Enhancing host defense against bacterial pore-forming toxin by suppressing HMG-CoA reductase pathway in airway epithelial cells (112.13)
Bibliographic record
Abstract
Abstract Pneumolysin and α-hemolysin are the main pore-forming toxins known to play critical roles in bacterial pneumonia caused by the infections of Streptococcus pneumoniae and Staphylococcus aureus, respectively. Airway epithelia are the initial and the primary targets of these air-borne bacterial infections. Several epidemiological studies have linked the use of statin to the improvement in pneumonia outcomes, but the nature of the mechanism is still unknown. Using primary normal human bronchial epithelial (NHBE) cells and an immortalized normal bronchial epithelial cell line, HBE1, we confirmed the effects of simvastatin pre-treatment in enhancing host defense against these bacterial toxins. The protective effects could be further demonstrated in vivo with simvastatin administration prior to intra-tracheal instillation of these toxins. We further found that the protection requires protein synthesis and is calcium dependent. Using siRNA gene silencing, pharmacological treatment with inhibitors, immuno fluorescence microscopy, Western blot and qRT-PCR approaches, we have delineated the protection mechanisms in airway epithelial cells through HMG-CoA-Reductase pathways. Our results also suggest that the inhibition of HMG-CoA reductase pathway may enhance host defense molecule synthesis in airway epithelium. It is plausible that this study may lead to the development of an adjuvant therapy against pore-forming toxin-related bacterial infections in lung.
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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) | 0.001 | 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".