Extracellular vesicles derived from creeping fat stem cells promote lymphatic function and restrain inflammation of Crohn's disease
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disease in the intestinal tract. Mesenteric fat wrapping and thickening, or creeping fat (CrF), is a typical characteristic of CD and it involves lymphangiogenesis and altered lymphatic function. By releasing extracellular vesicles (EVs), adipose tissue-derived stem cells (ADSCs) can regulate their adjacent cells. However, the regulating roles of ADSC-EVs in CrF (CrF-EVs) in CD, especially in modulating lymphatic function and mitigating the progression of mesenteritis and colitis, remains elusive. METHODS: ) mice were used to assess the biological functions of CrF-EVs in spontaneous mesenteritis and colitis. Moreover, tissue and serum from various cohorts of CD patients were used to determine the prognostic value of miR-132-3p. RESULTS: mice via promoting lymphangiogenesis and lymphatic drainage. Using high-throughput sequencing, we demonstrated that CrF-EVs significantly increased HLEC proliferation, migration, tube formation and CCL-21 production in a miR-132-3p/RASA1/ERK1/2 axis-dependent manner. Accordingly, upregulated miR-132-3p was observed in patient CrF, positively correlated with lymphangiogenesis while negatively correlated with inflammatory factors (tumour necrosis factor-α and IL-6) level. Moreover, serum miR-132-3p demonstrated a positive correlation with disease activity. CONCLUSIONS: EVs derived from CrF ADSCs, containing elevated levels of miR-132-3p, could promote lymphatic function and restrain inflammation of CD. Our results provide a novel insight into the role of mesenteric lymphatics in CD progression and reveal a new potential therapeutic. KEY POINTS: Extracellular vesicles (EVs) of creeping fat (CrF) derived adipose stem cells effectively attenuate chronic mesenteritis and colitis in Crohn's disease (CD). The lymphatic vessels play an important role in disease development of CD and their functions are improved by CrF-EV-miR-132-3p through RASA1/ERK1/2 signaling. MiR-132-3p expression is upregulated in CrF and serum of CD patients, and tightly linked with inflammation and disease activity.
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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 | 0.000 | 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 | 0.000 |
| 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 it