J Nanobiotechnology. 2026 May 22. doi: 10.1186/s12951-026-04565-1. Online ahead of print.

ABSTRACT

BACKGROUND: Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) are a promising treatment for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), but traditional delivery methods have limitations. Therefore, this study presents a noninvasive therapeutic approach for ALI/ARDS, offering new mechanistic insights and identifying potential therapeutic targets.

RESULTS: We established a nebulized LPS-induced ALI model that was characterized by diffuse lung injury and high homogeneity. Following inhalation, hUCMSC-Exos were observed to be internalized by pulmonary microvascular endothelial cells. Analysis revealed that hUCMSC-Exos alleviated ALI by reducing the severity of histological damage, pulmonary oedema, lung inflammation and ferroptosis. Additionally, hUCMSC-Exos improved the mitochondrial function of human pulmonary microvascular endothelial cells (HPMECs) via the transfer of mitochondrial components. Subsequent proteomic sequencing of mitochondria isolated from HPMECs receiving different treatments revealed the significant differential expression of ribosomal proteins among the groups. The most significantly upregulated protein, RPS11, was identified as a key mediator; its knockdown blocked the ability of hUCMSC-Exos to suppress ferroptosis and restore mitochondrial function in HPMECs. Mechanistically, hUCMSC-Exos exert their effects by enhancing mitochondria-encoded protein translation.

CONCLUSIONS: We report a mechanism whereby hUCMSC-Exos upregulate RPS11 to promote mitochondria-encoded protein translation, rescuing mitochondrial function, inhibiting ferroptosis in HPMECs, and ultimately alleviating ALI. Validated across multiple models and supported by multi-omics analyses, our findings collectively establish nebulized hUCMSC-Exos as a promising cell-free therapy targeting mitochondrial homeostasis in HPMECs for the treatment of ALI.

PMID:42174606 | DOI:10.1186/s12951-026-04565-1

Chem Biol Drug Des. 2026 Apr;107(4):e70297. doi: 10.1111/cbdd.70297.

ABSTRACT

This study identifies fat mass and obesity-associated protein (FTO) as a pivotal link between metabolic predisposition and pathogenesis associated with Staphylococcus aureus in chronic rhinosinusitis (CRS). These findings were established through the application of an integrative multi-omics framework. We demonstrate that S. aureus upregulates FTO, which functions as an m⁶A demethylase to stabilize the Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1). This molecular axis suppresses GSK-3β and promotes β-catenin nuclear translocation, thereby driving epithelial-mesenchymal transition (EMT) and pathological mucosal remodeling. By mapping the FTO-MALAT1-GSK-3β/β-catenin signaling network, this research elucidates how metabolic susceptibility facilitates infection-triggered epithelial reprogramming. These findings establish FTO as a promising biomarker and potential therapeutic target, providing a systemic foundation for personalized CRS treatment strategies.

PMID:41973807 | DOI:10.1111/cbdd.70297