This 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.
A 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.
In 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.
These 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.
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.
Wang D, Ruan X, Liu X, et al. SUMOylation of PUM2 promotes the vasculogenic mimicry of glioma cells via regulating CEBPD. Clin Transl Med. 2020;10(5):e168. doi:10.1002/ctm2.168
[Description of error]
In Figure 2g, the image of the U251 control group was inadvertently taken from an earlier draft version rather than the finalised version. Consequently, the control group image may appear to display a slightly higher apparent cell density compared with the sh-NC group, which could lead to a minor visual misinterpretation.
After carefully re-examining all original data, we confirmed that this mistake was due to the incorrect selection of a representative image for the control group. Therefore, this correction does not alter the results, statistical analyses, or conclusions of the paper.
The corrected version of Figure 2g is provided below. We sincerely apologise for this oversight and for any confusion it may have caused.
Acute respiratory distress syndrome (ARDS) frequently develops after cardiopulmonary bypass (CPB), with lung ischemia/reperfusion injury (LIRI) as a major contributing factor. However, the role of fatty acid-binding protein 4 (FABP4) in the pathogenesis of CPB-associated ARDS remains poorly understood.
Experimental LIRI models were established in vivo and in vitro to investigate the role of FABP4 in alveolar epithelial injury. Lipid droplets (LDs) accumulation, fatty acid (FA) metabolism, epithelial-mesenchymal transition (EMT), and alveolar epithelial barrier (AEB) integrity were assessed using molecular, cellular, and functional approaches. Pharmacological and genetic interventions were applied to evaluate the contribution of FABP4-mediated signaling pathways.
LIRI induced autocrine FABP4 signaling in alveolar epithelial cells, leading to pronounced LDs accumulation and disruption of AEB integrity. FABP4 activation enhanced FA metabolism and promoted EMT, which played a critical role in epithelial barrier dysfunction. Mechanistically, FABP4 activated the p38 MAPK pathway, resulting in ULK1 phosphorylation, suppression of lipophagy, and subsequent LDs formation, thereby driving EMT. Inhibition of LDs accumulation effectively attenuated EMT and alleviated AEB disruption.
FABP4 serves as a key metabolic regulator linking lipid reprogramming to EMT and alveolar epithelial barrier disruption during LIRI. Targeting FABP4-mediated lipid metabolism may represent a promising therapeutic strategy for preventing ARDS following CPB.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：