Sepsis-induced skeletal muscle wasting may lead to various severe clinical consequences. Understanding molecular mechanisms of the regulation of the loss of skeletal muscle mass in septic patients remains a significant clinical challenge. The current study was conducted to establish septic mice models to explore the relationship between microRNA (miR)-351 and the transcription element apical (TEA) domain transcription factor (Tead)-4 gene and to investigate its effects on the skeletal muscle through mediating the Hippo signaling pathway in mice with acute sepsis. A total of 60 mice were collected to establish mouse models of acute sepsis. The positive expression rate of Tead-4 and the apoptotic index (AI) were measured. A dual-luciferase reporter gene assay was conducted to verify the targeting relationship between miR-351 and Tead-4. Furthermore, the muscle fiber diameter (MFD) and area (MFA) and the content of 3-methylhistidine (3-MH) and tyrosine (Tyr) were assessed. The expression levels of miR-351, p38-MAPK, Yes-associated protein, Tead-4, B-cell lymphoma X protein (Bax), and Caspase-3 were determined with quantitative RT-PCR and Western blot analysis. Finally, cell viability, apoptosis, and levels of inflammatory factors, including IL-1β, IL-6, IGF-1, TNF-α, and monocyte chemoattractant protein-1 were detected by 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and ELISA. Initially, Tead-4 protein expression was higher in skeletal muscle tissues of mice with acute sepsis. Tead-4 was identified to negatively regulate miR-351. Upregulation of miR-351 increased MFA and MFD, muscle weight water content, Bcl-2 expression levels, and cell viability. Up-regulation of miR-351 reduced AI; 3-MH and Tyr content; positive expression of Tead-4 protein; the expression levels of p38-MAPK, Yap, Tead-4, Bax, and Caspase-3; apoptosis; and inflammatory responses. The current study demonstrated that up-regulation of miR-351 inhibits the degradation of skeletal muscle protein and the atrophy of skeletal muscle in mice with acute sepsis by targeting Tead-4 through suppression of the Hippo signaling pathway. Thus, miR-351 overexpression may be a future therapeutic strategy for acute sepsis.-Zhang, L.-N., Tian, H., Zhou, X.-L., Tian, S.-C., Zhang, X.-H., Wu, T.-J. Upregulation of microRNA-351 exerts protective effects during sepsis by ameliorating skeletal muscle wasting through the Tead-4-mediated blockade of the Hippo signaling pathway.

ObjectiveTo analyze the predictive value of renal resistance index (RRI) and plasma cystatin C (pCysC) in pregnancy-related acute kidney injury (PR-AKI).MethodsThis study included 182 pregnant women admitted to the intensive care unit (ICU) between May 2016 and June 2021. Intensivists who had received full-time bedside ultrasound Doppler training performed RRI measurements, and blood was drawn to monitor serum creatinine (Scr) and pCysC concentrations. The study continued for 3 consecutive days, marked as the first day, the second day, and the third day, during which the hourly urine output (UO) was monitored and recorded. According to the AKI diagnostic staging criteria, patients with AKI were divided into stages I, II, and III and comprised the study group (Group A), and patients without AKI served as the control group (Group B).ResultsOf the 182 enrolled patients, 35 (19.2%) were diagnosed with AKI, including 23 (65.7%) with stage I, 9 with stage II (25.7%), and 3 with stage III (8.6%). Three were excluded owing to the requirement of continuous blood purification. Therefore, 179 patients, 32 in Group A and 147 in Group B, were included. The Scr, pCysC, and RRI of Group A increased on the first, second, and third days, but there was a gradual decrease over time. Each period was compared with the corresponding period in Group B, and there were significant differences (P<0.05). All patients in Group A met the diagnostic criterion of Scr concentration in AKI, and only 34.4% of the patients met the diagnostic criterion of UO. According to the D1 monitoring results, the proportions of increased pCysC and RRI in Group A were 87.5% and 81.3%, respectively. They were significantly different from those in Group B (P<0.001). The three variables of pCysC, RRI, and the combination of pCysC and RRI all independently correlated with AKI. The sensitivity and specificity of pCysC concentration for the prediction of PR-AKI were 87.5% and 84.35%, respectively, and those of RRI were 81.25% and 76.87%, respectively. The sensitivity and specificity of the combination of the two were 96.88% and 72.11%, respectively. Receiver operating characteristic curve analysis showed that these indicators had a significant predictive power for PR-AKI. Although the length of stay in the ICU and hospital in Group A was longer (P<0.05), there was no difference in hospital mortality between the two groups (P>0.05).ConclusionThe diagnosis of PR-AKI based only on Scr and UO was insufficient. RRI and pCysC were important supplements for diagnosing PR-AKI, with good sensitivity and specificity. However, combining the two was better.