Venous thromboembolism (VTE) is a prevalent public health issue worldwide. Before treatment, spatiotemporally accurate thrombus detection is essential. However, with the currently available imaging technologies, this is challenging. Herein, the development of a novel fibrin-specific nanoprobe (NP) based on the conjugation of poly(lactic-co-glycolic acid) with the pentapeptide Cys-Arg-Glu-Lys-Ala (CREKA) for selective and semiquantitative imaging in vivo is presented. By integrating Fe O and NIR fluorochrome (IR780), the NP can function as a highly sensitive sensor for the direct analysis of thrombi in vivo. The fibrin-specific NP distinguishes fibrin-rich thrombi from collagen-rich or erythrocyte-rich thrombi, which can be beneficial for future individually tailored therapeutic strategy. Furthermore, loading NPs with the ketotifen fumarate results in mast cell degranulation inhibition, and hence, NPs can prevent thrombosis without the risk of excessive bleeding. Thus, the use of fibrin-specific NPs may serve as a safe alternative approach for the detection and prevention of VTEs in susceptible populations in the future.
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http://dx.doi.org/10.1002/adma.202109955 | DOI Listing |
bioRxiv
November 2024
Department of Pediatrics, University of Michigan, Ann Arbor, MI.
Venous thrombosis is a well-known complication of sex hormone therapy, with onset typically within weeks to months after initiation. Worldwide, more than 100 million pre-menopausal women use combined oral contraceptives, with tens to hundreds of thousands developing thrombosis annually, resulting in significant morbidity and mortality. Although it is known that estrogens can alter expression of coagulation factors, the pathways and mechanisms that connect the two systems, as well as the proteins involved in progression to thrombosis, are poorly understood.
View Article and Find Full Text PDFJ Med Chem
November 2024
Bayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Chymase is a serine-protease produced by mast cells. In the past few decades, its role in fibrotic diseases triggered the search for orally available chymase inhibitors. Aiming at reducing adverse cardiac remodeling after myocardial infarction, our research efforts resulted in the discovery of fulacimstat (BAY 1142524).
View Article and Find Full Text PDFJ Clin Neurosci
August 2024
Department of Neurology, Haining People's Hospital, Jiaxing, China. Electronic address:
Background: Mechanical thrombectomy has emerged as the primary endovascular treatment for acute ischemic stroke. Numerous studies have investigated the relationship between thrombus composition and factors such as pharmacological thrombolysis, stroke etiology, mechanical thrombectomy, and radiological imaging. However, limited research has explored the association between thrombus composition and clinical outcomes.
View Article and Find Full Text PDFPLoS One
May 2024
Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America.
Background: Mechanical thrombectomy (MT) has become the gold standard care for treating acute ischemic stroke (AIS) due to large vessel occlusion. Emerging evidence suggests that understanding the composition of clots prior to intervention could be useful for the selection of neuroendovascular techniques, potentially improving the efficacy of treatments. However, current imaging modalities lack the ability to distinguish clot composition accurately and reliably.
View Article and Find Full Text PDFStroke
July 2024
Stroke Unit, University Hospital La Timone, AP-HM, Marseille, France (E.D., C.S., L.S.).
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