Quantitative analysis of small bowel epithelial gaps in IL-10 knockout and control 129 Sv/Ev mice
Notice bibliographique
Résumé
The interleukin-10 knockout (IL-10 -/-) mouse is a homozygous IL-10 deficient strain generated on a 129 Sv/Ev genetic background. It is a well-established rodent IBD model that universally develop colitis after weaning at 8 weeks of age. Impaired barrier function has been implicated in the pathogenesis of inflammatory bowel disease. Confocal Endo-Microscopy (CEM) has demonstrated the existence of epithelial cell gaps resulting from cell shedding in the rodent model. We hypothesize that increased epithelial cell shedding, as measured by an increase in epithelial gaps, contributes to the abnormal intestinal permeability in the IL-10 -/- model. In this study, we measured the epithelial gaps normalized for epithelial cells in IL-10 -/- and compared to the background 129 Sv/Ev strain. We performed CEM on 8-week old IL-10 -/- mice (n= 15) and control 129 Sv/Ev mice (n= 10) using previously described methods. We confirmed the presence of minimal intestinal inflammation prior to the onset of colitis symptoms in the IL-10 -/- mice. We consistently imaged both the jejunum, at 10 cm distal to the ligament of Treitz, and ileum, at 10 cm proximal to the cecum, in each animal. In brief, segments of jejunum and ileum were exteriorized. The lumen was cut open the tissue was stained topically with 0.5 mmol/L with acriflavine hydrochloride, and then washed with saline. Cross-sectional images along the z-axis of the tissues (z-stacks) were obtained with the Five 1 Fluorescence in vivo confocal endomicroscopy system (Optiscan Ltd, Victoria, Australia). The cross-sectional images were aligned and the features extrapolated to create a surface relief of the small intestinal segment. Interpolation between the twodimensional (2-D) frames in each stack was performed using a feature-guided, shapebased computer method to adequately manage translation, rotation, and scaling. The three-dimensional (3-D) relief was analyzed to isolate and quantify the shape, extent, and position of the lesions created where cells had been shed (epithelial gap). Cellular features were analyzed from the 3-D reconstruction of cross-sectional images obtained from the rodent small intestine. Adequately imaged villi, defined as en face villi with 75% surface visualized in the CEM images, were used for the analysis. Ten villi from each animal were manually counted for epithelial cells and the number of epithelial gaps. The gap density function is defined as the number of epithelial gaps (gaps) divided by the number of intestinal epithelial cells (cells) counted in the 10 adequately imaged villi (gap density = gaps/cells). The mean number of epithelial cells per villi counted was 290 for control 129 Sv/Ev mice and 218 for the IL-10 -/- mice. The mean gap density (mean ± standard error) was 6.46±1.36 gaps/1000 cells for 129 Sv/Ev mice that were significantly lower than for the IL-10 -/- mice (17.40 ± 2.09 gaps/1000 cells; p<0.01). The epithelial gap density is significantly higher for IL-10 -/- mice compared to control 129 Sv/Ev mice. The significance of increased epithelial gaps in the pathogenesis of inflammatory bowel disease warrants further investigation.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».