Project description:Pancreatic cancer has a dismal prognosis partly due to late diagnosis, where a reliable non-invasive diagnosis is urgently wanted. We here explored, whether serum-derived PaCa exosomes may provide a diagnostic means and microRNA may be advantageous. Exosomes were collected from the serum of 133 patients with pancreatic cancer, 22 patients with non-malignant pancreatic tumors, 25 patients with chronic pancreatitis and 20 healthy donors. Exosomes were isolated by ultracentrifugation and used qRT-PCR for miRNA quantification and miRCURY LNA microRNA Array for miRNA analysis.
Project description:This study aimed to investigate the proteomic landscape of plasma exosomes from patients diagnosed with PDAC and IPMN, compared to healthy controls (CT), in order to identify potential biomarkers with prognostic and diagnostic values. Additionally, the study aimed to understand the functional role of the exosome's proteome in pancreatic neoplasia. We isolated the plasma exosomes and analyzed its proteome by nano electrospray tandem mass spectrometry (nanoLC-MS/MS), and performed downstream statistical and bioinformatics analysis, using the Perseus (v. 6.2.2), MSigDB (v. 2023.1), STRING (v. 11.5), and NCG (v. 7.1) databases. A total of 319 differentially expressed proteins (DEPs) were identified among the exosome samples, but our analyses focused on the 135 proteins that were expressed in at least 70% of each group's samples to ensure their representative proteomes. Comparing PDAC and IPMN exosome proteomes to controls, we identified 24 and 33 differentially expressed proteins, respectively. Some of the most upregulated proteins in PDAC exosomes were CPN1, IGHV2-26, ITIH3, and CLU, while some of the most downregulated were C4BPB, APOB, CFH, and C1QB. In IPMN exosomes, KLKB1, LBP, CFB, and SERPINA1 were the most upregulated proteins while C5, APOD, C3, and C1QA were downregulated. In general, the protein-protein networks and enrichment analyses revealed interesting interaction clusters and pathways related to cancer development, such as the immune system, complement cascade, clotting-related and vesicle-mediated processes, regulation of insulin-like growth factor transport, platelet activation signaling, and G-protein signaling. Our analyses also highlighted candidate cancer drivers, including the upregulated IGLL, LBP, SERPINA1, SERPINA4, SERPING1, and the downregulated APOB, and C3, which were identified in these pathways and may have potential roles in pancreatic tumorigenesis.
Project description:827 human miRNA standard human panel Plasma derived extracellular vesicles (EV)/exosomes can serve as markers of cell damage/disease but can also have therapeutic utility depending on the nature of their cargo, such as miRNA. Currently there are challenges and lack of innovations regarding early diagnosis and therapeutic options within different aspects of management of patients suffering from chronic pancreatitis (CP). Use of exosomes as biomarkers for pancreatic health, and/or or as adjuvant therapy would make a difference in management of these patients. To explore the feasibility of this approach, we characterized the miRNA cargo of exosomes purified from CP patients, and compared it to those from healthy participants. Methods: EVs were isolated from plasma of 15 CP patients and 10 healthy controls. Nanoparticle Tracking Analysis was used to determine frequency and size while NanoString technology was used to characterize the miRNA cargo. Relevant clinical parameters were correlated with these EV/exosome characteristics. Results: ~30 miRNA species were identified to have significantly (p<0.05) different expression in exosomes from individuals with CP compared to healthy individuals; ~40 miRNA were differentially expressed in exosomes from pre-diabetic versus non-diabetic CP patients. miR-579-3p, while exhibiting significantly lower (~16-fold) expression in exosomes from CP compared to healthy individuals and lower (~24-fold) in CP narcotic users compared to the less severe CP in non-users, is actually enriched (~32-fold) within exosomes in pre-diabetic CP patients compared to non-diabetic CP patients. A unique pattern was identified in female CP patients. Conclusions: These first of a kind data support the prospect of using a bioinformatics approach to assess pancreatic health, and their therapeutic potential in CP patients.
Project description:Detailed understanding of host pathogen interaction in tuberculosis is an important avenue for identifying novel therapeutic targets. Extracellular vesicles like exosomes that are rich in protein, nucleic acids and lipids, act as messenger and may show altered composition in infection. In this case control study, we isolated exosomes from serum of 52 subjects (all male, 33 (17-70) in years) including drug naïve active tuberculosis (ATB: n=20), non-tuberculosis (NTB: n=16) and healthy subjects (n=16). Serum exosomal proteome analysis was carried out using isobaric tag for relative and absolute quantification (iTRAQ) experiments and an independent test sample sets (n=36) was used for validation. A set of 132 and 68 proteins were identified in iTRAQ-I (ATB/Healthy) and iTRAQ-II (ATB/NTB) experiments respectively. Analysis of data identified a set of 4 important proteins (KYAT3, SERPINA1, HP and APOC3) that could differentiate ATB subjects from healthy controls successfully and Western data corroborated iTRAQ findings. Identification of such a protein panel in circulating exosomes besides providing novel insights into their role in tuberculosis may prove to be useful targets to develop novel host-directed therapeutic intervention.
Project description:microRNA profiles of Exosomes from Pooled NPC Patients serum comparing Control Exosomes from Healthy donors serum Two-condition experiment, Exosomes from Pooled Healthy donors serum vs. Exosomes from Pooled NPC Patients serum. Biological replicates: 1 Exosomes from Pooled Healthy donors serum, 1 Exosomes from Pooled NPC Patients serum,
Project description:To explore expression levels of tsRNAs in serumal exosomes, 4 serum specimens were chosen from patients with metastatic breast cancer and 4 samples from healthy subjects. The exosomes were isolated and sent for tsRNA-sequencing.
Project description:In the present study, the isolated serum exosomes from healthy adults, rats and mice were comparatively characterized; the small RNA compositions were analyzed; the serum exosome miRNA profiles and exosome depleted serum miRNA profiles were obtained by small RNAseq, and the distributions of miRNA component inside and outside of the serum exosomes were also compared.
Project description:In the present study, the isolated serum exosomes from healthy adults, rats, and mice were comparatively characterized; the small RNA compositions were analyzed; the serum exosome miRNA profiles and exosome depleted serum miRNA profiles were obtained by small RNAseq, and the distributions of miRNA component inside and outside of the serum exosomes were also compared.
Project description:We report the differential expression of miRNA in serum exosome of heat strok patints. Compared with those from healthy volunteers, exosomes from patients with HS showed substantial changes in the expression of 202 exosomal miRNAs (154 upregulated and 48 downregulated miRNAs). The most upregulated miRNAs included miR-511-3p, miR-122-5p, miR-155-3p, miR-1290, and let7-5p, whereas the most downregulated ones included miR-150-3p, 146a-5p, and 151a-3p. Gene ontology enrichment of the miRNAs of patients with HS compared with control subjects were associated mostly with inflammatory response, including T cell activation, B cell receptor signaling, dendritic cell chemotaxis and leukocyte migration, and platelet activation and blood coagulation. The identified miRNAs were primarily enriched to the signal transduction pathways namely, T cell receptor signaling, Ras signaling, chemokine signaling, platelet activation, and leukocyte transendothelial migration, all of which are associated with inflammation and hemostasis. Multiple targeted mRNAs associated with the inflammatory response, blood coagulation, and platelet activation were further verified in serum exosomes. Exosomes from patients with HS convey miRNAs and mRNAs associated with pathogenic pathways, including inflammatory response and coagulation cascade. Exosomes may represent a novel mechanism for intercellular communication during HS.