ArticleDigestive diseases and sciences2025
Protease Inhibitor VR23 Alleviates Severe Acute Pancreatitis with High Trypsin Synthesis in Mice.
Article in Digestive diseases and sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
backgroundAcute pancreatitis (AP), characterized by pancreatic autodigestion and systemic inflammation, remains a life-threatening condition with a high mortality rate in severe cases. Cholinergic signaling through muscarinic receptors (mAChRs) regulates pancreatic exocrine secretion, yet the role of chronic cholinergic hyperactivation in AP progression is poorly understood. Protease inhibitors like VR23, a potent trypsin-selective compound, hold therapeutic potential but lack evaluation in AP models.
objectiveThis study aimed to investigate the effects of prolonged cholinergic stimulation on AP severity and evaluate the efficacy of VR23 in mitigating pancreatic injury.
methodsMale C57BL/6 mice were pretreated with intragastric carbachol (5 mg/kg, twice daily for 7 days) to mimic chronic cholinergic hyperactivation, followed by intraperitoneal caerulein (100 μg/kg, 10 hourly doses) to induce AP. VR23 (30 mg/kg) was administered intraperitoneally 12 h and 3 h before caerulein. Pancreatic injury was assessed via histopathology (HE-staining), serum amylase/lipase activity, western blot (trypsin/amylase), RT-qPCR (TNF-α, IL-1β, IL-6, IL-18), MPO immunohistochemistry (neutrophil infiltration), HMGB1 immunohistochemistry (necrosis) and TUNEL staining (apoptosis).
resultsLong-term carbachol stimulation induced acinar cell hypertrophy and elevated intracellular trypsin synthesis, exacerbating caerulein-induced AP with increased pancreas-to-body weight ratio, histopathological scores, serum amylase/lipase, and pro-inflammatory cytokines. Neutrophil infiltration and apoptosis were significantly amplified. VR23 pretreatment attenuated pancreatic injury, reducing histopathological scores, serum enzymes, inflammatory cytokines, neutrophil infiltration, and apoptosis.
conclusionLong-term chronic cholinergic stimulation exacerbates AP by enhancing trypsin synthesis, inflammatory responses, and apoptosis. VR23 demonstrates therapeutic efficacy by inhibiting protease activity and modulating inflammation, highlighting its potential as a targeted treatment for AP.
Indexed as
Identifiers
40455346What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.