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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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Chimeric antigen receptor (CAR) T-cell products axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel) are approved for relapsed/refractory large B-cell lymphoma (R/R LBCL). Emerging evidence indicates that delayed CAR T-cell infusion, including prolonged time from leukapheresis to infusion, known as vein-to-vein time (V2Vt), may adversely impact clinical outcomes. We conducted a systematic literature review (SLR) and meta-analysis to identify differences in V2Vt in patients with R/R LBCL treated with axi-cel, tisa-cel, or liso-cel.

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In plasma, the zymogens factor XII (FXII) and prekallikrein reciprocally convert each other to the proteases FXIIa and plasma kallikrein (PKa). PKa cleaves high-molecular-weight kininogen (HK) to release bradykinin, which contributes to regulation of blood vessel tone and permeability. Plasma FXII is normally in a "closed" conformation that limits activation by PKa.

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Background: Previous research suggested that parent-administered pediatric tuina could improve symptoms of attention-deficit/hyperactivity disorder (ADHD), such as sleep quality and appetite.

Objective: This study aimed to explore the experiences and perceptions of parents administering pediatric tuina to school-aged children with ADHD in Hong Kong.

Methods: This qualitative study was embedded in a pilot randomized controlled trial on parent-administered pediatric tuina for improving sleep and appetite in school-aged children diagnosed with ADHD.

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Background: Transitional-aged youth have a high burden of mental health difficulties in Canada, with Indigenous youth, in particular, experiencing additional circumstances that challenge their well-being. Mobile health (mHealth) approaches hold promise for supporting individuals in areas with less access to services such as Northern Ontario.

Objective: The primary objective of this study is to evaluate the effectiveness of the JoyPop app in increasing emotion regulation skills for Indigenous transitional-aged youth (aged 18-25 years) on a waitlist for mental health services when compared with usual practice (UP).

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