HMGB1 mediated LPS‐induced myocardial dysfunction in mice
Bibliographic record
Abstract
The mechanism involved in the endotoxin‐induced myocardial dysfunction is not fully understood. The purpose of the present study was to demonstrate that myocardial dysfunction in endotoxinemia is mediated via an increase in myocyte production of high mobility group box 1 protein (HMGB1). In vivo, mouse model of endotoxinemia in mice was induced by i.p. injection of LPS (10 mg/kg) and myocardial function was evaluated 24 hrs later. LPS induced a decrease in myocardial contractility (end‐systolic and end‐diastolic volume relation). The decrease in myocardial contractility was diminished when the mice were received either a HMGB1 antagonist (A‐box) or an inhibitor of HMGB1 (glycyrrhizic acid). Expression of myocardial HMGB1 was increased in the heart of mice treated with LPS (immunoflorescence staining). Further, recombinant HMGB1 (10–20 μg/mouse, i.p.) resulted in a dose dependent decrease in myocardial contractility. To confirm that the source of HMGB1 was the cardiac myocytes in the hearts, isolated cardiac myocytes were exposed to LPS (10 μg/ml). Treatment of cardiac myocytes with LPS increased in intracellular levels of HMGB1 and release HMGB1 by myocytes to the supernatant (Western). Taken together, our study suggests LPS‐induced myocardial dysfunction is a result of increase in myocyte HMGB1. (CIHR MOP 81303).
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How this classification was reachedexpand
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".