Evidence map›Paper›PMID 36098401›Full record

ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2022

Urolithin A attenuates severity of chronic pancreatitis associated with continued alcohol intake by inhibiting PI3K/AKT/mTOR signaling.

Siddharth Mehra, Supriya Srinivasan, Samara Singh, Zhiqun Zhou, Vanessa Garrido, Iago De Castro Silva, Tulasigeri M Totiger, Austin R Dosch, Xizi Dai, Rajinder K Dawra and 6 more

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In one paragraph

Article in American journal of physiology. Gastrointestinal and liver physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 5% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
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  12. A Review of Gut Microbiota-Derived Metabolites in Tumor Progression and Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review
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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

16 authors at 4 institutions in 1 country.

Siddharth MehraDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Supriya SrinivasanDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Samara SinghDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Zhiqun ZhouDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Vanessa GarridoDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Iago De Castro SilvaDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Tulasigeri M TotigerDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Austin R DoschDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Xizi DaiDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Rajinder K DawraDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Venkatakrishna Rao JalaDepartment of Microbiology and Immunology, University of Louisville, Louisville, Kentucky.
Chanjuan ShiDepartment of Pathology, Duke University School of Medicine, Durham, North Carolina.
Jashodeep DattaDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Michael VanSaunDepartment of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas.
Nipun MerchantDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Nagaraj NagathihalliDepartment of Surgery, University of Miami Miller School of Medicine, Miami, Florida.ORCID 0000-0003-2373-3293
University of Miami · USDuke University · USThe University of Kansas Cancer Center · USUniversity of Louisville · US

Funding

Tumor Biology Research ProgramP30CA240139 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI George S. Grills · 2019 to 2026
$24.1M
University of Louisville Center for Integrative Environmental Health SciencesP30ES030283 · NIEHS · UNIVERSITY OF LOUISVILLE · PI Amanda Jo LeBlanc · 2020 to 2026
$10.0M
Stat3 Signaling in Pancreas CancerR01CA161976 · NCI · VANDERBILT UNIVERSITY · PI MERCHANT, NIPUN B. · 2012 to 2022
$3.4M
Research Training Program in Surgical OncologyT32CA211034 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI MERCHANT, NIPUN B. · 2016 to 2025
$2.7M
Combining Immunotherapy with Urolithin A to Improve Pancreatic Cancer SurvivalR03CA249401 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI NAGATHIHALLI, NAGARAJ S. · 2020 to 2021
$154k
NCI NIH HHS P30 CA240139NCI NIH HHS R01 CA161976NCI NIH HHS R03 CA249401NCI NIH HHS T32 CA211034NIEHS NIH HHS P30 ES030283
6 · The paper itself

Abstract

Heavy alcohol consumption is the dominant risk factor for chronic pancreatitis (CP); however, treatment and prevention strategies for alcoholic chronic pancreatitis (ACP) remains limited. The present study demonstrates that ACP induction in C57BL/6 mice causes significant acinar cell injury, pancreatic stellate cell (PSC) activation, exocrine function insufficiency, and an increased fibroinflammatory response when compared with alcohol or CP alone. Although the withdrawal of alcohol during ACP recovery led to reversion of pancreatic damage, continued alcohol consumption with established ACP perpetuated pancreatic injury. In addition, phosphokinase array and Western blot analysis of ACP-induced mice pancreata revealed activation of the phosphatidylinositol 3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) and cyclic AMP response element binding protein (CREB) signaling pathways possibly orchestrating the fibroinflammatory program of ACP pathogenesis. Mice treated with urolithin A (Uro A, a gut-derived microbial metabolite) in the setting of ACP with continued alcohol intake (during the recovery period) showed suppression of AKT and P70S6K activation, and acinar damage was significantly reduced with a parallel reduction in pancreas-infiltrating macrophages and proinflammatory cytokine accumulation. These results collectively provide mechanistic insight into the impact of Uro A on attenuation of ACP severity through suppression of PI3K/AKT/mTOR signaling pathways and can be a useful therapeutic approach in patients with ACP with continuous alcohol intake.

Indexed as

Pancreatitis, AlcoholicProto-Oncogene Proteins c-aktAlcohol DrinkingAnimalsCoumarinsCyclic AMP Response Element-Binding ProteinCytokinesMammalsMiceMice, Inbred C57BLPhosphatidylinositol 3-KinasesRibosomal Protein S6 Kinases, 70-kDaSignal TransductionSirolimusTOR Serine-Threonine Kinases3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-oneCoumarinsCyclic AMP Response Element-Binding ProteinCytokinesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRibosomal Protein S6 Kinases, 70-kDaSirolimusTOR Serine-Threonine Kinasesalcoholic pancreatitisfibrosisinflammationPI3K/AKT/mTORurolithin A

Identifiers

PMID36098401
PMCPMC9602784
OpenAlexW4295366725

What Socratic 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 Socratic graph.