Platelets最新文献_第5页

A splice mutation in RASGRP2 gene in the patient with recurrent epistaxis and nasal vascular malformation. 反复鼻衄和鼻腔血管畸形患者的 RASGRP2 基因剪接突变。

IF 2.5 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-11-08 DOI: 10.1080/09537104.2024.2425664

Zhong-Yu Shi, Qing-Ling Lei, Shao-Qin Duan, Yan Zhou, Ting-Ting Cui, Yun-Bi Lin, Chun-Hui Yang, Chun-Yan Song, Chun-Lian Fang, Xin Tian, Xian-Wen Zhang, Ti-Long Huang

{"title":"A splice mutation in RASGRP2 gene in the patient with recurrent epistaxis and nasal vascular malformation.","authors":"Zhong-Yu Shi, Qing-Ling Lei, Shao-Qin Duan, Yan Zhou, Ting-Ting Cui, Yun-Bi Lin, Chun-Hui Yang, Chun-Yan Song, Chun-Lian Fang, Xin Tian, Xian-Wen Zhang, Ti-Long Huang","doi":"10.1080/09537104.2024.2425664","DOIUrl":"https://doi.org/10.1080/09537104.2024.2425664","url":null,"abstract":"Platelet type bleeding disorder-18 (BDPLT18) caused by mutations of Ras guanyl releasing protein 2 (RASGRP2) is a relatively rare, new autosomal recessive disorder. Here, we reported a splice mutation in RASGRP2 gene in the patient with recurrent epistaxis and nasal vascular malformation. The patient, an 8-year-old girl, suffered from anemia due to frequently severe recurrent epistaxis, requiring regular blood transfusions every 2-3 months. Hematological investigations showed moderate anemia (Hb: 89 g/L), normal platelet count, morphology, and platelet glycoproteins. Arachidonic acid and adenosine diphosphate induced platelet aggregation was markedly reduced in the patient. A homozygous splice variant (C.74-1 G>C) in RASGRP2 gene, located within the exon 3, was detected by next-generation sequencing. Interestingly, we identified nasal vascular malformation by percutaneous super-selective angiography during the treatment of an intractable epistaxis. Our case further support that genetic testing should be performed for some unexplained bleeding diseases.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2425664"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606164","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

Alterations in platelet activity and endothelial glycocalyx biomarkers by treatment with an angiotensin converting enzyme inhibitor or an alpha-1 adrenoceptor antagonist in patients with hypertension: results from the DoRa study. 血管紧张素转换酶抑制剂或α -1肾上腺素受体拮抗剂治疗高血压患者血小板活性和内皮糖萼生物标志物的改变：来自DoRa研究的结果

IF 2.5 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-12-16 DOI: 10.1080/09537104.2024.2437768

Mikael Ekholm, Andreas Jekell, Kristina Lundwall, Joakim Alfredsson, Tomas L Lindahl, Håkan Wallén, Thomas Kahan

{"title":"Alterations in platelet activity and endothelial glycocalyx biomarkers by treatment with an angiotensin converting enzyme inhibitor or an alpha-1 adrenoceptor antagonist in patients with hypertension: results from the DoRa study.","authors":"Mikael Ekholm, Andreas Jekell, Kristina Lundwall, Joakim Alfredsson, Tomas L Lindahl, Håkan Wallén, Thomas Kahan","doi":"10.1080/09537104.2024.2437768","DOIUrl":"10.1080/09537104.2024.2437768","url":null,"abstract":"Drugs blocking the renin-angiotensin-aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We have shown antithrombin effects by treatment with the angiotensin converting enzyme (ACE) inhibitor ramipril. As thrombin is a key inducer of platelet aggregation, we hypothesized that treatment with ramipril could modulate platelet reactivity and endothelial glycocalyx (eGCX) function. This study assessed platelet activity (CD40 ligand and P-selectin) and eGCX markers (E-selectin, hyaluronan, syndecan-1, and thrombomodulin) in 59 individuals with mild-to-moderate hypertension, randomized double-blind to ramipril 10 mg or doxazosin 8 mg od for 12 weeks. Ramipril and doxazosin similarly reduced blood pressure. Antihypertensive treatment reduced CD40 ligand (p < .001) with no interaction (p = .405) by treatment group (reductions by ramipril and doxazosin were 8.7 ± 30.8 ng/L, p = .044, and 13.4 ± 25.5 ng/L, p = .002, respectively). There were no changes in P-selectin by treatment within (p = .556) or between (p = .256) treatment groups. No changes were observed in E-selectin, hyaluronan, syndecan-1, or thrombomodulin by antihypertensive treatment (p = .091-.991), or between ramipril and doxazosin (p = .223-.999). Our results show a potential reduction of platelet activity by ACE inhibitor treatment. Also, the alpha 1-adrenoceptor antagonist doxazosin may reduce platelet activation. Neither drug influenced eGCX markers.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2437768"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838631","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

Glycan-Lectin interactions between platelets and tumor cells drive hematogenous metastasis. 血小板与肿瘤细胞之间的糖蛋白-肌球蛋白相互作用推动了血源性转移。

IF 3.3 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-02-19 DOI: 10.1080/09537104.2024.2315037

Longqiang Shu, Shanyi Lin, Shumin Zhou, Ting Yuan

{"title":"Glycan-Lectin interactions between platelets and tumor cells drive hematogenous metastasis.","authors":"Longqiang Shu, Shanyi Lin, Shumin Zhou, Ting Yuan","doi":"10.1080/09537104.2024.2315037","DOIUrl":"10.1080/09537104.2024.2315037","url":null,"abstract":"Glycosylation is a ubiquitous cellular or microenvironment-specific post-translational modification that occurs on the surface of normal cells and tumor cells. Tumor cell-associated glycosylation is involved in hematogenous metastasis. A wide variety of tumors undergo aberrant glycosylation to interact with platelets. As platelets have many opportunities to engage circulating tumor cells, they represent an important avenue into understanding the role glycosylation plays in tumor metastasis. Platelet involvement in tumor metastasis is evidenced by observations that platelets protect tumor cells from damaging shear forces and immune system attack, aid metastasis through the endothelium at specific sites, and facilitate tumor survival and colonization. During platelet-tumor-cell interactions, many opportunities for glycan-ligand binding emerge. This review integrates the latest information about glycans, their ligands, and how they mediate platelet-tumor interactions. We also discuss adaptive changes that tumors undergo upon glycan-lectin binding and the impact glycans have on targeted therapeutic strategies for treating tumors in clinical settings.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2315037"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139900279","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

Small volume platelet concentrates for neonatal use are more susceptible to shear-induced storage lesion. 用于新生儿的小容量血小板浓缩物更容易受到剪切力引起的储存病变的影响。

IF 2.5 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-08-22 DOI: 10.1080/09537104.2024.2389967

Dean Pym, Amanda J Davies, Jessica O Williams, Christine Saunders, Chloë E George, Philip E James

{"title":"Small volume platelet concentrates for neonatal use are more susceptible to shear-induced storage lesion.","authors":"Dean Pym, Amanda J Davies, Jessica O Williams, Christine Saunders, Chloë E George, Philip E James","doi":"10.1080/09537104.2024.2389967","DOIUrl":"https://doi.org/10.1080/09537104.2024.2389967","url":null,"abstract":"The impact of the biophysical environment on the platelet storage lesion (PSL) has mainly focused on reduced temperature storage, overlooking the significance of storage-induced shear stress. Shear stress in platelet storage refers to the frictional force acting parallel to the bag surface and exists solely through the implementation of agitation. This study investigates whether minimizing exposure to agitation-induced shear stress can alleviate the unexplained loss of function in stored platelet concentrates for neonatal transfusion (neonatal PCs). Using particle tracking analysis, fluid motion was measured in neonatal and adult platelet storage bags under agitation frequencies ranging from 20-60 rpm. Platelets stored at 20-60 rpm agitation over 8 days were examined by biochemical analysis, aggregation, and expression of activation markers. Results indicate that neonatal PCs experience significantly higher storage-induced shear stress compared to adult doses, leading to reduced functionality and increased activation from day 2 of storage. Adjusting the neonatal PC agitation frequency to 20 rpm improved functionality in early storage, while 40 rpm maintains this improvement throughout storage with reduced activation, compared to 60 rpm storage. This study confirms that small volume PC storage for neonatal use contributes to the PSL through the induction of shear stress, suggesting further evaluation of the recommended agitation frequency for neonatal PCs or postponement of the production of neonatal PCs until requested for neonatal transfusion.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2389967"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018324","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

Impact of thrombocytopenia-associated c.-118C>T and c.-140C>G ANKRD26 5'UTR variants in three-generational pedigree. 三代血统中血小板减少症相关 c.-118C>T 和 c.-140C>G ANKRD26 5'UTR 变异的影响。

IF 2.5 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-08-30 DOI: 10.1080/09537104.2024.2388103

Jakub Trizuljak, Paulína Likavcová, Kateřina Staňo Kozubík, Zuzana Vrzalová, Jakub Hynšt, Tereza Deissová, Jiří Štika, Lenka Radová, Marie Prudková, Jana Vaculová, Ivona Blaháková, Petr Smejkal, Jan Kamelander, Šárka Pospíšilová, Michael Doubek

{"title":"Impact of thrombocytopenia-associated c.-118C>T and c.-140C>G ANKRD26 5'UTR variants in three-generational pedigree.","authors":"Jakub Trizuljak, Paulína Likavcová, Kateřina Staňo Kozubík, Zuzana Vrzalová, Jakub Hynšt, Tereza Deissová, Jiří Štika, Lenka Radová, Marie Prudková, Jana Vaculová, Ivona Blaháková, Petr Smejkal, Jan Kamelander, Šárka Pospíšilová, Michael Doubek","doi":"10.1080/09537104.2024.2388103","DOIUrl":"10.1080/09537104.2024.2388103","url":null,"abstract":"Inherited thrombocytopenias (ITs) encompass a group of rare disorders characterized by diminished platelet count. Recent advancements have unveiled various forms of IT, with inherited thrombocytopenia 2 (THC2) emerging as a prevalent subtype associated with germline variants in the critical 5' untranslated region of the ANKRD26 gene. This region is crucial in regulating the gene expression of ANKRD26, particularly in megakaryocytes. THC2 is an autosomal dominant disorder presenting as mild-to-moderate thrombocytopenia with minimal symptoms, with an increased risk of myeloproliferative malignancies. In our study of a family with suspected IT, three affected individuals harbored the c.-118C>T ANKRD26 variant, while four healthy members carried the c.-140C>G ANKRD26 variant. We performed a functional analysis by studying platelet-specific ANKRD26 gene expression levels using quantitative real-time polymerase-chain reaction. Functional analysis of the c.-118C>T variant showed a significant increase in ANKRD26 expression in affected individuals, supporting its pathogenicity. On the contrary, carriers of the c.-140C>G variant exhibited normal platelet counts and no significant elevation in the ANKRD26 expression, indicating the likely benign nature of this variant. Our findings provide evidence confirming the pathogenicity of the c.-118C>T ANKRD26 variant in THC2 and suggest the likely benign nature of the c.-140C>G variant.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2388103"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111212","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

Effects of different doses of tirofiban combined with dual antiplatelet drugs on platelet indices, vascular endothelial function, and major adverse cardiovascular events in patients with acute ST-segment elevated myocardial infarction undergoing percutaneous coronary intervention. 不同剂量的替罗非班联合双联抗血小板药物对接受经皮冠状动脉介入治疗的急性 ST 段抬高型心肌梗死患者的血小板指数、血管内皮功能和主要不良心血管事件的影响。

IF 2.5 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-09-26 DOI: 10.1080/09537104.2024.2402301

Xia Li, Xiaofan Guo, Naijin Zhang, Ye Chang, Yingxian Sun

{"title":"Effects of different doses of tirofiban combined with dual antiplatelet drugs on platelet indices, vascular endothelial function, and major adverse cardiovascular events in patients with acute ST-segment elevated myocardial infarction undergoing percutaneous coronary intervention.","authors":"Xia Li, Xiaofan Guo, Naijin Zhang, Ye Chang, Yingxian Sun","doi":"10.1080/09537104.2024.2402301","DOIUrl":"https://doi.org/10.1080/09537104.2024.2402301","url":null,"abstract":"This trial targeted to analyze the effects of different doses of tirofiban combined with dual antiplatelet drugs on platelet indices, vascular endothelial function, and major adverse cardiovascular events (MACE) in patients with acute ST-segment elevated myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). A total of 180 patients with STEMI who underwent PCI were divided into Group A, Group B, and Group C (60 cases per group). Group A was given conventional medication, and Groups B and C were given a standard dose (10 μg/kg) and a high dose (20 μg/kg) of tirofiban on the basis of Group A, respectively. Thrombolysis in myocardial infarction (TIMI) myocardial perfusion grade and TIMI blood flow grade were compared. Myocardial enzymes, platelet indices, vascular endothelial function, inflammatory factors, and cardiac function indices were detected. In-hospital bleeding events and follow-up MACE were recorded. After PCI, Group C had a higher number of TIMI myocardial perfusion grade III and TIMI blood flow grade III versus Group A. Group C achieved the greatest changes in myocardial enzymes, platelet indices, vascular endothelial function-related factors, inflammatory factors, and cardiac function indices, followed by Group B and Group A. The incidence of bleeding events was higher in Group C than in Group A, and that of MACE in Group C was lower than in Group A. The addition of high-dose tirofiban to PCI and dual antiplatelet drugs for STEMI patients can improve myocardial blood perfusion, cardiac function, and vascular endothelial function, inhibit platelet activation and aggregation, and reduce the occurrence of MACE.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2402301"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352570","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

Molecular insights on Eltrombopag: potential mitogen stimulants, angiogenesis, and therapeutic radioprotectant through TPO-R activation. 关于 Eltrombopag 的分子见解：潜在的有丝分裂原刺激物、血管生成和通过 TPO-R 激活的治疗性放射保护剂。

IF 3.3 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-06-04 DOI: 10.1080/09537104.2024.2359028

Rajasekaran Subbarayan, Dhasarathdev Srinivasan, Salman Shadula Osmania, Dinesh Murugan Girija, Shoeb Ikhlas, Nityanand Srivastav, Ranjith Balakrishnan, Rupendra Shrestha, Ankush Chauhan

{"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":"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.","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}

引用次数: 0

Platelet rich fibrin as a bioactive matrix with proosteogenic and proangiogenic properties on human healthy primary cells in vitro. 富血小板纤维蛋白作为一种生物活性基质，对体外人类健康原代细胞具有促生长和促血管生成特性。

IF 3.3 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-02-23 DOI: 10.1080/09537104.2024.2316744

Eva Dohle, Lena Schmeinck, Kamelia Parkhoo, Robert Sader, Shahram Ghanaati

{"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":"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 in vitro 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.","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}

引用次数: 0

Phosphorylation of (Ser 291) in the linker insert of Syk negatively regulates ITAM signaling in platelets. Syk 连接插入物中的磷酸化（Ser 291）对血小板中的 ITAM 信号传导有负向调节作用。

IF 2.5 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-06-21 DOI: 10.1080/09537104.2024.2369766

Carol Dangelmaier, Hymavathi Reddy Vari, Dhruv N Vajipayajula, Manal Elzoheiry, Monica Wright, Ashvin Iyer, Alexander Y Tsygankov, Satya P Kunapuli

{"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":"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 in vitro but also reveals its multifaceted nature demonstrated by the differential effects on physiological responses in vivo.","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}

引用次数: 0

Neurosurgical bleeding in platelet storage pool disorder: a case report. 血小板贮存池紊乱导致的神经外科出血：病例报告。

IF 2.5 3区医学

Platelets Pub Date : 2024-12-01 Epub Date: 2024-07-23 DOI: 10.1080/09537104.2024.2380374

Clifford Pierre, Kirsten W Alcorn, Dong Chen, Joanna Fesler, Daniel Landis, Zachary N Litvack, Barbara A Konkle, Livia Hegerova

{"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":"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.","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}

引用次数: 0