{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:06:43Z","timestamp":1792786003389,"version":"4.5.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003655","name":"National Institute of Food and Drug Safety Evaluation","doi-asserted-by":"publisher","award":["21184MFDS326"],"award-info":[{"award-number":["21184MFDS326"]}],"id":[{"id":"10.13039\/501100003655","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bio & Medical Technology Development Program of the National Research Foundation","award":["RS-2024-00509361"],"award-info":[{"award-number":["RS-2024-00509361"]}]},{"DOI":"10.13039\/501100008003","name":"Korea Institute of Radiological and Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008003","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and Information and Communication Technology","doi-asserted-by":"publisher","award":["50539\u20132026"],"award-info":[{"award-number":["50539\u20132026"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Konkuk University Researcher Fund in 2024","id":[{"id":"https:\/\/ror.org\/025h1m602","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Radiation-induced lung injury, a well-recognized complication of thoracic radiotherapy, can progress to pulmonary fibrosis, sharing pathological features with idiopathic pulmonary fibrosis. Although nintedanib is widely used as an antifibrotic agent, the therapeutic benefit of combination strategies remains partially understood. Therefore, in this study, we aimed to evaluate the effects of combined metformin and nintedanib treatment in a mouse model of irradiation-induced lung fibrosis. Female C57BL\/6 mice were subjected to localized irradiation of 90\u00a0Gy in the left lung and treated daily with metformin, nintedanib or both drugs for 6\u00a0weeks. Lung fibrosis was assessed using gross examination, hydroxyproline quantification, histopathological scoring and quantitative image analysis. Changes in fibrosis- and injury-related proteins were examined by western blotting, including transforming growth factor-\u03b2 (TGF-\u03b2), a profibrotic cytokine; SMAD family member 7 (SMAD7), an inhibitory regulator of TGF-\u03b2 signaling; and surfactant protein D (SP-D), a lung epithelial injury-associated protein. Nintedanib-containing treatments improved histological lung injury in irradiated mice, including reduced collagen deposition, low pathological scores and preserved air space structure. Hydroxyproline content was also lower in the combination treatment group than in the other groups. The nintedanib-containing treatments suppressed irradiation-induced upregulation of transforming growth factor-\u03b2 expression, and SMAD7 expression was selectively upregulated following combined treatment. In addition, elevated SP-D level following irradiation was partially reduced following nintedanib administration. These findings suggest that combined metformin and nintedanib treatment may provide a broader protective profile against radiation-induced pulmonary fibrosis, particularly in association with SMAD7 upregulation, although further studies are required to clarify whether the combination provides significant advantages over nintedanib monotherapy.<\/jats:p>","DOI":"10.1093\/jrr\/rrag057","type":"journal-article","created":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T13:22:49Z","timestamp":1785072169000},"page":"715-723","source":"Crossref","is-referenced-by-count":0,"title":["Effects of combination metformin and nintedanib therapy in a mouse model of irradiation-induced pulmonary fibrosis"],"prefix":"10.1093","volume":"67","author":[{"given":"Ji-Hun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University , 120 Neungdong-ro, Gwangjin-gu, Seoul 05029 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Bi","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University , 120 Neungdong-ro, Gwangjin-gu, Seoul 05029 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Seon","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University , 120 Neungdong-ro, Gwangjin-gu, Seoul 05029 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2655-539X","authenticated-orcid":false,"given":"Na-Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University , 120 Neungdong-ro, Gwangjin-gu, Seoul 05029 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Min","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University , 120 Neungdong-ro, Gwangjin-gu, Seoul 05029 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Jun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University , 120 Neungdong-ro, Gwangjin-gu, Seoul 05029 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4969-5443","authenticated-orcid":false,"given":"Yang-Kyu","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University , 120 Neungdong-ro, Gwangjin-gu, Seoul 05029 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5719-6281","authenticated-orcid":false,"given":"Jin-Hee","family":"Seo","sequence":"additional","affiliation":[{"name":"Korea Radioisotope Center for Pharmaceuticals, Korea Institute of Radiological & Medical Sciences , Seoul 01812 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,26]]},"reference":[{"key":"2026100906572425600_ref1","doi-asserted-by":"publisher","first-page":"316","DOI":"10.4143\/crt.2021.290","article-title":"Prediction of cancer incidence and mortality in Korea, 2021","volume":"53","author":"Jung","year":"2021","journal-title":"Cancer Res Treat"},{"key":"2026100906572425600_ref2","doi-asserted-by":"publisher","first-page":"89","DOI":"10.4046\/trd.2020.0134","article-title":"Recent trends of lung cancer in Korea","volume":"84","author":"Lee","year":"2021","journal-title":"Tuberc Respir Dis"},{"key":"2026100906572425600_ref3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/resp.13870","article-title":"Radiotherapy treatment for lung cancer: current status and future directions","volume":"25","author":"Vinod","year":"2020","journal-title":"Respirology"},{"key":"2026100906572425600_ref4","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1186\/s12943-024-02142-4","article-title":"Anti irradiation nanoparticles shelter immune organ from radio-damage via preventing the IKK\/I\u03baB\/NF-\u03baB activation","volume":"23","author":"Huang","year":"2024","journal-title":"Mol Cancer"},{"key":"2026100906572425600_ref5","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2020.585756","article-title":"Scarred lung. 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