{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:14:15Z","timestamp":1783674855154,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260808"],"award-info":[{"award-number":["82260808"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Exploring the targeted regulatory effect of isorhynchophylline on lipopolysaccharide (LPS)\u2010induced acute lung injury (ALI) by constructing a drug delivery system of GEF\u2010modified exosomes derived from M2 macrophages (M2\u2010Exos) loaded with isorhynchophylline (GEF\u2010M2\u2010Exos\u2010IRN; GMI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      GMI was constructed using an ultrasonic method with M2\u2010Exos and isorhynchophylline. Targeting GMI was traced using immunofluorescence of mouse lung tissue frozen sections and BEAS\u20102B\/A549 cells. Haematoxylin and eosin staining was used to detect pathological changes and Terminal deoxynucleotidyl transferase dUTP Nick\u2010End Labelling (TUNEL) was employed to detect cell apoptosis. Expression levels of\n                      <jats:italic>\u03b1<\/jats:italic>\n                      \u2010SMA, iNOS and Arg1 were detected via immunohistochemistry and fluorescence. GMI intervention in acute lung injury were analysed by transcriptome sequencing and key differential genes were verified by quantitative reverse transcription polymerase chain reaction (RT\u2010qPCR).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      GMI drug lung targeting delivery system was successfully constructed. GMI reduced the percentage of apoptotic cells, down\u2010regulate the expression of\n                      <jats:italic>\u03b1<\/jats:italic>\n                      \u2010SMA, inhibit M1 phenotype and activated M2 phenotype. Transcriptome sequencing showed that LPS promoted Th17 differentiation through the NF\u2010\u03baB\/MAPK\/JAK\u2013STAT pathway, causing an IL\u20106\/TNF\u2010\n                      <jats:italic>\u03b1<\/jats:italic>\n                      inflammatory storm, inducing metabolic\u2010oxidative stress aggravating the injury. GMI reversed the injury inhibiting Th17\/CXCL axis, activating Treg\/TGF\u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      axis, restoring glycolysis\/cholesterol metabolism, epigenetically regulating SOCS3 and promoting tissue barrier reconstruction. Gene interaction network identified\n                      <jats:italic>Spib<\/jats:italic>\n                      \u2010\n                      <jats:italic>Pou2f1<\/jats:italic>\n                      \u2010\n                      <jats:italic>Aicda<\/jats:italic>\n                      \/\n                      <jats:italic>Tnfrsf4<\/jats:italic>\n                      as the core hub, mediating the immune\u2010inflammatory reaction. The key differential genes were consistent with the sequencing results after RT\u2010qPCR verification.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>GMI alleviates LPS\u2010induced acute lung injury through a multi\u2010factorial network of \u2018inflammation\u2010metabolism\u2010epigenetics\u2019, providing a new strategy for lung\u2010targeted anti\u2010inflammatory treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70403","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T23:05:23Z","timestamp":1778799923000},"page":"4855-4878","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted peptide\u2010modified M2 exosomes drug delivery system for the targeted regulation of the lung injury microenvironment with isorhynchophylline (IRN): based on the inflammatory\u2013metabolic\u2013epigenetic synergy mechanism"],"prefix":"10.1111","volume":"183","author":[{"given":"Jin\u2010Ru","family":"Zou","sequence":"first","affiliation":[{"name":"Baotou Medical College  Baotou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Yang","sequence":"additional","affiliation":[{"name":"Baotou Medical College  Baotou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan\u2010Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Baotou Medical College  Baotou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Baotou Medical College  Baotou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao\u2010Nan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Baotou Medical College  Baotou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Song","sequence":"additional","affiliation":[{"name":"Baotou Medical College  Baotou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Bing","family":"Ma","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Baotou Medical College  Baotou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Baotou Medical College  Baotou China"},{"name":"The First Affiliated Hospital of Baotou Medical College  Baotou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Qiu","sequence":"additional","affiliation":[{"name":"Baotou Medical College  Baotou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70233"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70229"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c11858"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1530849"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-023-00838-9"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17441"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-024-01665-1"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01757-9"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bjd\/ljae230"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2025.117130"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1250719"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107100"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05057-4"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.12.053"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202303782"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021337"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00841"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1397498"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.174971"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e20387"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-019-0563-2"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c01900"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/BPH.15178"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2023.123321"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs20210879"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/js9.0000000000000789"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1113\/jp282799"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.12.027"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2013.01.018"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-022-00500-w"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199805000-00022"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102655"},{"issue":"2","key":"e_1_2_13_36_1","first-page":"97","article-title":"Pharmacological actions of Uncaria alkaloids, rhynchophylline and isorhynchophylline","volume":"24","author":"Shi J. S.","year":"2003","journal-title":"Acta Pharmacologica Sinica"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02595-w"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2025.137381"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/rti.0000000000000820"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01462-1"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2023.123069"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.111580"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2025.146575"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.69533"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/cm9.0000000000003181"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07452-z"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-01093-y"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.10.034"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-023-01886-3"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-06031-8"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.03.017"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-024-05150-1"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.8015"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70403","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.70403","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70403","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T08:25:56Z","timestamp":1783671956000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":52,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/bph.70403"],"URL":"https:\/\/doi.org\/10.1111\/bph.70403","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]},"assertion":[{"value":"2025-08-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}