{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T08:34:06Z","timestamp":1775032446349,"version":"3.50.1"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a severe condition with an unclear pathogenesis. Here, we investigated the effects of baricitinib on lung fibrosis progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A collagen-induced arthritis (CIA) mouse model was established. Lung tissues were analyzed using Western blotting, immunofluorescence staining, immunohistochemical staining, Masson\u2019s trichrome and hematoxylin and eosin staining. Protein expression was assessed\n                      <jats:italic>in vitro<\/jats:italic>\n                      using Western blotting and immunofluorescence staining. The cytokine levels in supernatants were measured using ELISA, and macrophage-derived exosomes were identified using transmission electron microscopy and Western blotting, followed by microRNA sequencing analyses. miR-126a-3p-regulated genes were identified using dual-luciferase reporter assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vivo<\/jats:italic>\n                      , baricitinib reduced iNOS, CD206 and MerTK levels and collagen deposition in the lungs of CIA mice through the JAK\/STAT pathway.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , baricitinib downregulated the expression of arginase-1, CD206 and MerTK in macrophages and TGF-\u03b2 and IL-10 in supernatants. Baricitinib also increased miR-126a-3p expression in macrophage-derived exosomes. miR-126a-3p exerted antifibrotic effects by regulating apoptosis and autophagy via the PI3K\/AKT1\/mTOR pathway. Silencing JAK1 reduced JAK1 and JAK2 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Baricitinib targets the JAK\/STAT signaling pathway in macrophages, thereby exerting dual anti-inflammatory and anti-fibrotic inhibitory effects on CIA-ILD mice. Meanwhile, it increases miR-126a-3p secretion by suppressing M2 polarization, further contributing to its anti-fibrotic activity\n                      <jats:italic>in vitro<\/jats:italic>\n                      using NIH3T3 cell.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1747540","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:41:34Z","timestamp":1775022094000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Baricitinib alleviates interstitial lung disease in CIA mice by inhibiting macrophage polarization and increase exosomal miR-126a-3p with anti-fibrotic activity in vitro"],"prefix":"10.3389","volume":"17","author":[{"given":"Xi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Geriatrics, Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Geriatrics, Chongqing General Hospital, Chongqing University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Geriatrics, Chongqing General Hospital, Chongqing University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Chongqing General Hospital, Chongqing University","place":["Chongqing, China"]},{"name":"Neuro Immune Connections and Repair Lab, Department of Immunology and Infection, Biomedical Research Institute, Hasselt University","place":["Diepenbeek, Belgium"]},{"name":"University MS Centrum (UMSC), Biomedical Research Institute, Hasselt University","place":["Diepenbeek, Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Geriatrics, Chongqing General Hospital, Chongqing University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1549277","DOI":"10.3389\/fimmu.2025.1549277","article-title":"PI3K\/Akt in IPF: untangling fibrosis and charting therapies","volume":"16","author":"Bhatt","year":"2025","journal-title":"Front. Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.1038\/s41467-023-38177-2","article-title":"Lung endothelial cells regulate pulmonary fibrosis through FOXF1\/R-Ras signaling","volume":"14","author":"Bian","year":"2023","journal-title":"Nat. Commun."},{"key":"B3","doi-asserted-by":"publisher","first-page":"103637","DOI":"10.1016\/j.autrev.2024.103637","article-title":"The intervention of macrophages in progressive fibrosis characterizing systemic sclerosis: a systematic review","volume":"23","author":"Campitiello","year":"2024","journal-title":"Autoimmun. Rev."},{"key":"B4","doi-asserted-by":"publisher","first-page":"436","DOI":"10.3390\/cells10020436","article-title":"Macrophages in lung injury, repair, and fibrosis","volume":"10","author":"Cheng","year":"2021","journal-title":"Cells"},{"key":"B5","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1186\/s13075-021-02691-9","article-title":"CTLA4-Ig treatment induces M1-M2 shift in cultured monocyte-derived macrophages from healthy subjects and rheumatoid arthritis patients","volume":"23","author":"Cutolo","year":"2021","journal-title":"Arthritis Res. Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1038\/s41484-025-01279-w","article-title":"Dynamic macrophage phenotypes in autoimmune and inflammatory rheumatic diseases","volume":"21","author":"Cutolo","year":"2025","journal-title":"Nat. Rev. Rheumatol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"155687","DOI":"10.1016\/j.phymed.2024.155687","article-title":"Icariside II modulates pulmonary fibrosis via PI3K\/Akt\/\u03b2-catenin pathway inhibition of M2 macrophage program","volume":"130","author":"Deng","year":"2024","journal-title":"Phytomedicine"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1038\/s41467-020-14344-7","article-title":"Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis","volume":"11","author":"Dinh","year":"2020","journal-title":"Nat. Commun."},{"key":"B9","doi-asserted-by":"publisher","first-page":"106748","DOI":"10.1016\/j.intimp.2020.106748","article-title":"Efficacy of baricitinib in treating rheumatoid arthritis: modulatory effects on fibrotic and inflammatory biomarkers in a real-life setting","volume":"86","author":"d\u2019Alessandro","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.yjmcc.2015.04.025","article-title":"Curcumin induces M2 macrophage polarization by secretion IL-4 and\/or IL-13","volume":"85","author":"Gao","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1093\/bib\/bbx014","article-title":"Circular RNA identification based on multiple seed matching","volume":"19","author":"Gao","year":"2018","journal-title":"Brief. Bioinform."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.3390\/cells12091254","article-title":"A novel CD206 targeting peptide inhibits bleomycin-induced pulmonary fibrosis in mice","volume":"12","author":"Ghebremedhin","year":"2023","journal-title":"Cells"},{"key":"B13","doi-asserted-by":"publisher","first-page":"283","DOI":"10.3389\/fgene.2013.00283","article-title":"Circ2Traits: a comprehensive database for circular RNA potentially associated with disease and traits","volume":"4","author":"Ghosal","year":"2013","journal-title":"Front. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.3390\/molecules28052195","article-title":"Baricitinib attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-\u03b21 signaling pathway","volume":"28","author":"Gu","year":"2023","journal-title":"Molecules"},{"key":"B15","doi-asserted-by":"publisher","first-page":"117953","DOI":"10.1016\/j.biopha.2025.117953","article-title":"MicroRNA-126: from biology to therapeutics","volume":"185","author":"Guo","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"B16","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.cyto.2018.08.030","article-title":"Src promotes anti-inflammatory (M2) macrophage generation via the IL-4\/STAT6 pathway","volume":"111","author":"Hu","year":"2018","journal-title":"Cytokine"},{"key":"B17","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1097\/CM9.0000000000002577","article-title":"Diffuse lung involvement in rheumatoid arthritis: a respiratory physician's perspective","volume":"136","author":"Huang","year":"2023","journal-title":"Chin. Med. J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"507","DOI":"10.2144\/000112729","article-title":"Standardized quantification of pulmonary fibrosis in histological samples","volume":"44","author":"H\u00fcbner","year":"2008","journal-title":"Biotechniques"},{"key":"B19","doi-asserted-by":"publisher","first-page":"991","DOI":"10.2147\/DDDT.S353494","article-title":"Therapeutic potential of janus kinase inhibitors for the management of interstitial lung disease","volume":"16","author":"Huo","year":"2022","journal-title":"Drug Des. Devel. Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"8629","DOI":"10.3390\/ijms22168629","article-title":"MiR-126-3p is dynamically regulated in endothelial-to-mesenchymal transition during fibrosis","volume":"22","author":"Jordan","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e12124","DOI":"10.1002\/jev2.12124","article-title":"Human bronchial epithelial cell-derived extracellular vesicle therapy for pulmonary fibrosis via inhibition of TGF-\u03b2-WNT crosstalk","volume":"10","author":"Kadota","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"B22","doi-asserted-by":"publisher","first-page":"210011","DOI":"10.1183\/16000617.0011-2021","article-title":"Rheumatoid arthritis-interstitial lung disease: manifestations and current concepts in pathogenesis and management","volume":"30","author":"Kadura","year":"2021","journal-title":"Eur. Respir. Rev."},{"key":"B23","doi-asserted-by":"publisher","first-page":"8327","DOI":"10.3390\/ijms25158327","article-title":"JAK inhibitors in rheumatoid arthritis: immunomodulatory properties and clinical efficacy","volume":"25","author":"Kie\u0142bowski","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"14509","DOI":"10.3390\/ijms241914509","article-title":"Etiology and pathogenesis of rheumatoid arthritis-interstitial lung disease","volume":"24","author":"Kim","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/nature11303","article-title":"Heterodimeric JAK-STAT activation as a mechanism of persistence to JAK2 inhibitor therapy","volume":"489","author":"Koppikar","year":"2012","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/j.immuni.2016.01.001","article-title":"Macrophage Akt1 kinase-mediated mitophagy modulates apoptosis resistance and pulmonary fibrosis","volume":"44","author":"Larson-Casey","year":"2016","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with burrows-wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1089621","DOI":"10.3389\/fimmu.2022.1089621","article-title":"Clinical effect and biological mechanism of exercise for rheumatoid arthritis: a mini review","volume":"13","author":"Li","year":"2023","journal-title":"Front. Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s12986-021-00596-7","article-title":"Asiatic acid alleviates Ang-II induced cardiac hypertrophy and fibrosis via miR-126\/PIK3R2 signaling","volume":"18","author":"Li","year":"2021","journal-title":"Nutr. Metab."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.3390\/ph15101276","article-title":"The emerging role of extracellular vesicles from mesenchymal stem cells and macrophages in pulmonary fibrosis: insights into miRNA delivery","volume":"15","author":"Li","year":"2022","journal-title":"Pharmaceuticals"},{"key":"B31","doi-asserted-by":"publisher","first-page":"945129","DOI":"10.3389\/fimmu.2022.945129","article-title":"Natural medicines of targeted rheumatoid arthritis and its action mechanism","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s42358-023-00325-z","article-title":"Baricitinib improves pulmonary fibrosis in mice with rheumatoid arthritis-associated interstitial lung disease by inhibiting the Jak2\/Stat3 signaling pathway","volume":"63","author":"Liu","year":"2023","journal-title":"Adv. Rheumatol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"7458","DOI":"10.21037\/jtd-24-882","article-title":"Experimental study of the effects of pirfenidone and nintedanib on joint inflammation and pulmonary fibrosis in a rheumatoid arthritis-associated interstitial lung disease mouse model","volume":"16","author":"Liu","year":"2024","journal-title":"J. Thorac. Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e128060","DOI":"10.1172\/jci.insight.128060","article-title":"Mesenchymal stromal cell exosomes prevent and revert experimental pulmonary fibrosis through modulation of monocyte phenotypes","volume":"4","author":"Mansouri","year":"2019","journal-title":"JCI Insight"},{"key":"B35","doi-asserted-by":"publisher","first-page":"15046","DOI":"10.1038\/s41598-023-41626-z","article-title":"miRNA-126a plays important role in myoblast and endothelial cell interaction","volume":"13","author":"Mierzejewski","year":"2023","journal-title":"Sci. Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1084\/jem.20162152","article-title":"Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span","volume":"214","author":"Misharin","year":"2017","journal-title":"J. Exp. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"6211","DOI":"10.3390\/ijms22126211","article-title":"Role of JAK\/STAT in interstitial lung diseases; molecular and cellular mechanisms","volume":"22","author":"Montero","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbrc.2009.09.061","article-title":"MicroRNA isolation and stability in stored RNA samples","volume":"390","author":"Mraz","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1007\/s10753-023-01825-2","article-title":"Nintedanib ameliorates bleomycin-induced pulmonary fibrosis, inflammation, apoptosis, and oxidative stress by modulating PI3K\/Akt\/mTOR pathway in mice","volume":"46","author":"Pan","year":"2023","journal-title":"Inflammation"},{"key":"B40","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"B41","doi-asserted-by":"publisher","first-page":"175184","DOI":"10.1016\/j.ejphar.2022.175184","article-title":"Eucalyptol prevents bleomycin-induced pulmonary fibrosis and M2 macrophage polarization","volume":"931","author":"Rui","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s40744-022-00505-1","article-title":"Evaluation of VTE, MACE, and serious infections among patients with RA treated with baricitinib compared to TNFi: a multi-database study of patients in routine care using disease registries and claims databases","volume":"9","author":"Salinas","year":"2022","journal-title":"Rheumatol. Ther."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e20190418","DOI":"10.1084\/jem.20190418","article-title":"Biology and therapeutic potential of interleukin-10","volume":"217","author":"Saraiva","year":"2020","journal-title":"J. Exp. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"5471","DOI":"10.1093\/rheumatology\/keaf314","article-title":"Baricitinib in rheumatoid arthritis-interstitial lung disease: a literature review and national multicentre study of 72 patients","volume":"64","author":"Serrano-Combarro","year":"2025","journal-title":"Rheumatology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/s12931-023-02424-3","article-title":"Elevated expression of macrophage MERTK exhibits profibrotic effects and results in defective regulation of efferocytosis function in pulmonary fibrosis","volume":"24","author":"She","year":"2023","journal-title":"Respir. Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1186\/s13287-021-02296-8","article-title":"Extracellular vesicles derived from umbilical cord mesenchymal stromal cells alleviate pulmonary fibrosis by means of transforming growth factor-\u03b2 signaling inhibition","volume":"12","author":"Shi","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"B47","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s13075-024-03308-7","article-title":"Nintedanib downregulates the profibrotic M2 phenotype in cultured monocyte-derived macrophages obtained from systemic sclerosis patients affected by interstitial lung disease","volume":"26","author":"Soldano","year":"2024","journal-title":"Arthritis Res. Ther."},{"key":"B48","doi-asserted-by":"publisher","first-page":"102397","DOI":"10.1016\/j.autrev.2019.102397","article-title":"Macrophage M1\/M2 polarization and rheumatoid arthritis: a systematic review","volume":"18","author":"Tardito","year":"2019","journal-title":"Autoimmun. Rev."},{"key":"B49","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1136\/annrheumdis-2020-219012","article-title":"JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib","volume":"80","author":"Traves","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"B50","doi-asserted-by":"publisher","first-page":"407","DOI":"10.5114\/reum.2020.102006","article-title":"Baricitinib for the treatment of rheumatoid arthritis","volume":"58","author":"Urits","year":"2020","journal-title":"Rheumatology"},{"key":"B51","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.apsb.2021.07.023","article-title":"Targeting PI3K\/AKT signaling for treatment of idiopathic pulmonary fibrosis","volume":"12","author":"Wang","year":"2022","journal-title":"Acta Pharm. Sin. B."},{"key":"B52","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.trsl.2024.02.001","article-title":"Nebulized platelet-derived extracellular vesicles attenuate chronic cigarette smoke-induced Murine emphysema","volume":"269","author":"Xuan","year":"2024","journal-title":"Transl. Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"106549","DOI":"10.1016\/j.intimp.2020.106549","article-title":"Chronotherapy targeting cytokine secretion attenuates collagen-induced arthritis in mice","volume":"84","author":"Yaekura","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"3806","DOI":"10.3390\/jcm10173806","article-title":"Decision-making strategy for the treatment of rheumatoid arthritis-associated interstitial lung disease (RA-ILD)","volume":"10","author":"Yamakawa","year":"2021","journal-title":"J. Clin. Med."},{"key":"B55","doi-asserted-by":"publisher","first-page":"114962","DOI":"10.1016\/j.intimp.2025.114962","article-title":"Ruxolitinib attenuates bleomycin-induced pulmonary fibrosis in mice by modulating macrophage polarization through the JAK\/STAT signaling pathway","volume":"161","author":"Yang","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"6567","DOI":"10.1038\/s41598-025-89733-3","article-title":"Machine learning selection of basement membrane-associated genes and development of a predictive model for kidney fibrosis","volume":"15","author":"Yuan","year":"2025","journal-title":"Sci. Rep."},{"key":"B57","doi-asserted-by":"publisher","first-page":"17534666221140972","DOI":"10.1177\/17534666221140972","article-title":"The role of autophagy in idiopathic pulmonary fibrosis: from mechanisms to therapies","volume":"16","author":"Yue","year":"2022","journal-title":"Ther. Adv. Respir. Dis."},{"key":"B58","doi-asserted-by":"publisher","first-page":"107178","DOI":"10.1016\/j.phrs.2024.107178","article-title":"IL20Rb aggravates pulmonary fibrosis through enhancing bone marrow derived profibrotic macrophage activation","volume":"203","author":"Zhu","year":"2024","journal-title":"Pharmacol. Res."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1747540\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:41:37Z","timestamp":1775022097000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1747540\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":58,"alternative-id":["10.3389\/fphar.2026.1747540"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1747540","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]},"article-number":"1747540"}}