Impact of ENaC downregulation in transgenic mice on the outcomes of acute lung injury induced by bleomycin
Bibliographic record
Abstract
NEW FINDINGS: What is the central question of this study? How does the downregulation of ENaC, the major driving force for alveolar fluid clearance, impact acute lung injury outcomes induced by bleomycin, featuring alveolar damage, as observed during ARDS exudative phase? What is the main finding and its importance? ENaC downregulation in αENaC(-/-)Tg+ mice did not elicit a substantial worsening impact on the main bleomycin outcomes. In ARDS patients, both ENaC alteration and alveolar damage are observed. Thus, novel therapeutic avenues, favouring alveolar integrity restauration, in addition to lung oedema resolution capacity, mainly driven by ENaC, would be essential. ABSTRACT: reabsorption through ENaC channels is a major driving force for alveolar fluid clearance (AFC) in physiological and pathological conditions. It has previously been shown that partial αENaC impairment in transgenic (αENaC(-/-)Tg+) mice results in reduced AFC in basal conditions and increased wet/dry ratio after thiourea-induced lung oedema, a model in which the integrity of the alveolar epithelium is preserved. The goal of this study was to further investigate the impact of αENaC downregulation in αENaC(-/-)Tg+ mice using an experimental model of acute lung injury induced by bleomycin. A non-significant trend in enhanced weight loss and mortality rates was observed after the bleomycin challenge in αENaC(-/-)Tg+ compared to wild-type (WT) mice. Bronchoalveolar lavage analyses revealed increased TNFα levels and protein concentrations, as indexes of lung inflammation and alveolar damage, in αENaC(-/-)Tg+ mice, compared to WT, at day 3 post-bleomycin, although a statistical difference was no longer measured at day 7. Differential immune cell counts were similar in WT and αENaC(-/-)Tg+ mice challenged with bleomycin. Moreover, lung weight measurements indicated similar oedema levels in WT mice and in transgenic mice with impaired ENaC channels. Altogether, our data indicated that change in ENaC expression does not elicit a significant impact on lung oedema level/resolution in the bleomycin model, featuring alveolar damage.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".