Sudden cardiac death (SCD) caused by acute ischemic heart disease (IHD) is a major cause of sudden death worldwide. Circular RNAs (circRNAs) are abundant in the heart and play important roles in cardiovascular diseases, but the role of circRNAs as biomarkers in the forensic diagnosis of SCD caused by acute IHD remains poorly characterized. To investigate the potential of two heart-enriched circRNAs, circNFIX and circSLC8A1, we explored the expression of these two circRNAs in different kinds of commonly used IHD models, and further verified their expressions in forensic autopsy cases. The results from both the IHD rat and H9c2 cell models revealed that circSlc8a1 level was upregulated, while the circNfix level was elevated in the early stage of ischemia and subsequently downregulated. The time-dependent expression patterns of the two circRNAs suggested their potential as SCD biomarkers. In autopsy cases, the results showed that the expression of these two circRNAs in the myocardium with acute IHD-related SCDs corresponded to the observations in the ischemic models. Further analysis related to myocardial ischemia indicated that circSLC8A1 showed high sensitivity and specificity for myocardial infarction and was positively correlated with creatine kinase MB in pericardial fluid. Downregulated circNFIX level could indicate the ischemic myocardial damage, and it was negatively correlated with the coronary artery stenosis grade. The combination of circSLC8A1 and circNFIX had better performance to discriminate IHD-related SCDs. The results suggested that circSLC8A1 and circNFIX may be used as auxiliary diagnostic markers for SCD caused by acute IHD in forensic medicine.
Parkinson’s disease (PD) is an aging disorder related to vesicle transport dysfunctions and neurotransmitter secretion. Secretory granules (SGs) are large dense-core vesicles for the biosynthesis of neuropeptides and hormones. At present, the involvement of SGs impairment in PD remains unclear. In the current study, we found that the number of SGs in tyrosine hydroxylase-positive neurons and the marker proteins secretogranin III (Scg3) significantly decreased in the substantia nigra and striatum regions of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) exposed mice. Proteomic study of SGs purified from the dopaminergic SH-sy5Y cells under 1-methyl-4-phenylpyridinium (MPP+) treatments (ProteomeXchange PXD023937) identified 536 significantly differentially expressed proteins. The result indicated that disabled lysosome and peroxisome, lipid and energy metabolism disorders are three characteristic features. Protein-protein interaction analysis of 56 secretory proteins and 140 secreted proteins suggested that the peptide processing mediated by chromogranin/secretogranin in SGs was remarkably compromised, accompanied by decreased candidate proteins and peptides neurosecretory protein (VGF), neuropeptide Y, apolipoprotein E, and an increased level of proenkephalin. The current study provided an extensive proteinogram of SGs in PD. It is helpful to understand the molecular mechanisms in the disease.
The present HRM assay is a reliable and rapid method for genotyping R1628P and G2385R loci in LRRK2 gene, and multiplex HRM analysis results in high throughput and has the potential to facilitate a wide range of genotyping studies on PD susceptibility genes.
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