Evidence map›Paper›PMID 41601959›Full record

ArticleFrontiers in pharmacology2025

Development of an

William A Murphy, Sarina Kyburz, Henry Ho, Matthew Shane Loop, John K Fallon, Jacqueline B Tiley, Thomas Kralj, Kim L R Brouwer

Abstract read
In one paragraph

Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

William A MurphyDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Sarina KyburzDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Henry HoDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Matthew Shane LoopDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
John K FallonDivision of Pharmacoengineering and Molecular Pharmaceutics, and Center for Nanotechnology in Drug Delivery, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Jacqueline B TileyDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Thomas KraljPharmaron Lab Services Inc., Germantown, MD, United States.
Kim L R BrouwerDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

Funding

Mechanisms of Altered Hepatic Transport: Impact on Drug TherapyR35GM122576 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KIM L.R. BROUWER · 2017 to 2026
$5.7M
Shared LC-MS/MS for Quantitative Targeted ProteomicsS10OD032350 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FALLON, JOHN KEVIN · 2023 to 2023
$600k
NIGMS NIH HHS R35 GM122576NIH HHS S10 OD032350
6 · The paper itself

Abstract

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is estimated to affect ∼30% of adults globally. The progressive form of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), is a leading cause of chronic liver disease. MASH is marked by hepatocellular fat accumulation (steatosis), ballooning, and inflammation. Although many Methods: Lipid-cytokine treatments were first optimized using differentiated HuH-7 cells based on cellular toxicity and their ability to induce a MASH-like phenotype. Three final treatments-all including TNF-α (1 ng/mL) and IL-6 (1.2 ng/mL)-were selected for SCHH evaluation: (1) oleic acid (OA):palmitic acid (PA) (1:2, 0.5 mM), (2) a lipid mix (lysophospholipids mixture + OA:PA), and (3) lipid mix + 0.01 mM cholesterol. Treatments were incubated for 72 h with SCHH from three donors. Quantitative targeted absolute proteomics (QTAP) assessed the transporter and DME concentrations, whereas B-CLEAR Results: All three treatments significantly increased lipid droplet formation and peroxidation in SCHH with minimal toxicity. These treatments also altered DME and transporter concentrations in a manner similar to the changes observed in liver tissue from patients with MASH. Across treatments, concentrations of the bile salt export pump (BSEP), sodium taurocholate co-transporting polypeptide (NTCP), organic anion transporting polypeptide (OATP) 1B1, OATP1B3, and multidrug resistance-associated protein (MRP) 2 were reduced by 0.66-0.57-fold, 0.71-0.52-fold, 0.74-0.63-fold, 0.82-0.80-fold, and 0.71-0.48-fold, respectively. Correspondingly, the TCA apparent uptake clearance and biliary clearance were reduced by 0.70-0.26-fold and 0.61-0.27-fold, respectively. E Discussion: These findings demonstrate that lipid-cytokine treatments induce MASH-like changes in SCHH, including clinically relevant reductions in DME and transporter concentrations and function. This model may serve as a valuable tool for predicting altered hepatobiliary drug disposition in MASH.

Indexed as

fatty liver disease modelhepatobiliary transportintracellular lipid droplet formationlipid–cytokine treatmentslysophospholipidsMASHquantitative targeted absolute proteomics (QTAP)sandwich-cultured human hepatocytes (SCHH)

Identifiers

PMID41601959
PMCPMC12832903

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.