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This multi-dimensional (clinical-cell-animal) study investigated the myeloperoxidase (MPO)-DNA complex, a marker of neutrophil extracellular traps (NETs), and the combination of AZD5904 (an MPO inhibitor) and DNase I (a NETs-DNA degrader). Key findings include: First, integrated evidence from bronchoalveolar lavage fluid analysis and immunofluorescence identified the MPO-DNA complex as a biomarker significantly associated with\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    -associated bronchiectasis severity (e.g., lung lobe involvement, Bronchiectasis Severity Index). Mendelian randomization (MR) analysis revealed a potential causal link with bronchiectasis risk but not with several other chronic respiratory diseases. Second, in cellular models,\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    PAO1-induced NETs were associated with epithelial damage, as evidenced by the upregulation of reactive oxygen species, malondialdehyde, interleukin-1\u03b2, and interleukin-6, and the reduction of BEAS-2B cell viability. Third, in\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    -infected bronchiectasis rat models, AZD5904 combined with DNase I alleviated lung pathology, inflammation, and NETs accumulation more effectively than monotherapy. This study suggests the MPO-DNA complex as a potential biomarker and pathogenic factor associated with disease severity, and proposes a dual-target combined intervention strategy worthy of further preclinical investigation for\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    -associated bronchiectasis.\n                  <\/jats:p>","DOI":"10.1186\/s13568-026-02012-w","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T19:35:49Z","timestamp":1769110549000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Myeloperoxidase-DNA complex: a marker and combined target for Pseudomonas aeruginosa-associated bronchiectasis"],"prefix":"10.1186","volume":"16","author":[{"given":"Shaochu","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinling","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cao","family":"Qing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongxi","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangkang","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinliang","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"2012_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2022.100779","volume":"26","author":"M Ali","year":"2022","unstructured":"Ali M, Fulci G, Grigalavicius M, Pulli B, Li A, Wojtkiewicz GR, Wang C, Hsieh KL, Linnoila JJ, Theodossiou TA, Chen JW (2022) Myeloperoxidase exerts anti-tumor activity in glioma after radiotherapy. 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Approval was granted by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (Approval Number: 2024-E339-01, 2025-E0932). All participants had informed consent to the study and signed an informed consent form. The use of experimental animals complied with the National Regulations for the Administration of Experimental Animals and was approved by the Animal Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (2025-D0486). Our Study was reported according to the ARRIVE guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17"}}