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Alliance"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:p>Acute-on-chronic liver failure (ACLF) is clinical syndrome with high mortality rate. This study aimed to perform detailed transcriptomic analysis in liver cirrhosis\u2013based ACLF rats to elucidate ACLF pathogenesis. ACLF was induced by combined porcine serum with D-galactosamine and lipopolysaccharide. Gene expression profile of liver tissues from ACLF rats was generated by transcriptome sequencing to reveal the molecular mechanism. ACLF rats successfully developed with typical characteristics. Total of 2,354\/3,576 differentially expressed genes were identified when ACLF was compared to liver cirrhosis and normal control, separately. The functional synergy analysis revealed prominent immune dysregulation at ACLF stage, whereas metabolic disruption was significantly down-regulated. Relative proportions of innate immune\u2013related cells showed significant elevation of monocytes and macrophages, whereas adaptive immune\u2013related cells were reduced. The seven differentially expressed genes underlying the ACLF molecular mechanisms were externally validated, among them <jats:italic>THBS1<\/jats:italic>, <jats:italic>IL-10<\/jats:italic>, and <jats:italic>NR4A3<\/jats:italic> expressions were confirmed in rats, patient transcriptomics, and liver biopsies, verifying their potential value in the ACLF pathogenesis. This study indicates immune-metabolism disorder in ACLF rats, which may provide clinicians new targets for improving intervention strategies.<\/jats:p>","DOI":"10.26508\/lsa.202101189","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T20:05:14Z","timestamp":1638389114000},"page":"e202101189","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Transcriptomics reveals immune-metabolism disorder in acute-on-chronic liver failure in rats"],"prefix":"10.26508","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9463-6007","authenticated-orcid":true,"given":"Hozeifa M","family":"Hassan","sequence":"first","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, 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