Chromofungin ameliorates colitis and reduces endoplasmic reticulum stress and P53-apoptotic pathways
Bibliographic record
Abstract
Crohn’s disease (CD) and ulcerative colitis (UC) are chronic idiopathic inflammatory bowel diseases (IBD) with an estimated prevalence in Canada of around 15/100000 persons. Biological agents are expensive, require indefinite use to ensure a sustained response, and raise concerns about infections and other complications thus limiting enthusiasm for introducing them earlier in the treatment for IBD. The essential cells in the innate immune system that coordinates the inflammatory process are the macrophages (MØ), where MØs have been demonstrated to be increased in areas of inflammation in IBD. MØs are a heterogeneous population of two different phenotypes: group 1: “inflammatory, classically activated MØs: M1” and alternative activated MØs: M2. MØs polarization and plasticity depend on specific combinations of cytokines and peptides within the microenvironment. Mucosal changes in IBD are characterized by inflammation and are linked to hyperplasia in the chromogranin-A (CHGA)-producing enterochromaffin (EC) cells. CHGA cleavages generate several biologically active peptides, including chromofungin (CHGA47-66 [CFG]). Our lab demonstrated that CFG is an essential peptide in MØs regulation. Genome-wide associated studies in IBD have revealed that in IBD and within the epithelium, endoplasmic reticulum (ER) stress and intestinal epithelial apoptosis figure strikingly. A p53-apoptotic pathway mediates intestinal epithelial apoptosis through the activation of the p53-upregulated modulator of apoptosis (PUMA), Bcl-2 associated-X protein (BAX), Bcl-2 associated death promoter (BAD), Bcl-2 antagonist/killer-1 (BAK1), Caspase-3 and Caspase-8 proteins. Polymorphisms of X-box binding protein 1 (XBP1) gene, a main UPR signalling protein (GRP78), that develop enteritis and subsequent apoptotic cell death and is associated with an increased risk of IBD, The deletion of CHGA leads to an increase in GRP78 expression in diabetes. Currently, there is a gap of knowledge in understanding the influence of CHR on macrophages, ER stress, and apoptosis markers during the development of experimental colitis. Therefore, we hypothesize that Chromofungin plays a critical role in colonic inflammation via modulating ER stress and apoptotic pathways in macrophages
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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) | 0.002 | 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".