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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.

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Background And Objectives: Mitochondrial disorders are multiorgan disorders resulting in significant morbidity and mortality. We aimed to characterize death-associated factors in an international cohort of deceased individuals with mitochondrial disorders.

Methods: This cross-sectional multicenter observational study used data provided by 26 mitochondrial disease centers from 8 countries from January 2022 to March 2023.

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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.

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The growing sophistication of tumor molecular profiling has helped to slowly transition oncologic care toward a more personalized approach in different tumor types, including in bladder cancer. The National Comprehensive Cancer Network recommends that all patients with stage IVA and stage IVB urothelial carcinoma have molecular analysis that integrates at least testing to help facilitate the selection of future therapeutic options. Sequencing of tumor-derived tissue is the mainstay to obtain this genomic testing, but as in other cancers, there has been extensive research into the integration of liquid biopsies in longitudinal management.

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Seed color is a critical quality trait in numerous plant species. In oilseed crops, including rapeseed and mustard, yellow seeds are distinguished by their significantly higher oil content and faster germination rates compared to black or brown counterparts. Despite the agronomic significance of the yellow seeds being a prime breeding target, the mechanisms underlying elevated oil content remain obscure.

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