Platelets最新文献

{"title":"Molecular insights on Eltrombopag: potential mitogen stimulants, angiogenesis, and therapeutic radioprotectant through TPO-R activation.","authors":"Rajasekaran Subbarayan, Dhasarathdev Srinivasan, Salman Shadula Osmania, Dinesh Murugan Girija, Shoeb Ikhlas, Nityanand Srivastav, Ranjith Balakrishnan, Rupendra Shrestha, Ankush Chauhan","doi":"10.1080/09537104.2024.2359028","DOIUrl":"https://doi.org/10.1080/09537104.2024.2359028","url":null,"abstract":"<p><p>The purpose of this study is to investigate the molecular interactions and potential therapeutic uses of Eltrombopag (EPAG), a small molecule that activates the cMPL receptor. EPAG has been found to be effective in increasing platelet levels and alleviating thrombocytopenia. We utilized computational techniques to predict and confirm the complex formed by the ligand (EPAG) and the Thrombopoietin receptor (TPO-R) cMPL, elucidating the role of RAS, JAK-2, STAT-3, and other essential elements for downstream signaling. Molecular dynamics (MD) simulations were employed to evaluate the stability of the ligand across specific proteins, showing favorable characteristics. For the first time, we examined the presence of TPO-R in human umbilical cord mesenchymal stem cells (hUCMSC) and human gingival mesenchymal stem cells (hGMSC) proliferation. Furthermore, treatment with EPAG demonstrated angiogenesis and vasculature formation of endothelial lineage derived from both MSCs. It also indicated the activation of critical factors such as RUNX-1, GFI-1b, VEGF-A, MYB, GOF-1, and FLI-1. Additional experiments confirmed that EPAG could be an ideal molecule for protecting against UVB radiation damage, as gene expression (JAK-2, ERK-2, MCL-1, NFkB, and STAT-3) and protein CD90/cMPL analysis showed TPO-R activation in both hUCMSC and hGMSC. Overall, EPAG exhibits significant potential in treating radiation damage and mitigating the side effects of radiotherapy, warranting further clinical exploration.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2359028"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238033","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}

{"title":"Platelet rich fibrin as a bioactive matrix with proosteogenic and proangiogenic properties on human healthy primary cells in vitro.","authors":"Eva Dohle, Lena Schmeinck, Kamelia Parkhoo, Robert Sader, Shahram Ghanaati","doi":"10.1080/09537104.2024.2316744","DOIUrl":"10.1080/09537104.2024.2316744","url":null,"abstract":"<p><p>Blood concentrates like platelet rich fibrin (PRF) have been established as a potential autologous source of cells and growth factors with regenerative properties in the field of dentistry and regenerative medicine. To further analyze the effect of PRF on bone tissue regeneration, this study investigated the influence of liquid PRF matrices on human healthy primary osteoblasts (pOB) and co-cultures composed of pOB and human dermal vascular endothelial cells (HDMEC) as <i>in</i> <i>vitro</i> model for bone tissue regeneration. Special attention was paid to the PRF mediated influence on osteoblastic differentiation and angiogenesis. Based on the low-speed centrifugation concept, cells were treated indirectly with PRF prepared with a low (44 g) and high relative centrifugal force (710 g) before the PRF mediated effect on osteoblast proliferation and differentiation was assessed via gene and protein expression analyses and immunofluorescence. The results revealed a PRF-mediated positive effect on osteogenic proliferation and differentiation accompanied by increased concentration of osteogenic growth factors and upregulated expression of osteogenic differentiation factors. Furthermore, it could be shown that PRF treatment resulted in an increased formation of angiogenic structures in a bone tissue mimic co-culture of endothelial cells and osteoblasts induced by the PRF mediated increased release of proangiogenic growth factors. The effects on osteogenic proliferation, differentiation and vascularization were more evident when low RCF PRF was applied to the cells. In conclusion, PRF possess proosteogenic, potentially osteoconductive as well as proangiogenic properties, making it a beneficial tool for bone tissue regeneration.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2316744"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932585","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}

{"title":"Phosphorylation of (Ser 291) in the linker insert of Syk negatively regulates ITAM signaling in platelets.","authors":"Carol Dangelmaier, Hymavathi Reddy Vari, Dhruv N Vajipayajula, Manal Elzoheiry, Monica Wright, Ashvin Iyer, Alexander Y Tsygankov, Satya P Kunapuli","doi":"10.1080/09537104.2024.2369766","DOIUrl":"10.1080/09537104.2024.2369766","url":null,"abstract":"<p><p>Receptor-induced tyrosine phosphorylation of spleen tyrosine kinase (Syk) has been studied extensively in hematopoietic cells. Metabolic mapping and high-resolution mass spectrometry, however, indicate that one of the most frequently detected phosphorylation sites encompassed S297 (S291 in mice) located within the linker B region of Syk. It has been reported that Protein kinase C (PKC) phosphorylates Syk S297, thus influencing Syk activity. However, conflicting studies suggest that this phosphorylation enhances as well as reduces Syk activity. To clarify the function of this site, we generated Syk S291A knock-in mice. We used platelets as a model system as they possess Glycoprotein VI (GPVI), a receptor containing an immunoreceptor tyrosine-based activation motif (ITAM) which transduces signals through Syk. Our analysis of the homozygous mice indicated that the knock-in platelets express only one isoform of Syk, while the wild-type expresses two isoforms at 69 and 66 kDa. When the GPVI receptor was activated with collagen-related peptide (CRP), we observed an increase in functional responses and phosphorylations in Syk S291A platelets. This potentiation did not occur with AYPGKF or 2-MeSADP, although they also activate PKC isoforms. Although there was potentiation of platelet functional responses, there was no difference in tail bleeding times. However, the time to occlusion in the FeCl₃ injury model was enhanced. These data indicate that the effects of Syk S291 phosphorylation represent a significant outcome on platelet activation and signaling <i>in vitro</i> but also reveals its multifaceted nature demonstrated by the differential effects on physiological responses <i>in vivo</i>.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2369766"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurosurgical bleeding in platelet storage pool disorder: a case report.","authors":"Clifford Pierre, Kirsten W Alcorn, Dong Chen, Joanna Fesler, Daniel Landis, Zachary N Litvack, Barbara A Konkle, Livia Hegerova","doi":"10.1080/09537104.2024.2380374","DOIUrl":"10.1080/09537104.2024.2380374","url":null,"abstract":"<p><p>Dense-granule deficiency (DGD) is an inherited platelet disorder due to the absence of dense granules essential for activation of platelets in the event of vascular injury. Decreased platelet dense granules can be detected by electron microscopy, while other tests of hemostasis, including platelet function analyzer (PFA®) closure times, may be normal. The present case report describes a patient with a lifelong history of mucocutaneous bleeding and excessive hemorrhage with resection of vestibular Schwannoma. After hemostasis was obtained the case was aborted and the neurosurgeon noted bleeding resembled as if patient was on an antiplatelet drug. Subsequent hematologic workup revealed a severe platelet function disorder. There is a paucity of literature on management of intracranial neurosurgery in patients with inherited platelet disorders. Patients undergoing major surgical procedures often receive tranexamic acid (TXA), desmopressin, and/or human-leukocyte antigen (HLA)-matched platelet transfusions. We review the clinical management of intracranial tumor surgery, as well as Cyberknife radiosurgery, in our patient with DGD. After diagnosis was known, thoughtful hemostatic planning with empiric platelet transfusions and TXA prevented recurrent bleeding.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2380374"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748937","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}

{"title":"Platelet mass cytometry reveals dysregulation of prothrombotic pathways in essential thrombocythemia.","authors":"Veronika Dill, Kilian Kirmes, Jiaying Han, Melissa Klug, Marc Rosenbaum, Giacomo Viggiani, Moritz von Scheidt, Markus List, Peter Herhaus, Jürgen Ruland, Florian Bassermann, Karl-Ludwig Laugwitz, Katharina S Götze, Philipp J Jost, Stefanie Jilg, Conor J Bloxham, Philip W J Raake, Isabell Bernlochner, Dario Bongiovanni","doi":"10.1080/09537104.2024.2358244","DOIUrl":"https://doi.org/10.1080/09537104.2024.2358244","url":null,"abstract":"<p><p>Thromboembolic events are common in patients with essential thrombocythemia (ET). However, the pathophysiological mechanisms underlying the increased thrombotic risk remain to be determined. Here, we perform the first phenotypical characterization of platelet expression using single-cell mass cytometry in six ET patients and six age- and sex-matched healthy individuals. A large panel of 18 transmembrane regulators of platelet function and activation were analyzed, at baseline and after <i>ex-vivo</i> stimulation with thrombin receptor-activating peptide (TRAP). We detected a significant overexpression of the activation marker CD62P (p-Selectin) (<i>p</i> = .049) and the collagen receptor GPVI (<i>p</i> = .044) in non-stimulated ET platelets. In contrast, ET platelets had a lower expression of the integrin subunits of the fibrinogen receptor GPIIb/IIIa CD41 (<i>p</i> = .036) and CD61 (<i>p</i> = .044) and of the von Willebrand factor receptor CD42b (<i>p</i> = .044). Using the FlowSOM algorithm, we identified 2 subclusters of ET platelets with a prothrombotic expression profile, one of them (cluster 3) significantly overrepresented in ET (22.13% of the total platelets in ET, 2.94% in controls, <i>p</i> = .035). Platelet counts were significantly increased in ET compared to controls (<i>p</i> = .0123). In ET, MPV inversely correlated with platelet count (<i>r</i>=-0.96). These data highlight the prothrombotic phenotype of ET and postulate GPVI as a potential target to prevent thrombosis in these patients.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2358244"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284593","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}

{"title":"Measurement of platelet thrombus formation in patients following severe thermal injury.","authors":"Ali Asiri, Joshua M J Price, Jon Hazeldine, Kirsty C McGee, Amanda V Sardeli, Yung-Yi Chen, Jack Sullivan, Naiem S Moiemen, Paul Harrison","doi":"10.1080/09537104.2024.2420952","DOIUrl":"10.1080/09537104.2024.2420952","url":null,"abstract":"<p><p>Severe thermal injury significantly impacts upon hemostasis and is associated with classical changes to the circulating platelet count with a nadir followed by a rebound thrombocytosis at days ~3 and ~15 post-injury, respectively. To date, few studies have assessed platelet function following thermal injury as platelet tests often require large quantities of blood, are not representative of normal platelet pathophysiology, and are usually dependent on a normal platelet count. The purpose of this study was to measure platelet thrombus formation <i>in vitro</i> using a whole blood flow chip-based system following thermal injury and to study how platelet counts may impact upon the measurement. Adult (≥16 years) patients (<i>N</i> = 10) with ≥ 20% total burn surface area (TBSA) burn were recruited within 24 h of injury. Healthy controls (<i>N</i> = 25) were also recruited. Whole blood counts were measured using a hematology analyzer (Sysmex XN-1000). Platelet function was measured using the Total Thrombus-formation Analyzer System (T-TAS) within chips coated with tissue factor and collagen at shear rates of either 600 sec^-1 (AR chips) or 1200 sec^-1 (HD chips), the latter test being independent of platelet count. We confirmed the classical nadir in platelet counts following severe thermal injury at days 2, 3, 4 (<i>p</i> < 0.0001) and day 5 (<i>p</i> < 0.01) post-injury compared to healthy controls. Physiological platelet thrombus formation was significantly (<i>p</i> < 0.01) abnormal at day 3 post-injury using the AR chips but was related to the platelet count. However, although platelet dysfunction was not significant using HD chips, some of the results were independent of platelet count. A small number of samples, however, still gave abnormal results suggesting that there can be an underlying acquired platelet functional abnormality. Furthermore, the AR chip Area Under the Curve (AUC) was significantly lower on day 1 post-injury and negatively associated with severity of injury (TBSA, <i>p</i> < 0.05) and higher platelet function (AUC) positively associated with survival (<i>p</i> < 0.05). This study suggests that measuring platelet dysfunction within a more physiological <i>in vitro</i> test may have potential clinical utility. Larger studies are required to fully understand the impact of platelet dysfunction following severe thermal injury.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2420952"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569463","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}

{"title":"The potential utilization of platelet-derived extracellular vesicles in clinical treatment","authors":"Zhijia Fan, Yixiao Gan, Yanwei Hu","doi":"10.1080/09537104.2024.2397592","DOIUrl":"https://doi.org/10.1080/09537104.2024.2397592","url":null,"abstract":"Platelet-derived extracellular vesicles (PEVs) are released by platelets in the blood circulation, which carry a rich bio-molecular cargo influential in intercellular communications. PEVs can enter...","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"10 1","pages":"2397592"},"PeriodicalIF":3.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258472","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}

{"title":"The safety and efficacy of indobufen or aspirin combined with clopidogrel in patients with acute myocardial infarction after percutaneous coronary intervention","authors":"Wen-Bo Dai, Jia-Yi Ren, Su-Tao Hu, Yu-Kun Zhang, Tian-Shu Gu, Xue Wu, Jing-Kun Zhang, Jing-Jin Che, Xiang-Hong Ma, Tong Liu, Guang-Ping Li, Kang-Yin Chen","doi":"10.1080/09537104.2024.2364748","DOIUrl":"https://doi.org/10.1080/09537104.2024.2364748","url":null,"abstract":"Currently, the standard treatment for patients who have undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (MI) involves dual antiplatelet therapy (DAPT) with ...","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"6 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141509900","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}

{"title":"Storage of plasma-derived exosomes: evaluation of anticoagulant use and preserving temperatures","authors":"Caiting Yang, Jie Han, Hai Liu, Yuyu He, Zhenhua Zhang, Xiaochun Liu, Farooq Waqas, Lizhong Zhang, Huiping Duan, Jing He, Li Dong","doi":"10.1080/09537104.2024.2337255","DOIUrl":"https://doi.org/10.1080/09537104.2024.2337255","url":null,"abstract":"Exosomes carry large cargo of proteins, lipids, and nucleic acids, serving as versatile biomarkers for disease diagnosis and vehicles for drug delivery. However, up to date, no well recognized stan...","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"14 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617886","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}

{"title":"Activation of AMPK in platelets promotes the production of offspring","authors":"Tong Zhang, Mengnan Yang, Shujun Li, Rong Yan, Kesheng Dai","doi":"10.1080/09537104.2024.2334701","DOIUrl":"https://doi.org/10.1080/09537104.2024.2334701","url":null,"abstract":"Platelets are terminally differentiated anucleated cells, but they still have cell-like functions and can even produce progeny platelets. However, the mechanism of platelet sprouting has not been e...","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"69 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140612800","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}