Treatment with doxorubicin (DOX), which is an effective anticancer agent, is limited by cardiotoxicity. CUE domain-containing 2 (CUEDC2) serves a role in numerous cellular processes. The present study aimed to elucidate the potential function of CUEDC2 in DOX-induced cardiotoxicity. Cell Counting kit-8 assay demonstrated that DOX induced cytotoxicity of H9c2 cells in a dose-dependent manner. Flow cytometry demonstrated that downregulation of CUEDC2 reduced the levels of DOX-induced reactive oxygen species. Furthermore, compared with in the DOX-treated group, the activity of superoxide dismutase was increased in the DOX + small interfering RNA (si)CUEDC2 group; whereas, the malondialdehyde content was reduced in the DOX + siCUEDC2 group. In addition, flow cytometric analysis indicated that mitochondrial membrane potential was maintained following the depletion of CUEDC2. Furthermore, CUEDC2 downregulation significantly inhibited DOX-induced apoptosis. The expression levels of proapoptotic genes, including B-cell lymphoma 2 (Bcl-2)-associated X protein, cleaved caspase-3 and cytochrome c were inhibited by the depletion of CUEDC2. Conversely, the expression levels of the anti-apoptotic gene Bcl-2 were elevated in the CUEDC2 knockdown group. Downregulation of CUEDC2 also increased phosphorylation of protein kinase B and forkhead box O3a, and decreased the expression of Bcl-2-like protein 11 according to western blot analysis. Taken together, the present study demonstrated that CUEDC2 downregulation prevented DOX-induced cardiotoxicity in H9c2 cells. Therefore, CUEDC2 may be a promising target for the prevention of DOX-induced cardiotoxicity.

Remodeling of atrial electrophysiology and structure is the primary feature of atrial fibrillation (AF). Evidence suggests that abnormalities in the expression levels of embryological cardiovascular development‑associated transcription factors, including Nkx2.5, are crucial for the development of AF. Rat atrial myocardial cells (AMCs) in culture dishes were placed in an electric field and stimulated. Transmission electron microscopy was used to observe the ultrastucture prior to and following rapid pacing. The action potential durations and effective refractory periods were measured. RT‑PCR and western blotting were performed to investigate the effect of rapid pacing on the expression levels of ion channel and nuclear proteins in AMCs. Nkx2.5 short interfering RNA (siRNA) transfection was performed. Through this in vitro rat AMC culture and rapid pacing model, it was demonstrated that rapid pacing shortened the action potential and downregulated the expression levels of L‑type calcium and potassium channels. Expression levels of Nkx2.5 and cardiac ankyrin repeat protein (CARP) were significantly upregulated by rapid pacing at the mRNA and protein levels. siRNA‑mediated Nkx2.5 silencing attenuated the rapid pacing‑induced downreglation of ion channel levels. These results suggest that the Nkx2.5/CARP signaling pathway contributes to the early electrical remodeling process of AF.

Background: Patients with acute aortic dissection type A (AADA) often have hypoxemia (partial pressure of oxygen [PaO2]/fraction of inspired oxygen [FiO2] <300 mmHg) before weaning in the intensive care unit (ICU). This study compared the efficacy of high-flow nasal cannula (HFNC) with that of conventional oxygen therapy (COT) in patients with AADA following Sun's procedure.Methods: The medical records of 87 adult patients with AADA who underwent Sun's procedure and met the inclusion criteria (PaO2/FiO2 <300 mmHg before weaning) were retrospectively analyzed. After surgery, 41 patients were treated with HFNC and 46 were treated with COT. The oxygenation level, FiO2, partial pressure of carbon dioxide, heart rate, respiratory rate, subjective discomfort, and reintubation rate were recorded. The difference in lung volume loss between the HFNC and COT groups was assessed using the radiological atelectasis score (chest radiograph) or calculated from three-dimensional (3D) reconstructed computed tomography (CT) images.Results: From day 1 to day 5 after weaning, there was no significant difference in PaO2/FiO2 between the HFNC and COT groups, although the FiO2 was significantly lower in the HFNC group than in the COT group (P < 0.05). Further studies indicated that the percentage of lung volume loss (pleural effusion and/or pulmonary atelectasis) by 3D reconstruction of CT images at 4–8 days post-operation was significantly lower in the HFNC group (P < 0.05). The subjective experience of breathing discomfort, reintubation rate, and length of stay in the ICU were significantly reduced in the HFNC group (P < 0.05). There was no significant difference in readmission to the ICU and in-hospital mortality between the two groups.Conclusions: HFNC can be used as an effective oxygen therapy for AADA patients with hypoxemia after Sun's procedure.