Although SCA6 has, so far, not been reported in mainland Chinese, we found a geographic cluster of families with SCA6 on Taiwan. Genotyping studies suggest a founder effect in the Taiwanese patients with SCA6.
It has been previously shown that inhaled zinc oxide nanoparticles (ZnO-NPs) can modulate inflammation. MicroRNAs (miRNAs) enclosed in exosomes have been identified as an important signature for inflammatory responses. However, the role of exosomal miRNAs during pathogenic inflammation has not been investigated. Healthy rats were exposed to ZnO-NPs (41.7 nm; 2, 4, and 8 mg/kg) or saline (control) via oropharyngeal aspiration. ZnO-NPs induced significant increases in the serum levels of interleukin 8 (IL-8), interleukin-1 beta (IL-1β), and tumor necrosis factor α (TNF-α), and elevated the number of cells and the percentage of neutrophils in the blood. Moreover, exposure to ZnO-NPs increased the levels of lactate dehydrogenase (LDH) activity and total protein in bronchoalveolar lavage fluid (BALF). Differential profiling of miRNAs in isolated serum exosomes revealed that 16 miRNAs were up-regulated and 7 down-regulated in ZnO-NP-treated rats compared with the controls. Functional and pathway analysis indicated that miRNAs may participate in inflammation directly and indirectly through protein and vesicle-mediated transport or regulation of IL-1, oxidative stress, apoptosis, and autophagy. These results suggest that miRNAs in serum exosomes are involved in pulmonary neutrophilic inflammation induced by ZnO-NPs.
Purpose
Circular RNAs (circRNAs) are involved in the development of diseases by regulating gene expression and become promising novel biomarkers for diseases. The aim of the present study was to identify the circulating circRNA biomarkers for early detection of type 2 diabetes (T2D).
Methods
circRNA expression profiles were screened by microarray between five new T2D cases and five healthy controls. The expression of candidate circRNAs that may be involved in the insulin PI3K/Akt signaling pathway were validated by RT-qPCR in a second sample with 30 T2D cases and 30 controls. The association between circRNAs and T2D and their clinical significances were further assessed by logistic regression model, correlation analysis and ROC curve in a large cohort composed of 313 subjects. The miRNA targets of circRNAs were verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.
Results
Low expressed circ_0063425 and hsa_circ_0056891 were independent predictors of T2D, IFG and insulin resistance. The two-circRNA panel had a high diagnostic accuracy for discriminating T2D and IFG from healthy controls, especially when body mass index (BMI) was integrated. miR-19a-3p and miR-1-3p were identified as the miRNA targets of hsa_circ_0063425 and hsa_circ_0056891, respectively. Significantly positive correlations were found between the expression levels of AKT and hsa_circ_0063425, PI3K and hsa_circ_0056891, in the total sample and subgroups stratified by glucose levels.
Conclusion
Downregulated hsa_circ_0063425 and hsa_circ_0056891 might contribute to the pathogenesis of T2D. They are valuable circulating biomarkers for early detection of T2D, which may be involved in regulation of PI3K/AKT signaling.
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