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Abstract 13112: Theranostic Properties of Porphysome Nanoparticles in Atherosclerotic Cardiovascular Disease

2022· article· en· W4380795153 on OpenAlexaff
Victoria Nankivell, Achini K. Vidanapathirana, Maneesha A. Rajora, Peter J. Psaltis, Joanne T. M. Tan, William Tieu, Gang Zheng, Christina A. Bursill

Bibliographic record

VenueCirculation · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer, Lipids, and Metabolism
Canadian institutionsUniversity Health Network
Fundersnot available
KeywordsMedicineIn vivoScavenger receptorEx vivoInflammationLipopolysaccharideMannose receptorMacrophageIn vitroPathologyCholesterolInternal medicineLipoproteinChemistryBiochemistryBiology

Abstract

fetched live from OpenAlex

Introduction: ‘Porphysome’ nanoparticles contain porphyrin-lipid which permits fluorescent imaging and can be radiolabelled for positron emission tomography (PET) imaging. The outer shell contains the R4F peptide that interacts with scavenger receptor SR-B1, enabling macrophage targeting and therapeutic effects. Aim: To investigate anti-atherosclerotic and imaging properties of porphysomes. Methods: In vitro, porphysome or PBS-treated macrophages were assessed for uptake (fluorescence microscopy), [ 3 H]-cholesterol efflux and inflammatory responses following lipopolysaccharide stimulation (qRT-PCR/ELISA). In vivo, high-fat diet (HFD) fed apolipoprotein ( Apo)e -/- mice were infused for 8 weeks with porphysomes (3x/week, 40mg/kg) or PBS. 64 Cu-porphysomes were detected by fluorescence (IVIS)/PET imaging. Aortas were digested for flow cytometry. Results: In vitro , porphysomes were internalised by macrophages and increased cholesterol efflux (80%, P <0.05), compared to PBS controls. Porphysomes reduced macrophage mRNA levels of inflammatory factors Il-1β (88%), Il-18 (54%) and Ccl5 (75%), and protein secretion of IL-1β (69%) and CCL5 (82%), P <0.05. Porphysomes suppressed inflammasome components Rela (38%), Nlrp3 (69%) and Asc (36%), P <0.05. In Apoe -/- mice, porphysomes were detected in aortic sinus plaque by fluorescence, co-localised with CD68 + macrophages, and by IVIS in aortic arch plaque, with higher fluorescence intensity in HFD (55%) than chow-fed mice. PET imaging found porphysomes localised in hearts. Porphysome uptake was higher in aortic macrophages than endothelial (9-fold) or smooth muscle (4.5-fold) cells ( P <0.05). Porphysome-treated mice had less aortic macrophages (49%) of the M2-like phenotype (60%), than PBS controls. Conclusions: Porphysomes exhibit multi-modal imaging capabilities for identifying plaque and have athero-protective properties, demonstrating theranostic potential for atherosclerosis.

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 score0.002
Threshold uncertainty score0.008

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 integrity0.0000.000
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 head0.019
GPT teacher head0.209
Teacher spread0.190 · 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".

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Citations2
Published2022
Admission routes1
Has abstractyes

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