Evidence map›Paper›PMID 38607090›Full record

ArticleCells2024

Antagonizing Activin A/p15

Sowmya Mekala, Ravi Rai, Samantha Loretta Reed, Bill Bowen, George K Michalopoulos, Joseph Locker, Reben Raeman, Michael Oertel

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, 2024. 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
0.7field-weighted citation impact, top 31% of its field
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, 2 citations in OpenAlex.

  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 at 1 institution in 1 country.

Sowmya MekalaDepartment of Pathology, Division of Experimental Pathology, University of Pittsburgh, 200 Lothrop Street-BST S-404, Pittsburgh, PA 15261, USA.
Ravi RaiDepartment of Pathology, Division of Experimental Pathology, University of Pittsburgh, 200 Lothrop Street-BST S-404, Pittsburgh, PA 15261, USA.ORCID 0000-0003-2550-3811
Samantha Loretta ReedDepartment of Pathology, Division of Experimental Pathology, University of Pittsburgh, 200 Lothrop Street-BST S-404, Pittsburgh, PA 15261, USA.
Bill BowenDepartment of Pathology, Division of Experimental Pathology, University of Pittsburgh, 200 Lothrop Street-BST S-404, Pittsburgh, PA 15261, USA.
George K MichalopoulosDepartment of Pathology, Division of Experimental Pathology, University of Pittsburgh, 200 Lothrop Street-BST S-404, Pittsburgh, PA 15261, USA.
Joseph LockerDepartment of Pathology, Division of Experimental Pathology, University of Pittsburgh, 200 Lothrop Street-BST S-404, Pittsburgh, PA 15261, USA.
Reben RaemanDepartment of Pathology, Division of Experimental Pathology, University of Pittsburgh, 200 Lothrop Street-BST S-404, Pittsburgh, PA 15261, USA.
Michael OertelDepartment of Pathology, Division of Experimental Pathology, University of Pittsburgh, 200 Lothrop Street-BST S-404, Pittsburgh, PA 15261, USA.
University of Pittsburgh · US

Funding

Pittsburgh Liver Research CenterP30DK120531 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DAVID A GELLER · 2019 to 2026
$10.9M
Blocking hepatocyte senescence as a novel therapeutic strategy for chronic liver diseasesR01DK130949 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI OERTEL, MICHAEL, RAEMAN, REBEN · 2021 to 2024
$2.4M
NIDDK NIH HHS P30 DK120531NIDDK NIH HHS R01 DK130949NIH HHS P30 DK120531NIH HHS R01 DK130949
6 · The paper itself

Abstract

BACKGROUND/

aimActivin A is involved in the pathogenesis of human liver diseases, but its therapeutic targeting is not fully explored. Here, we tested the effect of novel, highly specific small-molecule-based activin A antagonists (NUCC-474/555) in improving liver regeneration following partial hepatectomy and halting fibrosis progression in models of chronic liver diseases (CLDs).

methodsCell toxicity of antagonists was determined in rat hepatocytes and Huh-7 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Hepatocytes and hepatic stellate cells (HSCs) were treated with activin A and NUCC-555 and analyzed by reverse transcription-polymerase chain reaction and immunohistochemistry. Partial hepatectomized Fisher (F)344 rats were treated with NUCC-555, and bromodeoxyuridine (BrdU) incorporation was determined at 18/24/36/120/240 h. NUCC-555 was administered into thioacetamide- or carbon tetrachloride-treated F344 rats or C57BL/6 mice, and the fibrosis progression was studied.

resultsNUCC-474 showed higher cytotoxicity in cultured hepatic cells; therefore, NUCC-555 was used in subsequent studies. Activin A-stimulated overexpression of cell cycle-/senescence-related genes (e.g.,

conclusionsOur studies demonstrate that activin A antagonist NUCC-555 promotes liver regeneration and halts fibrosis progression in CLD models, suggesting that blocking activin A signaling may represent a new approach to treating people with CLD.

Indexed as

ActivinsLiver DiseasesSignal TransductionAnimalsBromodeoxyuridineFibrosisHumansMiceMice, Inbred C57BLRatsRats, Inbred F344activin AActivinsBromodeoxyuridineactivin antagonistcell cycle arrestliver fibrosisliver regenerationsenescence

Identifiers

PMID38607090
PMCPMC11011318
OpenAlexW4394566101

What OpenQuestion 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 OpenQuestion graph.