Evidence map›Paper›PMID 26244639›Full record

ArticlePloS one2015

Modification of β-Defensin-2 by Dicarbonyls Methylglyoxal and Glyoxal Inhibits Antibacterial and Chemotactic Function In Vitro.

Janna G Kiselar, Xiaowei Wang, George R Dubyak, Caroline El Sanadi, Santosh K Ghosh, Kathleen Lundberg, Wesley M Williams

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 19% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
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  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. COVID-19 and type 1 diabetes: dealing with the difficult duo.International journal of diabetes in developing countries · 2020
    Review
  13. Potential Benefits and Harms of Novel Antidiabetic Drugs During COVID-19 Crisis.International journal of environmental research and public health · 2020
    Article
  14. Review
  15. COVID's Razor: RAS Imbalance, the Common Denominator Across Disparate, Unexpected Aspects of COVID-19.Diabetes, metabolic syndrome and obesity : targets and therapy · 2020
    Review
  16. SAGE open medicine · 2019
    Article
  17. Diabetic foot infection: A critical complication.International wound journal · 2018
    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

7 authors at 1 institution in 1 country.

Janna G KiselarCenter for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, Ohio, United States of America.
Xiaowei WangDepartment of Periodontics, Case Western Reserve University, Cleveland, Ohio, United States of America.
George R DubyakDepartment of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, United States of America.
Caroline El SanadiDepartment of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, United States of America.
Santosh K GhoshDepartment of Biological Sciences, Case Western Reserve University, Cleveland, Ohio, United States of America.
Kathleen LundbergCenter for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, Ohio, United States of America.
Wesley M WilliamsDepartment of Biological Sciences, Case Western Reserve University, Cleveland, Ohio, United States of America.
Case Western Reserve University · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
TRANSMEMBRANE SIGNALLING IN SMOOTH MUSCLE CELL LINESR01GM036387 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI DUBYAK, GEORGE R · 1987 to 2014
$4.5M
NCATS NIH HHS UL1 TR000439NIGMS NIH HHS R01 GM036387
6 · The paper itself

Abstract

backgroundBeta-defensins (hBDs) provide antimicrobial and chemotactic defense against bacterial, viral and fungal infections. Human β-defensin-2 (hBD-2) acts against gram-negative bacteria and chemoattracts immature dendritic cells, thus regulating innate and adaptive immunity. Immunosuppression due to hyperglycemia underlies chronic infection in Type 2 diabetes. Hyperglycemia also elevates production of dicarbonyls methylgloxal (MGO) and glyoxal (GO).

methodsThe effect of dicarbonyl on defensin peptide structure was tested by exposing recombinant hBD-2 (rhBD-2) to MGO or GO with subsequent analysis by MALDI-TOF MS and LC/MS/MS. Antimicrobial function of untreated rhBD-2 vs. rhBD-2 exposed to dicarbonyl against strains of both gram-negative and gram-positive bacteria in culture was determined by radial diffusion assay. The effect of dicarbonyl on rhBD-2 chemotactic function was determined by chemotaxis assay in CEM-SS cells.

resultsMGO or GO in vitro irreversibly adducts to the rhBD-2 peptide, and significantly reduces antimicrobial and chemotactic functions. Adducts derive from two arginine residues, Arg22 and Arg23 near the C-terminus, and the N-terminal glycine (Gly1). We show by radial diffusion testing on gram-negative E. coli and P. aeruginosa, and gram-positive S. aureus, and a chemotaxis assay for CEM-SS cells, that antimicrobial activity and chemotactic function of rhBD-2 are significantly reduced by MGO.

conclusionsDicarbonyl modification of cationic antimicrobial peptides represents a potential link between hyperglycemia and the clinical manifestation of increased susceptibility to infection, protracted wound healing, and chronic inflammation in undiagnosed and uncontrolled Type 2 diabetes.

Indexed as

Adaptive ImmunityAnti-Bacterial AgentsBacteriaBacterial Infectionsbeta-DefensinsGlyoxalHumansImmunity, InnateMethylationRecombinant ProteinsSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationAnti-Bacterial Agentsbeta-DefensinsDEFB4A protein, humanGlyoxalRecombinant Proteins

Identifiers

PMID26244639
PMCPMC4526640
OpenAlexW1855568823

What OpenQuestion holds

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LicenceCC BY
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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.