Evidence map›Paper›PMID 27418337›Full record

ArticleJournal of gastroenterology2017

A small molecule inhibitor of NFκB blocks ER stress and the NLRP3 inflammasome and prevents progression of pancreatitis.

Mazhar A Kanak, Rauf Shahbazov, Gumpei Yoshimatsu, Marlon F Levy, Michael C Lawrence, Bashoo Naziruddin

Abstract read
PubMed Publisher
In one paragraph

Article in Journal of gastroenterology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
6.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Lysine acetylation and its role in the pathophysiology of acute pancreatitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Blockade of the protease ADAM17 ameliorates experimental pancreatitis.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Mazhar A KanakInstitute of Biomedical Studies, Baylor University, Waco, TX, USA. mazhar.kanak@vcuhealth.org.
Rauf ShahbazovDepartment of Surgery, University of Virginia, Charlottesville, VA, USA.
Gumpei YoshimatsuIslet Cell Laboratory, Baylor Research Institute, Dallas, TX, USA.
Marlon F LevyDepartment of Surgery, Transplantation Division, Virginia Commonwealth University, Richmond, VA, USA.
Michael C LawrenceIslet Cell Laboratory, Baylor Research Institute, Dallas, TX, USA.
Bashoo NaziruddinIslet Cell Laboratory, Baylor Research Institute, Dallas, TX, USA. BashooN@BaylorHealth.edu.
Baylor University · USUniversity of Virginia · USVirginia Commonwealth University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe underlying molecular mechanism that leads to development of chronic pancreatitis remains elusive. The aim of this study is to understand the downstream inflammatory signaling involved in progression of chronic pancreatitis, and to use withaferin A (WA), a small molecule inhibitor of nuclear factor κB (NFκB), to prevent progression of chronic pancreatitis.

methodsTwo different protocols were used to induce pancreatitis in mice: standard and stringent administration of cerulein. The severity of pancreatitis was assessed by means of pancreatic histology and serum amylase levels. Immunohistochemistry and flow-cytometric analysis was performed to visualize immune cell infiltration into the pancreas. Real-time PCR and Western blot were used to analyze the downstream signaling mechanism involved in the development of chronic pancreatitis.

resultsThe severity of cerulein-induced pancreatitis was reduced significantly by WA, used as either preventive or curative treatment. Immune cell infiltration into the pancreas and acinar cell death were efficiently reduced by WA treatment. Expression of proinflammatory and proapoptotic genes regulated by NFκB activation was increased by cerulein treatment, and WA suppressed these genes significantly. Sustained endoplasmic reticulum stress activation by cerulein administration was reduced. NLRP3 inflammasome activation in cerulein-induced pancreatitis was identified, and this was also potently blocked by WA. The human pancreatitis tissue gene signature correlated with the mouse model.

conclusionsOur data provide evidence for the role of NFκB in the pathogenesis of chronic pancreatitis, and strongly suggest that WA could be used as a potential therapeutic drug to alleviate some forms of chronic pancreatitis.

Indexed as

Acute DiseaseAnimalsAnti-Inflammatory AgentsCytokinesCytoprotectionDisease Models, AnimalDisease ProgressionDrug Evaluation, PreclinicalEndoplasmic Reticulum StressFemaleInflammasomesInflammation MediatorsMaleMice, Inbred C57BLNF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinAnti-Inflammatory AgentsCytokinesInflammasomesInflammation MediatorsNF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseTranscription Factor RelAwithaferin AWithanolidesInflammationNuclear factor κBPancreatitisWithaferin A

Identifiers

PMID27418337
OpenAlexW2470546554

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.