Evidence mapPaperPMID 39890799Full record

ArticleCell death & disease2025

Estrogen-dependent activation of TRX2 reverses oxidative stress and metabolic dysfunction associated with steatotic disease.

Alfredo Smiriglia, Nicla Lorito, Marina Bacci, Angela Subbiani, Francesca Bonechi, Giuseppina Comito, Marta Anna Kowalik, Andrea Perra, Andrea Morandi

Abstract read
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. Protective effects ofRedox report : communications in free radical research · 2026
    Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
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

9 authors.

Alfredo SmirigliaDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Nicla LoritoDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Marina BacciDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Angela SubbianiDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Francesca BonechiDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Giuseppina ComitoDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Marta Anna KowalikDepartment of Biomedical Sciences, University of Cagliari, 09042, Monserrato, Italy.
Andrea PerraDepartment of Biomedical Sciences, University of Cagliari, 09042, Monserrato, Italy.ORCID http://orcid.org/0000-0002-8098-899X
Andrea MorandiDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy. andrea.morandi@unifi.it.ORCID http://orcid.org/0000-0002-9222-5332

Funding

Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) IG22941Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research) 2022RCFZZ3
6 · The paper itself

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of hepatic disorders, ranging from simple steatosis to steatohepatitis, with the most severe outcomes including cirrhosis, liver failure, and hepatocellular carcinoma. Notably, MASLD prevalence is lower in premenopausal women than in men, suggesting a potential protective role of estrogens in mitigating disease onset and progression. In this study, we utilized preclinical in vitro models-immortalized cell lines and hepatocyte-like cells derived from human embryonic stem cells-exposed to clinically relevant steatotic-inducing agents. These exposures led to lipid droplet (LD) accumulation, increased reactive oxygen species (ROS) levels, and mitochondrial dysfunction, along with decreased expression of markers associated with hepatocyte functionality and differentiation. Estrogen treatment in steatotic-induced liver cells resulted in reduced ROS levels and LD content while preserving mitochondrial integrity, mediated by the upregulation of mitochondrial thioredoxin 2 (TRX2), an antioxidant system regulated by the estrogen receptor. Furthermore, disruption of TRX2, either pharmacologically using auranofin or through genetic interference, was sufficient to counteract the protective effects of estrogens, highlighting a potential mechanism through which estrogens may prevent or slow MASLD progression.

Indexed as

EstrogensFatty LiverOxidative StressThioredoxinsFemaleHepatocytesHumansLipid DropletsMitochondriaReactive Oxygen SpeciesReceptors, EstrogenEstrogensReactive Oxygen SpeciesReceptors, EstrogenThioredoxins

Identifiers

PMID39890799
PMCPMC11785963

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.