Glycine Improves Ischemic Stroke Through miR-19a-3p/AMPK/GSK-3?/HO-1 Pathway.
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ABSTRACT:
SUBMITTER: Chen Z
PROVIDER: S-EPMC7260540 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Project description:Blood circulating microRNAs (c-miRs) are potential biomarkers to trace aging and longevity trajectories to identify molecular targets for anti-aging therapies. Based on a cross-sectional study, a discovery phase was performed on 12 donors divided into four groups: young, old, healthy, and unhealthy centenarians. The identification of healthy and unhealthy phenotype was based on cognitive performance and capabilities to perform daily activities. Small RNA sequencing identified 79 differentially expressed c-miRs when comparing young, old, healthy centenarians, and unhealthy centenarians. Two miRs, that is, miR-19a-3p and miR-19b-3p, were found increased at old age but decreased at extreme age, as confirmed by RT-qPCR in 49 donors of validation phase. The significant decrease of those miR levels in healthy compared to unhealthy centenarians appears to be due to the presence of isomiRs, not detectable with RT-qPCR, but only with a high-resolution technique such as deep sequencing. Bioinformatically, three main common targets of miR-19a/b-3p were identified, that is, SMAD4, PTEN, and BCL2L11, converging into the FoxO signaling pathway, known to have a significant role in aging mechanisms. For the first time, this study shows the age-related increase of plasma miR-19a/b-3p in old subjects but a decrease in centenarians. This decrease is more pronounced in healthy centenarians and was confirmed by the modified pattern of isomiRs comparing healthy and unhealthy centenarians. Thus, our study paves the way for functional studies using c-miRs and isomiRs as additional parameter to track the onset of aging and age-related diseases using new potential biomarkers.
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Project description:BACKGROUND MicroRNAs (miRNAs) are attracting substantial interest as promising noninvasive biomarkers for gastric cancer (GC). Our study aimed to identify circulating miRNAs that are potential noninvasive markers for precancerous lesions and early gastric cancers (EGCs). MATERIAL AND METHODS Plasma specimens were obtained from 58 gastritis subjects, 54 patients with precancerous lesions, and 38 EGC patients for study. RESULTS Significant differences in the plasma expression levels of miR-19a-3p, miR-22-3p, miR-146a-5p, and miR-483-5p (all P<0.05) were observed between EGC patients and gastritis subjects. Multivariable analysis showed that age (OR, 1.054; 95% CI, 1.006-1.104), miR-19a-3p expression (OR, 3.676; 95% CI, 1.914-7.061), and miR-483-5p expression (OR, 1.589; 95% CI, 1.242-2.033) were independently associated with EGCs and precancerous lesions. A combined diagnostic model incorporating these 3 variables for the prediction of EGCs and precancerous lesions was derived. The area under the receiver operating characteristic curve (AUC) of the model was 0.84; the sensitivity was 87.7% and the specificity was 62.8% at the cutoff value of -0.08. CONCLUSIONS Plasma miR-19a-3p and miR-483-5p are promising and powerful noninvasive markers for the early detection of GC. Patients are more willing to undergo noninvasive diagnostic procedures than gastroscopy for cancer screening, economizing limited medical resources.
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