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Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.
J Med Chem
January 2025
Ma̅tai Ha̅ora - Centre for Redox Biology and Medicine, Department of Biomedical Science and Pathology, University of Otago, Christchurch, Christchurch 8140, New Zealand.
In humans, the 2-oxoglutarate-dependent dioxygenases (2-OGDDs) catalyze hydroxylation reactions involved in cell metabolism, the biosynthesis of small molecules, DNA and RNA demethylation, the hypoxic response and the formation of collagen. The reaction is catalyzed by a highly oxidizing ferryl-oxo species produced when the active site non-heme iron engages molecular oxygen. Enzyme activity is specifically stimulated by l-ascorbic acid (ascorbate, vitamin C), an effect not well mimicked by other reducing agents.
View Article and Find Full Text PDFOral Cyclophosphamide for Patients With Metastatic Castration-Resistant Prostate Cancer in a Scenario of Limited Health Care Resources.
JCO Glob Oncol
January 2025
Genitourinary Medical Oncology Service, Instituto do Câncer do Estado de São Paulo (ICESP), University of São Paulo, São Paulo, Brazil.
Purpose: Prior noncontemporary studies showed that oral cyclophosphamide is an active treatment of metastatic castration-resistant prostate cancer (mCRPC). However, cyclophosphamide is currently underutilized in routine clinical practice given the lack of survival benefit and the emergence of more effective treatments.
Methods: We retrospectively reviewed our institutional database to identify patients with mCRPC treated with cyclophosphamide.
Longer recreational screen time contributes to the risk of age-related macular degeneration: a UK Biobank cohort study and two-sample Mendelian randomisation.
J Glob Health
January 2025
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background: Recreational screen time (RST) has been found to be associated with cognitive decline and neurodegenerative diseases. However, the association between RST and age-related macular degeneration (AMD), an ocular neurodegenerative disease, is still unclear. We aimed to elucidate the association between RST and AMD.
View Article and Find Full Text PDFEffects of Chemical Pretreatments of Wood Cellulose Nanofibrils on Protein Adsorption and Biological Outcomes.
ACS Appl Mater Interfaces
January 2025
Center of Translational Oral Research (TOR), Department of Clinical Dentistry, University of Bergen, Bergen 5009, Norway.
Wood-based nanocellulose is emerging as a promising nanomaterial in the field of tissue engineering due to its unique properties and versatile applications. Previously, we used TEMPO-mediated oxidation (TO) and carboxymethylation (CM) as chemical pretreatments prior to mechanical fibrillation of wood-based cellulose nanofibrils (CNFs) to produce scaffolds with different surface chemistries. The aim of the current study was to evaluate the effects of these chemical pretreatments on serum protein adsorption on 2D and 3D configurations of TO-CNF and CM-CNF and then to investigate their effects on cell adhesion, spreading, inflammatory mediator production , and the development of foreign body reaction (FBR) .
View Article and Find Full Text PDFNexinhib20 inhibits JFC1-mediated mobilization of a subset of CD11b/CD18+ vesicles decreasing integrin avidity, but does not inhibit Rac1.
J Leukoc Biol
January 2025
Department of Molecular and Cellular Biology, The Scripps Research Institute, La Jolla, CA.
Regulated sequential exocytosis of neutrophil granules is essential in orchestrating the innate immune response, while uncontrolled secretion causes inflammation. We developed and characterized Nexinhib20, a small-molecule inhibitor that targets azurophilic granule exocytosis in neutrophils by blocking the interaction between the small GTPase Rab27a and its effector JFC1. Its therapeutic potential has been demonstrated in several pre-clinical models of inflammatory disease.
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