remodeling and angiogenesis for vascular constructs","volume":"11","author":"Sung","year":"2005","journal-title":"Tissue Eng."},{"key":"B51","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1002\/fft2.494","article-title":"Structural insights and biological activities of flavonoids: implications for novel applications","volume":"6","author":"Tang","year":"2025","journal-title":"Food Front."},{"key":"B52","doi-asserted-by":"publisher","first-page":"5204","DOI":"10.1038\/s41467-020-19025-z","article-title":"Structural analysis reveals TLR7 dynamics underlying antagonism","volume":"11","author":"Tojo","year":"2020","journal-title":"Nat. Commun."},{"key":"B53","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/sj.jid.5700500","article-title":"Collagenase-3 (MMP-13) enhances remodeling of three-dimensional collagen and promotes survival of human skin fibroblasts","volume":"127","author":"Toriseva","year":"2007","journal-title":"J. Invest. Dermatol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"230172","DOI":"10.1183\/16000617.0172-2023","article-title":"A narrative review of chemokine receptors CXCR1 and CXCR2 and their role in acute respiratory distress syndrome","volume":"33","author":"Toya","year":"2024","journal-title":"Eur. Respir. Rev."},{"key":"B55","doi-asserted-by":"publisher","first-page":"5351","DOI":"10.3390\/ijms25105351","article-title":"Human and murine Toll-like receptor-driven disease in systemic lupus erythematosus","volume":"25","author":"von Hofsten","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.gene.2017.04.027","article-title":"Carbonic anhydrase XII functions in health and disease","volume":"623","author":"Waheed","year":"2017","journal-title":"Gene"},{"key":"B57","doi-asserted-by":"publisher","first-page":"589","DOI":"10.7150\/jca.64017","article-title":"TOP2A promotes proliferation and metastasis of hepatocellular carcinoma regulated by miR-144-3p","volume":"13","author":"Wang","year":"2022","journal-title":"J. Cancer"},{"key":"B58","doi-asserted-by":"publisher","first-page":"126","DOI":"10.3892\/mmr.2024.13249","article-title":"Oroxylin A inhibits inflammatory cytokines in periodontitis via HO-1","volume":"30","author":"Wang","year":"2024","journal-title":"Mol. Med. Rep."},{"key":"B59","doi-asserted-by":"publisher","first-page":"2201713","DOI":"10.1002\/aenm.202201713","article-title":"Surface reconstruction of water splitting electrocatalysts","volume":"12","author":"Zeng","year":"2022","journal-title":"Adv. Energy Mater"},{"key":"B60","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.ard.2025.01.011","article-title":"Somatic gain-of-function mutation in TLR7 causes early-onset systemic lupus erythematosus","volume":"84","author":"Zeng","year":"2025","journal-title":"Ann. Rheum. Dis."},{"key":"B61","doi-asserted-by":"publisher","first-page":"6610543","DOI":"10.1155\/2021\/6610543","article-title":"Protective effects of oroxylin A against doxorubicin-induced cardiotoxicity via the activation of Sirt1 in mice","volume":"2021","author":"Zhang","year":"2021","journal-title":"Oxid. Med. Cell Longev."}],"container-title":["Frontiers in Chemistry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchem.2026.1863132\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:34:47Z","timestamp":1782916487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchem.2026.1863132\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":61,"alternative-id":["10.3389\/fchem.2026.1863132"],"URL":"https:\/\/doi.org\/10.3389\/fchem.2026.1863132","relation":{},"ISSN":["2296-2646"],"issn-type":[{"value":"2296-2646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"article-number":"1863132"}}