Up-regulation of lncRNA WT1-AS ameliorates Aß-stimulated neuronal injury through modulation of miR-186-5p/CCND2 axis in Alzheimer's disease.

As a common neurodegenerative disorder, Alzheimer's disease (AD) seriously threatens human life. Long non-coding RNAs (lncRNAs) exhibit essential functions in AD development. Nevertheless, the detailed effects and possible mechanisms of lncRNA Wilms tumor 1 Antisense RNA (WT1-AS) in AD are largely unknown. In our studies, a total of 30 serum samples from AD patients were collected, and WT1-AS expressions were detected through qRT-PCR analysis. Additionally, an in vitro AD model was constructed by treating Aß1-42 in human neuroblastoma cells. Functional assays were implemented to assess the impacts of WT1-AS on Aß1-42-stimulated human neuroblastoma cell proliferation together with apoptosis. Moreover, relationship of WT1-AS, microRNA (miR)-186-5p as well as cyclin D2 (CCND2) could be predicted through bioinformatics tools as well as proved via dual-luciferase reporter experiments. Our results showed that WT1-AS together with CCND2 were low-expressed, while miR-186-5p presented high expression in AD serum samples together with Aß1-42-stimulated human neuroblastoma cells. WT1-AS over-expression or miR-186-5p depletion notably promoted the proliferation, reduced the apoptosis, and decreased the p-Tau protein expressions of human neuroblastoma cells induced with Aß1-42. Moreover, miR-186-5p combined with WT1-AS, and CCND2 was modulated by miR-186-5p. Furthermore, CCND2 elevation partially offsets the impacts of miR-186-5p elevation on Aß1-42-stimulated cell proliferation as well as apoptosis mediated with WT1-AS up-regulation. Our results indicated that up-regulation of lncRNA WT1-AS ameliorated Aß-stimulated neuronal damage through modulating miR-186-5p/CCND2 axis, offering a novel direction for AD therapy.

Tenecteplase thrombolysis for stroke up to 24 hours after onset with perfusion imaging selection: the umbrella phase IIa CHABLIS-T randomised clinical trial.

BACKGROUND: The performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the promise of efficacy and safety of different doses of tenecteplase manufactured in China, in patients who had an acute ischaemic stroke with large/medium vessel occlusion beyond 4.5-hour time window. METHODS: The CHinese Acute tissue-Based imaging selection for Lysis In Stroke-Tenecteplase was an investigator-initiated, umbrella phase IIa, open-label, blinded-endpoint, Simon's two-stage randomised clinical trial in 13 centres across mainland China. Participants who had salvageable brain tissue on automated perfusion imaging and presented within 4.5-24 hours from time of last seen well were randomised to receive 0.25 mg/kg tenecteplase or 0.32 mg/kg tenecteplase, both with a bolus infusion over 5-10 s. The primary outcome was proportion of patients with promise of efficacy and safety defined as reaching major reperfusion without symptomatic intracranial haemorrhage at 24-48 hours after thrombolysis. Assessors were blinded to treatment allocation. All participants who received tenecteplase were included in the analysis. RESULTS: A total of 86 patients who had an acute ischaemic stroke identified with anterior large/medium vessel occlusion or severe stenosis were included in this study from November 2019 to December 2021. All of the 86 patients enrolled either received 0.25 mg/kg (n=43) or 0.32 mg/kg (n=43) tenecteplase, and were available for primary outcome analysis. Fourteen out of 43 patients in the 0.25 mg/kg tenecteplase group and 10 out of 43 patients in the 0.32 mg/kg tenecteplase group reached the primary outcome, providing promise of efficacy and safety for both doses based on Simon's two-stage design. DISCUSSION: Among patients with anterior large/medium vessel occlusion and significant penumbral mismatch presented within 4.5-24 hours from time of last seen well, tenecteplase 0.25 mg/kg and 0.32 mg/kg both provided sufficient promise of efficacy and safety. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04086147, https://clinicaltrials.gov/ct2/show/NCT04086147).

Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Ischemic Stroke Within 4.5 Hours of Stroke Onset: A Phase 3 Randomized Clinical Trial.

Importance: Recombinant human prourokinase (rhPro-UK) is a thrombolytic agent that has shown promising findings in a phase 2 clinical trial in patients with acute ischemic stroke (AIS). Objective: To evaluate the efficacy and safety of rhPro-UK thrombolysis within 4.5 hours of symptom onset in patients with AIS. Design, Setting, and Participants: This randomized, alteplase-controlled, open-label, phase 3 clinical trial was conducted from May 2018 to May 2020 at 35 medical centers in China. A total of 684 patients were screened and 674 patients were enrolled. Included patients were aged 18 to 80 years with a diagnosis of AIS and received treatment within 4.5 hours of stroke onset. Data were analyzed from June to October 2020. Interventions: Eligible patients were randomly assigned (1:1) to receive intravenous rhPro-UK or alteplase. Main Outcomes and Measures: The primary objective was to assess whether rhPro-UK was noninferior to alteplase. The noninferiority margin was a between-group difference of less than 10%. The primary outcome was a modified Rankin Scale score of 0 to 1 at 90 days. Results: Among 663 patients in the modified intention-to-treat population (mean [SD] age, 61.00 [10.20] years; 161 females [24.3%]), there were 330 patients in the rhPro-UK group and 333 patients in the alteplase group. The median (IQR) baseline National Institutes of Health Stroke Scale score was 6.00 (5.00-9.00). There were 23 deaths, and 619 patients (93.4%) completed the 3-month follow-up. The primary outcome occurred in 215 patients (65.2%) in the rhPro-UK group and 214 patients (64.3%) in the alteplase group (risk difference, 0.89; 95.4% CI, -6.52 to 8.29). Symptomatic intracerebral hemorrhage occurred in 5 patients (1.5%) in the rhPro-UK group and 6 patients (1.8%) in the alteplase group (P > .99). Systemic bleeding within 90 days occurred more frequently in the alteplase group (141 patients [42.2%]) than the rhPro-UK group (85 patients [25.8%]) (P < .001). By 90 days, 5 thrombolysis-related deaths each had occurred in the rhPro-UK group (1.5%) and alteplase group (1.5%) (P > .99). Conclusions and Relevance: This study found that intravenous rhPro-UK within 4.5 hours of AIS onset was noninferior to alteplase. The rhPro-UK group showed a similar rate of symptomatic ICH but fewer cases of systemic bleeding than the alteplase group. Trial Registration: ClinicalTrials.gov Identifier: NCT03541668.

Plasma Lipoprotein-Associated Phospholipase A2 Affects Cognitive Impairment in Patients with Cerebral Microbleeds.

Purpose: The plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker of cerebral microbleeds (CMBs) and may be related to the occurrence, development, and prognosis of cognitive impairment. The present study aimed to investigate the impact of plasma Lp-PLA2 level on the cognitive impairment in patients with CMBs. Methods: In this study, 213 patients with CMBs confirmed by 3.0 T brain magnetic resonance imaging (MRI) were analyzed. Lp-PLA2 levels were determined by magnetic particle chemiluminescence immunoassay technology, and cognitive function was assessed using the Montreal Cognitive Assessment Scale (MoCA). The cognitive functions of patients with CMBs were divided into three groups according to the MoCA scale, including normal cognition (NC), mild cognitive impairment (MCI), and moderate-severe cognitive impairment (MSCI). Clinical, laboratory and radiological data of the three groups were analysed. The relationship between plasma Lp-PLA2 and MoCA score in patients with CMBs was investigated through rank correlation analysis and multivariate regression analysis, and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of Lp-PLA2. Results: CMBs were detected in 213 (30.2%) of 705 patients who underwent 3.0 T MRI. Multiple comparisons showed that plasma Lp-PLA2 in patients with CMBs with normal cognitive scores was significantly lower than that in the other two groups with cognitive impairment (p < 0.05). In the single factor correlation analysis, high level of plasma Lp-PLA2 was negatively correlated with the decrease of MoCA score in patients with CMBs (r =-0.389, p < 0.01). Multivariate regression analysis showed that high plasma Lp-PLA2 was an independent risk factor for a low MoCA score in patients with CMBs (odds ratio [OR]=1.014; 95% confidence interval [CI], 1.002-1.026; p=0.025). Conclusion: A high level of plasma Lp-PLA2 is positively correlated with the generation of cognitive impairment in patients with CMBs and negatively correlated with the degree of impairment. Plasma Lp-PLA2 is an important indicator of cognitive impairment in patients with CMBs and may provide a therapeutic target for preventing CMB-induced cognitive impairment.

Correlation of lipoprotein-associated phospholipase A2 and cerebral microbleeds in patients with acute ischaemic stroke.

BACKGROUND AND AIMS: Cerebral microbleeds (CMBs) increase the risk of stroke occurrence and recurrence,and affect the prognosis of stroke patients. Therefore, identifying biological markers that predict CMBs after stroke is urgently needed. This study explored whether high levels of lipoprotein-associated phospholipase A2(Lp-PLA2) are associated with an increased risk of CMBs in patients with acute ischaemic stroke (AIS). METHODS: From April 2020 to October 2021, we enrolled 242 patients with AIS. At admission, the plasma levels of Lp-PLA2 were measured in all patients as well as the number of CMBs and white matter lesions. According to the results of the Susceptibility Weighted Imaging (SWI), the patients were divided into a CMB group and a no-CMB group. The groups were compared with univariate and multivariate analyses to clarify the correlation between Lp-PLA2 levels and CMBs, and the optimal cut-off value of Lp-PLA2 that predicted CMBs was determined from the receiver-operating characteristic curve. RESULTS: CMBs were detected in 71 (29.3%) of the 242 AIS patients. The median Lp-PLA2 level was 182.79 ng/ml. Using the 1st quartile of Lp-PLA2 levels (the lowest levels) as the reference group, univariate logistic regression analysis showed that individuals in the 4th quartile (the highest levels) had a higher risk of CMBs (odds ratio [OR] = 1.460, 95% confidence interval [CI]: 1.188-1.795, P = 0.000). This correlation persisted after adjusting for relevant risk factors (OR = 1.370, 95% CI: 1.096-1.713, P = 0.006). The optimal cut-off value of Lp-PLA2 that predicted the occurrence of CMBs was 184.36 ng/ml; at this threshold, the sensitivity was 69.0%, and the specificity was 60.2%. CONCLUSIONS: Our data suggest that a high level of Lp-PLA2 in patients with AIS is a potential risk factor for CMBs.

Efficacy of Guhong injection versus Butylphthalide and Sodium Chloride Injection for mild ischemic stroke: A multicenter controlled study.

BACKGROUND: Most studies on Guhong injection have involved a single center with a small sample size, and the level of clinical evidence is low. AIM: To assess the safety and efficacy of Guhong injection for mild ischemic stroke (IS). METHODS: A total of 399 IS patients treated at six hospitals from August 2018 to August 2019 were retrospectively analyzed. The patients were given Guhong injection (experimental group) or Butylphthalide and Sodium Chloride Injection (control group). Changes in National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were observed before treatment and at 1, 2, and 3 wk after treatment in each group. The efficacy and safety of Guhong injection for IS were assessed. Other medications taken by the patients were confounding factors for efficacy assessment. These factors were controlled by propensity score matching, and the results were further analyzed based on the matching. RESULTS: The marked response rates at three follow-up visits were 64.64%, 74.7%, and 66.7% in the experimental group, and 48.26%, 45.4%, and 22.2% in the control group. The marked response rates increased significantly in the experimental group compared with the control group (P < 0.05). The overall response rate at the first visit (days 7 ± 2) did not differ significantly between the two groups, but differed significantly at the second (days 14 ± 2) and third visits (days 21 ± 3) (P < 0.05). The proportion of patients without any symptoms in the experimental group was significant different at the first visit (P < 0.05), but not significantly different at the second visit. The two groups showed no significant difference in the baseline distribution of mRS scores. At the first and second visits, the change in mRS scores was -2 and -1 in the experimental and control groups, respectively, which were significantly different (P < 0.05). After propensity score matching, the overall response rate and marked response rate were 97.29% and 100% in the experimental group (P > 0.05) and 64.0% and 47.7% in the control group (P < 0.05) at the first visit, respectively. The decreased NIHSS scores in the two groups were significant different (P < 0.05). The overall response rate and marked response rate differed significantly between the two groups at the second visit (P < 0.05). There was no significant difference in the incidence of adverse events between the two groups. No severe adverse events occurred in either group. CONCLUSION: Guhong injection is safe and more effective than Butylphthalide and Sodium Chloride Injection for treatment of IS.

The Relationship Between APOE Gene Polymorphism and In-stent Restenosis After Stenting at the Beginning of the Vertebral Artery.

OBJECTIVE: To retrospectively investigate the relationship between apolipoprotein E (APOE) gene polymorphism and in-stent restenosis (ISR) after stenting at the beginning of the vertebral artery. METHODS: The study included 155 patients who successfully underwent stenting at the beginning of the vertebral artery and had postoperative digital subtraction angiography or computed tomography angiography. Based on the follow-up results, they were divided into the restenosis (ISR) group and non-restenosis (non-ISR) group. The clinical information and APOE genotypes of both groups were analyzed. A binary logistic regression model was used to analyze independent risk factors for ISR. RESULTS: After 1 year of follow-up, 49 (31.6%) patients had ISR and 106 (68.4%) did not. Binary logistic regression analysis showed that serum low-density lipoprotein cholesterol (LDL-C), serum lipoprotein-related phospholipase A2 (Lp-PLA2), and E3/E4 genotype were independent risk factors for ISR after stenting at the beginning of the vertebral artery. In addition, the LDL-C level of patients with the E3/E4 genotype was higher compared with the E3/E3 genotype group (P < 0.05). CONCLUSIONS: APOE gene polymorphism is associated with ISR, and the E3/E4 genotype is an independent risk factor for ISR after stenting at the beginning of the vertebral artery. Further genetic studies can identify risk genotypes to facilitate the early prediction and identification of high-risk patients with ISR.

miR-190a-3p Promotes Proliferation and Migration in Glioma Cells via YOD1.

INTRODUCTION: To investigate the function of miR-190a-3p on the proliferation and migration of glioma. METHODS: Twenty glioma samples and 6 normal brain tissue samples were collected. Normal human glial cell line HEB and glioma cell lines were used for the experiments. We then used TargetScan to predict the target genes of miR-190a-3p. Dual-luciferase reporter assay was also used to validate. RESULTS: Combined with dual-luciferase reporter experiment, we finally verified that YOD1 was the aim, and it was low-expressed in glioma. Besides, a series of mechanism experiments then proved that miR-190a-3p negatively regulates YOD1 expression. CONCLUSIONS: Our research was the first to demonstrate the promoting function of miR-190a-3p in the proliferation and migration of glioma and provided new views for the treatment of glioma. miR-190a-3p was expected to be a new target for molecular therapy of glioma.

High plasma levels of trimethylamine N-oxide are associated with poor outcome in intracerebral hemorrhage patients.

BACKGROUND AND AIMS: As a gut microbiota-dependent metabolite, trimethylamine N-oxide (TMAO) has been implicated in cardiovascular diseases. We aimed to investigate the relationship between the clinical outcomes and plasma TMAO concentrations in patients with acute intracerebral hemorrhage. METHODS: From January 2019 to October 2019, we prospectively enrolled intracerebral hemorrhage patients diagnosed within 6 h of symptoms onset. Plasma TMAO levels was measured for all patients within 24 h after admission. The primary outcome was functional outcome at 3 months. Patients were dichotomized as good (modified Rankin scale 0-3) and poor (modified Rankin scale 4-6). Secondary outcome included early neurological deterioration (END) and hematoma enlargement (HE). RESULTS: There were 307 patients (57.7% male) with a mean age of 66.8 years included in the study. The median TMAO levels was 3.2 µmol/L. END, HE, and 3-month poor outcome were detected in 59 (19.2%), 54 (17.6%), and 139 (45.3%) patients, respectively. After adjusting for potential confounders, the odds ratio for the highest quartile of TMAO compared with the lowest quartile was 3.65 (95% confidence interval, 1.43-9.30) for 3-month poor outcome. Furthermore, multiple-adjusted spline regression model showed a linear association between TMAO levels and poor outcome at 3 months (P = 0.013 for linearity). Similar significant findings were observed when functional outcome was analyzed by continuous mRS score. No association was found between TMAO levels and END and HE. CONCLUSIONS: The present study demonstrated that increased TMAO levels were independently correlated with 3-month function outcome after intracerebral hemorrhage.

Prognostic Value of Plasma Trimethylamine N-Oxide Levels in Patients with Acute Ischemic Stroke.

Trimethylamine N-oxide (TMAO) has emerged as a newly identified gut microbiota-dependent metabolite contributing to a variety of diseases, such as diabetes, atherosclerosis, and cardiovascular diseases. The aim of our study was to determine whether a relatively high TMAO level is associated with an increased risk of poor outcome in ischemic stroke patients. From June 2018 to December 2018, we prospectively recruited acute ischemic stroke patients diagnosed within 24 h of symptom onset. The plasma TMAO level was measured at admission for all patients. Functional outcome was evaluated at 3 months after the stroke using the modified Rankin Scale (mRS) and then dichotomized as favorable (mRS 0-2) or unfavorable (mRS 3-6). A multivariate logistic regression analysis was conducted to evaluate the association between TMAO concentration and poor functional outcome and mortality at 3 months. Of the 225 acute ischemic stroke patients included in the analysis, the median TMAO concentration was 3.8 µM (interquartile range, 1.9-4.8 µM). At 3 months after admission, poor functional outcome was observed in 116 patients (51.6%), and 51 patients had died (22.7%). After adjusting for potential confounders, patients with TMAO levels in the highest quartile were more likely to have higher risks of poor functional outcome [compared with the lowest quartile, odds ratio (OR) 3.63; 95% confidence interval (CI) 1.34-9.82; P = 0.011] and mortality (OR 4.27; 95% CI 1.07-17.07; P = 0.040). Our data suggest that a high plasma TMAO level upon admission may predict unfavorable clinical outcomes in acute ischemic stroke patients.

The Impacts of Peptic Ulcer on Functional Outcomes of Ischemic Stroke.

BACKGROUND AND PURPOSE: Studies have shown that peptic ulcer increased the risk of ischemic stroke and stroke recurrence. This study aimed to evaluate the impacts of peptic ulcer on functional outcomes of ischemic stroke. METHODS: Patients with first-ever ischemic stroke were grouped as with and without history of peptic ulcer. Functional outcomes were evaluated with modified Rankin scale at 90 days after the index stroke. Favorable functional outcomes were defined as with a modified Rankin scale score of 0-2. Logistic regression was used to identify predictors for favorable functional outcomes at 90 days. RESULTS: Among the 2577 enrolled patients with ischemic stroke, 129 (5.0%) had a history of peptic ulcer. The proportion of favorable outcome was higher in patients without peptic ulcer than those with (59.3% versus 42.6%, P < .001). Multivariate logistic analysis detected that history of peptic ulcer (odds ratio [OR] = 2.89, 95% confidence interval [CI], 1.03-8.10, P = .043), National Institute of Health Stroke Scale score (OR = 2.11, 95% CI, 1.79-2.48, P < .001), and large-artery atherosclerosis stroke subtype (OR = 4.08, 95% CI, 1.11-15.03, P = .035) decreased the likelihood of favorable outcomes. CONCLUSIONS: Ischemic stroke patients with peptic ulcer may have an increased risk of less favorable neurological outcome at 90 days after the index stroke.

Role of plasminogen activator inhibitor-1 in the diagnosis and prognosis of patients with Parkinson's disease.

Parkinson's disease is a neurodegenerative disease that frequently results in memory disorders, cognitive decline and dementia. Previous studies have reported that plasminogen activator inhibitor-1 (PAI-1) serves an important role in cardiovascular disease risk, adiposity, insulin resistance and inflammation. However, the role of PAI-1 in diagnosis and prognosis of patients with Parkinson's disease following deep brain stimulation (DBS) has not reported, to the best of our knowledge. Therefore, the purpose of the present study was to investigate the clinical significance of PAI-1 in patients with Parkinson's disease. Plasma PAI-1 levels were measured in 102 patients with Parkinson's disease who underwent DBS. It was demonstrated that plasma PAI-1 levels were significantly increased in patients with Parkinson's disease compared with healthy individuals (P<0.01). Patients with Parkinson's disease received DBS presented significantly improved cognitive competence compared with controls (P<0.01). DBS significantly decreased plasma PAI-1 levels in patients with Parkinson's disease compared with controls (P<0.05). It was also observed that plasma PAI-1 levels were significantly negatively associated with cognitive function for patients with Parkinson's disease (P<0.01). In conclusion, these findings demonstrated that the degree of Parkinson's disease severity is positively associated with circulating levels of plasma PAI-1 levels, which suggests that PAI-1 may be a potential diagnostic and prognostic marker for patients with Parkinson's disease.

2-(2-benzofuranyl)-2-imidazoline (2-BFI) improved the impairments in AD rat models by inhibiting oxidative stress, inflammation and apoptosis.

Alzheimer's Disease (AD) is one of the commonest neural degeneration in aging population, and has become a global health challenge. 2-(2-benzofuranyl)-2-imidazoline (2-BFI) was reported to effectively improved the damage of patients with neuropathological disorders. In the present study, we investigated the effect of 2-BFI on the improvement of antioxidative, inflammation, and apoptosis in AD rats. Sprague-Dawley rats (2 months old, n=40) were used in this study and after injection of Aß1-42 into hippocampal CA1 (Cornu Ammonis) region, the rats were given high, moderate and low dose of 2-BFI though intraperitoneal (i.p.) injection. Then spatial memory and navigation ability were analyzed by Morrize Water Maze. For the molecular testing, chemical colorimetry, ELISA and immunoblotting were performed to measure the activities of antioxidative enzymes, the abundance of immune cytokines and expression of apoptotic proteins, respectively. Hematoxylin and Eosin staining was used to analyze the pathological changes. We observed that 2-BFI significantly ameliorated the learning and memory abilities in rat models with AD by dosage treatment, as demonstrated by the shorten learning latency and greater times of travel across the platform quadrant. Additionally, reactive oxygen species (ROS) and malondialdehyde (MDA), were decreased after treatment of 2-BFI with dosage dependency, while the activities of superoxidase dismutase (SOD) and (GPX) Glutathione peroxidase were in turn enhanced, suggesting that 2-BFI could protect the antioxidative enzymes and reduce the oxidative stress in the hippocampus. Moreover, the expression of inflammatory factors including TNF-a and IL-1ß were decreased after 2-BFI treatment. Additionally, the neuronal apoptosis was also attenuated, as shown by Western blot results. Taken together, the cognitive impairment in AD rats could be significantly improved by 2-BFI in a dose-dependent manner through suppressing oxidants accumulation, inhibiting of inflammatory response, as well as enhancing the neural viability.

Execution time determines the outcome of the multicenter randomized controlled trials.

OBJECTIVES: Multicenter randomized controlled trials are the core of evidence-based medicine. Our study aimed to investigate the key factor which determined the outcome of the multicenter randomized controlled trials. METHODS: We searched publications in PubMed for multicenter randomized controlled trials reporting primary data on treating and preventing cardiovascular diseases circulation area. The data were extracted from the including trials and used for analysis. RESULTS: A total of 1075 trials for treating and preventing cardiovascular diseases were included, of which 979 were involved in the heart diseases and 96 involved in stroke. The execution time significantly contributed to the outcome of trials with shorter time related to significant outcome. However, the numbers of participated centers and their locations and participants had no effect on the outcome of trials. Moreover, the number of centers showed no significant relationship with execution time. CONCLUSIONS: Execution time but not centers or participants contributed to the outcome of multicenter randomized controlled trials.

Mesenchymal stem cells protect neurons against hypoxic-ischemic injury via inhibiting parthanatos, necroptosis, and apoptosis, but not autophagy.

Cellular therapy with mesenchymal stem cells (MSCs) protects cortical neurons against hypoxic-ischemic injury of stroke. Although sorts of efforts have been made to confirm the neuroprotective effect of MSCs on neurons against hypoxic-ischemic injury, the mechanism is until now far away from clear. Here in this study, oxygen-glucose deprivation (OGD)-injured neuron model was applied to mimic the neuronal hypoxic-ischemic injury in vitro. Co-culturing with MSCs in a transwell co-culture system, the OGD injured neurons were rescued by 75.0 %. Further data demonstrated that co-culturing with MSCs protected the cortical neurons from the OGD-induced parthanatos by alleviating apoptosis-inducing factor (AIF) nuclear translocation; attenuated the neuronal necroptosis by down-regulating the expression of the two essential kinases in necroptosis, receptor interacting protein kinase1 (RIP1) and 3 (RIP3); rescued the neurons from apoptosis by deactivating caspase-3; whilst performed no significant influence on OGD-induced neuronal autophagy, according to its failed regulation on Beclin1. In conclusion, MSCs potentially protect the cortical neurons from OGD-injury in vitro, through rescuing neurons from the cell death of parthanatos, necroptosis, and apoptosis, but not autophagy, which could provide some evidence to the mechanism explanation on stem cell treatment for ischemic stroke.

Association of GWAS-Supported Variants rs556621 on Chromosome 6p21.1 with Large Artery Atherosclerotic Stroke in a Southern Chinese Han Population.

Recent genome-wide association study associated rs556621 on chromosome 6p21.1 with the risk of large artery atherosclerotic (LAA) stroke in Caucasians. However, subsequent replicate studies showed conflict results in different ethnicities. This study aimed to evaluate whether rs556621 was associated with LAA stroke in Chinese Han population. In this case-control study, 659 patients with LAA stroke and 650 healthy controls were enrolled. Associations between rs556621 genotypes and LAA stroke were analyzed with logistic regression model. Rs556621 variants were associated with increased risks of LAA stroke (codominant model: OR 1.42; 95 % CI 1.01-1.99; P = 0.010; recessive model: OR 1.40; 95 % CI 1.05-1.86; P = 0.003). When subjects were stratified by sex, TT genotype of SNP rs556621 was associated with an increased risk of LAA stroke in female when tested with recessive model (OR 2.36; 95 % CI 1.28-4.36, P = 0.006). In male subjects, however, no significant association was detected. Smoking status, sex did not significantly influence the relationship between genotypes of rs556621 and risk of LAA stroke (P interaction = 0.140, P interaction = 0.076). Rs556621 may play an important role in the development of LAA stroke in female Chinese of Han ethnicity. Larger studies with subjects of different ethnicities are warranted to confirm these findings.