COT-3 Exosomal microRNA expression signature in blood and cerebrospinal fluid of glioblastoma patients

Abstract Analysis of exosomes derived from plasma or cerebrospinal fluid (CSF) has emerged as a promising biomarker platform for therapeutic monitoring in glioblastoma patients. However, the contents of the various subpopulations of exosomes in these clinical specimens remain poorly defined. Here we characterize the relative abundance of miRNA species in exosomes derived from the plasma and CSF of glioblastoma patients. To this end, we first employed miRNA arrays to measure the expression of exosomal miRNAs in the plasma from glioblastoma patients (n = 24) and healthy volunteers (n = 7) as control. In addition, we performed global miRNA profiling of exosomal miRNAs in the CSF from glioblastoma patients (n = 5) and non-tumoral patients (n = 3; hydrocephalus patients) as control. In plasma derived exosomes, 80 miRNAs were altered by >2-fold in glioblastoma patients compared to controls. In CSF, 92 miRNAs were altered by >2-fold in glioblastoma patients compared to controls. Combined analysis of plasma and CSF revealed a similar fold difference in eight miRNAs. Next, we measured these eight miRNAs expression in in the plasma from pre- and post-operative glioblastoma patients (n = 9). Among these eight miRNAs, we identified only one miRNA (miR-34b-3p) that was upregulated in exosomes from pre-operative glioblastoma patients. Our results suggest that miR-34b-3p might have a potential as a novel diagnostic marker or a therapeutic tool for glioblastoma patients.

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Exosomal MicroRNA: Diagnostic Marker and Therapeutic Tool for Lung Diseases

Current Pharmaceutical Design ◽

10.2174/1381612827666210608150640 ◽

2021 ◽

Vol 27 ◽

Author(s):

Yu Hua ◽

Yan Ding ◽

Yapeng Hou ◽

Yanhong Liu ◽

Kejun Mao ◽

...

Keyword(s):

Lung Diseases ◽

Diagnostic Marker ◽

Treatment Strategies ◽

Diagnostic Methods ◽

Chronic Obstructive ◽

Target Cells ◽

High Morbidity ◽

Therapeutic Tool ◽

Obstructive Pulmonary Disease ◽

Exosomal Microrna

: Lung diseases are common clinical illnesses with high morbidity and mortality, which seriously threaten human health. In recent years, increasing evidence suggests that exosomes play a pivotal role in intercellular communication by delivering their cargo to pulmonary target cells，such as microRNAs. Physiologically, exosomes have been shown to be a critical mediator in maintaining homeostasis function in the complex thin-walled lung tissue and airway structure. Apart from being a diagnostic and prognostic biomarker, exosomes also participate in the progression of some lung diseases, such as chronic obstructive pulmonary disease, asthma, pulmonary fibrosis, acute lung injury, lung cancer, interstitial lung disease, and tuberculosis. Here, we summarize the recent findings on the involvement of exosomes and exosomal microRNAs in the pathogenesis, diagnosis, and therapy of lung diseases, aiming to provide more information to discover novel diagnostic methods and treatment strategies for these disorders.

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Rapid Shell Vial Culture Technique for Detection of Enteroviruses and Adenoviruses in Fecal Specimens: Comparison with Conventional Virus Isolation Method

Journal of Clinical Microbiology ◽

10.1128/jcm.36.10.2865-2868.1998 ◽

1998 ◽

Vol 36 (10) ◽

pp. 2865-2868 ◽

Cited By ~ 33

Author(s):

G. J. J. Van Doornum ◽

J. C. De Jong

Keyword(s):

Cell Culture ◽

Cerebrospinal Fluid ◽

Virus Isolation ◽

Adenovirus Type ◽

Isolation Procedure ◽

Enzyme Linked Immunosorbent Assay ◽

Shell Vial ◽

Clinical Specimens ◽

Conventional Culture ◽

Stool Specimens

Detection of enteroviruses and adenoviruses mainly in fecal specimens by rapid culture with inoculation onto cell monolayers in flat-bottom tubes by centrifugation and immunofluorescence staining with genus-specific monoclonal antibodies was compared with that by the conventional virus isolation procedure. For both conventional culture and shell vial culture human lung fibroblast cells and tertiary monkey kidney cells were used. For enterovirus detection, 979 clinical specimens (916 stool specimens, 56 cerebrospinal fluid specimens, and 7 nasopharyngeal swabs) were used. Conventional culture detected 74 enterovirus isolates. A cytopathic effect compatible with the presence of an enterovirus after 3 days of incubation occurred in 25 of the 74 (34%) specimens that eventually became positive. The detection rate for enteroviruses by rapid cell culture after 2 to 3 days of incubation was 42 of 74 (57%). The genus-specific enterovirus monoclonal antibody did not react with strains of echovirus types 22 and 23 or enterovirus type 71. Rapid cell culture for the detection of adenoviruses was performed with 567 clinical specimens (536 stool specimens, 25 cerebrospinal fluid specimens, and 6 miscellaneous specimens), in which 42 adenoviruses were found by conventional culture. Nine of the 42 (21%) adenovirus isolates were detected by conventional culture within 3 days after inoculation, whereas 21 (50%) were found by rapid cell culture within 2 to 3 days. Only two of the nine specimens found to be positive for the enteric adenovirus type 41 by conventional culture as well by a type-specific enzyme-linked immunosorbent assay (ELISA) tested positive by rapid cell culture. In conclusion, the rapid shell vial assay allows the early detection and identification of enteroviruses and adenoviruses in clinical specimens but is markedly less sensitive than the conventional isolation procedure according to the eventual results of the conventional isolation procedure. Conventional cell culture remains a prerequisite for serotyping of enteroviral isolates. On the basis of the results for adenovirus type 41, the rapid detection of adenoviruses was not considered to be useful for the detection of clinically relevant adenoviruses in fecal samples.

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Comparison of diagnostic clinical samples and environmental sampling for enterovirus and parechovirus surveillance in Scotland, 2010 to 2012

Eurosurveillance ◽

10.2807/1560-7917.es2014.19.15.20772 ◽

2014 ◽

Vol 19 (15) ◽

Cited By ~ 56

Author(s):

H Harvala ◽

J Calvert ◽

D Van Nguyen ◽

L Clasper ◽

N Gadsby ◽

...

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Rapid Identification ◽

Clinical Samples ◽

Environmental Sampling ◽

Clinical Specimens ◽

Young Infants ◽

Coxsackievirus A6 ◽

The Family ◽

Common Causes

Human enteroviruses (EV) and parechoviruses (HPeV) within the family Picornaviridae are the most common causes of viral central nervous system (CNS)-associated infections including meningitis and neonatal sepsis-like disease. The frequencies of EV and HPeV types identified in clinical specimens collected in Scotland over an eight-year period were compared to those identified in sewage surveillance established in Edinburgh. Of the 35 different EV types belonging to four EV species (A to D) and the four HPeV types detected in this study, HPeV3 was identified as the most prevalent picornavirus in cerebrospinal fluid samples, followed by species B EV. Interestingly, over half of EV and all HPeV CNS-associated infections were observed in young infants (younger than three months). Detection of species A EV including coxsackievirus A6 and EV71 in clinical samples and sewage indicates that these viruses are already widely circulating in Scotland. Furthermore, species C EV were frequently identified EV in sewage screening but they were not present in any of 606 EV-positive clinical samples studied, indicating their likely lower pathogenicity. Picornavirus surveillance is important not only for monitoring the changing epidemiology of these infections but also for the rapid identification of spread of emerging EV and/or HPeV types.

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Plasma Exosomal MiRNAs Expression Profile in Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis: Case-Control Study and Analysis of Potential Functions

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2020.584828 ◽

2020 ◽

Vol 13 ◽

Author(s):

Li-Gang Huang ◽

Yun-He Luo ◽

Ji-Wen Xu ◽

Qin-Chi Lu

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Case Control Study ◽

Hippocampal Sclerosis ◽

Mesial Temporal Lobe Epilepsy ◽

Case Control ◽

Exosomal Mirnas ◽

Mesial Temporal Lobe ◽

Mirnas Expression ◽

Control Study

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Development of Antibody–Oligonucleotide Complexes for Targeting Exosomal MicroRNA

Pharmaceutics ◽

10.3390/pharmaceutics12060545 ◽

2020 ◽

Vol 12 (6) ◽

pp. 545 ◽

Cited By ~ 1

Author(s):

Asako Yamayoshi ◽

Shota Oyama ◽

Yusuke Kishimoto ◽

Ryo Konishi ◽

Tsuyoshi Yamamoto ◽

...

Keyword(s):

Drug Delivery ◽

Inhibitory Effects ◽

Exosomal Mirnas ◽

Functional Inhibition ◽

Novel Drug Delivery System ◽

Exosomal Mirna ◽

Novel Drug ◽

Exosomal Microrna

MicroRNAs in exosomes (exosomal miRNAs) are considered as significant targets for cancer therapy. Anti-miR oligonucleotides are often used for the functional inhibition of miRNAs; however, there are no studies regarding the regulation of exosomal miRNA functions. In this study, we attempted to develop a novel drug delivery system using anti-exosome antibody–anti-miR oligonucleotide complexes (ExomiR-Tracker) to hijack exosomes to carry anti-miR oligonucleotides inside exosome-recipient cells. We found that ExomiR-Tracker bound to the exosomes, and then the complexes were introduced into the recipient cells. We also found that anti-miR oligonucleotides introduced into the recipient cells can exhibit inhibitory effects on exosomal miRNA functions in vitro and in vivo. We believe that our strategy would be a promising one for targeting exosomal miRNAs.

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Specificity and Diagnostic Utility of Cerebrospinal Fluid CXCL13 in Lyme Neuroborreliosis

Clinical Infectious Diseases ◽

10.1093/cid/ciaa335 ◽

2020 ◽

Cited By ~ 1

Author(s):

Elizabeth A Eckman ◽

Dana M Clausen ◽

Aimee R Herdt ◽

Javier Pacheco-Quinto ◽

John J Halperin

Keyword(s):

Cerebrospinal Fluid ◽

Diagnostic Marker ◽

Leukocyte Count ◽

Rank Correlation ◽

Lyme Neuroborreliosis ◽

Early Infection ◽

Igg Synthesis ◽

Specific Igg ◽

Active Inflammation ◽

Spearman Rank Correlation Test

Abstract Background Demonstration of intrathecal production of Borrelia-specific antibodies (ITAb) is considered the most specific diagnostic marker of Lyme neuroborreliosis (LNB). Limitations include delayed detectability in early infection and continued presence long after successful treatment. Markers of active inflammation—increased cerebrospinal fluid (CSF) leukocytes, protein, and CXCL13—provide nonspecific markers of active infection. To assess the utility of CSF CXCL13, we measured its concentration in 132 patients with a broad spectrum of neuroinflammatory disorders, including LNB. Methods CSF CXCL13 was measured by immunoassay. Spearman rank correlation test was performed to explore its relationship to conventional markers of neuroinflammation and Borrelia-specific ITAb production. Results In non-LNB neuroinflammatory disorders, CSF CXCL13 elevation correlated with CSF immunoglobulin G (IgG) synthesis and leukocyte count. In LNB, CXCL13 concentration was far greater than expected from overall CSF IgG synthesis, and correlated with Borrelia-specific ITAb synthesis. Median CSF CXCL13 concentration in ITAb-positive LNB patients was > 500 times greater than in any other group. Conclusions Intrathecal CXCL13 and IgG production are closely interrelated. CXCL13 is disproportionately increased in “definite LNB,” defined as having demonstrable Borrelia-specific ITAb, but not “probable LNB,” without ITAb. This disproportionate increase may help identify patients with very early infection or those with active vs treated LNB, or may help to differentiate ITAb-defined active LNB from other neuroinflammatory disorders. However, its reported specificity is closely related to the diagnostic requirement for ITAb. It may add little specificity to the demonstration of a pleocytosis or increased overall or specific IgG production in the CSF.

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Interleukin 6 in Cerebrospinal Fluid of Patients with Meningitis is not a Useful Diagnostic Marker in the Differential Diagnosis of Meningitis

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456329703400206 ◽

1997 ◽

Vol 34 (2) ◽

pp. 165-169 ◽

Cited By ~ 14

Author(s):

L F López-Cortés ◽

M Cruz-Ruiz ◽

J Gómez-Mateos ◽

D Jiménez-Hernández ◽

P Viciana-Fernández ◽

...

Keyword(s):

Central Nervous System ◽

Monoclonal Antibody ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Differential Diagnosis ◽

Interleukin 6 ◽

Diagnostic Marker ◽

Neurological Diseases ◽

Central Nervous System Infections ◽

Pyogenic Meningitis

We assayed interleukin 6 (IL-6) concentrations in cerebrospinal fluid (CSF) from patients affected by meningitis of different aetiologies, and verified whether IL-6 can be used as a diagnostic marker in the differential diagnosis of meningitis. We used a monoclonal antibody enzyme immunoassay to test 98 CSF samples classified as pyogenic (15), viral (15), self-resolving aseptic meningitis (20), other infectious meningitis (9), neoplastic (4) and normal CSF from patients with (20) and without (15) non-infectious neurological diseases. CSF IL-6 concentrations were increased in pyogenic meningitis (100%) and in more than 50% of viral and other subarachnoid space infections, and rarely in patients without central nervous system infections. Though patients affected by pyogenic meningitis showed the highest levels of CSF IL-6, only a cut-off point ≥10000 pg/mL was able to discriminate pyogenic meningitis from those of other aetiologies with a specificity ≥94% and a positive predictive value of ≥0·75 but the sensitivity was ≤60%. Therefore, CSF IL-6 concentration is not a good diagnostic marker in the differential diagnosis of meningitis.

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Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease

Neuroscience Letters ◽

10.1016/s0304-3940(99)00476-0 ◽

1999 ◽

Vol 270 (2) ◽

pp. 91-94 ◽

Cited By ~ 106

Author(s):

Koichi Ishiguro ◽

Hideto Ohno ◽

Hiroyuki Arai ◽

Haruyasu Yamaguchi ◽

Katsuya Urakami ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Diagnostic Marker ◽

Phosphorylated Tau ◽

Human Cerebrospinal Fluid

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Triplex Real-Time PCR without DNA Extraction for the Monitoring of Meningococcal Disease

Diagnostics ◽

10.3390/diagnostics8030058 ◽

2018 ◽

Vol 8 (3) ◽

pp. 58 ◽

Cited By ~ 1

Author(s):

Melissa Whaley ◽

Laurel Jenkins ◽

Fang Hu ◽

Alexander Chen ◽

Seydou Diarra ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Real Time ◽

Dna Extraction ◽

Sensitivity And Specificity ◽

Real Time Pcr ◽

Limit Of Detection ◽

Detection Range ◽

Clinical Specimens ◽

Large Numbers ◽

Pcr Assays

Detection of Neisseria meningitidis has become less time- and resource-intensive with a monoplex direct real-time PCR (drt-PCR) to amplify genes from clinical specimens without DNA extraction. To further improve efficiency, we evaluated two triplex drt-PCR assays for the detection of meningococcal serogroups AWX and BCY. The sensitivity and specificity of the triplex assays were assessed using 228 cerebrospinal fluid (CSF) specimens from meningitis patients and compared to the monoplex for six serogroups. The lower limit of detection range for six serogroup-specific drt-PCR assays was 178–5264 CFU/mL by monoplex and 68–2221 CFU/mL by triplex. The triplex and monoplex showed 100% agreement for six serogroups and the triplex assays achieved similar sensitivity and specificity estimates as the monoplex drt-PCR assays. Our triplex method reduces the time and cost of processing CSF specimens by characterizing six serogroups with only two assays, which is particularly important for testing large numbers of specimens for N. meningitidis surveillance.

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