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Sepsis-induced acute liver injury (ALI) is common in intensive care units. Angiotensin-converting enzyme 2 (ACE2) plays a vital role in hepatic fibrosis and steatosis; however, its role in sepsis-induced ALI remains unclear. This study found that hepatic ACE2 expression in cecal ligation and puncture (CLP)-treated mice significantly decreased 24 h after CLP. ACE2-transgenic (TG) mice exhibited a significant improvement in CLP-induced ALI, accompanied by the inhibition of hepatocyte apoptosis, oxidative stress, and inflammation, while ACE2-knockout mice demonstrated an opposite trend. During sepsis-induced ALI, ACE2-TG could also elevate the Ang-(1-7) and Mas receptor (MasR) levels in liver tissues. Interestingly, the MasR inhibitor A779 abrogated the favorable effects of ACE2 on CLP-induced ALI. In a bone marrow transplantation experiment, the ACE2-TG transplantation group showed significantly improved inflammation and liver dysfunction, less hepatocyte apoptosis, and reduced oxidative stress after CLP compared with the wild-type transplantation group. In contrast, the ACE2-knockout group showed poor inflammatory response and liver dysfunction, significantly more hepatocyte apoptosis, and elevated oxidative stress than the wild-type transplantation group after CLP. ACE2 protects against sepsis-induced ALI by inhibiting hepatocyte apoptosis, oxidative stress, and inflammation via the Ang-(1-7)-Mas receptor axis. Thus, targeting ACE2 may be a promising novel strategy for preventing and treating sepsis-induced ALI., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sepsis-induced cardiomyopathy (SIC), caused by a dysregulated host response to infection, is a major contributor to high mortality. Angiotensin-converting enzyme 2 (ACE2), a crucial component of the renin-angiotensin system (RAS), has protective effects against several cardiovascular diseases, such as myocardial infarction and heart failure. However, the role of ACE2 in the pathogenesis of SIC and underlying mechanisms remain unknown. The present study was designed to examine the effects of ACE2 activation or inhibition on SIC in C57BL/6 mice. The ACE2 activator diminazene aceturate (DIZE) and ACE2 inhibitor MLN-4760 were applied for treatment. Myocardial function, inflammatory response, oxidative stress, apoptosis and mitochondrial biogenesis were investigated. Major assays were echocardiography, H&E staining, immunofluorescence staining, DHE staining, TUNEL staining, Western blot, qPCR analysis, ELISA and corresponding kits. We confirmed that ACE2 was markedly downregulated in septic heart tissues. Pharmacological activation of ACE2 by DIZE ameliorated cecal ligation puncture (CLP)-induced mortality, cardiac dysfunction, inflammatory response, oxidative stress and the cardiomyocyte apoptosis by promoting MasR-Sirt1-mediated mitochondrial biogenesis. In contrast, SIC was aggravated via inhibiting MasR-Sirt1-mediated mitochondrial biogenesis by the use of ACE2 inhibitor MLN-4760. Consequently, activation of ACE2 may protect against SIC by promoting MasR-Sirt1-mediated mitochondrial biogenesis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Severe influenza is often associated with bacterial coinfection and can trigger sepsis, which increases the severity, complexity and mortality of the disease. To determine an effective method for predicting 28-day mortality of emergency department (ED) patients with influenza, we investigated the Mortality in Emergency Department Sepsis (MEDS) score, procalcitonin (PCT) and other relevant biomarkers., Methods: We conducted a retrospective, observational, monocentric study, and the endpoint was 28-day mortality. Independent predictors were identified and a new combination predictive model was created both by logistic regression, and the model was evaluated by a receiver operating characteristic (ROC) curve., Results: A total of 364 consecutive ED admitted patients with influenza were enrolled and 45 patients died within 28 days. For predicting 28-day mortality, the MEDS score and PCT were independent predictors with adjusted odds ratio of 1.318 (95% CI 1.206-1.439) and 1.038 (95% CI 1.010-1.065), and with AUCs of 0.817 (95% CI 0.756-0.878) and 0.793 (95% CI 0.725-0.861), respectively. The new combination of the MEDS score with PCT significantly improved the efficacy for predicting 28-day mortality with an AUC of 0.857 (95% CI 0.809-0.905), and was superior to the SOFA score with an AUC of 0.837 (95% CI 0.779-0.894)., Conclusion: The MEDS score and PCT, especially when combined, perform well for predicting mortality of ED admitted patients with influenza., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)