Twist1 contributes to developing and sustaining corticosteroid resistance in ulcerative colitis
Bibliographic record
Abstract
Rationale: Corticosteroid resistance (CR) is a serious drawback to steroid therapy in patients with ulcerative colitis (UC); the underlying mechanism is incompletely understood.Twist1 protein (TW1) is an apoptosis inhibitor and has immune regulatory functions.This study aims to elucidate the roles of TW1 in inducing and sustaining the CR status in UC.Methods: Surgically removed colon tissues of patients with ulcerative colitis (UC) were collected, from which neutrophils were isolated by flow cytometry.The inflammation-related gene activities in neutrophils were analyzed by RNA sequencing.A CR colitis mouse model was developed with the dextran sulfate sodium approach in a hypoxia environment.Results: Higher TW1 gene expression was detected in neutrophils isolated from the colon tissues of UC patients with CR and the CR mouse colon tissues.TW1 physically interacted with glucocorticoid receptor (GR)α in CR neutrophils that prevented GRα from interacting with steroids; which consequently abrogated the effects of steroids on regulating the cellular activities of neutrophils.STAT3 (Signal Transducer and Activator of Transcription-3) interacted with Ras protein activator like 1 to sustain the high TW1 expression in colon mucosal neutrophils of CR patients and CR mice.Inhibition of TW1 restored the sensitivity to corticosteroid of neutrophils in the colon tissues of a CR murine model.Conclusions: UC patients at CR status showed high TW1 expression in neutrophils.TW1 prevented steroids from regulating neutrophil activities.Inhibition of TW1 restored the sensitivity to corticosteroids in the colon tissues at the CR status.
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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".