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JOURNAL ARTICLE
Alberto Zanetto, Serena Toffanin, Elena Campello, Claudia Maria Radu, Sabrina Gavasso, Patrizia Burra, Francesco Paolo Russo, Marco Senzolo, Paolo Simioni
BACKGROUND: Reticulated platelets (RePLT) are emergency circulating platelets released to contrast peripheral platelet destruction. AIM: We conducted a prospective study to [a] characterize RePLT in cirrhosis; [b] evaluate the association between RePLT and hepatic decompensation/death. METHODS: Cirrhosis patients without hepatocellular carcinoma were prospectively recruited and underwent assessment of RePLT and thrombopoietin (TPO). RePLT were evaluated by cytofluorimetry and immuno-fluorescence microscopy...
March 28, 2024: Digestive and Liver Disease
#2
REVIEW
Beata Olas
Hyperactivation of blood platelets, one of the causes of heart attack, and other cardiovascular diseases (CVDs), is influenced by various dietary components, including phenolic compounds from vegetables, fruits, teas, wines, cocoa and its products, including chocolate. The present paper sheds new light on the effect of cocoa and its products, especially dark chocolate, on the number and function of blood platelets, and the anti-platelet activity of their constituent phenolic compounds. A review was performed of papers identified in various electronic databases, including PubMed, Science Direct, Scopus, Web of Knowledge, and Google Scholar, with the aim of determining whether their anti-platelet activity may serve as part of a sweet strategy in countering CVDs...
2024: Frontiers in Pharmacology
#3
JOURNAL ARTICLE
Fanghui Chen, Chris Tang, Fan Yang, Asari Ekpenyong, Richard Qin, Jin Xie, Fatemeh Momen-Heravi, Nabil F Saba, Yong Teng
Glycolytic metabolism may account for antitumor immunity failure. Pyruvate kinase M2 (PKM2) and platelet phosphofructokinase (PFKP), two key enzymes involved in the glycolytic pathway, are hyperactivated in head and neck squamous cell carcinoma (HNSCC). Using ganetespib as a drug model for heat shock protein 90 (HSP90) inhibition and combining results from clinical trials and animal treatment, we demonstrated that HSP90 inhibition leads to a blockade of glycolytic flux in HNSCC cells by simultaneously suppressing PKM2 and PFKP at both the transcriptional and posttranslational levels...
February 23, 2024: Science Advances
#4
REVIEW
Christos-Georgios Kontovazainitis, Dimitra Gialamprinou, Theodoros Theodoridis, Georgios Mitsiakos
Pre-eclampsia (PE) is a placenta-mediated disease and remains a major cause of maternal and neonatal mortality and morbidity. As PE develops, normal pregnancy's hypercoagulable balance is disrupted, leading to platelet hyperactivation, excessive pathological hypercoagulability, and perturbed fibrinolysis. This narrative review aims to summarize the current knowledge regarding hemostasis in PE compared with healthy gestation and the potential effects of maternal PE on neonatal hemostasis. Finally, it aims to discuss hemostasis assessments for normal pregnancies and PE, emphasizing the role of viscoelastic tests, namely, thromboelastography (TEG) and thromboelastometry (ROTEM), for monitoring PE-associated hemostatic alterations...
February 5, 2024: Diagnostics
#5
Alessandro Morotti, Cristina Barale, Michele Sornatale, Emilia Giugliano, Vittorio Emanuele Muccio, Chiara Frascaroli, Marisa Pautasso, Alessandro Fornari, Isabella Russo
Essential thrombocythemia (ET) is a myeloproliferative neoplasm variant characterized by excessive production of platelets. Since the most common cause of mortality and morbidity in ET patients is thrombosis, the excessive production of platelets may cause thrombotic events. However, little is known about the function of platelets in ET. We report a female patient who presented as asymptomatic, without a remarkable medical history, and ET was diagnosed after an incidental finding of moderate thrombocytosis...
December 22, 2023: International Journal of Molecular Sciences
#6
JOURNAL ARTICLE
Francesca Maiorca, Ludovica Lombardi, Ramona Marrapodi, Davide Pallucci, Annamaria Sabetta, Maria Antonella Zingaropoli, Valentina Perri, Davide Flego, Giulio Francesco Romiti, Bernadette Corica, Marzia Miglionico, Gianluca Russo, Patrizia Pasculli, Maria Rosa Ciardi, Claudio M Mastroianni, Franco Ruberto, Francesco Pugliese, Fabio Pulcinelli, Valeria Raparelli, Roberto Cangemi, Marcella Visentini, Stefania Basili, Lucia Stefanini
BACKGROUND: Severe COVID-19 is associated with an excessive immunothrombotic response and thromboinflammatory complications. Vaccinations effectively reduce the risk of severe clinical outcomes in patients with COVID-19, but their impact on platelet activation and immunothrombosis during breakthrough infections is not known. OBJECTIVES: To investigate how preemptive vaccinations modify the platelet-immune crosstalk during COVID-19 infections. METHODS: Cross-sectional flow cytometry study of the phenotype and interactions of platelets circulating in vaccinated ( n = 21) and unvaccinated patients with COVID-19, either admitted to the intensive care unit (ICU, n = 36) or not (non-ICU, n = 38), in comparison to matched SARS-CoV-2-negative patients ( n = 48), was performed...
November 2023: Research and Practice in Thrombosis and Haemostasis
#7
JOURNAL ARTICLE
Valentine Léopold, Osoul Chouchane, Joe M Butler, Alex R Schuurman, Erik H A Michels, Justin de Brabander, Bauke V Schomakers, Michel van Weeghel, Daisy I Picavet-Havik, Anita E Grootemaat, Renée A Douma, Tom D Y Reijnders, Augustijn M Klarenbeek, Brent Appelman, W Joost Wiersinga, Nicole N van der Wel, Jeroen den Dunnen, Riekelt H Houtkooper, Cornelis Van't Veer, Tom van der Poll
BACKGROUND: Alterations in platelet function have been implicated in the pathophysiology of COVID-19 since the beginning of the pandemic. While early reports linked hyperactivated platelets to thromboembolic events in COVID-19, subsequent investigations demonstrated hyporeactive platelets with a procoagulant phenotype. Mitochondria are important for energy metabolism and the function of platelets. OBJECTIVES: Here, we sought to map the energy metabolism of platelets in a cohort of noncritically ill COVID-19 patients and assess platelet mitochondrial function, activation status, and responsiveness to external stimuli...
October 2023: Research and Practice in Thrombosis and Haemostasis
#8
JOURNAL ARTICLE
Stien De Coninck, Renate De Smedt, Beatrice Lintermans, Lindy Reunes, Hansen J Kosasih, Alexandra Reekmans, Lauren M Brown, Nadine Van Roy, Bruno Palhais, Juliette Roels, Malaika Van der Linden, Jo Van Dorpe, Panagiotis Ntziachristos, Frederik W Van Delft, Marc R Mansour, Tim Pieters, Tim Lammens, Barbara De Moerloose, Charles E De Bock, Steven Goossens, Pieter Van Vlierberghe
T cell acute lymphoblastic leukemia (T-ALL) and T cell lymphoblastic lymphoma (T-LBL) are rare aggressive hematological malignancies. Current treatment consists of intensive chemotherapy, leading to 80% overall survival but are associated with severe toxic side effects. Furthermore, 10-20% of patients still die from relapsed or refractory disease providing a strong rationale for more specific, targeted therapeutic strategies with less toxicities. Here, we report a novel MYH9::PDGFRB fusion in a T-LBL patient and demonstrate that this fusion product is constitutively active and sufficient to drive oncogenic transformation in vitro and in vivo...
November 9, 2023: Haematologica
#9
JOURNAL ARTICLE
Sagar S Matharu, Cassidy S Nordmann, Kurtis R Ottman, Rahul Akkem, Douglas Palumbo, Denzel R D Cruz, Kenneth Campbell, Gail Sievert, Jamie Sturgill, James Z Porterfield, Smita Joshi, Hammodah R Alfar, Chi Peng, Irina D Pokrovskaya, Jeffrey A Kamykowski, Jeremy P Wood, Beth Garvy, Maria A Aronova, Sidney W Whiteheart, Richard D Leapman, Brian Storrie
Platelets contribute to COVID-19 clinical manifestations, of which microclotting in the pulmonary vasculature has been a prominent symptom. To investigate the potential diagnostic contributions of overall platelet morphology and their α-granules and mitochondria to the understanding of platelet hyperactivation and micro-clotting, we undertook a 3D ultrastructural approach. Because differences might be small, we used the high-contrast, high-resolution technique of focused ion beam scanning EM (FIB-SEM) and employed deep learning computational methods to evaluate nearly 600 individual platelets and 30 000 included organelles within three healthy controls and three severely ill COVID-19 patients...
December 2023: Platelets
#10
JOURNAL ARTICLE
Andrea C Wong, Ashwarya S Devason, Iboro C Umana, Timothy O Cox, Lenka Dohnalová, Lev Litichevskiy, Jonathan Perla, Patrick Lundgren, Zienab Etwebi, Luke T Izzo, Jihee Kim, Monika Tetlak, Hélène C Descamps, Simone L Park, Stephen Wisser, Aaron D McKnight, Ryan D Pardy, Junwon Kim, Niklas Blank, Shaan Patel, Katharina Thum, Sydney Mason, Jean-Christophe Beltra, Michaël F Michieletto, Shin Foong Ngiow, Brittany M Miller, Megan J Liou, Bhoomi Madhu, Oxana Dmitrieva-Posocco, Alex S Huber, Peter Hewins, Christopher Petucci, Candice P Chu, Gwen Baraniecki-Zwil, Leila B Giron, Amy E Baxter, Allison R Greenplate, Charlotte Kearns, Kathleen Montone, Leslie A Litzky, Michael Feldman, Jorge Henao-Mejia, Boris Striepen, Holly Ramage, Kellie A Jurado, Kathryn E Wellen, Una O'Doherty, Mohamed Abdel-Mohsen, Alan L Landay, Ali Keshavarzian, Timothy J Henrich, Steven G Deeks, Michael J Peluso, Nuala J Meyer, E John Wherry, Benjamin A Abramoff, Sara Cherry, Christoph A Thaiss, Maayan Levy
Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction...
October 9, 2023: Cell
#11
JOURNAL ARTICLE
Pan Pan, Jie Chen, Fei Xie, Yinghua Guo, Xudong Liu, Dong Zhang, Lixin Xie, Longxiang Su
Platelets are highly involved in inflammation and organ injury under pathological conditions. The mitophagy in platelets may restrict hyperactivation of the inflammasome and relieve acute kidney injury (AKI). Cecal ligation puncture (CLP)/LPS-induced AKI Triggering receptor expressed on myeloid cells (TREM-1)-knockout mice models were established. Additionally, septic patients with AKI were also included. TREM-1 expression in platelets and inflammasome activation were examined. Platelet transfer assays were performed to investigate the contribution of platelet TREM-1 to renal injury...
November 2023: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
#12
JOURNAL ARTICLE
Wei Huang, Wendong Yao, Yayun Weng, Xianze Xie, Jiali Jiang, Shuo Zhang, Zheng Shi, Qiao-Mei Fan
Pathological platelet activation plays a vital role in the prevalence of cardiovascular diseases. Hydroxysafflor yellow A (HSYA) has been shown to have significant anti-platelet aggregation and anti-activation effects, but its mechanism of action is unclear. Our study showed that HSYA inhibited the expression of platelet surface glycoproteins IIβ/III α (GPIIβ/III α) and thromboxane A2 (TXA2) during platelet activation and reduced platelet Ca2+ accumulation. HSYA significantly reduced the number of platelets and inhibited adrenaline-induced platelet hyperaggregation in rats...
September 23, 2023: Archives of Biochemistry and Biophysics
#13
REVIEW
Amanuel Kelem, Tiruneh Adane, Elias Shiferaw
BACKGROUND: Insulin has an inhibitory effect on platelets; however, this is compromised in circumstances of Insulin Resistance (IR), leading to platelet hyperactivity. Platelet parameters such as mean platelet volume, platelet count, and platelet distribution width are simple and accessible potential biomarkers for the early diagnosis and prognosis of IR. Therefore, the aim of this review is to provide insight on the current status of knowledge regarding IR-induced platelet hyperactivation and the potential biomarker role of platelet parameters...
2023: Diabetes, Metabolic Syndrome and Obesity
#14
JOURNAL ARTICLE
Sonali Munshaw, Andia N Redpath, Benjamin T Pike, Nicola Smart
Atherosclerosis is a progressive, degenerative vascular disease and a leading cause of morbidity and mortality. In response to endothelial damage, platelet derived growth factor (PDGF)-BB induced phenotypic modulation of medial smooth muscle cells (VSMCs) promotes atherosclerotic lesion formation and destabilisation of the vessel wall. VSMC sensitivity to PDGF-BB is determined by endocytosis of Low density lipoprotein receptor related protein 1 (LRP1)-PDGFR β complexes to balance receptor recycling with lysosomal degradation...
February 2023: International Immunopharmacology
#15
REVIEW
Yan Ma, Qian Jiang, Bingxin Yang, Xiaoyu Hu, Gang Shen, Wei Shen, Jing Xu
Dysfunction of the immune response is regarded as a prominent feature of neurological diseases, including neurodegenerative diseases, malignant tumors, acute neurotraumatic insult, and cerebral ischemic/hemorrhagic diseases. Platelets play a fundamental role in normal hemostasis and thrombosis. Beyond those normal functions, platelets are hyperactivated and contribute crucially to inflammation and immune responses in the central nervous system (CNS). Mitochondria are pivotal organelles in platelets and are responsible for generating most of the ATP that is used for platelet activation and aggregation (clumping)...
2023: Frontiers in Physiology
#16
JOURNAL ARTICLE
Olha M Koval, Emily K Nguyen, Dylan J Mittauer, Karima Ait-Aissa, William C Chinchankar, Isabella M Grumbach
Type 2 diabetes (T2D) is associated with increased risk of atherosclerotic vascular disease due to excessive vascular smooth muscle cell (VSMC) proliferation. Here, we investigated the role of mitochondrial dysfunction and Ca2+ levels in VSMC proliferation in T2D. VSMCs were isolated from normoglycemic and T2D-like mice induced by diet. The effects of mitochondrial Ca2+ uptake were studied using mice with selectively inhibited mitochondrial Ca2+/calmodulin-dependent kinase II (mtCaMKII) in VSMCs. Mitochondrial transition pore (mPTP) was blocked using ER-000444793...
August 17, 2023: International Journal of Molecular Sciences
#17
JOURNAL ARTICLE
Joshua H Bourne, Joana Campos, Sophie J Hopkin, Katharine Whitworth, James Palis, Yotis A Senis, Julie Rayes, Asif J Iqbal, Alexander Brill
BACKGROUND: The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome has been described in both immune cells and platelets, but its role in the megakaryocyte (MK) lineage remains elusive. OBJECTIVE: The aim of this study was to explore the role of NLRP3 inflammasome in megakaryocytes and platelets. METHODS: We generated Nlrp3 A350V/+ / Gp1ba- CreKI/+ mice carrying a mutation genetically similar to the one observed in human Muckle-Wells syndrome, which leads to hyperactivity of NLRP3 specifically in MK and platelets...
2023: Frontiers in Immunology
#18
JOURNAL ARTICLE
Zihan Tang, Yanyan Xu, Yun Tan, Hui Shi, Peipei Jin, Yunqi Li, Jialin Teng, Honglei Liu, Haoyu Pan, Qiongyi Hu, Xiaobing Cheng, Junna Ye, Yutong Su, Yue Sun, Jianfen Meng, Zhuochao Zhou, Huihui Chi, Xuefeng Wang, Junling Liu, Yong Lu, Feng Liu, Jing Dai, Chengde Yang, Saijuan Chen, Tingting Liu
Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and mediates hyperactivation of human and mouse platelets through the p38 MAPK-NF-κB signaling pathway...
August 21, 2023: Nature Communications
#19
JOURNAL ARTICLE
Natalia Sławińska, Agata Rolnik, Anna Stochmal, Beata Olas
Paulownia Clon in Vitro 112, also called the Oxytree, is a fast-growing hybrid of two trees belonging to the Paulowniaceae family - P. elongata and P. fortunei. It demonstrates a wide range of biological effects (including antioxidant, anti-inflammatory, antibacterial, and neuroprotective) due to the high concentration of secondary metabolites. Our previous results showed an in vitro antioxidant and antiplatelet activity of the extract and four fractions (A-D) from the leaves of Paulownia Clon in Vitro 112 in human plasma and washed blood platelets...
September 2023: Biomedicine & Pharmacotherapy
#20
JOURNAL ARTICLE
Sakshi Agarwal, Riya Ghosh, Garima Verma, Rajesh Khadgawat, Prasenjit Guchhait
The interplay between platelets and leukocytes contributes to the pathogenesis of inflammation, thrombosis and cardiovascular diseases (CVDs) in type 2 diabetes (T2D). Our recent studies described alpha-ketoglutarate (αKG), a Krebs cycle intermediate metabolite as an inhibitor to platelets and leukocytes activation by suppressing phosphorylated-Akt (pAkt) through augmentation of prolyl hydroxylase-2 (PHD2). Dietary supplementation with a pharmacological concentration of αKG significantly inhibited lung inflammation in mice with either SARS-CoV-2 infection or exposed to hypoxia treatment...
July 27, 2023: Clinical and Experimental Immunology
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