Evidence mapPaperPMID 34140262Full record

ArticleRedox biology2021

Molecular processes mediating hyperhomocysteinemia-induced metabolic reprogramming, redox regulation and growth inhibition in endothelial cells.

Michael Jan, Ramon Cueto, Xiaohua Jiang, Liu Lu, Jason Sardy, Xinyu Xiong, Justine E Yu, Hung Pham, Mohsin Khan, Xuebing Qin and 3 more

Open access · goldAbstract read
In one paragraph

Article in Redox biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
5.4field-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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Piezo1 disrupts blood-brain barrier via CaMKII/Nrf2 in ischemic stroke.Cellular and molecular life sciences : CMLS · 2025
    Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. The interplay of hydrogen sulfide and microRNAs in cardiovascular diseases: insights and future perspectives.Mammalian genome : official journal of the International Mammalian Genome Society · 2024
    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.

Michael JanCenter for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United States; Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, United States.
Ramon CuetoCenter for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United States.
Xiaohua JiangCenter for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United States.
Liu LuCenter for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United States.
Jason SardyCenter for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United States.
Xinyu XiongCenter for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United States.
Justine E YuCenter for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United States.
Hung PhamCenter for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United States.
Mohsin KhanCenter for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United States.
Xuebing QinTulane National Primate Research Center, School of Medicine, Tulane University, Covington, LA, United States.
Yong JiKey Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China.
Xiao-Feng YangCenter for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United States; Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA, United States.
Hong WangCenter for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United States; Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA, United States. Electronic address: hongw@temple.edu.
Temple University · USNanjing Medical University · CNOtsuka (United States) · USTulane University · US

Funding

Tulane National Primate Research CenterP51OD011104 · TULANE UNIVERSITY OF LOUISIANA · 2025 to 2025
$9.3M
NIH HHS P51 OD011104
6 · The paper itself

Abstract

Hyperhomocysteinemia (HHcy) is an established and potent independent risk factor for degenerative diseases, including cardiovascular disease (CVD), Alzheimer disease, type II diabetes mellitus, and chronic kidney disease. HHcy has been shown to inhibit proliferation and promote inflammatory responses in endothelial cells (EC), and impair endothelial function, a hallmark for vascular injury. However, metabolic processes and molecular mechanisms mediating HHcy-induced endothelial injury remains to be elucidated. This study examined the effects of HHcy on the expression of microRNA (miRNA) and mRNA in human aortic EC treated with a pathophysiologically relevant concentration of homocysteine (Hcy 500 μM). We performed a set of extensive bioinformatics analyses to identify HHcy-altered metabolic and molecular processes. The global functional implications and molecular network were determined by Gene Set Enrichment Analysis (GSEA) followed by Cytoscape analysis. We identified 244 significantly differentially expressed (SDE) mRNA, their relevant functional pathways, and 45 SDE miRNA. HHcy-altered SDE inversely correlated miRNA-mRNA pairs (45 induced/14 reduced mRNA) were discovered and applied to network construction using an experimentally verified database. We established a hypothetical model to describe the biochemical and molecular network with these specified miRNA/mRNA axes, finding: 1) HHcy causes metabolic reprogramming by increasing glucose uptake and oxidation, by glycogen debranching and NAD

Indexed as

Diabetes Mellitus, Type 2HyperhomocysteinemiaEndothelial CellsHomocysteineHumansOxidation-ReductionSignal TransductionHomocysteineDegradationEndothelial injuryGlobal mRNA/miRNA expressionHomocysteineInflammationMetabolic reprogrammingProliferationRedox signaling

Identifiers

PMID34140262
PMCPMC8282538
OpenAlexW3165176909

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.