ArticleJournal of translational medicine2020
Suppression of p66Shc prevents hyperandrogenism-induced ovarian oxidative stress and fibrosis.
Article in Journal of translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
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Who cites it
44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Oxidative stress gene expression, DNA methylation, and gut microbiota interaction trigger Crohn's disease: a multi-omics Mendelian randomization study.BMC medicine · 2023Pooled it
- Resveratrol and Markers of Polycystic Ovary Syndrome: a Systematic Review of Animal and Clinical Studies.Reproductive sciences (Thousand Oaks, Calif.) · 2022Pooled it
- Disulfidptosis in PCOS pathogenesis: Multi-omics identification of LRPPRC as a diagnostic biomarker and therapeutic target.iScience · 2026Article
- Oxidative homeostasis and survival instincts of chicken egg, embryo and adult.Poultry science · 2026Review
- Atractylenolide III improves ovarian dysfunction and endometrial receptivity in a PCOS rat model by regulating Cybb-mediated oxidative stress.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Aberrant DNMTs Promote TXNIP Upregulation and Ovarian Fibrosis in PCOS.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Identification of A p300-SP1-BRD4 Transcriptional Axis as a Key Driver of AR Hyperactivation in Polycystic Ovarian Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Oxidative stress and the therapeutic potential of dietary antioxidants in polycystic ovary syndrome: a narrative review.Journal of ovarian research · 2026Review
- Inflammatory bowel disease leads to long-term ovarian dysfunction via immune-mediated follicular aging.Cellular and molecular life sciences : CMLS · 2026Article
- Sleep deprivation impairs follicular development attributable to granulosa cell pyroptosis mediated by S100A8/A9-driven macrophage M1 polarization.Science advances · 2026Article
- Acetylation reader BRD4-driven TXNIP transcription enhances NLRP3 inflammasome activation in PCOS.Cellular and molecular life sciences : CMLS · 2025Article
- Decreased Sirtuin1 Protein and Aromatase Activity Index in Follicular Fluid is Correlated with Increased Germinal Vesicle Count in Polycystic Ovary Syndrome.Chonnam medical journal · 2025Article
- New Perspectives on the Use of Resveratrol in the Treatment of Metabolic and Estrogen-Dependent Conditions Through Hormonal Modulation and Anti-Inflammatory Effects.Current issues in molecular biology · 2025Review
- Hyperandrogenism-mediated YAP activation drives ovarian inflammation and pyroptosis in PCOS: implications for follicular dysfunction.Journal of ovarian research · 2025Article
- Sirtuins and their role in ovarian aging-related fibrosis predisposing to ovarian cancer.npj aging · 2025Review
- Extracellular matrix dysregulation in PCOS: pathogenesis, therapeutic strategies, and innovative technologies.Journal of biological engineering · 2025Review
- The Role of p66Shc in Cancer: Molecular Mechanisms and Therapeutic Implications.Journal of cellular and molecular medicine · 2025Review
- The potential of low-intensity pulsed ultrasound to apply the long-term ovary protection from injury induced by 4-vinylcyclohexene diepoxide through inhibiting granulosa cell apoptosis.Bioengineering & translational medicine · 2025Article
- LncPrep + 96kb inhibits ovarian fibrosis by upregulating prolyl oligopeptidase expression.Molecular medicine reports · 2025Article
- Transcriptomic analysis of the effects exerted by curcumin on dihydrotestosterone-induced ovarian granulosa cells.Frontiers in endocrinology · 2025Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRats with hyperandrogen-induced polycystic ovary syndrome (PCOS) have been shown to develop ovarian oxidative stress (OS) and fibrosis. The Sirt1 agonist, resveratrol, can reduce OS through inhibiting p66Shc in other models of OS.
methodsWe created a rat PCOS model with increased OS levels following treatment with one of the two androgens, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT). The PCOS related features were determined by measurement of malondialdehyde (MDA) and superoxide dismutase (SOD) levels or by examining the reactive oxygen species (ROS) levels using the DCF-DA probe. The potential mechanisms by which p66Shc/Sirt1 mediates ovarian fibrosis were explored by western blotting, quantitative reverse transcription-PCR, immunofluorescence staining, and immunohistochemistry.
resultsHyperandrogen dramatically augmented OS and activation of fibrotic factors in the ovary. Our data demonstrated that treatment with resveratrol enhanced Sirt1 and decreased ovarian OS as well as inhibited phosphorylation of p66Shc both in vivo and in vitro. The treatment suppressed fibrotic factor activation and improved ovarian morphology. Lentivirus- or siRNA-mediated p66Shc knockdown resulted in a dramatic enhancement of Sirt1 expression, down-regulation of ROS and suppression of fibrotic factors in granulosa cells. Moreover, p66Shc overexpression markedly increased the expression of fibrotic factors. Additionally, silencing Sirt1 induced a dramatic increase in p66Shc and enhanced activation of fibrotic factors.
conclusionsp66Shc may be a direct target of Sirt1 for inducing ROS and thus promoting fibrosis. Further exploration of the mechanisms of p66Shc in both fibrosis and OS may provide novel therapeutic strategies that will facilitate the improvement in PCOS symptoms and reproductive functions.
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Registered trials
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.