FLUSH OR NEW THERAPEUTIC OPTIONS
Bibliographic record
Abstract
Introduction: The endocannabinoid system (ECS) consists of the cannabinoid receptors 1 (CB1) and 2 (CB2), endogenous ligands (lipids) and endocannabinoid-degrading mechanisms. To date the best characterized endogenous cannabinoids are anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG). Both act as agonists on CB1 and CB2 receptors. Several studies suggest that activation of the ECS results in anti-inflammatory effects. Aims: Aim of our study was to study possible anti-inflammatory effects in an experimental model of acute pancreatitis. Methods: Pancreatitis was induced by six hourly intraperitoneal injections of cerulein (50μg/kg bw) in wild-type C57/bl and CB1 −/− mice. HU210, a synthetic and specific CB1 agonist, or AM 281, a specific CB1 receptor antagonist, was administered 30 min prior to the first cerulein injection. Severity of pancreatitis was determined measuring serum amylase, IL-6 levels, trypsinogen activation, MPO activity and histological examinations. Pancreatic lysates were investigated by western blotting using phospho specific antibodies against p38 and JNK. Results: Administration of a single dose of HU210 significantly ameliorates the degree of pancreatitis showing reduced serum amylase, IL-6 levels, trypsinogen activation and improved histology. These protective effects were abolished by co-administration of the CB1 antagonist AM281. Administration of cerulein in CB1 −/− mice revealed the same degree of pancreatitis as in C57/bl wild-type mice, whereas administration of HU210 in CB1 −/− had no effect. Western blot analysis of p38 showed no significant differences in HU210 treated animals compared to cerulein-only treatment, while HU210 treatment resulted in decreased JNK-activation. Conclusion: Cannabinoids protect against cerulein-induced pancreatitis. The CB1 receptor plays an important role in the mediation of the protective effects. We furthermore show that the CB1 mediated anti-inflammatory effects comprise inhibition of JNK signaling in pancreatic acini.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.119 | 0.036 |
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".