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The Mechanism of Astragaloside IV in NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome-mediated Pyroptosis after Intracerebral Hemorrhage. 黄芪皂苷 IV 在脑出血后 NOD 样受体家族含吡啶域 3 炎症体介导的脓毒症中的作用机制
Pub Date : 2024-01-01 DOI: 10.2174/0115672026295640240212095049
Honggang Wu, Shu Chen, Guoliang You, Bo Lei, Li Chen, Jiachuan Wu, Niandong Zheng, Chao You

Background: Intracerebral hemorrhage (ICH) is one of the most common subtypes of stroke.

Objectives: This study aimed to investigate the mechanism of Astragaloside IV (AS-IV) on inflammatory injury after ICH.

Methods: The ICH model was established by the injection of collagenase and treated with ASIV (20 mg/kg or 40 mg/kg). The neurological function, water content of the bilateral cerebral hemisphere and cerebellum, and pathological changes in brain tissue were assessed. The levels of interleukin-1 beta (IL-1β), IL-18, tumor necrosis factor-alpha, interferon-gamma, and IL-10 were detected by enzyme-linked immunosorbent assay. The levels of Kruppel-like factor 2 (KLF2), NOD-like receptor family pyrin domain containing 3 (NLRP3), GSDMD-N, and cleaved-caspase-1 were detected by reverse transcription-quantitative polymerase chain reaction and Western blot assay. The binding relationship between KLF2 and NLRP3 was verified by chromatin-immunoprecipitation and dual-luciferase assays. KLF2 inhibition or NLRP3 overexpression was achieved in mice to observe pathological changes.

Results: The decreased neurological function, increased water content, severe pathological damage, and inflammatory response were observed in mice after ICH, with increased levels of NLRP3/GSDMD-N/cleaved-caspase-1/IL-1β/IL-18 and poorly-expressed KLF2 in brain tissue. After AS-IV treatment, the neurological dysfunction, high brain water content, inflammatory response, and pyroptosis were alleviated, while KLF2 expression was increased. KLF2 bonded to the NLRP3 promoter region and inhibited its transcription. Down-regulation of KLF2 or upregulation of NLRP3 reversed the effect of AS-IV on inhibiting pyroptosis and reducing inflammatory injury in mice after ICH.

Conclusion: AS-IV inhibited NLRP3-mediated pyroptosis by promoting KLF2 expression and alleviated inflammatory injury in mice after ICH.

背景:脑出血(ICH)是中风最常见的亚型之一:脑出血(ICH)是中风最常见的亚型之一:本研究旨在探讨黄芪皂苷 IV(AS-IV)对 ICH 后炎性损伤的作用机制:方法:通过注射胶原酶建立 ICH 模型,并用 ASIV(20 mg/kg 或 40 mg/kg)治疗。评估神经功能、双侧大脑半球和小脑的含水量以及脑组织的病理变化。酶联免疫吸附试验检测了白细胞介素-1β(IL-1β)、IL-18、肿瘤坏死因子-α、γ干扰素和IL-10的水平。反转录-定量聚合酶链反应和 Western 印迹法检测了 Kruppel 样因子 2(KLF2)、NOD 样受体家族含 pyrin 结构域 3(NLRP3)、GSDMD-N 和裂解-caspase-1 的水平。染色质免疫沉淀和双荧光素酶试验验证了 KLF2 和 NLRP3 之间的结合关系。在小鼠体内抑制 KLF2 或过表达 NLRP3,观察病理变化:结果:小鼠 ICH 后出现神经功能下降、含水量增加、严重病理损伤和炎症反应,脑组织中 NLRP3/GSDMD-N/cleaved-caspase-1/IL-1β/IL-18 水平升高,KLF2 表达低下。经过AS-IV治疗后,神经功能障碍、脑含水量高、炎症反应和热蛋白沉积等症状得到缓解,而KLF2的表达却有所增加。KLF2 与 NLRP3 启动子区域结合并抑制其转录。KLF2的下调或NLRP3的上调逆转了AS-IV在抑制小鼠ICH后的脓毒症和减轻炎症损伤方面的作用:结论:AS-IV通过促进KLF2的表达抑制了NLRP3介导的脓毒症,减轻了ICH后小鼠的炎症损伤。
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引用次数: 0
Evaluation of Quantitative and Selective Sensory Fiber Dysfunction in Patients with Cirrhosis. 评估肝硬化患者的定量和选择性感觉纤维功能障碍
Pub Date : 2024-01-01 DOI: 10.2174/0115672026289490240115075046
Nan-Nan Zhang, Zhi-Yong Wang, Jian-Min Chen, Zhi-Peng Yan, Guo-Xin Ni, Jun Ni

Background: Chronic liver disease has been reported to be associated with peripheral neuropathy. However, which sensory fibers are affected remains unknown. The objective of this study was to examine the function of sensory nerve fibers in patients with cirrhosis using the current perception threshold (CPT) test, as well as the correlation between blood biochemical indicators related to cirrhosis and CPT values.

Methods: We recruited 44 patients with liver cirrhosis and 37 healthy controls of the same age and gender. The Neurometer® system for the CPT test was used to stimulate the median nerve on the right index finger, as well as the deep and superficial peroneal nerves on the right hallux, using three distinct parameters (2000 Hz, 250 Hz, and 5 Hz). Comparative analysis was performed on the CPT values of the sensory nerves. Additionally, the correlation between CPT values and biochemical blood indicators in the study participants was analyzed.

Results: Under 2000 Hz electrical stimulation, there was a significant difference between the cirrhosis and healthy control groups in the median nerve as well as the deep and superficial peroneal nerves (p < 0.05). In addition, the median nerve CPT value of the cirrhosis group was significantly higher than that of the control group at an electrical stimulation frequency of 250 Hz (p = 0.005). There was no correlation between CPT values and blood biochemical indicators.

Conclusion: According to the results, the sensory peripheral neuropathy in liver cirrhosis is mainly manifested as Aβ fiber neuropathy.

背景:据报道,慢性肝病与周围神经病变有关。然而,哪些感觉纤维会受到影响仍是未知数。本研究的目的是使用电流感知阈值(CPT)测试法检测肝硬化患者感觉神经纤维的功能,以及与肝硬化相关的血液生化指标与 CPT 值之间的相关性:我们招募了 44 名肝硬化患者和 37 名同年龄、同性别的健康对照者。使用用于 CPT 测试的 Neurometer® 系统,以三种不同的参数(2000 Hz、250 Hz 和 5 Hz)刺激右手食指的正中神经以及右手拇指的腓深神经和腓浅神经。对感觉神经的 CPT 值进行了比较分析。此外,研究人员还分析了 CPT 值与血液生化指标之间的相关性:结果:在 2000 Hz 电刺激下,肝硬化组和健康对照组的正中神经、腓深神经和腓浅神经均存在显著差异(P < 0.05)。此外,在电刺激频率为 250 Hz 时,肝硬化组的正中神经 CPT 值明显高于对照组(p = 0.005)。CPT值与血液生化指标之间没有相关性:结果显示,肝硬化患者的感觉性周围神经病变主要表现为 Aβ 纤维神经病变。
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引用次数: 0
TRUST Technique for Neurointervention: A Promising Alternative for Complex Cases. 神经干预 TRUST 技术:复杂病例的可行替代方案。
Pub Date : 2024-01-01 DOI: 10.2174/0115672026291503240105093155
Xinzhao Jiang, Peng Wang, Fang Liu, Huadong Wu, Peng Jiang, Ruozhen Yuan, Sheng Zhang, Zongjie Shi

Background: Neurointervention via Transradial Access (TRA) is becoming increasingly popular as experience with this technique increases. However, approximately 8.6-10.3% of complex TRA cases are converted to femoral access due to a lack of support or radial artery spasm. This study aimed to assess the efficacy and safety of the TRUST (trans-radial coaxial catheter technique using a short sheath, Simmons catheter, and Tethys intermediate catheter) technique in interventional procedures via TRA.

Methods: This was a single-center retrospective analysis of 16 patients admitted to our institute between January 2023 to May 2023 to undergo endovascular interventions with the TRUST technique via the TRA.

Results: The mean age of the study population was 63.8 years, and 62.5% were male (10/16). The most common procedure was intracranial atherosclerotic stenosis (93.75%, 15/16). All procedures were performed successfully, and the most common procedures in our cohort were ballooning (50.0%, 8/16), stenting (18.75%, 3/16), and both procedures combined (31.25%, 1/16). All procedures were performed using the TRA, and the distal and proximal radial arteries were used for access in 31.35% (5/16) and 68.75% (11/16) of the cases, respectively. Technical success was achieved in all patients and most cases demonstrated mTICI ≥2b recanalization (93.75%, 15/16). In this case, no major access-site complications occurred.

Conclusion: The TRUST technique is technically safe and feasible and had a high technical success rate and low complication rate in our study. These results demonstrate that the TRUST technique is a promising alternative for patients undergoing complex neurointerventions.

背景:随着经桡动脉入路(TRA)神经介入技术经验的增加,这种技术越来越受欢迎。然而,约有 8.6%-10.3% 的复杂 TRA 病例因缺乏支持或桡动脉痉挛而转为股动脉入路。本研究旨在评估 TRUST(使用短鞘、Simmons 导管和 Tethys 中间导管的经桡动脉同轴导管技术)技术在经 TRA 介入手术中的有效性和安全性:这是一项单中心回顾性分析,研究对象是2023年1月至2023年5月期间在我院住院,通过TRA使用TRUST技术进行血管内介入治疗的16名患者:研究对象的平均年龄为63.8岁,62.5%为男性(10/16)。最常见的手术是颅内动脉粥样硬化性狭窄(93.75%,15/16)。所有手术均成功实施,在我们的队列中,最常见的手术是球囊扩张术(50.0%,8/16)、支架植入术(18.75%,3/16)以及两种手术的合并(31.25%,1/16)。所有手术均使用 TRA,分别有 31.35% (5/16)和 68.75% (11/16)的病例使用桡动脉远端和近端入路。所有患者都取得了技术成功,大多数病例都显示出 mTICI ≥2b 的再通率(93.75%,15/16)。结论:TRUST 技术在技术上是安全的:结论:TRUST 技术在技术上安全可行,在我们的研究中技术成功率高,并发症发生率低。这些结果表明,对于接受复杂神经介入治疗的患者来说,TRUST 技术是一种很有前途的选择。
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引用次数: 0
Analysis of the Relationship between Recent Small Subcortical Infarcts and Autonomic Nervous Dysfunction. 近期皮层下小梗塞与自主神经功能障碍的关系分析
Pub Date : 2024-01-01 DOI: 10.2174/0115672026303708240321035356
Wenxin Yuan, Lu An, Yunchao Wang, Ce Zong, Yinghao Yang, Hua Jin, Yuan Gao, Limei Wang, Yusheng Li, Yuming Xu, Yan Ji

Objective: Autonomic Nervous System (ANS) dysfunction may be involved in the pathogenesis of Cerebral Small Vessel Disease (CSVD). The study aimed to explore the relationship between Recent Small Subcortical Infarct (RSSI) and Blood Pressure Variability (BPV), and Heart Rate Variability (HRV).

Methods: A total of 588 patients from the CSVD registration research database of Henan Province were included in this study, and were divided into two groups according to the presence of RSSI. Clinical data, including demographic characteristics, disease history, laboratory indexes, 24-hour ambulatory blood pressure and electrocardiogram indicators, and imaging markers of CSVD, were collected. Univariate and binary logistic regression analyses were used to study the relationship between RSSI and indicators of laboratory, HRV and BPV in the CSVD population.

Results: Multivariate analysis showed that higher 24-hour mean Diastolic Blood Pressure (DBP)[Odds Ratios (OR)=1.083,95% Confidence Intervals (CI)=(1.038,1.129), p < 0.001], Standard Deviation (SD) of 24-hour DBP [OR=1.059,95%CI=(1.000,1.121), p = 0.049], nocturnal mean Systolic Blood Pressure (SBP) [OR=1.020,95%CI=(1.004,1.035), p = 0.012], nocturnal mean DBP [OR=1.025,95%CI=(1.009,1.040), p = 0.002] were independent risk factors for RSSI. In contrast, the decrease of the standard deviation of N-N intervals (SDNN) [OR=0.994,95%CI=(0.989,1.000), p = 0.035] was beneficial to the occurrence of RSSI. In addition, neutrophil counts [OR=1.138,95%CI=(1.030,1.258), p = 0.011], total cholesterol (TC) [OR=1.203,95%CI=(1.008,1.437), p = 0.041] and High-Density Lipoprotein (HDL) [OR=0.391, 95%CI=(0.195,0.786), p = 0.008] were also independently associated with the occurrence of RSSI. After adjusting for confounding factors, except for TC, the other factors remained associated with the occurrence of RSSI.

Conclusion: Increased 24-hour mean DBP, nocturnal mean SBP and DBP, SD of 24-hour DBP and decreased SDNN were independently correlated with RSSI occurrence, suggesting that sympathetic overactivity plays a role in the pathogenesis of RSSI.

目的:自律神经系统(ANS)功能障碍可能与脑小血管病(CSVD)的发病机制有关。本研究旨在探讨近期皮层下小梗死(RSSI)与血压变异性(BPV)和心率变异性(HRV)之间的关系:方法:从河南省CSVD登记研究数据库中选取588例患者作为研究对象,根据RSSI的存在情况分为两组。收集临床数据,包括人口统计学特征、病史、实验室指标、24 小时动态血压和心电图指标以及 CSVD 影像学标志物。采用单变量和二元逻辑回归分析研究CSVD人群中RSSI与实验室指标、心率变异和血压变异之间的关系:多变量分析显示,较高的 24 小时平均舒张压(DBP)[Odds Ratios (OR)=1.083,95% Confidence Intervals (CI)=(1.038,1.129), p < 0.001]、24 小时 DBP 的标准差(SD)[OR=1.059,95%CI=(1.000,1.121),p = 0.049]、夜间平均收缩压(SBP)[OR=1.020,95%CI=(1.004,1.035),p = 0.012]、夜间平均DBP[OR=1.025,95%CI=(1.009,1.040),p = 0.002]是RSSI的独立危险因素。相反,N-N 间期标准偏差(SDNN)的降低[OR=0.994,95%CI=(0.989,1.000), p = 0.035]有利于 RSSI 的发生。此外,中性粒细胞计数[OR=1.138,95%CI=(1.030,1.258), p = 0.011]、总胆固醇(TC)[OR=1.203,95%CI=(1.008,1.437), p = 0.041]和高密度脂蛋白(HDL)[OR=0.391,95%CI=(0.195,0.786), p = 0.008]也与RSSI的发生独立相关。在对混杂因素进行调整后,除 TC 外,其他因素仍与 RSSI 的发生相关:结论:24 小时平均 DBP、夜间平均 SBP 和 DBP、24 小时 DBP 的 SD 值以及 SDNN 值的降低均与 RSSI 的发生独立相关,表明交感神经过度活跃在 RSSI 的发病机制中起作用。
{"title":"Analysis of the Relationship between Recent Small Subcortical Infarcts and Autonomic Nervous Dysfunction.","authors":"Wenxin Yuan, Lu An, Yunchao Wang, Ce Zong, Yinghao Yang, Hua Jin, Yuan Gao, Limei Wang, Yusheng Li, Yuming Xu, Yan Ji","doi":"10.2174/0115672026303708240321035356","DOIUrl":"10.2174/0115672026303708240321035356","url":null,"abstract":"<p><strong>Objective: </strong>Autonomic Nervous System (ANS) dysfunction may be involved in the pathogenesis of Cerebral Small Vessel Disease (CSVD). The study aimed to explore the relationship between Recent Small Subcortical Infarct (RSSI) and Blood Pressure Variability (BPV), and Heart Rate Variability (HRV).</p><p><strong>Methods: </strong>A total of 588 patients from the CSVD registration research database of Henan Province were included in this study, and were divided into two groups according to the presence of RSSI. Clinical data, including demographic characteristics, disease history, laboratory indexes, 24-hour ambulatory blood pressure and electrocardiogram indicators, and imaging markers of CSVD, were collected. Univariate and binary logistic regression analyses were used to study the relationship between RSSI and indicators of laboratory, HRV and BPV in the CSVD population.</p><p><strong>Results: </strong>Multivariate analysis showed that higher 24-hour mean Diastolic Blood Pressure (DBP)[Odds Ratios (OR)=1.083,95% Confidence Intervals (CI)=(1.038,1.129), p < 0.001], Standard Deviation (SD) of 24-hour DBP [OR=1.059,95%CI=(1.000,1.121), p = 0.049], nocturnal mean Systolic Blood Pressure (SBP) [OR=1.020,95%CI=(1.004,1.035), p = 0.012], nocturnal mean DBP [OR=1.025,95%CI=(1.009,1.040), p = 0.002] were independent risk factors for RSSI. In contrast, the decrease of the standard deviation of N-N intervals (SDNN) [OR=0.994,95%CI=(0.989,1.000), p = 0.035] was beneficial to the occurrence of RSSI. In addition, neutrophil counts [OR=1.138,95%CI=(1.030,1.258), p = 0.011], total cholesterol (TC) [OR=1.203,95%CI=(1.008,1.437), p = 0.041] and High-Density Lipoprotein (HDL) [OR=0.391, 95%CI=(0.195,0.786), p = 0.008] were also independently associated with the occurrence of RSSI. After adjusting for confounding factors, except for TC, the other factors remained associated with the occurrence of RSSI.</p><p><strong>Conclusion: </strong>Increased 24-hour mean DBP, nocturnal mean SBP and DBP, SD of 24-hour DBP and decreased SDNN were independently correlated with RSSI occurrence, suggesting that sympathetic overactivity plays a role in the pathogenesis of RSSI.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"166-176"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cerebral Small Vessel Disease Burden in Patients with Transient Global Amnesia and its Relationship with Recurrence. 短暂性全面失忆患者的脑小血管疾病负担及其与复发的关系
Pub Date : 2024-01-01 DOI: 10.2174/0115672026309418240322060729
Zhi-Li Wang, Simeng Wang, Dongtao Liu, Yuelei Lyu, Wei Qin, Wenli Hu

Objective: Cerebral Small Vessel Disease (CSVD) has not been systematically studied in patients with Transient Global Amnesia (TGA). We aimed to investigate the CSVD burden in patients with TGA and its relationship with TGA recurrence.

Methods: We retrospectively examined 69 patients diagnosed with TGA in a single center between January 2015 and November 2023. The overall CSVD burden and single CSVD imaging markers, including enlarged perivascular spaces in the hippocampus (H-EPVS), were measured in each patient and compared with those in 69 age- and sex-matched healthy controls. Multivariate logistic regression was performed to determine independent predictors of recurrence.

Results: Of the 69 included patients, 40 (58%) were female, and the median age was 67 years (range 42-83 years). Twenty-one patients (30.4%) showed dot-like hippocampal hyperintensities on diffusion-weighted imaging (DWI). The mean follow-up was 51 months. Sixteen patients (23.2%) experienced TGA recurrence. The burden of overall CSVD, lacunes, WMH, EPVS, and extensive H-EPVS was higher in TGA patients than in controls. TGA patients who experienced recurrence had a heavier overall CSVD burden, lower frequency of hippocampal DWI hyperintensities, and longer follow-up duration than those who had with single episode. In the multivariate analysis, only follow-up duration was an independent predictor of TGA recurrence.

Conclusion: The overall CSVD burden and extensive H-EPVS burden were higher in patients with TGA than healthy controls. Follow-up duration but not overall CSVD burden may predict TGA recurrence.

目的:尚未对短暂性全面遗忘(TGA)患者的脑小血管疾病(CSVD)进行系统研究。我们旨在研究 TGA 患者的 CSVD 负担及其与 TGA 复发的关系:我们对 2015 年 1 月至 2023 年 11 月期间在一个中心确诊的 69 例 TGA 患者进行了回顾性研究。我们测量了每位患者的总体 CSVD 负担和单一 CSVD 影像标记物,包括海马血管周围间隙增大(H-EPVS),并与 69 位年龄和性别匹配的健康对照者进行了比较。采用多变量逻辑回归法确定复发的独立预测因素:在 69 名患者中,40 人(58%)为女性,中位年龄为 67 岁(42-83 岁)。21名患者(30.4%)在弥散加权成像(DWI)中出现点状海马高密度。平均随访时间为 51 个月。16名患者(23.2%)经历了TGA复发。与对照组相比,TGA患者的总体CSVD、裂隙、WMH、EPVS和广泛H-EPVS负担较重。与单发患者相比,复发的TGA患者总体CSVD负担更重,海马DWI高密度的频率更低,随访时间更长。在多变量分析中,只有随访时间是TGA复发的独立预测因素:结论:与健康对照组相比,TGA患者的总体CSVD负担和广泛H-EPVS负担更高。随访持续时间而非总体 CSVD 负荷可能会预测 TGA 复发。
{"title":"Cerebral Small Vessel Disease Burden in Patients with Transient Global Amnesia and its Relationship with Recurrence.","authors":"Zhi-Li Wang, Simeng Wang, Dongtao Liu, Yuelei Lyu, Wei Qin, Wenli Hu","doi":"10.2174/0115672026309418240322060729","DOIUrl":"10.2174/0115672026309418240322060729","url":null,"abstract":"<p><strong>Objective: </strong>Cerebral Small Vessel Disease (CSVD) has not been systematically studied in patients with Transient Global Amnesia (TGA). We aimed to investigate the CSVD burden in patients with TGA and its relationship with TGA recurrence.</p><p><strong>Methods: </strong>We retrospectively examined 69 patients diagnosed with TGA in a single center between January 2015 and November 2023. The overall CSVD burden and single CSVD imaging markers, including enlarged perivascular spaces in the hippocampus (H-EPVS), were measured in each patient and compared with those in 69 age- and sex-matched healthy controls. Multivariate logistic regression was performed to determine independent predictors of recurrence.</p><p><strong>Results: </strong>Of the 69 included patients, 40 (58%) were female, and the median age was 67 years (range 42-83 years). Twenty-one patients (30.4%) showed dot-like hippocampal hyperintensities on diffusion-weighted imaging (DWI). The mean follow-up was 51 months. Sixteen patients (23.2%) experienced TGA recurrence. The burden of overall CSVD, lacunes, WMH, EPVS, and extensive H-EPVS was higher in TGA patients than in controls. TGA patients who experienced recurrence had a heavier overall CSVD burden, lower frequency of hippocampal DWI hyperintensities, and longer follow-up duration than those who had with single episode. In the multivariate analysis, only follow-up duration was an independent predictor of TGA recurrence.</p><p><strong>Conclusion: </strong>The overall CSVD burden and extensive H-EPVS burden were higher in patients with TGA than healthy controls. Follow-up duration but not overall CSVD burden may predict TGA recurrence.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"234-242"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Whole Transcriptome Sequencing of Peripheral Blood Identifies the Alzheimer's Disease-Related circRNA-miRNA-lncRNA Pathway. 外周血全转录组测序发现阿尔茨海默病相关的 circRNA-miRNA-lncRNA 通路
Pub Date : 2024-01-01 DOI: 10.2174/0115672026305417240209062508
Yucheng Gu, Nihong Chen, Lin Zhu, Xiangliang Chen, Teng Jiang, Yingdong Zhang

Background: Previous studies on transcriptional profiles suggested dysregulation of multiple RNA species in Alzheimer's disease. However, despite recent investigations revealing various aspects of circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) networks in Alzheimer's Disease (AD) pathogenesis, few genome-wide studies have explored circRNA-associated profiles in AD patients exhibiting varying degrees of cognitive loss.

Objective: To investigate the potential pathogenesis-related molecular biological changes in the various stages of AD progression.

Methods: Whole transcriptome sequencing was performed on the peripheral blood of 7 normal cognition (NC) subjects, 8 patients with mild cognitive impairment, 8 AD patients with mild dementia (miD), and 7 AD patients with moderate dementia (moD). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to predict the potential functions of the maternal genes of microRNAs (miRNAs), circRNAs and long non-coding RNAs (lncRNAs). The construction of ceRNA network was performed between the NC group and each diseased group based on the differently expressed RNAs.

Results: In total, 3568 messenger RNAs (mRNAs), 142 miRNAs, 990 lncRNAs, and 183 circRNAs were identified as significantly differentially expressed across the four groups. GO and KEGG enrichment analysis revealed the significant roles of GTPase activity and the MAPK signaling pathway in AD pathogenesis. A circRNA-miRNA-lncRNA ceRNA pathway, characterized by the downregulated hsa-miR-7-5p and upregulated hsa_circ_0001170, was identified based on the differentially expressed RNAs between the NC group and the moD group.

Conclusion: The study suggests that circRNAs may be independent of mRNAs in AD pathogenesis and holds promise as potential biomarkers for AD clinical manifestations and pathological changes.

背景:以前对转录谱的研究表明,阿尔茨海默病中存在多种 RNA 的失调。然而,尽管最近的研究揭示了阿尔茨海默病(AD)发病机制中与环状RNA(circRNA)相关的竞争性内源性RNA(ceRNA)网络的各个方面,但很少有全基因组研究对表现出不同程度认知能力丧失的AD患者的环状RNA相关谱进行探讨:研究AD不同进展阶段潜在的发病机制相关分子生物学变化:对 7 名正常认知(NC)受试者、8 名轻度认知障碍患者、8 名轻度痴呆(miD)AD 患者和 7 名中度痴呆(moD)AD 患者的外周血进行全转录组测序。通过基因本体(GO)分析和京都基因组百科全书(KEGG)通路分析,预测了微RNA(miRNA)、环RNA和长非编码RNA(lncRNA)母体基因的潜在功能。根据不同表达的RNA构建了NC组与各患病组之间的ceRNA网络:结果:四组中共有 3568 个 mRNA、142 个 miRNA、990 个 lncRNA 和 183 个 circRNA 有显著差异表达。GO和KEGG富集分析显示,GTPase活性和MAPK信号通路在AD发病机制中起着重要作用。根据NC组与moD组之间差异表达的RNA,确定了一条circRNA-miRNA-lncRNA ceRNA通路,其特征是hsa-miR-7-5p下调,hsa_circ_0001170上调:该研究表明,循环RNA在AD发病机制中可能独立于信使RNA(mRNA),有望成为AD临床表现和病理变化的潜在生物标记物。
{"title":"Whole Transcriptome Sequencing of Peripheral Blood Identifies the Alzheimer's Disease-Related circRNA-miRNA-lncRNA Pathway.","authors":"Yucheng Gu, Nihong Chen, Lin Zhu, Xiangliang Chen, Teng Jiang, Yingdong Zhang","doi":"10.2174/0115672026305417240209062508","DOIUrl":"10.2174/0115672026305417240209062508","url":null,"abstract":"<p><strong>Background: </strong>Previous studies on transcriptional profiles suggested dysregulation of multiple RNA species in Alzheimer's disease. However, despite recent investigations revealing various aspects of circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) networks in Alzheimer's Disease (AD) pathogenesis, few genome-wide studies have explored circRNA-associated profiles in AD patients exhibiting varying degrees of cognitive loss.</p><p><strong>Objective: </strong>To investigate the potential pathogenesis-related molecular biological changes in the various stages of AD progression.</p><p><strong>Methods: </strong>Whole transcriptome sequencing was performed on the peripheral blood of 7 normal cognition (NC) subjects, 8 patients with mild cognitive impairment, 8 AD patients with mild dementia (miD), and 7 AD patients with moderate dementia (moD). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to predict the potential functions of the maternal genes of microRNAs (miRNAs), circRNAs and long non-coding RNAs (lncRNAs). The construction of ceRNA network was performed between the NC group and each diseased group based on the differently expressed RNAs.</p><p><strong>Results: </strong>In total, 3568 messenger RNAs (mRNAs), 142 miRNAs, 990 lncRNAs, and 183 circRNAs were identified as significantly differentially expressed across the four groups. GO and KEGG enrichment analysis revealed the significant roles of GTPase activity and the MAPK signaling pathway in AD pathogenesis. A circRNA-miRNA-lncRNA ceRNA pathway, characterized by the downregulated hsa-miR-7-5p and upregulated hsa_circ_0001170, was identified based on the differentially expressed RNAs between the NC group and the moD group.</p><p><strong>Conclusion: </strong>The study suggests that circRNAs may be independent of mRNAs in AD pathogenesis and holds promise as potential biomarkers for AD clinical manifestations and pathological changes.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"184-197"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Safety of Mechanical Thrombectomy for Acute Ischemic Stroke in Patients with Thrombocytopenia. 机械血栓切除术治疗血小板减少症患者急性缺血性中风的安全性。
Pub Date : 2024-01-01 DOI: 10.2174/0115672026296867240626120014
Sujie Zheng, Fang Liu, Liang Yu, Xinzhao Jiang, Xiaoyan Wen, Xu Wang, Zongjie Shi

Background and aim: The impact of low platelet count on outcomes in patients with Acute Ischemic Stroke (AIS) undergoing Mechanical Thrombectomy (MT) is still unclear. In this study we have further explored the effect of thrombocytopenia on the safety and efficacy of MT in patients with anterior circulation Large Vessel Occlusion (LVO) stroke.

Materials and methods: Patients with AIS who underwent MT at our center between June 2015 and November 2021 were examined. Based on the platelet count recorded on admission patients were divided into two groups: those with thrombocytopenia (<150 × 109/L) and those without thrombocytopenia (≥ 150 × 109/L). Symptomatic Intracranial Hemorrhage (sICH) was the primary safety outcome. The efficacy outcome was functional independence defined as a 90-day modified Rankin Scale (mRS) score of 0-2. Multivariate logistic regression models were used to determine the risk factors for post-procedure sICH and 90-day functional outcomes.

Results: Among 302 patients included in the study, thrombocytopenia was detected in 111 (36.8%) cases. Univariate analysis showed age, the proportion of atrial fibrillation, the rates of sICH, 90-day poor outcomes, and mortality to be higher in patients with thrombocytopenia (all p <0.05). Multivariable analysis showed thrombocytopenia to be independently associated with a higher rate of sICH (OR 2.022, 95% CI 1.074-3.807, p =0.029) however, thrombocytopenia did not affect the 90-day functional outcomes (OR 1.045, 95%CI 0.490-2.230, p =0.909) and mortality (OR 1.389, 95% CI 0.467- 4.130 p = 0.554).

Conclusion: Thrombocytopenia may increase the risk of sICH but not affect the 90-day functional outcomes and mortality in patients with AIS treated with MT.

背景和目的:接受机械血栓切除术(MT)的急性缺血性卒中(AIS)患者中,血小板计数低对预后的影响尚不明确。在本研究中,我们进一步探讨了血小板减少对前循环大血管闭塞(LVO)卒中患者接受机械取栓术的安全性和有效性的影响:研究对象为2015年6月至2021年11月期间在本中心接受MT治疗的AIS患者。根据入院时记录的血小板计数,将患者分为两组:血小板减少组(结果:302 例患者中,有 1 例血小板减少,1 例血小板减少,1 例血小板减少,1 例血小板减少,1 例血小板减少在纳入研究的 302 例患者中,111 例(36.8%)发现血小板减少。单变量分析显示,血小板减少患者的年龄、心房颤动比例、sICH发生率、90天不良预后和死亡率均较高(均为p <;0.05)。多变量分析显示,血小板减少与较高的 sICH 发生率独立相关(OR 2.022,95% CI 1.074-3.807,p =0.029),但血小板减少并不影响 90 天功能预后(OR 1.045,95% CI 0.490-2.230,p =0.909)和死亡率(OR 1.389,95% CI 0.467-4.130 p =0.554):结论:血小板减少可能会增加接受 MT 治疗的 AIS 患者发生 sICH 的风险,但不会影响 90 天的功能预后和死亡率。
{"title":"Safety of Mechanical Thrombectomy for Acute Ischemic Stroke in Patients with Thrombocytopenia.","authors":"Sujie Zheng, Fang Liu, Liang Yu, Xinzhao Jiang, Xiaoyan Wen, Xu Wang, Zongjie Shi","doi":"10.2174/0115672026296867240626120014","DOIUrl":"10.2174/0115672026296867240626120014","url":null,"abstract":"<p><strong>Background and aim: </strong>The impact of low platelet count on outcomes in patients with Acute Ischemic Stroke (AIS) undergoing Mechanical Thrombectomy (MT) is still unclear. In this study we have further explored the effect of thrombocytopenia on the safety and efficacy of MT in patients with anterior circulation Large Vessel Occlusion (LVO) stroke.</p><p><strong>Materials and methods: </strong>Patients with AIS who underwent MT at our center between June 2015 and November 2021 were examined. Based on the platelet count recorded on admission patients were divided into two groups: those with thrombocytopenia (<150 × 10<sup>9</sup>/L) and those without thrombocytopenia (≥ 150 × 10<sup>9</sup>/L). Symptomatic Intracranial Hemorrhage (sICH) was the primary safety outcome. The efficacy outcome was functional independence defined as a 90-day modified Rankin Scale (mRS) score of 0-2. Multivariate logistic regression models were used to determine the risk factors for post-procedure sICH and 90-day functional outcomes.</p><p><strong>Results: </strong>Among 302 patients included in the study, thrombocytopenia was detected in 111 (36.8%) cases. Univariate analysis showed age, the proportion of atrial fibrillation, the rates of sICH, 90-day poor outcomes, and mortality to be higher in patients with thrombocytopenia (all p <0.05). Multivariable analysis showed thrombocytopenia to be independently associated with a higher rate of sICH (OR 2.022, 95% CI 1.074-3.807, p =0.029) however, thrombocytopenia did not affect the 90-day functional outcomes (OR 1.045, 95%CI 0.490-2.230, p =0.909) and mortality (OR 1.389, 95% CI 0.467- 4.130 p = 0.554).</p><p><strong>Conclusion: </strong>Thrombocytopenia may increase the risk of sICH but not affect the 90-day functional outcomes and mortality in patients with AIS treated with MT.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"286-291"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mendelian Randomization Highlights Gut Microbiota of Short-chain Fatty Acids' Producer as Protective Factor of Cerebrovascular Disease. 孟德尔随机化突显短链脂肪酸的肠道微生物群是脑血管疾病的保护因素。
Pub Date : 2024-01-01 DOI: 10.2174/0115672026299307240321090030
Shihang Luo, Rui Mao, Yi Li

Background: Recent research advancements have indicated a potential association between gut microbiota and cerebrovascular diseases, although the precise causative pathways and the directionality of this association remain to be fully elucidated.

Objective: This study utilized a bidirectional two-sample Mendelian Randomization (MR) methodology to explore the causal impact of gut microbiota compositions on the risk of cerebrovascular disease.

Methods: Genome-wide Association Study (GWAS) data pertaining to gut microbiota were obtained from the MiBioGen consortium. For Ischemic Stroke (IS), Transient Ischemic Attack (TIA), Vascular Dementia (VD), and Subarachnoid Hemorrhage (SAH), GWAS summary data were sourced from the FinnGen consortium, the IEU Open GWAS project, and the GWAS catalog, respectively.

Results: Our MR analyses identified that specific bacterial strains, notably those involved in the production of Short-chain Fatty Acids (SCFAs), including Barnesiella, Ruminococcus torques group, and Coprobacter, serve as protective factors against IS, TIA, and SAH. Linkage Disequilibrium Score Regression (LDSC) analysis corroborated a significant genetic correlation between these gut microbiota strains and various forms of cerebrovascular disease. In contrast, reverse MR analysis failed to establish a bidirectional causal relationship between genetically inferred gut microbiota profiles and these cerebrovascular conditions.

Conclusion: This investigation has pinpointed particular strains of gut microbiota that play protective or detrimental roles in cerebrovascular disease pathogenesis. These findings offer valuable insights that could be pivotal for the clinical management, prevention, and treatment of cerebrovascular diseases.

背景:最近的研究进展表明,肠道微生物群与脑血管疾病之间存在潜在关联:最近的研究进展表明,肠道微生物群与脑血管疾病之间存在潜在关联,但这种关联的确切致病途径和方向性仍有待全面阐明:本研究采用双向双样本孟德尔随机化(MR)方法,探讨肠道微生物群组成对脑血管疾病风险的因果影响:全基因组关联研究(GWAS)中有关肠道微生物群的数据来自 MiBioGen 联盟。缺血性中风(IS)、短暂性脑缺血发作(TIA)、血管性痴呆(VD)和蛛网膜下腔出血(SAH)的全基因组关联研究(GWAS)摘要数据分别来自FinnGen联盟、IEU开放GWAS项目和GWAS目录:我们的磁共振分析发现,特定的细菌菌株,尤其是那些参与生产短链脂肪酸(SCFAs)的菌株,包括Barnesiella、Ruminococcus torques group和Coprobacter,是IS、TIA和SAH的保护因子。连锁变异平衡分数回归(LDSC)分析证实了这些肠道微生物群菌株与各种脑血管疾病之间存在显著的遗传相关性。与此相反,反向磁共振分析未能在基因推断的肠道微生物群特征与这些脑血管疾病之间建立双向因果关系:这项调查确定了在脑血管疾病发病机制中起保护或有害作用的特定肠道微生物菌株。这些发现为脑血管疾病的临床管理、预防和治疗提供了宝贵的见解。
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引用次数: 0
Activation of Src Kinase Mediates the Disruption of Adherens Junction in the Blood-labyrinth Barrier after Acoustic Trauma. 声外伤后 Src 激酶的活化介导了血迷宫屏障粘连接头的破坏。
Pub Date : 2024-01-01 DOI: 10.2174/0115672026320884240620070951
Jianbin Sun, Tong Zhang, Chaoying Tang, Shuhang Fan, Qin Wang, Da Liu, Na Sai, Qi Ji, Weiwei Guo, Weiju Han

Background: Adherens junction in the blood-labyrinth barrier is largely unexplored because it is traditionally thought to be less important than the tight junction. Since increasing evidence indicates that it actually functions upstream of tight junction adherens junction may potentially be a better target for ameliorating the leakage of the blood-labyrinth barrier under pathological conditions such as acoustic trauma.

Aims: This study was conducted to investigate the pathogenesis of the disruption of adherens junction after acoustic trauma and explore potential therapeutic targets.

Methods: Critical targets that regulated the disruption of adherens junction were investigated by techniques such as immunofluorescence and Western blotting in C57BL/6J mice.

Results: Upregulation of Vascular Endothelial Growth Factor (VEGF) and downregulation of Pigment Epithelium-derived Factor (PEDF) coactivated VEGF-PEDF/VEGF receptor 2 (VEGFR2) signaling pathway in the stria vascularis after noise exposure. Downstream effector Src kinase was then activated to degrade VE-cadherin and dissociate adherens junction, which led to the leakage of the blood-labyrinth barrier. By inhibiting VEGFR2 or Src kinase, VE-cadherin degradation and blood-labyrinth barrier leakage could be attenuated, but Src kinase represented a better target to ameliorate blood-labyrinth barrier leakage as inhibiting it would not interfere with vascular endothelium repair, neurotrophy and pericytes proliferation mediated by upstream VEGFR2.

Conclusion: Src kinase may represent a promising target to relieve noise-induced disruption of adherens junction and hyperpermeability of the blood-labyrinth barrier.

背景:血-迷宫屏障中的粘连接头在很大程度上尚未被研究,因为传统上认为它不如紧密连接重要。越来越多的证据表明,粘连接头实际上在紧密连接的上游发挥作用,因此粘连接头有可能成为改善声外伤等病理情况下血流-迷宫屏障渗漏的更好靶点:方法:采用免疫荧光和 Western 印迹等技术对 C57BL/6J 小鼠进行了研究:结果:噪声暴露后,血管内皮生长因子(VEGF)的上调和色素上皮衍生因子(PEDF)的下调共同激活了血管纹中的VEGF-PEDF/VEGF受体2(VEGFR2)信号通路。下游效应因子 Src 激酶随后被激活,降解 VE-cadherin,解离粘连接头,从而导致血迷宫屏障渗漏。通过抑制血管内皮生长因子受体2或Src激酶,可减轻VE-adherin降解和血迷宫屏障渗漏,但Src激酶是改善血迷宫屏障渗漏的更好靶点,因为抑制它不会干扰由上游血管内皮生长因子受体2介导的血管内皮修复神经萎缩和周细胞增殖:结论:Src 激酶可能是缓解噪声引起的粘连接头破坏和血迷宫屏障高渗透性的一个有前途的靶点。
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引用次数: 0
Migraine Disorders, Neurovascular Disease, and the Underlying Role of Oxidative Stress. 偏头痛、神经血管疾病和氧化应激的潜在作用。
Pub Date : 2024-01-01 DOI: 10.2174/1567202621999240223164624
Kenneth Maiese
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引用次数: 0
期刊
Current neurovascular research
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