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mPGES-1 as a novel target for arthritis

2004· review· en· W2088665109 on OpenAlexaff
Hassan Fahmi

Bibliographic record

VenueCurrent Opinion in Rheumatology · 2004
Typereview
Languageen
FieldMedicine
TopicInflammatory mediators and NSAID effects
Canadian institutionsCentre Hospitalier de l’Université de MontréalHôpital Notre-DameUniversité de Montréal
Fundersnot available
KeywordsArthritisProinflammatory cytokinePathogenesisMedicineInflammatory arthritisProstaglandin E2InflammationTumor necrosis factor alphaCyclooxygenaseImmunologyIn vivoTranscription factorEnzymeEndocrinologyBiologyGeneBiochemistryGenetics

Abstract

fetched live from OpenAlex

PURPOSE OF REVIEW: Prostaglandin E2 (PGE2) is by far the major prostanoid synthesized in the joint and plays an important role in inflammation and pathogenesis of arthritis. Moreover, increased levels of PGE2 have been detected in serum and synovial fluids from arthritic patients. Little was known about the enzyme(s) involved in the isomerization of PGH2 into PGE2 synthesis until recent identification of PGE synthase (PGES). Several isoforms were characterized, among which microsomal PGES-1 (mPGES-1) has received much attention, because this enzyme is inducible and functionally linked with cyclooxygenase-2. This review focuses on recent findings regarding the regulation of mPGES-1 expression and the possible role of this enzyme in arthritis. RECENT FINDINGS: Various in vitro and in vivo studies demonstrated that proinflammatory stimuli, such as interleukin-1beta and tumor necrosis factor-alpha upregulate the expression of mPGES-1 at the protein and mRNA level. Promoter analysis indicates that the transcription factor Egr-1 is involved in the positive regulation of mPGES-1. Studies from mPGES-1-deficient mice and animal models of inflammatory arthritis strongly suggest a role of mPGES-1 in the production of PGE2 and the pathogenesis of arthritis. SUMMARY: This article reviews the regulation of mPGES-1 expression and provides evidence for a role of mPGES-1 in inducible PGE2 production and arthritis. Future studies using selective inhibitors of mPGES-1 activity or expression would clarify the role of this enzyme in arthritis.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.797
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0030.001
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)0.0000.000

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 head0.082
GPT teacher head0.413
Teacher spread0.331 · 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 teacher head, not a consensus.

Study designNot applicable
Domainnot available
GenreReview

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

Citations75
Published2004
Admission routes1
Has abstractyes

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