共查询到20条相似文献，搜索用时 31 毫秒
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The misfolding of amyloid-β (Aβ) peptides from the natural unfolded state to β-sheet structure is a critical step, leading to abnormal fibrillation and formation of endogenous Aβ plaques in Alzheimer''s disease (AD). Previous studies have reported inhibition of Aβ fibrillation or disassembly of exogenous Aβ fibrils in vitro. However, soluble Aβ oligomers have been reported with increased cytotoxicity; this might partly explain why current clinical trials targeting disassembly of Aβ fibrils by anti-Aβ antibodies have failed so far. Here we show that Au23(CR)14 (a new Au nanocluster modified by Cys-Arg (CR) dipeptide) is able to completely dissolve exogenous mature Aβ fibrils into monomers and restore the natural unfolded state of Aβ peptides from misfolded β-sheets. Furthermore, the cytotoxicity of Aβ40 fibrils when dissolved by Au23(CR)14 is fully abolished. More importantly, Au23(CR)14 is able to completely dissolve endogenous Aβ plaques in brain slices from transgenic AD model mice. In addition, Au23(CR)14 has good biocompatibility and infiltration ability across the blood–brain barrier. Taken together, this work presents a promising therapeutics candidate for AD treatment, and manifests the potential of nanotechnological approaches in the development of nanomedicines. 相似文献
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BackgroundAlzheimer's disease (AD) is a chronic, progressive neurodegenerative disease. Recent studies have reported the close association between cognitive function in AD and purinergic receptors in the central nervous system. In the current study, we investigated the effect of CD73 inhibitor α, β-methylene ADP (APCP) on cognitive impairment of AD in mice, and to explore the potential underlying mechanisms.ResultsWe found that acute administration of Aβ1–42 (i.c.v.) resulted in a significant increase in adenosine release by using microdialysis study. Chronic administration of APCP (10, 30 mg/kg) for 20 d obviously mitigated the spatial working memory impairment of Aβ1–42-treated mice in both Morris water maze (MWM) test and Y-maze test. In addition, the extracellular adenosine production in the hippocampus was inhibited by APCP in Aβ-treated mice. Further analyses indicated expression of acetyltransferase (ChAT) in hippocampus of mice of was significantly reduced, while acetylcholinesterase (AChE) expression increased, which compared to model group. We observed that APCP did not significantly alter the NLRP3 inflammasome activity in hippocampus, indicating that anti-central inflammation seems not to be involved in APCP effect.ConclusionsIn conclusion, we report for the first time that inhibition of CD73 by APCP was able to protect against memory loss induced by Aβ1–42 in mice, which may be due to the decrease of CD73-driven adenosine production in hippocampus. Enhancement of central cholinergic function of the central nervous system may also be involved in the effects of APCP.How to cite: Song W, Tang Y, Wei L, et al. Protective effect of CD73 inhibitor α, β-methylene ADP against amyloid-β-Induced cognitive impairment by inhibiting adenosine production in hippocampus. Electron J Biotechnol 2020;48. https://doi.org/10.1016/j.ejbt.2020.09.002 相似文献
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R. Dhananjayan K. S. Srivani Koundinya T. Malati Vijay Kumar Kutala 《Indian journal of clinical biochemistry : IJCB》2016,31(4):372-379
Endothelial dysfunction is an imbalance in the production of vasodilator factors and when this balance is disrupted, it predisposes the vasculature towards pro-thrombotic and pro-atherogenic effects. This results in vasoconstriction, leukocyte adherence, platelet activation, mitogenesis, pro-oxidation, impaired coagulation and nitric oxide production, vascular inflammation, atherosclerosis and thrombosis. Endothelial dysfunction is focussed as it is a potential contributor to the pathogenesis of vascular disease in diabetes mellitus. Under physiological conditions, there is a balanced release of endothelial-derived relaxing and contracting factors, but this delicate balance is altered in diabetes mellitus and atherosclerosis, thereby contributing to further progression of vascular and end-organ damage. This review focuses on endothelial dysfunction in atherosclerosis, insulin resistance, metabolic syndrome, oxidative stress associated with diabetes mellitus, markers and genetics that are implicated in endothelial dysfunction. 相似文献
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Sandra Prez-Rodríguez Stephanie A. Huang Carlos Borau Jos Manuel García-Aznar William J. Polacheck 《Biomicrofluidics》2021,15(5)
Extravasation of circulating cells is an essential process that governs tissue inflammation and the body''s response to pathogenic infection. To initiate anti-inflammatory and phagocytic functions within tissues, immune cells must cross the vascular endothelial barrier from the vessel lumen to the subluminal extracellular matrix. In this work, we present a microfluidic approach that enables the recreation of a three-dimensional, perfused endothelial vessel formed by human endothelial cells embedded within a collagen-rich matrix. Monocytes are introduced into the vessel perfusate, and we investigate the role of luminal flow and collagen concentration on extravasation. In vessels conditioned with the flow, increased monocyte adhesion to the vascular wall was observed, though fewer monocytes extravasated to the collagen hydrogel. Our results suggest that the lower rates of extravasation are due to the increased vessel integrity and reduced permeability of the endothelial monolayer. We further demonstrate that vascular permeability is a function of collagen hydrogel mass concentration, with increased collagen concentrations leading to elevated vascular permeability and increased extravasation. Collectively, our results demonstrate that extravasation of monocytes is highly regulated by the structural integrity of the endothelial monolayer. The microfluidic approach developed here allows for the dissection of the relative contributions of these cues to further understand the key governing processes that regulate circulating cell extravasation and inflammation. 相似文献
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《Information processing & management》2022,59(4):102965
Structural Magnetic Resonance Image (sMRI) and functional MRI (fMRI) are two of the most important modalities to unveil brain disorders for Alzheimer's disease (AD) analysis. Comprehensively utilizing both modalities is the way to ensure an accurate AD diagnosis. Currently, the most common computational approach to aid the AD diagnosis is to formulate the sMRI and fMRI into graphs and then extract discriminative features through Graph Neural Networks (GNNs). However, most GNNs rely heavily on the aggregation operation on each node, which exploits the local topological information from the neighborhood nodes but does not fully respect the characteristics of the global graph topology. Also, only a few works addressed the structural and functional coupling problem on the graphs. In this paper, a novel Riemannian manifold-based model, called Cross-Modal Riemannian Network (CMRN), is proposed to solve the above issues, which respects the global topologies and invariant characteristics of the sMRI and fMRI graphs by fully operating on the Riemannian Manifold. Furthermore, a novel cross-modal attention mechanism is proposed to enable the interactions between two modalities on the Riemannian manifold, which helps the model comprehensively utilize both modalities to identify the most discriminative information for AD diagnosis. Extensive experimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset demonstrate the effectiveness of the proposed method. 相似文献
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Microinjection with ultra-fine glass capillaries is widely used to introduce cryoprotective agents and other foreign molecules into animal cells, oocytes, and embryos. The fragility of glass capillaries makes difficult the microinjection of fish eggs and embryos, which are usually protected by a hard outer shell, called the chorion. In this study, we introduce a new electromechanical approach, based on the electropiercing of fish eggs with a stationary needle electrode. The electropiercing setup consists of two asymmetric electrodes, including a μm-scaled nickel needle placed opposite to a mm-scaled planar counter-electrode. A fish egg is immersed in low-conductivity solution and positioned between the electrodes. Upon application of a short electric pulse of sufficient field strength, the chorion is electroporated and the egg is attracted to the needle electrode by positive dielectrophoresis. As a result, the hard chorion and the subjacent yolk membrane are impaled by the sharp electrode tip, thus providing direct access to the egg yolk plasma. Our experiments on early-stage medaka fish embryos showed the applicability of electro-microinjection to fish eggs measuring about 1 mm in diameter. We optimized the electropiercing of medaka eggs with respect to the field strength, pulse duration, and conductivity of bathing medium. We microscopically examined the injection of dye solution into egg yolk and the impact of electropiercing on embryos'' viability and development. We also analyzed the mechanisms of electropiercing in comparison with the conventional mechanical microinjection. The new electropiercing method has a high potential for automation, e.g., via integration into microfluidic devices, which would allow a large-scale microinjection of fish eggs for a variety of applications in basic research and aquaculture. 相似文献
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Hao Wang Qingyuan Zhu Lufeng Ding Yan Shen Chao-Yu Yang Fang Xu Chang Shu Yujie Guo Zhiwei Xiong Qinghong Shan Fan Jia Peng Su Qian-Ru Yang Bing Li Yuxiao Cheng Xiaobin He Xi Chen Feng Wu Jiang-Ning Zhou Fuqiang Xu Hua Han Pak-Ming Lau Guo-Qiang Bi 《国家科学评论(英文版)》2019,6(5):982
The speed of high-resolution optical imaging has been a rate-limiting factor for meso-scale mapping of brain structures and functional circuits, which is of fundamental importance for neuroscience research. Here, we describe a new microscopy method of Volumetric Imaging with Synchronized on-the-fly-scan and Readout (VISoR) for high-throughput, high-quality brain mapping. Combining synchronized scanning beam illumination and oblique imaging over cleared tissue sections in smooth motion, the VISoR system effectively eliminates motion blur to obtain undistorted images. By continuously imaging moving samples without stopping, the system achieves high-speed 3D image acquisition of an entire mouse brain within 1.5 hours, at a resolution capable of visualizing synaptic spines. A pipeline is developed for sample preparation, imaging, 3D image reconstruction and quantification. Our approach is compatible with immunofluorescence methods, enabling flexible cell-type specific brain mapping and is readily scalable for large biological samples such as primate brains. Using this system, we examined behaviorally relevant whole-brain neuronal activation in 16 c-Fos-shEGFP mice under resting or forced swimming conditions. Our results indicate the involvement of multiple subcortical areas in stress response. Intriguingly, neuronal activation in these areas exhibits striking individual variability among different animals, suggesting the necessity of sufficient cohort size for such studies. 相似文献
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Hanaa H. Ahmed Selim F. Estefan Ehab M. Mohamd Abd El-Razik H. Farrag Rania S. Salah 《Indian journal of clinical biochemistry : IJCB》2013,28(4):381-389
This study aimed to elucidate the mechanisms of melatonin to manage neurological damage in Alzheimer’s disease (AD) induced in ovariectomized rats. Forty adult female rats were enrolled in our study and were classified as; gonad intact control, ovariectomized control group, ovariectomized rats received melatonin, ovariectomized rats injected with AlCl3 to induce AD and AD-induced rats treated with melatonin. Hydrogen peroxide (H2O2), malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), B cell lymphoma 2 (Bcl-2), brain derived neurotrophic factor (BDNF), acetylcholinesterase (AchE) and acetylcholine (Ach) were estimated in the brain tissues of the different groups. Treatment of AD-induced rats with melatonin produced marked improvement in the most studied biomarkers which was confirmed by histological investigation of the brain. In Conclusion, melatonin significantly ameliorates the neurodegeneration characteristic of AD in experimental animal model due to its antioxidant, antiapoptotic, neurotrophic and anti-amyloidogenic activities. 相似文献
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Giovanna Tomaiuolo 《Biomicrofluidics》2014,8(5)
Red blood cells (RBCs) possess a unique capacity for undergoing cellular deformation to navigate
across various human microcirculation vessels, enabling them to pass through capillaries that are
smaller than their diameter and to carry out their role as gas carriers between blood and tissues.
Since there is growing evidence that red blood cell deformability is impaired in some pathological
conditions, measurement of RBC deformability has been the focus of numerous studies over the past
decades. Nevertheless, reports on healthy and pathological RBCs are currently limited and, in many
cases, are not expressed in terms of well-defined cell membrane parameters such as elasticity and
viscosity. Hence, it is often difficult to integrate these results into the basic understanding of
RBC behaviour, as well as into clinical applications. The aim of this review is to summarize
currently available reports on RBC deformability and to highlight its association with various human
diseases such as hereditary disorders (e.g., spherocytosis, elliptocytosis, ovalocytosis, and
stomatocytosis), metabolic disorders (e.g., diabetes, hypercholesterolemia, obesity), adenosine
triphosphate-induced membrane changes, oxidative stress, and paroxysmal nocturnal hemoglobinuria.
Microfluidic techniques have been identified as the key to develop state-of-the-art dynamic
experimental models for elucidating the significance of RBC membrane alterations in pathological
conditions and the role that such alterations play in the microvasculature flow dynamics. 相似文献
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In this paper, we present a movement-based assay to observe adaptability in Caenorhabditis elegans locomotion behavior. The assay comprises a series of sinusoidal microchannels with a fixed wavelength and modulating (increasing or decreasing) amplitude. The channel width is comparable to the body diameter of the organism. Worms are allowed to enter the channel from the input port and migrate toward the output port. Within channel sections that closely match the worm's natural undulations, the worm movement is relatively quick and steady. As the channel amplitude increases or decreases along the device, the worm faces difficulty in generating the propulsive thrust, begins to slow down and eventually fails to move forward. A set of locomotion parameters (i.e., average forward velocity, number and duration of stops, range of contact angle, and cut-off region) is defined for worm locomotion in modulated sinusoidal channels and extracted from the recorded videos. The device is tested on wild-type C. elegans (N2) and two mutants (lev-8 and unc-38). We anticipate this passive, movement-based assay can be used to screen nematodes showing difference in locomotion phenotype. 相似文献
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探讨了胰腺癌血管受累的ＣＴ分型与肿瘤手术可切除性的关系．对４３例经手术、病理证实的胰腺癌进行薄层ＣＴ动态扫描，根据确定的ＣＴ标准，观察肿瘤与血管的关系，并与手术结果对照．发现胰腺癌血管受累以Ｃ型最常见，占３７．２％，Ａ型１０例，肿瘤切除率１００％（１０／１０），Ｂ型９例，切除率为７７．８％（７／９），Ｃ型、Ｄ型２４例，均不可切除．表明薄层ＣＴ动态扫描能提高胰腺癌血管受累的诊断正确率，血管受累ＣＴ分型对外科制定手术计划具有一定价值． 相似文献
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依照国家对科技人才发展要求,实施专业型硕士人才教育和管理改革是高级人才发展的当务之急。硕士研究生导师绩效考评作为考察教育工作主体能力与成果的基本手段,担负着指挥棒的作用。目前,我国各研究生培养单位针对专业型硕士研究生导师的绩效考评体系适用性不足,影响了这一功能的发挥。文章通过探讨目前专业型硕士研究生导师绩效考评体系的现状和问题,从人才培养的目标出发,整理必要性绩效考评指标。以中国科学院为例,采用矩阵建模及专家评价法对绩效考评体系进行优化设计,为保障专业型硕士人才培养质量建立出一套可有效反映专业型研究生导师能力和工作质量的考评方案。 相似文献
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Napapan Meepadung John C.S. Tang Do Ba Khang 《The Journal of High Technology Management Research》2009,20(2):145-152
Data envelopment analysis (DEA) is an ideal tool to assess a bank branch's operating and profit efficiency. This study went a step further to also explore the impact of IT-based retail banking services on branch efficiency, and found that IT-based transactions at the branch level have a significant impact on profit efficiency, and therefore have a significant role to play in profit maximization. Improving bank branch technology to best support service delivery is also a practical way to achieve greater efficiency, which in turn, contributes to a commercial bank's overall profitability. 相似文献
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目的 设计气 液交界式浴槽,并用于探讨海马脑片H2O2损伤的机制.方法 气 液交界式浴槽包括内室和外室.内室的主要结构为嵌入体,用于放置海马脑片.外室的主要作用是为海马脑片提供足够的氧气.另外用生化、形态学、电生理的方法来验证浴槽的可行性.最后观察H2O2对海马脑片群峰电位的影响.结果 浴槽能够长时间(1～8h)的维持海马脑片活性.H2O2能够浓度依赖性损伤海马脑片,同时NMDA受体阻断剂氯胺酮对H2O2诱导的海马脑片损伤具有明显的保护作用.结论 浴槽可以适用于生化和形态学以及电生理等研究,并发现海马脑片H2O2损伤至少部分是通过NMDA受体发挥作用的. 相似文献
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2020年的诺贝尔生理学或医学奖授予了在发现丙肝病毒(HCV)方面作出突出贡献的哈维·阿尔特(Harvey J. Alter)、迈克尔·霍顿(Michael Houghton)和查尔斯·赖斯(Charles M. Rice)。然而,从1989年霍顿捕获HCV到1997年赖斯证明HCV能引发肝炎,间隔了8年时间。这看似一步之遥的距离何以耗时如此之久?文章通过回顾文献,对这一时期的研究脉络进行了梳理,明确了包括赖斯团队在内的不同研究者对于推进HCV相关认识所作的具体贡献。同时,针对研究过程中的两个关键节点——病毒RNA基因组3′末端的准确测序和感染性分子克隆的建立,文章从技术储备、路径依赖和目标定位的角度分析了赖斯团队为何能在科学研究竞争中拔得头筹。 相似文献
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以“益村”平台为研究对象，从服务技术、服务内容、服务效果三个维度设计33个服务质量评价的影响因素，先后进行传统KANO分析、混合类分析以及Better-Worse指数分析，结果表明：期望因素为应用界面设计美观等7个，必备因素为平台访问快速性等12个，无差异因素为支付异常冻结账户等5个，魅力因素为界面信息简洁直观等9个。根据每个因素的分类情况与重要程度，提出以村民体验、需求与反馈为基础，加快平台服务技术升级、服务内容优化、服务效果提升等对策建议，以促进新时代农村信息化服务平台高质量发展，增强乡村全面振兴的信息化动能。 相似文献