ROLE OF RETINOID-X RECEPTOR-α IN THE SUPPRESSION OF RAT BILE ACID COENZYME A-AMINO ACID N-ACYLTRANSFERASE IN LIVER DURING SEPSIS
Bibliographic record
Abstract
Sepsis causes intrahepatic cholestasis and leads to hepatic failure. However, the pathophysiology of hepatic events is unclear. Expression of rat hepatic bile acid coenzyme A-amino acid N-acyltransferase (rBAT), a major enzyme for the conjugation of bile acids, is significantly decreased during sepsis. rBAT transcriptional regulation is mainly by a heterodimer of farnesoid-X receptor (FXR) and retinoid-X receptor-alpha (RXR-alpha) via the inverted repeat 1 sequence. During sepsis, nuclear receptors and translocation of RXR-alpha from cytosol to nucleus decrease. The purpose of this study was to further clarify the mechanisms of RXR-alpha-mediated rBAT regulation during polymicrobial sepsis and with dexamethasone treatment. Polymicrobial sepsis was induced in rats by cecal ligation and puncture (CLP). Liver tissues obtained 3, 6, 9, and 18 h after CLP were studied, and hepatocytes were isolated from rats with sepsis. Post-CLP decreases were observed in mRNA levels of rBAT (6 h), protein levels of rBAT (6 h), RXR-alpha (6 h), and FXR (9 h). DNA binding activity of FXR/RXR significantly decreased at 6 h after CLP. Dexamethasone reversed sepsis-inhibited RXR-alpha expression and the binding activity of FXR/RXR to rBAT DNA as well as rBAT protein expression. The results suggest that suppression of rBAT occurs at the transcriptional level, and the decrease in RXR-alpha by septic insult may play a critical role in rBAT suppression at the early stage of polymicrobial sepsis.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.000 | 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) | 0.001 | 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".