Evidence map›Paper›PMID 38435523›Full record

ArticleACS central science2024

Integrating Phenotypic and Chemoproteomic Approaches to Identify Covalent Targets of Dietary Electrophiles in Platelets.

Ivy A Guan, Joanna S T Liu, Renata C Sawyer, Xiang Li, Wanting Jiao, Yannasittha Jiramongkol, Mark D White, Lejla Hagimola, Freda H Passam, Denise P Tran and 5 more

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

Article in ACS central science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 33% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. 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

15 authors at 3 institutions in 3 countries.

Ivy A GuanSchool of Chemistry, Faculty of Science, The University of Sydney, Sydney, New South Wales 2006, Australia.
Joanna S T LiuThe Heart Research Institute, The University of Sydney, Newtown, New South Wales 2042, Australia.
Renata C SawyerSchool of Chemistry, Faculty of Science, The University of Sydney, Sydney, New South Wales 2006, Australia.
Xiang LiDepartment of Medicine, Washington University in St. Louis, St. Louis, Missouri 63110, United States.
Wanting JiaoFerrier Research Institute, Victoria University of Wellington, Wellington 6140, New Zealand.ORCID https://orcid.org/0000-0002-0234-7206
Yannasittha JiramongkolSchool of Chemistry, Faculty of Science, The University of Sydney, Sydney, New South Wales 2006, Australia.
Mark D WhiteSchool of Chemistry, Faculty of Science, The University of Sydney, Sydney, New South Wales 2006, Australia.
Lejla HagimolaSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales 2006, Australia.
Freda H PassamSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales 2006, Australia.
Denise P TranSydney Mass Spectrometry, The University of Sydney, Camperdown, New South Wales 2006, Australia.ORCID https://orcid.org/0000-0002-4445-5600
Xiaoming LiuSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales 2006, Australia.
Simone M SchoenwaelderThe Heart Research Institute, The University of Sydney, Newtown, New South Wales 2042, Australia.
Shaun P JacksonThe Heart Research Institute, The University of Sydney, Newtown, New South Wales 2042, Australia.
Richard J PayneSchool of Chemistry, Faculty of Science, The University of Sydney, Sydney, New South Wales 2006, Australia.ORCID https://orcid.org/0000-0002-3618-9226
Xuyu LiuSchool of Chemistry, Faculty of Science, The University of Sydney, Sydney, New South Wales 2006, Australia.ORCID https://orcid.org/0000-0003-4096-3090
The University of Sydney · AUJames S. McDonnell Foundation · USVictoria University of Wellington · NZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A large variety of dietary phytochemicals has been shown to improve thrombosis and stroke outcomes in preclinical studies. Many of these compounds feature electrophilic functionalities that potentially undergo covalent addition to the sulfhydryl side chain of cysteine residues within proteins. However, the impact of such covalent modifications on the platelet activity and function remains unclear. This study explores the irreversible engagement of 23 electrophilic phytochemicals with platelets, unveiling the unique antiplatelet selectivity of sulforaphane (SFN). SFN impairs platelet responses to adenosine diphosphate (ADP) and a thromboxane A2 receptor agonist while not affecting thrombin and collagen-related peptide activation. It also substantially reduces platelet thrombus formation under arterial flow conditions. Using an alkyne-integrated probe, protein disulfide isomerase A6 (PDIA6) was identified as a rapid kinetic responder to SFN. Mechanistic profiling studies revealed SFN's nuanced modulation of PDIA6 activity and substrate specificity. In an electrolytic injury model of thrombosis, SFN enhanced the thrombolytic activity of recombinant tissue plasminogen activator (rtPA) without increasing blood loss. Our results serve as a catalyst for further investigations into the preventive and therapeutic mechanisms of dietary antiplatelets, aiming to enhance the clot-busting power of rtPA, currently the only approved therapeutic for stroke recanalization that has significant limitations.

Identifiers

PMID38435523
PMCPMC10906253
OpenAlexW4391323151

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.