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Haloacetonitriles Induce Structure-Related Cellular Toxicity Through Distinct Proteome Thiol Reaction Mechanisms.
ACS Environ Au
January 2025
Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.
Haloacetonitriles (HANs) are a class of toxic drinking water disinfection byproducts (DBPs). However, the toxicity mechanisms of HANs remain unclear. We herein investigated the structure-related in vitro toxicity of 6 representative HANs by utilizing complementary bioanalytical approaches.
View Article and Find Full Text PDFComparative analysis of allowable total error specifications for coagulation factor assays utilizing China National External quality assessment scheme data and biological variation data.
Clin Chim Acta
January 2025
National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology, PR China. Electronic address:
Background: It is necessary and challenging to establish reasonable and feasible total error specifications for coagulation factor assays for quality control and assessment. The aim of this study is to establish new total error specifications for coagulation factor assays by combining External Quality Assessment data with reliable biological variation data.
Methods: Data from China National External Quality Assessment Scheme (28,408 results from 1,381 laboratories) were analyzed, stratifying External Quality Assessment data by reference intervals to establish concentration-dependent total error specifications.
A Highly Sensitive Triple Quad LC-MS/MS Method Development and Validation for the Determination of Bexicaserin (LP352) in Human Plasma and Urine Matrices.
Biomed Chromatogr
February 2025
Department of Clinical Pharmacology and Pharmacometrics, Longboard Pharmaceuticals, Inc. is a part of Lundbeck as a wholly owned subsidiary of Lundbeck LLC, La Jolla, California, USA.
Bexicaserin is a highly selective agonist at the 5-HT receptor in clinical development for the treatment of seizures associated with developmental and epileptic encephalopathies (DEEs). We report an LC-MS/MS method for the quantitative estimation of bexicaserin in human plasma and urine. The sample preparation involves the extraction of bexicaserin and internal standard (CD-bexicaserin; IS) from 150 μL plasma and 50 μL urine using a solid phase extraction method.
View Article and Find Full Text PDFIron metabolism in a mouse model of hepatocellular carcinoma.
Sci Rep
January 2025
Institute of Comparative Molecular Endocrinology, Ulm University, 89081, Ulm, Germany.
Hepatocellular carcinoma (HCC) remains the most prevalent type of primary liver cancer worldwide. p53 is one of the most frequently mutated tumor-suppressor genes in HCC and its deficiency in hepatocytes triggers tumor formation in mice. To investigate iron metabolism during liver carcinogenesis, we employed a model of chronic carbon tetrachloride injections in liver-specific p53-deficient mice to induce liver fibrosis, cirrhosis and subsequent carcinogenesis.
View Article and Find Full Text PDFComparison of RT-qPCR With Branched DNA to Quantify a Lipid Nanoparticle-Encapsulated mRNA Therapeutic in Serum and Liver Tissue Samples From Nonclinical PK Studies.
AAPS J
January 2025
Moderna, Inc., Cambridge, Massachusetts, USA.
While the branched DNA (bDNA) assay is an established bioanalytical method for measurement of lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) pharmacokinetic parameters, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) has been considered as an alternative platform. RT-qPCR and bDNA platforms were compared for sensitivity, specificity, correlation, and overall assay performance using serum and tissue samples from 2 nonclinical mouse studies of a therapeutic mRNA candidate, LNP-PAH-mRNA, which encodes for human phenylalanine hydroxylase enzyme. Pharmacokinetic parameter noncompartmental analysis was completed using Phoenix WinNonlin.
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