There is plenty of evidence that proves the beneficial and reliable effects of rehabilitation therapy,making it the most common treatment for patients with chronic stroke.It is believed that rehabilitation improves fu...There is plenty of evidence that proves the beneficial and reliable effects of rehabilitation therapy,making it the most common treatment for patients with chronic stroke.It is believed that rehabilitation improves functional recovery through neural network remodeling,which is observed as a motor map reorganization or functional connectivity change assessed by intracortical microstimulation or functional magnetic resonance imaging（MRI）.展开更多
Motor imagery is the mental representation of an action without overt movement or muscle activation. However, the effects of motor imagery on stroke-induced hand dysfunction and brain neural networks are still unknown...Motor imagery is the mental representation of an action without overt movement or muscle activation. However, the effects of motor imagery on stroke-induced hand dysfunction and brain neural networks are still unknown. We conducted a randomized controlled trial in the China Rehabilitation Research Center. Twenty stroke patients, including 13 males and 7 females, 32–51 years old, were recruited and randomly assigned to the traditional rehabilitation treatment group（PP group, n = 10） or the motor imagery training combined with traditional rehabilitation treatment group（MP group, n = 10）. All patients received rehabilitation training once a day, 45 minutes per session, five times per week, for 4 consecutive weeks. In the MP group, motor imagery training was performed for 45 minutes after traditional rehabilitation training, daily. Action Research Arm Test and the Fugl-Meyer Assessment of the upper extremity were used to evaluate hand functions before and after treatment. Transcranial magnetic stimulation was used to analyze motor evoked potentials in the affected extremity. Diffusion tensor imaging was used to assess changes in brain neural networks. Compared with the PP group, the MP group showed better recovery of hand function, higher amplitude of the motor evoked potential in the abductor pollicis brevis, greater fractional anisotropy of the right dorsal pathway, and an increase in the fractional anisotropy of the bilateral dorsal pathway. Our findings indicate that 4 weeks of motor imagery training combined with traditional rehabilitation treatment improves hand function in stroke patients by enhancing the dorsal pathway. This trial has been registered with the Chinese Clinical Trial Registry（registration number： Chi CTR-OCH-12002238）.展开更多
Studies have shown that functional network connection models can be used to study brain net- work changes in patients with schizophrenia. In this study, we inferred that these models could also be used to explore func...Studies have shown that functional network connection models can be used to study brain net- work changes in patients with schizophrenia. In this study, we inferred that these models could also be used to explore functional network connectivity changes in stroke patients. We used independent component analysis to find the motor areas of stroke patients, which is a novel way to determine these areas. In this study, we collected functional magnetic resonance imaging datasets from healthy controls and right-handed stroke patients following their first ever stroke. Using independent component analysis, six spatially independent components highly correlat- ed to the experimental paradigm were extracted. Then, the functional network connectivity of both patients and controls was established to observe the differences between them. The results showed that there were 11 connections in the model in the stroke patients, while there were only four connections in the healthy controls. Further analysis found that some damaged connections may be compensated for by new indirect connections or circuits produced after stroke. These connections may have a direct correlation with the degree of stroke rehabilitation. Our findings suggest that functional network connectivity in stroke patients is more complex than that in hea- lthy controls, and that there is a compensation loop in the functional network following stroke. This implies that functional network reorganization plays a very important role in the process of rehabilitation after stroke.展开更多
目的:采用网络药理学和分子对接技术预测竹沥-生姜配伍治疗中风病的作用靶点,探讨其治疗中风病的潜在分子作用机制和有效物质。方法:利用PubChem、SwissTargetPrediction和UniProt数据库挖掘竹沥-生姜药对的潜在活性成分及药物靶点,通过...目的:采用网络药理学和分子对接技术预测竹沥-生姜配伍治疗中风病的作用靶点,探讨其治疗中风病的潜在分子作用机制和有效物质。方法:利用PubChem、SwissTargetPrediction和UniProt数据库挖掘竹沥-生姜药对的潜在活性成分及药物靶点,通过GeneCards数据库筛选疾病靶点。将药物靶点与疾病靶点匹配所得交集靶点导入STRING构建蛋白质-蛋白质相互作用网络。借助Cytoscape软件筛选关键靶点,将关键靶点与对应成分联系起来绘制网络图,筛选关键成分;对关键靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。通过AutoDock软件对关键活性成分与潜在作用靶点进行分子对接验证。结果:筛选得到药组活性成分41个,相关靶点291个,中风病相关靶基因729个,以及竹沥-生姜药对治疗中风病的交集靶点67个。这些交集靶点主要参与细胞炎症反应、细胞活化、细胞免疫反应等过程,并与癌症的途径、脂质与动脉粥样硬化及糖尿病并发症中的晚期糖基化终末产物(Advanced Glycation EndProduct,AGE)-晚期糖基化终末产物受体(Receptor for Advanced Glycation End Products,RAGE)信号通路等相关。分子对接结果显示,竹沥、生姜的主要活性成分与中风病的潜在作用靶点间具有一定的结合活性。结论:竹沥-生姜可通过多成分、多靶点、多通路发挥对中风病的治疗作用。本研究为后续药理机制探索提供方向,为该药对临床应用提供了理论依据。展开更多
基金supported by a Grant-in-Aid for Scientific Research(grant No.17K01493to NO) from the Japan Society for the Promotion of Science
文摘There is plenty of evidence that proves the beneficial and reliable effects of rehabilitation therapy,making it the most common treatment for patients with chronic stroke.It is believed that rehabilitation improves functional recovery through neural network remodeling,which is observed as a motor map reorganization or functional connectivity change assessed by intracortical microstimulation or functional magnetic resonance imaging（MRI）.
文摘目的采用网络药理学方法探究益气活血方脑络欣通治疗缺血性脑卒中(ischemic stroke,IS)的作用机制,并通过分子对接技术进行初步验证。方法通过TCMSP、ETCM、化学专业数据库及文献筛选脑络欣通活性成分及作用靶点,通过OMIM、DisGeNET、GeneCards以及Drugbank数据库挖掘IS相关靶点;将交集靶点导入STRING平台和Cytoscape 3.8.2软件构建PPI网络并通过拓扑分析获得核心靶点,同时构建“中药—活性成分—核心靶点—疾病”可视化网络图;运用R软件进行GO功能及KEGG通路富集分析。最后借助Auto Dock Tools软件以及PyMOL软件进行分子对接和可视化。结果脑络欣通的潜在活性成分78个,治疗IS的潜在作用靶点200个,核心靶点包括STAT3、JUN、MAPK1、TP53等;作用较突出的活性成分包括槲皮素、β-谷甾醇、山柰酚、木犀草素等。进一步的生物功能分析获得150条信号通路,包括PI3K-AKT信号通路、HIF-1信号通路、FoxO信号通路等关键通路。分子对接结果表明关键活性成分与核心靶点之间存在分子结合位点,并有较强的结合活性。结论益气活血方脑络欣通可能是通过多成分、多靶点协同作用于氧化应激、炎症反应、细胞凋亡、自噬等生理病理环节,从而发挥治疗IS的作用。
基金supported by the National Natural Science Foundation of China,No.U1613228a grant from the Sub-Project under National “Twelfth Five-Year” Plan for Science & Technology Support Project in China,No.2011BAI08B11+1 种基金a grant from the Beijing Municipal Science & Technology Commission in China,No.Z161100002616018the Special Fund for Basic Scientific Research Business of Central Public Scientific Research Institutes in China,No.2014CZ-5,2015CZ-30
文摘Motor imagery is the mental representation of an action without overt movement or muscle activation. However, the effects of motor imagery on stroke-induced hand dysfunction and brain neural networks are still unknown. We conducted a randomized controlled trial in the China Rehabilitation Research Center. Twenty stroke patients, including 13 males and 7 females, 32–51 years old, were recruited and randomly assigned to the traditional rehabilitation treatment group（PP group, n = 10） or the motor imagery training combined with traditional rehabilitation treatment group（MP group, n = 10）. All patients received rehabilitation training once a day, 45 minutes per session, five times per week, for 4 consecutive weeks. In the MP group, motor imagery training was performed for 45 minutes after traditional rehabilitation training, daily. Action Research Arm Test and the Fugl-Meyer Assessment of the upper extremity were used to evaluate hand functions before and after treatment. Transcranial magnetic stimulation was used to analyze motor evoked potentials in the affected extremity. Diffusion tensor imaging was used to assess changes in brain neural networks. Compared with the PP group, the MP group showed better recovery of hand function, higher amplitude of the motor evoked potential in the abductor pollicis brevis, greater fractional anisotropy of the right dorsal pathway, and an increase in the fractional anisotropy of the bilateral dorsal pathway. Our findings indicate that 4 weeks of motor imagery training combined with traditional rehabilitation treatment improves hand function in stroke patients by enhancing the dorsal pathway. This trial has been registered with the Chinese Clinical Trial Registry（registration number： Chi CTR-OCH-12002238）.
基金supported by the National Natural Science Foundation of China,No.60905024
文摘Studies have shown that functional network connection models can be used to study brain net- work changes in patients with schizophrenia. In this study, we inferred that these models could also be used to explore functional network connectivity changes in stroke patients. We used independent component analysis to find the motor areas of stroke patients, which is a novel way to determine these areas. In this study, we collected functional magnetic resonance imaging datasets from healthy controls and right-handed stroke patients following their first ever stroke. Using independent component analysis, six spatially independent components highly correlat- ed to the experimental paradigm were extracted. Then, the functional network connectivity of both patients and controls was established to observe the differences between them. The results showed that there were 11 connections in the model in the stroke patients, while there were only four connections in the healthy controls. Further analysis found that some damaged connections may be compensated for by new indirect connections or circuits produced after stroke. These connections may have a direct correlation with the degree of stroke rehabilitation. Our findings suggest that functional network connectivity in stroke patients is more complex than that in hea- lthy controls, and that there is a compensation loop in the functional network following stroke. This implies that functional network reorganization plays a very important role in the process of rehabilitation after stroke.
文摘目的:采用网络药理学和分子对接技术预测竹沥-生姜配伍治疗中风病的作用靶点,探讨其治疗中风病的潜在分子作用机制和有效物质。方法:利用PubChem、SwissTargetPrediction和UniProt数据库挖掘竹沥-生姜药对的潜在活性成分及药物靶点,通过GeneCards数据库筛选疾病靶点。将药物靶点与疾病靶点匹配所得交集靶点导入STRING构建蛋白质-蛋白质相互作用网络。借助Cytoscape软件筛选关键靶点,将关键靶点与对应成分联系起来绘制网络图,筛选关键成分;对关键靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。通过AutoDock软件对关键活性成分与潜在作用靶点进行分子对接验证。结果:筛选得到药组活性成分41个,相关靶点291个,中风病相关靶基因729个,以及竹沥-生姜药对治疗中风病的交集靶点67个。这些交集靶点主要参与细胞炎症反应、细胞活化、细胞免疫反应等过程,并与癌症的途径、脂质与动脉粥样硬化及糖尿病并发症中的晚期糖基化终末产物(Advanced Glycation EndProduct,AGE)-晚期糖基化终末产物受体(Receptor for Advanced Glycation End Products,RAGE)信号通路等相关。分子对接结果显示,竹沥、生姜的主要活性成分与中风病的潜在作用靶点间具有一定的结合活性。结论:竹沥-生姜可通过多成分、多靶点、多通路发挥对中风病的治疗作用。本研究为后续药理机制探索提供方向,为该药对临床应用提供了理论依据。
文摘目的运用网络药理学、分子对接方法,挖掘熊果酸(ursolic acid,UA)治疗缺血性脑卒中的作用靶点及其潜在的分子机制。方法通过中药系统药理学数据库与分析平台及SwissTargetPrediction数据库对UA进行靶点预测,在Gene Cards数据库中获取缺血性脑卒中的靶点,并构建UA-缺血性脑卒中交叠靶点,通过String平台构建交叠靶点蛋白互作(protein-protein interaction,PPI)网络图,应用Cytoscape 3.9.1软件对PPI网络图进行拓扑属性分析,筛选出关键靶点后,进行基因本体论(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,最后进行靶点-UA分子对接进行验证。结果共筛选得到UA相关靶点122个和3509个缺血性脑卒中靶点;获得UA-缺血性脑卒中交叠靶点98个及19个关键靶点;其中白细胞介素-6(interleukin 6,IL-6)、肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素-1β(interleukin 1β,IL-1β)、信号转导及转录激活因子3(signal transducers and activators of transcription,STAT3)、过氧化物酶体增殖激活受体γ(peroxisome proliferative activated receptor gamma,PPARG)是排名前5的核心靶点;KEGG通路富集分析结果显示关键靶点主要富集在血脂和动脉粥样硬化、TNF信号通路、白细胞介素17(interleukin 17,IL-17)信号通路、晚期糖基化终末产物-受体(advanced glycation end products-receptor for advanced glycation end products,AGE-RAGE)信号通路;GO功能富集分析显示关键靶点主要涉及转录因子活性、神经元凋亡过程的正向调节、炎症反应等过程;分子对接结果显示UA和排名前5的核心靶点可以稳定的结合,结合能均小于0 kcal/mol。结论UA可能通过调节IL-6、TNF、IL-1β、STAT3、PPARG影响血脂和动脉粥样硬化、TNF信号通路、IL-17信号通路、AGE-RAGE信号通路,发挥抗炎、神经保护等作用,以治疗缺血性脑卒中。
