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Human enteroid monolayers: A novel, functionally stable model for investigating oral drug disposition.
Drug Metab Dispos
January 2025
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington. Electronic address:
To further the development of an in vitro model that faithfully recapitulates drug disposition of orally administered drugs, we investigated the utility of human enteroid monolayers to simultaneously assess intestinal drug absorption and first-pass metabolism processes. We cultured human enteroid monolayers from 3 donors, derived via biopsies containing duodenal stem cells that were propagated and then differentiated atop permeable Transwell inserts, and confirmed transformation into a largely enterocyte population via RNA sequencing analysis and immunocytochemistry (ICC) assays. Proper cell morphology was assessed and confirmed via bright field microscopy and ICC imaging of tight junction proteins and other apically and basolaterally localized proteins.
View Article and Find Full Text PDFE. Coli cytotoxic necrotizing factor-1 promotes colorectal carcinogenesis by causing oxidative stress, DNA damage and intestinal permeability alteration.
J Exp Clin Cancer Res
January 2025
Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy.
Background: Bacterial toxins are emerging as promising hallmarks of colorectal cancer (CRC) pathogenesis. In particular, Cytotoxic Necrotizing Factor 1 (CNF1) from E. coli deserves special consideration due to the significantly higher prevalence of this toxin gene in CRC patients with respect to healthy subjects, and to the numerous tumor-promoting effects that have been ascribed to the toxin in vitro.
View Article and Find Full Text PDFEffect of Essential Oil on Model Lipid Membranes.
Biomolecules
December 2024
Drug Chemistry and Technology Department, Sapienza University of Rome, Piazzale Aldo Moro 2, 00185 Rome, Italy.
essential oil is a natural substance able to inhibit the growth of several pathogens. This antimicrobial effect is often attributed to its ability to penetrate cellular structures and disrupt them. Although these properties are recognized as playing a key role in the mechanism of action of this substance, many unresolved issues still exist, and fundamental studies focused on such aspects are scarce.
View Article and Find Full Text PDFDisrupting of IGF2BP3-stabilized CLDN11 mRNA by TNF-α increases intestinal permeability in obesity-related severe acute pancreatitis.
Mol Med
January 2025
Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P. R. China.
Background: Obesity is a significant risk factor for severe acute pancreatitis (SAP) and is typically associated with increased intestinal permeability. Understanding the role of specific molecules can help reduce the risk of developing SAP. Claudin 11 (CLDN11), a member of the Claudin family, regulates the permeability of various internal barriers.
View Article and Find Full Text PDFA Comparative Study of the In Vitro Intestinal Permeability of Pinnatoxins and Portimine.
Mar Drugs
January 2025
Toxicology of Contaminants Unit, Fougères Laboratory, ANSES (French Agency for Food, Environmental and Occupational Health & Safety), 35306 Fougères, France.
The pinnatoxins (PnTXs) and portimines, produced by , have been detected in several countries, raising concerns for human health. Although no human poisoning from these toxins has been reported so far, they have been shown to distribute throughout the rodent body after oral administration. Therefore, we investigated the impact of PnTX analogs (PnTX-A, -E, -F, -G, and -H) and portimine (8, 16, and 32 ng/mL) on intestinal barrier integrity and their oral bioavailability using human Caco-2 cell monolayers treated for 2, 6, and 24 h.
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