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Academy of Engineering Consulting Key Project","award":["YDZJ202203CGZH050"],"award-info":[{"award-number":["YDZJ202203CGZH050"]}]},{"name":"Jilin Provincial Department of Science and Technology\u2013Chinese Academy of Engineering Consulting Key Project","award":["20220508049RC"],"award-info":[{"award-number":["20220508049RC"]}]},{"name":"Jilin Provincial Department of Science and Technology\u2013Chinese Academy of Engineering Consulting Key Project","award":["20230101193JC"],"award-info":[{"award-number":["20230101193JC"]}]},{"name":"Jilin Provincial Department of Science and Technology\u2013Chinese Academy of Engineering Consulting Key Project","award":["JL2023-07"],"award-info":[{"award-number":["JL2023-07"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Anti-inflammatory drugs have become the second-largest class of common drugs after anti-infective drugs in animal clinical care worldwide and are often combined with other drugs to treat fever and viral diseases caused by various factors. In our previous study, a novel serine protease inhibitor-encoding gene (MDSPI16) with improved anti-inflammatory activity was selected from a constructed suppressive subducted hybridization library of housefly larvae. This protein could easily induce an immune response in animals and had a short half-life, which limited its wide application in the clinic. Thus, in this study, mPEG-succinimidyl propionate (mPEG-SPA, Mw = 5 kDa) was used to molecularly modify the MDSPI16 protein, and the modified product mPEG-SPA-MDSPI16, which strongly inhibited elastase production, was purified. It had good stability and safety, low immunogenicity, and a long half-life, and the IC50 for elastase was 86 nM. mPEG-SPA-MDSPI16 effectively inhibited the expression of neutrophil elastase and decreased ROS levels. Moreover, mPEG-SPA-MDSPI16 exerted anti-inflammatory effects by inhibiting activation of the NF-\u03baB signaling pathway and the MAPK signaling pathway in neutrophils. It also exerted therapeutic effects on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. In summary, mPEG-SPA-MDSPI16 is a novel anti-inflammatory protein modified with PEG that has the advantages of safety, nontoxicity, improved stability, and strong anti-inflammatory activity in vivo and in vitro and is expected to become an effective anti-inflammatory drug.<\/jats:p>","DOI":"10.3390\/ijms25084567","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T07:44:09Z","timestamp":1713771849000},"page":"4567","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Long-Acting Serine Protease Inhibitor mPEG-SPA-MDSPI16 Alleviates LPS-Induced Acute Lung Injury"],"prefix":"10.3390","volume":"25","author":[{"given":"Jingrui","family":"Chen","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China"},{"name":"The Key Laboratory of New Veterinary Drug Research and Development of Jilin Province, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinjun","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Life Science, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Dai","sequence":"additional","affiliation":[{"name":"College of Life Science, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Science, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihan","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Science, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haipeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Science, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China"},{"name":"The Engineering Research Center of Bioreactor and Drug Development, Ministry of Education, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingcong","family":"Kong","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China"},{"name":"The Key Laboratory of New Veterinary Drug Research and Development of Jilin Province, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongxia","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China"},{"name":"The Key Laboratory of New Veterinary Drug Research and Development of Jilin Province, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China"},{"name":"College of Life Science, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China"},{"name":"The Engineering Research Center of Bioreactor and Drug Development, Ministry of Education, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1042\/CS20210879","article-title":"Pathogenesis of pneumonia and acute lung injury","volume":"136","author":"Long","year":"2022","journal-title":"Clin. 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