Explanipedia

TRIPLE Score: GPVI and CD36 Expression Predict a Prothrombotic Platelet Function Phenotype Open

Alexander P. Bye, Neline Kriek, Carly Kempster, Joanne L. Dunster, Joanne Mitchell , et al. · 2025

Multiple myeloma and its treatment contribute to increased platelet reactivity Open

Joanne Mitchell, Dalia Khan, Rekha Rana, Neline Kriek, Amanda J. Unsworth , et al. · 2023

Multiple myeloma (MM) and its precursor states, smoldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with increased incidence of thrombosis, however the cause of this is unknown. Lenalidomide…

Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19 Open

Chiara E. Geyer, Hung‐Jen Chen, Alexander P. Bye, Xue D. Manz, Denise Guerra , et al. · 2023

Previously, we and others have shown that SARS-CoV-2 spike-specific IgG antibodies play a major role in disease severity in COVID-19 by triggering macrophage hyperactivation, disrupting endothelial barrier integrity, and inducing thrombus …

Delineating Zinc Influx Mechanisms during Platelet Activation Open

Sahithi J. Kuravi, Niaz S. Ahmed, Kirk A. Taylor, Emily Capes, Alexander P. Bye , et al. · 2023

Zinc (Zn2+) is released by platelets during a hemostatic response to injury. Extracellular zinc ([Zn2+]o) initiates platelet activation following influx into the platelet cytosol. However, the mechanisms that permit Zn2+ influx are unknown…

Platelet factor XIII-A regulates platelet function and promotes clot retraction and stability Open

Joanne Mitchell, Gemma Little, Alexander P. Bye, Renato Simões Gaspar, Amanda J. Unsworth , et al. · 2023

The rate of platelet activation determines thrombus size and structure at arterial shear Open

Joanne L. Mitchell, Joanne L. Dunster, Neline Kriek, Amanda J. Unsworth, Tanya Sage , et al. · 2023

For the first time, we have shown that platelet response rate corresponds to thrombus size and structure, wherein faster responders form larger, more densely packed thrombi at arterial, but crucially not venous, shear. We have demonstrated…

Identification of New Drugs to Counteract Anti-Spike IgG-Induced Hyperinflammation in Severe COVID-19 Open

Chiara E. Geyer, Hung‐Jen Chen, Alexander P. Bye, Xue D. Manz, Denise Guerra , et al. · 2023

Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19 Open

Chiara E. Geyer, Hung‐Jen Chen, Alexander P. Bye, Xue D. Manz, Denise Guerra , et al. · 2022

Summary Previously, we and others have shown that SARS-CoV-2 spike-specific IgG antibodies play a major role in disease severity in COVID-19 by triggering macrophage hyperactivation, disrupting endothelial barrier integrity, and inducing t…

Pirtobrutinib results in reversible platelet dysfunction compared to ibrutinib and acalabrutinib Open

Alexander P. Bye, Neline Kriek, Tanya Sage, Suzannah J. Rawlings, Catherine Prodger , et al. · 2022

Not available.

Cucurbitacins Elicit Anti-Platelet Activity via Perturbation of the Cytoskeleton and Integrin Function Open

Neline Kriek, Sophie H. Nock, Tanya Sage, Badrija Khalifa, Alexander P. Bye , et al. · 2022

Cucurbitacins are dietary compounds that have been shown to elicit a range of anti-tumour, anti-inflammatory and anti-atherosclerotic activities. Originally identified as signal transducer and activator of transcription, STAT, inhibitors, …

1,8-Cineole Affects Agonists-Induced Platelet Activation, Thrombus Formation and Haemostasis Open

Kahdr Alatawi, Divyashree Ravishankar, Pabitra Hriday Patra, Alexander P. Bye, Alexander R. Stainer , et al. · 2021

1,8-cineole, a monoterpenoid is a major component of eucalyptus oil and has been proven to possess numerous beneficial effects in humans. Notably, 1,8-cineole is the primary active ingredient of a clinically approved drug, Soledum® which i…

Multiparameter phenotyping of platelet reactivity for stratification of human cohorts Open

Joanne L. Dunster, Alexander P. Bye, Neline Kriek, Tanya Sage, Joanne Mitchell , et al. · 2021

Accurate and comprehensive assessment of platelet function across cohorts of donors may be key to understanding the risk of thrombotic events associated with cardiovascular disease, and, hence, to help personalize the application of antipl…

Aberrant glycosylation of anti-SARS-CoV-2 spike IgG is a prothrombotic stimulus for platelets Open

Alexander P. Bye, Willianne Hoepel, Joanne Mitchell, Sophie Jégouic, Silvia Loureiro , et al. · 2021

A subset of patients with coronavirus disease 2019 (COVID-19) become critically ill, suffering from severe respiratory problems and also increased rates of thrombosis. The causes of thrombosis in severely ill patients with COVID-19 are sti…

Maternal and offspring high-fat diet leads to platelet hyperactivation in male mice offspring Open

Renato Simões Gaspar, Amanda J. Unsworth, Alaa Al‐Dibouni, Alexander P. Bye, Tanya Sage , et al. · 2021

Maternal over-nutrition increases the risk of diabetes and cardiovascular events in offspring. While prominent effects on cardiovascular health are observed, the impact on platelet physiology has not been studied. Here, we examined whether…

Structural, functional, and mechanistic insights uncover the fundamental role of orphan connexin-62 in platelets Open

Khaled A. Sahli, Gagan D. Flora, Parvathy Sasikumar, Ali H. A. Maghrabi, Lisa‐Marie Holbrook , et al. · 2020

Connexins oligomerise to form hexameric hemichannels in the plasma membrane that can further dock together on adjacent cells to form gap junctions and facilitate intercellular trafficking of molecules. In this study, we report the expressi…

Maternal High-fat Diet During Pregnancy Programs Platelet Hyperactivation in Male Mouse Offspring Open

Renato Simões Gaspar, Amanda J. Unsworth, Alexander P. Bye, Tanya Sage, Michelle Stewart , et al. · 2020

Background: Maternal over-nutrition increases the risk of diabetes and cardiovascular events in offspring. While prominent effects on cardiovascular health are observed, the impact of this on platelet physiology has not been studied. Here,…

Antiplatelet properties of Pim kinase inhibition are mediated through disruption of thromboxane A2 receptor signaling Open

Amanda J. Unsworth, Alexander P. Bye, Tanya Sage, Renato Simões Gaspar, Nathan Eaton , et al. · 2020

Pim kinases are upregulated in several forms of cancer, contributing to cell survival and tumour development, but their role in platelet function and thrombotic disease has not been explored. We report for the first time that Pim-1 is expr…

Ca <sup>2+</sup> waves coordinate purinergic receptor–evoked integrin activation and polarization Open

Alexander P. Bye, Jonathan M. Gibbins, Martyn P. Mahaut‐Smith · 2020

Two distinct P2Y receptors are required for full activation of platelet integrin and fibrinogen binding.

Novel anti-platelet properties of dietary cucurbitacins Open

Alexander P. Bye, Neline Kriek, Tanya Sage, Joanne Mitchell, Dylan Donaghy , et al. · 2019

Cucurbitacins are naturally occurring tetracyclic terpenes, present in foods such as cucumber and pumpkin, which elicit a range of anti-tumour, anti-inflammatory and anti-atherosclerotic effects. These dietary compounds modulate cellular f…

Interspecies differences in protein expression do not impact the spatiotemporal regulation of glycoprotein VI mediated activation Open

Joanne L. Dunster, Amanda J. Unsworth, Alexander P. Bye, Elizabeth J. Haining, Marcin A. Sowa , et al. · 2019

The Metabolites of the Dietary Flavonoid Quercetin Possess Potent Antithrombotic Activity, and Interact with Aspirin to Enhance Antiplatelet Effects Open

Alexander R. Stainer, Parvathy Sasikumar, Alexander P. Bye, Amanda J. Unsworth, Lisa‐Marie Holbrook , et al. · 2019

Quercetin, a dietary flavonoid, has been reported to possess antiplatelet activity. However, its extensive metabolism following ingestion has resulted in difficulty elucidating precise mechanisms of action. In this study, we aimed to chara…

Cobimetinib and trametinib inhibit platelet MEK but do not cause platelet dysfunction Open

Amanda J. Unsworth, Alexander P. Bye, Neline Kriek, Tanya Sage, Ashley Osborne , et al. · 2018

The MEK inhibitors cobimetinib and trametinib are used in combination with BRAF inhibitors to treat metastatic melanoma but increase rates of hemorrhage relative to BRAF inhibitors alone. Platelets express several members of the MAPK signa…

Move along, nothing to see here: Btk inhibitors stop platelets sticking to plaques Open

Alexander P. Bye, Jonathan M. Gibbins · 2018

Platelets have evolved an intricate array of overlapping mechanisms to respond effectively to vessel damage by forming a clot to minimize blood loss. Unfortunately, these same responses may also be triggered by atherosclerotic lesions in d…

The chaperone protein HSP47: a platelet collagen binding protein that contributes to thrombosis and hemostasis Open

Parvathy Sasikumar, K.S. AlOuda, W.J. Kaiser, Lisa‐Marie Holbrook, Neline Kriek , et al. · 2018

Severe platelet dysfunction in NHL patients receiving ibrutinib is absent in patients receiving acalabrutinib Open

Alexander P. Bye, Amanda J. Unsworth, Michael Desborough, Catherine Hildyard, Niamh Appleby , et al. · 2017

The Bruton tyrosine kinase (Btk) inhibitor ibrutinib induces platelet dysfunction and causes increased risk of bleeding. Off-target inhibition of Tec is believed to contribute to platelet dysfunction and other side effects of ibrutinib. Th…

Farnesoid X Receptor and Liver X Receptor Ligands Initiate Formation of Coated Platelets Open

Amanda J. Unsworth, Alexander P. Bye, Dionne Tannetta, Michael Desborough, Neline Kriek , et al. · 2017

Objectives— The liver X receptors (LXRs) and farnesoid X receptor (FXR) have been identified in human platelets. Ligands of these receptors have been shown to have nongenomic inhibitory effects on platelet activation by platelet agonists. …

RXR Ligands Negatively Regulate Thrombosis and Hemostasis Open

Amanda J. Unsworth, Gagan D. Flora, Parvathy Sasikumar, Alexander P. Bye, Tanya Sage , et al. · 2017

Objective— Platelets have been found to express intracellular nuclear receptors including the retinoid X receptors (RXRα and RXRβ). Treatment of platelets with ligands of RXR has been shown to inhibit platelet responses to ADP and thrombox…

Platelet-Derived Inhibitors of Platelet Activation Open

Amanda J. Unsworth, Alexander P. Bye, Jonathan M. Gibbins · 2017

PPARγ agonists negatively regulate αIIbβ3 integrin outside‐in signaling and platelet function through up‐regulation of protein kinase A activity Open

Amanda J. Unsworth, Neline Kriek, Alexander P. Bye, K. Naran, Tanya Sage , et al. · 2016

Farnesoid X Receptor and Its Ligands Inhibit the Function of Platelets Open

Leonardo A. Moraes, Amanda J. Unsworth, Sakthivel Vaiyapuri, Marfoua S. Ali, Parvathy Sasikumar , et al. · 2016

Objective— Although initially seemingly paradoxical because of the lack of nucleus, platelets possess many transcription factors that regulate their function through DNA-independent mechanisms. These include the farnesoid X receptor (FXR),…

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