Carbon monoxide (CO)‐dependent modulation of polymorphonuclear leukocyte (PMN) adhesion to human cerebrovascular endothelial cells in an in vitro model of endotoxemia
Bibliographic record
Abstract
CO liberated from a water‐soluble CO‐releasing molecule (CORM‐3) suppresses sepsis‐induced inflammation. However, the exact mechanisms are poorly understood. In this study we examined the mechanisms of CORM‐3‐dependent modulation of PMN adhesion in an in vitro model of endotoxemia employing human‐derived cerebrovascular endothelial cells, hCMEC/D3 (provided by Dr. P. Couraud, INSERM, Paris). hCMEC/D3 were stimulated with LPS (1μg/mL) for 6 hrs. In some experiments hCMEC/D3 were: 1) pre‐treated, 2) co‐treated, or 3) treated with CORM‐3 or inactive CORM‐3 (iCORM‐3) (200μM) before/during/following stimulation with LPS, respectively. PMN rolling/adhesion to hCMEC/D3 was assessed under conditions of flow (shear stress 0.7dyn/cm 2 ). In parallel, MAPK‐signaling (phosphorylation of p38, ERK1/2 and JNK1/2; Western Blot) and expression of adhesion molecules (E‐selectin, ICAM‐1 and VCAM‐1; RT‐PCR) were also assessed. CORM‐3 significantly reduced PMN adhesion to hCMEC/D3 with the most profound effects seen in “pre‐treatment” group. This was accompanied by decreased levels of JNK1/2 Tyr‐phosphorylation and suppressed expression of E‐selectin and VCAM‐1. The results indicate that CORM‐3 interferes with activation of JNK1/2 phosphorylation and expression of hCMEC/D3 pro‐adhesive phenotype, thus potentially could be used to reduce systemic inflammation (HSFO‐393, HSFO‐NA6914, IRF‐04–79)
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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) | 0.001 | 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".