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Record W4412391795 · doi:10.1016/j.jcjd.2025.06.008

Blood Characteristics of Adults With Type 2 Diabetes and Response of Their Peripheral Blood Mononuclear Cells to Inhibitors of the NLRP3 Inflammasome and Caspase-1

2025· article· en· W4412391795 on OpenAlexvenueno aff
Joyce de Paula Souza, Karine Jeanneau, Cyril Allard, Eline Angevaare, Dominik Aschenbrenner, Ursula Bodendorf, Benjamin Demarco, John Gounarides, Saskia Killmer, Jiří Kovařík, Sabina Pfister, Hong Yin, Vithushan Ratnarasa, Marianne Bo Ni-Schnetzler, Matthias Hepprich, Daniel T. Meier, Grazyna Wieczorek, Marc Y. Donath

Bibliographic record

VenueCanadian Journal of Diabetes · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammasome and immune disorders
Canadian institutionsnot available
FundersNovartis PharmaUniversitätsspital ZürichNovartis Institutes for BioMedical ResearchUniversität BaselStaatssekretariat für Bildung, Forschung und InnovationSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungNovartis
KeywordsInflammasomePeripheral blood mononuclear cellMedicineImmunologyInflammationImmune systemType 2 diabetesInnate immune systemNEFAEx vivoDiabetes mellitusSystemic inflammationInternal medicineIn vivoEndocrinologyBiologyInsulinIn vitro

Abstract

fetched live from OpenAlex

OBJECTIVES: Obesity and aging are associated with increased activity of the innate immune system. This chronic systemic inflammation contributes to the development of type 2 diabetes and long-term complications and is partly driven by the activation of the NLRP3 inflammasome. METHODS: We conducted a comparative analysis of clinical parameters, nonesterified fatty acid(s) (NEFA) profiles, immune cell subsets, and inflammatory responses of peripheral blood mononuclear cells (PBMCs) obtained from both healthy individuals and those diagnosed with type 2 diabetes. RESULTS: Plasma NEFA profiling revealed a dysregulation in patients with type 2 diabetes, indicating potential modulation of immune cell responses by lipids, along with leukocytosis, elevated serum levels of inflammatory cytokines, the inflammasome-related protein apoptosis-associated speck-like protein with a caspase recruitment domain, interleukin (IL)-1 receptor antagonist, and IL-18 binding protein. Surprisingly, functional assessments demonstrated comparable NLRP3 inflammasome activity in PBMCs from both groups, suggesting that systemic inflammation in type 2 diabetes is driven by elevated leukocyte numbers or resident tissue macrophages. Treatment of PBMCs with NLRP3 and caspase-1 inhibitors attenuated the release of pro-inflammatory cytokines ex vivo. CONCLUSIONS: Inhibition of inflammasome activation has emerged as a promising therapeutic strategy for management of diabetes-related complications.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.002
GPT teacher head0.162
Teacher spread0.160 · 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 designObservational
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

Citations2
Published2025
Admission routes1
Has abstractyes

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