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Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells.
Nat Aging
January 2025
Translational Science and Therapeutics Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Somatic stem cell pools comprise diverse, highly specialized subsets whose individual contribution is critical for the overall regenerative function. In the bone marrow, myeloid-biased hematopoietic stem cells (myHSCs) are indispensable for replenishment of myeloid cells and platelets during inflammatory response but, at the same time, become irreversibly damaged during inflammation and aging. Here we identify an extrinsic factor, semaphorin 4A (Sema4A), which non-cell-autonomously confers myHSC resilience to inflammatory stress.
View Article and Find Full Text PDFA cell-based model to study mechanisms of endothelial-dependent thrombin generation in response to inflammation and its modulation by hydroxychloroquine.
Res Pract Thromb Haemost
January 2025
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Background: Inflammation is a driver of thrombosis, but the phenomenon of thromboinflammation has been defined only recently, bringing together the multiple pathways involved. models can support the development of new therapeutics targeting the endothelium and also assess the existing immunomodulatory drugs, such as hydroxychloroquine, in modulating the inflammation-driven endothelial prothrombotic phenotype.
Objectives: To develop a model for thrombin generation (TG) on the surface of human endothelial cells (ECs) to assess pro/antithrombotic properties in response to inflammation.
Argonaute2 modulates megakaryocyte development and sex-specific control of platelet protein expression and reactivity.
Sci Rep
January 2025
Department of Medicine, Division of Hematology, Cardeza Foundation for Hematologic Research, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Platelets are enriched in miRNAs and harbor Ago2 as the principal RNA silencing Argonaute. However, roles in thrombopoiesis and platelet function remain poorly understood. We generated megakaryocyte/platelet-specific Ago2-deleted (Ago2 KO) mice and assessed proteomic and functional effects.
View Article and Find Full Text PDFPlatelet-white cell ratio is more strongly associated with mortality than other common risk ratios derived from complete blood counts.
Nat Commun
January 2025
Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Complete blood count indices and their ratios are associated with adverse clinical outcomes for many acute illnesses, but the mechanisms generating these associations are not fully understood. Recent identification of a consistent pattern of white blood cell and platelet count co-regulation during acute inflammatory recovery provides a potentially unifying explanation. Here we show that the platelet-to-white-cell ratio, which was selected based on this conserved recovery pattern, is more strongly associated with mortality than other blood count markers and ratios in four important illnesses involving acute inflammation: COVID-19, acute heart failure, myocardial infarction, and stroke.
View Article and Find Full Text PDFParsimonious versus extensive bleeding score: can we simplify risk stratification after percutaneous coronary intervention and reduce bleeding events by de-escalation of the antiplatelet strategy?
Open Heart
January 2025
Cardiology, Radboudumc, Nijmegen, The Netherlands
Background And Aims: Due to the multitude of risk factors outlined in the guidelines, personalised dual antiplatelet therapy (DAPT) guidance after percutaneous coronary intervention (PCI) is complex. A simplified method was created to facilitate the use of risk stratification. We aimed to compare the predictive and prognostic value of the 'Zuidoost Nederland Hart Registratie' (ZON-HR) classification for bleeding risk with the PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent DAPT (PRECISE-DAPT) score and to determine the effect of ticagrelor monotherapy versus DAPT in patients with or without high bleeding risk (HBR).
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