Rui Huang

Atherosclerosis (AS) manifests with arterial intimal injury, lipid deposition and chronic inflammation, which is a key pathogenic cause of cardio-cerebrovascular disorders. LncRNA MIR4697HG was downregulated in human advanced atherosclerotic plaques. This study probed the precise biological functions and downstream regulatory mechanisms of MIR4697HG during AS progression. MIR4697HG levels in atherosclerotic plaque tissues and normal arterial intima were measured by RT-qPCR. An injury model of human umbilical vein endothelial cells (HUVECs) was induced through treating with oxidative low-density lipoprotein (ox-LDL). MIR4697HG overexpression plasmids (pcDNA-MIR4697HG) was transfected into ox-LDL-treated HUVECs, and then cell viability, apoptosis, reactive oxygen species (ROS) level, oxidative stress marker protein malondialdehyde (MDA) level and superoxide dismutase (SOD) activity, and adhesion molecule intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels in HUVECs were determined. Moreover, the binding between MIR4697HG and fused in sarcoma (FUS) was checked with RNA pull-down assay. The interaction between FUS and annexin A5 (ANXA5) was gauged with Co-immunoprecipitation. Then MIR4697HG/FUS/ANXA5 axis mediated HUVEC functions were accessed with rescue experiments. Additionally, an AS model was established via feeding a high-fat diet for ApoE^−/− mice, and lentivirus MIR4697HG overexpression vector (Lv-MIR4697HG) was injected into AS mice followed by detection of atherosclerotic plaque area in mice. MIR4697HG was downregulated in atherosclerotic plaque tissues and HUVECs stimulated by ox-LDL. MIR4697HG overexpression attenuated ox-LDL-induced HUVEC viability inhibition, apoptosis, oxidative stress and adhesion molecule release. Moreover, MIR4697HG bound with FUS and facilitated FUS expression in HUVECs. FUS knockdown abrogated the functions of lncRNA MIR4697HG overexpression in ox-LDL induced HUVEC injury. Besides, FUS could bind with ANXA5. FUS overexpression inhibited ox-LDL induced HUVEC injury, while ANXA5 knockdown reversed these effects. Additionally, Lv-MIR4697HG reduced atherosclerotic plaque area in ApoE^−/− mice. LncRNA MIR4697HG mitigated ox-LDL-induced apoptosis, oxidative stress and adhesion molecule release in HUVECs and alleviated AS progression in mice through the FUS/ANXA5 axis. Graphical Abstract

Circular RNAs (circRNAs) have been noted to express in the brain and thus participate in various diseases related to the central nervous system. However, the potential role of circRNAs in cerebral ischemia (CI)-induced vertigo remains unknown. We initially predicted through bioinformatics analysis the poor expression of circ_0000811 related to CI. A mouse model of CI-induced vertigo was then established, which was validated by measurement of escape latency and medial vestibular nucleus (MVN) blood flow, with NeuN/Annexin counterstaining utilized to detect cell apoptosis in the MVN. An oxygen glucose deprivation (OGD)-exposed neuron-like cell model was further established for in vitro gain- and loss- of function assays, with flow cytometry performed to detect cell apoptosis. The poorly expressed circ_0000811, up-regulated miR-15b expression, and down-regulated Prkar2a expression were observed in both mice with CI-induced vertigo and OGD-exposed cells. Our data then demonstrated that circ_0000811 restoration alleviated CI-induced vertigo in mouse models, and that circ_0000811 acted as a miR-15b sponge to inhibit miR-15b expression. Prkar2a was validated as the target gene of miR-15b. Prkar2a restoration was subsequently revealed to repress OGD-induced neuronal apoptosis through JAK2/STAT1 signaling pathway inactivation. Furthermore, inactivation of the JAK2/STAT1 signaling pathway exerted an anti-apoptotic effect in OGD-induced neurons and an alleviatory effect in mice with CI-induced vertigo with Prkar2a overexpression and circ_0000811 overexpression. Taken together, our work suggests that circ_0000811 is involved in neuronal apoptosis of CI-induced vertigo and may be used as a biomarker for ameliorating CI-induced vertigo.

Parkinson’s disease (PD) is a clinically common neurodegenerative disease of the central nervous system (CNS) characterized by loss of dopamine neurons in the substantia nigra. Microglia (MG), as an innate immune cell in the CNS, are involved in a variety of immunity and inflammatory responses in the CNS. A number of studies have shown that the overactivation of MG is one of the critical pathophysiological mechanisms underlying PD. MicroRNAs (miRNAs) are considered to be an important class of gene expression regulators and are involved in a variety of physiological and pathological mechanisms, including immunity and inflammation. In addition, miRNAs can affect the progress of PD by regulating the expression of various MG genes and the polarization state of the MG. Here, we summarize recent articles and describe the important role of MG pathological polarization in the progression of PD, the diverse mechanisms responsible for how miRNAs regulate MG, and the potential therapeutic prospects of miRNAs for PD. We also propose that the regulation of miRNAs may be a novel protective approach against the pathogenesis of PD.

To investigate the application value of transcranial Doppler (TCD) in the prognosis assessment of nerve function in patients with acute cerebral infarction (ACI) after intracranial mechanical thrombectomy. A retrospective analysis was conducted. The clinical data of 43 patients with acute anterior circulation cerebral infarction who received intra-arterial mechanical thrombotomy for recanalization admitted to Taizhou Central Hospital from January 2018 to December 2019 were analyzed. The modified Rankin scale (mRS) score of patients were followed up by telephone at 3 months after surgery to evaluate the prognosis of neurologic outcome. Patients with mRS score 0-2 were enrolled in the good prognosis group, while those with a score of 3-6 were enrolled in the poor prognosis group. The gender, age, past history, underlying diseases, occluded arteries, atherosclerotic stenosis and bridging treatment, time from onset to reperfusion, blood flow dynamics under TCD at 1 day after thrombectomy, and National Institutes of Health stroke scale (NIHSS) scores before and 1, 7, and 14 days after thrombectomy were compared between the two groups. Multivariate Logistic regression analysis was used to screen the prognostic factors of nerve function at 3 months after mechanical thrombectomy in patients with ACI. The receiver operating characteristic (ROC) curve was drawn to evaluate the prognostic value for neurological function assessed by TCD. Forty-three patients were enrolled in the final analysis, with 23 patients in the good prognosis group and 20 in the poor prognosis group. The recanalization was successfully achieved in both groups without complications. However, the hemodynamics of intracranial arteries evaluated by TCD 1 day after operation in both groups still showed partial or complete occlusion, and the hemodynamics of patients in the poor prognosis group was worse than that in the good prognosis group (poor blood flow: 40.0% vs. 0%, inadequate blood flow: 30.0% vs. 17.4%, good blood flow: 30.0% vs. 82.6%), and the differences were statistically significant (all P < 0.01). Before thrombotomy, there was no significant difference in NIHSS score between the two groups. After thrombotomy, the NIHSS score of the two groups gradually decreased with the extension of time, but the NIHSS score at 14 days after operation of the poor prognosis group was still significantly higher than that of the good prognosis group (10.55±2.93 vs. 4.65±1.70, P < 0.01). Univariate analysis showed that compared with the good prognosis group, the proportion of patients with diabetes and arteriosclerosis stenosis in the poor prognosis group were significantly increased (30.0% vs. 4.3%, 45.0% vs. 17.4%, both P < 0.05), and the time from onset to reperfusion was prolonged (minutes: 385.9±96.2 vs. 294.5±95.1, P < 0.01). Multivariable Logistic regression analysis showed that the therosclerosis stenosis [odds ratio (OR) = 9.334, 95% confidence interval (95%CI) was 1.092-79.775, P = 0.041] and the reperfusion time (OR = 1.016, 95%CI was 1.006-1.027, P = 0.002) were associated with prognosis of nerve function at 3 months after mechanical thrombectomy in patients with ACI. ROC curve analysis suggested that the evaluation of intracranial hemodynamics by TCD might be able to predict the prognosis of neurological function in patients with ACI after 3 months of intracranial mechanical thrombectomy, the area under ROC curve (AUC) was 0.768 (95%CI was 0.620-0.917), the sensitivity was 65.0%, the specificity was 87.0%, the positive predictive value was 82.6%, and the negative predictive value was 70.0%. The evaluation of intracranial hemodynamics assessed by TCD is helpful in early judging the prognosis of neurological function in patients with ACI after intracranial mechanical thrombectomy.