{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:45:14Z","timestamp":1786977914038,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp; Disease"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the therapeutic mechanism of propolis flavonoids (PF) in chronic osteomyelitis (COM) through transcriptional coactivator with PDZ\u2010binding motif (TAZ)\u2010mediated regulation of regulatory T cell (Treg)\/T helper 17 (Th17) cell homeostasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixty 3\u2010month\u2010old Wistar rats were randomly divided into control, model, and PF\u2010treated groups. In vitro, human peripheral blood mononuclear cells (PBMCs) and rat PBMCs were stratified into five treatment groups: control (10% healthy control (HC) serum), osteomyelitis model (15\u2009ng\/mL transforming growth factor\u2010\u03b21 \u2009+\u200910% HC serum), model+PF , TEA domain transcription factor 1 (TEAD1)+model , and TEAD1+model+PF. TAZ signaling components (TAZ, RAR\u2010related orphan receptor gamma t (ROR\u03b3t), Forkhead box P3 (FOXP3)), inflammatory cytokines (interleukin (IL)\u221217, IL\u201021, IL\u20102, IL\u201010), and T cell subsets (Th17\/Treg ratios) were analyzed via Western blot, enzyme\u2010linked immunosorbent assay (ELISA), and flow cytometry. Periosteal cell proliferation was quantified using 5\u2010ethynyl\u20102\u2019\u2010deoxyuridine (EdU) assay. Bacterial load in bone tissue was quantified using colony\u2010forming unit (CFU) counts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PF administration significantly upregulated TAZ protein expression compared to untreated osteomyelitis models (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). PF treatment significantly reduced bacterial burden in bone tissue (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). In the PF group, Th17 cell proportions increased (2.28\u2009\u00b1\u20090.35%) compared to the osteomyelitis model group (1.58\u2009\u00b1\u20090.31%) and ROR\u03b3t expression was elevated, coupled with reduced Treg populations (1.66\u2009\u00b1\u20090.27%) compared to the osteomyelitis model group (11.5\u2009\u00b1\u20090.29%) and reduced FOXP3 levels. Notably, pro\u2010inflammatory cytokines IL\u201017 and IL\u201021 decreased in PF\u2010treated groups, while anti\u2010inflammatory IL\u201010 and IL\u20102 increased. Periosteal cell proliferation rates improved significantly with PF intervention. TEAD1 overexpression attenuated PF\u2010mediated effects in both human and rat PBMCs, confirming TAZ's central regulatory role across species.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Propolis flavonoids ameliorate chronic osteomyelitis through TAZ\u2010dependent mechanisms that rebalance Treg\/Th17 polarization and promote bacterial clearance. This involves restoring Th17 cell populations while concurrently suppressing their key effector cytokines, ultimately reducing inflammatory pathology and promoting bone repair.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70432","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:49:13Z","timestamp":1780573753000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Propolis Flavonoids Ameliorate Chronic Osteomyelitis in a Rat Model by Modulating TAZ\u2010Regulated Treg\/Th17 Balance"],"prefix":"10.1002","volume":"14","author":[{"given":"Yujie","family":"Wang","sequence":"first","affiliation":[{"name":"Fourth Department of Orthopedics and Traumatology Hebei Hospital of Traditional Chinese Medicine Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaozhu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fourth Department of Orthopedics and Traumatology Hebei Hospital of Traditional Chinese Medicine Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Hebei Hospital of Traditional Chinese Medicine Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5968-4772","authenticated-orcid":false,"given":"Liqiang","family":"Li","sequence":"additional","affiliation":[{"name":"Fourth Department of Orthopedics and Traumatology Hebei Hospital of Traditional Chinese Medicine Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2022.07.014"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/1744666x.2023.2218088"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jbmr\/zjae141"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/d2nr02176e"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1163933"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2021.06.005"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000000970"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/02648725.2023.2166706"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2025.1526475"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.11.028"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-101819-025146"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.11.003"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.job.2022.02.001"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/203705"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0266673"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-022-21652-6"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/02652048.2023.2274059"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.15212\/bioi-2024-0001"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjbs.2021.08.022"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/10286020.2024.2355142"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0649-6"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e15867"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115568"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-022-00969-9"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000411"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1396592"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.4103\/REGENMED.REGENMED-D-25-00025"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10113039"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118463"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2013.02.014"}],"container-title":["Immunity, Inflammation and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iid3.70432","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/iid3.70432","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iid3.70432","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T05:13:34Z","timestamp":1782882814000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/iid3.70432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/iid3.70432"],"URL":"https:\/\/doi.org\/10.1002\/iid3.70432","archive":["Portico"],"relation":{},"ISSN":["2050-4527","2050-4527"],"issn-type":[{"value":"2050-4527","type":"print"},{"value":"2050-4527","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2025-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70432"}}