Intestinal paraoxonase regulation and its status in Crohn’s disease
Bibliographic record
Abstract
The current paradigm on the pathogenesis of Crohn’s disease (CD) focuses on the excessive secretion of numerous inflammatory mediators by the dense inflammatory cell infiltrates in response to luminal bacterial products such as lipopolysaccharide (LPS). Various studies have provided evidence of an important role of oxidant injury in intestinal epithelial cells. The objectives of the present investigation are to test the hypotheses that (i) the concentration and composition of high‐density lipoprotein (HDL) is altered in CD; (ii) as a consequence, paraoxonase (PON) contained in HDL may be reduced; and (iii) the gene expression of PON1, PON2 and PON3 in the intestine are modulated by lipid peroxides, inflammatory cytokines and LPS. Our results document that, concomitant with the occurrence of oxidative stress, marked abnormalities are observed in the chemical composition and concentration of HDL 2 and HDL 3 of patients with CD. Furthermore, the protein content of PON1 is decreased in HDL fractions. Finally, the transcripts of PON1, PON2 and PON3 in cultured Caco‐2 cells are distinctly modulated by iron‐ascorbate oxygen‐radical generating system, LPS, interferon‐γ and TNFα. For example, interferon‐γ decreased PON1, raised PON2 and remained without effect on PON3. Our data support the notion that paraoxonases are key factors involved in intestinal mucosal and peripheral defense against oxidative stress in CD. This study is supported by Crohn’s and Colitis Foundation of Canada.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".