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Record W2042496791 · doi:10.1002/bdd.682

1α,25‐dihydroxyvitamin D<sub>3</sub>triggered vitamin D receptor and farnesoid X receptor‐like effects in rat intestine and liver<i>in vivo</i>

2009· article· en· W2042496791 on OpenAlex
Edwin C.Y. Chow, Han‐Joo Maeng, Shanjun Liu, Ansar A. Khan, Geny M. M. Groothuis, K. Sandy Pang

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueBiopharmaceutics & Drug Disposition · 2009
Typearticle
Languageen
FieldMedicine
TopicDrug Transport and Resistance Mechanisms
Canadian institutionsUniversity of Toronto
FundersCanadian Institutes of Health ResearchUniversity of TorontoGovernment of Canada
KeywordsFarnesoid X receptorCalcitriol receptorInternal medicineBile acidEndocrinologyCholesterol 7 alpha-hydroxylaseSmall heterodimer partnerMultidrug resistance-associated protein 2G protein-coupled bile acid receptorSmall intestineBiologyIleumOrganic anion transporter 1Nuclear receptorChemistryVitamin D and neurologyBiochemistryTransporterATP-binding cassette transporterMedicineTranscription factor

Abstract

fetched live from OpenAlex

1alpha,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), a natural ligand of the vitamin D receptor (VDR), was found to increase the rat ileal Asbt and bile acid absorption. The effects of VDR, whose expression is low in liver, on hepatic transporters and enzymes are unknown. Protein and mRNA levels of target genes in the small intestine, colon and liver after intraperitoneal dosing of 1,25(OH)(2)D(3) (0-2.56 nmol/kg/day for 4 days) to the rat were determined by Western blotting and qPCR, respectively. The 1,25(OH)(2)D(3) treatment increased total Cyp3a protein and Cyp3a1 mRNA expressions in the proximal small intestine, and the short heterodimer partner (SHP), the fibroblast growth factor 15 (FGF15), organic solute transporter (Ostalpha and Ostbeta) mRNA and Asbt protein expressions in the ileum. About 50% higher portal bile acid concentration (65.1+/-14.9 vs 41.9+/-7.8 microm, p<0.05) and elevated expressions of the hepatic farnesoid X receptor (FXR) and SHP mRNA resulted with 1,25(OH)(2)D(3) treatment. Increased Bsep and Ostalpha mRNA expressions in liver and a>50% reduction in the Cyp7a1 protein level (p<0.05) and cholesterol metabolism in rat liver microsomes (p=0.002), likely consequences of the bile acid-FXR-SHP cascade and activation of the signaling pathway for Cyp7a1 inhibition by FGF15, were found. Increased hepatic multidrug resistance-associated protein (Mrp3) and multidrug resistance protein 1a (Mdr1a) mRNA and P-gp protein were also observed. It was concluded that the changes in hepatic transporters and enzymes in the rat were indirect, secondary effects of the liver FXR-SHP cascade due to increased intestinal absorption of bile acids and elevated levels of FGF15, events that led to the activation of FXR.

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.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
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 score0.022
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.007
GPT teacher head0.241
Teacher spread0.234 · 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