Evidence map›Paper›PMID 23974919›Full record

ArticleDiabetes2013

Gestational diabetes mellitus impairs Nrf2-mediated adaptive antioxidant defenses and redox signaling in fetal endothelial cells in utero.

Xinghua Cheng, Sarah J Chapple, Bijal Patel, William Puszyk, David Sugden, Xiaoke Yin, Manuel Mayr, Richard C M Siow, Giovanni E Mann

Open access · hybridAbstract read
In one paragraph

Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
11.9field-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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.

  1. Glycogen synthase kinase (GSK) 3 in pregnancy and parturition: a systematic review of literature.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2020
    Pooled it
  2. Ferroptosis-Mediated Placental Dysfunction in the Pathophysiology of Gestational Diabetes Mellitus.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Article
  3. Dynamics of the Mammalian Placental Metabolome in Placentogenesis and Embryonic Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  10. Status of Oxidative Stress during Low-Risk Labour: Preliminary Data.International journal of environmental research and public health · 2022
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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

9 authors at 2 institutions in 1 country.

Xinghua ChengCardiovascular Division, British Heart Foundation Centre of Research Excellence, King's College London, London, U.K.
Sarah J Chapple
Bijal Patel
William Puszyk
David Sugden
Xiaoke Yin
Manuel Mayr
Richard C M Siow
Giovanni E Mann
British Heart Foundation · GBKing's College London · GB

Funding

British Heart Foundation FS/10/59/28533British Heart Foundation FS/13/2/29892British Heart Foundation PG/13/1/29801
6 · The paper itself

Abstract

In utero exposure to gestational diabetes mellitus (GDM) is associated with an increased risk of type 2 diabetes and cardiovascular disease in later life, yet the underlying mechanisms remain to be elucidated. We examined the effects of GDM on the proteome, redox status, and nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant gene expression in human fetal endothelial cells. Proteomic analysis revealed that proteins involved in redox homeostasis were significantly altered in GDM and associated with increased mitochondrial superoxide generation, protein oxidation, DNA damage, and diminished glutathione (GSH) synthesis. In GDM cells, the lipid peroxidation product 4-hydroxynonenal (HNE) failed to induce nuclear Nrf2 accumulation and mRNA and/or protein expression of Nrf2 and its target genes NAD(P)H:quinone oxidoreductase 1 (NQO1), Bach1, cystine/glutamate transporter, and glutamate cysteine ligase. Although methylation of CpG islands in Nrf2 or NQO1 promoters was unaltered by GDM, decreased DJ-1 and increased phosphorylated glycogen synthase kinase 3β levels may account for impaired Nrf2 signaling. HNE-induced increases in GSH and NQO1 levels were abrogated by Nrf2 small interfering RNA in normal cells, and overexpression of Nrf2 in GDM cells partially restored NQO1 induction. Dysregulation of Nrf2 in fetal endothelium may contribute to the increased risk of type 2 diabetes and cardiovascular disease in offspring.

Indexed as

AdultAntioxidantsDiabetes, GestationalFemaleGlutathioneHumansHuman Umbilical Vein Endothelial CellsNF-E2-Related Factor 2Oxidation-ReductionPregnancyReactive Oxygen SpeciesSignal TransductionUp-RegulationAntioxidantsGlutathioneNFE2L2 protein, humanNF-E2-Related Factor 2Reactive Oxygen Species

Identifiers

PMID23974919
PMCPMC3837032
OpenAlexW2153706510

What OpenQuestion 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 OpenQuestion graph.