Role of dihydroceramides in the progression of acute-on-chronic liver failure in rats
Bibliographic record
Abstract
BACKGROUND: Previously, dihydroceramide (d18:0/24:0) (dhCer (d18:0/24:0)) was reported to be a potential biomarker for acute-on-chronic liver failure (ACLF) prognosis. In this study, we further explored the role of dhCer (d18:0/24:0) in the progression of ACLF to validate the biomarker using ACLF rat model. METHODS: ACLF rats were sacrificed at 4 and 8 h post-D-galactosamine (D-gal)/lipopolysaccharide (LPS) administration to investigate the liver biochemical markers, prothrombin time and liver histopathology. Change in dhCer and other sphingolipids levels were investigated by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Rats were treated with N-(4-hydroxyphenyl) retinamide (4-HPR) to examine the mortality rate and its role in improving ACLF. RESULTS: LPS/D-gal administration resulted in significant elevation in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Prothrombin time was prolonged and histopathological examination showed abnormality. HPLC-MS/MS results showed total dhCer levels in ACLF group (64.10 ± 8.90 pmol/100 μL, 64.22 ± 6.78 pmol/100 μL for 4 and 8 h, respectively) were decreased significantly compared with control group (121.61 ± 23.09 pmol/100 μL) (P < 0.05). In particular, dhCer (d18:0/24:0), dhCer (d18:0/20:0), and dhCer (d18:0/22:0) levels were decreased. Treatment with 4-HPR significantly increased the levels of dhCers, including dhCer (d18:0/24:0) compared with ACLF group, for the level of dhCer (d18:0/24:0) in 4-HPR group was 20.10 ± 8.60 pmol/100 μL and the level of dhCer (d18:0/24:0) in ACLF group was 9.74 ± 2.99 pmol/100 μL (P < 0.05). This was associated with reduced mortality rate and prolonged survival time. The ALT and AST in 4-HPR group were significantly decreased compared with ACLF group. The prothrombin time of 4-HPR group (41.49 s) was significantly lower than the prothrombin time of ACLF group (57.96 s) (P < 0.05). 4-HPR also decreased plasma ammonia levels slightly, as the plasma ammonia levels in 4-HPR group and ACLF group were 207.37 ± 60.43, 209.15 ± 60.43 μmol/L, respectively. Further, 4-HPR treatment improved histopathological parameters. CONCLUSIONS: DhCer, especially dhCer (d18:0/24:0), is involved in the progression of ACLF. Increasing the levels of dhCer can reduce the mortality rate of ACLF rats and alleviate liver injury.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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".