miR-181a targets PTEN to mediate the neuronal injury caused by oxygen-glucose deprivation and reoxygenation.

Evidence suggests that the microRNA-181 (miR-181) family performs various roles in the pathophysiology of cerebral ischemia and reperfusion injury (CIRI). MiR-181a has been identified as a critical determinant of neuronal survival. Moreover, the significance of miR-181a in controlling neuronal death after CIRI has received little attention. The objective of this study was to assess the role of miR-181a in neuronal cell injury after CIRI. To mimic the in-vitro and in-vivo CIRI, we developed an oxygen-glucose deficiency/reoxygenation (OGD/R) model in SH-SY5Y cells and a transient middle cerebral artery occlusion model in rats. MiR-181a expression was significantly higher in both in-vivo and in-vitro CIRI models. The overexpression of miR-181a increased cell damage and oxidative stress caused by OGD/R, whereas inhibition of miR-181a reduced both. PTEN has also been found to be a direct miR-181a target. PTEN overexpression reduced cell apoptosis and oxidative stress induced by miR-181a upregulation under an OGD/R condition. Furthermore, we found that the rs322931 A allele was related to increased miR-181a levels in IS peripheral blood and higher susceptibility to IS. The current results offer new insights into the understanding of the molecular pathophysiology of CIRI, as well as possible new treatment candidates.

Direct targeting of DOCK4 by miRNA-181d in oxygen-glucose deprivation/reoxygenation-mediated neuronal injury.

The miRNA-181 (miR-181) family regulates neuronal persistence during cerebral ischemia/reperfusion injury (CI/RI). Since the effect of miR-181d on CI/RI has never been studied, the current work sought to determine the involvement of miR-181d in neuronal apoptosis after brain I/R injury. To replicate in vivo and in vitro CI/RI, a transient middle cerebral artery occlusion (tMCAO) model in rats and an oxygen-glucose deficiency/reoxygenation (OGD/R) model in neuro 2A cells were developed. In both in vivo and in vitro stroke models, the expression of miR-181d was considerably higher. miR-181d suppression reduced apoptosis and oxidative stress in OGD/R-treated neuroblastoma cells, but miR-181d overexpression increased both. Furthermore, it was observed that miR-181d has a direct target in dedicator of cytokinesis 4 (DOCK4). The overexpression of DOCK4 partially overcame cell apoptosis and oxidative stress induced by miR-181d upregulation and OGD/R injury. Furthermore, the DOCK4 rs2074130 mutation was related to lower DOCK4 levels in ischemic stroke (IS) peripheral blood and higher susceptibility to IS. These findings suggest that downregulating miR-181d protects neurons from ischemic damage by targeting DOCK4, implying that the miR-181d/DOCK4 axis might be a novel therapeutic target for IS.

Genetic Variants of lncRNA GAS5 Contribute to Susceptibility of Ischemic Stroke among Southern Chinese Population.

Emerging evidence suggests that the long noncoding RNA (lncRNA) growth arrest special 5 (GAS5) plays crucial roles in the pathogenesis of ischemic stroke (IS). The current research is aimed at assessing the correlation between two functional GAS5 variants (rs145204276 and rs55829688) and susceptibility to IS in a Han Chinese population. This study genotyped the two GAS5 variants in 1086 IS patients as well as 1045 age-matched healthy controls by using an improved multitemperature ligase detection reaction (iMLDR-TM) genotyping technology. We observed a considerable change in the frequencies of the rs145204276 allele and genotype among the IS patients and healthy control group. The del-T haplotype was substantially more prevalent in the IS cases compared to the control individuals. When study participants were stratified according to environmental factors, we found that the rs145204276 del allele was correlated with a higher risk of IS in male, smokers, hypertensive, and those ≥65 years old. Additional stratification conforming to IS subtypes exhibited that individuals carrying the rs145204276 del allele conferred a higher risk of expanding a larger artery atherosclerosis stroke subset. Moreover, there was a significant association between the rs145204276 del allele and elevated expression of GAS5 in IS patients. In contrast, the frequency of the allele related to rs55829688 was not statistically correlated with IS in all analysis. Our study supports a model wherein the rs145204276 variant in the GAS5 lncRNA is associated with IS risk, thus representing a potentially viable biomarker for IS prevention and treatment.

Incremental diagnostic value of shear wave elastography combined with contrast-enhanced ultrasound in TI-RADS category 4a and 4b nodules.

PURPOSE: To evaluate the diagnostic value of shear wave elastography (SWE) combined with contrast-enhanced ultrasonography (CEUS) in diagnosing thyroid imaging reporting and data system (TI-RADS) category 4a and 4b nodules. METHODS: TI-RADS, SWE, and CEUS features of 71 thyroid nodules (23 benign, 48 malignant) confirmed by postoperative pathological results were retrospectively analyzed. The diagnostic efficiency of each single method and that of a combination of three methods were compared. RESULTS: The sensitivity and specificity in diagnosing thyroid nodules were 70.83% and 65.22% for TI-RADS, 68.75% and 91.30% for SWE, 77.08% and 78.26% for CEUS, and 91.67% and 95.65% for TI-RADS + SWE + CEUS, respectively. The area under the curve for TI-RADS, SWE, CEUS, and TI-RADS + SWE + CEUS in diagnosing thyroid nodules were 0.680, 0.839, 0.799, and 0.937, respectively. A significant difference was observed between a combination of the three methods and any of them alone (p < 0.05). CONCLUSION: Combining SWE and CEUS improves the differential diagnosis of TI-RADS category 4a and 4b nodules.