Understanding skin metabolism is important when considering drug discovery and safety assessment. This review compares xenobiotic skin metabolism in ex vivo skin to reconstructed human skin and reconstructed human epidermis models, concentrating on phase I and phase II enzymes. Reports on phase I enzymes are more abundant than for phase II enzymes with mRNA and protein expression far more reported than enzyme activity. Almost all of the xenobiotic metabolizing enzymes detected in human skin are also present in liver. However, in general the relative levels are lower in skin than in liver and fewer enzymes are reported.
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http://dx.doi.org/10.1016/j.drudis.2019.06.002 | DOI Listing |
BMJ Open
December 2024
INSERM UMR1231 Génétique des Anomalies du Développement (GAD), Université de Bourgogne, Dijon, France.
Introduction: The megalencephaly capillary malformation polymicrogyria (MCAP syndrome) results from mosaic gain-of-function variants. The main clinical features are macrocephaly, somatic overgrowth, neurodevelopmental delay and brain anomalies. Alpelisib (Vijoice) is a recently FDA-approved PI3Kα-specific inhibitor for patients with PIK3CA-related overgrowth spectrum (PROS).
View Article and Find Full Text PDFJ Transl Med
January 2025
School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, Guizhou, 550000, China.
Background: Human kinesin family member 11 (KIF11) plays a vital role in regulating the cell cycle and is implicated in the tumorigenesis and progression of various cancers, but its role in endometrial cancer (EC) is still unclear. Our current research explored the prognostic value, biological function and targeting strategy of KIF11 in EC through approaches including bioinformatics, machine learning and experimental studies.
Methods: The GSE17025 dataset from the GEO database was analyzed via the limma package to identify differentially expressed genes (DEGs) in EC.
BMC Vet Res
January 2025
Theriogenology Department, Faculty of Veterinary Medicine, New-Valley University, New Valley, 725211, Egypt.
Background: Saidi sheep are one of the most important farm animals in Upper Egypt, particularly in the Assiut governorate. Since they can provide meat, milk, fiber, and skins from low-quality roughages, sheep are among the most economically valuable animals bred for food in Egypt. Regarding breeding, relatively little is known about the Saidi breed.
View Article and Find Full Text PDFPlant Cell Rep
January 2025
Faculty of Science and Engineering, Southern Cross University, Lismore, NSW, 2480, Australia.
Cannabis trichome development progresses in distinct phases that underpin the dynamic biosynthesis of cannabinoids and terpenes. This study investigates the molecular mechanisms underlying cannabinoid and terpenoid biosynthesis in glandular trichomes of Cannabis sativa (CsGTs) throughout their development. Female Cannabis sativa c.
View Article and Find Full Text PDFAAPS J
January 2025
Clinical Pharmacology Modeling and Simulation, Amgen, One Amgen Center Drive, Thousand Oaks, CA, 91320-0777, USA.
Sotorasib is a novel KRAS inhibitor that has shown robust efficacy, safety, and tolerability in patients with KRAS mutation. The objectives of the population pharmacokinetic (PK) analysis were to characterize sotorasib population PK in healthy subjects and patients with advanced solid tumors with KRAS mutation from 6 clinical studies, evaluate the effects of intrinsic and extrinsic factors on PK parameters, and perform simulations to further assess the impact of identified covariates on sotorasib exposures. A two-compartment disposition model with three transit compartments for absorption and time-dependent clearance and bioavailability well described sotorasib PK.
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