{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:43:31Z","timestamp":1791485011838,"version":"4.3.4"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T00:00:00Z","timestamp":1643500800000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072145"],"award-info":[{"award-number":["82072145"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>\n                    Sepsis is a systemic inflammatory response syndrome caused by a dysregulated host response to infection. Peroxisome proliferator\u2010activated receptor gamma (PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    ) exerts anti\u2010inflammatory and antioxidative properties. To investigate the potential effects of PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    on sepsis\u2010induced liver injury and determine the related mechanisms, C57BL\/6 male mice were subjected to cecal ligation and puncture (CLP) to create a sepsis model which was treated with GW1929 or GW9662 to upregulate or downregulate the expression of PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    . We found that upregulation of PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    decreased the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), and liver pathological damage and improved the 5\u2010day survival rate. Increased expression of PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    also decreased sepsis\u2010induced reactive oxygen species (ROS) by promoting the expression of Nrf2. In addition, upregulated PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    inhibited the expression of the TXNIP\/NLRP3 signaling pathway by reducing ROS\u2010induced injury in the liver during sepsis, which further reduced NLRP3\u2010mediated pyroptosis and the inflammatory response. The role of PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    was further examined in in vitro experiments, where lipopolysaccharide\u2010 (LPS\u2010) treated HepG2 and Hep3B cells were incubated with GW1929 or GW9662 to upregulate or downregulate the expression of PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    . We found that upregulated PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    ameliorated LDH release and improved cell viability. Our results indicated that increased expression of PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    reduced ROS levels and inhibited the TXNIP\/NLRP3 signaling pathway, resulting in decreased pyroptosis and reduced liver dysfunction during sepsis.\n                  <\/jats:p>","DOI":"10.1155\/2022\/1269747","type":"journal-article","created":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T17:50:06Z","timestamp":1643565006000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["PPAR\n                    <i>\u03b3<\/i>\n                    Alleviates Sepsis\u2010Induced Liver Injury by Inhibiting Hepatocyte Pyroptosis via Inhibition of the ROS\/TXNIP\/NLRP3 Signaling Pathway"],"prefix":"10.1155","volume":"2022","author":[{"given":"Zeyu","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingmu","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixia","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1138-3727","authenticated-orcid":false,"given":"Kai","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7318-1004","authenticated-orcid":false,"given":"Chang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8227-9396","authenticated-orcid":false,"given":"Jingyao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,30]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1707170"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep23240"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101831"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000001310"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4756846"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.10.498"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19061809"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09663"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2014.5868"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2016.10.004"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.05.126"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-018-0894-4"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2015.01.008"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13280"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6660429"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks409"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101215"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000318"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.10.019"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/7067619"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/6565283"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.37496"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-019-01124-9"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-015-4054-0"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M809498200"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2019.03.021"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21963"},{"key":"e_1_2_11_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2006.10.381"},{"key":"e_1_2_11_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1651-9"}],"container-title":["Oxidative 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