Project description:Compared to whole serum miRNAs, miRNAs in serum small extracellular vesicles (sEVs) are well protected form RNA enzymes, thus provide a consistent source of miRNA for disease biomarker detection. Serum sEVs and their miRNA cargos released by injured liver cells could be promising biomarkers for diagnosis of liver diseases. We were very interested to find out the effects of liver injury on serum extracellular vesicles as well as the small RNA components they transported, if there is any difference between acute and chronic injury. Study in this regard will help us to identify new serum biomarkers for liver injury, and to find out if there are specific markers for acute or chronic liver injury. To identify potential biomarker for liver injury based on serum sEVs miRNAs, we established the carbon tetrachloride (CCL4) induced acute and chronic liver injury mice model, and examined the dynamic changes of small RNA components, especially miRNAs, in serum sEVs.
Project description:The key exosomal miRNAs in adaptive response to drug-induced liver (DILI) and liver regeneration were investigated and proved. This study aimed to decipher the mechanism of restorative events in the adaptive response to DILI by investigating circulating exosomal miRNAs. Using toosendanin-induced liver injury model, exosomal miR-106b-5p was identified as a robust driver in the adaptive response of TILI.
Project description:To explore how tumor-derived exosomes activate fibroblasts and foster lung metastasis of liver cancer. MiRNAs encapsulated in exosomes are abundant and play an important role in cell-cell communication. Therefore, we hypothesized that tumor-derived exosomal miRNAs mediate fibroblasts activation. To identify the specific miRNAs involved, we conducted microarrays to generate miRNAs profiles of exosomes derived from the four liver cancer cell lines with different migration and invasion abilities. CSQT-2 and HCC-LM3 cells were high metastatic cancer cells, versus to HepG2 and MHCC-97L cells. We divided them into the following groups: CSQT-2 versus HepG2 (with different origins), HCC-LM3 versus MHCC-97L (with the same origin) and compared the up-regulated miRNAs in both two high-metastatic cancer cells-derived exosomes. Then, these up-regulated miRNAs were subjected to validation to define the most important exosomal miRNAs in regulating fibroblast activation and contributing to lung metastasis of liver cancer.
Project description:Age-related bone degeneration is driven by structural deterioration, chronic inflammation, and impaired regenerative capacity, leading to an increased incidence of osteoarticular disorders. Mesenchymal stromal/stem cells (MSCs) have emerged as promising therapeutic candidates due to their immunomodulatory and regenerative properties, mediated largely through their secretome and extracellular vesicles (EVs). However, the therapeutic efficacy of MSC-derived products depends on both the cell source and the conditioning stimuli to which MSCs are exposed. In this study, we performed a comparative proteomic and exosomal microRNA (miRNA) profiling of secretomes derived from placenta-derived MSCs (PSCs) and adipose-derived MSCs (ASCs), and assessed the impact of priming strategies, including hypoxia, interferon-gamma (IFNγ), and interleukin-1 beta (IL1β), on paracrine properties of these cells. Proteomic analysis identified over 7,000 proteins, with PSC secretome enriched in pathways related to osteogenesis, chondrogenesis, extracellular matrix organization, angiogenesis, and immune regulation, whereas ASC secretome displayed limited enrichment in these processes. Functional scoring highlighted IL1β priming as the most effective strategy to enhance osteochondral and immunomodulatory protein signatures in PSCs. Differently, IFNγ priming selectively expanded the repertoire of exosomal miRNAs, with enrichment in signaling networks including Wnt/β-catenin, TGF-β, NF-κB, and T cell receptor pathways, underscoring its role in fine-tuning immune and regenerative functions. Together, these findings reveal that PSCs secrete a broader and more functionally relevant spectrum of bioactive molecules for osteoarticular applications compared with ASCs. Moreover, distinct priming strategies can differentially modulate their paracrine outputs. IL1β primarily enhances protein-driven regenerative and immunomodulatory activity, whereas IFNγ promotes a functionally enriched exosomal miRNA cargo. These results support PSC-derived secretomes as versatile candidates for next-generation, cell-free therapies in osteoarticular disease.
Project description:Acute myeloid leukemia (AML) cells release abundant exosomal miR-7977 that transfer into bone marrow (BM) mesenchymal stromal cells (MSCs). We have shown that exosomal miR-7977 was highly released from AML cells and was transferred into BM MSCs. It has been well known that a microRNA has multiple targets. In fact, miRDB predicted 633 targets. Based on these findings, control and miR-7977mimic were transferred into BM MSCs. Subsequently, alteration of transcriptome was analyzed to gain insight into the role of miR-7977 in bone marrow micro environment.
Project description:Circulating proteomic panels for diagnosis and risk stratification of acute-on-chronic liver failure in patients with viral hepatitis B
Project description:The role of exosomal miRNAs involved in the pathogenesis and development of pancreatic injury caused by obstructive sleep apnea (OSA) remains unclear. Here, miRNA sequencing (miRNA-seq) was used to investigate the expression profile of exosomal miRNAs in pancreatic tissue in a mouse model of chronic intermittent hypoxia (CIH) -induced pancreatic injury. A total of 55 newly predicted miRNAs and 277 existing miRNAs were identified in pancreatic tissue exosomes from the mouse model of chronic intermittent hypoxic-induced pancreatic injury. 3 up-regulated and 33 down-regulated miRNAs with differential expression were identified. 8 exosome-derived miRNAs were selected to construct CNC networks to predict target genes. Some targets and pathways were elucidated by GO analysis and KEGG analysis. Our work first comprehensively studied the expression profile of exosome-derived miRNA in pancreatic tissue of mouse models of OSA-induced pancreatic injury, bringing fresh perspectives on managing pancreatic injury brought on by OSA.
