A mounting body of evidence has suggested that long noncoding RNAs (lncRNAs) play critical roles in human diseases by acting as competing endogenous RNAs (ceRNAs). However, the functions and ceRNA mechanisms of lncRNAs in atrial fibrillation (AF) remain to date unclear. In this study, we constructed an AF‐related lncRNA‐mRNA network (AFLMN) based on ceRNA theory, by integrating probe reannotation pipeline and microRNA (miRNA)‐target regulatory interactions. Two lncRNAs with central topological properties in the AFLMN were first obtained. By using bidirectional hierarchical clustering, we identified two modules containing four lncRNAs, which were significantly enriched in many known pathways of AF. To elucidate the ceRNA interactions in certain disease or normal condition, the dysregulated lncRNA‐mRNA crosstalks in AF were further analyzed, and six hub lncRNAs were obtained from the network. Furthermore, random walk analysis of the AFLMN suggested that lncRNA RP11‐296O14.3 may function importantly in the pathological process of AF. All these eight lncRNAs that were identified from previous steps (RP11‐363E7.4, GAS5, RP11‐410L14.2, HAGLR, RP11‐421L21.3, RP11‐111K18.2, HOTAIRM1, and RP11‐296O14.3) exhibited a strong diagnostic power for AF. The results of our study provide new insights into the functional roles and regulatory mechanisms of lncRNAs in AF, and facilitate the discovery of novel diagnostic biomarkers or therapeutic targets.

Coronavirus disease 2019 (COVID-19) is a recently emerged disease with formidable infectivity and high mortality. Emerging data suggest that diabetes is one of the most prevalent comorbidities in patients with COVID-19. Although their causal relationship has not yet been investigated, preexisting diabetes can be considered as a risk factor for the adverse outcomes of COVID-19. Proinflammatory state, attenuation of the innate immune response, possibly increased level of ACE2, along with vascular dysfunction, and prothrombotic state in people with diabetes probably contribute to higher susceptibility for SARS-CoV-2 infection and worsened prognosis. On the other hand, activated inflammation, islet damage induced by virus infection, and treatment with glucocorticoids could, in turn, result in impaired glucose regulation in people with diabetes, thus working as an amplification loop to aggravate the disease. Therefore, glycemic management in people with COVID-19, especially in those with severe illness, is of considerable importance. The insights may help to reduce the fatality in the effort against COVID-19.

Doxorubicin (DOX) is an effective anticancer agent. Its clinical use is, however, limited due to its detrimental side effects, especially the cardiotoxicity caused by ROS, mitochondrial dysfunction and apoptosis. 3’,4’-dihydroxyflavonol (DiOHF) is a recently developed potent synthetic flavonoid which has been reported to exert anti-oxidative activity in myocardial ischemia–reperfusion injury and maintain the normal mitochondrial function. The aim of this study was to explore the protective effects of DiOHF on the DOX-induced cardiotoxicity. We established DOX-induced cardiotoxicity in H9C2 cells by incubation with 1 μM DOX and in BALB/c mice by DOX injection. DiOHF effectively prevented and reversed the DOX-induced cardiotoxicity, including ROS production, mitochondrial dysfunction, and apoptosis. The DOX-induced cardiotoxicity was accompanied by ERK1/2 activation and abolished by the silence of ERK1, rather than ERK2. Furthermore, DOX treatment in mice induced an increase in serum CK-MB level and myocardial fibrosis with a reduction in left ventricular (LV) function. These detrimental effects were blunted by DiOHF administration. Conclusion: DiOHF suppresses and reverses the DOX-induced cardiotoxicity by inhibiting ROS release, stabilizing mitochondrial function and reducing apoptosis through activation of the ERK1 signaling.

Objective: Kawasaki disease (KD) is a childhood febrile vasculitis with unknown etiology. Epigenetic regulation in the gene expression dynamics has become increasingly important in KD. Thus, we performed an integrated analysis of DNA methylation and gene expression data to identify novel molecular mechanisms and key functional genes in KD. Methods: DNA methylation (GSE84624) and gene expression (GSE68004) datasets were downloaded from Gene Expression Omnibus. Methylateddifferentially expressed genes (mDEGs) were documented as the overlapping genes between the differentially methylated genes (DMGs) in GSE84624 and differentially expressed genes (DEGs) in GSE68004. Functional enrichment analyses of the mDEGs were conducted using DAVID database. Protein-protein interaction (PPI) network was then constructed to obtain the hub genes involved in KD using STRING database.Results: A total of 1389 DMGs and 1362 DEGs were screened out between KD and control samples. Overlapping of them resulted in four hypermethylated/ downregulated and 187 hypomethylated/upregulated genes. These mDEGs were mainly enriched in inflammation response, innate immune response, and blood coagulation, and signaling pathways such as platelet activation, osteoclast differentiation, and chemokine signaling pathway. PPI network analyses identified MAPK14 and PHLPP1 as the hub genes involved in KD, which could distinguish KD from other common pediatric febrile diseases. In addition, the methylation and expression levels of MAPK14 and PHLPP1 were validated in other independent datasets. Conclusion:This study provides an integrated view of interactions among DNA methylation and gene expression in patients with KD. MAPK14 and PHLPP1 are the key genes influenced by methylation and may serve as candidate biomarkers for KD.

Heart failure (HF) remains a common complication after acute ST‐segment elevation myocardial infarction (STEMI). Here, we aim to identify critical genes related to the developed HF in patients with STEMI using bioinformatics analysis. The microarray data of GSE59867, including peripheral blood samples from nine patients with post‐infarct HF and eight patients without post‐infarct HF, were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between HF and non‐HF groups were screened by LIMMA package. Functional enrichment analyses of DEGs were conducted, followed by construction of a protein‐protein interaction (PPI) network. The dynamic messenger RNA (mRNA) level of the hub genes during the follow‐up was analyzed to further elucidate their role in HF development. A total of 58 upregulated and 75 downregulated DEGs were screen out. They were mainly enriched in biological processes about inflammatory response, extracellular matrix organization, response to cAMP, immune response, and positive regulation of cytosolic calcium ion concentration. Pathway analysis revealed that the DEGs were also involved in hematopoietic cell lineage, pathways in cancer, and extracellular matrix‐receptor interaction. In the PPI network consisting of 58 nodes and 72 interactions, CXCL8 (degree = 15), THBS1 (degree = 8), FOS (degree = 7), and ITGA2B (degree = 6) were identified as the hub genes. In the comparison of patients with and without post‐infarct HF, the mRNA level of these hub genes were all higher within 30 days but reached similar at 6 months after STEMI. In conclusion, CXCL8, THBS1, FOS, and ITGA2B may play important roles in the development of HF after acute STEMI.