Evidence map›Paper›PMID 33712031›Full record

ArticleJournal of neuroinflammation2021

X chromosome escapee genes are involved in ischemic sexual dimorphism through epigenetic modification of inflammatory signals.

Shaohua Qi, Abdullah Al Mamun, Conelius Ngwa, Sharmeen Romana, Rodney Ritzel, Arthur P Arnold, Louise D McCullough, Fudong Liu

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
10.9field-weighted citation impact, top 1% 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

47 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Histone demethylases in autophagy and inflammation.Cell communication and signaling : CCS · 2025
    Review
  11. Article
  12. Review
  13. Sex differences in disease: sex chromosome and immunity.Journal of translational medicine · 2024
    Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. 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

8 authors at 3 institutions in 1 country.

Shaohua Qi *Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX, 77030, USA.
Abdullah Al Mamun *Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX, 77030, USA.
Conelius NgwaDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX, 77030, USA.
Sharmeen RomanaDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX, 77030, USA.
Rodney RitzelDepartment of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Arthur P ArnoldDepartment of Integrative Biology and Physiology, UCLA, 610 Charles Young Drive South, Los Angeles, CA, 90095, USA.
Louise D McCulloughDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX, 77030, USA.
Fudong LiuDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Fudong.Liu@uth.tmc.edu.ORCID http://orcid.org/0000-0002-7684-9428
The University of Texas Health Science Center at Houston · USThe University of Texas Health Science Center · USUniversity of Maryland, Baltimore · US

Funding

Sex Differences in the Metabolic SyndromeU54DK120342 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 2018 to 2022
$7.6M
Contribution of the X Chromosome to Sex Differences in StrokeR01NS108779 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI LIU, FUDONG, MCCULLOUGH, LOUISE D. · 2018 to 2022
$2.7M
IRF5-IRF4 Regulatory Axis: A new Target for StrokeR01NS093042 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI LIU, FUDONG · 2015 to 2019
$1.7M
Epigenetic regulation of myocardial ischemia/reperfusion injury by X chromosomeR01HL131182 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARNOLD, ARTHUR P, EGHBALI, MANSOUREH · 2016 to 2019
$1.5M
NHLBI NIH HHS R01 HL131182NIDDK NIH HHS U54 DK120342NIH HHS NS093042NIH HHS NS108779NINDS NIH HHS R01 NS093042NINDS NIH HHS R01 NS108779
6 · The paper itself

Abstract

backgroundStroke is a sexually dimorphic disease. Previous studies have found that young females are protected against ischemia compared to males, partially due to the protective effect of ovarian hormones, particularly estrogen (E

methodsTo identify the X escapee genes involved in stroke, we performed RNA-seq in flow-sorted microglia from aged male and female wild type (WT) mice subjected to middle cerebral artery occlusion (MCAO). The expression of these genes (kdm5c/kdm6a) were confirmed in four core genotypes (FCG) mice and in post-mortem human stroke brains by immunohistochemistry (IHC), Western blot, and RT-PCR. Chromatin immunoprecipitation (ChIP) assays were conducted to detect DNA levels of inflammatory interferon regulatory factor (IRF) 4/5 precipitated by histone H3K4 and H3K27 antibodies. Manipulation of kdm5c/kdm6a expression with siRNA or lentivirus was performed in microglial culture, to determine downstream pathways and examine the regulatory roles in inflammatory cytokine production.

resultsKdm5c and kdm6a mRNA levels were significantly higher in aged WT female vs. male microglia, and the sex difference also existed in ischemic brains from FCG mice and human stroke patients. The ChIP assay showed the IRF 4/5 had higher binding levels to demethylated H3K4 or H3K27, respectively, in female vs. male ischemic microglia. Knockdown or over expression of kdm5c/kdm6a with siRNA or lentivirus altered the methylation of H3K4 or H3K27 at the IRF4/5 genes, which in turn, impacted the production of inflammatory cytokines.

conclusionsThe KDM-Histone-IRF pathways are suggested to mediate sex differences in cerebral ischemia. Epigenetic modification of stroke-related genes constitutes an important mechanism underlying the ischemic sexual dimorphism.

Indexed as

Sex CharacteristicsAgedAged, 80 and overAnimalsChromatin ImmunoprecipitationCytokinesEpigenesis, GeneticFemaleGenotypeHistone DemethylasesHumansInflammationIschemic StrokeMaleMiceMiddle AgedCytokinesHistone DemethylasesKdm5c protein, mouseRNA, Small InterferingUtx protein, mouseHistone demethylationInflammationIRFKDM5CKDM6AMicrogliaStroke

Identifiers

PMID33712031
PMCPMC7953638
OpenAlexW3134421517

What OpenQuestion holds

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LicenceCC BY
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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.