{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T10:58:45Z","timestamp":1791543525227,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"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":["The Kaohsiung J of Med Scie"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pediatric acute lung injury (ALI) is a life\u2010threatening syndrome defined by dysregulated pulmonary inflammation and impaired alveolar gas exchange, with limited therapeutic interventions. This study aims to evaluate the therapeutic efficacy and mechanistic basis of Olaparib, a clinically approved PARP inhibitor, using in\u00a0vitro and in\u00a0vivo models of pediatric ALI. In LPS\/ATP\u2010stimulated THP\u20101\u2010derived macrophages, Olaparib induced metabolic reprogramming, as indicated by a reduced NAD\n                    <jats:sup>+<\/jats:sup>\n                    \/NADH ratio and an elevated AMP\/ATP ratio, leading to activation of the AMPK\/ULK1 signaling pathway. This activation enhanced autophagic flux, as evidenced by increased LC3\u2010II conversion, p62 degradation, and analysis of the mRFP\u2010GFP\u2010LC3 reporter. Enhanced autophagy was associated with attenuation of oxidative stress, including reductions in mitochondrial and intracellular reactive oxygen species and malondialdehyde levels, and suppression of NLRP3 inflammasome activation, as evidenced by decreased cleaved caspase\u20101, IL\u20101\u03b2, and IL\u201018. In a juvenile murine model of LPS\u2010induced ALI, Olaparib administration reduced histopathological lung injury, inflammatory cell infiltration, and pulmonary edema. It also restored alveolar\u2013capillary barrier integrity by upregulating junctional proteins, including ZO\u20101, claudin\u20105, and VE\u2010cadherin, and reduced apoptosis. The protective effects of Olaparib on autophagy, oxidative stress, inflammasome activity, and lung tissue repair were attenuated by pharmacological inhibition of AMPK using compound C. In conclusion, these findings demonstrate that Olaparib ameliorates pediatric ALI through AMPK\u2010dependent induction of autophagic flux via metabolic reprogramming, attenuating oxidative stress and inhibiting NLRP3 inflammasome activation. These results support the therapeutic potential of Olaparib in pediatric ALI.\n                  <\/jats:p>","DOI":"10.1002\/kjm2.70275","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T10:44:57Z","timestamp":1791542697000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Olaparib Blocks Oxidative Stress\u2010Dependent\n                    <scp>NLRP3<\/scp>\n                    Inflammasome in Pediatric Acute Lung Injury by Metabolic Reprogramming via\n                    <scp>AMPK<\/scp>\n                    \u2010Driven Autophagic Flux"],"prefix":"10.1002","author":[{"given":"Fen","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Children's Hospital of Soochow University  Jiangsu Province China"},{"name":"Department of Pediatrics The Second Affiliated Hospital of Bengbu Medical University  Bengbu Anhui People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei\u2010Ling","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Bengbu Medical University  Bengbu Anhui People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng\u2010Rong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Children's Hospital of Soochow University  Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Li","sequence":"additional","affiliation":[{"name":"Pediatrics Research Institute Children's Hospital of Soochow University  Suzhou P. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Sang","sequence":"additional","affiliation":[{"name":"Deputy Chief Physician of Pediatrics First Affiliated Hospital of Bengbu Medical University  Bengbu Anhui People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6858-5558","authenticated-orcid":false,"given":"Yong\u2010Dong","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Children's Hospital of Soochow University  Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"issue":"2","key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.pccm.2024.04.002","article-title":"Mechanisms of Pulmonary Endothelial Barrier Dysfunction in Acute Lung Injury and Acute Respiratory Distress Syndrome","volume":"2","author":"Su Y.","year":"2024","journal-title":"Chinese Medical Journal Pulmonary and Critical Care Medicine"},{"issue":"1","key":"e_1_2_8_3_1","first-page":"3","article-title":"Current Concepts of Immune Interventions in Children With Respiratory Diseases","volume":"61","author":"Bellanti J. 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