{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:33:53Z","timestamp":1790948033869,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2025BRA015"],"award-info":[{"award-number":["2025BRA015"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273811"],"award-info":[{"award-number":["82273811"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22577033"],"award-info":[{"award-number":["22577033"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470380"],"award-info":[{"award-number":["82470380"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304340"],"award-info":[{"award-number":["82304340"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470423"],"award-info":[{"award-number":["82470423"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2021M701330"],"award-info":[{"award-number":["2021M701330"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA0910500"],"award-info":[{"award-number":["2021YFA0910500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sepsis, a life\u2010threatening dysregulated host response to infection, is frequently exacerbated by pyroptosis\u2014a programmed, proinflammatory cell death process mediated by Gasdermin D (GSDMD) activation. Using high\u2010throughput screening, we identified emestrin\u2010type epidithiodiketopiperazines (ETPs) as potent inhibitors of GSDMD cleavage during pyroptosis in Tohoku Hospital Pediatrics\u20101 (THP\u20101, a human acute monocytic Leukemia cell line)\u2010derived macrophages. Combined surface plasmon resonance and western blotting analyses demonstrated that these ETPs activate caspase\u20103\/7, which in turn cleaves GSDMD at aspartic acid residue 87 to generate a p10 fragment. This process prevents the formation of the pore\u2010forming p30 fragment, thereby mitigating its associated inflammatory effects. Building on these results, in vivo studies showed that a low dose of the lead emestrin\u2010type ETP (compound\n                    <jats:bold>2<\/jats:bold>\n                    ) protected against lethal lipopolysaccharide (LPS)\u2010induced septic shock and attenuated lung inflammation. This protective effect was further validated in the clinically relevant cecal ligation and puncture (CLP) model, where compound\n                    <jats:bold>2<\/jats:bold>\n                    significantly enhanced survival by suppressing the infiltration of GSDMD\u2010positive neutrophils and monocytes. scRNA\u2010seq of murine lung tissue showed that compound\n                    <jats:bold>2<\/jats:bold>\n                    suppressed LPS\u2010induced systemic inflammation by inhibiting moDC maturation. Collectively, these findings establish the therapeutic potential of targeting GSDMD\u2010driven pyroptosis with ETPs in sepsis and suggest their promise for clinical translation.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70548","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:36:45Z","timestamp":1768293405000},"source":"Crossref","is-referenced-by-count":1,"title":["Emestrin\u2010Type Epidithiodiketopiperazines Inhibited Gasdermin D\u2010Mediated Pyroptosis via Caspase\u20103\/7 Activation"],"prefix":"10.1002","volume":"7","author":[{"given":"Bingchuan","family":"Geng","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Fuwai Central China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University  Zhengzhou China"},{"name":"Henan Provincial Clinical Research Center For Cardiovascular Disease  Zhengzhou China"},{"name":"Department of Cardiovascular Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Lin","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Institute of Pharmaceutical Process Hubei Province Key Laboratory of Occupational Hazard Identification and Control School of Medicine Wuhan University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Yen","family":"Yim","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguang","family":"Sun","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cao","family":"Ma","sequence":"additional","affiliation":[{"name":"Fuwai Central China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fuwai Central China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Guo","sequence":"additional","affiliation":[{"name":"Fuwai Central China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Gao","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanxiao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7713-7230","authenticated-orcid":false,"given":"Qingyi","family":"Tong","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengfeng","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jincheng","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muwei","family":"Li","sequence":"additional","affiliation":[{"name":"Fuwai Central China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University  Zhengzhou China"},{"name":"Henan Provincial Clinical Research Center For Cardiovascular Disease  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengxi","family":"Hu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Shizhen Laboratory  Wuhan China"},{"name":"Hubei Jiangxia Laboratory  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCE.0000000000000775"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina58070844"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-023-01453-7"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.962139"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-022-01624-9"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00630-3"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1178662"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2023.101805"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.893912"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.05.020"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161208784980617"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1943"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2121-3"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.711939"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016931"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15541"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.139"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0669-6"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aat2738"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb9818"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi9284"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28093690"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21050559"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01522-6"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2017.03.009"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.05.027"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio814"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04499-4"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.108782"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2024.110868"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-024-02740-2"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-018-0756-5"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2013.03.004"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1250684"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-01033-z"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.167297"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-021-01959-x"},{"issue":"6","key":"e_1_2_11_39_1","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/d41573-020-00084-2","article-title":"Gasdermin D Inhibitor Protects Against Sepsis","volume":"19","author":"Crunkhorn S.","year":"2020","journal-title":"Nature Reviews Drug Discovery"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019101638"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-82377-z"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1289194"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-021-03775-3"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40779-022-00417-9"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20215376"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17040472"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17030268"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.781003"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16050981"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri746"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08118"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07314-2"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1159\/000515740"}],"container-title":["MedComm"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.70548","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mco2.70548","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.70548","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T07:12:57Z","timestamp":1769152377000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mco2.70548"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/mco2.70548"],"URL":"https:\/\/doi.org\/10.1002\/mco2.70548","archive":["Portico"],"relation":{},"ISSN":["2688-2663","2688-2663"],"issn-type":[{"value":"2688-2663","type":"print"},{"value":"2688-2663","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"article-number":"e70548"}}