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Your search keyword '"James S. O’ Donnell"' showing total 3 results
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3 results on '"James S. O’ Donnell"'

1. Dimethyl fumarate and 4-octyl itaconate are anticoagulants that suppress Tissue Factor in macrophages via inhibition of Type I Interferon

Author

Tristram A. J. Ryan, Alexander Hooftman, Aisling M. Rehill, Matt D. Johansen, Eóin C. O’ Brien, Juliana E. Toller-Kawahisa, Mieszko M. Wilk, Emily A. Day, Hauke J. Weiss, Pourya Sarvari, Emilio G. Vozza, Fabian Schramm, Christian G. Peace, Alessia Zotta, Stefan Miemczyk, Christina Nalkurthi, Nicole G. Hansbro, Gavin McManus, Laura O’Doherty, Siobhan Gargan, Aideen Long, Jean Dunne, Clíona Ní Cheallaigh, Niall Conlon, Michael Carty, Padraic G. Fallon, Kingston H. G. Mills, Emma M. Creagh, James S. O’ Donnell, Paul J. Hertzog, Philip M. Hansbro, Rachel M. McLoughlin, Małgorzata Wygrecka, Roger J. S. Preston, Zbigniew Zasłona, and Luke A. J. O’Neill

Subjects
Science
Abstract

Abstract Excessive inflammation-associated coagulation is a feature of infectious diseases, occurring in such conditions as bacterial sepsis and COVID-19. It can lead to disseminated intravascular coagulation, one of the leading causes of mortality worldwide. Recently, type I interferon (IFN) signaling has been shown to be required for tissue factor (TF; gene name F3) release from macrophages, a critical initiator of coagulation, providing an important mechanistic link between innate immunity and coagulation. The mechanism of release involves type I IFN-induced caspase-11 which promotes macrophage pyroptosis. Here we find that F3 is a type I IFN-stimulated gene. Furthermore, F3 induction by lipopolysaccharide (LPS) is inhibited by the anti-inflammatory agents dimethyl fumarate (DMF) and 4-octyl itaconate (4-OI). Mechanistically, inhibition of F3 by DMF and 4-OI involves suppression of Ifnb1 expression. Additionally, they block type I IFN- and caspase-11-mediated macrophage pyroptosis, and subsequent TF release. Thereby, DMF and 4-OI inhibit TF-dependent thrombin generation. In vivo, DMF and 4-OI suppress TF-dependent thrombin generation, pulmonary thromboinflammation, and lethality induced by LPS, E. coli, and S. aureus, with 4-OI additionally attenuating inflammation-associated coagulation in a model of SARS-CoV-2 infection. Our results identify the clinically approved drug DMF and the pre-clinical tool compound 4-OI as anticoagulants that inhibit TF-mediated coagulopathy via inhibition of the macrophage type I IFN-TF axis.

Published
2023
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2. Publisher Correction: Dimethyl fumarate and 4-octyl itaconate are anticoagulants that suppress Tissue Factor in macrophages via inhibition of Type I Interferon

Author

Tristram A. J. Ryan, Alexander Hooftman, Aisling M. Rehill, Matt D. Johansen, Eóin C. O’ Brien, Juliana E. Toller-Kawahisa, Mieszko M. Wilk, Emily A. Day, Hauke J. Weiss, Pourya Sarvari, Emilio G. Vozza, Fabian Schramm, Christian G. Peace, Alessia Zotta, Stefan Miemczyk, Christina Nalkurthi, Nicole G. Hansbro, Gavin McManus, Laura O’Doherty, Siobhan Gargan, Aideen Long, Jean Dunne, Clíona Ní Cheallaigh, Niall Conlon, Michael Carty, Padraic G. Fallon, Kingston H. G. Mills, Emma M. Creagh, James S. O’ Donnell, Paul J. Hertzog, Philip M. Hansbro, Rachel M. McLoughlin, Małgorzata Wygrecka, Roger J. S. Preston, Zbigniew Zasłona, and Luke A. J. O’Neill

Subjects
Science
Published
2023
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3. A systematic review of physical activity in people with haemophilia and its relationship with bleeding phenotype and treatment regimen

Author

Philip O'Gorman, Michelle Lavin, James S O' Donnell, Brian O'Mahony, Megan Kennedy, John Gormley, Niamh M O'Connell, Peter Turecek, and Ann Monaghan

Subjects
medicine.medical_specialty, MEDLINE, Physical activity, haemophilia, physical activity, Hemorrhage, Review Article, CINAHL, 030204 cardiovascular system & hematology, Hemophilia A, Haemophilia, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Intensive care medicine, Review Articles, Genetics (clinical), exercise, treatment, business.industry, Quality assessment, Treatment regimen, Hematology, General Medicine, bleeding, medicine.disease, Checklist, Critical appraisal, Cross-Sectional Studies, Phenotype, prophylaxis, business, 030215 immunology
Abstract

Introduction Although the measurement of physical activity (PA) amongst people with haemophilia (PWH) has become increasingly widespread in recent years, the relationship between PA and bleeding phenotype remains poorly understood. In addition, the influence of various treatment regimens on this relationship has not been defined. Aim This review aimed to systematically assess the data that are available regarding PA levels amongst PWH, as well as the relationship between PA and bleeding. Methods A systematic search of the online databases EMBASE, Cochrane, MEDLINE Ovid, CINAHL and Web of Science was conducted by two independent reviewers. Quality assessment was undertaken using the AXIS Critical Appraisal Tool for Cross‐sectional Studies and the STROBE checklist. Results Of 1902 sources identified overall, 36 articles were included. Low‐to‐moderate transparency of reporting and various sources of bias were identified. PA levels varied amongst heterogeneous samples of PWH. The relationship between PA and bleeds was inconclusive, although there was evidence that improvements in treatment over recent decades have appeared to enable PWH to become more physically active. Conclusion Based upon the limited available evidence, the relationship between PA and bleeding phenotype in PWH remains unclear. However, with the development of improved prophylaxis treatment regimens in recent years, there is evidence that PA levels have increased, especially amongst people with severe haemophilia. The use of validated outcome measures of PA and more robust reporting of bleeds and treatment regimen are warranted in future research, especially in a rapidly evolving era of new treatments for PWH.

Published
2021
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