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1.
Biomédica (Bogotá) ; 41(3): 555-589, jul.-set. 2021. tab, graf
Article in Spanish | LILACS | ID: biblio-1345403

ABSTRACT

Resumen En la última década se ha incrementado el número de estudios y publicaciones sobre las vesículas extracelulares y los exosomas. En Colombia, ha habido interés y avances en su estudio, lo que se evidencia en el aumento de publicaciones y proyectos de investigación. Sin embargo, este es un campo de investigación aún en desarrollo, con desafíos analíticos y limitaciones técnicas, por lo cual, en el planteamiento de los proyectos de investigación y desarrollo, es necesario considerar cuál es el estado del campo científico a nivel mundial en cuanto a la nomenclatura y la clasificación de las vesículas extracelulares, las técnicas, recursos, requisitos y especificaciones de calidad y las instituciones que regulan el campo. La respuesta a esta pregunta permitirá desarrollar estudios que cumplan con los estándares internacionales, y las exigencias y recomendaciones institucionales. Sin embargo, la información científica disponible se encuentra dispersa y no todos los aspectos son tratados a cabalidad. En este actualización se condensa la información disponible y se presentan los términos oficiales para denominar las vesículas extracelulares y la nomenclatura aceptada actualmente, así como la evolución del campo, la homogenización de los parámetros experimentales, el establecimiento de autoridades científicas, instituciones y recursos, y las recomendaciones que se han generado a nivel mundial para el desarrollo de investigaciones en vesículas extracelulares, incluidos su aislamiento, caracterización y estudio funcional. Por último, se analiza el contexto nacional de una forma crítica, teniendo en cuenta las fortalezas institucionales, los errores usualmente cometidos, y las técnicas y tecnologías analíticas disponibles.


Abstract In the last decade, the number of studies and publications on extracellular vesicles (EV) and exosomes has boomed. Colombia has displayed interest and progress in their study as shown in the increase of research project publications and products. However, this research field is still developing and has its own analytical challenges and technical limitations. For planning research projects and developing EV studies it is necessary to consider what is the state of the scientific field worldwide concerning EV nomenclature and classification, available techniques, resources, requirements and quality specifications, and the institutions that regulate the field. Answering this question will elicit EV studies that comply with international standards and respond to institutional demands and recommendations. However, the scientific information available is scattered and not all the aspects are considered in full. In this update, the available information is condensed and the official terms and currently defined nomenclature is presented, as well as the evolution of the field, the homogenization of the experimental parameters, the establishment of scientific authorities, institutions, and resources, and the recommendations generated worldwide for their development and research including their isolation, characterization, and functional studies. Finally, I analyzed the national context in a critical way, considering institutional strengths, common mistakes, and available analytical techniques and technologies.


Subject(s)
Extracellular Vesicles , Chemistry Techniques, Analytical , Resource Guide , Cell-Derived Microparticles , Exosomes , Chemical Phenomena , Terminology as Topic
2.
Rev. cuba. invest. bioméd ; 40(1): e930, ene.-mar. 2021. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1289453

ABSTRACT

Introducción: Las enfermedades infecciosas del tracto respiratorio se encuentran entre las primeras causas de entidades respiratorias en edades extremas de la vida. Objetivo: Describir las bases inmunológicas de la enfermedad y el nuevo candidato vacunal conjugado antineumocócico PCV7-TT desarrollado en Cuba. Métodos: Se realizó una búsqueda en las bases de datos Medline, Pubmed, SciELO, LILACS, Cochrane Library y Web of Science, de documentos publicados entre mayo del 2018 y marzo del 2020. Se seleccionaron los 64 artículos de mayor relevancia y novedad. Resultados: Streptococcus pneumoniae es el agente etiológico de la enfermedad neumocócica; se le atribuye alrededor de un millón de defunciones anuales, principalmente en países en vías de desarrollo. Es un coco Gram-positivo, anaerobio facultativo y encapsulado que se encuentra dividido en 48 serogrupos y 97 serotipos tipificados. Presenta varios factores de virulencia que garantizan su mecanismo de patogenicidad; uno de los más importantes es el polisacárido capsular que constituye la diana de las vacunas antineumocócicas conjugadas y no conjugadas existentes. En el presente artículo se consideró la proteína de superficie C del neumococo como un posible candidato en la investigación y desarrollo de vacunas preventivas. Asimismo, las vesículas extracelulares podría ser un posible candidato para adyuvante vacunal con fines preventivos y terapéuticos. Conclusiones: El neumococo es un problema de salud a nivel global y el uso de vacunas conjugadas antineumocócicas constituye la herramienta más eficaz para su prevención. El candidato vacunal PCV7-TT desarrollado en Cuba es seguro, bien tolerado, inmunogénico y no inferior a las vacunas actualmente registradas(AU)


Introduction: Infectious diseases of the respiratory tract are among the leading causes of respiratory conditions in patients at extreme ages. Objective: Describe the immunological bases of the disease and the new conjugate pneumococcal vaccine candidate PCV7-TT developed in Cuba. Methods: A search was conducted in the databases Medline, Pubmed, SciELO, LILACS, Cochrane Library and Web of Science for documents published from May 2018 to March 2020. The 64 most relevant and novel papers were selected. Results: Streptococcus pneumoniae is the causative agent of pneumococcal disease, a condition causing about one million deaths a year worldwide, mainly in developing countries. It is a Gram-positive facultative anaerobic encapsulated coccus divided into 48 serogroups and 97 typified serotypes. Several virulence factors ensure its pathogenicity mechanism. One of the most important of these is the capsular polysaccharide constituting the target of the existing conjugate and non-conjugate pneumococcal vaccines. The study considered pneumococcal surface protein C as a possible candidate for the research and development of preventive vaccines. On the other hand, extracellular vesicles could be a possible vaccine adjuvant candidate for preventive and therapeutic use. Conclusions: Pneumococcus is a global health problem, and the use of conjugate pneumococcal vaccines is the most effective tool for its prevention. The vaccine candidate PCV7-TT developed in Cuba is safe, well-tolerated, immunogenic and not inferior to the vaccines so far registered(AU)


Subject(s)
Humans , Polysaccharides , Streptococcus pneumoniae , Communicable Diseases , Pneumococcal Vaccines , Virulence Factors , Extracellular Vesicles , Membrane Proteins
3.
Clinics ; 76: e2081, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249582

ABSTRACT

OBJECTIVES: Extracellular vesicle microRNAs (EV-miRNAs) have been demonstrated to be reliable candidate biomarkers for clinical applications. However, the clinical application potential of serum EV-miR-215-5p for gastric cancer (GC) remains poorly understood. The goal of our study was to determine the efficacy of serum EV-miR-215-5p in predicting the prognosis of GC. METHODS: Blood samples were collected from 118 patients with GC, 60 patients with benign gastric disease and BGD and 70 healthy controls. The relative levels of serum EV-miR-215-5p were measured using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Compared to patients with BGD and normal controls, GC patients exhibited remarkably higher serum EV-miR-215-5p level, especially those with early tumor recurrence (ETR). Receiver operating characteristic (ROC) curve analysis showed that serum EV-miR-215-5p was able to distinguish GC patients from BGD patients or healthy controls and GC patients with ETR from those without ETR. In addition, increased serum EV-miR-215-5p levels were notably correlated with invasive depth, TNM stage, and lymph node metastasis. Moreover, serum EV-miR-215-5p levels were greatly decreased after surgical treatment, but increased at the time of ETR. Survival analysis showed that patients with higher serum EV-miR-215-5p had shorter survival. Furthermore, serum EV-miR-215-5p was an independent risk factor for GC. CONCLUSIONS: Serum EV-miR-215-5p might be a novel biomarker for predicting ETR and prognosis of GC.


Subject(s)
Humans , Stomach Neoplasms/genetics , MicroRNAs , Extracellular Vesicles , Prognosis , Biomarkers, Tumor , Neoplasm Recurrence, Local
4.
Article in English | WPRIM | ID: wpr-880641

ABSTRACT

Traumatic brain injury (TBI) is a main cause of death and disability worldwide, posing a serious threat to public health. But currently, the diagnosis and treatments for TBI are still very limited. Exosomes are a group of extracellular vesicles and participate in multiple physiological processes including intercellular communication and substance transport. Non-coding RNAs (ncRNA) are of great abundancy as cargo of exosomes. Previous studies have shown that ncRNAs are involved in several pathophysiological processes of TBI. However, the concrete mechanisms involved in the effects induced by exosome-derived ncRNA remain largely unknown. As an important component of exosomes, ncRNA is of great significance for diagnosis, precise treatment, response evaluation, prognosis prediction, and complication management after TBI.


Subject(s)
Brain Injuries, Traumatic/genetics , Cell Communication , Exosomes/genetics , Extracellular Vesicles , Humans , RNA, Untranslated/genetics
5.
Article in English | WPRIM | ID: wpr-878319

ABSTRACT

Objective@#Epidemiological studies reveal that exposure to fine particulate matter (aerodynamic diameter ≤ 2.5 μm, PM @*Methods@#EVs were isolated from the serum of healthy subjects, quantified @*Results@#PM @*Conclusions@#EVs treatment promotes cell survival and attenuates PM


Subject(s)
A549 Cells , Air Pollutants/toxicity , Apoptosis/drug effects , Cell Survival/drug effects , Extracellular Vesicles , Humans , Male , Middle Aged , Particulate Matter/toxicity , Protective Agents/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Serum
6.
São Paulo; s.n; 2021. 126 p. ilus.
Thesis in Portuguese | ColecionaSUS, LILACS, ColecionaSUS, SES-SP, SESSP-CTDPROD, SES-SP, SESSP-TESESESSP, SES-SP | ID: biblio-1358653

ABSTRACT

Toxoplasma gondii é causador da toxoplasmose, uma das doenças mais prevalentes no mundo. Estudos recentes mostraram que vesículas extracelulares (EVs) liberadas por parasitas participam no processo de invasão e replicação no hospedeiro, porém o mecanismo de infecção ainda não está completamente elucidado. O objetivo desse trabalho foi identificar e caracterizar EVs produzidas por taquizoítos das cepas RH, ME-49 e VEG de T. gondii e a participação na patogênese da toxoplasmose. Purificação de EVs liberadas das três cepas de T. gondii foi realizada por cromatografia de exclusão de tamanho seguida por ELISA. Concentração e tamanho das vesículas isoladas foram analisados por Nanoparticle Tracking Analysis, o qual mostrou que as três cepas possuem perfis de liberação de EVs similares, com maior produção observada pela cepa RH. Quando analisados diferentes tempos de incubação, observou-se que em 2 horas de incubação ocorreu maior liberação de EVs do que em 24 horas de incubação, para as três cepas. A maior parte das vesículas encontradas possuía tamanho entre 100-200 nm, caracterizadas como microvesículas. Observou-se através de imagens capturadas por Microscopia Eletrônica de Varredura que a cepa RH liberou mais EVs do que as cepas VEG e ME-49. Após a análise de taquizoítos da cepa RH por Microscopia Eletrônica de Transmissão, observou-se que no


Subject(s)
Toxoplasma , Cytokines , Extracellular Vesicles
7.
J. venom. anim. toxins incl. trop. dis ; 27: e20200187, 2021. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1351016

ABSTRACT

Background: The efficacy of bone marrow mesenchymal stromal cells (BM-MSC) and its extracellular vesicles has been demonstrated for a broad spectrum of indications, including kidney diseases. However, BM-MSC donor characteristics and their potential are not usually considered. Therefore, the present work aims to evaluate the nephroprotective capacity of sEV secreted by BM-MSC from trained rats inunilateral ureteral obstruction (UUO) model. Methods: BM-MSC was characterized by their differentiation potential and immunophenotypic markers. The sEV were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis and western blot. Its miRNA cargo was examined by quantitative PCR analysis for miR-26a, 126a, and 296. Wistar rats were submitted to UUO procedure and concomitantly treated with sEV secreted by BM-MSC from the untrained andtrained rats. The kidney tissue from all groups was evaluated for fibrosis mediators (transforming growth factor beta1 and collagen), CD34-angiogenesis marker, and hypoxia-inducible factor 1 alpha (HIF-1α). Results: Treadmill training stimulated in BM-MSC the production of sEV loaded with pro-angiogenic miR-296. The treatment with this sEVin UUO-rats was able to attenuate collagen accumulation and increase CD34 and HIF-1α in the kidney tissue when compared to untrained ones. Tubular proximal cells under hypoxia and exposed to BM-MSC sEV demonstrate accumulation in HIF-1α and NFR-2 (nuclear factor erythroid 2-related factor 2), possibly to mediate the response to hypoxia and oxidative stress, under these conditions. Conclusion: The BM-MSC sEV from trained animals presented an increased nephroprotective potential compared to untrained vesicles by carrying 296-angiomiR and contributing to angiogenesis in UUO model.(AU)


Subject(s)
Ureteral Obstruction , Extracellular Vesicles , Kidney Diseases , Hypoxia , Oxidative Stress
9.
J. venom. anim. toxins incl. trop. dis ; 26: e20190067, 2020. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1135161

ABSTRACT

Extracellular vesicles (EVs) are small membrane-bound vesicles of growing interest in vetetinary parasitology. The aim of the present report was to provide the first isolation, quantification and protein characterization of EVs from buffalo (Bubalus bubalis) sera infected with Theileria spp. Methods: Infected animals were identified through optical microscopy and PCR. EVs were isolated from buffalo sera by size-exclusion chromatography and characterized using western blotting analysis, nanoparticle tracking analysis and transmission electron microscopy. Subsequently, the proteins from isolated vesicles were characterized by mass spectrometry. Results: EVs from buffalo sera have shown sizes in the 124-140 nm range and 306 proteins were characterized. The protein-protein interaction analysis has evidenced biological processes and molecular function associated with signal transduction, binding, regulation of metabolic processes, transport, catalytic activity and response to acute stress. Five proteins have been shown to be differentially expressed between the control group and that infected with Theileria spp., all acting in the oxidative stress pathway. Conclusions: EVs from buffaloes infected with Theileria spp. were successfully isolated and characterized. This is an advance in the knowledge of host-parasite relationship that contributes to the understanding of host immune response and theileriosis evasion mechanisms. These findings may pave the way for searching new EVs candidate-markers for a better production of safe biological products derived from buffaloes.(AU)


Subject(s)
Animals , Buffaloes/microbiology , Communicable Diseases , Theileria , Nanoparticles , Extracellular Vesicles , Biological Phenomena , Proteomics
10.
Chinese Journal of Biotechnology ; (12): 632-642, 2020.
Article in Chinese | WPRIM | ID: wpr-827005

ABSTRACT

Extracellular vesicles (EVs) refer to bilayer membrane transport vesicles secreted by cells. EVs can take macromolecules from cells and transfer them to receptor cells. Among these macromolecular substances, the most studied are microRNAs (miRNAs). miRNA is non-coding RNA involved in the regulation of gene expression. It has been confirmed that there are different non-coding RNAs in mammalian follicular fluid EVs. EVs carrying miRNA can act as an alternative mechanism for autocrine and paracrine, affecting follicular development. This paper systematically introduced the kinds, characteristics and methods of isolation and identification of EVs, focusing on the effects of EVs and miRNAs on follicular development, including early follicular development, oocyte maturation, follicular dominance and effects on granulosa cell function. At the same time, the authors prospected the future research of EVs and microRNAs in follicular fluid, and provided ideas and directions for the research and application of EVs and miRNA functions in follicular fluid.


Subject(s)
Animals , Extracellular Vesicles , Metabolism , Female , Follicular Fluid , Chemistry , Granulosa Cells , MicroRNAs , Pharmacology , Oogenesis
11.
Article in English | WPRIM | ID: wpr-785393

ABSTRACT

Methods for reproducibly isolating and enriching small extracellular vesicles (EVs) from blood are essential for clinical utilization of small EVs in cancer patients. We combined ultracentrifugation (UC) with polymer-based precipitation (ExoQuick [EQ] or Total Exosome Isolation [TEI] kit) to isolate small EVs (diameter, 30–150 nm) from the serum of breast cancer patients. We compared the performance of four cycles of UC (UC4x) with that of two cycles of UC followed by enrichment using the EQ (UC2x→EQ) or TEI (UC2x→TEI) kits. The mean concentration of small EVs isolated from 1 mL of serum using UC2x→EQ (139.0±29.1 µg) and UC2x→TEI (140.4±5.0 µg) did not differ from that obtained using UC4x (141.8±26.9 µg). The mean number of EV particles obtained using UC4x was 29.2±9.9×109 per mL of serum, whereas UC2x→EQ and UC2x→TEI yielded higher numbers of EVs (50.7±17.0×10⁹ and 59.3±20.6×10⁹, respectively). Concentrations of EV microRNAs, including miR-21 and miR-155, did not differ between the three methods. In conclusion, performing UC prior to the use of polymer-based precipitation kits could be feasible for isolating small EVs from human serum in large sample-based translational researches.


Subject(s)
Breast Neoplasms , Extracellular Vesicles , Humans , MicroRNAs , Translational Medical Research , Ultracentrifugation
12.
Article in English | WPRIM | ID: wpr-880849

ABSTRACT

Macrophages play an important role in material-related immune responses and bone formation, but the functionality of macrophage-derived extracellular vesicles (EVs) in material-mediated bone regeneration is still unclear. Here, we evaluated intracellular communication through small extracellular vesicles (sEVs) and its effects on endogenous bone regeneration mediated by biomimetic intrafibrillarly mineralized collagen (IMC). After implantation in the bone defect area, IMC generated more neobone and recruited more mesenchymal stem cells (MSCs) than did extrafibrillarly mineralized collagen (EMC). More CD63


Subject(s)
Biomimetics , Bone Regeneration , Cell Differentiation , Collagen , Extracellular Vesicles , Macrophages , Osteogenesis
13.
Rev. méd. Chile ; 147(12): 1503-1509, dic. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1094183

ABSTRACT

Background During pregnancy, there is an increase in the amount of extracellular vesicles, especially placental exosomes, in maternal plasma. Aim To isolate and characterize extracellular vesicles from blood during the three trimesters of pregnancy and to evaluate their capacity to identify patients at risk of developing gestational diabetes. Material and Methods A case-control study was conducted in a cohort of 50 pregnant women with plasma samples taken in each trimester. Six women who developed gestational diabetes were paired with three healthy controls per case (a total of 19). Clinical characteristics were recorded at first prenatal appointment, and blood samples were obtained during the first, second and third trimesters. Extracellular vesicles were isolated from plasma by the commercial kit, ExoQuick™. Nanoparticle tracking analysis, was used to characterize the obtained extracellular vesicles. Results The total concentration of extracellular particles isolated from maternal plasma increased along with gestational age. The size of the extracellular vesicles obtained in the first trimester of pregnancy was very similar between groups (144 ± 37 nm for controls and 143 ± 34 nm for patients with gestational diabetes mellitus). Moreover, the concentration of extracellular vesicles collected in the first trimester, was significantly higher in patients who developed gestational diabetes mellitus later in pregnancy compared to normoglycemic pregnant women (7.94 x 10 8 and 5.15 x 10 8 , p = 0.03). Conclusions Our results provide an insight into the potential capacity of first trimester plasma extracellular vesicles as early biomarkers for the prediction of gestational diabetes mellitus.


Subject(s)
Humans , Female , Pregnancy , Adult , Diabetes, Gestational/blood , Extracellular Vesicles/metabolism , Biomarkers/blood , Case-Control Studies , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity , Diabetes, Gestational/diagnosis
14.
Article in Chinese | WPRIM | ID: wpr-812997

ABSTRACT

Extracellular vesicles (EVs), including apoptotic bodies, microvesicles and exosomes, play a crucial role in cell-to-cell communication. EVs derived from various cell types have the potential to deliver complex information to endothelial cells and to induce either pro- or anti-angiogenic signaling.


Subject(s)
Cell-Derived Microparticles , Endothelial Cells , Extracellular Vesicles , Humans , Neovascularization, Pathologic
15.
Article | WPRIM | ID: wpr-785411

ABSTRACT

Skeletal mineralization is initiated in matrix vesicles (MVs), the small extracellular vesicles derived from osteoblasts and chondrocytes. Calcium and inorganic phosphate (Pi) taken up by MVs form hydroxyapatite crystals, which propagate on collagen fibrils to mineralize the extracellular matrix. Insufficient calcium or phosphate impairs skeletal mineralization. Because active vitamin D is necessary for intestinal calcium absorption, vitamin D deficiency is a significant cause of rickets/osteomalacia. Chronic hypophosphatemia also results in rickets/osteomalacia. Excessive action of fibroblast growth factor 23 (FGF23), a key regulator of Pi metabolism, leads to renal Pi wasting and impairs vitamin D activation. X-linked hypophosphatemic rickets (XLH) is the most common form of hereditary FGF23-related hypophosphatemia, and enhanced FGF receptor (FGFR) signaling in osteocytes may be involved in the pathogenesis of this disease. Increased extracellular Pi triggers signal transduction via FGFR to regulate gene expression, implying a close relationship between Pi metabolism and FGFR. An anti-FGF23 antibody, burosumab, has recently been developed as a new treatment for XLH. In addition to various forms of rickets/osteomalacia, hypophosphatasia (HPP) is characterized by impaired skeletal mineralization. HPP is caused by inactivating mutations in tissue-nonspecific alkaline phosphatase, an enzyme rich in MVs. The recent development of enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase has improved the prognosis, motor function, and quality of life in patients with HPP. This links impaired skeletal mineralization with various conditions, and unraveling its pathogenesis will lead to more precise diagnoses and effective treatments.


Subject(s)
Absorption , Alkaline Phosphatase , Calcium , Chondrocytes , Collagen , Diagnosis , Durapatite , Enzyme Replacement Therapy , Extracellular Matrix , Extracellular Vesicles , Familial Hypophosphatemic Rickets , Fibroblast Growth Factors , Gene Expression , Humans , Hypophosphatasia , Hypophosphatemia , Metabolism , Miners , Osteoblasts , Osteocytes , Prognosis , Quality of Life , Receptors, Fibroblast Growth Factor , Rickets , Signal Transduction , Vitamin D , Vitamin D Deficiency
16.
Article in Chinese | WPRIM | ID: wpr-774321

ABSTRACT

Bone marrow (BM) microenvironment appears to play an important role in the pathogenesis of hematological malignancies. Apart from soluble factors and direct cell-cell contact, the extracellular vesicles (EVs) were identified as a third mediator for cell communication within BM microenvironment. Recently, more and more evidences have demonstrated that EVs are also involved in the dysregulation of the BM microenvironment in patients with hematological malignancies. Therefore this review focuses on the biological characteristics of EVs, the clinical value of EVs as biomarkers, the BM microenvironment reprogramming in hematological malignancies by EVs, and the potential role of EVs in drug resistance and therapy of hematological malignancies.


Subject(s)
Bone Marrow , Cell Communication , Extracellular Vesicles , Hematologic Neoplasms , Humans
17.
Article in English | WPRIM | ID: wpr-759014

ABSTRACT

The exocyst is a highly conserved eight-subunit protein complex (EXOC1–8) involved in the targeting and docking of exocytic vesicles translocating from the trans-Golgi network to various sites in renal cells. EXOC5 is a central exocyst component because it connects EXOC6, bound to the vesicles exiting the trans-Golgi network via the small GTPase RAB8, to the rest of the exocyst complex at the plasma membrane. In the kidney, the exocyst complex is involved in primary ciliognesis, cystogenesis, and tubulogenesis. The exocyst, and its regulators, have also been found in urinary extracellular vesicles, and may be centrally involved in urocrine signaling and repair following acute kidney injury. The exocyst is centrally involved in the development of other organs, including the eye, ear, and heart. The exocyst is regulated by many different small GTPases of the RHO, RAL, RAB, and ARF families. The small GTPases, and their guanine nucleotide exchange factors and GTPase-activating proteins, likely give the exocyst specificity of function. The recent development of a floxed Exoc5 mouse line will aid researchers in studying the role of the exocyst in multiple cells and organ types by allowing for tissue-specific knockout, in conjunction with Cre-driver mouse lines.


Subject(s)
Acute Kidney Injury , Animals , Cell Membrane , Ear , Exocytosis , Extracellular Vesicles , GTP Phosphohydrolases , GTPase-Activating Proteins , Guanine Nucleotide Exchange Factors , Heart , Humans , Kidney , Mice , Monomeric GTP-Binding Proteins , Sensitivity and Specificity , trans-Golgi Network
18.
Article in English | WPRIM | ID: wpr-728028

ABSTRACT

Decursin is a major biological active component of Angelica gigas Nakai and is known to induce apoptosis of metastatic prostatic cancer cells. Recently, other reports have been commissioned to examine the anticancer activities of this plant. In this study, we evaluated the inhibitory activity and related mechanism of action of decursin against glioblastoma cell line. Decursin demonstrated cytotoxic effects on U87 and C6 glioma cells in a dose-dependent manner but not in primary glial cells. Additionally, decursin increased apoptotic bodies and phosphorylated JNK and p38 in U87 cells. Decursin also down-regulated Bcl-2 as well as cell cycle dependent proteins, CDK-4 and cyclin D1. Furthermore, decursin-induced apoptosis was dependent on the caspase activation in U87 cells. Taken together, our data provide the evidence that decursin induces apoptosis in glioblastoma cells, making it a potential candidate as a chemotherapeutic drug against brain tumor.


Subject(s)
Angelica , Apoptosis , Brain Neoplasms , Cell Cycle , Cell Cycle Checkpoints , Cell Line , Cyclin D1 , Extracellular Vesicles , Glioblastoma , Glioma , Neuroglia , Plants , Prostatic Neoplasms
19.
Article in English | WPRIM | ID: wpr-761908

ABSTRACT

BACKGROUND: Exosomes are membrane-enclosed extracellular vesicles implicated in cell-cell communication. Exosomes contain proteins, mRNAs, non-coding RNAs (miRNAs and lncRNAs) and lipids that are derived from producing cells. These nano-sized vesicles are present in biofluids including blood, urine, saliva, amniotic fluid, semen and conditioned media of cultured cells. METHODS: This review summarizes current progress on the strategies of development of diagnostic biomarkers and drug loading onto exosomes for overcoming cancer progression. RESULTS: A number of studies indicate that the exosome appears to be a key player in tissue repair and regeneration of in a number of animal disease models. In addition, alterations of the molecular profiles in exosomes are known to be correlated with the disease progression including cancer, suggesting their usefulness in disease diagnosis and prognosis. Studies utilizing engineered exosomes either by chemical or biological methods have demonstrated promising results in a number of animal models with cancer. CONCLUSION: Understanding the molecular and cellular properties of exosomes offer benefits for cancer diagnosis by liquid biopsy and for their application in therapeutic drug delivery systems. Studies have shown that genetic or molecular engineering of exosomes augmented their target specificity and anticancer activity with less toxicity. Thus, deeper understanding of exosome biology will facilitate their therapeutic potential as an innovative drug delivery system for cancer.


Subject(s)
Amniotic Fluid , Biology , Biomarkers , Biopsy , Cells, Cultured , Culture Media, Conditioned , Diagnosis , Disease Models, Animal , Disease Progression , Drug Delivery Systems , Exosomes , Extracellular Vesicles , Female , Models, Animal , Prognosis , Regeneration , RNA, Messenger , RNA, Untranslated , Saliva , Semen , Sensitivity and Specificity
20.
Article in English | WPRIM | ID: wpr-760655

ABSTRACT

A better understanding of the underlying mechanisms by which signals from the fetus initiate human parturition is required. Our recent findings support the core hypothesis that oxidative stress (OS) and cellular senescence of the fetal membranes (amnion and chorion) trigger human parturition. Fetal membrane cell senescence at term is a natural physiological response to OS that occurs as a result of increased metabolic demands by the maturing fetus. Fetal membrane senescence is affected by the activation of the p38 mitogen activated kinase-mediated pathway. Similarly, various risk factors of preterm labor and premature rupture of the membranes also cause OS-induced senescence. Data suggest that fetal cell senescence causes inflammatory senescence-associated secretory phenotype (SASP) release. Besides SASP, high mobility group box 1 and cell-free fetal telomere fragments translocate from the nucleus to the cytosol in senescent cells, where they represent damage-associated molecular pattern markers (DAMPs). In fetal membranes, both SASPs and DAMPs augment fetal cell senescence and an associated ‘sterile’ inflammatory reaction. In senescent cells, DAMPs are encapsulated in extracellular vesicles, specifically exosomes, which are 30–150 nm particles, and propagated to distant sites. Exosomes traffic from the fetus to the maternal side and cause labor-associated inflammatory changes in maternal uterine tissues. Thus, fetal membrane senescence and the inflammation generated from this process functions as a paracrine signaling system during parturition. A better understanding of the premature activation of these signals can provide insights into the mechanisms by which fetal signals initiate preterm parturition.


Subject(s)
Aging , Cellular Senescence , Cytosol , Exosomes , Extracellular Vesicles , Extraembryonic Membranes , Female , Fetus , Humans , Inflammation , Membranes , Obstetric Labor, Premature , Oxidative Stress , Paracrine Communication , Parturition , Phenotype , Pregnancy , Premature Birth , Risk Factors , Rupture , Telomere
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