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Res."],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective and design<\/jats:title>\n                    <jats:p>To elucidate Sirt1\u2019s role in gouty arthritis inflammation and its potential mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material<\/jats:title>\n                    <jats:p>Constructed murine models of gouty arthritis and conducted THP-1 cell experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Treatment<\/jats:title>\n                    <jats:p>1\u00a0mg of MSU crystals injected into mice ankle joints for a 72-h intervention. After a 3-h pre-treatment with Sirt1-specific inhibitor (EX527) and agonist (SRT2104), inflammation was induced for 21\u00a0h using lipopolysaccharide (LPS) plus MSU crystals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We assessed gouty arthritis severity through joint inflammation index, swelling, and hematoxylin and eosin (H&amp;E) staining, and measured CD68 mononuclear macrophages and Sirt1 expression in synovial tissue via immunohistochemistry. ELISA, NO assay, RT-qPCR, Flow cytometry, and Western blot were utilized to examine macrophage inflammatory factors, polarization, reactive oxygen species(ROS), MAPK\/NF-\u03baB\/AP-1 and Nrf2\/HO-1 pathways proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Significant joint swelling, synovial tissue edema, and inflammatory cell infiltration were observed. CD68 mononuclear macrophages and Sirt1 expression were elevated in synovium. Sirt1 activation decreased inflammatory factors, M1 polarization, and ROS generation. Sirt1 activation reduced p38\/JNK phosphorylation, thereby inhibiting downstream NF-\u03baB p65\/AP-1 and enhancing Nrf2\/HO-1, thus suppressing inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Sirt1 alleviates M1 macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK\/NF-\u03baB\/AP-1 pathway and activating the Nrf2\/HO-1 pathway. Thus, activating Sirt1 may provide a new therapeutic target for gouty arthritis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00011-024-01890-9","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T09:03:07Z","timestamp":1715590987000},"page":"1173-1184","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Sirt1 inhibits macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK\/NF-\u03baB\/AP-1 pathway and activating the Nrf2\/HO-1 pathway"],"prefix":"10.1007","volume":"73","author":[{"given":"Xu","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiquan","family":"Shuai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"key":"1890_CR1","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1016\/S0140-6736(21)00569-9","volume":"397","author":"N Dalbeth","year":"2021","unstructured":"Dalbeth N, Gosling AL, Gaffo A, Abhishek A. 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