Evidence map›Paper›PMID 37341931›Full record

ArticleClinical and experimental medicine2023

NSAIDs use history: impact on the genome-wide DNA methylation profile and possible mechanisms of action.

Pedro S Marra, Yoshitaka Nishizawa, Takehiko Yamanashi, Eleanor J Sullivan, Katie R Comp, Kaitlyn J Crutchley, Nadia E Wahba, Kazuki Shibata, Tsuyoshi Nishiguchi, Kyosuke Yamanishi and 3 more

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In one paragraph

Article in Clinical and experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.3field-weighted citation impact, top 37% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
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

13 authors at 4 institutions in 2 countries.

Pedro S MarraDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 3165 Porter Dr. Room 2175, Palo Alto, CA, 94304, USA.
Yoshitaka NishizawaDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 3165 Porter Dr. Room 2175, Palo Alto, CA, 94304, USA.
Takehiko YamanashiDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 3165 Porter Dr. Room 2175, Palo Alto, CA, 94304, USA.
Eleanor J SullivanDepartment of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Katie R CompDepartment of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Kaitlyn J CrutchleyCollege of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Nadia E WahbaDepartment of Psychiatry, Oregon Health and Science University School of Medicine, Portland, OR, USA.
Kazuki ShibataDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 3165 Porter Dr. Room 2175, Palo Alto, CA, 94304, USA.
Tsuyoshi NishiguchiDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 3165 Porter Dr. Room 2175, Palo Alto, CA, 94304, USA.
Kyosuke YamanishiDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 3165 Porter Dr. Room 2175, Palo Alto, CA, 94304, USA.
Nicolas O NoiseuxDepartment of Orthopedic Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Matthew D KaramDepartment of Orthopedic Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Gen ShinozakiDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 3165 Porter Dr. Room 2175, Palo Alto, CA, 94304, USA. gens@stanford.edu.
Stanford University · USUniversity of Iowa · USOregon Health & Science University · USUniversity of Nebraska Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveNSAIDs inhibit cyclooxygenase, but their role in aging and other diseases is not well understood. Our group previously showed the potential benefit of NSAIDs in decreasing the risk of delirium and mortality. Concurrently, epigenetics signals have also been associated with delirium. Therefore, we sought to find differentially methylated genes and biological pathways related to exposure with NSAIDs by comparing the genome-wide DNA methylation profiles of patients with and without a history of NSAIDs use.

methodsWhole blood samples were collected from 171 patients at the University of Iowa Hospital and Clinics from November 2017 to March 2020. History of NSAIDs use was assessed through a word-search function in the subjects' electronic medical records. DNA was extracted from the blood samples, processed with bisulfite conversion, and analyzed using Illumina's EPIC array. The analysis of top differentially methylated CpG sites and subsequent enrichment analysis were conducted using an established pipeline using R statistical software.

resultsGene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) showed several biological pathways relevant to NSAIDs' function. The identified GO terms included "arachidonic acid metabolic process," while KEGG results included "linoleic acid metabolism," "cellular senescence," and "circadian rhythm." Nonetheless, none of the top GO and KEGG pathways and the top differentially methylated CpG sites reached statistical significance.

conclusionOur results suggest a potential role of epigenetics in the mechanisms of the action of NSAIDs. However, the results should be viewed with caution as exploratory and hypothesis-generating given the lack of statistically significant findings.

Indexed as

DeliriumDNA MethylationAgingCpG IslandsEpigenesis, GeneticHumansArachidonic acidCell senescenceCircadian rhythmDNA methylationEpigeneticsLinoleic acidNSAIDs

Identifiers

PMID37341931
OpenAlexW4381470154

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Registered trials

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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.