Purpose Myocardial fibrosis (MF) after acute myocardial infarction (AMI) ultimately results in heart failure, which is a serious threat to human life. This study aimed to excavate critical biomarkers associated with MF after AMI. Materials and Methods RNA-sequencing was performed to obtain differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) in AMI and MF after AMI. Results Abundant DEmRNAs, DEmiRNAs and DElncRNAs were identified in AMI and MF after AMI. The ceRNA network, which contained 9 lncRNA-miRNA pairs and 9 miRNA-mRNA pairs, was acquired. In AMI, all candidate markers generally exhibited the same pattern as that in our RNA-seq results; while in MF after AMI, except for CENPB, JAK2 and hsa-miR-197-3p, the expression of the others in the qRT-PCR results exhibited the same pattern as that in our RNA-seq results. Conclusion We speculated that LINC00664/hsa-miR-197-3p/JAK2 and GAS6-AS1/SNHG22/hsa-miR-135a-5p/CENPB/BCL9L interaction pairs may serve as potential biomarkers in MF after AMI.

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Objective: Early infantile epileptic encephalopathy (EIEE) is a group of disorders affecting children at early stages of infancy, which is characterized by frequent seizures, epileptiform activity on EEG, and developmental retardation or regression. Salt-inducible kinases (SIKs) syndrome is a newly described EIEE, caused by heterozygous mutations in the salt-inducible kinase SIK1, which can present as early myoclonic encephalopathy, Ohtahara syndrome, and infantile spasms. Methods: In this study, we investigated a patient with early onset epilepsy. DNA sequencing of the whole coding region revealed a de novel heterozygous nucleotide substitution (c.880G>A) causing a missense mutation (p.A294T). This mutation was classified as variant of unknown significance (VUS) by American College of Medical Genetics and Genomics (ACMG). To further investigate the pathogenicity and pathogenesis of this mutation, we established a human neuroblastoma cell line (SH-SY5Y) stably-expressing wild type SIK1 and A294T mutant, and compared the transcriptome and metabolomics profiles. Results: We presented a pediatric patient suffering from infantile onset epilepsy. Early EEG showed a boundary dysfunction of activity and MRI scan of the brain was normal. The patient responded well to single anti-epileptic drug treatment. Whole-exome sequencing found a missense mutation of SIK1 gene (c.880G>A chr21: 43420326 p. A294T). Dysregulated transcriptome and metabolome in cell models expressing WT and MUT SIK1 confirmed the pathogenicity of the mutation. Specifically, we found MEF2C target genes, certain epilepsy causing genes and metabolites are dysregulated by SIK1 mutation.We found MEF2C target genes, certain epilepsy causing genes and metabolites are dysregulated by SIK1 mutation. Significance: Our finding further expanded the disease spectrum and provided novel mechanistic insights of SIK1 syndrome.