Molnupiravir is an antiviral agent recently used for treating coronavirus disease 2019 (COVID-19). Here, we demonstrate that N4-hydroxycytidine (NHC), a molnupiravir metabolite, treated with cytidine deaminase (CDA) induced Cu(II)-mediated oxidative DNA damage in isolated DNA. A colorimetric assay revealed hydroxylamine generation from CDA-treated NHC. The site specificity of DNA damage also suggested involvement of hydroxylamine in the damage. Furthermore, Cu(I) and H2O2 play an important role in the DNA damage. We propose oxidative DNA damage via CDA-mediated metabolism as a possible mutagenic mechanism of NHC, highlighting the need for careful risk assessment of molnupiravir use in therapies for viral diseases, including COVID-19.
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http://dx.doi.org/10.1093/infdis/jiac477 | DOI Listing |
Nat Biotechnol
January 2025
Institute for Intelligent Biotechnologies (iBIO), Helmholtz Center Munich, Neuherberg, Germany.
Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental and deep learning pipeline to comprehensively quantify the targeting of nanocarriers throughout the whole mouse body at single-cell resolution. SCP-Nano reveals the tissue distribution patterns of lipid nanoparticles (LNPs) after different injection routes at doses as low as 0.
View Article and Find Full Text PDFCommun Biol
January 2025
Laboratory of Intensive Care, Laboratory for Prevention and Translation of Geriatric Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou, China.
Cellular senescence (CS) is recognized as a critical driver of aging and age-related disorders. Recent studies have emphasized the roles of ion channels as key mediators of CS. Nonetheless, the roles and regulatory mechanisms of chloride intracellular channels (CLICs) during CS remain largely unexplored.
View Article and Find Full Text PDFNPJ Precis Oncol
January 2025
College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC.
Anaplastic thyroid carcinoma (ATC) is an aggressive cancer that requirements rapid diagnosis and multimodal treatment. Next-generation sequencing (NGS) aids in personalized therapies and improved trial enrollment. The role of liquid-based NGS in ATC remains unclear.
View Article and Find Full Text PDFNat Commun
January 2025
Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Middle-aged obesity, characterized by excessive fat accumulation and systemic energy imbalance, often precedes various health complications. Recent research has unveiled a surprising link between DNA damage response and energy metabolism. Here, we explore the role of Eepd1, a DNA repair enzyme, in regulating adipose tissue function and obesity onset.
View Article and Find Full Text PDFSci Total Environ
January 2025
School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III Da Varano, I-62032 Camerino, MC, Italy. Electronic address:
Nowadays, marine pollution is a global problem which finds in microplastics (MPs) and emerging pollutants, such as perfluoroalkyl substances (PFASs), two of the main culprits. Sea cucumbers are a group of marine benthic invertebrates that show ecological, economic and social relevance. As deposit/suspension feeders, sea cucumbers show high susceptibility to bioaccumulate marine pollutants, including PFASs and MPs.
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