blood coagulation

血液凝固
  • 文章类型: Journal Article
    已证明凝血和纤溶状态异常与炎症性肠病有关。然而,目前还没有研究系统地研究凝血和纤溶相关基因在溃疡性结肠炎(UC)诊断中的作用.UC相关数据集(GSE169568和GSE94648)来源于基因表达综合数据库。通过结合差异表达分析和机器学习算法来鉴定与凝血和纤维蛋白溶解相关的生物标志物。此外,进行基因集富集分析和免疫分析。共有4种生物标志物(MAP2K1、CREBBP、TAF1和HP)被识别,和生物标志物在与免疫相关的途径中显著富集,如T细胞受体信号通路,原发性免疫缺陷,趋化因子信号通路,等。总的来说,UC和对照组之间4种免疫细胞的浸润丰度明显不同,即嗜酸性粒细胞,巨噬细胞M0,静息的肥大细胞,和调节性T细胞。所有生物标志物均与嗜酸性粒细胞显著相关。我们的发现检测到4种凝血和纤溶相关生物标志物(MAP2K1,CREBBP,TAF1和HP)适用于UC,这有助于UC的进一步临床研究。
    Abnormalities in coagulation and fibrinolytic status have been demonstrated to be relevant to inflammatory bowel disease. Nevertheless, there is no study to methodically examine the role of the coagulation and fibrinolysis-related genes in the diagnosis of ulcerative colitis (UC). UC-related datasets (GSE169568 and GSE94648) were originated from the Gene Expression Omnibus database. The biomarkers related to coagulation and fibrinolysis were identified through combining differentially expressed analysis and machine learning algorithms. Moreover, Gene Set Enrichment Analysis and immune analysis were carried out. A total of 4 biomarkers (MAP2K1, CREBBP, TAF1, and HP) were identified, and biomarkers were markedly enriched in pathways related to immunity, such as T-cell receptor signaling pathway, primary immunodeficiency, chemokine signaling pathway, etc. In total, the infiltrating abundance of 4 immune cells between UC and control was markedly different, namely eosinophils, macrophage M0, resting mast cells, and regulatory T cells. And all biomarkers were significantly relevant to eosinophils. Our findings detected 4 coagulation and fibrinolysis-related biomarkers (MAP2K1, CREBBP, TAF1, and HP) for UC, which contributed to the advancement of UC for further clinical investigation.
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  • 文章类型: Journal Article
    背景:本研究旨在评估华法林的应用价值和安全性,利伐沙班,和达比加群治疗老年房颤患者。
    方法:对我院收治的180例老年心房颤动患者进行回顾性分析。根据他们的抗凝治疗方案,将患者分为三组:华法林(57例),利伐沙班(61例),达比加群(62例)。收集了一般人口统计信息,和凝血功能指标-包括纤维蛋白原(FIB),凝血酶时间(PT),活化部分凝血酶时间(APTT),和D-二聚体(D-D)-以及肝功能指标-包括总胆红素(TbiL),碱性磷酸酶(ALP),天冬氨酸转氨酶(AST),治疗前和治疗4周后比较丙氨酸转移酶(ALT)。
    结果:人口统计学特征没有显着差异,例如性别,年龄,身体质量指数,或病程在三组之间。华法林组的总有效率(84.21%)明显低于利伐沙班组(98.36%)和达比加群组(96.77%)(p<0.05)。然而,利伐沙班组和达比加群组总有效率比较,差异无统计学意义(p>0.05)。此外,三种药物对凝血功能的影响没有显着差异,肝功能,或出血的发生率(p=0.052)。
    结论:华法林,利伐沙班,达比加群可有效预防老年房颤患者血栓形成,利伐沙班和达比加群显示出较好的疗效。这三种药物的出血事件发生率相似,对凝血和肝功能没有显著影响。
    BACKGROUND: This study aimed to evaluate the application value and safety of Warfarin, Rivaroxaban, and Dabigatran in elderly patients with atrial fibrillation.
    METHODS: A total of 180 elderly patients with atrial fibrillation admitted to our hospital were retrospectively analyzed. According to their anticoagulant treatment regimen, patients were divided into three groups: Warfarin (57 cases), Rivaroxaban (61 cases), and Dabigatran (62 cases). General demographic information was collected, and coagulation function indicators-including fibrinogen (FIB), thrombin time (PT), activated partial thrombin time (APTT), and D-dimer (D-D)-as well as liver function indexes-including total bilirubin (TbiL), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine transferase (ALT)-were compared before and after 4 weeks of treatment.
    RESULTS: There were no significant differences in demographic characteristics such as gender, age, body mass index, or disease course among the three groups. The total effective rate in the Warfarin group (84.21%) was significantly lower than in the Rivaroxaban (98.36%) and Dabigatran (96.77%) groups (p < 0.05). However, there was no significant difference in the total effective rate between the Rivaroxaban and Dabigatran groups (p > 0.05). Additionally, no significant differences were found in the effects of the three drugs on coagulation function, liver function, or the incidence of bleeding (p = 0.052).
    CONCLUSIONS: Warfarin, Rivaroxaban, and Dabigatran can effectively prevent thrombosis in elderly patients with atrial fibrillation, with Rivaroxaban and Dabigatran showing superior effectiveness. All three drugs demonstrated similar low rates of bleeding events and had no significant impact on coagulation and liver function.
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  • 文章类型: Journal Article
    不可控制的不可压缩出血,通常伴有凝血功能障碍,是平民和军人遭受创伤后死亡的主要原因。在这项研究中,通过将受控的三聚磷酸钠交联与氢咖啡酸(HCA)移植相结合,制备了具有快速形状恢复的不依赖凝血病的可注射儿茶酚修饰的壳聚糖(CS-HCA)止血材料。CS-HCA表现出强大的机械强度和快速的血液触发形状恢复。此外,CS-HCA表现出优越的凝血能力,增强血细胞粘附和激活,和更大的蛋白质吸附比商业止血纱布和Celox。CS-HCA在兔致命性肝穿孔伤口模型中显示出增强的促凝血和止血能力,特别是肝素化的兔子。CS-HCA适用于批量生产,并有望成为临床上可翻译的止血剂。
    Uncontrolled non-compressible hemorrhage, which is often accompanied by coagulopathy, is a major cause of mortality following traumatic injuries in civilian and military populations. In this study, coagulopathy-independent injectable catechol-modified chitosan (CS-HCA) hemostatic materials featuring rapid shape recovery were fabricated by combining controlled sodium tripolyphosphate-crosslinking with hydrocaffeic acid (HCA) grafting. CS-HCA exhibited robust mechanical strength and rapid blood-triggered shape recovery. Furthermore, CS-HCA demonstrated superior blood-clotting ability, enhanced blood cell adhesion and activation, and greater protein adsorption than commercial hemostatic gauze and Celox. CS-HCA showed enhanced procoagulant and hemostatic capacities in a lethal liver-perforation wound model in rabbits, particularly in heparinized rabbits. CS-HCA is suitable for mass manufacturing and shows promise as a clinically translatable hemostat.
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  • 文章类型: English Abstract
    目的:探讨急性心肌梗死(AMI)患者循环微粒的特点及其促凝血的可能机制。
    方法:进行前瞻性病例对照研究。纳入2023年6月至11月在哈尔滨市第一医院心内科二科收治的冠心病患者,根据患者是否发生AMI进行分组。入学那天,计算弥散性血管内凝血(DIC)评分.同时,采集空腹静脉血,以及D-二聚体的水平,检测纤维蛋白降解产物(FDP)和主要凝血因子的活性。通过微粒捕集法确定循环微粒的水平。通过组织因子(TF)依赖性FXa产生测定法检测携带组织因子(TFMP)的微粒水平。采用Spearman相关法分析各指标间的相关性。
    结果:共纳入52例冠心病患者,其中AMI组26例,非AMI组26例。性别差异无统计学意义,年龄,体重指数(BMI),潜在的疾病,吸烟史,两组患者入院前治疗,这表明两组的基线数据是平衡和可比的。与非AMI组相比,DIC评分和D-二聚体,AMI组的FDP水平显着增加[DIC评分:3(3,4)vs.3(2,3),D-二聚体(mg/L):8.80(6.84,15.66)vs.2.13(1.64,3.86),FDP(mg/L):30.13(19.30,52.54)vs.20.00(13.51,28.37),所有P<0.01],提示AMI患者凝血激活程度更为严重。AMI组的凝血途径中主要凝血因子的消耗比非AMI组重[FII:59.45%(49.65%,71.25%)与63.65%(49.98%,73.22%),FV:96.95%(73.50%,112.78%)与105.05%(73.48%,131.48%),FVII:42.30%(36.98%,51.98%)与53.40%(46.58%,69.88%),FX:60.90%(48.22%,80.82%)与73.50%(56.80%,85.98%),FXI:82.45%(62.90%,99.10%)与92.40%(73.90%,114.25%),FXII:29.90%(12.42%,42.38%)与34.65%(16.32%,48.20%),均P<0.05]。AMI组循环TF+MP水平明显高于非AMI组[nmol/L:0.13(0.06,0.20)vs.0.08(0.04,0.15),P<0.05]。AMI组和非AMI组之间的循环微粒水平没有显着差异[nmol/L:1.24(0.71,3.77)。1.35(0.73,2.14),P>0.05]。相关性分析显示,冠心病患者循环TF+MP水平与凝血指标DIC评分呈显著正相关(r=0.307,P=0.027)。D-二聚体(r=0.696,P<0.001)和FDP(r=0.582,P<0.001),与外源性途径因子FVII(r=-0.521,P<0.001)和共同途径因子FX(r=-0.332,P=0.016)呈强负相关。
    结论:AMI患者循环TF+MP水平明显高于非AMI患者。TF+MP可能在激活外源性凝血途径中起重要作用,加剧凝血因子消耗,并在AMI发生期间促进血凝块形成。
    OBJECTIVE: To investigate the characteristic of circulating microparticle in patients with acute myocardial infarction (AMI) and its possible mechanism of promoting coagulation.
    METHODS: A prospective case-control study was conducted. The patients with coronary heart disease admitted to the second department of cardiology in Harbin First Hospital from June to November 2023 were enrolled, and they were grouped according to whether the patients occurred AMI or not. On the day of admission, disseminated intravascular coagulation (DIC) score was calculated. At the same time, fasting venous blood was collected, and the levels of D-dimer, fibrin degradation product (FDP) and the activities of major coagulation factors were detected. The level of circulating microparticle was determined by microparticle trapping method. The microparticle carrying tissue factor (TF+MP) level was detected by tissue factor (TF) dependent F Xa production assay. Spearman correlation method was used to analyze the correlation among the indicators.
    RESULTS: A total of 52 patients with coronary heart disease were enrolled, including 26 patients in AMI group and 26 patients in non-AMI group. There was no significant difference in gender, age, body mass index (BMI), underlying diseases, smoking history, and pre-admission treatment of patients between the two groups, indicating that the baseline data of the two groups were balanced and comparable. Compared with the non-AMI group, the DIC score and D-dimer, FDP levels in the AMI group were significantly increased [DIC score: 3 (3, 4) vs. 3 (2, 3), D-dimer (mg/L): 8.80 (6.84, 15.66) vs. 2.13 (1.64, 3.86), FDP (mg/L): 30.13 (19.30, 52.54) vs. 20.00 (13.51, 28.37), all P < 0.01], indicating that the degree of coagulation activation in AMI patients was more severe. The consumption of major coagulation factors in the coagulation pathway in the AMI group was heavier than that in the non-AMI group [F II: 59.45% (49.65%, 71.25%) vs. 63.65% (49.98%, 73.22%), F V: 96.95% (73.50%, 112.78%) vs. 105.05% (73.48%, 131.48%), F VII: 42.30% (36.98%, 51.98%) vs. 53.40% (46.58%, 69.88%), F X: 60.90% (48.22%, 80.82%) vs. 73.50% (56.80%, 85.98%), F XI: 82.45% (62.90%, 99.10%) vs. 92.40% (73.90%, 114.25%), F XII: 29.90% (12.42%, 42.38%) vs. 34.65% (16.32%, 48.20%), all P < 0.05]. The circulating TF+MP level in the AMI group was significantly higher than that in the non-AMI group [nmol/L: 0.13 (0.06, 0.20) vs. 0.08 (0.04, 0.15), P < 0.05]. There was no significant difference in the level of circulating microparticle between AMI group and non-AMI group [nmol/L: 1.24 (0.71, 3.77) vs. 1.35 (0.73, 2.14), P > 0.05]. Correlation analysis showed that circulating TF+MP level in the patients with coronary heart disease was significantly positively correlated with coagulation indicator DIC score (r = 0.307, P = 0.027), D-dimer (r = 0.696, P < 0.001) and FDP (r = 0.582, P < 0.001), and there was a strong negative correlation with exogenous pathway factor F VII (r = -0.521, P < 0.001) and common pathway factor F X (r = -0.332, P = 0.016).
    CONCLUSIONS: The circulating TF+MP level in AMI patients was significantly higher than that in the non-AMI patients. TF+MP may play an important role in activating the extrinsic coagulation pathway, exacerbating coagulation factor consumption, and promoting clot formation during AMI occurrence.
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  • 文章类型: Case Reports
    柴油吸入中毒是一种罕见但严重的医疗状况,由于其可能引起严重的呼吸窘迫和凝血功能障碍,因此需要及时就医。本病例研究描述了一名40多岁的男性患者的独特临床表现,该患者在发动机维修过程中无意吸入柴油后经历了急性呼吸窘迫并表现出凝血因子VII缺乏。患者出现胸闷、呼吸困难等症状,指示化学吸入性肺炎,伴随着不可预见的凝血异常。治疗涉及严格的干预,包括气管内插管,机械通气,和药物治疗,包括氨溴索,二羟丙基,和甲基强的松龙.此外,程序性措施,如反复支气管镜肺泡灌洗,病原体培养,有针对性的抗生素治疗,用于减轻呼吸系统并发症。病人的凝血障碍是用输血治疗的,他出院了。本案例强调了在吸入柴油的情况下立即进行医疗干预以避免进一步的临床恶化和不利结果的必要性。此外,它强调了扩大研究工作的必要性,旨在阐明柴油吸入对凝血级联的间接影响,在医学文献中仍然相对未充分开发的领域。
    Diesel inhalation poisoning represents a rare yet critical medical condition necessitating prompt medical attention due to its potential to induce severe respiratory distress and coagulation dysfunction. The present case study describes the distinctive clinical presentation of a male patient in his early 40s who experienced acute respiratory distress and manifested coagulation factor VII deficiency subsequent to unintentional inhalation of diesel oil during engine repair. The patient demonstrated symptoms including chest tightness and dyspnea, indicative of chemical aspiration pneumonia, alongside an unforeseen coagulation abnormality. Treatment involved rigorous intervention, comprising endotracheal intubation, mechanical ventilation, and administration of pharmacotherapy, including ambroxol, dihydroxypropylline, and methylprednisolone. Moreover, procedural measures, such as repeated bronchoscopic alveolar lavage, pathogen culture, and targeted antibiotic therapy, were employed to mitigate respiratory complications. The patient\'s clotting disorder was treated with blood transfusions, and he was discharged with improvement. The present case highlights the imperative nature of immediate medical intervention in instances of diesel inhalation to avert further clinical deterioration and unfavorable outcomes. Additionally, it underscores the necessity for expanded research endeavors aimed at elucidating the indirect repercussions of diesel inhalation on the coagulation cascade, an area that remains relatively underexplored within the medical literature.
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  • 文章类型: English Abstract
    OBJECTIVE: To explore the key factors affecting plasma clot retraction and optimize the experimental method of plasma clot retraction, in order to study the regulation of platelet function and evaluate the modulatory effects of drugs on plasma clot retraction.
    METHODS: The effects of different concentrations of thrombin, Ca2 + and platelets on plasma clot retraction were studied, and the detection system of plasma clot retraction was optimized. The availability of the detection system was then validated by analyzing the regulatory effects of multiple signaling pathway inhibitors on plasma clot retraction.
    RESULTS: Through the optimization study of multiple factors, platelet rich plasma (PRP) containing 0.5 mmol/L Ca2 + and 40×109/L platelets was treated with 0.2 U/ml thrombin to perform plasma clot retraction analysis. After treatment with thrombin for 15 min, plasma clot retracted significantly. After treatment with thrombin for 30 min, the percentage of plasma clot retraction was more than 50%. The regulatory effects of multiple signaling pathway inhibitors on plasma clot retraction were studied in this detection system. PKC inhibitor Go 6983 exhibited a significant inhibitory effect on plasma clot retraction, while PI3K inhibitor Ly294002 and p38 MAPK inhibitor SB203580 slightly suppressed plasma clot retraction.
    CONCLUSIONS: PRP containing 0.5 mmol/L Ca2 + and 40×109/L platelets can be induced with 0.2 U/ml thrombin to conduct plasma clot retraction analysis, which can be used to study the regulation of platelet function and evaluate the modulatory effects of drugs on plasma clot retraction.
    UNASSIGNED: 血浆凝块收缩功能实验方法学研究.
    UNASSIGNED: 探讨影响血浆凝块收缩功能的关键因素,优化血浆凝块收缩功能实验方法,以用于研究血小板功能调控和评价药物对血浆凝块收缩功能的调节作用。.
    UNASSIGNED: 依次研究不同浓度的凝血酶、Ca2+以及血小板对血浆凝块收缩率的影响,优化血浆凝块收缩检测体系。通过检测多种血小板信号通路抑制剂对血浆凝块收缩的调节作用验证该检测体系的有效性。.
    UNASSIGNED: 通过对凝血酶浓度、Ca2+浓度和血小板浓度的优化研究,利用0.2 U/ml凝血酶处理含0.5 mmol/L Ca2+以及40×109/L血小板的富血小板血浆(PRP)进行血浆凝块收缩分析。在此条件下,凝血酶处理15 min能够显著诱导血浆凝块收缩反应,处理30 min诱导的血浆凝块收缩率大于50%。利用此检测条件研究抑制剂对血浆凝块收缩的调节作用,PKC抑制剂Go 6983能够强烈抑制血浆凝块收缩反应,PI3K抑制剂Ly294002和p38 MAPK抑制剂SB203580能够轻度抑制血浆凝块收缩反应。.
    UNASSIGNED: 利用0.2 U/ml凝血酶处理含0.5 mmol/L Ca2+和40×109/L血小板的PRP进行血浆凝块收缩检测,可以用于研究血小板功能调控和评价药物对血浆凝块收缩的调节作用。.
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  • 文章类型: Journal Article
    空气污染暴露与凝血功能有关。然而,空气污染之间的关系证据有限,人体凝血功能和代谢组学。我们从中国柴鸭山乡招募了130名农村老人,所有这些人都没有预先存在的心血管疾病,并提供了住址信息。我们进行了临床检查,并从这些农村老年人中收集了血液样本,以检测凝血生物标志物(例如g,活化部分凝血活酶时间,纤维蛋白原,凝血酶时间,和凝血酶原时间)和非靶向代谢物在2021年12月和2022年8月。我们使用小型环境空气质量监测器来测量五种空气污染物的平均水平(例如,PM2.5,SO2,NO2,CO和O3)在采集血样前1至2周内。Mummichog途径分析用于鉴定潜在的代谢特征和途径。在这项研究中,我们确定了与空气污染和凝血功能相关的5条途径,并进一步确定了这些途径中的八个代谢特征。这些特征中的大多数是脂质,包括花生四烯酸和亚油酸。总的来说,这项研究的结果提供了对潜在机制的见解,特别是脂质代谢,这可能是空气污染和凝血功能之间联系的基础。
    Air pollution exposure has been linked with coagulation function. However, evidence is limited for the relationships between air pollution, coagulation function and metabolomics in humans. We recruited a panel of 130 rural elderly from the Chayashan township in China, all of whom were free of pre-existing cardiovascular diseases and had provided residential address information. We conducted clinical examinations and collected blood samples from these rural elderly for the detection of coagulation biomarkers (e.g, activated partial thromboplastin time, fibrinogen, thrombin time, and prothrombin time) and untargeted metabolites in both December 2021 and August 2022. We used mini ambient air quality monitor to measure the mean levels of five air pollutants (e.g., PM2.5, SO2, NO2, CO and O3) during 1 to 2 weeks before blood sample collection. The Mummichog pathway analysis was used to identified potential metabolic features and pathways. In this study, we identified 5 pathways associated with both air pollution and coagulation function, and further pinpointed eight metabolic features within these pathways. The majority of these features were lipids, including arachidonic acid and linoleic acid. Overall, the findings of this study offer insights into potential mechanisms, particularly lipid metabolism, that may underlie the association between air pollution and coagulation function.
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  • 文章类型: Journal Article
    背景:下肢深静脉血栓(DVT)是全膝关节置换术(TKA)后常见的并发症。本研究的目的是评估TKA后DVT的危险因素,并分析TKA前后miR-199b-5p和一氧化氮(NO)的表达。以及它们对DVT的预测价值。
    方法:对121例TKA患者的基本临床资料进行回顾性分析。RT-qPCR检测TKA治疗前后患者miR-199b-5p的相对表达水平。基于DVT的发生,将患者分为DVT和非DVT组.Logistic回归分析评价DVT的危险因素。受试者工作特征(ROC)曲线评估术后miR-199b-5p水平的预测价值,术前NO水平,以及它们在DVT中的组合。使用生物信息学分析对miR-199b-5p的靶基因及其功能进行了预测和注释。
    结果:TKA后miR-199b-5p水平明显高于TKA前(P<0.001)。TKA术后121例患者中有20例发生DVT,发病率为16.53%。多因素分析显示,年龄,DVT家族史,NO降低和miR-199b-5p升高是TKA后发生DVT的危险因素(P<0.05)。ROC曲线显示miR-199b-5p和NO均对DVT有一定的诊断价值,但miR-199b-5p和NO的组合具有最高的诊断准确性(P<0.001)。
    结论:本研究显示TKA后miR-199b-5p的表达上调,DVT患者的miR-199b-5p水平高于非DVT患者。miR-199b-5p结合NO对TKA术后DVT的诊断具有重要价值。
    BACKGROUND: Deep vein thrombosis (DVT) of lower extremity is a common complications after total knee arthroplasty (TKA). The purpose of this study was to evaluate the risk factors for DVT after TKA and analyze the expression of miR-199b-5p and nitric oxide (NO) before and after TKA, as well as their predictive value for DVT.
    METHODS: Basic clinical information of 121 patients with TKA was analyzed retrospectively. RT-qPCR was used to detect the relative expression level of miR-199b-5p in patients before and after TKA treatment. Based on the occurrence of DVT, patients were divided into DVT and non-DVT groups. Logistic regression analysis evaluated the risk factors of DVT. The receiver operating characteristic (ROC) curve assessed the predictive value of postoperative miR-199b-5p level, preoperative NO level, and their combination in DVT. The target genes of miR-199b-5p and their functions were predicted and annotated using bioinformatics analysis.
    RESULTS: The level of miR-199b-5p after TKA was upregulated compared with that before TKA (P < 0.001). DVT occurred in 20 of 121 patients after TKA, with an incidence of 16.53%. Multivariate analysis showed that age, family history of DVT, decrease of NO and increase of miR-199b-5p were risk factors for DVT after TKA (P < 0.05). The ROC curve showed that both miR-199b-5p and NO had certain diagnostic value for DVT, but the combination of miR-199b-5p and NO had the highest diagnostic accuracy (P < 0.001).
    CONCLUSIONS: This study showed that the expression of miR-199b-5p was up-regulated after TKA, and miR-199b-5p levels were higher in DVT patients than in non-DVT patients. miR-199b-5p combined with NO is of great value in the diagnosis of DVT after TKA.
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  • 文章类型: Journal Article
    肌萎缩侧索硬化症(ALS)是一种以进行性运动神经元变性为特征的致命疾病,缺乏有效的临床治疗方法。在这项研究中,我们评估了间充质干细胞来源的小细胞外囊泡(sEVs)鼻内递送是否是使用SOD1G93A小鼠治疗ALS的一种策略.体内追踪显示,鼻内递送的sEV进入中枢神经系统,并被脊髓神经元和一些小胶质细胞广泛吸收。鼻内接受sEV给药的SOD1G93A小鼠在运动性能和存活时间方面显示出显著的改善。sEV管理后,病理变化,包括脊髓运动神经元死亡和突触去神经,轴突脱髓鞘,神经肌肉接头变性和电生理缺陷,线粒体空泡化明显减轻。sEV给药减弱了促炎细胞因子和神经胶质反应的升高。蛋白质组学和转录组学分析揭示了SO1G93A小鼠脊髓中补体和凝血级联和NF-κB信号通路的上调,sEV给药显著抑制。通过使用Western印迹检测C1q和NF-κB表达进一步证实了变化。总之,sEV的鼻内给药通过抑制神经炎症和补体和凝血级联和NF-κB信号通路的过度激活有效地延迟ALS的进展,并且是ALS治疗的潜在选择。
    Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive motoneuron degeneration, and effective clinical treatments are lacking. In this study, we evaluated whether intranasal delivery of mesenchymal stem cell-derived small extracellular vesicles (sEVs) is a strategy for ALS therapy using SOD1G93A mice. In vivo tracing showed that intranasally-delivered sEVs entered the central nervous system and were extensively taken up by spinal neurons and some microglia. SOD1G93A mice that intranasally received sEV administration showed significant improvements in motor performances and survival time. After sEV administration, pathological changes, including spinal motoneuron death and synaptic denervation, axon demyelination, neuromuscular junction degeneration and electrophysiological defects, and mitochondrial vacuolization were remarkably alleviated. sEV administration attenuated the elevation of proinflammatory cytokines and glial responses. Proteomics and transcriptomics analysis revealed upregulation of the complement and coagulation cascade and NF-ĸB signaling pathway in SOD1G93A mouse spinal cords, which was significantly inhibited by sEV administration. The changes were further confirmed by detecting C1q and NF-ĸB expression using Western blots. In conclusion, intranasal administration of sEVs effectively delays the progression of ALS by inhibiting neuroinflammation and overactivation of the complement and coagulation cascades and NF-ĸB signaling pathway and is a potential option for ALS therapy.
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  • 文章类型: English Abstract
    为了探索凝血功能之间的因果关系,包括血管性血友病因子(vWF),具有血小板反应蛋白1型基序的解整合素和金属蛋白酶,成员13(ADAMTS13),活化部分凝血活酶时间(aPTT),凝血因子VIII(FVIII),凝血因子XI(FXI),凝血因子VII(FVII),凝血因子(FXX),内源性凝血酶电位(ETP),纤溶酶原激活物抑制剂-1(PAI-1),蛋白C,和纤溶酶,和妊娠糖尿病(GDM)使用两个样本双向孟德尔随机(MR),为凝血功能与GDM发病机制的相关性提供遗传学证据。
    使用R包TwoSampleMR(v0.5.6)访问了IEUOpenGWAS数据库,以获取GDM的全基因组关联研究(GWAS)摘要的统计数据。通过逆方差加权法(IVW)对11项凝血功能与GDM之间的因果关系进行MR分析,MR-Egger方法,和加权中位数法(WM)。
    在这项研究中,GDM的GWAS汇总统计数据(涵盖5687例和117892例对照)用于MR分析.发现预测的血浆FVIII水平与GDM风险之间存在因果关系(IVW:[优势比,OR]=0.28,95%置信区间[CI]:0.10-0.75,P<0.001;WM:OR=0.30,95%CI:0.09-0.98,P<0.001)。其他凝血功能与GDM风险之间无因果关系(P>0.05)。
    血浆FVIII水平与GDM的风险之间存在显着因果关系。这一发现强调了妊娠期间凝血功能和糖代谢之间的复杂相互作用,但对这一发现的进一步研究是有必要的。
    UNASSIGNED: To explore the causal association between coagulation function, including von Willebrand factor (vWF), a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13), activated partial thromboplastin time (aPTT), coagulation factor Ⅷ (FⅧ), coagulation factor Ⅺ (FⅪ), coagulation factor Ⅶ (FⅦ), coagulation factor Ⅹ (FⅩ), endogenous thrombin potential (ETP), plasminogen activator inhibitor-1 (PAI-1), protein C, and plasmin, and gestational diabetes mellitus (GDM) using two-sample two-way Mendelian randomization (MR), and to provide genetic evidence for the association between coagulation function and the pathogenesis of GDM.
    UNASSIGNED: The IEU OpenGWAS database was accessed using the R package TwoSampleMR (v 0.5.6) to obtain the statistical data of the genome-wide association study (GWAS) summary of GDM. MR analysis of the causal association between 11 coagulation function and GDM was performed by the inverse-variance weighted method (IVW), the MR-Egger method, and the weighted median method (WM).
    UNASSIGNED: In this study, the GWAS summary statistics of GDM (covering 5 687 cases and 117 892 controls) were used for MR analysis. It was found that there was a causal relationship between the predicted plasma FⅧ level and the risk for GDM (IVW: [odds ratio, OR]=0.28, 95% confidence interval [CI]: 0.10-0.75, P<0.001; WM: OR=0.30, 95% CI: 0.09-0.98, P<0.001). There was no causal relationship between other coagulation function and the risk for GDM (P>0.05).
    UNASSIGNED: There is a significant causal relationship between the plasma FⅧ level and the risk for GDM. This finding highlights the complex interaction between coagulation function and glucose metabolism during pregnancy, but further research on this finding is warranted.
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