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Overexpression of the cytochrome P450 monooxygenase CYP392A16 has been previously associated with abamectin resistance using transcriptional analysis in the two-spotted spider mite , an important pest species worldwide; however, this association has not been functionally validated in vivo despite the demonstrated ability of CYP392A16 to metabolize abamectin in vitro. We expressed CYP392A16 in vivo via a Gal4 transcription activator protein/Upstream Activating Sequence (GAL4/UAS) system in flies, driving expression with detoxification tissue-specific drivers. We demonstrated that CYP392A16 expression confers statistically significant abamectin resistance in toxicity bioassays in only when its homologous redox partner, cytochrome P450 reductase (TuCPR), is co-expressed in transgenic flies. Our study shows that the model can be further improved, to facilitate the functional analysis of insecticide resistance mechanisms acting alone or in combination.
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http://dx.doi.org/10.3390/insects11120829 | DOI Listing |
Mol Ther Methods Clin Dev
June 2025
Eisai Co., Ltd., Tsukuba Research Laboratories, 5-1-3, Tokodai, Tsukuba, Ibaraki 300-2635, Japan.
Liver-humanized chimeric mice (PXB-mice) are widely utilized for predicting human pharmacokinetics (PK) and as human disease models. However, residual metabolic activity of mouse hepatocytes in chimeric mice can interfere with accurate human PK estimation. Lipid nanoparticle (LNP)-formulated small interfering RNA (siRNA) treatment makes it possible to eliminate the shortcomings of chimeras and create new models.
View Article and Find Full Text PDFFront Vet Sci
August 2025
College of Food Science, Guangdong Provincial Key Laboratory of Food Quality and Safety, South China Agricultural University, Guangzhou, China.
Introduction: Tenvermectin (TVM) is a novel avermectin-class drug that has attracted attention for its superior antiparasitic potency, low toxicity, and broad-spectrum activity. However, uncertainty about its interaction with cytochrome P450 enzymes (CYPs) has raised concerns about potential therapeutic failure, increased risk of toxicity, dangerous drug combinations, and prolonged discontinuation periods.
Method: To address these critical safety concerns, we conducted a systematic comparative study using a highly selective and quantitatively accurate substrate conversion assay to assess and compare the effects of TVM and ivermectin (IVM) on the activities of key CYPs (CYP1A1/2, 2B1, 2C6, 2D2, and 3A1/2).
FEBS Lett
September 2025
Laboratory of Molecular Diagnostics and Biotechnology, Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, Minsk, Belarus.
Genetic variants of various cytochrome P450 (CYP) enzymes significantly impact pharmacokinetics. The highly polymorphic hepatic CYP2C9 metabolizes ~ 15% of clinically used drugs. This study aimed to characterize the ligand-binding properties of the understudied CYP2C9.
View Article and Find Full Text PDFEnviron Sci Technol
September 2025
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China.
Ambroxol (AMB), a common expectorant, enters aquatic environments via wastewater, yet its ecological risks remain unclear. Under UV exposure (15 mJ·cm, λ = 185-400 nm), AMB undergoes photolysis, among the photoproducts, 4-((2-amino-3-bromobenzyl)amino) cyclohexanol (P1) and 2-amino-3,5-dibromobenzaldehyde (DBA) are major species, comprising over 50% of the total photoproduct peak area at the photolytic plateau. Acute toxicity tests with AMB, P1, and DBA in four aquatic species at different trophic levels revealed: the highest sensitivity in (LC = 0.
View Article and Find Full Text PDFHum Reprod
September 2025
Institut National de la Santé et de la Recherche Médicale, Ecole des Hautes Etudes en Santé Publique, Institut de recherche en santé, environnement et travail, Université de Rennes-UMR_S1085, Rennes, France.
Study Question: What is the direct effect of mumps virus (MuV) replication within the human testis on the tissue innate immune responses and testicular cell functions?
Summary Answer: MuV induces an early pro-inflammatory response in the human testis ex vivo and infects both Leydig cells and Sertoli cells, which drastically alters testosterone and inhibin B production.
What Is Known Already: Despite widespread vaccination efforts, orchitis remains a significant complication of MuV infection, especially in young men, which potentially results in infertility in up to 87% of patients with bilateral orchitis. Our understanding of MuV pathogenesis in the human testis has been limited by the lack of relevant animal models, impairing the development of effective treatments.