HMGB1/TLR4 axis contributes to A/R‐induced cardiomyocyte apoptosis through potentiating TNFα/JNK pathway
Bibliographic record
Abstract
The present study is to explore the role of HMGB1/TLR4 axis in the myocyte apoptosis‐induced by A/R (an in vitro counterpart to I/R). Methods cardiomyocytes derived from wild type or TLR4 deficient mice were challenged with an A/R. HMGB1, TNFα expression (Western blot and ELISA), myocyte apoptosis (caspase 3 activity and cell death ELISA) and JNK and NFκB activation (p65 phosphorylation) (Western blot) assessed. Results A/R challenge to myocytes resulted in an increase in HMGB1 expression and extracellular release. Inhibition of HMGB1 attenuated the apoptosis and A/R‐induced TNFα production. Treatment of cardiomyocytes with recombinant HMGB1 (1–5 μg/ml) did not lead to myocyte apoptosis and TNFα production. Exogenous TNFα induced a moderate pro‐apoptotic effect on the myocytes; an effect substantially potentiated by HMGB1. TNFα activated both JNK and NFκB. However, degree of TNFα–induced JNK activation was greater than NFκB in the presence of HMGB1. Inhibition of JNK diminished the myocytes apoptosis‐induced by either TNFα or TNFα/HMGB1 cocktail. A/R‐challenge to TLR4 deficient myocytes increased HMGB1 but not apoptosis, TNFα production and JNK activation. Conclusions our results indicate myocyte HMGB1/TLR4 axis and TNFα work in concert to promote A/R‐induced myocyte apoptosis via JNK activation. (HSFO NA‐6316).
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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 | 0.001 | 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 | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".