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TAK-994 Mechanistic Investigation into Drug-Induced Liver Injury.
Toxicol Sci
January 2025
Takeda Development Center Americas, Inc, Cambridge, MA, USA.
The frequency of drug-induced liver injury (DILI) in clinical trials remains a challenge for drug developers despite advances in human hepatotoxicity models and improvements in reducing liver-related attrition in preclinical species. TAK-994, an oral orexin receptor 2 agonist, was withdrawn from phase II clinical trials due to the appearance of severe DILI. Here, we investigate the likely mechanism of TAK-994 DILI in hepatic cell culture systems examined cytotoxicity, mitochondrial toxicity, impact on drug transporter proteins, and covalent binding.
View Article and Find Full Text PDFInteractions between cellulose nanocrystals and conventional/gemini surfactants.
Carbohydr Polym
March 2025
Department of Chemical Engineering, Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada. Electronic address:
Research on the interaction between surfactants and cellulose nanocrystals (CNC) has mainly focused on the interaction between CNC and conventional surfactants, and there are no reported studies on the interaction between CNC and gemini surfactants. The interactions between CNC and conventional surfactant (tetradecyltrimethylammonium bromide, termed as TTAB), asymmetric gemini surfactant ([CH(CH)N(CH)N(CH)CH]Br (14-6-6)) or symmetric gemini surfactant ([CH(CH)N(CH)N(CH)CH]Br (14-6-14)) were examined. With increasing surfactant concentration, interaction of TTAB/CNC was described by three regions, i.
View Article and Find Full Text PDFRole of voltage-gated Ca channels and Ano1 Ca-activated Cl channels in M2 muscarinic receptor-dependent contractions of murine airway smooth muscle.
Am J Physiol Lung Cell Mol Physiol
January 2025
Smooth Muscle Research Centre, Dundalk Institute of Technology, Dublin Road, Dundalk, Co. Louth, Ireland.
Cholinergic tone is elevated in obstructive lung conditions such as COPD and asthma, but the cellular mechanisms underlying cholinergic contractions of airway smooth muscle (ASM) are still unclear. Some studies report an important role for L-type Ca channels (LTCC) and Ano1 Ca-activated Cl™ channels (CACC) in these responses, but others dispute their importance. Cholinergic contractions of ASM involve activation of M3Rs, however stimulation of M2Rs exerts a profound hypersensitisation of these responses.
View Article and Find Full Text PDFMass Spectrometric Based Metabolomics of the Saudi Cultivar of Fenugreek ( L.): A Combined GC-MS, Antimicrobial and Computational Approach.
Pharmaceuticals (Basel)
December 2024
Department of Biology, College of Science, Qassim University, Buraydah 51452, Saudi Arabia.
In Saudi Arabia, numerous plant species with promising medicinal properties are cultivated, widely traded, and commonly utilized in traditional medicine, including fenugreek (). This study aimed to comprehensively assess the phytochemical composition and antimicrobial potential of the Saudi cultivar of fenugreek using an integrative approach combining in vitro and in silico methodologies. A comprehensive investigation was conducted on the ethanol extract of fenugreek seeds, assessing its antibacterial, antifungal, properties.
View Article and Find Full Text PDFSensitivity Analysis of to Quinone-Outside Inhibitor and 14α-Demethylase Inhibitor Fungicides in Latvia.
Pathogens
December 2024
Latvian Biomedical Research and Study Centre, Ratsupites Street 1, k-1, LV-1067 Riga, Latvia.
Tan spot caused by is a severe threat to wheat production in all major wheat-growing regions. Sustainable tan spot control can be achieved by an integrated approach, including responsible management of fungicide sprays. The data about the sensitivity of to various fungicides in the Baltic Sea region are rare.
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