A102 REGULATION OF ENDPLASMIC RETICULUM STRESS/P53-APOPTITIC PATHWAYS BY CHROMOFUNGIN IN THE CONTEXT OF EXPERIEMENTAL COLITIS
Bibliographic record
Abstract
Chromogranin-A produced by epithelial enterochromaffin cells is implicated in the development of ulcerative colitis (UC). In an animal model of UC, the lack of CHGA regulates the plasticity of macrophages and p/53 caspase activation in colitis. Over the last years, progresses have been done in understanding the implications of multiple chromogranin-A derived peptides in several pathologies. In UC and macrophages, the transcription factor X-linked binding protein (XBP1) is a key component of the endoplasmic reticulum (ER) stress response, which induces intestinal mucosal injury and epithelial apoptosis. Intestinal epithelial apoptosis is mediated by p53-apoptotic pathway through the activation of p53-upregulated modulator of apoptosis (PUMA), Bcl-2 associated-X protein (BAX), Bcl-2 associated death promoter (BAD) and Bcl-2 antagonist/killer-1 (BAK1) proteins. Previously, we showed that chromofungin (CHGA47-66; CHR) protects against acute colitis by regulating macrophage-cytokines production. However, the effects of CHR on ER stress/p53-dependent apoptosis in colitis are still unknown. We aimed to investigate whether CHR suppress inflammation-induced epithelial apoptosis through ER stress/p53-apoptosis in colitis UC-related colitis was induced in C57BL/6 mice (7 weeks) by administering DSS (5%, 5 days). Preventive CHR (2.5 mg/kg/day) or vehicle (Saline) treatments started 1-day before colitis induction and lasted for 5-days. Disease activity index, histologic scores, XBP1, and modulator of apoptosis, PUMA, BAD, BAX, BAK1were quantified using whole colonic sections and q-RT-PCR. Naive peritoneal macrophages were exposed to CHR (200 ng/ml, 2h) or PBS and then to LPS (100 ng/ml, 6h) to promote classically activated macrophages (M1) and the same markers were studied. In colitic conditions, CHR treatment ameliorated the onset and severity of colitis, which was associated with a significant reduction in ER stress/p53-dependent apoptosis as reflected by a significant decrease of Xbp1, Puma, Bad, Bax and Bak1. In vitro, compared to untreated group, LPS-stimulated macrophages treated with CHR demonstrated a significant decrease of Xbp1, Puma, Bad, Bax and Bak1 when compared to LPS PBS-treated macrophages. CHR decreases the severity of colitis and the inflammatory process via the suppression of mucosal and pro-inflammatory macrophages-related ER stress and p53-dependent apoptosis. Functional analysis of CHGA may lead to a novel therapy for IBD. CCC
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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) | 0.000 | 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 | 0.001 |
| 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".