Objective. Pirarubicin (THP) is one of anthracycline anticancer drugs. It is widely used in the treatment of various cancers, but its hepatotoxicity cannot be ignored. Schisandrin B (SchB) is a traditional liver‐protecting drug, which has the ability to promote mitochondrial function and upregulate cellular antioxidant defense mechanism. However, whether it can resist THP‐induced hepatotoxicity has not been reported. The purpose of this study was to observe and explore the effect of SchB on THP‐induced hepatotoxicity and its potential mechanism by adding SchB to the diet of rats with THP‐induced hepatotoxicity. Methods. The rat model of THP‐induced hepatotoxicity was established and partly treated with SchB diet. The changes of serum liver function indexes ALT and AST were observed. The histomorphological changes of liver were observed by HE staining. The biomarker levels of oxidative stress in rat serum and liver were measured to observe oxidative stress state. The expressions of ferroptosis‐related protein GPX4 and oxidative stress‐related protein were detected by Western blot. Primary hepatocytes were prepared and cocultured with THP, SchB, and Fer‐1 to detect the production of reactive oxygen species (ROS) and verify the above signal pathways. Results. THP rats showed a series of THP‐induced hepatotoxicity changes, such as liver function damage, oxidative stress, and ferroptosis. SchB diet effectively alleviated these adverse reactions. Further studies showed that SchB had strong antioxidant and antiferroptosis abilities in THP‐induced hepatotoxicity. Conclusion. SchB has obvious protective effect on THP‐induced hepatotoxicity. The mechanism may be closely related to inhibiting oxidative stress and ferroptosis in the liver.

Pirarubicin (THP) is one of the classic chemotherapy drugs for cancer treatment. It is often clinically limited because of its cardiotoxicity. The occurrence and development of THP-mediated chemotherapy-related cardiotoxicity (CRC) may be reversed by RING finger protein 10 (RNF10). This study was performed with the aim of evaluating the inhibitory effect of RNF10 on THP-mediated CRC and its molecular mechanism. In vivo, we found that the expression of RNF10 decreased in THP-induced CRC rats, accompanied by Meox2 inhibition and AP-1 activation, resulting in increased cardiomyocyte apoptosis. After small interfering RNA (siRNA) and lentivirus transfection (Lv) of RNF10 in vitro, the expression of RNF10, Meox2, and AP-1 proteins and the degree of cardiomyocyte apoptosis were detected. We found that overexpression of RNF10 in H9C2 cardiomyocytes significantly promoted Meox2 and inhibited AP-1, alleviated apoptosis, and showed further inhibitory activity on THP-induced cardiomyocyte toxicity. Silencing RNF10 showed the opposite result. Our study showed that RNF10 inhibited THP-induced CRC through the activity of Meox2 and AP-1 proteins. RNF10 may be the next drug target for the treatment of CRC and other related cardiovascular diseases.

Corrigendum: Schisandrin B Antagonizes Cardiotoxicity Induced by Pirarubicin by Inhibiting Mitochondrial Permeability Transition Pore (mPTP) Opening and Decreasing Cardiomyocyte Apoptosis

Background: The role of Forkhead Box D2 (FOXD2) in head and neck squamous cell carcinoma (HNSC) has never been studied. Objectives: Our object was to explore the role of FOXD2 in HNSC. Methods: Clinical data for patients with HNSC was obtained from TCGA. Our study examined the atypical expression of FOXD2 in both HNSC and pan-cancer, along with its diagnostic and prognostic implications, as well as the association between FOXD2 expression and clinical characteristics, immune infiltration, immune checkpoint genes, and MSI. Gene set enrichment analysis (GESA) was used to investigate the potential regulation network of FOXD2 in HNSC. We analyze the genomic alterations of FOXD2 in HNSC. GSE13397 and qRT-PCR were used for the validation of FOXD2 expression. Results: FOXD2 was aberrantly expressed in 24 tumors. FOXD2 was significantly up-regulated in HNSC compared to normal head and neck tissue (p < 0.001). High FOXD2 expression was associated with the histologic grade of the patient with HNSC (p < 0.001), lymphovascular infiltration (p = 0.002) and lymph node neck dissection (p = 0.002). In HNSC, an autonomous correlation between FOXD2 expression and OS was observed (HR: 1.36; 95% CI: 1.04-1.78; p = 0.026). FOXD2 was associated with the neuronal system, neuroactive ligand-receptor interaction, and retinoblastoma gene in cancer. FOXD2 was associated with immune infiltration, immune checkpoints, and MSI. The somatic mutation rate of FOXD2 in HNSC was 0.2%. FOXD2 was significantly up-regulated in HNSC cell lines. Conclusion: Our findings suggest that FOXD2 has the potential to serve as a prognostic biomarker and immunotherapeutic target for individuals with HNSC.

Introduction: ICl,stretch have been reported to be involved in the development of atrial fibrillation, so we observed the changes of transcription and translation levels of ICl,stretch in isolated atrial myocardium of heart failure canine models. Material and methods: In the control group (N = 10), five dogs were untreated and the other five received sham operation, while dogs in the heart failure group (N = 10) were implanted with cardiac pacemakers and underwent right ventricular pacing to induce heart failure. Cardiac structure and function were evaluated. The gene expression and protein level of ICl,stretch in the left atrial appendage were detected. Results: The left atrial diameter, right atrial dimension, left ventricular diastolic dimension, and right ventricular diastolic dimension were significantly larger in the heart failure group (P < 0.05). In contrast, the ejection fraction and the left ventricular shorten fraction were higher in the control group (P < 0.05). Both the mRNA and protein expression levels of ICl,stretch in atrial myocardium of the heart failure group were significantly higher compared with the control group. Conclusion: ICl,stretch might play an important role in the vulnerability to atrial fibrillation in dilated atria with heart failure and could be a potential therapeutic target for atrial fibrillation.