A248 ETHANOL-INDUCED MUCOSAL IRRITATION DISRUPTS LOCAL AND SYSTEMIC PROTECTIVE EFFECTS OF NON-INVASIVE TRANSCUTANEOUS AURICULAR VAGUS NERVE STIMULATION (TAVNS)
Bibliographic record
Abstract
Abstract Background The integrity of the mucosal barrier is vital for gastrointestinal homeostasis. Previously, we demonstrated that non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) decreases inflammatory and pro-apoptotic markers while increasing anti-inflammatory markers in homeostatic conditions. However, its effectiveness in case of slight mucosal irritation remains unclear. Aims To assess whether slight mucosal irritation affects taVNS efficacy in modulating pro- and anti-inflammatory cytokines and apoptosis-related markers in the colon and spleen. Methods Male C57BL/6 mice were given a single intrarectal dose of 30% ethanol (ETOH group, 100 µl), while the control (CTRL) group received no ethanol. Preventive taVNS (10V, 20Hz & 500us, 10min/day) or no stimulation (clipping only) began one day before ethanol injection and continued for four days. Colonic and splenic levels of interleukin (IL)-10, tumor growth factor (TGF)-β, tumor necrosis factor (TNF)-α, pro-apoptotic markers Bcl-2-associated X protein (BAX), Bcl-2 homologous antagonist killer (BAK1), caspase8, and pro-survival BCL2 associated agonist of cell death (BAD) were measured using qRT-PCR and ELISA. Results taVNS significantly increased IL-10 mRNA expression (p<0.0001) and both mRNA (p<0.015) and protein (p<0.0001) levels of TGF-β in CTRL conditions, with no changes in the ETOH group. Mice demonstrated unchanged IL-10 protein levels in the colon in the presence or absence of taVNS. However, in CTRL conditions, taVNS downregulated BAX (p<0.0001), BAK1(p<0.0001), and caspase8 (p<0.0002) mRNA expression significantly, with no effect in the ETOH group. Additionally, BAD (p<0.0001) mRNA expression increased significantly in CTRL conditions but remained unchanged in the ETOH group. In the spleen, taVNS decreased TNF-α (p<0.04) and increased TGF-β (p<0.0007) protein levels in CTRL conditions without impacting the ETOH group. Conclusions Our findings demonstrated that taVNS successfully regulated systemic and local cytokines and apoptosis-related markers in control mice. However, a slight irritation induced by ethanol abolished its effects, indicating that ethanol associated with a slight mucosa irritation can modify the taVNS outcome. Funding Agencies CIHR
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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 | 0.000 |
| 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".