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1.
目的：运用网络药理学方法探讨参芪复方治疗2型糖尿病（T2DM）的作用靶点及机制。方法：采用TCMSP平台筛选出参芪复方8味中药的活性成分及成分相关靶点,运用GeneCards、OMIM数据库筛选出与T2DM相关的疾病靶点,成分靶点与疾病靶点的交集基因即为参芪复方治疗T2DM的潜在作用靶点。通过STRING数据库和Cytoscape 3.7.2 软件构建可视化网络并寻找核心作用靶点,利用DAVID数据库对核心靶点进行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析。结果：筛选出参芪复方药物活性成分152种及成分相关靶点218个,T2DM的相关靶点12648个,成分与疾病的交集靶点共210个,其中AKT丝氨酸/苏氨酸激酶1（AKT1）、肿瘤蛋白P53（TP53）、白细胞介素6（IL-6）、血管内皮生长因子A（VEGFA）、丝裂原活化蛋白激酶1（MAPK1）等可能是参芪复方发挥效应的关键靶点;GO功能分析共涉及255个条目,主要涉及细胞核、RNA转录、DNA等,KEGG通路分析共涉及96条通路,主要包括核因子激活的B细胞的κ-轻链增强（NF-κB）信号通路、环磷酸腺苷（cAMP）信号通路、雷帕霉素靶蛋白（mTOR）信号通路、转化生成因子-β（TGF-β）信号通路等。结论：参芪复方可能通过多种活性成分介导多靶点、多通路发挥治疗T2DM的作用。 相似文献
2.
目的：探讨黄芪治疗糖尿病肾病的作用机制。方法：本研究通过中药系统药理学分析平台（TCMSP）数据库获取黄芪中含有的活性成分及成分所对应的靶点,通过GeneCards数据库挖掘糖尿病肾病疾病靶点,结合化合物及疾病靶点,构建成分-靶点网络图,并针对靶点进行基因本体（GO）富集分析及KEGG通路富集分析。结果：黄芪中含有 24个活性成分,对应糖尿病肾病110个靶点,可通过AGE-RAGE 信号通路、PI3K-AKT信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、白细胞介素（IL）-17信号通路等调控糖尿病肾病增殖、凋亡、炎症等过程。结论：网络药理学研究表明黄芪可通过多种通路途经发挥作用,可为今后开展黄芪治疗糖尿病肾病相关实验验证提供依据。 相似文献
3.
目的：应用网络药理学与分子对接技术探讨青风藤治疗膝骨关节炎（KOA）的作用机制。方法：从TCMSP数据库中提取青风藤的化学成分,获得药物靶点及疾病相关基因,筛选交集靶点,获得青风藤治疗 KOA 的作用靶点。对交集靶点及相关信号通路利用数据库进行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析。通过分子对接平台进行分子对接。结果：获得青风藤化合物主要化学成分6种、疾病基因643个、药物与疾病交集靶点11个。网络分析结果显示,青风藤通过调控肿瘤信号通路、糖尿病并发症中的糖基化终末产及其受体信号通路（AGE-RAGE）、细胞凋亡信号通路、肿瘤抑制蛋白p53 信号通路（p53）、血清素突触信号通路等作用于前列腺素 G/H 合酶 1（PTGS1）、前列腺素-内过氧化物酶合酶 2（PTGS2）、过氧化物酶体增殖物激活受体（PPARG）、B淋巴细胞瘤-2（Bcl-2）、转化生长因子β-1前蛋白（TGFB1）、胱天蛋白酶3（CASP3）等关键靶点,通过干预细胞凋亡、抑制炎症等发挥治疗KOA的作用。分子对接结果显示,青风藤核心成分β-谷甾醇（beta-sitosterol）、青藤碱（Sinomenine）与核心靶点结合高度稳定。结论：青风藤治疗KOA是多通路、多靶点共同作用的结果,其作用机制与细胞凋亡、炎症关系最为密切。 相似文献
4.
目的：运用网络药理学和分子对接技术探讨罗汉果治疗糖尿病的作用机制。方法：通过TCMSP平台和Swiss Target Prediction数据库筛选出罗汉果的活性成分及其靶点;利用GeneCard、TTD、OMIM数据库筛选出糖尿病潜在靶点;采用Cytoscape 3.7.2软件构建药物-活性成分-疾病-靶点的可视化网络;通过STRING数据库对关键靶点构建蛋白质-蛋白质相互作用（PPI）网络;利用Metascape数据库进行基因本体（GO）功能以及京都基因与基因组百科全书（KEGG）通路富集分析;利用Autodock4和Pymol软件对关键活性成分和关键靶点进行分子对接分析和可视化。结果：筛选出有效成分18种,糖尿病靶点146个。GO功能富集分析得到GO条目572条,KEGG通路富集分析得到信号通路167条。分子对接结果显示β-谷甾醇、山柰酚、罗汉果醇等关键活性成分与原癌基因酪氨酸蛋白激酶（SRC）等关键靶点的亲和力较高。结论：罗汉果通过多靶点、多通路发挥抗糖尿病的作用,其关键活性成分通过与SRC、丝氨酸/苏氨酸蛋白激酶1（AKT1）、丝裂原活化蛋白激酶3（MAPK-3）等靶点调节晚期糖基化终末产物-糖基化终末产物受体（AGE-RAGE）、缺氧诱导因子1（HIF-1）、磷脂酰肌醇-3-激酶/蛋白激酶（PI3K-Akt）等信号通路起到治疗糖尿病的作用。 相似文献
5.
目的：基于网络药理学方法探讨党参治疗2型糖尿病(T2DM)的潜在作用机制。方法：通过中药系统药理学分析平台数据库（TCMSP）及OMIM、TTD、Drugbank等网络数据库分别获取药物有效成分、活性靶点、疾病靶点,并取药物成分和疾病的交集靶点,构建药物活性成分与关键靶点网络、蛋白质相互作用（PPI）网络,并对靶蛋白进行GO富集分析和KEGG通路分析。结果：得到药效活性成分21种,药物靶点108个,T2DM靶点2402个,两者匹配映射得到关键靶点28个。党参治疗T2DM的主要成分为木樨草素、7-甲氧基-2-甲基-异黄酮、豆甾醇、黄豆黄素等,关键靶点为白细胞介素-6（IL-6）、血管内皮生长因子A（VEGFA）、过氧化物酶体增殖物激活受体r（PPARG）等,关键的生物学进程包括药物反应、葡萄糖稳态;关键通路为PI3K-Akt 信号通路、AMPK信号通路、FoxO信号通路、胰岛素抵抗。结论：党参治疗T2DM具有多成分、多靶点、多途径的特点。 相似文献
6.
目的：基于数据挖掘分析中药治疗寒湿型腰痛的核心药物,并采用网络药理学探析其作用机制。方法：检索中国知网（CNKI）、万方数据（WANFANG DATA）、维普中文科技期刊数据库（VIP）、中国生物医学文献数据库（CBM）、中国中医药数据库中2012年1月1日至2021年10月31日收录的中药治疗寒湿型腰痛的相关文献,根据纳入和排除标准进行筛选。对纳入文献运用SPSS 25.0、IBM SPSS Modeler 18进行统计分析,探究中药治疗寒湿型腰痛的核心药物。应用TCMSP平台检索核心药物的有效成分及靶点,利用David数据库对核心药物作用靶点进行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析。结果：通过检索数据库筛选及运用K-core（k核算法）分析得到治疗寒湿腰痛的核心药物为桑寄生、川乌、杜仲、牛膝和甘草。对5味核心药物的潜在靶点进行预测,得到血管内皮生长因子A（VEGFA）、缺氧诱导因子1A（HIF1A）、表皮生长因子受体（EGFR）等10个关键靶点,靶点主要富集在分子功能中的蛋白结合以及等离子体膜、细胞质等细胞组分方面,预测可能作用于癌症通路、神经活性配体-受体相互作用通路、钙离子信号通道、丝裂原活化蛋白激酶（MAPK）信号通道和环磷酸腺苷（cAMP）信号通路。结论：中药治疗寒湿型腰痛以桑寄生、川乌、杜仲、牛膝和甘草为核心药物,核心药物的关键成分可通过调控VEFGA、HIF1A等关键靶点,作用于MAPK、cAMP等信号通路发挥作用。 相似文献
7.
目的：运用网络药理学方法挖掘桂枝-柴胡治疗慢性心力衰竭（CHF）伴抑郁（MDD）的主要活性成分、靶点及信号通路,探究其潜在作用机制。方法：通过TCMSP数据库和相关文献检索桂枝-柴胡主要活性成分及其作用靶点,经BATMAN-TCM平台对预测靶点予以补充,构建药物靶点库;通过GeneCards、DisGeNET数据库分别获取CHF与抑郁相关靶标,二者取交集,建立疾病靶标库;利用R语言将药物靶点库与疾病靶标库取交集,构建Venn图;通过STRING数据库和Cytoscape 3.7.1软件及其内在插件构建化合物-靶标网络及PPI核心网络;最后利用DAVID数据库对核心网络靶点进行GO富集和KEGG通路注释分析。结果：筛选出桂枝-柴胡有27个活性成分,288个靶基因;筛选出CHF伴MDD相关靶基因882个,药物与疾病Venn图提取关键靶点83个,PPI核心网络构建筛选出12个关键基因;GO分析（P＜0.05且靶点基因富集度>10%）得到19条生物过程,13条细胞组分表达过程,8个分子功能相关过程;KEGG分析（P＜0.05）显示72条信号通路,包括HIF-1信号通路、TNF信号通路、PI3K-Akt信号通路、神经活性配体-受体相互作用信号通路等。结论：桂枝-柴胡活性成分通过多成分、多靶点、多通路发挥CHF伴MDD的治疗作用。 相似文献
8.
目的：通过网络药理学方法和分子对接技术,寻找“卷柏-猕猴桃根”药对的主要活性成分,探讨其在肺结节治疗中的作用机制。方法：在TCMSP网站中检索草药卷柏和猕猴桃根,获得两药所含化合物。经过ADME筛选与文献检索,确定药对主要活性化合物。利用PubChem、ChEMBL寻找该药对化合物的预测靶点。利用GeneCard、DisGeNET寻找肺结节的相关基因。利用Venny 2.1在线工具进行韦恩分析,寻找药对与肺结节共有的基因靶点。在OmicShare tools中进行基因本体（GO）功能、京都基因与基因组百科全书（KEGG）通路富集分析。在KEGG ORTHOLOGY数据库中进行基因靶点KO映射。利用分子对接技术验证化合物与预测靶点的对接能力,并进行筛选。在Cytoscape 3.7.1软件中,构建对接成功的“药物-关键化合物-关键靶点-关键通路”网络。结果：本研究共获得9种关键化合物、21个关键靶点。卷柏和猕猴桃根的关键化合物为苏铁黄酮、穗花杉双黄酮、秦皮素、儿茶素、芹菜素、表儿茶素、芦荟大黄素、香草酸、原儿茶酸。关键靶点为磷脂酰肌醇-4,5-二磷酸3-激酶催化亚单位δ（PIK3CD）、磷酸二酯酶4D（PDE4D）、热休克蛋白90α家族A类成员1（HSP90AA1）、醛酮还原酶家族1成员B10（AKR1B10）、囊性纤维化跨膜转导调节因子（CFTR）、原癌基因酪氨酸蛋白激酶（ROS1）、髓样细胞白血病蛋白1（MCL1）等,关键作用通路为磷脂酰肌醇-3-激酶-蛋白激酶B（PI3K-Akt）信号通路、叉头框蛋白O（FoxO）信号通路、凋亡（Apoptosis）、环磷酸腺苷（cAMP）信号通路等。结论：“卷柏-猕猴桃根”的多种活性化合物通过作用于多通路的靶点蛋白而发挥治疗肺结节的作用。 相似文献
9.
目的：运用网络药理学方法研究苗药杜仙健骨方治疗膝骨关节炎(KOA)并骨质疏松症（OP）的生物活性成分和潜在作用机制。方法：运用中药系统药理学数据库和分析平台（TCMSP）,根据苗药所对应的中药,筛选出杜仙健骨方全方的主要活性成分及其相关作用靶标,借助OMIM、Drugbank、Genecards数据库,筛选出药物-疾病的共同作用靶标,并通过Venny 2.1.0绘制韦恩（Venn）图,利用Cytoscape软件绘制出药物-活性成分-靶点-疾病调控网络,将数据输入String数据库构建蛋白互作（PPl）网络和条形图,筛选核心靶标。最后通过Metascape软件进行基因本体（GO）功能及京都基因与基因组百科全书（KEGG）通路富集分析。结果：杜仙健骨方中发挥治疗KOA并OP作用的主要有效成分有槲皮素(Quercetin)、山柰酚(Kaempferol)、木犀草素(Luteolin)、β-谷甾醇(Beta-sitosterol)、黄芩素(Baicalein)等66个;关键靶基因230个,包括肿瘤坏死因子(TNF)、蛋白激酶B(AKT1)、癌基因(JUN)等;GO富集分析得到1266个生物学过程;KEGG通路分析明确了366条信号通路。结论：杜仙健骨方主要通过糖尿病并发症中的AGE-RAGE信号通路、癌症的途径、膀胱癌、破骨细胞分化的信号通路等的特点,调节细胞增殖-分化-凋亡过程,发挥抑制骨质疏松、控制炎症等作用,从而达到治疗KOA并OP的效果。 相似文献
10.
目的：基于网络药理学探讨肾复舒颗粒治疗慢性肾衰竭的相关靶点及其作用机制。方法：采用多个数据库获取肾复舒颗粒的化学成分、活性成分靶点及慢性肾衰竭的疾病靶点，获取药物-疾病的共同靶点，构建药物靶点-疾病靶点的蛋白质-蛋白质相互作用（PPI）网络以及核心靶点；对潜在作用靶点进行基因本体（GO）功能、京都基因与基因组百科全书（KEGG）通路富集分析；蛋白质免疫印迹实验检测5/6肾切除模型大鼠肾脏组织中磷酸化信号转录活化因子3（p-stat3）/信号转录活化因子3（stat3）以及抑癌基因（p53）蛋白的表达。结果：肾复舒颗粒共含有122个潜在活性成分，其对应872个药物靶点；共获得慢性肾衰竭的疾病靶点1159个；二者取交集后获得药物-疾病共同靶点137个。拓扑分析结果显示非受体酪氨酸激酶（SRC）、信号传导和转录激活因子3（STAT3）、p53、磷脂酰肌醇-4，5-二磷酸肌醇-3-激酶（PIK3CA）、丝裂原活化蛋白激酶1（MAPK1）等蛋白为核心靶点。GO功能富集分析结果显示肾复舒颗粒的作用靶点与基因表达的正向调控、MAPK激酶活性的正向调控、负调节凋亡过程有关。KEGG通路富集分析结果显示肾复舒颗粒的作用靶点与糖尿病并发症的晚期糖基化终产物及其受体（AGE-RAGE）信号通路、低氧诱导因子-1（HIF-1）信号通路、流体剪切应力和MAPK信号通路有关。动物实验结果表明肾复舒颗粒可抑制p-stat3/stat3以及p53的表达。结论：肾复舒颗粒可通过多成分、多靶点和多通路治疗慢性肾衰竭。 相似文献
11.
Derek V. Ellis 《Marine Georesources & Geotechnology》2001,19(1):51-63
This article reviews information recently available from existing marine and coastal mining for responses to environmental issues affecting marine mining at different depths. It is particularly but not exclusively concerned with those issues affecting seabed biodiversity impact and recovery. Much information has been gathered in the past 10 years from shallow mining operations for construction aggregate, diamonds, and gold, from coastal mines discharging tailings to shallow and deep water, and from experimental deep mining tests. The responses to issues identified are summarized in a series of eight tables intended to facilitate site-specific consideration. Since impacts can spread widely in the surface mixing layer SML, and can affect the biologically productive euphotic zone, the main issues considered arise from the depth of mining relative to the SML of the sea. Where mining is below the SML, the issue is whether it is environmentally better to bring the extraction products to the surface vessel for processing (and waste discharge), or to process the extraction products as much as possible on the seabed. Responses to the issues need to be sitespecific, and dependent on adequate preoperational environmental impact and recovery prediction. For deep tailings disposal from a surface vessel, there are four important environmental unknowns: (1) the possible growth of "marine snow" (bacterial flocs) utilizing the enormous quantities of fine tailings particles (hundreds or thousands of metric tons per day) as nuclei for growth, (2) the possibility that local keystone plankton and nekton species may migrate diurnally down to and beyond the depth of deep discharge and hence be subjected to tailings impact at depth, (3) the burrow-up capability of deep benthos and their ability to survive high rates of tailings deposition, and (4) the pattern and rate of dispersion of a tailings density current through the deep water column from discharge point to seabed. Actions to obtain relevant information in general and site-specifically are suggested. 相似文献
12.
G. Parthiban 《Marine Georesources & Geotechnology》2000,18(3):223-235
Particle fluxes were measured 7 m above the sea bottom during the predisturbance, disturbance, and postdisturbance periods by using time series sediment traps attached to seven deep-sea moorings deployed in the INDEX experiment site in the Central Indian Basin. The predisturbance particle fluxes varied between 22.3 to 55.1 mg m -2 day -1 . Increased and variable particle fluxes were recorded by the sediment traps during the disturbance period. The increase observed was 0.5 to 4 times more than the background predisturbance fluxes. The increases in particle fluxes (~4 times) recorded by the sediment trap located in the southwestern direction (DMS-1) were the greatest, which could be the result of preferential movement of resuspended particles generated during the deep-sea benthic disturbance along the general current direction prevailing in this area during the experimental period. Also, the traps located closer to the disturbance area recorded greater fluxes than did the traps far away, across the Deep Sea Sediment Resuspension System path. This variability in recorded particle fluxes by the traps around the disturbance area clearly indicates that physical characteristics such as grain size and density of the resuspended particles produced during the disturbance had an important effect on particle movement. The postdisturbance measurements during ~5 days showed a reduction in particle fluxes of ~50%, indicating rapid particle settlement. 相似文献
13.
Arne Schnack-Friedrichsen Angela M. Davis Jim D. Bennell Dei G. Huws 《Marine Georesources & Geotechnology》2001,19(4):221-243
The interdependence between the seismo-acoustic properties of a marine sediment and its geotechnical/physical parameters has been known for many years, and it has been postulated that this should allow the extraction of geotechnical information from seismic data. Though in the literature many correlations have been published for the surficial layer, there is a lack of information for greater sediment depths. In this article, a desktop study on a synthetic seafloor model illustrates how the application of published near-surface prediction equations to subsurface sediments (up to several tens of meters burial depth) can lead to spurious predictions. To test this further, acoustic and geotechnical properties were measured on a number of sediment core samples, some of which were subjected to loading in acoustically-equipped consolidation cells (oedometers) to simulate greater burial depth conditions. For low effective pressures (representing small burial depths extending to around 10 meters subsurface), the general applicability of established relationships was confirmed: the prediction of porosity, bulk density, and mean grain size from acoustic velocity and impedance appears generally possible for the investigated sedimentary environments. As effective pressure increases through, the observed relationships deviate more and more from the established ones for the near-surface area. For the samples tested in this study, in some instances increasing pressure even resulted in decreasing velocities. There are several possible explanations for this abnormal behavior, including the presence of gas, overconsolidation, or bimodal grain size distribution. The results indicate that an appropriate depth correction must be introduced into the published prediction equations in order to obtain reliable estimates of physical sediment properties for greater subsurface depths. 相似文献
14.
海上大直径钢管桩打桩过程中,桩周土体受到强烈扰动而发生强度弱化,掌握桩周土体强度弱化规律对于准确预测打桩过程、保证工程安全具有重要意义。为研究土体强度弱化规律,开展了环剪试验模拟打桩对桩周土体的扰动,测试土体强度随剪切速率的变化规律,建立了描述土体强度弱化规律的拟合公式,引入到打桩分析软件中。研究结果表明：土体的强度折减程度不仅与土体本身的性质有关还受到土体的埋深和剪切速率的影响,埋深越深土体强度折减程度越低,剪切速率越高土体强度折减越高,在打桩分析中可采用这里推荐的线性折减方法来模拟不同深度处土体强度的折减规律。 相似文献
15.
The advanced piston corer (APC) has been used by the Ocean Drilling Program since 1985 for recovering soft sediments from the ocean floor. The pullout force measured on extracting the core barrel from the sediment is shown to correlate with the average shear strength of the sediment core measured in the ship's laboratory. A simple rule of thumb is derived relating the shear strength of the sediment to the pullout force. Multiple APC holes at individual sites allow the consistency of the pullout measurements to be assessed. The effects of different operational procedures during APC coring are also explored. Although generally applicable, the correlation between pullout force and laboratory measurements of shear strength breaks down for some APC holes, possibly because of the disturbance of some sediment types during the APC coring process. A better understanding of the physical process of APC coring, and its effect on the properties of the sediment both inside and immediately outside the core barrel, would indicate what confidence can be put on the measurement of pullout force as a way of evaluating the in situ shear strength of deep sea sediments. 相似文献
16.
Shigehisa Nakamura 《Marine Geodesy》2000,23(1):55-61
Specific properties of the interannual sea level variations and annual tides in the Northwestern Pacific were studied. Several tide stations were monitored. The monthly mean sea level for the year of 1995 was analyzed at each tide station. A seismic event in 1995, some tectonic activity around the subject area, and the Kuroshio (the oceanic western boundary current) may possibly contaminate results which would have occurred from the astronomical annual tide alone. 相似文献
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《海洋学报(英文版)》2014,(11):161-F0003
<正>Acta Oceanologica Sinica(AOS)is a comprehensive academic journal edited by the Editorial Committee of Acta Oceanologica Sinica and is designed to provide a forum for important research papers of the marine scientific community which reflect the information on a worldwide basis.The journal publishes scholarly papers on marine science and technology,including physics,chemistry,biology, 相似文献