{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T12:36:30Z","timestamp":1771331790603,"version":"3.50.1"},"reference-count":34,"publisher":"IOP Publishing","issue":"7","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/iop-standard\/v1"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/questions\/alternative-author-rights-policies\/"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/questions\/alternative-author-rights-policies\/"}],"funder":[{"DOI":"10.13039\/501100004775","name":"Gansu Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["24JRRA704"],"award-info":[{"award-number":["24JRRA704"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Nanotechnology"],"published-print":{"date-parts":[[2026,2,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Sepsis-induced acute respiratory distress syndrome (ARDS) is a life-threatening condition with uncontrolled inflammation and lung damage. Current therapies are limited, and reprogramming macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotypes via STAT6\/IRF4 activation offers a promising strategy. Dexamethasone-loaded glycyrrhiza protein nanoparticles (Dex@GNPs) were synthesized by extracting GP, denaturing it with phosphoric acid, cross-linking with glutaraldehyde, and encapsulating dexamethasone. Physicochemical properties (size,\n                    <jats:italic>\u03b6<\/jats:italic>\n                    -potential, drug release) were characterized.\n                    <jats:italic>In vitro<\/jats:italic>\n                    studies used lipopolysaccharide (LPS)-stimulated MH-S macrophages;\n                    <jats:italic>in vivo<\/jats:italic>\n                    efficacy was evaluated in murine ARDS models (LPS intratracheal injection or cecal ligation and puncture). Macrophage polarization (flow cytometry, immunofluorescence), STAT6\/IRF4 pathway activation (Western blot), lung histopathology (H&amp;E), and inflammation markers (bronchoalveolar lavage fluid cytokines, ELISA) were assessed. Dex@GNPs exhibited favorable physicochemical properties (hydrodynamic diameter: 374 \u00b1 12 nm;\n                    <jats:italic>\u03b6<\/jats:italic>\n                    -potential: \u221222 \u00b1 4 mV) with pH-responsive drug release (79% cumulative release at pH 5.5 within 24 h).\n                    <jats:italic>In vitro<\/jats:italic>\n                    , Dex@GNPs significantly reprogrammed M1 macrophages to M2 phenotypes, increasing CD206\n                    <jats:sup>+<\/jats:sup>\n                    cells from 5% to 25% and upregulating STAT6\/IRF4 expression compared to LPS-stimulated cells.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , Dex@GNPs selectively targeted inflamed lungs, reduced alveolar damage, suppressed pro-inflammatory cytokines (TNF-\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , IL-6, MCP-1 reduced by 81%, 83%, 86% respectively), and restored alveolar\u2013capillary barrier integrity, outperforming free dexamethasone. Dex@GNPs synergize GP\u2019s targeting and dexamethasone\u2019s anti-inflammatory effects to alleviate sepsis-induced ARDS by STAT6\/IRF4-mediated macrophage polarization, offering a biocompatible nanotherapeutic platform.\n                  <\/jats:p>","DOI":"10.1088\/1361-6528\/ae376b","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T22:49:05Z","timestamp":1768344545000},"page":"075101","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dexamethasone-loaded glycyrrhiza protein nanoparticles reprogram macrophages to an anti-inflammatory phenotype via STAT6\/IRF4 activation for alleviating sepsis-induced acute respiratory distress syndrome"],"prefix":"10.1088","volume":"37","author":[{"given":"Xin","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxian","family":"Ke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0857-6464","authenticated-orcid":true,"given":"Yanxia","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"nanoae376bbib1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.70075","type":"journal-article","article-title":"FKBP5 mediates alveolar fibroblast necroptosis during acute respiratory distress syndrome","volume":"59","author":"Zhang","year":"2025","journal-title":"Cell Prolif."},{"key":"nanoae376bbib2","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1186\/s12964-024-01620-y","type":"journal-article","article-title":"Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications","volume":"22","author":"Qiao","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"nanoae376bbib3","doi-asserted-by":"publisher","first-page":"6737","DOI":"10.1038\/s41467-024-51209-9","type":"journal-article","article-title":"Gut-derived memory \u03b3\u03b4 T17 cells exacerbate sepsis-induced acute lung injury in mice","volume":"15","author":"Xie","year":"2024","journal-title":"Nat. Commun."},{"key":"nanoae376bbib4","doi-asserted-by":"publisher","first-page":"e219","DOI":"10.1097\/CCM.0000000000006172","type":"journal-article","article-title":"2024 focused update: guidelines on use of corticosteroids in sepsis, acute respiratory distress syndrome, and community-acquired pneumonia","volume":"52","author":"Chaudhuri","year":"2024","journal-title":"Crit. Care Med."},{"key":"nanoae376bbib5","doi-asserted-by":"publisher","first-page":"3187","DOI":"10.2147\/JIR.S460259","type":"journal-article","article-title":"Overactivated MX1 positive natural killer cells promote the progression of sepsis-induced acute respiratory distress syndrome","volume":"17","author":"Liu","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"nanoae376bbib6","doi-asserted-by":"publisher","first-page":"9119","DOI":"10.2147\/JIR.S488463","type":"journal-article","article-title":"Role of cellular senescence genes and immune infiltration in sepsis and sepsis-induced ARDS based on bioinformatics analysis","volume":"17","author":"Wu","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"nanoae376bbib7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1146612","type":"journal-article","article-title":"Alpha-linolenic acid pretreatment alleviates NETs-induced alveolar macrophage pyroptosis by inhibiting pyrin inflammasome activation in a mouse model of sepsis-induced ALI\/ARDS","volume":"14","author":"Liu","year":"2023","journal-title":"Front. Immunol."},{"key":"nanoae376bbib8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1209438","type":"journal-article","article-title":"The role of macrophages polarization in sepsis-induced acute lung injury","volume":"14","author":"Wang","year":"2023","journal-title":"Front. Immunol."},{"key":"nanoae376bbib9","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123563","type":"journal-article","article-title":"Therapeutic mitochondrial transfer via mesenchymal stem cell-derived microvesicles for macrophage modulation in myocardial infarction complicated by diabetes","volume":"325","author":"Dong","year":"2025","journal-title":"Biomaterials"},{"key":"nanoae376bbib10","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.115212","type":"journal-article","article-title":"Myricetin alleviates DNCB-induced atopic dermatitis by modulating macrophage M1\/M2 polarization","volume":"163","author":"Zhang","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"nanoae376bbib11","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.156513","type":"journal-article","article-title":"Panax notoginseng saponins ameliorate LPS-induced acute lung injury by promoting STAT6-mediated M2-like macrophage polarization","volume":"139","author":"Wang","year":"2025","journal-title":"Phytomedicine"},{"key":"nanoae376bbib12","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110554","type":"journal-article","article-title":"Inhibition of IL-4\/STAT6\/IRF4 signaling reduces the epithelial-mesenchymal transition in eosinophilic chronic rhinosinusitis with nasal polyps","volume":"121","author":"Chen","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"nanoae376bbib13","doi-asserted-by":"publisher","first-page":"2707","DOI":"10.2147\/JIR.S357012","type":"journal-article","article-title":"Dexmedetomidine activates Akt, STAT6 and IRF4 modulating cytoprotection and macrophage anti-inflammatory phenotype against acute lung injury in vivo and in vitro","volume":"15","author":"Chen","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"nanoae376bbib14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1277161","type":"journal-article","article-title":"Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup","volume":"14","author":"Xu","year":"2023","journal-title":"Front. Immunol."},{"key":"nanoae376bbib15","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s40779-023-00448-w","type":"journal-article","article-title":"Biomimetic natural biomaterials for tissue engineering and regenerative medicine: new biosynthesis methods, recent advances, and emerging applications","volume":"10","author":"Liu","year":"2023","journal-title":"Mil. Med. Res."},{"key":"nanoae376bbib16","doi-asserted-by":"publisher","first-page":"7251","DOI":"10.3390\/ijms23137251","type":"journal-article","article-title":"Dipotassium glycyrrhizinate on melanoma cell line: inhibition of cerebral metastases formation by targeting NF-kB genes-mediating MicroRNA-4443 and MicroRNA-3620-dipotassium glycyrrhizinate effect on melanoma","volume":"23","author":"Bonaf\u00e9","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"nanoae376bbib17","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.jconrel.2024.03.029","type":"journal-article","article-title":"In situ neutrophil apoptosis and macrophage efferocytosis mediated by Glycyrrhiza protein nanoparticles for acute inflammation therapy","volume":"369","author":"Liu","year":"2024","journal-title":"J. Control. Release"},{"key":"nanoae376bbib18","doi-asserted-by":"publisher","first-page":"5279","DOI":"10.1007\/s12274-022-5199-0","type":"journal-article","article-title":"De novo engineering of nanoformulation from traditional Chinese medicine mixtures for psoriasis","volume":"16","author":"Li","year":"2023","journal-title":"Nano Res."},{"key":"nanoae376bbib19","doi-asserted-by":"publisher","first-page":"9354","DOI":"10.1021\/acs.jafc.9b03208","type":"journal-article","article-title":"Boiling licorice produces self-assembled protein nanoparticles: a novel source of bioactive nanomaterials","volume":"67","author":"Zhou","year":"2019","journal-title":"J. Agric Food Chem."},{"key":"nanoae376bbib20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1583235","type":"journal-article","article-title":"TSLP pretreatment inhibits M1 macrophage polarization and attenuates LPS-induced iNKT cell-dependent acute lung injury","volume":"16","author":"Zhou","year":"2025","journal-title":"Front. Immunol."},{"key":"nanoae376bbib21","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-11224-2","type":"journal-article","article-title":"Interfering with USP50 expression inhibits macrophage pyroptosis in sepsis-induced acute lung injury by degrading NLRP3 protein","volume":"15","author":"Hu","year":"2025","journal-title":"Sci. Rep."},{"key":"nanoae376bbib22","doi-asserted-by":"publisher","first-page":"9646","DOI":"10.1111\/jcmm.15481","type":"journal-article","article-title":"MCTR1 enhances the resolution of lipopolysaccharide-induced lung injury through STAT6-mediated resident M2 alveolar macrophage polarization in mice","volume":"24","author":"Wang","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"nanoae376bbib23","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s12865-022-00500-9","type":"journal-article","article-title":"Lack of STAT6 enhances murine acute lung injury through NLRP3\/p38 MAPK signaling pathway in macrophages","volume":"23","author":"Hu","year":"2022","journal-title":"BMC Immunol."},{"key":"nanoae376bbib24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2025.167735","type":"journal-article","article-title":"Activation of aryl hydrocarbon receptor attenuates intestinal inflammation by enhancing IRF4-mediated macrophage M2 polarization","volume":"1871","author":"Li","year":"2025","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"nanoae376bbib25","doi-asserted-by":"publisher","first-page":"eadw5133","DOI":"10.1126\/sciadv.adw5133","type":"journal-article","article-title":"Biomimetic targeted self-adaptive nanodrug for inflammation optimization and AT2 cell modulation in precise ARDS therapy","volume":"11","author":"Chen","year":"2025","journal-title":"Sci. Adv."},{"key":"nanoae376bbib26","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.jconrel.2022.03.028","type":"journal-article","article-title":"Lung targeted liposomes for treating ARDS","volume":"346","author":"Arber Raviv","year":"2022","journal-title":"J Control. Release"},{"key":"nanoae376bbib27","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.actbio.2018.12.046","type":"journal-article","article-title":"Size-dependent anti-inflammatory activity of a peptide-gold nanoparticle hybrid in vitro and in a mouse model of acute lung injury","volume":"85","author":"Gao","year":"2019","journal-title":"Acta Biomater."},{"key":"nanoae376bbib28","doi-asserted-by":"publisher","first-page":"7634","DOI":"10.1021\/acsnano.3c12532","type":"journal-article","article-title":"Enhancing lung recovery: inhaled poly(lactic-co-glycolic) acid encapsulating FTY720 and nobiletin for lipopolysaccharide-induced lung injury, with advanced inhalation tower technology","volume":"19","author":"Zhang","year":"2025","journal-title":"ACS Nano"},{"key":"nanoae376bbib29","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.jconrel.2024.09.013","type":"journal-article","article-title":"Natural pachypodol integrated, lung targeted and inhaled lipid nanomedicine ameliorates acute lung injury via anti-inflammation and repairing lung barrier","volume":"375","author":"Sun","year":"2024","journal-title":"J. Control. Release"},{"key":"nanoae376bbib30","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202402421","type":"journal-article","article-title":"Spontaneous inflammation resolution inspired nanoparticles promote neutrophil apoptosis and macrophage efferocytosis for acute respiratory distress syndrome treatment","volume":"14","author":"Wang","year":"2025","journal-title":"Adv. Healthc. Mater."},{"key":"nanoae376bbib31","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s12951-025-03219-y","type":"journal-article","article-title":"Promotion of NLRP3 autophagosome degradation by PV-K nanodevice for protection against macrophage pyroptosis-mediated lung injury","volume":"23","author":"Fan","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"nanoae376bbib32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.139550","type":"journal-article","article-title":"Polysialic acid-based nanoparticles for enhanced targeting and controlled dexamethasone release in pulmonary inflammation treatment","volume":"297","author":"Li","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"nanoae376bbib33","doi-asserted-by":"publisher","first-page":"23606","DOI":"10.1021\/acsnano.5c01226","type":"journal-article","article-title":"Tolerogenic dendritic cell- and M2 macrophage polarization-inducible hybrid nanoparticles alleviate asthma in mice","volume":"19","author":"An","year":"2025","journal-title":"ACS Nano"},{"key":"nanoae376bbib34","doi-asserted-by":"publisher","DOI":"10.1016\/j.clay.2021.106333","type":"journal-article","article-title":"PEGylated green halloysite\/spinel ferrite nanocomposites for pH sensitive delivery of dexamethasone: a potential pulmonary drug delivery treatment option for COVID-19","volume":"216","author":"Jermy","year":"2021","journal-title":"Appl. Clay Sci."}],"container-title":["Nanotechnology"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ae376b","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ae376b\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ae376b","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ae376b\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ae376b\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ae376b\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ae376b\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ae376b\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T11:55:44Z","timestamp":1771329344000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ae376b"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,17]]},"references-count":34,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,2,17]]},"published-print":{"date-parts":[[2026,2,20]]}},"URL":"https:\/\/doi.org\/10.1088\/1361-6528\/ae376b","relation":{},"ISSN":["0957-4484","1361-6528"],"issn-type":[{"value":"0957-4484","type":"print"},{"value":"1361-6528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,17]]},"assertion":[{"value":"Dexamethasone-loaded glycyrrhiza protein nanoparticles reprogram macrophages to an anti-inflammatory phenotype via STAT6\/IRF4 activation for alleviating sepsis-induced acute respiratory distress syndrome","name":"article_title","label":"Article Title"},{"value":"Nanotechnology","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2026 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2025-08-31","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-01-13","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-02-17","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}