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At least 19 recordsLinked to original sources
PubMed2007

Rapid isolation of urinary exosomal biomarkers using a nanomembrane ultrafiltration concentrator.

Urinary exosomes are excreted from all nephron segments and may serve as biomarkers for classifying renal diseases. Isolation of urinary exosomes by the established ultracentrifugation method has some limitations for use in a clinical laboratory. We sought a rapid and simple way to obtain urinary exosomes. We used a commercially available nanomembrane concentrator to enrich exosomes from urine by centrifugation at 3,000 g for 10-30 min. Urinary exosomal markers tumor susceptibility gene 101, aquaporin-2, neuron-specific enolase, annexin V, angiotensin-converting enzyme, and podocalyxin (PODXL) were recovered from the nanomembrane concentrator and detected by Western blotting, and typical features of urinary vesicles were found by electron microscopy. Exosomal markers were detected in as little as 0.5 ml of urine. By the nanomembrane method, exosomal proteins could be recovered from urine samples frozen at -80 degrees C or refrigerated overnight at 4 degrees C then stored at -80 degrees C. By enriching exosomes we could detect PODXL, a podocyte marker, which decreased by 71% in five male patients with focal segmental glomerulosclerosis and abundant proteinuria. We conclude that 1) use of a nanomembrane concentrator simplifies and accelerates the enrichment of urinary exosomes; and 2) the nanomembrane concentrator can concentrate exosomal proteins from clinical urine samples. This enhanced method may accelerate the translation of urinary exosomal biomarkers from bench to bedside for the diagnosis, classification, and prognostication of renal diseases.

Biomarkers↗
PubMed2006

Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery.

Urinary exosomes containing apical membrane and intracellular fluid are normally secreted into the urine from all nephron segments, and may carry protein markers of renal dysfunction and structural injury. We studied methods for collection, storage, and preservation of urinary exosomal proteins. We collected urine from healthy volunteers, added protease inhibitors, and stored urine samples at 4, -20, and -80 degrees C for 1 week or 7 months. Samples were thawed with and without extensive vortexing, and three fractions were isolated: urinary sediment, supernatant, and exosome fraction. Protein concentration, electrophoresis patterns, and abundance of seven exosome-associated proteins were measured. Exosome-associated proteins were not detected in sediment or supernatant fractions. Protease inhibitors prevented degradation of exosome-associated proteins. Freezing at -20 degrees C caused a major loss in exosomes compared to fresh urine. In contrast, recovery after freezing at -80 degrees C was almost complete. Extensive vortexing after thawing markedly increased exosome recovery in urine frozen at -20 or -80 degrees C, even if frozen for 7 months. The recovery from first and second morning urine was similar. The abundance of cytosolic exosome-associated proteins did not decrease during long-term storage. We concluded: (1) protease inhibitors are essential for preservation; (2) storage at -80 degrees C with extensive vortexing after thawing maximizes the recovery of urinary exosomes; (3) the difference between first and second morning urine exosome-associated protein was small, suggesting minimal protein degradation in the urinary tract/bladder; (4) urinary exosomes remain intact during long-term storage. These urine collection, storage, and processing conditions may be useful for future biomarker discovery efforts.

Biomarkers↗
PubMed2022

An Exosomal miRNA Biomarker for the Detection of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) remains a difficult tumor to diagnose and treat. To date, PDAC lacks routine screening with no markers available for early detection. Exosomes are 40-150 nm-sized extracellular vesicles that contain DNA, RNA, and proteins. These exosomes are released by all cell types into circulation and thus can be harvested from patient body fluids, thereby facilitating a non-invasive method for PDAC detection. A bioinformatics analysis was conducted utilizing publicly available miRNA pancreatic cancer expression and genome databases. Through this analysis, we identified 18 miRNA with strong potential for PDAC detection. From this analysis, 10 (MIR31, MIR93, MIR133A1, MIR210, MIR330, MIR339, MIR425, MIR429, MIR1208, and MIR3620) were chosen due to high copy number variation as well as their potential to differentiate patients with chronic pancreatitis, neoplasms, and PDAC. These 10 were examined for their mature miRNA expression patterns, giving rise to 18 mature miRs for further analysis. Exosomal RNA from cell culture media was analyzed via RTqPCR and seven mature miRs exhibited statistical significance (miR-31-5p, miR-31-3p, miR-210-3p, miR-339-5p, miR-425-5p, miR-425-3p, and miR-429). These identified biomarkers can potentially be used for early detection of PDAC.

Humans↗
PubMed2006

Exosomal Fetuin-A identified by proteomics: a novel urinary biomarker for detecting acute kidney injury.

Urinary exosomes containing apical membrane and intracellular fluid are normally secreted into the urine from all nephron segments, and may carry protein markers of renal dysfunction and structural injury. We aimed to discover biomarkers in urinary exosomes to detect acute kidney injury (AKI), which has a high mortality and morbidity. Animals were injected with cisplatin. Urinary exosomes were isolated by differential centrifugation. Protein changes were evaluated by two-dimensional difference in gel electrophoresis and changed proteins were identified by mass spectrometry. The identified candidate biomarkers were validated by Western blotting in individual urine samples from rats subjected to cisplatin injection; bilateral ischemia and reperfusion (I/R); volume depletion; and intensive care unit (ICU) patients with and without AKI. We identified 18 proteins that were increased and nine proteins that were decreased 8 h after cisplatin injection. Most of the candidates could not be validated by Western blotting. However, exosomal Fetuin-A increased 52.5-fold at day 2 (1 day before serum creatinine increase and tubule damage) and remained elevated 51.5-fold at day 5 (peak renal injury) after cisplatin injection. By immunoelectron microscopy and elution studies, Fetuin-A was located inside urinary exosomes. Urinary Fetuin-A was increased 31.6-fold in the early phase (2-8 h) of I/R, but not in prerenal azotemia. Urinary exosomal Fetuin-A also increased in three ICU patients with AKI compared to the patients without AKI. We conclude that (1) proteomic analysis of urinary exosomes can provide biomarker candidates for the diagnosis of AKI and (2) urinary Fetuin-A might be a predictive biomarker of structural renal injury.

Acute Kidney Injury↗
PubMed2026

Plasma Exosome Metabolomics Reveal Stage-Specific Alterations in Elderly Women With Premetabolic and Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a chronic disorder that poses a major threat to global health. Exosomes have emerged as promising biomarkers for diagnosing and monitoring chronic diseases. However, stage-specific alterations in the exosomal metabolome during MetS development remain poorly understood. This study aimed to characterize the plasma exosomal metabolome and explore candidate exosomal biomarkers in individuals with MetS. METHODS: This study included 20 patients with MetS, 23 individuals with pre-MetS, and 45 healthy controls. Plasma exosomes were isolated and analyzed using untargeted liquid chromatography-mass spectrometry-based metabolomics. Differential metabolites were defined by a dual-threshold, that is, p&#x2009;<&#x2009;0.05 from t-test and variable importance in projection >&#x2009;1 from partial least squares discriminant analysis, with fold change indicating their expression changes. Further, we employed machine learning algorithms to predict MetS status. RESULTS: We identified 27 differential metabolites between the pre-MetS and control groups, mainly enriched in histidine metabolism and the tricarboxylic acid cycle. Of these, 12 metabolites were upregulated, and 15 were downregulated, with 1-methylhistidine and isocitrate playing central regulatory roles. Comparison between the MetS and control groups revealed 45 differentially expressed metabolites, mainly enriched in thiamine metabolism, including 13 upregulated and 32 downregulated. In the pre-MetS group, cladribine showed the highest area under the curve (AUC) (0.743, p&#x2009;<&#x2009;0.05), whereas 3-methylxanthine yielded the largest AUC (0.714, p&#x2009;<&#x2009;0.05) in the MetS group. CONCLUSION: Our study characterized stage-dependent alterations in the plasma exosome-derived metabolome in MetS and suggests that exosomal metabolomics may provide complementary molecular information on early MetS metabolic perturbations.

exosomal features↗
PubMed2005

Prospects for urinary proteomics: exosomes as a source of urinary biomarkers.

Recent progress in biotechnology offers the promise of better medical care at lower costs. Among the techniques that show the greatest promise is mass spectrometry of proteins, which can identify proteins present in body fluids and tissue specimens at a large scale. Because urine can be collected in large amounts in a non-invasive fashion, the potential exists to use mass spectrometry to discover urinary biomarkers that are early predictors of renal disease, or useful in making therapeutic choices. Recently, the authors demonstrated that both membrane proteins and cytosolic proteins from renal epithelia are highly enriched in low-density urinary structures identified as exosomes. Exosomes were found to contain many disease-associated proteins including aquaporin-2, polycystin-1, podocin, non-muscle myosin II, angiotensin-converting enzyme, Na+ K+ 2Cl- cotransporter (NKCC2), thiazide-sensitive Na-Cl cotransporter (NCC), and epithelial sodium channel (ENaC). Potentially, other disease biomarkers could be discovered by mass spectrometry-based proteomic studies in well-defined patient populations. Herein is described the advantages of using urinary exosomes as a starting material for biomarker discovery. In addition, the purpose of this review is to present an overall strategy for biomarker discovery in urine using exosomes and for developing cost-effective clinical assays for these biomarkers, which can potentially be used for early detection of disease, as a means of differential diagnosis, or as a means of guiding therapy. Finally, potential barriers that need to be overcome before urinary proteomics can be applied clinically, are emphasized.

Biomarkers↗
PubMed2026

Recent advancements in exosomal content analysis: the future of liquid biopsy.

Exosomes are widely acknowledged as an essential agent that carries biomarkers for specific diseases, representing the molecular status of their parent cells and providing extremely useful diagnostic insights. They can be isolated from different body fluids and contain a range of cargo molecules, including proteins, lipids, metabolites, and nucleic acids. Recent advancements in technology have greatly accelerated exosome research. Proteomics provides protein signatures linked to many pathological conditions, enabling quick and clinically scalable diagnostic tools, whereas high-throughput RNA-sequencing can be used to perform detailed transcriptome profiling. Exosomal biomarkers are showing promising clinical results in early detection of neurological diseases, infectious and cardiovascular disorders, oncology, and other medical conditions, hence accelerating therapeutic monitoring. Despite these advances, several challenges continue to hinder clinical translation including the lack of standardized isolation protocol, variability in exosome yield and purity, biological heterogeneity, and limited large-scale clinical validation. Addressing these limitations will be critical for the successful integration of exosome-based liquid biopsy into routine clinical practice. Overall, exosomes having significant potential as diagnostic tool, represent a transformative horizon in biomedical liquid biopsy research to redefine the landscape of less-invasive diagnostics and tailored clinical applications.

Humans↗
PubMed2026

An Exosomal Signature for Preoperative Detection of Occult Liver Metastasis in Pancreatic Cancer.

IMPORTANCE: Early liver metastasis (early-LiM) after pancreatectomy represents an aggressive biological phenotype of pancreatic ductal adenocarcinoma (PDAC) and is associated with markedly poor survival. Reliable preoperative biomarkers to identify occult hepatic micrometastasis remain lacking. OBJECTIVE: To develop and externally validate a circulating exosomal microRNA (exo-miRNA)-based machine learning model for preoperative detection of occult early-LiM in PDAC. DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective case-control study included 3 phases: genome-wide discovery using exo-miRNA sequencing (discovery cohort), model development (training cohort), and independent external validation (2 validation cohorts). The study took place at 4 medical centers in China, Japan, and South Korea. A total of 372 patients were enrolled between 2011 and 2024. Data were analyzed from July 2024 to November 2025. EXPOSURES: Circulating plasma-derived exosomal miRNA expression profiles. MAIN OUTCOMES AND MEASURES: The primary outcome was early-LiM, defined as liver recurrence within 6 months after curative-intent resection. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and survival outcomes were assessed using Kaplan-Meier analysis. RESULTS: Among 372 patients with PDAC (median [IQR] age, 67 [59-73] years; 229 [61.6%] male and 143 [38.4%] female; median follow-up among survivors, 969 days),early-LiM was associated with significantly worse overall survival compared with other recurrence patterns (median OS, 9.1 months vs 26.6-31.8 months; log-rank P&#x2009;<&#x2009;.001). A 7-exo-miRNA extreme gradient boosting model demonstrated discrimination in the training cohort (AUC, 0.899; 95% CI, 0.822-0.976) and maintained performance in external testing cohorts (AUC, 0.876; 95% CI, 0.846-0.951 and AUC, 0.862; 95% CI, 0.744-0.981). The exo-miRNA panel score remained an independent identifier of early-LiM in multivariable analysis (odds ratio, 26.49; 95% CI, 18.45-55.28; P&#x2009;<&#x2009;.001) and stratified overall survival (log-rank P&#x2009;<&#x2009;.001). Decision curve analysis suggested improved net clinical benefit compared with conventional clinicopathologic variables. CONCLUSION AND RELEVANCE: In this multicenter study, a circulating exo-miRNA-based machine learning model enabled preoperative detection of occult early liver metastasis risk in PDAC. These findings support the potential of exosomal biomarkers to inform biology-guided treatment sequencing and warrant prospective validation.

Journal Article↗
PubMed2026

The investigation of human cerebrospinal fluid exosome in spinal cord injury.

Spinal cord injury (SCI) leads to severe neurological and functional impairments, yet reliable biomarkers for assessing injury severity and predicting recovery remain limited. Cerebrospinal fluid (CSF) is in direct contact with the central nervous system and provides a valuable source for detecting molecular changes after SCI. Although exosomal microRNAs (miRNAs) and proteins are increasingly recognized as mediators of intercellular communication, the role of human CSF exosomes in SCI has not been systematically investigated. To identify exosome-based biomarkers and potential therapeutic targets, we analyzed CSF and serum exosomes from patients with acute SCI using RNA sequencing and proteomic profiling. Weighted gene co-expression network analysis identified 6 gene modules significantly associated with injury severity and neurological recovery at 3 months. Proteomic analysis revealed a 5-protein panel that distinguished complete from incomplete SCI and a 4-protein panel that predicted neurological improvement. Additionally, 15 CSF-specific and 9 serum-specific exosomal miRNAs were identified independent of injury severity. Among 10 tested miRNAs associated with neurological recovery, 7 regulated astrocyte proliferation, and 6 promoted neurite extension and synapse formation. Overall, this study provides a comprehensive characterization of CSF exosomal miRNAs and proteins in human SCI and identifies molecular signatures associated with injury severity and recovery.

Humans↗
PubMed2025

Liquid Biopsy in Hematologic Malignancies: Advances, Challenges, and Future Directions.

Hematologic malignancies are cancers that affect the bone marrow, lymphatic system, and hematopoietic cells, resulting in various cancer subtypes and clinical manifestations. Currently, tissue biopsy in hematological malignancies is typically performed for genomic profiling and has limitations such as invasiveness, lengthy procedures, and high expense. On the other hand, liquid biopsy serves as an emerging tool used for examining the blood or other bodily fluids of patients, for the purpose of identifying genetic mutations, biomarkers, or cancer-related substances. Liquid biopsy biomarkers include circulating tumor DNA (ctDNA), microRNA (miRNA), and exosomes. In the context of hematological malignancies, these biomarkers offer valuable insights into disease etiology, enabling effective disease monitoring and guiding treatment decisions owing to their differential expression patterns. This review critically examines the recent advancements and effectiveness of liquid biopsy biomarkers in the areas of diagnosis, therapy, and monitoring. The challenges and future directions of liquid biopsy for hematological malignancies are also discussed.

Humans↗
PubMed1995

Coexistence of scleromyositis associated with PM-Scl antibody and myasthenia.

Myasthenia gravis coexists in about 15% of the cases with other autoimmune diseases. Association with polymyositis or dermatomyositis is very rare, although myasthenic reaction is not infrequent in typical polymyositis and myopathic changes may occur in cases of myasthenia. This is the first case of coexistence of myasthenia and scleromyositis, associated with PM-Scl antibody as an immune marker. The patient was found to have persistent thymus. Myasthenia preceded scleromyositis for 9 yr, was at periods asymptomatic, and recurred simultaneously with development of scleromyositis. Scleromyositis should be added to the list of autoimmune disorders coexistent with myasthenia.

Autoantibodies↗
PubMed2004

Identification and proteomic profiling of exosomes in human urine.

Urine provides an alternative to blood plasma as a potential source of disease biomarkers. One urinary biomarker already exploited in clinical studies is aquaporin-2. However, it remains a mystery how aquaporin-2 (an integral membrane protein) and other apical transporters are delivered to the urine. Here we address the hypothesis that these proteins reach the urine through the secretion of exosomes [membrane vesicles that originate as internal vesicles of multivesicular bodies (MVBs)]. Low-density urinary membrane vesicles from normal human subjects were isolated by differential centrifugation. ImmunoGold electron microscopy using antibodies directed to cytoplasmic or anticytoplasmic epitopes revealed that the vesicles are oriented "cytoplasmic-side inward," consistent with the unique orientation of exosomes. The vesicles were small (<100 nm), consistent with studies of MVBs and exosomes from other tissues. Proteomic analysis of urinary vesicles through nanospray liquid chromatography-tandem mass spectrometry identified numerous protein components of MVBs and of the endosomal pathway in general. Full liquid chromatography-tandem MS analysis revealed 295 proteins, including multiple protein products of genes already known to be responsible for renal and systemic diseases, including autosomal dominant polycystic kidney disease, Gitelman syndrome, Bartter syndrome, autosomal recessive syndrome of osteopetrosis with renal tubular acidosis, and familial renal hypomagnesemia. The results indicate that exosome isolation may provide an efficient first step in biomarker discovery in urine.

Adult↗
PubMed2005

[PM-Scl antibody positive systemic sclerosis associated with inclusion-body myositis].

We describe a 72- year-old patient with a ten year history of anti-PM-Scl positive systemic sclerosis associated with inclusion-body myositis. While the association of dermatomyositis and polymyositis with anti-PM-Scl positive systemic sclerosis is frequently reported, inclusion-body myositis was, to the best of our knowledge, only previously described once in association with anti-PM-Scl-positive systemic sclerosis. The distinction between inclusion-body myositis and other forms of inflammatory myopathy, like the histopathologically well distinguishable polymyositis or dermatomyositis, is relevant because of the poor response of inclusion- body myositis to immunosuppressive treatment. Our case underlines that in patients with anti-PM-Scl-positive systemic sclerosis and treatment resistant progressive myopathy the diagnosis of inclusion body myositis should be considered.

Aged↗
PubMed2026

Comparative Multiomics Analysis of Cerebral Organoid-Derived Exosomes during Organoid Maturation.

Cerebral organoids derived from human pluripotent stem cells recapitulate key features of early brain development and provide a physiologically relevant model for neurogenesis. Exosomes secreted by these organoids carry bioactive cargo and offer a noninvasive means to monitor maturation and intercellular communication. We performed comprehensive multiomics profiling of exosomes collected from cerebral organoids at defined developmental stages to evaluate their utility as biomarkers of neuronal differentiation. Metabolomic analysis revealed a progressive decline in amino acids, including glutamic acid, consistent with increased metabolic demand during neurogenesis. Lipidomic and neurosteroid profiling showed dynamic increases in phosphatidylethanolamine and pregnenolone, reflecting synaptic membrane formation and signaling. Transcriptomic and proteomic analyses identified stage-specific neurodevelopmental signatures, with key markers mirroring those of parent organoids. Collectively, cerebral organoid-derived exosomes faithfully reflect organoid maturation and provide a robust platform for tracking in vitro brain development.

Humans↗
PubMed2026

Low-Dose Radiation-Induced Expression of Exosomal miRNAs in the Serum of Medical Radiation Workers.

Objective: Long-term low-dose ionizing radiation may alter genomes and cause diseases. This study examined serum exosomal miRNA differences among radiation-exposed medical workers by work types. Methods: High-throughput sequencing screened serum exosomal miRNAs in diagnostic radiologists, interventional radiologists, and nuclear medicine doctors. qRT-PCR validated differentially expressed miRNAs. Results: 410 differentially expressed miRNAs, including 102 downregulated and 308 upregulated miRNAs, enriched in 15 KEGG pathways. Four miRNAs were validated. miR-30e-5p, miR-155-5p and miR-486-5p differed significantly among groups(P<0.01).The expression levels of these three miRNAs were lower in the nuclear medicine group than in the diagnostic group (0.25&#xb1;0.05vs3.89&#xb1;8.62,0.10&#xb1;0.15vs7.03&#xb1;15.75,0.37&#xb1;0.39vs4.46&#xb1;9.64;Z=3.542,3.335,9.859;P<0.01), whereas miR-155-5p was lower in the interventional group than in the diagnostic group(1.32&#xb1;2.43vs 7.03&#xb1;15.75;H=11.889,P=0.003), miR-486-5p was higher(9.54&#xb1;19.39vs4.46&#xb1;9.64; H=9.859,P=0.007). All four miRNAs showed higher expression in the 14-31-year work-experience group, and all four also showed age-dependent differences, with miR-30d-5p and miR-486-5p showing the age-related differences (P<0.01). Combined detection of the four miRNAs improved discrimination among occupational categories (AUC=0.784). Multiple linear regression analysis showed that sex was associated with all four miRNAs, whereas work type was associated with miR-30d-5p and miR-155-5p (P<0.05). Conclusion: Serum exosomal miR-30e-5p, miR-155-5p, and miR-486-5p are promising biomarkers for monitoring radiation-induced damage, supporting occupational protection and health management.

exosomes↗
PubMedDate not supplied

Exosome Display technology: applications to the development of new diagnostics and therapeutics.

Exosome Display is a novel methodology enabling the manipulation of exosome protein content. This technology stems from the identification of addressing domains that mediate the specific distribution of proteins on exosomes. More particularly, Lactadherin expressed in non-mammary gland tissue has been found to localize to exosomes via binding of its C1C2 domain to exosome lipids. Exosome Display of soluble antigens and extracellular domains of membrane proteins that are not naturally found on exosomes occurs upon fusion of proteins with the Lactadherin C1C2 domain. Exosome Display of native full-length membrane proteins can also be achieved by non-restricted expression or sampling of membrane proteins on exosomes. These novel findings enable us to manipulate exosome composition and tailor exosomes with new desirable properties. The Exosome Display technology is very versatile since soluble, membrane-bound, trans-membrane or multimeric antigens that are not naturally found on exosomes can now be efficiently expressed at their surface in a native conformation. The technology was applied to the generation of antibodies against tumor biomarkers such as HLA/peptide complex. This antibody method called ExoMAb can be used to generate antibodies against any drug target candidates, notably including G-protein coupled receptors. The potential of Exosome Display technology for developing a broad range of novel diagnostics and therapeutics is discussed.

Antibodies↗