{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T12:05:06Z","timestamp":1776081906786,"version":"3.50.1"},"reference-count":57,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T00:00:00Z","timestamp":1684195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Council of Science and Technology","award":["CRC21021-100"],"award-info":[{"award-number":["CRC21021-100"]}]},{"name":"National Research Council of Science and Technology","award":["KRIBB KGM5242322"],"award-info":[{"award-number":["KRIBB KGM5242322"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sepsis, characterized by an uncontrolled host inflammatory response to infections, remains a leading cause of death in critically ill patients worldwide. Sepsis-associated thrombocytopenia (SAT), a common disease in patients with sepsis, is an indicator of disease severity. Therefore, alleviating SAT is an important aspect of sepsis treatment; however, platelet transfusion is the only available treatment strategy for SAT. The pathogenesis of SAT involves increased platelet desialylation and activation. In this study, we investigated the effects of Myristica fragrans ethanol extract (MF) on sepsis and SAT. Desialylation and activation of platelets treated with sialidase and adenosine diphosphate (platelet agonist) were assessed using flow cytometry. The extract inhibited platelet desialylation and activation via inhibiting bacterial sialidase activity in washed platelets. Moreover, MF improved survival and reduced organ damage and inflammation in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. It also prevented platelet desialylation and activation via inhibiting circulating sialidase activity, while maintaining platelet count. Inhibition of platelet desialylation reduces hepatic Ashwell\u2013Morell receptor-mediated platelet clearance, thereby reducing hepatic JAK2\/STAT3 phosphorylation and thrombopoietin mRNA expression. This study lays a foundation for the development of plant-derived therapeutics for sepsis and SAT and provides insights into sialidase-inhibition-based sepsis treatment strategies.<\/jats:p>","DOI":"10.3390\/ijms24108863","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T02:04:05Z","timestamp":1684289045000},"page":"8863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Myristica fragrans Extract Inhibits Platelet Desialylation and Activation to Ameliorate Sepsis-Associated Thrombocytopenia in a Murine CLP-Induced Sepsis Model"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4611-7322","authenticated-orcid":false,"given":"Seong-Hun","family":"Jeong","sequence":"first","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea"},{"name":"Laboratory of Veterinary Pathology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Young","family":"Park","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea"},{"name":"Center for Companion Animal New Drug Development, Jeonbuk Branch, Korea Institute of Toxicology, Jeongeup 53212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Bae","family":"Ryu","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo Sik","family":"Kim","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8748-9731","authenticated-orcid":false,"given":"In-Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea"},{"name":"Center for Companion Animal New Drug Development, Jeonbuk Branch, Korea Institute of Toxicology, Jeongeup 53212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju-Hong","family":"Kim","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dohoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Hye","family":"Ha","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ba-Wool","family":"Lee","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiyoung","family":"Nam","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoung-Oh","family":"Cho","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0196-4672","authenticated-orcid":false,"given":"Hyung-Jun","family":"Kwon","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea"},{"name":"Center for Companion Animal New Drug Development, Jeonbuk Branch, Korea Institute of Toxicology, Jeongeup 53212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/s41392-021-00816-9","article-title":"Signaling pathways and intervention therapies in sepsis","volume":"6","author":"Zhang","year":"2021","journal-title":"Signal Transduct. 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