The significance of exosomes in the development and treatment of hepatocellular carcinoma

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: Jan. 4, 2020

Abstract Hepatocellular carcinoma (HCC) is the most commonmalignancy. Exsome plays a significant role in elucidation of signal transduction pathways between hepatoma cells, angiogenesis and early diagnosis HCC. Exosomes are small vesicular structures that mediate interaction different types contain variety components (including DNA, RNA, proteins). Numerous studies have shown these substances exosomes involved growth, metastasis liver cancer, then inhibited growth cancer by blocking signaling pathway cells. In addition, exosomal could also be used as markers for screening cancer. this review, we summarized to reveal significance occurrence, development, treatment HCC, which turn might help us further elucidate mechanism promote use clinical

Language: Английский

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Microglial exosomes facilitate α-synuclein transmission in Parkinson’s disease

Brain, Journal Year: 2020, Volume and Issue: 143(5), P. 1476 - 1497

Published: March 15, 2020

Abstract Accumulation of neuronal α-synuclein is a prominent feature in Parkinson’s disease. More recently, such abnormal protein aggregation has been reported to spread from cell and exosomes are considered as important mediators. The focus research, however, primarily neurons. Given the increasing recognition importance non-cell autonomous-mediated neurotoxicity, it critical investigate contribution glia spread. Microglia primary phagocytes brain have well-documented inducers neuroinflammation. How what extent microglia their impact pathology not well delineated. We report here that when treated with human preformed fibrils, containing released by fully capable inducing recipient Additionally, combined microglial proinflammatory cytokines, these further increased Inhibition exosome synthesis reduced transmission. vivo significance was demonstrated stereotaxic injection isolated fibrils into mouse striatum. Phosphorylated observed multiple regions consistent connectivity. These animals also exhibited neurodegeneration nigrostriatal pathway time-dependent manner. Depleting dramatically suppressed transmission after fibrils. Mechanistically, we impaired autophagy flux upregulating PELI1, which turn, resulted degradation LAMP2 activated microglia. importantly, purifying microglia/macrophage derived CSF disease patients, confirmed presence oligomer CD11b+ exosomes, were able induce neurons, supporting translational aspect this study. Taken together, our study supports view contribute progression therefore, they may serve promising therapeutic target for

Language: Английский

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Increased miR‐124‐3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowthviatheir transfer into neurons

The FASEB Journal, Journal Year: 2017, Volume and Issue: 32(1), P. 512 - 528

Published: Sept. 21, 2017

Neuronal inflammation is the characteristic pathologic change of acute neurologic impairment and chronic traumatic encephalopathy after brain injury (TBI). Inhibiting excessive inflammatory response essential for improving outcome. To clarify regulatory mechanism microglial exosomes on neu-ronal in TBI, we focused studying impact exosomal miRNAs injured neurons this research. We used a repetitive (r)TBI mouse model harvested extracts from to phase TBI treat cultured BV2 microglia vitro. The were collected miRNA microarray analysis, which showed that expression level miR-124-3p increased most apparently miRNAs. found promoted anti-inflamed M2 polarization microglia, inhibited neuronal scratch-injured neurons. Further, mammalian target rapamycin (mTOR) signaling was implicated as being involved regulation by Gene Ontology Kyoto Encyclopedia Genes Genomes pathway analyses. Using mTOR activator MHY1485 confirmed inhibitory effect exerted suppressing activity signaling. PDE4B predicted be gene analysis. proved it directly targeted with luciferase reporter assay. overexpressed lentivirus transfection system, suggested suppressed mainly through inhibiting PDE4B. In addition, neurite outgrowth scratch injury, characterized an increase number branches total length, decreasedexpressiononRhoAand neurodegenerative proteins [Aß-peptide p-Tau]. It also improved outcome neuro-inflammation mice rTBI. Taken together, can inhibit contribute via their transfer into these effects targeting PDE4B, thus Therefore, could promising therapeutic interventions TBI. manipulated may provide novel therapy other diseases.—Huang, S., Ge, X., Yu, J., Han, Z., Yin, Li, Y., Chen, F., Wang, H., Zhang, Lei, P. Increased following inhibits contributes FASEB J. 32, 512-528 (2018). www.fasebj.org

Language: Английский

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Exosomes: new molecular targets of diseases

Acta Pharmacologica Sinica, Journal Year: 2017, Volume and Issue: 39(4), P. 501 - 513

Published: Dec. 7, 2017

Language: Английский

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In Vivo Neuroimaging of Exosomes Using Gold Nanoparticles

ACS Nano, Journal Year: 2017, Volume and Issue: 11(11), P. 10883 - 10893

Published: Sept. 29, 2017

Exosomes are emerging as effective therapeutic tools for various pathologies. These extracellular vesicles can bypass biological barriers, including the blood-brain barrier, and serve powerful drug gene therapy transporters. However, progress of development is impeded by several challenges, insufficient data on exosome trafficking biodistribution difficulty to image deep brain structures in vivo. Herein, we established a method noninvasive vivo neuroimaging tracking exosomes, based glucose-coated gold nanoparticle (GNP) labeling computed tomography imaging. Labeling exosomes with GNPs was achieved directly, opposed typical less efficient indirect mode through parent cells. On mechanistic level, found that were uptaken into MSC-derived via an active, energy-dependent mechanism mediated glucose transporter GLUT-1 involves endocytic proteins. Next, determined optimal parameters size administration route; demonstrated 5 nm enabled improved intranasal, compared intravenous, led superior accumulation thus enhanced neuroimaging. Furthermore, using mouse model focal ischemia, noninvasively tracked intranasally administered GNP-labeled which showed increased at lesion site over 24 h, nonspecific migration clearance from control brains same period. Thus, this technique diagnostic tool disorders could potentially enhance exosome-based treatments neuronal recovery.

Language: Английский

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Exosome Biochemistry and Advanced Nanotechnology for Next‐Generation Theranostic Platforms

Advanced Materials, Journal Year: 2018, Volume and Issue: 31(2)

Published: Aug. 20, 2018

Recent marked technological advances in the field of exosome nanotechnology have provided unprecedented opportunities to bloom developments exosome-related biology, chemistry, pathology, and therapeutics, which laid a solid basis for scientific community design exosome-based nanotheranostic platforms. The unique structural/compositional/morphological characteristics exosomes as natural nanocarriers, well their fascinating physicochemical/biochemical properties, underpin special physiopathological roles, triggered concept that these cell-derived nanovesicles with intrinsic biological functions can be highly competent establishment next-generation nanomedicine. Herein, efforts are made give comprehensive overview on recent based representative examples current state art research, ranging from formation, function, preparation, characterization extensive nanomedical applications. It is expected better clearer elucidation fundamental principles advanced constructing theranostic nanoplatforms, integrating advantages endogenous nanocarriers methodology traditional nanomedicine, will help unlock innate powers nanoplatforms.

Language: Английский

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Extracellular vesicles in neurodegenerative disease — pathogenesis to biomarkers

Nature Reviews Neurology, Journal Year: 2016, Volume and Issue: 12(6), P. 346 - 357

Published: May 13, 2016

Language: Английский

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Prediction of conversion from mild cognitive impairment to dementia with neuronally derived blood exosome protein profile

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Journal Year: 2016, Volume and Issue: 3(1), P. 63 - 72

Published: Jan. 1, 2016

Levels of Alzheimer's disease (AD)-related proteins in plasma neuronal derived exosomes (NDEs) were quantified to identify biomarkers for prediction and staging mild cognitive impairment (MCI) AD.Plasma extracted, precipitated, enriched source by anti-L1CAM antibody absorption. NDEs characterized size (Nanosight) shape (TEM) extracted NDE protein ELISAs. Plasma cargo was injected into normal mice, results immunohistochemistry determine pathogenic potential.Plasma levels P-T181-tau, P-S396-tau, Aβ1-42 significantly higher, whereas those neurogranin (NRGN) the repressor element 1-silencing transcription factor (REST) lower AD MCI converting (ADC) patients compared cognitively controls (CNC) subjects stable patients. Mice with from ADC displayed increased P-tau (PHF-1 antibody)-positive cells CA1 region hippocampus CNC patients.Abnormal P-tau, Aβ1-42, NRGN, REST accurately predict conversion dementia. demented seeded tau aggregation induced AD-like neuropathology mouse CNS.

Language: Английский

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Cargo proteins of plasma astrocyte‐derived exosomes in Alzheimer's disease

The FASEB Journal, Journal Year: 2016, Volume and Issue: 30(11), P. 3853 - 3859

Published: Aug. 10, 2016

Efficient intercellular transfer of RNAs, proteins, and lipids as protected exosomal cargo has been demonstrated in the CNS, but distinct physiologic pathologic roles have not well defined for this pathway. The capacity to isolate immunochemically human plasma neuron-derived exosomes (NDEs), containing neuronspecific cargo, permitted characterization CNS-derived living humans. Constituents amyloid β-peptide (Aβ)42-generating system now are examined 2 sets neural cells by quantification astrocyte-derived (ADEs) NDEs, enriched separately from plasmas patients with Alzheimer's disease (AD) or frontotemporal dementia (FTD) andmatched cognitively normal controls. ADE levels β-site precursor protein-cleaving enzyme 1 (BACE-1), γ-secretase, soluble Aβ42, protein (sAPP)β, sAPPα, glial-derived neurotrophic factor (GDNF), P-T181-tau, P-S396-tau were significantly (3- 20-fold) higher than NDEs BACE-1 also a mean 7-fold ADEs cultured rat type-specific cells. Levels sAPPβ GDNF lower AD those controls, different FTD Abundant proteins Aβ42 peptide-generating may sustain neurons. be useful studies mechanisms cellular interactions effects inhibitors AD.—Goetzl, E. J., Mustapic, M., Kapogiannis, D., Eitan, E., Lobach, I. V., Goetzl, L., Schwartz, J. B., Miller, B. L. Cargo disease. FASEB 30, 3853–3859 (2016) www.fasebj.org

Language: Английский

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Neutrophil-Based Drug Delivery Systems

Advanced Materials, Journal Year: 2018, Volume and Issue: 30(22)

Published: March 26, 2018

Abstract White blood cells (WBCs) are a major component of immunity in response to pathogen invasion. Neutrophils the most abundant WBCs humans, playing central role acute inflammation induced by pathogens. Adhesion vasculature and tissue infiltration neutrophils key processes inflammation. Many inflammatory/autoimmune disorders cancer therapies have been found be involved activation neutrophils. A promising strategy develop novel targeted drug delivery systems is targeting exploitation activated Herein, new platform based on reviewed. There two types systems: as carriers neutrophil‐membrane‐derived nanovesicles. It discussed how nanoparticles hijack vivo deliver therapeutics across vessel barriers nanovesicles target inflamed vasculature. Finally, potential applications neutrophil‐based treating cancers presented.

Language: Английский

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