The ceRNA network involving circular RNAs (circRNAs) is essential in the cardiovascular system. We investigated the underlying ceRNA network involving circHIPK3 in myocardial infarction (MI). After an MI model was established, cardiac function was verified, and myocardial tissue damage in mice with MI was evaluated. A hypoxia model of cardiomyocytes was used to simulate MI in vivo, and the expression of and targeting relationships among circHIPK3, miR-93-5p, and Rac1 were verified. The apoptosis of cardiomyocyte was identified. Gain- and loss-of-functions were performed to verify the ceRNA mechanism. The MI-modeled mice showed cardiac dysfunction and enlarged infarct size. CircHIPK3 was highly expressed in mouse and cell models of MI. Silencing circHIPK3 reduced infarct size, myocardial collagen deposition, and myocardial apoptosis rate and improved cardiac function. CircHIPK3 sponged miR-93-5p, and miR-93-5p targeted Rac1. Overexpression of miR-93-5p inhibited MI-induced cardiomyocyte injury and eliminated the harmful effect of circHIPK3. CircHIPK3 acted as ceRNA to absorb miR-93-5p, thus promoting the activation of the Rac1/PI3K/AKT pathway. We highlighted that silencing circHIPK3 can upregulate miR-93-5p and then inhibit the activation of Rac1/PI3K/Akt pathway, which can improve MI-induced cardiac dysfunction.
Background
Glucocorticoids may impact the accuracy of serum cystatin C (sCysC) in reflecting renal function. We aimed to assess the effect of glucocorticoids on the performance of sCysC in detecting acute kidney injury (AKI) in critically ill patients.
Methods
A prospective observational cohort study was performed in a general intensive care unit (ICU). Using propensity score matching, we successfully matched 240 glucocorticoid users with 960 non-users among 2716 patients. Serum creatinine (SCr) and sCysC were measured for all patients at ICU admission. Patients were divided into four groups based on cumulative doses of glucocorticoids within 5 days before ICU admission (Group I: non-users; Group II: 0 mg < prednisone ≤50 mg; Group III: 50 mg < prednisone ≤150 mg; Group IV: prednisone > 150 mg). We compared the performance of sCysC for diagnosing and predicting AKI in different groups using the area under the receiver operator characteristic curve (AUC).
Results
A total of 240 patients received glucocorticoid medication within 5 days before ICU admission. Before and after matching, the differences of sCysC levels between glucocorticoid users and non-users were both significant (P < 0.001). The multiple linear regression analysis revealed that glucocorticoids were independently associated with sCysC (P < 0.001). After matching, the group I had significantly lower sCysC levels than the group III and group IV (P < 0.05), but there were no significant differences in sCysC levels within different glucocorticoids recipient groups (P > 0.05). Simultaneously, we did not find significant differences in the AUC between any two groups in the matched cohort (P > 0.05).
Conclusions
Glucocorticoids did not impact the performance of sCysC in identifying AKI in critically ill patients.
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