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Record W3130287505 · doi:10.1038/s41598-021-84063-6

Dj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophages

2021· article· en· W3130287505 on OpenAlexafffund
Tharini Sivasubramaniyam, Jiaqi Yang, Henry S. Cheng, Alexandra Zyla, Angela Li, Rickvinder Besla, Idit Dotan, Xavier S. Revelo, Sally Yu Shi, Helen Le, Stephanie A. Schroer, David W. Dodington, Yoo Jin Park, Min Jeong Kim, Daniella Febbraro, Isabelle L. Ruel, Jacques Genest, Raymond H. Kim, Tak W. Mak, Daniel A. Winer, Clinton S. Robbins, Minna Woo

Bibliographic record

VenueScientific Reports · 2021
Typearticle
Languageen
FieldImmunology and Microbiology
TopicAtherosclerosis and Cardiovascular Diseases
Canadian institutionsDiscovery CentreSinai Health SystemMcGill University Health CentreRoyal Victoria Regional Health CentreRoyal Victoria HospitalToronto General HospitalUniversity of TorontoUniversity Health Network
FundersCanadian Liver FoundationCanadian Institutes of Health ResearchNovo NordiskDiabetes CanadaBanting and Best Diabetes Centre, University of TorontoHeart and Stroke Foundation of Canada
KeywordsInflammationMedicineImmunology

Abstract

fetched live from OpenAlex

Abstract Inflammation is a key contributor to atherosclerosis with macrophages playing a pivotal role through the induction of oxidative stress and cytokine/chemokine secretion. DJ1, an anti-oxidant protein, has shown to paradoxically protect against chronic and acute inflammation. However, the role of DJ1 in atherosclerosis remains elusive. To assess the role ofDj1in atherogenesis, we generated whole-bodyDj1-deficient atherosclerosis-proneApoenull mice (Dj1−/−Apoe−/−). After 21 weeks of atherogenic diet,Dj1−/−Apoe−/−mice were protected against atherosclerosis with significantly reduced plaque macrophage content. To assess whether haematopoietic or parenchymalDj1contributed to atheroprotection inDj1-deficient mice, we performed bone-marrow (BM) transplantation and show thatDj1-deficient BM contributed to their attenuation in atherosclerosis. To assess cell-autonomous role of macrophageDj1in atheroprotection, BM-derived macrophages fromDj1-deficient mice andDj1-silenced macrophages were assessed in response to oxidized low-density lipoprotein (oxLDL). In both cases, there was an enhanced anti-inflammatory response which may have contributed to atheroprotection inDj1-deficient mice. There was also an increased trend of plasma DJ-1 levels from individuals with ischemic heart disease compared to those without. Our findings indicate an atheropromoting role ofDj1and suggests that targetingDj1may provide a novel therapeutic avenue for atherosclerosis treatment or prevention.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.204
Teacher spread0.196 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations6
Published2021
Admission routes2
Has abstractyes

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