Renal unilateral ischemia-reperfusion injury(UIRI)constitutes a significant global health challenge,with poor recovery leading to chronic kidney disease and subsequent renal fibrosis.Extracellular vesicles(EVs)present...Renal unilateral ischemia-reperfusion injury(UIRI)constitutes a significant global health challenge,with poor recovery leading to chronic kidney disease and subsequent renal fibrosis.Extracellular vesicles(EVs)present substantial potential benefits for renal diseases.However,the limited yield and efficacy of EVs produced through traditional methodologies(2D-EVs)severely restrict their widespread application.Moreover,the efficient and effective strategies for using EVs in UIRI treatment and their mechanisms remain largely unexplored.In this study,we propose an innovative approach by integrating bioprinted mesenchymal stem cell microfiber extracellular vesicles production technology(3D-EVs)with a tail vein injection method,introducing a novel treatment strategy for UIRI.Our comparison of the biological functions of 2D-EVs and 3D-EVs,both in vitro and in vivo,reveals that 3D-EVs significantly outperform 2D-EVs.Specifically,in vitro,3D-EVs demonstrate a superior capacity to enhance the proliferation and migration of NRK-52E cells and mitigate hypoxia/reoxygenation(H/R)-induced injuries by reducing epithelial-mesenchymal transformation,extracellular matrix deposition,and ferroptosis.In vivo,3D-EVs exhibit enhanced therapeutic effects,as evidenced by improved renal function and decreased collagen deposition in UIRI mouse kidneys.We further elucidate the mechanism by which 3D-EVs derived from KLF15 ameliorate UIRI-induced tubular epithelial cells(TECs)ferroptosis through the modulation of SLC7A11 and GPX4 expression.Our findings suggest that bioprinted mesenchymal stem cells microfiberderived EVs significantly ameliorate renal UIRI,opening new avenues for effective and efficient EV-based therapies in UIRI treatment.展开更多
The authors regret that two images in Fig.3A were originally misplaced by a careless mistake.The corrected versions of these images are provided below.These corrections do not alter any findings and conclusions report...The authors regret that two images in Fig.3A were originally misplaced by a careless mistake.The corrected versions of these images are provided below.These corrections do not alter any findings and conclusions reported in this article.No additional text corrections are needed in the article.The authors would like to apologise for any inconvenience caused.展开更多
Copy number variations(CNVs), which can affect the role of long non-coding RNAs(lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between l...Copy number variations(CNVs), which can affect the role of long non-coding RNAs(lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer(BLCA). Messenger RNA(mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis(WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely NR2 F1-AS1, LINC01138, THUMPD3-AS1, LOC101928489, and TMEM147-AS1, and a risk-score signature related to overall survival in BLCA was identified. Moreover, validated results in another independent Gene Expression Omnibus(GEO) dataset, GSE31684, were consistent with these results. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis revealed that the mitogen-activated protein kinase(MAPK) signaling pathway, focal adhesion pathway, and Janus kinase-signal transducers and activators of transcription(JAK-STAT) signaling pathway were enriched in a high-risk score pattern, suggesting that imbalance in these pathways is closely related to tumor development. We revealed the prognosis-related lncRNAs by analyzing the expression profiles of lncRNAs and CNVs, which can be used as prognostic biomarkers for BLCA.展开更多
基金supported by the Natural Science Foundation of China(Grant No.52075285)the Natural Science Foundation of Guang Dong Province(2019A1515010386,2024A1515010266).
文摘Renal unilateral ischemia-reperfusion injury(UIRI)constitutes a significant global health challenge,with poor recovery leading to chronic kidney disease and subsequent renal fibrosis.Extracellular vesicles(EVs)present substantial potential benefits for renal diseases.However,the limited yield and efficacy of EVs produced through traditional methodologies(2D-EVs)severely restrict their widespread application.Moreover,the efficient and effective strategies for using EVs in UIRI treatment and their mechanisms remain largely unexplored.In this study,we propose an innovative approach by integrating bioprinted mesenchymal stem cell microfiber extracellular vesicles production technology(3D-EVs)with a tail vein injection method,introducing a novel treatment strategy for UIRI.Our comparison of the biological functions of 2D-EVs and 3D-EVs,both in vitro and in vivo,reveals that 3D-EVs significantly outperform 2D-EVs.Specifically,in vitro,3D-EVs demonstrate a superior capacity to enhance the proliferation and migration of NRK-52E cells and mitigate hypoxia/reoxygenation(H/R)-induced injuries by reducing epithelial-mesenchymal transformation,extracellular matrix deposition,and ferroptosis.In vivo,3D-EVs exhibit enhanced therapeutic effects,as evidenced by improved renal function and decreased collagen deposition in UIRI mouse kidneys.We further elucidate the mechanism by which 3D-EVs derived from KLF15 ameliorate UIRI-induced tubular epithelial cells(TECs)ferroptosis through the modulation of SLC7A11 and GPX4 expression.Our findings suggest that bioprinted mesenchymal stem cells microfiberderived EVs significantly ameliorate renal UIRI,opening new avenues for effective and efficient EV-based therapies in UIRI treatment.
文摘The authors regret that two images in Fig.3A were originally misplaced by a careless mistake.The corrected versions of these images are provided below.These corrections do not alter any findings and conclusions reported in this article.No additional text corrections are needed in the article.The authors would like to apologise for any inconvenience caused.
基金supported by the Natural Science Foundation of Guangdong Province (No. 2017A030313898)the Guangzhou Science and Technology Plan Projects (No. 201707010113), China。
文摘Copy number variations(CNVs), which can affect the role of long non-coding RNAs(lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer(BLCA). Messenger RNA(mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis(WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely NR2 F1-AS1, LINC01138, THUMPD3-AS1, LOC101928489, and TMEM147-AS1, and a risk-score signature related to overall survival in BLCA was identified. Moreover, validated results in another independent Gene Expression Omnibus(GEO) dataset, GSE31684, were consistent with these results. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis revealed that the mitogen-activated protein kinase(MAPK) signaling pathway, focal adhesion pathway, and Janus kinase-signal transducers and activators of transcription(JAK-STAT) signaling pathway were enriched in a high-risk score pattern, suggesting that imbalance in these pathways is closely related to tumor development. We revealed the prognosis-related lncRNAs by analyzing the expression profiles of lncRNAs and CNVs, which can be used as prognostic biomarkers for BLCA.
