IF 3.3 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-02-21 DOI: 10.1080/09537104.2024.2313362

Tuukka Helin, Mari Palviainen, Marja Lemponen, Katariina Maaninka, Pia Siljander, Lotta Joutsi-Korhonen

{"title":"Increased circulating platelet-derived extracellular vesicles in severe COVID-19 disease.","authors":"Tuukka Helin, Mari Palviainen, Marja Lemponen, Katariina Maaninka, Pia Siljander, Lotta Joutsi-Korhonen","doi":"10.1080/09537104.2024.2313362","DOIUrl":"10.1080/09537104.2024.2313362","url":null,"abstract":"Coagulation disturbances are major contributors to COVID-19 pathogenicity, but limited data exist on the involvement of extracellular vesicles (EVs) and residual cells (RCs). Fifty hospitalized COVID-19 patients stratified by their D-dimer levels into high (>1.5 mg/L, n = 15) or low (≤1.5 mg/l, n = 35) and 10 healthy controls were assessed for medium-sized EVs (mEVs; 200-1000 nm) and large EVs/RCs (1000-4000 nm) by high sensitivity flow cytometry. EVs were analyzed for CD61, CD235a, CD45, and CD31, commonly used to detect platelets, red blood cells, leukocytes or endothelial cells, respectively, whilst phosphatidyl serine EVs/RCs were detected by lactadherin-binding implicating procoagulant catalytic surface. Small EV detection (sEVs; 50-200 nm) and CD41a (platelet integrin) colocalization with general EV markers CD9, CD63, and CD81 were performed by single particle interferometric reflectance imaging sensor. Patients with increased D-dimer exhibited the highest number of RCs and sEVs irrespective of cell origin (p < .05). Platelet activation, reflected by increased CD61+ and lactadherin+ mEV and RC levels, associated with coagulation disturbances. Patients with low D-dimer could be discriminated from controls by tetraspanin signatures of the CD41a+ sEVs, suggesting the changes in the circulating platelet sEV subpopulations may offer added prognostic value during COVID progression.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Appraising non-linear association between pre-diagnostic platelet counts and cancer survival outcomes: observational and genetic analysis. 评估诊断前血小板计数与癌症生存结果之间的非线性关联：观察和遗传分析。

IF 2.5 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-07-29 DOI: 10.1080/09537104.2024.2379815

Changtao Li, Junhua Chen, Deqian Han, Chi Shu, Jun Huang, Linru Wei, Haoran Luo, Qingbin Wu, Xin Chen, Yazhou He, Yanhong Zhou

{"title":"Appraising non-linear association between pre-diagnostic platelet counts and cancer survival outcomes: observational and genetic analysis.","authors":"Changtao Li, Junhua Chen, Deqian Han, Chi Shu, Jun Huang, Linru Wei, Haoran Luo, Qingbin Wu, Xin Chen, Yazhou He, Yanhong Zhou","doi":"10.1080/09537104.2024.2379815","DOIUrl":"https://doi.org/10.1080/09537104.2024.2379815","url":null,"abstract":"Previous studies have reported inconsistent associations between platelet count (PLT) and cancer survival. However, whether there is linear causal effect merits in-depth investigations. We conducted a cohort study using the UK Biobank and a two-sample Mendelian randomization (MR) analysis. PLT levels were measured prior to cancer diagnosis. We adopted overall survival (OS) as the primary outcome. Cox models were utilized to estimate the effects of PLTs on survival outcomes at multiple lag times for cancer diagnosis. We employed 34 genetic variants as PLT proxies for MR analysis. Linear and non-linear effects were modeled. Prognostic effects of gene expression harboring the instrumental variants were also investigated. A total of 65 471 cancer patients were included. We identified a significant association between elevated PLTs (per 100 × 109/L) and inferior OS (HR: 1.07; 95% CI: 1.04-1.10; p < .001). Similar significant associations were observed for several cancer types. We further observed a U-shaped relationship between PLTs and cancer survival (p < .001). Our MR analysis found null evidence to support a causal association between PLTs and overall cancer survival (HR: 1.000; 95% CI: 0.998-1.001; p = .678), although non-linear MR analysis unveiled a potential greater detrimental effect at lower PLT range. Expression of eleven PLT-related genes were associated with cancer survival. Early detection of escalated PLTs indicated possible occult cancer development and inferior subsequent survival outcomes. The observed associations could potentially be non-linear. However, PLT is less likely to be a promising therapeutic target.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The efficacy of platelet rich plasma on women with poor ovarian response: a systematic review and meta-analysis. 富血小板血浆对卵巢反应不良妇女的疗效：系统综述和荟萃分析。

IF 3.3 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-01-12 DOI: 10.1080/09537104.2023.2292612

Lingling Wu, Fenfang Su, Peixin Luo, Qingqing Dong, Mengni Ma, Guangyong Ye

{"title":"The efficacy of platelet rich plasma on women with poor ovarian response: a systematic review and meta-analysis.","authors":"Lingling Wu, Fenfang Su, Peixin Luo, Qingqing Dong, Mengni Ma, Guangyong Ye","doi":"10.1080/09537104.2023.2292612","DOIUrl":"10.1080/09537104.2023.2292612","url":null,"abstract":"Background: Platelet-rich plasma (PRP) is a therapeutic approach that is gaining attention for its potential in the treatment of poor ovarian response. This meta-analysis aimed to systematically review and analyze clinical studies to evaluate the impact of PRP on poor responders undergoing ovarian stimulation for IVF.Methods: A comprehensive search was conducted in electronic databases, including PubMed, Embase, Scopus, Web of Science, and the Cochrane Library to identify relevant studies published in English. The pooled data, such as pregnancy outcome, number of MII oocytes, number of transferable embryos, and ovarian reserve markers were analyzed using R version 4.2.3.Results: A total of 10 trials were enrolled in the present meta-analysis. Following PRP treatment, live birth rate was found to be 16.6% (95% CI 8.8%-26.1%), while clinical pregnancy rate was observed to be 25.4% (95% CI 13.1%-39.9%). PRP pretreatment resulted in a higher number of MII oocytes (MD 1.073, 95% CI 0.720 to 1.427), a higher number of embryos (MD 0.946, 95% CI 0.569 to 1.323), a higher antral follicle count (MD 1.117; 95% CI 0.689 to 1.544), and the change of hormone levels.Conclusions: Among the studies evaluated in this review, PRP showed promising results in poor responder. Further research is required to clarify the potential role of PRP in female reproductive health.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139425387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hemin regulates platelet clearance in hemolytic disease by binding to GPIbα. 血红蛋白通过与 GPIbα 结合调节溶血性疾病中的血小板清除。

IF 2.5 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-07-29 DOI: 10.1080/09537104.2024.2383642

Man Zhao, Dongxin Peng, Yuxuan Li, Minwei He, Yulong Zhang, Qianqian Zhou, Sujing Sun, Ping Ma, Liping Lv, Xiaohui Wang, Linsheng Zhan

{"title":"Hemin regulates platelet clearance in hemolytic disease by binding to GPIbα.","authors":"Man Zhao, Dongxin Peng, Yuxuan Li, Minwei He, Yulong Zhang, Qianqian Zhou, Sujing Sun, Ping Ma, Liping Lv, Xiaohui Wang, Linsheng Zhan","doi":"10.1080/09537104.2024.2383642","DOIUrl":"10.1080/09537104.2024.2383642","url":null,"abstract":"Hemolysis is associated with thrombosis and vascular dysfunction, which are the pathological components of many diseases. Hemolytic products, including hemoglobin and hemin, activate platelets (PLT). Despite its activation, the effect of hemolysis on platelet clearance remains unclear, It is critical to maintain a normal platelet count and ensure that circulating platelets are functionally viable. In this study, we used hemin, a degradation product of hemoglobin, as a potent agonist to treat platelets and simulate changes in vivo in mice. Hemin treatment induced activation and morphological changes in platelets, including an increase in intracellular Ca2+ levels, phosphatidylserine (PS) exposure, and cytoskeletal rearrangement. Fewer hemin-treated platelets were cleared by macrophages in the liver after transfusion than untreated platelets. Hemin bound to glycoprotein Ibα (GPIbα), the surface receptor in hemin-induced platelet activation and aggregation. Furthermore, hemin decreased GPIbα desialylation, as evidenced by reduced Ricinus communis agglutinin I (RCA- I) binding, which likely extended the lifetime of such platelets in vivo. These data provided new insight into the mechanisms of GPIbα-mediated platelet activation and clearance in hemolytic disease.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Real-life clinical practice in Spain in the setting of new drug availability for ITP treatment. A Delphi-based Spanish expert panel consensus. 在新药上市的背景下西班牙治疗 ITP 的实际临床实践。基于德尔菲法的西班牙专家小组共识。

IF 3.3 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-05-14 DOI: 10.1080/09537104.2024.2336104

Tomás José González-López, Abelardo Bárez, Ángel Bernardo-Gutiérrez, Silvia Bernat, Fernando Fernández-Fuertes, José María Guinea de Castro, Reyes Jiménez-Bárcenas, Isidro Jarque

{"title":"Real-life clinical practice in Spain in the setting of new drug availability for ITP treatment. A Delphi-based Spanish expert panel consensus.","authors":"Tomás José González-López, Abelardo Bárez, Ángel Bernardo-Gutiérrez, Silvia Bernat, Fernando Fernández-Fuertes, José María Guinea de Castro, Reyes Jiménez-Bárcenas, Isidro Jarque","doi":"10.1080/09537104.2024.2336104","DOIUrl":"https://doi.org/10.1080/09537104.2024.2336104","url":null,"abstract":"Immune thrombocytopenia (ITP) is a common autoimmune hematological disorder. Despite this, diagnosis is still challenging due to clinical heterogeneity and the lack of a specific diagnostic test. New findings in the pathology and the availability of new drugs have led to the development of different guidelines worldwide. In the present study, the Delphi methodology has been used to get a consensus on the management of adult patients with ITP in Spain and to help in decision-making. The Delphi questionnaire has been designed by a scientific ad hoc committee and has been divided into 13 topics, with a total of 127 items, covering the maximum possible scenarios for the management of ITP. As a result of the study, a total consensus of 81% has been reached. It is concluded that this Delphi consensus provides practical recommendations on topics related to diagnosis and management of ITP patients to help doctors to improve outcomes. Some aspects remain unclear, without consensus among the experts. Thus, more advances are needed to optimize ITP management.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Finding and following: a deep learning-based pipeline for tracking platelets during thrombus formation in vivo and ex vivo. 寻找和跟踪：基于深度学习的管道，用于在体内和体外血栓形成过程中跟踪血小板。

IF 3.3 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-05-09 DOI: 10.1080/09537104.2024.2344512

Abigail S McGovern, Pia Larsson, Volga Tarlac, Natasha Setiabakti, Leila Shabani Mashcool, Justin R Hamilton, Niklas Boknäs, Juan Nunez-Iglesias

{"title":"Finding and following: a deep learning-based pipeline for tracking platelets during thrombus formation in vivo and ex vivo.","authors":"Abigail S McGovern, Pia Larsson, Volga Tarlac, Natasha Setiabakti, Leila Shabani Mashcool, Justin R Hamilton, Niklas Boknäs, Juan Nunez-Iglesias","doi":"10.1080/09537104.2024.2344512","DOIUrl":"https://doi.org/10.1080/09537104.2024.2344512","url":null,"abstract":"The last decade has seen increasing use of advanced imaging techniques in platelet research. However, there has been a lag in the development of image analysis methods, leaving much of the information trapped in images. Herein, we present a robust analytical pipeline for finding and following individual platelets over time in growing thrombi. Our pipeline covers four steps: detection, tracking, estimation of tracking accuracy, and quantification of platelet metrics. We detect platelets using a deep learning network for image segmentation, which we validated with proofreading by multiple experts. We then track platelets using a standard particle tracking algorithm and validate the tracks with custom image sampling - essential when following platelets within a dense thrombus. We show that our pipeline is more accurate than previously described methods. To demonstrate the utility of our analytical platform, we use it to show that in vivo thrombus formation is much faster than that ex vivo. Furthermore, platelets in vivo exhibit less passive movement in the direction of blood flow. Our tools are free and open source and written in the popular and user-friendly Python programming language. They empower researchers to accurately find and follow platelets in fluorescence microscopy experiments.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A case of acquired transient bleeding diathesis associated with acquired platelet storage pool deficiency and defective thromboxane A2 production. 一例与获得性血小板储存池缺乏症和血栓素 A2 生成缺陷有关的获得性一过性出血综合症。

IF 2.5 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-06-04 DOI: 10.1080/09537104.2024.2358241

Mariangela Scavone, Bianca Clerici, Eti Alessandra Femia, Claudia Ghali, Antonella Fioretti, Elena Bossi, Marco Cattaneo, Gian Marco Podda

{"title":"A case of acquired transient bleeding diathesis associated with acquired platelet storage pool deficiency and defective thromboxane A2 production.","authors":"Mariangela Scavone, Bianca Clerici, Eti Alessandra Femia, Claudia Ghali, Antonella Fioretti, Elena Bossi, Marco Cattaneo, Gian Marco Podda","doi":"10.1080/09537104.2024.2358241","DOIUrl":"10.1080/09537104.2024.2358241","url":null,"abstract":"Acquired disorders of platelet function are an underdiagnosed cause of bleeding tendency. A 14-year-old girl developed moderate mucocutaneous bleeding two weeks after a Mycoplasma pneumoniae infection successfully treated with clarithromycin. The patient was referred to us 7 months later for laboratory investigation of the persisting bleeding diathesis. The patient's personal and family histories were negative for bleeding disorders. Complete blood count, von Willebrand Factor levels and coagulation tests were normal; platelet aggregation, ATP secretion, δ-granules content and serum thromboxane B2 levels were defective. At follow-up visits, laboratory parameters and the bleeding diathesis progressively normalized within 2 years. The patient's condition is compatible with a diagnosis of acquired Storage Pool Deficiency (SPD), associated with defective thromboxane A2 production. To our knowledge, this is the first case of acquired, transient SPD with spontaneous remission. The pathogenic role of Mycoplasma pneumoniae infection or clarithromycin is possible, albeit uncertain.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhanced platelet sensitization is accompanied by increased expression of the transporter MRP4 and elevated plasma S1P levels in mild COVID-19 convalescents. 在轻度 COVID-19 康复者中，伴随着转运体 MRP4 表达的增加和血浆 S1P 水平的升高，血小板致敏性增强。

IF 2.5 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-10-30 DOI: 10.1080/09537104.2024.2413713

Céline Tolksdorf, Andrea Seidel, Christian Baume, Eileen Moritz, Karen Saljé, Kathrin Lehmann, Karsten Becker, Ulrike Garscha, Thomas Thiele, Edzard Schwedhelm, Mirjam von Lucadou, Mladen V Tzvetkov, Stefan Engeli, Gabriele Jedlitschky, Bernhard H Rauch

{"title":"Enhanced platelet sensitization is accompanied by increased expression of the transporter MRP4 and elevated plasma S1P levels in mild COVID-19 convalescents.","authors":"Céline Tolksdorf, Andrea Seidel, Christian Baume, Eileen Moritz, Karen Saljé, Kathrin Lehmann, Karsten Becker, Ulrike Garscha, Thomas Thiele, Edzard Schwedhelm, Mirjam von Lucadou, Mladen V Tzvetkov, Stefan Engeli, Gabriele Jedlitschky, Bernhard H Rauch","doi":"10.1080/09537104.2024.2413713","DOIUrl":"https://doi.org/10.1080/09537104.2024.2413713","url":null,"abstract":"Viral infections can lead to platelet activation and hemostatic complications. However, the extent to which platelet reactivity remains altered after convalescence, contributing to long-term health impairments as observed after COVID-19 is not yet fully understood. Therefore, we conducted a cohort study (DRKS00025217) to determine platelet function in individuals convalesced from mild COVID-19. Assays were performed ex vivo with blood from convalescents at 2-15 weeks and 6-10 months after convalescence, focusing on platelet aggregation, activation markers, and thrombin formation. In addition, two other potentially relevant factors for platelet function were examined: the immunomodulatory mediator sphingosine-1-phosphate (S1P) and the platelet expression of the transporter MRP4 (ABCC4). Our findings indicate that robust platelet functions, including platelet aggregation determined by light transmission aggregometry, and thrombin formation, were not altered in convalescents compared to matched control individuals. However, an elevation in subtle platelet activation markers, such as P-selectin surface expression and activation of glycoprotein IIb/IIIa, was observed 2-15 weeks after convalescence. This was accompanied by an increased expression of MRP4 in platelets and significantly elevated levels of S1P in platelet-poor plasma. Our findings suggest increased platelet sensitization and a pro-inflammatory state even after convalescence from mild COVID-19, pointing toward MRP4 and S1P as associated factors.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatial and temporal characterization of cytoskeletal reorganizations in adherent platelets. 粘附血小板细胞骨架重组的空间和时间特征。

IF 2.5 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-11-04 DOI: 10.1080/09537104.2024.2422437

Clotilde Joubert, Alexei Grichine, Monika Dolega, Sophie Michallet, Florence Appaix, Isabelle Tardieux, Laurence Lafanechère, Karin Sadoul

{"title":"Spatial and temporal characterization of cytoskeletal reorganizations in adherent platelets.","authors":"Clotilde Joubert, Alexei Grichine, Monika Dolega, Sophie Michallet, Florence Appaix, Isabelle Tardieux, Laurence Lafanechère, Karin Sadoul","doi":"10.1080/09537104.2024.2422437","DOIUrl":"https://doi.org/10.1080/09537104.2024.2422437","url":null,"abstract":"The functional role of platelets is intricately linked to the dynamic organization of two main components of the cytoskeleton, microtubules and actin fibers. Throughout the phases of platelet activation, spreading, and retraction, both of these essential polymers undergo continuous and orchestrated reorganization. Our investigation of the dynamic cytoskeletal changes during these phases highlights a sequential remodeling of the actin cytoskeleton in adherent platelets from the formation of initial actin nodules through the development of stress fibers and a subsequent return to nodular structures. Concurrently, the marginal ring of microtubules, characteristic of resting platelets, undergoes a re-organization induced by marginal band extension and coiling toward the formation of star-like bundles of microtubules. Subsequently, these bundles are dispersed into individual microtubules, which are re-bundled at later stages before ring-like structures are formed again. These findings suggest a compelling tendency for both cytoskeletal components to revert to their original configurations. Notably, the early steps of platelet cytoskeleton reorganizations have previously been shown to be regulated by the signaling cascade triggered during platelet activation, which leads to an increase of cytosolic calcium concentrations. We show here that later steps are potentially regulated by a progressive decrease of intracellular calcium concentrations as platelets approach the end of their functional lifespan.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Application of the Cellular Thermal Shift Assay (CETSA) to validate drug target engagement in platelets. 应用细胞热转移分析法 (CETSA) 验证血小板中的药物靶点参与。

IF 3.3 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-05-20 DOI: 10.1080/09537104.2024.2354833

Joanna-Marie Howes, Matthew T Harper

{"title":"Application of the Cellular Thermal Shift Assay (CETSA) to validate drug target engagement in platelets.","authors":"Joanna-Marie Howes, Matthew T Harper","doi":"10.1080/09537104.2024.2354833","DOIUrl":"https://doi.org/10.1080/09537104.2024.2354833","url":null,"abstract":"Small molecule drugs play a major role in the study of human platelets. Effective action of a drug requires it to bind to one or more targets within the platelet (target engagement). However, although in vitro assays with isolated proteins can be used to determine drug affinity to these targets, additional factors affect target engagement and its consequences in an intact platelet, including plasma membrane permeability, intracellular metabolism or compartmentalization, and level of target expression. Mechanistic interpretation of the effect of drugs on platelet activity requires comprehensive investigation of drug binding in the proper cellular context, i.e. in intact platelets. The Cellular Thermal Shift Assay (CETSA) is a valuable method to investigate target engagement within complex cellular environments. The assay is based on the principle that drug binding to a target protein increases that protein's thermal stability. In this technical report, we describe the application of CETSA to platelets. We highlight CETSA as a quick and informative technique for confirming the direct binding of drugs to platelet protein targets, providing a platform for understanding the mechanism of action of drugs in platelets, and which will be a valuable tool for investigating platelet signaling and function.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Platelets最新文献