Regulatory Mechanism of MicroRNA-30b on Neonatal Hypoxic-Ischemic Encephalopathy (HIE)

ObjectiveThis study is to investigate the role of microRNA (miR)-30b in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonates.MethodsTotally 26 cases of neonatal HIE were included in this study. The protein expression levels of CD26P and PAI-1 were detected with ELISA. Serum levels of miR-30b and PAI-1 mRNA was measured by quantitative real-time PCR. Human brain microvascular endothelial cells (HBMECs) were cultured under hypoxic condition, and the intracellular expression levels of miR-30b and PAI-1 were evaluated. Dual-luciferase reporter assay was performed to confirm the interaction between miR-30b and PAI-1.ResultsCompared with the control group, both the mRNA and protein expression levels of PAI-1 in the serum were up-regulated in the neonates with HIE, together with up-regulated serum CD26P levels. However, the serum expression level of miR-30b was down-regulated in neonatal HIE. In hypoxia-induced HBMECs, the mRNA and protein expression levels of PAI-1 were significantly up-regulated, while the miR-30b expression level was significantly down-regulated. Dual-luciferase reporter assay showed that PAI-1 was the direct target of miR-30b.ConclusionNeonatal HIE is accompanied with abnormal platelet activation, significantly up-regulated serum PAI-1 expression levels, and down-regulated miR-30b expression. MiR-30b might regulate the disease pathogenesis and immune responses via modulating PAI-1.     

Dynamic changes in miR-124 levels in patients with acute cerebral infarction

Objective: To investigate the changes in serum miR-124 levels in patients with acute cerebral infarction (ACI) and elucidate the underlying mechanism by a dynamic monitor.

Methods: Fifty-four patients with ACI and 51 healthy controls were included in our study. Baseline characteristics and blood samples were collected for further analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the serum miR-124 levels. The dual-luciferase reporter assay was used to evaluate the effect of miR-124 on iASPP, a protein that inhibits apoptosis stimulating proteins in the p53 family.

Results: Compared with normal controls, the miR-124 levels in the ACI group rapidly decreased at phase 1 (within 24?h after ischemia) (p?<?0.001) and then gradually increased at phase 2 (48?～?72?h after ischemia) (p?<?0.001) and phase 3 (the 7th day after ischemia) (p?<?0.001). The dual-luciferase reporter assay showed that miR-124 down-regulates iASPP expression in 293T cells.

Conclusion: The miR-124 levels are down-regulated in ACI patients. The dynamic changes of miR-124 might provide a possible method for the detection of ischemic stroke.

• Highlights

• The difference in miR-124 expression levels between ACI patients and normal controls.

• Dynamic changes of miR-124 expression levels in ACI patients.

• The down-regulation of miR-124 upon iASPP expression.

     

脑梗死患者血清miR-497,TNF-α表达水平变化及其临床意义

目的 探讨急性脑梗死(Acute cerebral infarction,ACI)患者血清微小RNA-497(MicroRNA-497,miR-497)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)的表达水平变化及其临床意义。方法 选取2016年1月-2019年11月本院收治的96例ACI患者,称ACI组,并选取本院同期98例体检健康者,称对照组; 采用实时荧光定量PCR(Real-time fluorescent quantitative PCR,qRT-PCR)法检测所有研究对象血清miR-497表达水平; 采用酶联免疫吸附法(Enzyme-linked immunosorbent assay,ELISA)检测所有研究对象血清肿瘤坏死因子-α水平; 评估ACI患者神经功能缺损程度、计算脑梗死体积,比较不同神经功能缺损程度/脑梗死体积的ACI患者血清miR-497、TNF-α水平; Pearson法分析ACI患者血清miR-497、TNF-α水平与神经功能缺损程度评分(National institutes of health stroke scale,NIHSS)、脑梗死体积的关系; 采用受试者工作特征曲线(Receiver operating characteristic curve,ROC)评价血清miR-497、TNF-α对ACI的诊断价值。结果 ACI组血清miR-497、TNF-α水平均明显高于对照组(P<0.05); ACI患者血清miR-497、TNF-α水平随神经功能缺损程度加重、脑梗死体积增加均呈递增趋势(P均<0.05); ACI患者血清miR-497、TNF-α水平与脑梗死体积、NIHSS评分均呈正相关(r=0.423,0.514,0.542,0.399,P均<0.05); 血清miR-497、TNF-α对ACI诊断的曲线下面积(Area under curve,AUC)为0.848、0.806,截断值分别为1.29、1.27,相应灵敏度分别为82.3%、81.3%,特异度分别为76.5%、77.6%; 两者联合诊断ACI的AUC为0.907,其灵敏度、特异度分别为81.3%、90.8%。结论 miR-497、TNF-α在ACI患者血清中表达均上调,且与神经功能缺损程度、脑梗死体积有关,均可能在ACI进展中起一定作用,两者联合可有效提高ACI的诊断效能,有助于诊断、评估ACI患者的病情。     

A preliminary analysis of association between the down-regulation of microRNA-181b expression and symptomatology improvement in schizophrenia patients before and after antipsychotic treatment

Despite the growing evidences on the relation of altered expression of miRNAs and schizophrenia, most schizophrenia subjects have an extensive antipsychotic treatment history and the pharmacological effects on miRNA expression are largely unknown. This study aimed to investigate the change of plasma microRNA-181b level and improvement of symptomatology before and after six-week antipsychotic treatment in schizophrenia patients, and explore their association. A total of 20 schizophrenia patients absent of antipsychotics and 20 age-and gender-matched normal controls were enrolled, and tested for 9 schizophrenia-associated microRNA (miR-30e, miR-34a, miR-181b, miR-195, miR-346, miR-432, miR-7, miR-132 and miR-212) expression levels in plasma using quantitative RT-PCR and for symptomatology improvement using Positive And Negative Syndrome Scale (PANSS) before and after treatment (olanzapine, quetiapine, ziprasidone and risperidone) for the patients only. Compared with the normal control group, the expression levels of miRNA-181b, miRNA-30e, miRNA-34a and miRNA-7 of the patients group were significantly higher (p < 0.05). Compared with those before treatment in the patient group, the symptomatology scores were significantly lower (p < 0.001), and the expression level of microRNA-181b was significantly down-regulated after treatment (p < 0.05). The change of miRNA-181b expression was positively correlated with the improvement of negative symptoms and lack of response symptoms (r = 0.502 and 0.557, P < 0.05, accounting for 20.2% and 26.4% respectively), and their therapeutic effects with OR being 11.283 and 5.119 respectively. We conclude that miRNA-181b, miRNA-30e, miRNA-34a and miRNA-7 are probably involved in pathogenesis of SZ, and the significant down-regulation of miRNA-181b expression predicts improvement of negative symptoms to treatment, and thus can serve as a potential plasmamolecular marker for antipsychotic responses.     

MicroRNA-29b is a therapeutic target in cerebral ischemia associated with aquaporin 4

MicroRNA-29b (miR-29b) is involved in regulating ischemia process, but the molecular mechanism is unclear. In this work, we explored the function of miR-29b in cerebral ischemia. The level of miR-29b in white blood cells was evaluated in patients and mice after ischemic stroke. Brain infarct volume and National Institute of Health stroke scale (NIHSS) scores were analyzed to determine the relationship between miR-29b expression and the severity of stroke. The relationship of miR-29b and aquaporin-4 (AQP4) was further studied in mice. We found that miR-29b was significantly downregulated in stroke patients (P<0.05). MiR-29b level negatively associated with NIHSS scores (r=−0.349, P<0.01) and brain infarct volume (r=−0.321, P<0.05). In ischemic mice, miR-29b in the brain and blood were both downregulated (r=0.723, P<0.05). MiR-29b overexpression reduced infarct volume (49.50±6.55 versus 35.48±2.28 mm³, P<0.05), edema (164±4% versus 108±4%, P<0.05), and blood–brain barrier (BBB) disruption compared with controls (15±9% versus 7±3%, P<0.05). Aquaporin-4 expression greatly decreased after miR-29b overexpression (28±7% versus 11±3%, P<0.05). Dual-luciferase reporter system showed that AQP-4 was the direct target of miR-29b (P<0.05). We concluded that miR-29b could potentially predict stroke outcomes as a novel circulating biomarker, and miR-29b overexpression reduced BBB disruption after ischemic stroke via downregulating AQP-4.     

血浆miR-424,FGF2水平与急性缺血性脑卒中患者血管介入术后出血转化的相关性分析

目的 探讨血浆微小RNA-424(MicroRNA,miR-424)、成纤维细胞生长因子2(Fibroblast growth factor 2,FGF2)水平与急性缺血性脑卒中(Acute ischemic stroke,AIS)患者血管介入术后出血转化(Hemorrhagic transformation,HT)的相关性。方法 选取2018年12月-2020年3月本院收治的AIS患者104例为研究对象,均行脑部血管机械取栓,根据术后患者头颅计算机X线断层扫描(Computed tomography,CT)复查表现将其分为HT组28例,非HT组76例,收集患者一般资料及入院时美国国立卫生研究院卒中量表(National institutes of health stroke scale,NIHSS)评分,采集患者术前及术后血浆样本,利用荧光定量聚合酶链反应(Polymerase chain reaction,PCR)技术检测血浆miR-424,FGF2 mRNA水平; Pearson法分析AIS发生HT患者血浆miR-424,FGF2水平的相关性; 利用多因素Logistic回归分析AIS患者血管介入术后HT的危险因素; 利用受试者工作特征曲线(Receiver operator characteristic curve,ROC)评价血浆miR-424,FGF2水平对AIS患者血管介入术后HT的预测价值。结果 HT组入院时NIHSS评分高于非HT组(P<0.05)。与非HT组相比较,术前HT组患者miR-424水平呈低表达(P<0.05),FGF2 mRNA水平呈高表达(P<0.05); 与术前比较,术后HT组和非HT组血浆miR-424水平均升高,且HT组低于非HT组; FGF2 mRNA水平均降低,且HT组高于非HT组(P均<0.05)。HT组血浆miR-424与FGF2水平呈负相关(r=-0.629,P<0.05)。多因素Logistic回归分析显示,入院NIHSS评分高、miR-424水平低、FGF2水平高是AIS患者血管介入术后HT的独立危险因素(P<0.05)。ROC显示,术前血浆miR-424,FGF2水平预测AIS患者发生HT的曲线下面积(Area of the under curve,AUC)分别为0.796、0.820,二者联合预测的AUC为0.905,敏感性和特异性分别为71.43%、94.74%。结论 血管介入术后发生HT的AIS患者血浆miR-424水平低、FGF2水平高,对AIS患者术后HT有一定的预测价值,有助于预后评估。     

急性脑梗死患者循环miR-124表达水平与脑梗死体积、神经功能缺损程度的关系及其诊断价值

目的 观察急性脑梗死(ACI)患者循环miR-124表达水平的变化及其与脑梗死体积和神经功能缺损程度的关系和其诊断价值。方法 选择ACI患者90例为观察组,另选取同期体检健康者40例作为对照组; 按梗死体积将ACI患者分为3个亚组:小梗死组(<5 cm³,n=38),中梗死组(5～10 cm³,n=31),大梗死组(>10 cm³,n=21); 根据美国国立卫生研究院卒中量表(NIHSS)评分,将ACI患者分为3个亚组:轻度组(≤6分,n=30)、中度组(7～14分,n=34)、重度组(≥15分,n=26)。通过定量逆转录聚合酶链反应(qRT-PCR)检测循环miR-124相对表达水平; 分析miR-124表达水平与脑梗死体积、神经功能缺损严重程度的关系。结果 观察组miR-124相对表达水平(2.93±1.21)明显高于对照组(1.09±0.55)(t=10.198,P<0.01); 不同脑梗死体积3个亚组间miR-124相对表达水平比较有明显差异(F=20.963,P<0.01),即脑梗死体积越大,miR-124相对表达水平越低; 相关性分析显示,miR-124相对表达水平与梗死体积呈负相关(r=-0.564,P<0.01); 不同NIHSS评分3个亚组间miR-124相对表达水平比较无明显差异(F=1.170,P>0.05)。结论 ACI患者循环miR-124水平明显升高,且其水平与脑梗死体积密切相关。     

Altered calmodulin degradation and signaling in non-neuronal cells from Alzheimer's disease patients

Previous work indicated that changes in Ca(2+)/calmodulin (CaM) signaling pathway are involved in the control of proliferation and survival of immortalized lymphocytes from Alzheimer's disease (AD) patients. We examined the regulation of cellular CaM levels in AD lymphoblasts. An elevated CaM content in AD cells was found when compared with control cells from age-matched individuals. We did not find significant differences in the expression of the three genes that encode CaM: CALM1, 2, 3, by real time RT-PCR. However, we observed that the half-life of CaM was higher in lymphoblasts from AD than in control cells, suggesting that degradation of CaM is impaired in AD lymphoblasts. The rate of CaM degradation was found to be dependent on cellular Ca(2+) and ROS levels. CaM degradation occurs mainly via the ubiquitin-proteasome system. Increased levels of CaM were associated with overactivation of PI3K/Akt and CaMKII. Our results suggest that increased levels of CaM synergize with serum to overactivate PI3K/Akt in AD cells by direct binding of CaM to the regulatory α-subunit (p85) of PI3K. The systemic failure of CaM degradation, and thus of Ca(2+)/CaM-dependent signaling pathways, may be important in the etiopathogenesis of AD.     

急性缺血性脑卒中患者血清miR-103,miR-29b的表达水平变化及其临床意义

目的 探讨急性缺血性脑卒中(AIS)患者血清miR-103,miR-29b的表达水平变化及其临床意义。方法 收集2016年1月-2019年12月本院神经内科收治的126例AIS患者(AIS组),根据美国国立卫生研究院卒中量表(NIHSS)评分将其分为轻度组(45例)、中度组(57例)和重度组(24例),根据改良Rankin量表(mRS)评分将其分为预后良好组(78例)和预后不良组(48例),另选择56例同期于本院门诊体检健康者为对照组,检测血清miR-103,miR-29b表达水平,Spearman秩相关性分析miR-103,miR-29b表达水平与NIHSS,mRS评分的相关性,受试者工作特征曲线(ROC)分析miR-103,miR-29b表达水平对神经功能预后的预测价值。结果 AIS组血清miR-103表达水平高于对照组(P<0.05),miR-29b表达水平低于对照组(P<0.05),血清miR-103表达水平随着AIS患者神经缺损程度加重而升高(P<0.05),miR-29b表达水平则降低(P<0.05)。预后不良组血清miR-103表达水平高于预后良好组(P<0.05),miR-29b表达水平低于预后良好组(P<0.05)。Spearman秩相关性分析显示AIS患者血清miR-103表达水平与NIHSS评分、mRS评分呈正相关(r₂=0.636、0.794,P<0.05),miR-29b表达水平与NIHSS评分、mRS评分呈负相关(r₂=-0.664、-0.659,P<0.05)。ROC分析显示miR-103,miR-29b表达水平预测AIS患者神经功能预后的曲线下面积(AUC)为0.713、0.741,联合miR-103,miR-29b表达水平预测AIS患者神经功能预后的AUC为0.918,高于单独miR-103,miR-29b表达水平(P<0.05)。结论 AIS患者血清miR-103表达水平升高,miR-29b表达水平降低,miR-103表达上调、miR-29b表达缺失均与AIS患者神经功能缺损程度和神经功能恶化有关,可以为患者神经功能预后评估提供参考。     

Circulating miR-126 and miR-130a levels correlate with lower disease risk,disease severity,and reduced inflammatory cytokine levels in acute ischemic stroke patients

To investigate the correlations of five angiogenesis-related miRNA (miR-126, miR-130a, miR-222, miR-218, and miR-185) expression levels with risk, severity, and inflammatory cytokines levels in acute ischemic stroke (AIS) patients. A total of 148 AIS patients and 148 age- and gender-matched controls were consecutively enrolled. Blood samples were collected from AIS patients and controls, and plasma was separated for miRNAs and cytokine level detection. Plasma levels of miRNAs were evaluated by real-time qPCR method, and inflammatory cytokine levels were detected using an enzyme-linked immunosorbent assay (ELISA). Plasma miR-126 and miR-130a expression levels in AIS patients were lower than those of controls, while the levels of miR-222, miR-218, and miR-185 were elevated in AIS patients compared with controls. After pooling the five miRNA expression levels together, the area under the curve (AUC) for predicting AIS risk was 0.840 (95% CI 0.795–0.885) with a sensitivity of 83.8% and a specificity of 69.6% at the best cut-off point. Plasma miR-126 (r?=???0.402, P?<?0.001) and miR-130a (r?=???0.161, P?=?0.050) levels were negatively correlated with NIHSS scores, while plasma miR-218 level was positively correlated with NIHSS scores (r?=?0.471, P?<?0.001). Most importantly, plasma miR-126 expression was negatively correlated with TNF-α (r?=???0.168, P?=?0.041), IL-1β (r?=???0.246, P?=?0.003), and IL-6 (r?=???0.147, P?=?0.035) levels, while miR-130a expression was negatively correlated with TNF-α (r?=???0.287, P?<?0.001), IL-1β (r?=???0.168, P?=?0.041), and IL-6 (r?=???0.239, P?=?0.003) expression levels and positively associated with IL-10 level (r?=?0.261, P?=?0.001). Circulating miR-126 and miR-130a levels correlate with lower disease risk, decreased disease severity, and reduced inflammatory cytokine levels in AIS patients.     

血浆和肽素水平对急性脑梗死患者预后的评估价值

目的 探讨血浆和肽素水平对急性脑梗死患者预后的评估价值.方法 对60例急性脑梗死患者(急性脑梗死组)和60例健康体检者(正常对照组)进行血浆和肽素水平检测;并对急性脑梗死患者进行血压、血糖、血清超敏C反应蛋白(hs-CRP)水平检测,应用美国国立卫生研究院卒中量表(NIHSS)进行评分,应用MRI测量脑梗死体积,3个月后采用改良的Rankin量表(mRS)评分评价预后;分析血浆和肽素水平对急性脑梗死患者预后的影响.结果 急性脑梗死组血浆和肽素水平[( 3.73±0.49) ng/ml]明显高于正常对照组[ (2.85±0.24) ng/ml](P＜0.01);脑梗死预后不良亚组(42例)[(3.84±0.44) ng/ml]明显高于预后良好亚组(18例)[ (3.47±0.53) ng/ml] (P＜0.05);两亚组间年龄、血糖、血清hs-CPR水平、NIHSS评分、脑梗死体积的差异有统计学意义(P ＜0.05 ～0.01);单因素Logistic回归分析显示,血浆和肽素水平、年龄、NIHSS评分是影响急性脑梗死患者预后的因素(P ＜0.05 ～0.01).ROC分析显示,影响急性脑梗死患者预后的因素中,血浆和肽素水平与年龄、hs-CRP水平、脑梗死体积、NIHSS评分间差异无统计学意义.结论血浆和肽素水平升高是预测急性脑梗死患者预后不良的因素之一.     

Serum microRNA-133b is associated with low ceruloplasmin levels in Parkinson's disease

IntroductionThe cause of low serum ceruloplasmin levels in Parkinson's disease (PD) remains to be clarified. In this study, we explored serum miR-133b expression to determine whether it correlates with serum ceruloplasmin level in PD patients.MethodsForty-six patients with PD and forty-six control subjects were evaluated for miR-133b expression using qRT-PCR. The serum ceruloplasmin levels in all of the subjects were also determined.ResultsSerum miR-133b expression levels were significantly decreased in PD patients compared with those in the control subjects. Furthermore, PD patients with low serum ceruloplasmin levels also exhibited significantly lower expression of miR-133b compared with that of patients with normal ceruloplasmin levels. MiR-133b expression was correlated with the ceruloplasmin level in patients with PD, whereas no correlation was found between miR-133b and disease severity or motor phenotype.ConclusionOur observations suggest that miR-133b might be involved in ceruloplasmin dysmetabolism in PD patients and a further investigation is warranted to confirm this hypothesis.     

急性动脉粥样硬化性脑梗死患者外周血CD137的表达特点及其临床意义

目的探讨急性动脉粥样硬化性脑梗死(atherosclerotic cerebral infarction,ACI)患者外周血肿瘤坏死因子受体超家族(tumor necrosis factor receptor super family,TNFRSF)成员CD137的表达特点及其临床意义。方法入选发病72h以内住院患者共46例,其中ACI组27例,无症状性颈动脉狭窄(asymptomatic carotid stenosis,ACS)组19例,另选择同期健康体检者20名为正常对照组(normal control,NC)。采用流式细胞术和流式细胞磁珠微阵列法(CBA)检测各组观察对象外周血CD4~+T细胞及其CD4~+CD28-T细胞亚群表面CD137的表达和血浆可溶性CD137水平。结果 ACI组外周血CD4~+CD28-T细胞比例[(14.13±4.42)%]、CD4~+CD28-T细胞CD137的表达[(2.60±2.14)%]、血浆sCD137[(3.43±2.48)pg/mL]水平显著高于ACS组[(9.03±4.60)%、(0.70±0.66)%、(2.07±0.814)pg/mL]和NC组[(8.08±3.30)%、(0.45±0.31)%、(1.26±0.70)pg/mL](P0.01),且ACI组CD4~+T细胞的CD137表达及血浆sCD137水平与NIHSS评分(P0.05)和梗死体积(P0.01)呈正相关。结论 ACI患者发病早期CD4~+CD28-T细胞、CD4~+T细胞及其CD4~+CD28-T细胞表面CD137、血浆sCD137水平升高,且CD4~+T细胞的CD137表达及血浆sCD137水平与NIHSS评分呈正相关,提示其可能作为评估脑梗死临床严重程度的外周生物学标志。     

The role of high high-sensitivity C-reactive protein levels at admission on poor prognosis after acute ischemic stroke

Objective: Plasma high hypersensitive C-reactive protein (hs-CRP) levels are associated with risk and prognosis of vascular diseases. The clinical implications of markedly elevated hs-CRP levels are more discovered in the onset and development of stroke. The aim of this study is to determine the association of plasma hs-CRP levels on the prognosis in patients with acute ischemic stroke.

Methods: Retrospective analysis of a single-center database of consecutive cases for acute cerebral infarction (ACI) from January 1 2012 to December 30 2016 was performed. Significant predictors of the dependent variable variance were identified by standard linear, univariate and multivariate, or binary logistic regression modeling. Multivariate regression analysis was introduced to investigate the relationship between plasma hs-CRP levels at admission and change in National Institutes of Health Stroke Scale (NIHSS) score at discharge.

Results: The percentages of hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, body mass index (BMI) and chronic kidney disease were raised with the increase of hs-CRP plasma concentration at admission among all patients (p?<?0.05). ACI patients with large-artery atherosclerosis had an increasing percentage with the increase of hs-CRP mean value (p?<?0.05). The initial NIHSS scores, the acute infection rate and age advance also increased with the increase of hs-CRP plasma concentration at admission (p?<?0.05). The ratio of neurological improvement increased with the decrease of plasma hs-CRP concentration (p?<?0.05). The neurological deterioration and poor prognosis increased with the increase of plasma hs-CRP concentration (p?<?0.05).

Conclusion: High plasma hs-CRP levels are associated with worse outcomes in the ACI patients. Monitoring plasma hs-CRP levels and cutting down the elevated plasma hs-CRP levels will be beneficial in screening and treatment decisions for the prognosis of acute ischemic stroke.     

Exosomal miR-3131 derived from endothelial cells with KRAS mutation promotes EndMT by targeting PICK1 in brain arteriovenous malformations

Aims

To explore the underlying mechanism by which low-frequency KRAS mutations result in extensive EndMT occurrence.

Methods

Exosomes derived from primarily cultured brain arteriovenous malformation (bAVMs) and human umbilical vein endothelial cells (HUVECs) transfected with KRAS^G12D, KRAS^WT, or KRAS^NC lentiviruses were isolated, and their effects on HUVECs were identified by western blotting and immunofluorescence staining. The expression levels of exosomal microRNAs (miRNAs) were evaluated by miRNA microarray, followed by functional experiments on miR-3131 and detection of its downstream target, and miR-3131 inhibitor in reversing the EndMT process induced by KRAS^G12D-transfected HUVECs and bAVM endothelial cells (ECs) were explored.

Results

Exosomes derived from KRAS^G12D bAVM ECs and KRAS^G12D-transfected HUVECs promoted EndMT in HUVECs. MiR-3131 levels were highest in the exosomes of KRAS^G12D-transfected HUVECs, and HUVECs transfected with the miR-3131 mimic acquired mesenchymal phenotypes. RNA-seq and dual-luciferase reporter assays revealed that PICK1 is the direct downstream target of miR-3131. Exosomal miR-3131 was highly expressed in KRAS^G12D bAVM^exos compared with non-KRAS-mutant bAVM^exos or HUVEC^exos. Finally, a miR-3131 inhibitor reversed EndMT in HUVECs treated with exosomes or the supernatant of KRAS^G12D-transfected HUVECs and KRAS^G12D bAVM ECs.

Conclusion

Exosomal miR-3131 promotes EndMT in KRAS-mutant bAVMs, and miR-3131 might be a potential biomarker and therapeutic target in KRAS^G12D-mutant bAVMs.     

蛋白质Z与动脉粥样硬化性脑梗死的相关性

目的 观察蛋白质Z（Protein Z,PZ）在动脉粥样硬化性脑梗死（Atherosclerotic cerebral infarction,ACI）患者急性期内的变化,分析PZ与D-二聚体（DD）、纤维蛋白原（FIB）在ACI患者中变化的相关性及血浆PZ的检测在ACI患者中的诊断价值及临床意义.方法 病例组选择发病在72h之内的ACI患者;对照组来自本院健康体检者.所有受检者均于入院即时及入院第14天抽取静脉血测定PZ和相关血凝因素等资料.另采用头颅CT或MRI测量与症状和体征相对应的最大低密度影面积,以及美国国立卫生研究院卒中量表（NIHSS）进行神经功能缺损评分.结果 ACI患者发病3d内血浆PZ、DD、FIB水平明显高于对照组;入院第14天所测的PZ、DD明显高于入院即时所测水平;在诊断ACI的过程中PZ的曲线下面积（AUC）、灵敏度和特异度均高于其他凝血因素,ACI患者血浆PZ浓度与梗死面积及NIHSS评分无相关性.结论 本研究证实了ACI急性期患者体内存在凝血-纤溶系统异常;PZ是脑梗死的一个的危险因素;通过对ACI急性期患者血浆PZ水平及其他血凝因素的检测,结合临床症状、体征及影像学检查,有助于对ACI的诊断和对病情作出判断.     

Plasma Levels of miR-125b-5p and miR-206 in Acute Ischemic Stroke Patients After Recanalization Treatment: A Prospective Observational Study

Introduction: Multiple microRNAs (miRNAs) participate in the response to hypoxic/ischemic and ischemia-reperfusion events. However, the expression of these miRNAs in circulation from patients with acute ischemic stroke (AIS) receiving recanalization treatment has not been examined, and whether they are associated with the severity and outcome of stroke is still unknown. Materials and methods: In this prospective cohort study, plasma levels of miR-125b-5p, miR-15a-3p, miR-15a-5p, and miR-206 were measured at 24 hours after thrombolysis with or without endovascular treatment in 94 patients with AIS, as determined by qRT-PCR. Stroke severity was assessed based on National Institutes of Health Stroke Scale (NIHSS) score and infarct lesion. Intracranial haemorrhage (ICH) was recorded. An unfavorable outcome was defined as a modified Rankin Scale score greater than 2 at day 90 after stroke. Results: miR-125b-5p and miR-206 levels were correlated with NIHSS scores (P = .014 and P = .002) and cerebral infarction volumes (P = .025 and P = .030). miR-125b-5p levels were significantly higher in patients with an unfavorable outcome than in patients with a favorable outcome (P = .002) and showed good diagnostic accuracy in discriminating the presence of an unfavorable outcome (area under the curve .735, 95% confidence interval .623-.829, P < .001). No association was found between different miRNAs and ICH. Conclusions: In AIS patients after thrombolysis with or without endovascular treatment, miR-125b-5p is a novel prognostic biomarker highly associated with an unfavorable outcome. miR-125b-5p and miR-206 levels are associated with stroke severity.     

急性脑梗死患者miR-210的表达及意义

目的探讨急性脑梗死(ACI)患者血清中缺氧激活因子微小RNA-210(miR-210)的表达情况及临床意义。方法选取2013-01—2015-01在我院治疗的ACI患者122例(ACI组),同时选择同期健康体检人群80例为对照组,采用反转录-聚合酶链反应(RT-PCR)检测血清miR-210表达水平。结果 ACI组miR-210表达量为(1.24±0.07)2~(-△△Ct),明显低于对照组的(2.02±0.11)2~(-△△Ct),差异有统计学意义(P0.05);男女ACI患者血清miR-210表达比较差异无统计学意义(P0.05);≤60岁和60岁ACI患者血清miR-210表达比较差异无统计学意义(P0.05);重度ACI患者血清miR-210表达为(1.10±0.08)2~(-△△Ct),明显低于轻度和中度患者,差异有统计学意义(P0.05);中度ACI患者血清miR-210表达为(1.29±0.10)2~(-△△Ct),低于轻度患者,差异有统计学意义(P0.05);miR-210对ACI的ROC曲线下面积为0.961,95%CI为0.926~0.996,截断值为(1.378)2~(-△△Ct),时,灵敏度为91.30%,特异度为97.54%。结论急性脑梗死患者血清中miR-210表达减弱,且与急性脑梗死严重程度有关,可作为急性脑梗死的诊断依据。