Long Noncoding RNA-H19 Contributes to Atherosclerosis and Induces Ischemic Stroke via the Upregulation of Acid Phosphatase 5

Objective: Atherosclerosis is closely associated with ischemic stroke, and long noncoding RNA-H19 (lncRNA-H19) might be a potential target for treating atherosclerosis. The present study aimed to investigate the function of lncRNA-H19 in atherosclerosis and to explore a novel therapeutic strategy for ischemic stroke.Methods: Differentially expressed genes (DEGs) in atherosclerosis were screened by searching public database. In combination with the lncRNA-H19-knockout database, potential lncRNA-H19-mediated gene was retrieved and their relationship was identified. In order to assess the detailed regulatory mechanism of lncRNA-H19, we used a lentivirus packaging system to upregulate Acp5 (Acid phosphatase 5) expression in vascular smooth muscle cells (VSMC) and human umbilical vein endothelial cells (HUVECs). The expression of ACP5 was determined by Western Blot, and evaluations of cell proliferation and apoptosis were detected. An ischemic stroke mouse model was established. Atherosclerosis was measured by using plaque area size. The effects H19 on the expression of ACP5 were explored by the overexpression or silence of H19.Results: H19 and ACP5 were associated with Acute Stroke Treatment (TOAST) subtypes of atherosclerotic patients. The target prediction program and dual-luciferase reporter confirmed ACP5 as a direct target of H19. Lentivirus-mediated H19-forced expression upregulated ACP5 protein levels, promoted cell proliferation and suppressed the apoptosis. The plaque area size was larger in ischemic models than controls. The overexpression or silence of H19 increased or reduced the plaque size. The overexpression or silence of H19 resulted in the expression or inhibition of ACP5.Conclusion: IncRNA-H19 promoting ACP5 protein expression contributed to atherosclerosis and increased the risk of ischemic stroke

Neuroprotective effect of arctigenin via upregulation of P-CREB in mouse primary neurons and human SH-SY5Y neuroblastoma cells.

Arctigenin (Arc) has been shown to act on scopolamine-induced memory deficit mice and to provide a neuroprotective effect on cultured cortical neurons from glutamate-induced neurodegeneration through mechanisms not completely defined. Here, we investigated the neuroprotective effect of Arc on H89-induced cell damage and its potential mechanisms in mouse cortical neurons and human SH-SY5Y neuroblastoma cells. We found that Arc prevented cell viability loss induced by H89 in human SH-SY5Y cells. Moreover, Arc reduced intracellular beta amyloid (Aβ) production induced by H89 in neurons and human SH-SY5Y cells, and Arc also inhibited the presenilin 1(PS1) protein level in neurons. In addition, neural apoptosis in both types of cells, inhibition of neurite outgrowth in human SH-SY5Y cells and reduction of synaptic marker synaptophysin (SYN) expression in neurons were also observed after H89 exposure. All these effects induced by H89 were markedly reversed by Arc treatment. Arc also significantly attenuated downregulation of the phosphorylation of CREB (p-CREB) induced by H89, which may contribute to the neuroprotective effects of Arc. These results demonstrated that Arc exerted the ability to protect neurons and SH-SY5Y cells against H89-induced cell injury via upregulation of p-CREB

Center volume and the outcomes of percutaneous transluminal angioplasty and stenting in patients with symptomatic intracranial vertebrobasilar stenoses: A meta-analysis

<div><p>Background</p><p>Evidence for the preventative effects of percutaneous transluminal angioplasty and stenting (PTAS) on the recurrence of stroke in patients with severe intracranial vertebrobasilar stenoses (IVBS) varies, and the influence of study characteristics on the study outcomes have not been determined.</p><p>Methods</p><p>A study level based meta-analysis was performed to investigate the influence of baseline characteristics on the 30-day and follow-up stroke recurrence or death in symptomatic IVBS patients receiving PTAS. Relevant single center studies were retrieved by searching PubMed and Embase. A random effect model was applied to synthesize the outcomes. Meta-regression and subgroup analyses were performed to evaluate the potential influence of study characteristics on outcomes.</p><p>Results</p><p>Fifteen cohort studies comprising 554 symptomatic IVBS patients were included. PTAS was associated with an 8% incidence of stroke recurrence or death (95% CI: 5% to 12%) in IVBS patients within 30 days, and 8 per 100 person-years (95% CI: 5 to 11 per 100 person-years) of cumulative stroke recurrence or death during follow-up. Meta-regression indicated that the center volume, as defined by the numbers of cases per year, was negatively correlated with 30-day (regression coefficient = -0.09, p = 0.02) and follow-up (regression coefficient = -0.60, p = 0.01) stroke recurrence or death. Age, gender, or comorbidities have no significant effect on the outcomes.</p><p>Conclusions</p><p>Centers of higher procedural volume may be associated with better clinical outcomes for symptomatic IVBS patients receiving PTAS.</p></div

Influence of center volume on the risks of stroke recurrence or mortality in symptomatic IVBS patients after PTAS.

<p>A, correlation of center volume with the incidence of stroke recurrence and death within 30 days after PTAS; B, correlation of center volume with the incidence of stroke recurrence and death during follow-up (per person year).</p

Impact of study characteristics on the outcomes stroke recurrence or death within 30 days after PTAS or during clinical follow-up.

<p>Impact of study characteristics on the outcomes stroke recurrence or death within 30 days after PTAS or during clinical follow-up.</p

Baseline characteristics of included studies.

<p>Baseline characteristics of included studies.</p

The forest plots of the meta-analysis of incidences of combined outcome of stroke recurrence and death in symptomatic IVBS patients after PTAS.

<p>A, forest plot for the incidence of combined outcome of stroke recurrence and death within 30 days after PTAS; forest plot for the incidence of combined outcome of stroke recurrence and death during follow-up (per person year).</p

Meta-analysis reveals protective effects of vitamin B on stroke patients

Stroke is the loss of brain function due to a disturbance in the blood supply to the brain resulting from either ischemia or hemorrhage. Previous studies have evaluated the clinical importance of nutritional interventions such as vitamin B supplementation in the management of acute strokes. However, it is still inconclusive whether or not vitamin B supplementation will benefit patients with acute strokes. Therefore, a meta-analysis was performed to assess the efficacy of vitamin B supplementation in the treatment of stroke patients. Medline, Embase, Scopus, and Cochrane Library databases were searched (from 1960 to June 2015) and forest plots were generated to illustrate the treatment effects. A systemic review of the electronic databases yielded 12 eligible studies consisting of 7474 patients. Forest plots from the meta-analyses of the included studies illustrated that vitamin B supplementation significantly lowered the plasma concentration of total homocysteine (SMD = -0.82; 95% CI: -0.77; Z = -29.06, p < 0.0001) and resulted in significant reduction in stroke recurrence (OR = 0.86%; 95% CI: 0.76, 0.97; Z = -2.41; p = 0.016) as well as a combined incidence of vascular events, including recurrent strokes, myocardial infarctions and vascular deaths (OR = 0.87%; 95% CI: 0.79, 0.96; Z= -2.73; p = 0.0063). Additionally, the nearly-symmetrical funnel plot (Egger’s test, t = −1.705, p = 0.1224) indicated the absence of publication bias regarding the meta-analysis that examined the effect of vitamin B supplementation on the plasma levels of homocysteine in acute stroke patients. These findings suggested that vitamin B supplementation presents a potential addition to the armamentarium for the management of acute stroke patients

Primary medullary hemorrhage in a patient with coagulopathy due to alcoholic cirrhosis: a case report

Mild-to-moderate alcoholic cirrhosis of the liver is related to spontaneous intracerebral hemorrhage (ICH). In terms of spontaneous brainstem hemorrhage, pontine is considered as the most common site in contrast to medulla oblongata where the hemorrhage is rarely seen. This rare primary medullary hemorrhage has been attributed so far to vascular malformation (VM), anticoagulants, hypertension, hemorrhagic transformation, and other undetermined factors.Herein, we describe a 53-year-old patient with 35-year history of alcohol abuse was admitted for acute-onset isolated hemianesthesia on the right side. He was normotensive on admission. A neurological examination revealed isolated hemihypoaesthesia on the right side. He had no history of hypertension, and viral hepatitis, and nil use of anticoagulants.Brain computed tomography (CT) image demonstrated hemorrhagic lesion in dorsal and medial medulla oblongata which was ruptured into the fourth ventricle. Brain magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA) demonstrated no evidence of VM. The laboratory tests implied liver dysfunction, thrombocytopenia, and coagulation disorders. Abdominal ultrasound, and CT image showed a small, and nodular liver with splenomegaly, suggestive of moderate alcoholic cirrhosis.Liver protection therapy and the management of coagulation disorders.After 14 days, he was discharged with mild hemianesthesia but with more improved parameters in laboratory tests. At the 6-month follow-up, brain MRI, MRA, and non-contrast MRI showed no significant findings except for a malacic lesion.We conclude that the patient had alcoholic cirrhosis with coagulopathy, and this may have resulted in primary medullary hemorrhage. This is a first case to report alcoholic cirrhosis as etiology of primary medullary hemorrhage