Inhibition of Wnt/β-catenin Signaling Pathway via XAV939 does not mitigate Dextran Sulfate Sodium-Induced Ulcerative Colitis Running Title: XAV939 does not mitigate Ulcerative Colitis
Bibliographic record
Abstract
Abstract The Wnt/β-catenin signaling pathway is known to be hyperactivated during the pathogenesis of ulcerative colitis (UC). This study aimed to explore the therapeutic efficacy of the Wnt/β-catenin signaling inhibitor, XAV939, in mitigating UC symptoms. Utilizing a dextran sulfate sodium (DSS)-induced UC mouse model, we aimed to evaluate the impact of XAV939 on intestinal morphology through hematoxylin and eosin (HE) staining and to measure the expression levels of critical proteins within the Wnt/β-catenin signaling cascade. Contrary to our expectations, XAV939 did not exert a significant influence on the morphological features and inflammatory status of the intestinal epithelium. Nonetheless, XAV939 was found to effectively suppress the Wnt/β-catenin signaling pathway and its downstream target SOX9. This suppression implies a reduction in the differentiation of intestinal stem cells (ISCs) into secretory cell progenitor cells. Additionally, XAV939 was ineffective in reversing the DSS-induced decline of Villin and PPAR-γ, suggesting that it does not facilitate the differentiation of intestinal absorptive cells. Our findings indicate that the Wnt/β-catenin signaling pathway may not be the predominant mechanism in the pathogenesis of DSS-induced UC.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".