Evidence map›Paper›PMID 34510484›Full record

ArticleHepatology (Baltimore, Md.)2022

Aging exaggerates acute-on-chronic alcohol-induced liver injury in mice and humans by inhibiting neutrophilic sirtuin 1-C/EBPα-miRNA-223 axis.

Ruixue Ren, Yong He, Dong Ding, Aoyuan Cui, Huarui Bao, Jing Ma, Xin Hou, Yu Li, Dechun Feng, Xiaoling Li and 3 more

Open access · greenAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
7.1field-weighted citation impact, top 2% 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, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
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  5. Review
  6. Article
  7. Review
  8. Article
  9. [Histone deacetylases and alcohol-related liver disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
    Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Non-coding RNAs in alcohol-associated liver disease.Liver research (Beijing, China) · 2025
    Review
  18. Article
  19. Article
  20. 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.

Ruixue RenDepartment of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
Yong HeLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Dong DingCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Aoyuan CuiCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Huarui BaoDepartment of Emergency, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
Jing MaLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Xin HouLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Yu LiCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0001-6910-5933
Dechun FengLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Xiaoling LiSignal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Suthat LiangpunsakulDivision of Gastroenterology and Hepatology, Department of Medicine, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Bin GaoLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Hua WangDepartment of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.ORCID 0000-0002-2605-5697
National Institutes of Health · USShanghai Institute of Nutrition and Health · CNAnhui Medical University · CNRichard L. Roudebush VA Medical Center · US

Funding

Sirtuins and nuclear receptors in aging and age-associated diseasesZIAES102205 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI LI, XIAOLING · 2009 to 2025
$42.4M
Pathogenesis and Novel Therapeutic Targets of Steatotic Liver Disease and CancerZIAAA000369 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI GAO, BIN · 2009 to 2025
$23.4M
Molecular mechanisms of liver injury, repair, and immunityZIAAA000368 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI GAO, BIN · 2009 to 2023
$16.1M
Intramural NIH HHS Z99 AA999999Intramural NIH HHS ZIA AA000369
6 · The paper itself

Abstract

BACKGROUND AND

aimsAging exacerbates liver neutrophil infiltration and alcohol-associated liver disease (ALD) in mice and humans, but the underlying mechanisms remain obscure. This study aimed to examine the effect of aging and alcohol consumption on neutrophilic Sirtuin 1 (SIRT1) and microRNA-223 (miR-223), and their contribution to ALD pathogeneses. APPROACH AND

resultsYoung and aged myeloid-specific Sirt1 knockout mice were subjected to chronic-plus-binge ethanol feeding. Blood samples from healthy controls and patients with chronic alcohol drinking who presented with acute intoxication were analyzed. Neutrophilic Sirt1 and miR-223 expression were down-regulated in aged mice compared with young mice. Deletion of the Sirt1 gene in myeloid cells including neutrophils exacerbated chronic-plus-binge ethanol-induced liver injury and inflammation and down-regulated neutrophilic miR-223 expression. Immunoprecipitation experiments revealed that SIRT1 promoted C/EBPα deacetylation by directly interacting with C/EBPα, a key transcription factor that controls miR-223 biogenesis, and subsequently elevated miR-223 expression in neutrophils. Importantly, down-regulation of SIRT1 and miR-223 expression was also observed in circulating neutrophils from middle-aged and elderly subjects compared with those from young individuals. Chronic alcohol users with acute intoxication had a reduction in neutrophilic SIRT1 expression in young and middle-aged patients, with a greater reduction in the latter group. The neutrophilic SIRT1 expression correlated with neutrophilic miR-223 and serum alanine transaminase levels in those patients.

conclusionsAging increases the susceptibility of alcohol-induced liver injury in mice and humans through the down-regulation of the neutrophilic SIRT1-C/EBPα-miR-223 axis, which could be a therapeutic target for the prevention and/or treatment of ALD.

Indexed as

LiverLiver Diseases, AlcoholicMicroRNAsAge FactorsAgingAlcohol DrinkingAnimalsChemical and Drug Induced Liver Injury, ChronicDown-RegulationGene Expression RegulationHumansMiceMice, KnockoutMyeloid CellsNeutrophil InfiltrationSirtuin 1MicroRNAsMIR223, humanMIRN223 microRNA, mouseSIRT1 protein, humanSirt1 protein, mouseSirtuin 1

Identifiers

PMID34510484
PMCPMC8844214
OpenAlexW3199037729

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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.