A83 CHROMOFUNGIN DECREASES INTESTINAL INFLAMMATION AND REGULATES DENDRITIC CELLS MARKERS
Bibliographic record
Abstract
Ulcerative colitis (UC) is characterized by altered levels of chromogranin-A (CHGA) and a dysregulation of dendritic cells (DCs). CHGA, a prohormone protein, can be cleaved into several bioactive peptides including chromofungin (CHR: CHGA47-66) encoded by CHGA Exon-IV. Previously, we demonstrated that CHR is reduced in active UC patients and protects against intestinal inflammation through modulation of the macrophages plasticity. Thus, we hypothesized that CHR regulates other antigen presenting cells functions like DCs during the progression of colitis. We aimed to investigate the association between CHR and DCs in patients with active UC, and underlay the effect of CHR treatment on DCs functions in dextran sulfate sodium (DSS)-induced colitis. mRNA levels of CHR (CHGA Exon-IV) and its association with DCs markers (interleukin (IL)-23, IL-12p40, CD86, CD11C, CRR7, CD74, IL-12A) were quantified in colonic biopsies of patients with active UC and healthy individuals. Colitis was induced in C57BL/6 mice (7–8 weeks) by 5% DSS (wt./vol.) for 5 days. Intra-rectal administration of CHR (2.5 mg/kg/day) started one-day before induction of colitis and lasted for 6 days. Disease activity index (DAI), macroscopic and microscopic scores were assessed. Colonic levels of interleukin (IL)-23, IL-12p40, cluster of differentiation (CD) 86, CD11C, C-C chemokine receptor (CCR)7, CD74 and IL-12A were determined using ELISA and/or RT-qPCR. In-vitro, splenic CD11c+ cells were isolated from naïve and colitic mice, cultured overnight in the presence or absence of CHR (10–6 M) and CD40, CD80, and CD86 markers were quantified using flow cytometry. In patients with active UC, CHR level is reduced and showed a negative relationship with DCs markers; IL23 (r= -0.3725), IL12p40 (r= -0.3706), CD11C (r= - 0.4647), CRR7 (r= -0.3709), IL12A (r = -0.4253), CD86 (r= -0.6765), and CD74 (r= -0.3647). In-vivo, CHR treatment reduced the severity of the colitis and is associated with a significant decrease in colonic levels of IL-23, IL-12p40, and CD86, and without significant changes in the levels of CD11c, CCR7, CD74, and IL-12A. In-vitro, CHR treatment reduced CD40 and CD80 expression in splenic CD11c+cells isolated from colitic mice when compared with PBS-treated group. No differences were detected in the expression of CD86. CHR regulates the development of colitis, and modulates CD11c+ cells markers of immune activation. Further studies are warranted to understand the possible effects of CHR on the crosstalk between CD11c+ cells and T-cells. These findings provide the foundation of future potential therapeutic strategies in UC. Mindel and Tom Olenick Scholarship in Gastroenterology
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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".