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Record W4415525558 · doi:10.1126/sciadv.adx3794

The designer cytokine IC7Fc attenuates atherosclerosis development by targeting hyperlipidemia in mice

2025· article· en· W4415525558 on OpenAlexaff
Wietse In het Panhuis, E Thiemann, Daisy Maria Alberta Hendrika van Dijk, Bibian Been, Kelsey E. Jarrett, Amber Meurs, Sander Kooijman, Milaine V. Hovingh, Melanie Modder, Bram W. van Os, Thijs J. Sluiter, Niek Blomberg, Amanda C. M. Pronk, Salwa Afkir, Trea C.M. Streefland, Reshma A. Lalai, Maria Taveras, Sen Zhang, Timothy E. Adams, Lauren V. Terry, Sarah M. Turpin-Nolan, Margreet R. de Vries, Martin Giera, Stefan Rose‐John, Noam Zelcer, Jan Freark de Boer, Thomas Q. de Aguiar Vallim, Mark A. Febbraio, Patrick C.N. Rensen, Milena Schönke

Bibliographic record

VenueScience Advances · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPeroxisome Proliferator-Activated Receptors
Canadian institutionsInstitute of Infection and Immunity
FundersNovo NordiskNederlandse Organisatie voor Wetenschappelijk OnderzoekUniversiteit Leiden
KeywordsHyperlipidemiaCytokineApolipoprotein BInflammationLipoproteinCholesterolLipogenesisReceptor

Abstract

fetched live from OpenAlex

The chimeric cytokine IC7Fc conveys the metabolic signaling properties of the glycoprotein 130 receptor cytokines interleukin-6 and ciliary neurotrophic factor via membrane-bound signaling. IC7Fc was previously shown to slow the progression of type 2 diabetes mellitus, and here, we demonstrate its effect on atherosclerotic development. In APOE*3-Leiden.CETP mice, an atherosclerosis-prone model with a humanized lipoprotein metabolism, IC7Fc markedly lowered plasma triglyceride and total cholesterol levels. This was mechanistically explained by an inhibition of de novo lipogenesis in the liver, increased synthesis of bile acids from cholesterol, and down-regulated apolipoprotein B synthesis, which resulted in decreased cholesterol secretion in very low-density lipoprotein particles. As a consequence, IC7Fc treatment considerably reduced atherosclerotic lesion formation and vascular inflammation compared with current antihyperlipidemic therapy. In conclusion, IC7Fc is a promising pharmacological treatment for cardiometabolic diseases targeting hyperlipidemia and inflammation.

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 score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
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 head0.007
GPT teacher head0.259
Teacher spread0.253 · 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

Citations1
Published2025
Admission routes1
Has abstractyes

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