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1.
Curr Protoc ; 2(1): e352, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35030291

RESUMO

Extracellular vesicles (EVs) in plants have emerged as key players in cell-to-cell communication and cross-kingdom RNAi between plants and pathogens by facilitating the exchange of RNA, proteins, and other molecules. In addition to their role in intercellular communication, plant EVs also show promise as potential therapeutics and indicators of plant health. However, plant EVs exhibit significant heterogeneity in their protein markers, size, and biogenesis pathways, strongly influencing their composition and functionality. While mammalian EVs can be generally classified as exosomes that are derived from multivesicular bodies (MVBs), microvesicles that are shed from the plasma membrane, or as apoptotic bodies that originate from cells undergoing apoptosis, plant EVs remain poorly studied in comparison. At least three subclasses of EVs have been identified in Arabidopsis leaves to date, including Tetraspanin-positive exosomes derived from MVBs, Penetration 1 (PEN1)-positive EVs, and EVs derived from exocyst-positive organelles (EXPO). Differences in the plant starting material and isolation techniques have resulted in different purities, quality, and compositions of the resulting EVs, complicating efforts to better understand the role of these EVs in plants. We performed a comparative analysis on commonly used plant EV isolation methods and have identified an effective protocol for extracting clean apoplastic washing fluid (AWF) and isolating high-quality intact and pure EVs of Arabidopsis thaliana. These EVs can then be used for various applications or studied to assess their cargos and functionality in plants. Furthermore, this process can be easily adapted to other plant species of interest. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Isolation of EVs from the apoplastic fluid of Arabidopsis thaliana Basic Protocol 2: Density gradient fractionation of EVs Basic Protocol 3: Immuno-isolation of EVs using Arabidopsis tetraspanin 8 (TET8) antibody.


Assuntos
Arabidopsis , Micropartículas Derivadas de Células , Exossomos , Vesículas Extracelulares , Animais , Folhas de Planta
2.
Anal Chim Acta ; 1191: 339279, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35033266

RESUMO

Exosomes are promising biomarkers for cancer screening, but the development of a robust approach that can sensitively and accurately detect exosomes remains challenging. In the present study, an aptasensor based on the multifunctional signal probe 10-benzyl-2-amino-acridone (BAA) was developed for the colorimetric and photoelectrochemical detection and quantitation of exosomes. Exosomes are captured by cholesterol DNA anchor-modified magnetic beads (MBs) through hydrophobic interactions. This capture process can be monitored under a confocal fluorescence microscope using BAA as the fluorescent signal probe. The aptamer modified copper oxide nanoparticles (CuO NPs) then bind to mucin 1 (MUC1) on the surface of the exosomes to form a sandwich structure (MBs-Exo-CuO NPs). Finally, the MBs-Exo-CuO NPs are dissolved in nitric acid to generate Cu2+, which inhibits the visible-light-induced oxidase mimic activity and photoelectrochemical activity of BAA simultaneously. The changes in absorbance and photocurrent intensities are directly proportional to the concentration of exosomes. In this dual-modal aptasensor, the colorimetric assay can achieve rapid screening and identification, which is especially useful for point-of-care testing. The UV-vis absorbance and photocurrent assays then provide quantitative information, with a limit of detection of 1.09 × 103 particles µL-1 and 1.38 × 103 particles µL-1, respectively. The proposed aptasensor thus performs dual-modal detection and quantitation of exosomes. This aptasensor provides a much-needed toolset for exploring the biological roles of exosomes in specific diseases, particularly in the clinical setting.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Exossomos , Acridonas , Colorimetria , Limite de Detecção
3.
Acta Neurol Taiwan ; 31(1): 1-6, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-34988948

RESUMO

Exosomes are believed to be secreted from multivesicular endosomes and containing proteins and nucleic acids, including mRNA and microRNAs, which have been implicated to play a role in neurodegenerative diseases. Neuron-derived exosomes at the circulation provide a unique potential as biomarkers towards assessment of Alzheimer's disease (AD), even at the pre-clinical stage. This review briefly discusses their biogenesis and transport, exosomal protein verses soluble protein, evidence for their role in AD, isolation of exosomes, and challenges and future directions to realize reliable blood-based biomarkers to meet phenomenal unmet clinical and pre-clinical need of AD.


Assuntos
Doença de Alzheimer , Exossomos , Doença de Alzheimer/diagnóstico , Biomarcadores , Humanos
4.
Ecotoxicol Environ Saf ; 229: 113084, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34915223

RESUMO

The deficiency of effective biomarker for the toxic effects of water pollutants greatly limits the application of biological monitoring. This study aimed to investigate the possibility of circulating exosomes of indigenous fish acting as biomarker for the ecotoxicity effect of water environment. The Helong Reservoir in Guangzhou, China, was chosen as the investigating field, of which the water quality belongs to Class V (2013) (GB 3838-2002, China). The clean drinking water source of the upper reaches of the Liuxihe Reservoir was selected as the control. Indigenous fishes including Oreochromis niloticus (Nile tilapia), Labeo rohita (Rohu), Carassius auratus (Crucian carp) were sampled during the period from July 2020 to April 2021. Circulating exosomes of fish samples were isolated by using ultracentrifugation, characterized with transmission electron microscopy (TEM) and quantified by using bicinchoninic acid (BCA) assay. Oxidative stress, DNA and chromosome damage in liver, kidney, brain, gill and blood of fish samples were measured. The results showed that there were significant differences in superoxide dismutase (SOD) activity, glutathione (GSH) and malondialdehyde (MDA) contents, DNA and chromosome damage in fish samples between the Helong Reservoir and the control. Interestingly, there were also significant differences in circulating exosome levels of fish samples between them. Our data suggested that circulating exosome level of indigenous fish may be a novel biomarker for the ecotoxicity effects of water environment.


Assuntos
Ciclídeos , Exossomos , Poluentes Químicos da Água , Animais , Biomarcadores/metabolismo , Ciclídeos/metabolismo , Carpa Dourada/metabolismo , Fígado/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade
5.
Oncol Rep ; 47(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34779497

RESUMO

Epstein­Barr virus (EBV) is endemic worldwide and is associated with a number of human tumors. EBV­associated tumors have unique mechanisms of tumorigenesis. EBV encodes multiple oncogenic molecules that can be loaded into exosomes released by EBV+ tumor cells to mediate intercellular communication. Moreover, different EBV+ tumor cells secrete exosomes that act on various target cells with various biological functions. In addition to oncogenicity, EBV+ exosomes have potential immunosuppressive effects. Investigating EBV+ exosomes could identify the role of EBV in tumorigenesis and progression. The present review summarized advances in studies focusing on exosomes and the functions of EBV+ exosomes derived from different EBV­associated tumors. EBV+ exosomes are expected to become a new biomarker for disease diagnosis and prognosis. Therefore, exosome­targeted therapy displays potential.


Assuntos
Carcinoma/patologia , Carcinoma/virologia , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Exossomos/patologia , Exossomos/virologia , Herpesvirus Humano 4 , Humanos
6.
Biosens Bioelectron ; 199: 113872, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34902643

RESUMO

The exosome is considered a useful biomarker for the early diagnosis of cancer. However, pretreatment of samples used in diagnosis is time-consuming. Herein, we fabricated a capacitance-based electrical biosensor that requires no pretreatment of the sample; it is composed of a DNA aptamer/molybdenum disulfide (MoS2) heterolayer on an interdigitated micro-gap electrode (IDMGE)/printed circuit board (PCB) system for detecting exosomes in an undiluted serum sample. The DNA aptamer detects the CD63 protein on the exosome as the biomarker, while the MoS2 nanoparticle enhances electrical sensitivity. In this study, for the first time, the IDMGE system was used to amplify the electrical signal efficiently for exosome detection. The IDMGE amplifies the capacitance signal as the gap between electrodes decreases, making it easy to detect the target by utilizing the heightened sensitivity. Moreover, it is possible to immobilize a bio-probe more efficiently than with an electrical sensitivity-enhancing electrode with the same area. The thiol-modified (SH-) CD63 DNA aptamer was introduced as the bio-probe that selectively binds to the CD63 protein on the exosome surface. The capacitance signal from the IDMGE electrical sensor increased linearly with the increase in the concentration of exosomes in human serum expressed on a logarithmic scale, the detection limit being 2192.6 exosomes/mL. The proposed biosensor can detect exosomes in undiluted human serum with high selectivity and sensitivity. A blind test was also carried out to test the reliability of the biosensor. The capacitance-based electrical biosensor thus offers a new platform for cancer diagnosis in the future.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Exossomos , Capacitância Elétrica , Humanos , Reprodutibilidade dos Testes
7.
Colloids Surf B Biointerfaces ; 209(Pt 1): 112163, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34736220

RESUMO

Mesenchymal stem cells (MSCs) are multipotent stem cells with the capacity to differentiate into several cell types under appropriate conditions. They also possess remarkable antitumor features that make them a novel choice to treat cancers. Accumulating evidence suggest that the MSCs-derived extracellular vesicles, known as exosomes, play an essential role in the therapeutic effects of MSCs mainly by carrying biologically active factors. However, limitations such as low yield of exosomes and difficulty in isolation and purification hinder their clinical applications. To overcome these issues, research on development of exosome-mimics has attracted great attention. This systematic review represents, to the best of our knowledge, the first thorough evaluations of the innate antineoplastic features of MSCs-derived exosomes or exosome-mimics, the methods of drug loading, application as drug delivery system and their impacts on targeted cancer therapy. Importantly, we dissect the commonalities and differences as well as address the shortcomings of work accumulated over the last two decades and discuss how this information can serve as a guide map for optimal experimental design implementation ultimately aiding the effective transition into clinical trials.


Assuntos
Exossomos , Vesículas Extracelulares , Células-Tronco Mesenquimais , Neoplasias , Portadores de Fármacos , Humanos , Neoplasias/tratamento farmacológico
8.
Mol Med Rep ; 25(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34821373

RESUMO

Coronavirus disease 2019 (COVID­19) is a global pandemic that can have a long­lasting impact on public health if not properly managed. Ongoing vaccine development trials involve classical molecular strategies based on inactivated or attenuated viruses, single peptides or viral vectors. However, there are multiple issues, such as the risk of reversion to virulence, inability to provide long­lasting protection and limited protective immunity. To overcome the aforementioned drawbacks of currently available COVID­19 vaccines, an alternative strategy is required to produce safe and efficacious vaccines that impart long­term immunity. Exosomes (key intercellular communicators characterized by low immunogenicity, high biocompatibility and innate cargo­loading capacity) offer a novel approach for effective COVID­19 vaccine development. An engineered exosome­based vaccine displaying the four primary structural proteins of SARS­CoV­2 (spike, membrane, nucleocapside and envelope proteins) induces humoral and cell mediated immunity and triggers long­lasting immunity. The present review investigated the prospective use of exosomes in the development of COVID­19 vaccines; moreover, exosome­based vaccines may be key to control the COVID­19 pandemic by providing enhanced protection compared with existing vaccines.


Assuntos
Vacinas contra COVID-19 , COVID-19/prevenção & controle , Exossomos , Materiais Biocompatíveis , Vacinas contra COVID-19/imunologia , Exossomos/imunologia , Humanos , Imunidade Celular , Imunogenicidade da Vacina , Pandemias/prevenção & controle , SARS-CoV-2
9.
Biosens Bioelectron ; 200: 113902, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34954570

RESUMO

Exosomes are regarded as a promising biomarker for the noninvasive diagnosis and treatment of diseases. The value of exosomes for medical research has promoted the search for a fast, efficient, and sensitive detection method. This study reported a sandwich-based evanescent wave fluorescent biosensor (S-EWFB) for exosome detection. A two-step strategy was implemented to take advantages of the simple binding of fluorescent probes with exosomes via the hydrophobic interaction between the cholesteryl and phospholipid bilayer membrane, as well as real-time detection on an evanescent wave liquid-solid interface based on CD63 aptamer-specific capture to form an exosome@fluorescence probe/aptamer sandwich structure. The one-to-many connection between exosomes and signal molecules and the aptamer-modified evanescent wave optical fiber detection platform reduced the detection limit of exosomes to 7.66 particles/mL, with a linear range of 47.5-4.75 × 106 particles/mL. The entire detection process was simple, rapid, and real-time and lasted about 1 h while requiring no separation and purification. Additionally, this platform showed excellent surface regeneration capability and exhibited good performance during the analysis of tumor and non-tumor-derived exosomes.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Exossomos , Corantes Fluorescentes , Oligonucleotídeos , Fibras Ópticas
10.
Methods Mol Biol ; 2393: 3-14, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34837171

RESUMO

Exosomes are nanosized (50-150 nm) extracellular vesicles released by all types of cells in the body. They transport various biological molecules, such as DNAs, RNAs, proteins, and lipids from parent cells to recipient cells for intercellular communication. Exosomes, especially those from tumor cells, are actively involved in caner development, metastasis, and drug resistance. Recently, many studies have shown that exosomal proteins are promising biomarkers for cancer screening, early detection and prognosis. Among many detection techniques, surface plasmon resonance (SPR) is a highly sensitive, label-free, and real-time optical detection method. Commercial prism-based wavelength/angular-modulated SPR sensors afford high sensitivity and resolution, but their large footprint and high cost limit their adaptability for clinical settings. We have developed an intensity-modulated, compact SPR biosensor (25 cm × 10 cm × 25 cm) for the detection of exosomal proteins. We have demonstrated the potential application of the compact SPR biosensor in lung cancer diagnosis using exosomal epidermal growth factor receptor (EGFR) and programmed death-ligand 1 (PD-L1) as biomarkers. The compact SPR biosensor offers sensitive, simple, fast, user-friendly, and cost-effective detection of exosomal proteins, which may serve as an in vitro diagnostic test for cancer.


Assuntos
Ressonância de Plasmônio de Superfície , Técnicas Biossensoriais , Detecção Precoce de Câncer , Exossomos , Humanos , Neoplasias Pulmonares
11.
Life Sci Alliance ; 5(3)2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34862272

RESUMO

Murine neural stem cells (NSCs) were recently shown to release piRNA-containing exosomes/microvesicles (Ex/Mv) for exerting antiviral immunity, but it remains unknown if these Ex/Mv could target SARS-CoV-2 and whether the PIWI-piRNA system is important for these antiviral actions. Here, using in vitro infection models, we show that hypothalamic NSCs (htNSCs) Ex/Mv provided an innate immunity protection against SARS-CoV-2. Importantly, enhanced antiviral actions were achieved by using induced Ex/Mv that were derived from induced htNSCs through twice being exposed to several RNA fragments of SARS-CoV-2 genome, a process that was designed not to involve protein translation of these RNA fragments. The increased antiviral effects of these induced Ex/Mv were associated with increased expression of piRNA species some of which could predictably target SARS-CoV-2 genome. Knockout of piRNA-interacting protein PIWIL2 in htNSCs led to reductions in both innate and induced antiviral effects of Ex/Mv in targeting SARS-CoV-2. Taken together, this study demonstrates a case suggesting Ex/Mv from certain cell types have innate and adaptive immunity against SARS-CoV-2, and the PIWI-piRNA system is important for these antiviral actions.


Assuntos
Proteínas Argonauta/metabolismo , COVID-19/imunologia , COVID-19/metabolismo , Micropartículas Derivadas de Células/metabolismo , Exossomos , RNA Interferente Pequeno/metabolismo , RNA/metabolismo , SARS-CoV-2 , Células A549 , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Genoma Viral , Humanos , Hipotálamo/metabolismo , Sistema Imunitário , Imunidade Inata , Técnicas In Vitro , Camundongos
12.
Virology ; 565: 22-28, 2022 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-34638006

RESUMO

Adeno-associated virus (AAV) are classified as non-enveloped ssDNA viruses. However, AAV capsids embedded within exosomes have been observed, and it has been suggested that the AAV membrane associated accessory protein (MAAP) may play a role in envelope-associated AAV (EA-AAV) capsid formation. Here, we observed and selected sufficient homogeneous EA-AAV capsids of AAV2, produced using the Sf9 baculoviral expression system, to determine the cryo-electron microscopy (cryo-EM) structure at 3.14 Å resolution. The reconstructed map confirmed that the EA-AAV capsid, showed no significant structural variation compared to the non-envelope capsid. In addition, the Sf9 expression system used implies the notion that MAAP may enhance exosome AAV encapsulation. Furthermore, we speculate that these EA-AAV capsids may have therapeutic benefits over the currently used non-envelope AAV capsids, with advantages in immune evasion and/or improved infectivity.


Assuntos
Proteínas do Capsídeo/ultraestrutura , Capsídeo/ultraestrutura , Dependovirus/ultraestrutura , Animais , Capsídeo/química , Proteínas do Capsídeo/química , Microscopia Crioeletrônica , Dependovirus/química , Exossomos , Evasão da Resposta Imune , Conformação Proteica , Células Sf9
13.
Exp Neurol ; 347: 113895, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34653510

RESUMO

Injury of oligodendrocytes (OLs) induces demyelination, and patients with neurodegenerative diseases exhibit demyelination concomitantly with neurological deficit and cognitive impairment. Oligodendrocyte progenitor cells (OPCs) are present in the adult central nervous system (CNS), and they can proliferate, differentiate, and remyelinate axons after damage. However, remyelination therapies are not in clinical use. Multiple sclerosis (MS) is a major demyelinating disease in the CNS. Mesenchymal stromal cells (MSCs) have demonstrated therapeutic promise in animal models and in clinical trials of MS. Exosomes are nanoparticles generated by nearly all cells and they mediate cell-cell communication by transferring cargo biomaterials. Here, we hypothesize that exosomes harvested from MSCs have a similar therapeutic effect on enhancement of remyelination as that of MSCs. In the present study we employed exosomes derived from rhesus monkey MSCs (MSC-Exo). Two mouse models of demyelination were employed: 1) experimental autoimmune encephalomyelitis (EAE), an animal model of MS; and 2) cuprizone (CPZ) diet model, a toxic demyelination model. MSC-Exo or PBS were intravenously injected twice a week for 4 weeks, starting on day 10 post immunization in EAE mice, or once a week for 2 weeks starting on the day of CPZ diet withdrawal. Neurological and cognitive function were tested, OPC differentiation and remyelination, neuroinflammation and the potential underlying mechanisms were investigated using immunofluorescent staining, transmission electron microscopy and Western blot. Data generated from the EAE model revealed that MSC-Exo cross the blood brain barrier (BBB) and target neural cells. Compared with the controls (p < 0.05), treatment with MSC-Exo: 1) significantly improved neurological outcome; 2) significantly increased the numbers of newly generated OLs (BrdU+/APC+) and mature OLs (APC+), and the level of myelin basic protein (MBP); 3) decreased amyloid-ß precursor protein (APP)+ density; 4) decreased neuroinflammation by increasing the M2 phenotype and decreasing the M1 phenotype of microglia, as well as their related cytokines; 5) inhibited the TLR2/IRAK1/NFκB pathway. Furthermore, we confirmed that the MSC-Exo treatment significantly improved cognitive function, promoted remyelination, increased polarization of M2 phenotype and blocked TLR2 signaling in the CPZ model. Collectively, MSC-Exo treatment promotes remyelination by both directly acting on OPCs and indirectly by acting on microglia in the demyelinating CNS. This study provides the cellular and molecular basis for this cell-free exosome therapy on remyelination and modulation of neuroinflammation in the CNS, with great potential for treatment of demyelinating and neurodegenerative disorders.


Assuntos
Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/patologia , Exossomos/transplante , Células-Tronco Mesenquimais/metabolismo , Remielinização , Animais , Feminino , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Remielinização/fisiologia
14.
Talanta ; 236: 122870, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635251

RESUMO

Exosomes encapsulate genomic and proteomic biomarkers for non-invasive diagnosis and disease monitoring. However, exosome surface-markers heterogeneity is a major drawback of current isolation methods. Here, we report a direct, one-step exosome sampling technology, ExoPRIME, for selective capture of CD63+ exosome subpopulations using an immune-affinity protocol. Microneedles (300µm × 30 mm), functionalized with anti-CD63 antibodies, were incubated under various experimental conditions in conditioned astrocyte medium and astrocyte-derived exosome suspension. The probe's capture efficiency and specificity were validated using FluoroCet assay, immunofluorescent imaging, and OMICS analyses. Significantly higher exosomes were captured by probes incubated for 16 h at 4 0C in enriched exosomal suspension (23 × 10 6 exosomes per probe) vis-à-vis 2 h at 4 0 C (12 × 10 6) and 16 h at 22 0C (3 × 10 6) in conditioned cell media. Our results demonstrate the application of ExoPRIME over a broad dynamic range of temperature and incubation parameters, offering flexibility for any desired application. ExoPRIME permits the use and re-use of minimal sample volumes (≤200 µL), can be multiplexed in arrays, and integrated into a lab-on-a-chip platform to achieve parallel, high-throughput isolation of different exosome classes in a semi-automated workstation. This platform could provide direct exosomal analysis of biological fluids since it can elegantly interface with existing room-temperature, picomolar-range nucleic acid assays to provide a clinical diagnostic tool at the point of care.


Assuntos
Exossomos , Proteômica , Biomarcadores , Dispositivos Lab-On-A-Chip
15.
Biosens Bioelectron ; 196: 113707, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34695686

RESUMO

Exosomal microRNAs (miRNAs) play a key role in cell-cell communication to regulate gene expression in target cells and have great potential as biomarkers for disease diagnosis. This paper reports an on-chip exosomal miRNA amplification and detection system for rapid analysis of exosomal miRNAs. The compact system consists of two connected flow cells for processing exosomes and detecting miRNAs, respectively. The miRNAs extracted from exosomes were quantitatively measured using the on-chip exponential amplification reaction (EXPAR) assay. The sensor chip was designed to store multiple oligonucleotide templates for the EXPAR, mix sample and reagent, and simultaneously analyze multiple exosomal miRNAs of interest. To facilitate the miRNA analysis, a portable detection instrument was built on an IoT platform using a low-cost microcontroller to execute the EXPAR assay, collect fluorescent images, and analyze amplification curves. Here, we studied the miRNA profiles carried by exosomes derived from three different phenotypes of tissue macrophages. The affordable instrument, rapid assay, multiplexed analysis, as well as disposable sensor chip, would boost the development of point-of-care liquid biopsy tests using exosomal miRNAs.


Assuntos
Técnicas Biossensoriais , Exossomos , MicroRNAs , Exossomos/genética , MicroRNAs/genética , Análise de Sequência com Séries de Oligonucleotídeos , Oligonucleotídeos
16.
Cell Biochem Funct ; 40(1): 49-59, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34921424

RESUMO

Exosomes can be secreted by various cells and function as intercellular communication vehicles by delivering specific cargoes from the donor cells to the recipient cells through their paracrine activity. Recently, an increasing number of studies have shown that non-coding RNAs (ncRNAs) could be entrapped in and transferred between cartilage-related cells as exosomal cargoes to modulate the expression of various target genes by regulation at post-transcriptional and post-translational levels. They are mainly comprised of microRNAs, long non-coding RNAs, and circular RNAs. Articular cartilage degeneration is one of the main pathological features of osteoarthritis. Exosomal ncRNAs are involved in pathological processes of osteoarthritis, such as proliferation, migration, chondrogenesis, chondrocyte differentiation induction, extracellular matrix formation, apoptosis, and inflammation. In this review, we summarize the biological functions of exosomal ncRNAs in cartilage homeostasis and osteoarthritis progression and discuss the perspectives and challenges of exosomal ncRNAs application for osteoarthritis patients in the future. Exosomal ncRNA has an important regulatory role in the pathogenesis of osteoarthritis, but more evidence is needed for clinical application.


Assuntos
Exossomos , MicroRNAs , Osteoartrite , RNA Longo não Codificante , Exossomos/genética , Humanos , MicroRNAs/genética , Osteoartrite/genética , RNA Longo não Codificante/genética , RNA não Traduzido/genética
17.
Exp Neurol ; 347: 113914, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34752783

RESUMO

Pregnancy is an inflammatory process that is carefully regulated by the placenta via immunomodulation and cell-to-cell communication of maternal and fetal tissues. Exosomes, types of extracellular vesicles, facilitate the intercellular communication and traffic biologically modifying cargo within the maternal-placental-fetal axis in normal and pathologic pregnancies. Chorioamnionitis is characterized by inflammation of chorioamniotic membranes that produces systemic maternal and fetal inflammatory responses of cytokine dysregulation and has been associated with brain injury and neurodevelopmental disorders. This review focuses on how pathologic placental exosomes propagate acute and chronic inflammation leading to brain injury. The evidence reviewed here highlights the need to investigate exosomes from pathologic pregnancies and those with known brain injury to identify new diagnostics, biomarkers, and potential therapeutic targets.


Assuntos
Lesões Encefálicas/metabolismo , Corioamnionite/metabolismo , Exossomos/metabolismo , Mediadores da Inflamação/metabolismo , Placenta/metabolismo , Lesões Encefálicas/patologia , Corioamnionite/patologia , Exossomos/patologia , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Placenta/patologia , Gravidez
18.
Chem Biol Interact ; 352: 109779, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-34922904

RESUMO

Growing evidence shows that cancer progression links with both heterogeneity of the tumor microenvironment and dysregulated activity of immune cells. Cancer-secreted exosomes are being recognized as indispensable mediators of the exchange cargo between cancer and immune cells. The M2-phenotype tumor-associated macrophages have the function of promoting tumor progression and drug resistance. Diffuse large B-cell lymphoma(DLBCL) is a highly heterogeneous and very common malignant non-Hodgkin's lymphoma. Here, we demonstrate that different subtype DLBCL cell-derived exosomes are internalized by macrophages, which can affect macrophages polarization. The mechanism of DLBCL-derived exosomes on macrophage polarization remains unclear currently. This study showed that DLBCL-secreted exosomes could induce the transformation of macrophages to a protumor M2-like phenotype, and block the drug-induced apoptosis of DLBCL cells in an indirect co-culture system. Different DLBCL-derived exosomes could change the phenotype of macrophages through the STAT3 signaling, which upregulated the expression of oncogenic genes and classical markers of M2-like phenotype macrophages, such as IL-10, CD206, and CD163. The addition of DLBCL-derived exosomes resulted in the activation of the STAT3 signaling pathway of M0/M2 macrophages in an indirect co-culture system. GP130 was highly enriched in DLBCL-derived exosomes, which triggered the activation of STAT3 of macrophages and subsequently induced the downstream targets such as BCL2, SURVIVIN, and BAX. The parallel changes of STAT3 and GP130 in macrophages confirmed that GP130 of DLBCL-derived exosomes promoted macrophage polarization by activating STAT3 signaling. Furthermore, all of these effects could be reversed by the GP130 inhibitor SC144. The data indicated that DLBCL-derived exosomes could trigger macrophages polarization into a pro-survival M2-like phenotype, which was at least partially through the GP130/STAT3 signaling pathway. Collectively, this study showed that DLBCL-derived exosomes could promote macrophages transformation to protumor M2-like phenotype in the tumor microenvironment.


Assuntos
Receptor gp130 de Citocina/imunologia , Exossomos/imunologia , Exossomos/metabolismo , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/metabolismo , Fator de Transcrição STAT3/metabolismo , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Linhagem Celular Tumoral , Receptor gp130 de Citocina/antagonistas & inibidores , Humanos , Hidrazinas/farmacologia , Imunofenotipagem , Modelos Biológicos , Fenótipo , Quinoxalinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/classificação
19.
Colloids Surf B Biointerfaces ; 209(Pt 2): 112218, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34801930

RESUMO

Regeneration of urethral defects has been difficult in the clinic. To address it, the collagen/ poly (L-lactide-co-caprolactone) (P(LLA-CL)) nanoyarn scaffold delivering adipose-derived stem cells' exosomes (ADSC-exos) was fabricated. The multipotential differentiation potential of ADSCs were confirmed by Adipogenic, osteogenic, and chondrogenic differentiation. The 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide assay shows that 50% concentration of ADSC-exos nanoyarn scaffold dramatically enhanced the cell viability of fibroblasts. The ADSC-exos nanoyarn scaffold for human foreskin fibroblasts (HFFs) and human urethral scar fibroblasts (HSFs) shows good biocompatibility: theproduction of inflammatory factors IL-6 and Col 1A1 was less, indicating that ADSC-exos had the minimal inflammatory effect of cells. Besides, the cells on the ADSC-exos nanoyarn scaffold did not appear to contribute to DNA damage in the same way as the normal cell's growth did. The HFFs seeding on the ADSC-exos nanoyarn scaffold shows a typical morphology of extending outwards. Urethral repair with ADSC-exos nanoyarn scaffold did not lead to either a sign of urethral stricture or scar formation after 4 weeks post-surgery. The deposition of collagen was less and the epithelial cells formed multiple layer epithelium. The treatment of ADSC-exos stimulated epithelization and vascularization. And the transition from an inflammatory state to a regenerative state was promoted. The ADSC-exos-treated group did not promote the over-proliferation of fibroblasts and the expression of Collagen I. Therefore, the ADSC-exos nanoyarn scaffold has evident, positive effects on wound healing and tissue fibrosis inhibition.


Assuntos
Exossomos , Nanofibras , Uretra , Tecido Adiposo , Colágeno , Humanos , Células-Tronco , Engenharia Tecidual , Cicatrização
20.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34647995

RESUMO

Seminal plasma contains a high concentration of extracellular vesicles (EVs). The heterogeneity of small EVs or the presence of nonvesicular extracellular matter (NV) pose major obstacles in understanding the composition and function of seminal EVs. In this study, we employed high-resolution density gradient fractionation to accurately characterize the composition and function of seminal EVs and NV. We found that the seminal EVs could be divided into 3 different subtypes-namely, high-density EV (EV-H), medium-density EV (EV-M), and low-density EV (EV-L)-after purification using iodixanol, while NV was successfully isolated. EVs and NV display different features in size, shape, and expression of some classic exosome markers. Both EV-H and NV could markedly promote sperm motility and capacitation compared with EV-M and EV-L, whereas only the NV fraction induced sperm acrosome reaction. Proteomic analysis results showed that EV-H, EV-M, EV-L, and NV had different protein components and were involved in different physiological functions. Further study showed that EV-M might reduce the production of sperm intrinsic reactive oxygen species through glutathione S-transferase mu 2. This study provides novel insights into important aspects of seminal EVs constituents and sounder footing to explore their functional properties in male fertility.


Assuntos
Vesículas Extracelulares/metabolismo , Proteômica/métodos , Sêmen/metabolismo , Motilidade Espermática , Reação Acrossômica , Biomarcadores/metabolismo , Biotinilação , Biologia Computacional , Exossomos/metabolismo , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Humanos , Masculino , Fosforilação , Proteínas Tirosina Fosfatases/química , Proteoma , Espécies Reativas de Oxigênio , Espermatozoides/metabolismo , Espermatozoides/fisiologia , Ácidos Tri-Iodobenzoicos/farmacologia
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