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1.
    
Hemostasis is a physiological process critical for survival. Meanwhile, thrombosis is amongst the leading causes of death worldwide, making antithrombotic therapy one of the most crucial aspects of modern medicine. Although antithrombotic therapy has progressed tremendously over the years, it remains far from ideal, and this is mainly due to the incomplete understanding of the exceptionally complex structural and functional properties of platelets. However, advances in biochemistry, molecular biology, and the advent of ‘omics’ continue to provide crucial information for our understanding of the complex structure and function of platelets, their interactions with the coagulation system, and their role in hemostasis and thrombosis. In this review, we provide a comprehensive view of the complex role that platelets play in hemostasis and thrombosis, and we discuss the major clinical implications of these fundamental blood components, with a focus on hemostatic platelet-related disorders and existing and emerging antithrombotic therapies. We also emphasize a number of questions that remain to be answered, and we identify hotspots for future research.  相似文献   

2.
    
Procoagulant platelets are a subtype of activated platelets that sustains thrombin generation in order to consolidate the clot and stop bleeding. This aspect of platelet activation is gaining more and more recognition and interest. In fact, next to aggregating platelets, procoagulant platelets are key regulators of thrombus formation. Imbalance of both subpopulations can lead to undesired thrombotic or bleeding events. COAT platelets derive from a common pro-aggregatory phenotype in cells capable of accumulating enough cytosolic calcium to trigger specific pathways that mediate the loss of their aggregating properties and the development of new adhesive and procoagulant characteristics. Complex cascades of signaling events are involved and this may explain why an inter-individual variability exists in procoagulant potential. Nowadays, we know the key agonists and mediators underlying the generation of a procoagulant platelet response. However, we still lack insight into the actual mechanisms controlling this dichotomous pattern (i.e., procoagulant versus aggregating phenotype). In this review, we describe the phenotypic characteristics of procoagulant COAT platelets, we detail the current knowledge on the mechanisms of the procoagulant response, and discuss possible drivers of this dichotomous diversification, in particular addressing the impact of the platelet environment during in vivo thrombus formation.  相似文献   

3.
    
Background: Vascular injury induces the exposure of subendothelial extracellular matrix (ECM) important to serve as substrate for platelets to adhere to the injured vessel wall to avoid massive blood loss. Different ECM proteins are known to initiate platelet adhesion and activation. In atherosclerotic mice, the small, leucine-rich proteoglycan biglycan is important for the regulation of thrombin activity via heparin cofactor II. However, nothing is known about the role of biglycan for hemostasis and thrombosis under nonatherosclerotic conditions. Methods: The role of biglycan for platelet adhesion and thrombus formation was investigated using a recombinant protein and biglycan knockout mice. Results: The present study identified biglycan as important ECM protein for the adhesion and activation of platelets, and the formation of three-dimensional thrombi under flow conditions. Platelet adhesion to immobilized biglycan induces the reorganization of the platelet cytoskeleton. Mechanistically, biglycan binds and activates the major collagen receptor glycoprotein (GP)VI, because reduced platelet adhesion to recombinant biglycan was observed when GPVI was blocked and enhanced tyrosine phosphorylation in a GPVI-dependent manner was observed when platelets were stimulated with biglycan. In vivo, the deficiency of biglycan resulted in reduced platelet adhesion to the injured carotid artery and prolonged bleeding times. Conclusions: Loss of biglycan in the vessel wall of mice but not in platelets led to reduced platelet adhesion at the injured carotid artery and prolonged bleeding times, suggesting a crucial role for biglycan as ECM protein that binds and activates platelets via GPVI upon vessel injury.  相似文献   

4.
    
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5.
    
New antithrombotic medications with less effect on haemostasis are needed for the long-term treatment of acute coronary syndromes (ACS). The platelet receptor glycoprotein VI (GPVI) is critical in atherothrombosis, mediating platelet activation at atherosclerotic plaque. The inhibition of spleen tyrosine kinase (Syk) has been shown to block GPVI-mediated platelet function. The aim of our study was to investigate if the Syk inhibitor fostamatinib could be repurposed as an antiplatelet drug, either alone or in combination with conventional antiplatelet therapy. The effect of the active metabolite of fostamatinib (R406) was assessed on platelet activation and function induced by atherosclerotic plaque and a range of agonists in the presence and absence of the commonly used antiplatelet agents aspirin and ticagrelor. The effects were determined ex vivo using blood from healthy volunteers and aspirin- and ticagrelor-treated patients with ACS. Fostamatinib was also assessed in murine models of thrombosis. R406 mildly inhibited platelet responses induced by atherosclerotic plaque homogenate, likely due to GPVI inhibition. The anti-GPVI effects of R406 were amplified by the commonly-used antiplatelet medications aspirin and ticagrelor; however, the effects of R406 were concentration-dependent and diminished in the presence of plasma proteins, which may explain why fostamatinib did not significantly inhibit thrombosis in murine models. For the first time, we demonstrate that the Syk inhibitor R406 provides mild inhibition of platelet responses induced by atherosclerotic plaque and that this is mildly amplified by aspirin and ticagrelor.  相似文献   

6.
    
Platelets are involved in tumor angiogenesis and cancer progression. Previous studies indicated that cancer could affect platelet content. In the current study, we investigated whether cancer-associated proteins can be discerned in the platelets of cancer patients, and whether antitumor treatment may affect the platelet proteome. Platelets were isolated from nine patients with different cancer types and ten healthy volunteers. From three patients, platelets were isolated before and after the start of antitumor treatment. Mass spectrometry-based proteomics of gel-fractionated platelet proteins were used to compare patients versus controls and before and after treatment initiation. A total of 4059 proteins were detected, of which 50 were significantly more abundant in patients, and 36 more in healthy volunteers. Eight of these proteins overlapped with our previous cancer platelet proteomics study. From these data, we selected potential biomarkers of cancer including six upregulated proteins (RNF213, CTSG, PGLYRP1, RPL8, S100A8, S100A9) and two downregulated proteins (GPX1, TNS1). Antitumor treatment resulted in increased levels of 432 proteins and decreased levels of 189 proteins. In conclusion, the platelet proteome may be affected in cancer patients and platelets are a potential source of cancer biomarkers. In addition, we found in a small group of patients that anticancer treatment significantly changes the platelet proteome.  相似文献   

7.
    
Platelets, which are small anuclear cell fragments, play important roles in thrombosis and hemostasis, but also actively release factors that can both suppress and induce viral infections. Platelet-released factors include sCD40L, microvesicles (MVs), and alpha granules that have the capacity to exert either pro-inflammatory or anti-inflammatory effects depending on the virus. These factors are prime targets for use in extracellular vesicle (EV)-based therapy due to their ability to reduce viral infections and exert anti-inflammatory effects. While there are some studies regarding platelet microvesicle-based (PMV-based) therapy, there is still much to learn about PMVs before such therapy can be used. This review provides the background necessary to understand the roles of platelet-released factors, how these factors might be useful in PMV-based therapy, and a critical discussion of current knowledge of platelets and their role in viral diseases.  相似文献   

8.
    
There is accumulating evidence that platelets play roles beyond their traditional functions in thrombosis and hemostasis, e.g., in inflammatory processes, infection and cancer, and that they interact, stimulate and regulate cells of the innate immune system such as neutrophils, monocytes and macrophages. In this review, we will focus on platelet activation in hemostatic and inflammatory processes, as well as platelet interactions with neutrophils and monocytes/macrophages. We take a closer look at the contributions of major platelet receptors GPIb, αIIbβ3, TLT-1, CLEC-2 and Toll-like receptors (TLRs) as well as secretions from platelet granules on platelet–neutrophil aggregate and neutrophil extracellular trap (NET) formation in atherosclerosis, transfusion-related acute lung injury (TRALI) and COVID-19. Further, we will address platelet–monocyte and macrophage interactions during cancer metastasis, infection, sepsis and platelet clearance.  相似文献   

9.
    
Organic nanomaterials have attracted considerable attention in the area of photodynamic and photothermal therapy, owing to their outstanding biocompatibility, potential biodegradability, well-defined chemical structure, and easy functionalization. However, it is still a challenge to develop a single organic molecule that obtains both photothermal and photodynamic effects. In this contribution, we synthesized a new boron-dipyrromethene (BODIPY)-based derivative (DPBDP) with an acceptor–donor–acceptor (A-D-A) structure by coupling 3,6-di(2-thienyl)-2,5-dihydropyrrolo [3,4-c] pyrrole-1,4-dione (DPP) and BODIPY. To enhance the hydrophilicity of the BODIPY derivative, the polyethylene glycol (PEG) chains were introduced to the meso- position of BODIPY core. The amphiphilic DPBDP was then self-assembled into related nanoparticles (DPBDP NPs) with improved hydrophilicity and enhanced absorbance in the NIR region. DPBDP NPs could simultaneously generate the singlet oxygen (1O2) and heat under the irradiation of a single laser (690 nm). The 1O2 quantum yield and photothermal conversion efficiency (PCE) of DPBDP NPs were calculated to be 14.2% and 26.1%, respectively. The biocompatibility and phototherapeutic effect of DPBDP NPs were evaluated through cell counting kit-8 (CCK-8) assay. Under irradiation of 690 nm laser (1.0 W/cm2), the half maximal inhibitory concentration (IC50) of DPBDP NPs was calculated to be 16.47 µg/mL. Thus, the as-prepared DPBDP NPs could be acted as excellent candidates for synergistic photodynamic/photothermal therapy.  相似文献   

10.
    
Photodynamic therapy (PDT) is a promising therapy due to its efficiency and accuracy. The photosensitizer is delivered to the target lesion and locally activated. Viral nanoparticles (VNPs) have been explored as delivery vehicles for PDT in recent years because of their favorable properties, including simple manufacture and good safety profile. They have great potential as drug delivery carriers in medicine. Here, we review the development of PDT photosensitizers and discuss applications of VNP-mediated photodynamic therapies and the performance of VNPs in the treatment of tumor cells and antimicrobial therapy. Furthermore, future perspectives are discussed for further developing novel viral nanocarriers or improving existing viral vectors.  相似文献   

11.
    
The development of drug-resistant microorganisms has become a critical issue for modern medicine and drug discovery and development with severe socio-economic and ecological implications. Since standard and conventional treatment options are generally inefficient, leading to infection persistence and spreading, novel strategies are fundamentally necessary in order to avoid serious global health problems. In this regard, both metal and metal oxide nanoparticles (NPs) demonstrated increased effectiveness as nanobiocides due to intrinsic antimicrobial properties and as nanocarriers for antimicrobial drugs. Among them, gold, silver, copper, zinc oxide, titanium oxide, magnesium oxide, and iron oxide NPs are the most preferred, owing to their proven antimicrobial mechanisms and bio/cytocompatibility. Furthermore, inorganic NPs can be incorporated or attached to organic/inorganic films, thus broadening their application within implant or catheter coatings and wound dressings. In this context, this paper aims to provide an up-to-date overview of the most recent studies investigating inorganic NPs and their integration into composite films designed for antimicrobial therapies.  相似文献   

12.
    
Confinement of Au nanoparticles (NPs) within the porous materials with few nanometers (2-3 nm) has been a well established research area in the past decades in heterogeneous catalysis mainly due to the unique behaviour of Au NPs than its bulk counterpart. In this aspect, Au NPs encapsulated within the pore volumes of metal−organic frameworks (MOFs) have been intensively explored as heterogeneous solid catalysts for wide range of reactions. In recent years, Au NPs confined within the porous MOFs along with the photosensitizer or drug have been effectively used for the treatment of tumor cells through the generation of reactive oxygen species via cascade reactions. This work highlights the benefits of MOFs pores in the preparation of nanomedicine with high efficiency by assembling Au NPs, photosensitizer/drug with the combination of laser either for imaging or treatment of tumor cells. Further, the existing literature is grouped based on the nature of porous materials employed in the preparation of nanomedicine. The final section comments on our view on future developments in the field.  相似文献   

13.
    
As integral parts of pathological arterial thrombi, platelets are the targets of pharmacological regimens designed to treat and prevent thrombosis. A detailed understanding of platelet biology and function is thus key to design treatments that prevent thrombotic cardiovascular disease without significant disruption of the haemostatic balance. Phosphoinositide 3-kinases (PI3Ks) are a group of lipid kinases critical to various aspects of platelet biology. There are eight PI3K isoforms, grouped into three classes. Our understanding of PI3K biology has recently progressed with the targeting of specific isoforms emerging as an attractive therapeutic strategy in various human diseases, including for thrombosis. This review will focus on the role of PI3K subtypes in platelet function and subsequent thrombus formation. Understanding the mechanisms by which platelet function is regulated by the various PI3Ks edges us closer toward targeting specific PI3K isoforms for anti-thrombotic therapy.  相似文献   

14.
用DEAE－SephadexA50离子交换层析结合亲和层析方法，从江浙蝮蛇（AgkistrodonhalysPallas）粗毒中分离纯化抗栓酶（EC3．4．21．28）。所得抗栓酶在SDS－PAGE上呈一条主区带及二条副区带，分子量在33～44KD之间，比活为14000USP单位／mg蛋白，回收率可达到60％以上，制品的出血毒及神经毒素均可合格，较本所原制备方法的纯度和得率分别提高10倍和4倍，且操作简单，适于大规模制备。  相似文献   

15.
In accordance with the World Cancer Report, cancer has become the leading cause of mortality worldwide, and various therapeutic strategies have been developed at the same time. In the present study, biocompatible magnetic nanoparticles were designed and synthesized as high-performance photothermal agents for near-infrared light mediated cancer therapy in vitro. Via a facile one-pot solvothermal method, well-defined PEGylated magnetic nanoparticles (PEG–Fe3O4) were prepared with cheap inhesion as a first step. Due to the successful coating of PEG molecules on the surface of PEG–Fe3O4, these nanoparticles exhibited excellent dispersibility and dissolvability in physiological condition. Cytotoxicity based on MTT assays indicated these nanoparticles revealed high biocompatibility and low toxicity towards both Hela cells and C6 cells. After near-infrared (NIR) laser irradiation, the viabilities of C6 cells were effectively suppressed when incubated with the NIR laser activated PEG–Fe3O4. In addition, detailed photothermal anti-cancer efficacy was evaluated via visual microscope images, demonstrating that our PEG–Fe3O4 were promising for photothermal therapy of cancer cells.  相似文献   

16.
光敏剂是光动力治疗的核心要素,普遍具有大环共轭结构。为了解决大环共轭类光敏剂存在的聚集诱导猝灭（ACQ）效应与强疏水性,本文引入不用长度的醚基柔性链合成了一系列水溶性聚卟啉（P-1O, P-3O, 和P-5O）,其中,P-5O具有最优的水溶性、最高的单线态氧产率（单线态氧产率是四羧基苯基卟啉单体的1.95倍）;在不借助外源载体的情况下自组装形成粒径在100 nm左右纳米粒,该纳米粒具有良好的pH稳定性、血清稳定性、稀释稳定性、冻干稳定性以及时间稳定性。本文对P-5O纳米粒进行了体外光暗毒性表征,结果表明,P-5O纳米粒在肿瘤细胞（Hep1-6）以及正常细胞（293T）中均具有较低的暗毒性（细胞存活率80%以上）,并且在Hep1-6中具有明显的光毒性（细胞存活率低于30%）,具有典型的光动力杀伤肿瘤的效果。  相似文献   

17.
以C60为原料,利用宾格尔环加成反应得到水溶性C60-COOH后,通过水热反应负载上MnO2纳米颗粒,最后利用氨基化聚乙二醇连接上肿瘤靶向分子叶酸,合成了一种多功能纳米复合物C60-Mn-PEG-FA。FTIR,UV-Vis,XPS和DLS确定了其结构组成和良好的水分散性。体外和细胞实验表明, C60-Mn-PEG-FA不仅可以实现低pH下的磁共振成像,还能改善乏氧;在40 ?g/mL的低剂量下,被100 mW/cm2强度的自然光照射5分钟就可以靶向杀伤82%的肿瘤细胞,而对正常细胞无损,为新型诊疗一体化制剂的设计提供了策略。  相似文献   

18.
    
The advent of cancer therapeutics brought a paradigm shift from conventional therapy to precision medicine. The new therapeutic modalities accomplished through the properties of nanomaterials have extended their scope in cancer therapy beyond conventional drug delivery. Nanoparticles can be channeled in cancer therapy to encapsulate active pharmaceutical ingredients and deliver them to the tumor site in a more efficient manner. This review enumerates various types of nanoparticles that have entered clinical trials for cancer treatment. The obstacles in the journey of nanodrug from clinic to market are reviewed. Furthermore, the latest developments in using nanoparticles in cancer therapy are also highlighted.  相似文献   

19.
蔡梅超 《化工时刊》2012,26(6):27-28
建立妇科止血灵胶囊高效液相色谱法测定芍药苷的方法。色谱柱：DiamonsilCl8（4．6mm×250mm,5μm）。流动相：乙腈-0．1％磷酸溶液（14：86）。流速：1．0mL·min-1。检测波长：230nm。柱温：35℃。进样量：10μg。芍药苷在12．6-252．0μg／mL范围内呈良好线性关系,r=0．9997。平均加样回收率为98．37％,RSD=1．34％（n=5）。所建立的方法简便准确、灵敏度高,可作为妇科止血灵胶囊的质量控制方法。  相似文献   

20.
The development of stimulus-responsive photosensitizer delivery systems that carry a high payload of photosensitizers is of great importance in photodynamic therapy. In this study, redox-responsive polysilsesquioxane nanoparticles (PSilQNPs) built by a reverse microemulsion approach using 5,10,15,20-tetrakis(carboxyphenyl) porphyrin (TCPP) silane derivatives as building blocks, were successfully fabricated. The structural properties of TCPP-PSilQNPs were characterized by dynamic light scattering (DLS)/ζ-potential, scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The photophysical properties were determined by UV-vis and fluorescence spectroscopy. The quantity of singlet oxygen generated in solution was measured using 1,3-diphenylisobenzofuran. The redox-responsive release of TCPP molecules was successfully demonstrated in solution in the presence of a reducing agent. The internalization of TCPP-PSilQNPs in cancer cells was investigated using laser scanning confocal microscopy. Phototoxicity experiments in vitro showed that the redox-responsive TCPP-PSilQNPs exhibited an improved phototherapeutic effect on cervical cancer cells compared to a non-responsive TCPP-PSilQNP control material.  相似文献   

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