Xanthine Oxidase-Dependent Activation of NLPR3 Inflammasome in Epithelial Cells Sustains Inflammation in Inflammatory Bowel Disease
Bibliographic record
Abstract
IMPORTANCE AND OBJECTIVE: Xanthine oxidase (XO) plays a key role in purine metabolism, catalyzing the oxidation of hypoxanthine to xanthine, and xanthine to uric acid (UA) with the production of superoxide anions. The accumulation of UA has been shown to initiate the inflammatory process through NLRP3 inflammasome, and the production of reactive oxygen species (ROS) contributes to inflammation-related tissue damage in different organs. This study aimed to investigate the role of XO in the pathogenesis of Inflammatory Bowel Disease (IBD) and the anti-inflammatory potential of XO inhibition. DESIGN: XO expression and activity were assessed in the mucosa of moderately-to-severely active ulcerative colitis (UC) and Crohn's disease (CD) patients. The functional role of XO, the activation of NLRP3 inflammasome, and the expression of proinflammatory cytokines were investigated in ex vivo intestinal organ cultures in the presence or absence of XO inhibitors. RESULTS: In silico and in vitro analysis showed that XO mRNA and protein expression were upregulated in the UC and CD intestinal mucosa compared to controls. XO overexpression in the inflamed mucosa was associated with increased enzymatic activity, accumulation of UA and functionally linked to NLRP3-dependent IL1beta and IL18 expression. Accordingly, XO inhibitors, Allopurinol and Febuxostat, prevented NLRP3 activation, reduced Caspase1 activity and IL1beta and IL18 expression in ex vivo organ cultures of inflamed intestinal mucosa from both UC and CD patients. CONCLUSIONS AND RELEVANCE: Overexpression of XO in IBD might contribute to inflammation by promoting NLRP3 inflammasome activation and proinflammatory cytokine production.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".