ArticleClinical and translational medicine2026
Melatonin-engineered MSCs-exosomes deliver USP4 to stabilise ARNTL and inhibit clock rhythmic ferroptosis for enhanced flap survival.
Article in Clinical and translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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.
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.
Who cites it
3 citing papers in PubMed.
- Unveiling the miR‑26a‑5p/MSMO1/7‑DHC Axis: A Novel Therapeutic Target in Myocardial Ischemia-Reperfusion Injury.Cardiovascular drugs and therapy · 2026Article
- Exosomes derived from bone marrow mesenchymal stem cells alleviate sepsis-induced ARDS via inhibition of HOXA9-mediated glycolysis in alveolar macrophages.Respiratory research · 2026Article
- Melatonin-engineered MSCs-exosomes deliver USP4 to stabilise ARNTL and inhibit clock rhythmic ferroptosis for enhanced flap survival.Clinical and translational medicine · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
backgroundThis study investigates the impact of sleep restriction (SR) on flap viability and its underlying mechanisms. It reveals that SR triggers clock rhythmic ferroptosis, which leads to impaired skin barrier function and increased flap necrosis.
methodsA retrospective analysis of sleep quality in 344 patients undergoing flap surgery proved that SR is a risk factor for flap necrosis. Further research demonstrated that SR increases the level of ferroptosis, disrupts the circadian rhythm of ferroptosis and exacerbates flap damage in human and murine models.
resultsIn order to address this clinical issue, the use of melatonin (MT)-preconditioned bone marrow mesenchymal stromal cells-derived exosomes (MEXOs) was found to enhance the therapeutic efficacy of flap repair by mitigating clock rhythmic ferroptosis. Mechanistically, MT increased m6A modification to stabilise and enhance the translation of ubiquitin-specific protease 4 (USP4) mRNA within MEXOs. USP4 delivered by MEXOs directly interacted with and deubiquitinated ARNTL, a core circadian regulator, stabilising its protein levels and suppressing ferroptosis in flap.
conclusionsThese findings identify SR-induced clock rhythmic ferroptosis as a critical pathological driver of flap failure and propose a novel exosome-based strategy targeting the USP4-ARNTL axis to enhance skin barrier integrity and flap survival, offering translational potential for clinical reconstructive surgery. KEY POINTS: This study identifies SR-induced clock rhythmic ferroptosis as a pivotal pathological process in flap necrosis. We reveal a potential therapeutic mechanism in which USP4-enriched MEXOs can effectively repair SR-induced flap necrosis. USP4-enriched MEXOs represent a novel therapy for SR-induced flap necrosis by stabilizing ARNTL to inhibit clock rhythmic ferroptosis.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.