Nuclear factor‐κB inhibition improves myocardial contractility in rats with cirrhotic cardiomyopathy
Bibliographic record
Abstract
BACKGROUND/AIMS: Cytokines such as tumour necrosis factor (TNF-alpha) contribute to the pathogenesis of cirrhotic cardiomyopathy. Nuclear factor-kappaB (NF-kappaB) is crucial for cytokine regulation, and induces cardiac dysfunction in several heart disease models. We aimed to elucidate possible NF-kappaB involvement in cirrhotic cardiomyopathy. METHODS: Rats were bile duct ligated (BDL) to produce cirrhosis; controls received sham operation. Animals were studied 4 weeks later. Two NF-kappaB inhibitors were used: pyrrolidine dithiocarbamate (PDTC) and Bay 11-7082. Four groups were studied in most protocols: sham control, sham+PDTC, BDL and BDL+PDTC. Additional contractility studies were performed with Bay 11-7082. Myocardial NF-kappaB and TNF-alpha expression was measured by Western blot and ELISA. The contractility of isolated cardiomyocytes was observed under direct microscopy. RESULTS: Nuclear factor-kappaB and TNF-alpha levels were increased in cirrhotic hearts compared with controls. PDTC significantly reduced NF-kappaB activity and TNF-alpha expression in cirrhotic hearts; controls were unaffected. Cirrhotic cardiomyocytes showed decreased systolic and diatolic velocity compared with sham controls. Both PDTC and Bay 11-7082 restored contractile function in cirrhotic cardiomyocytes, but did not affect controls. CONCLUSIONS: Inhibition of the increased NF-kappaB activity in cirrhotic hearts was associated with improvement of attenuated cardiomyocyte contractility. NF-kappaB, via effects on cytokine expression, may contribute to the pathogenesis of cirrhotic cardiomyopathy.
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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 | 0.000 |
| 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) | 0.002 | 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".