Synovial inflammation is a pivotal factor in the pathogenesis of osteoarthritis (OA). Platelet-rich plasma-derived Exosomes (PRP-Exos), known for their low immunogenicity, have demonstrated efficacy in modulating chondrocyte function. However, the specific effects and mechanisms of PRP-Exos in synovial inflammation remain unclear. This study aimed to investigate the therapeutic effects and mechanisms of PRP-Exos in synovial inflammation induced by destabilization of the medial meniscus (DMM) in mice.
PRP-Exos were extracted via ultracentrifugation. In vivo experiments revealed that PRP-Exos alleviated pain behaviors and synovial inflammation in DMM mice. Furthermore, it was discovered that PRP-Exos enhanced the synovial lymphatic function in DMM mice and promoted lymphangiogenesis. Meanwhile, the therapeutic effect of PRP-Exos on synovial inflammation was attenuated after inhibition of lymphatic function. In vitro studies demonstrated that PRP-Exos enhanced the proliferation, migration, and tube formation ability of lymphatic endothelial cells (LECs), via regulating the PI3K/Akt signaling pathway.
This research is the first to reveal that PRP-Exos alleviate pain behaviors and synovial inflammation in DMM mice through activation of the PI3K/Akt signaling pathway in LECs, thereby enhancing synovial lymphatic function and promoting the clearance of inflammatory cells and associated cytokines. These findings offer a novel theoretical foundation for the treatment of synovial inflammation and other inflammation-associated disorders.
© 2025. The Author(s).

Triple-negative breast cancer (TNBC) is the subtype of advanced breast cancer with the shortest survival time and the poorest prognosis, and treatment options are relatively limited. Exosomes, small extracellular vesicles enriched with bioactive molecules, are critical mediators of intercellular communication and have been implicated in cancer progression. The aim of this study was to investigate the molecular mechanism of exosomes promoting the proliferation and migration of TNBC.
In this study, exosomes were identified by Flow cytometry and transmission electron microscopy, and RNA sequencing (RNA-seq) was used to identify differentially expressed genes and downstream regulatory molecules in exosomes. RNA-seq results were supported by bioinformatics analysis and Western blot analysis. Functional assays including in vivo tumor formation, Colony formation Assay, Scratch migration and transwell assays were performed to study exosomes related phenomena and mechanism.
Serum-derived exosomes from patients with TNBC can induce TNBC progression in vitro and in vivo. lncRNA SNHG4 was most significantly up-regulated in exosomes, and overexpression of lncRNA SNHG4 significantly promoted the proliferation and migration of TNBC cells. In addition, lncRNA SNHG4 promotes TNBC cell proliferation and migration by upregulating the expression of Exportin 5(XPO5). Silencing XPO5 can effectively attenuate the tumor-promoting effect of serum exosomes in TNBC patients. Mechanistically, lncRNA SNHG4 acts through XPO5-mediated pathways. Silencing XPO5 can effectively inhibit the tumor-promoting effect mediated by lncRNA SNHG4.
Taken together, our study revealed that the exosome lncRNA SNHG4 exerts its oncogenic role by activating XPO5-mediated pathways, thereby regulating TNBC cell proliferation and migration. This can be considered as a potential target for TNBC molecular therapy.
Copyright © 2025 Wang, Yang, Guo, Li, Zhong, Jiang, Li, Yang, Zhou, Wang, Liao and Mao.

Mesenchymal stromal cells (MSCs) possess strong immunomodulatory properties, making them attractive candidates for regenerative medicine and immune-related therapies. Pre-activation, or licensing, of MSCs with cytokines such as interferon-gamma (IFN-γ) and transforming growth factor-beta 1 (TGF-β1) has been shown to enhance their immunosuppressive efficacy. Recent attention has turned to extracellular vesicles (EVs) released by licensed MSCs as a cell-free therapeutic alternative.
Small EVs were isolated from MSCs licensed with a combination of IFN-γ and TGF-β1. These EVs were characterized according to standardized criteria. Their immunomodulatory effects were assessed in vitro using two human immune models: a THP-1-derived macrophage polarization system and a peripheral blood mononuclear cell (PBMC) co-culture assay. Pro/anti-inflammatory molecules secretion, T cell proliferation, and regulatory T cell induction were quantified. Dimensionality reduction using t-distributed stochastic neighbor embedding (t-SNE) was applied to multiparametric flow cytometry data for immune profiling. In addition, publicly available transcriptomic datasets (GSE122091 and GSE46019) were analyzed to identify differentially expressed genes (DEGs) in IFN-γ- and TGF-β1-licensed MSCs, providing insight into potential molecular drivers of EV-mediated immunoregulation.
Licensed EVs significantly inhibited pro-inflammatory THP-1 macrophage activation and promoted an anti-inflammatory phenotype, with reduced secretion of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), increased IL-10 production, and decreased nitric oxide (NO) levels.. Compared to EVs from non-licensed MSCs, licensed EVs induced a greater proportion of regulatory T cells and exhibited enhanced suppression of allogeneic T cell proliferation. t-SNE analysis revealed a distinct immunoregulatory signature induced by licensed EVs, characterized by the emergence of a non-proliferative lymphocyte subset with elevated co-expression of CD4, CD25, and FOXP3. Transcriptomic analysis further revealed seven overlapping DEGs between IFN-γ- and TGF-β1-licensed MSCs, including both upregulated (GPR68, LIMK2, LIPG) and downregulated (EFNA5, PRKG1, DCLK1, TRIM2) genes, several of which are functionally implicated in EV-mediated immune regulation.
Small EVs derived from IFN-γ and TGF-β1-licensed MSCs exhibit demonstrate dose-dependent immunomodulatory trends in vitro, with enhanced effects observed at higher concentrations.. These findings suggest their potential utility in modulating both innate and adaptive immune responses, warranting further investigation for their application as a cell-free therapeutic strategy in immune-mediated conditions.
© 2025. The Author(s).

Metabolic reprogramming fuels cancer cell metastasis and remodels the immunosuppressive tumor microenvironment (TME). We report here that circPETH, a circular RNA (circRNA) transported via extracellular vesicles (EVs) from tumor-associated macrophages (TAMs) to hepatocellular carcinoma (HCC) cells, facilitates glycolysis and metastasis in recipient HCC cells. Mechanistically, circPETH-147aa, encoded by circPETH in an m6A-driven manner, promotes PKM2-catalyzed ALDOA-S36 phosphorylation via the MEG pocket. Furthermore, circPETH-147aa impairs anti-HCC immunity by increasing HuR-dependent SLC43A2 mRNA stability and driving methionine and leucine deficiency in cytotoxic CD8+ T cells. Importantly, through virtual and experimental screening, we find that a small molecule, Norathyriol, is an effective inhibitor that targets the MEG pocket on the circPETH-147aa surface. Norathyriol reverses circPETH-147aa-facilitated acquisition of metabolic and metastatic phenotypes by HCC cells, increases anti-PD1 efficacy, and enhances cytotoxic CD8+ T-cell function. Here we show that Norathyriol is a promising anti-HCC agent that contributes to attenuating the resistance of advanced HCC to immune checkpoint blocker (ICB) therapies.
© 2025. The Author(s).

To corroborate the efficacy of Jintiange capsules (JTGs) in the treatment of osteoarthritis (OA) by exploring the potential mechanism of action of synovial mesenchymal stem cell exosomes (SMSC-Exos) and articular chondrocytes (ACs) through transcriptome sequencing (RNA-seq).
Type II collagenase was used to induce OA in rats. The efficacy of JTGs was confirmed by macroscopic observation of articular cartilage, micro-CT observation, and safranin fast green staining. After SMSC-Exos and ACs were qualified, RNA-seq was used to screen differentially expressed miRNAs and mRNAs. The target genes of differentially expressed miRNAs in Synovial mesenchymal stem cells (SMSCs) were predicted based on the multiMiR R package. The co-differentially expressed genes of SMSC-Exos and ACs were obtained by venny 2.1.0. The miRNA-mRNA regulatory network was constructed by Cytoscape software. Based on the OmicShare platform, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed on the mRNA regulated by key miRNAs. Expression trend analysis was performed for co-differentially expressed genes. Correlation analysis was performed on micro-CT efficacy indicators, co-differentially expressed genes mRNA and miRNA.
The efficacy of each administration group of JTGs was significant compared with the model group. SMSC-Exos and ACs were identified by their characteristics. The expression of rno-miR-23a-3p, rno-miR-342-3p, rno-miR-146b-5p, rno-miR-501-3p, rno-miR-214-3p was down-regulated in OA pathological state, and the expression of rno-miR-222-3p, rno-miR-30e-3p, rno-miR-676, and rno-miR-192-5p expression was up-regulated, and the expression of all these miRNAs was reversed after the intervention with JTGs containing serum. The co-differentially expressed genes were enriched in the interleukin 17 signaling pathway, tumor necrosis factor signaling pathway, transforming growth factor-β signaling pathway, etc. The expression trends of Ccl7, Akap12, Grem2, Egln3, Arhgdib, Ccl20, Mmp12, Pla2g2a, and Nr4a1 were significant. There was a correlation between micro-CT pharmacodynamic index, mRNA, and miRNA.
JTGs can improve the degeneration of joint cartilage and achieve the purpose of cartilage protection, which can be used for the treatment of OA. SMSCs-related miRNA expression profiles were significantly altered after the intervention with JTGs containing serum. The 9 co-differentially expressed genes may be the key targets for the efficacy of JTGs in the treatment of OA rats, which can be used for subsequent validation.