Cystathione‐γ‐lyase deficiency protects mice from galactosamine/LPS‐induced acute liver failure
Bibliographic record
Abstract
Introduction Acute liver failure is a fatal syndrome attributed to massive hepatocyte death. Hydrogen sulfide (H2S) has been reported to exert cytoprotective effects in variety of organs. Here, we examined the role of cystathione‐γ‐lyase (CSE, an enzyme produces H2S) in the acute liver failure induced by galactosamine (Gal) and lipopolysaccharide (LPS). Methods Wild‐type (WT) and CSE‐deficient (CSEKO) mice were challenged with Gal/LPS. Results CSEKO exhibited better survival rate and lower plasma alanine aminotransferase (ALT) levels compared with WT after Gal/LPS challenge. Administration of DL‐propargylglycine (PAG, a CSE inhibitor) also prevented Gal/LPS‐induced increase of plasma ALT in WT. CSE deficiency markedly attenuated Gal/LPS‐induced upregulation of inflammatory cytokines and activation of caspase 3 and PARP in liver tissue. On the other hand, CSE deficiency increased nuclear translocation of Nrf2 and upregulated gene expression of anti‐oxidant proteins in the liver. Liver levels of thiosulfate was markedly increased in CSEKO compared to WT. Finally, administration of sodium thiosulfate attenuated the Gal/LPS‐induced increase of plasma ALT in WT. Conclusions These results suggest that CSE deficiency increases liver levels of thiosulfate and protects mice from acute liver failure at least in part by inhibition of caspase 3 activation and by augmentation of Nrf2 signaling pathway.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".