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Biocompatible covalent reactive groups (CRGs) play pivotal roles in several areas of chemical biology and the life sciences, including targeted covalent inhibitor design and preparation of advanced biologic drugs, such as antibody-drug conjugates. In this study, we present the discovery that the small, chlorinated polyketide natural product cyclohelminthiol II (CHM-II) acts as a new type of cysteine/thiol-targeting CRG incorporating both reversible and irreversible reactivity. We devise the first syntheses of four simple cyclohelminthols, (±)-cyclohelminthol I-IV, with selective chlorinations (at C and C) and a Ni-catalyzed reductive cross coupling between an enone, a vinyl bromide and triethylsilyl chloride as the key steps.
View Article and Find Full Text PDFPredictors of Antidepressant Use Among People With Multiple Sclerosis.
J Neuropsychiatry Clin Neurosci
January 2025
Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, and Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto (Freedman, Feinstein); Division of Neurology, Department of Medicine, St. Michael's Hospital, and Division of Neurology, Temerty Faculty of Medicine, University of Toronto, Toronto (Oh).
Objective: Anxiety and depression are common among individuals with multiple sclerosis (MS) but are often undertreated. Little is known about factors that influence the odds of antidepressant treatment for MS. The authors aimed to identify predictors of antidepressant use among people with MS.
View Article and Find Full Text PDFChemical exchange saturation transfer MRI for neurodegenerative diseases: an update on clinical and preclinical studies.
Neural Regen Res
January 2025
Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Chemical exchange saturation transfer magnetic resonance imaging is an advanced imaging technique that enables the detection of compounds at low concentrations with high sensitivity and spatial resolution and has been extensively studied for diagnosing malignancy and stroke. In recent years, the emerging exploration of chemical exchange saturation transfer magnetic resonance imaging for detecting pathological changes in neurodegenerative diseases has opened up new possibilities for early detection and repetitive scans without ionizing radiation. This review serves as an overview of chemical exchange saturation transfer magnetic resonance imaging with detailed information on contrast mechanisms and processing methods and summarizes recent developments in both clinical and preclinical studies of chemical exchange saturation transfer magnetic resonance imaging for Alzheimer's disease, Parkinson's disease, multiple sclerosis, and Huntington's disease.
View Article and Find Full Text PDFAssessment of relationships between epigenetic age acceleration and multiple sclerosis: a bidirectional mendelian randomization study.
Epigenetics Chromatin
January 2025
Department of Neurology, Tongji Shanxi Hospital, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan, China.
Background: The DNA methylation-based epigenetic clocks are increasingly recognized for their precision in predicting aging and its health implications. Although prior research has identified connections between accelerated epigenetic aging and multiple sclerosis, the chronological and causative aspects of these relationships are yet to be elucidated. Our research seeks to clarify these potential causal links through a bidirectional Mendelian randomization study.
View Article and Find Full Text PDFPediatric obesity and the risk of multiple sclerosis: a nationwide prospective cohort study.
Int J Obes (Lond)
January 2025
Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, S-141 57, Huddinge, Sweden.
Background: Emerging evidence implies a link between high pediatric body mass index (BMI) and an increased risk of multiple sclerosis (MS). However, previous research suggests this association is only present for adolescent obesity and not childhood obesity. The present study aimed to assess the association between pediatric obesity and risk of developing MS, and to investigate if degree of obesity and age at obesity treatment initiation affects the risk.
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