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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
31

A large-scale targeted proteomics of plasma extracellular vesicles shows utility for prognosis prediction subtyping in colorectal cancer / 血漿細胞外小胞体を対象とした大規模ターゲットプロテオミクスの大腸癌予後予測サブタイプ分類における有用性

Kasahara, Keiko 23 May 2023 (has links)
京都大学 / 新制・論文博士 / 博士(医学) / 乙第13561号 / 論医博第2290号 / 新制||医||1067(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 武藤 学, 教授 今中 雄一, 教授 村川 泰裕 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM
32

Determining the Application of Small Extracellular Vesicles (SEVs) as Biomarkers of Arsenic Induced Urothelial Injury and Carcinogenesis

Washuck, Nicole 06 December 2022 (has links)
Arsenic is a toxic metalloid that continues to contaminate the water and food sources of millions of people globally. Among the numerous health effects of arsenic exposure are urothelial toxicity and cancer. In recent years, small extracellular vesicles (SEVs) have been shown to be vital in intracellular communication and have been used in clinical studies as biomarkers of disease. The overall goal of this thesis is to understand the mechanisms of cell communication during arsenic exposure and to develop minimally invasive biomarkers for the toxic responses. The specific objectives are to: a) determine if SEVs released from arsenic exposed urothelial cells are responsible for mediating urothelial toxicity; and b) assess the application of urinary SEVs as novel biomarkers of arsenic exposure in an exposed population. The hypothesis leading this research is that the biology and protein packaging profile of urothelial SEVs are altered following arsenic exposure because of the induction of cell stress signaling pathways. I also hypothesize that urinary SEV proteins can be used as biomarkers of arsenic exposure because they are positively correlated with urinary arsenic concentrations in an exposed population. SVHUC1 human urothelial cells were dosed with sodium meta arsenite (1, 2, and 5 uM) for 48 hours. T24 urothelial carcinoma cells were also grown in parallel to compare for carcinogenicity. A label-free quantitative proteomics approach was used to assess the differentially expressed proteins in the cell lysate and the SEVs extracted from the culture media to determine the mechanistic pathways involved and how well the protein profiles in SEVs correlate with those in the cell lysate. SEVs were isolated from the archived urine samples of participants (n=36) enrolled in the Yellow Knife Health Effects Monitoring Program (YKHEMP) and two potential biomarkers, transforming growth factor beta receptor 1 (TGFBR1) and ribonuclease inhibitor 1 (RNH1), were measured by an enzyme linked immunosorbent assay (ELISA). SEVs in all samples were successfully characterized based on their size (50-200 nm) and positive antibody array for eight protein markers indicating their endosomal biogenesis. The total number of SEVs was not shown to increase following arsenic exposure in the in vitro study. However, the cancerous T24 cells had nearly four times higher numbers of SEVS compared to the non-cancerous SVHUC1 cells. The changes in the protein profiles in SEVs released following arsenic dosage indicated activation of pathways important for cell survival, viability, and migration and inactivation of pathways related to cell death and necrosis which were also observed in the paired cell lysate samples. Comparison between paired SEV and cell lysate samples, however, indicated selective SEV packaging of proteins which may be for the purpose of intracellular communication. Comparative assessment of SEVs from T24 and arsenic exposed SVHUC1 cells showed similar activation of cancer related pathways including those responsible for malignant tumors and increased proliferation rates. From the in vitro study results, we identified 8 potential SEV biomarkers. Of which, TGFBR1 showed the most promising association, having been positively associated with both inorganic arsenic and cadmium concentrations in urine samples. This thesis showed that SEVs are important mediators of arsenic exposure in urothelial cells and highlighted the comparability of SEV and cell lysate analysis. Furthermore, TGFBR1 was identified as a promising biomarker of arsenic exposure for its positive association with increased arsenic both in vitro and in human biomonitoring analysis.
33

Particle Balances in Therapeutic Extracellular Vesicle Development and in depth Characterization of Fluorescence Nanoparticle Tracking Analysis

Deighan, Clayton J. January 2015 (has links)
No description available.
34

Development of a Freeze-Drying Strategy to Store Human Bone Marrow Mesenchymal Stem/Stromal Derived Extracellular Vesicles for Applications in Stroke

Dorus, Brian 25 January 2023 (has links)
Mesenchymal stem/stromal cells (MSCs) release Extracellular vesicles (EVs) that are believed to play a major role in nerve regeneration after stroke. However, a major complication when trying to transition MSC-EVs from a pre-clinical to clinical setting is the convenient long-term storage of MSC-EVs. Therefore, we developed a strategy to freeze dry MSC-EVs to store them for more practical clinical applications. We first determined the optimal trehalose concentration for freeze drying the MSC-EVs, and we subsequently investigated the optimal freezing conditions. It was determined that 100 mM of trehalose and freezing temperature at -20°C were the optimal conditions to freeze dry the EVs. The therapeutic capabilities of the freeze-dried MSC-EVs was tested via tube formation assay and co-culturing them with neural stem/progenitor cells (NSPCs). It was found that human vein umbilical endothelial cells (HUVECs) treated with rehydrated MSCEVs promoted tube formation suggesting the trophic factors in the MSC-EVs survived the freeze-drying process. As for the NSPC co-culture, all treatments involving rehydrated MSC-EVs protected by trehalose during the freeze-drying process promoted proliferation and did not affect their ability to differentiate into oligodendrocytes, astrocytes, or neurons. Determining the optimum freezing-drying conditions allows us to stockpile a large amount of MSC-EVs at room temperature for on-demand applications.
35

Application of Circulating Large Extracellular Vesicles as Biomarkers in Type 1 Diabetes Mellitus and Pregnancy

Abolbaghaei, Akramalsadat 11 July 2023 (has links)
Levels of circulating large extracellular vesicles (L-EVs) are increased in individuals with type 1 diabetes mellitus (T1DM) and associated with increased cardiovascular risk. T1DM in pregnancy induces vascular injury leading to adverse maternal and neonatal outcomes. Conversely, exercise has been shown to improve cardiovascular and metabolic health in pregnancy and may represent a non-pharmacological approach to improving pregnancy outcomes. Assessment of vascular health may aid in the identification of individuals at risk of complications and allow for intervention with strategies to improve the maternal vasculature. Unfortunately, there is a paucity of strategies for assessing vascular health in pregnant women. L-EVs are membrane-encapsulated particles released from stressed/injured cells. They are emerging biomarkers of vascular health. The purpose of this thesis was to assess the impact of T1DM and pregnancy on L-EV levels and protein composition, the relationship between L-EVs and pregnancy outcomes and the effect of exercise on L-EV levels. In aim #1, I observed that high levels of L-EVs are predictive of adverse pregnancy outcomes. In aim # 2, I examined the protein composition of circulating L-EVs in hypertensive, diabetic and healthy mice models. Diabetes-enriched proteins were involved in inflammation, SNARE signaling and NAD+ biogenesis. The changes were found in L-EV protein content were consistent with proteins associated with inflammation, cytoskeletal organization, and angiogenesis. Finally, in aim #3, I examined the changes in plasma L-EVs after an acute bout of moderate-intensity aerobic exercise in healthy pregnant and non-pregnant women. I observed that circulating L-EVs significantly decreased after the acute exercise only in non-pregnant individuals. Taken together, my thesis work advances knowledge on L-EVs in T1DM, pregnancy, and hypertension and sets the stage for future work on L-EVs as predictive biomarkers, for molecular profiling, and for monitoring of vascular health interventions in pregnancy.
36

Gut Microbiota Extracellular Vesicles as Signaling Carriers in Host-Microbiota Crosstalk

Sultan, Salma 24 October 2023 (has links)
Microbiota-released extracellular vesicles (MEVs) have emerged as key players in intercellular signaling in host-microbiome communications. However, their role in gut-brain axis signaling has been poorly investigated. Here, we performed deep multi-omics profiling of MEVs generated ex-vivo and from stool samples to gain insight into their role in gut-brain-axis signaling. Metabolomics unveiled a wide array of metabolites embedded in MEVs, including many neurotransmitter-related compounds such as arachidonyl-dopamine (NADA), gabapentin, glutamate, and N-acylethanolamines. To test the biodistribution of MEVs from the gut to other parts of the body, Caco-2, RIN-14B, and hCMEC/D3 cells showed the capacity to internalize labeled MEVs through an endocytic mechanism. Additionally, MEVs exhibited dose-dependent paracellular transport through Caco-2 intestinal cells and hCMEC/D3 brain endothelial cells. Overall, our results revealed the capabilities of MEVs to cross the intestinal and blood-brain barriers to delivering their cargo to distant parts of the body.
37

Discovery of lipid profiles in plasma-derived extracellular vesicles as biomarkers for breast cancer diagnosis / 血漿由来細胞外小胞内の脂質プロファイルに注目した乳癌診断バイオマーカーの発見

Liu, Lin 23 January 2024 (has links)
京都大学 / 新制・課程博士 / 博士(医学) / 甲第24993号 / 医博第5027号 / 新制||医||1069(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 滝田 順子, 教授 岩田 想, 教授 万代 昌紀 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
38

Engineering Extracellular Vesicles for Therapeutic Applications

Salazar Puerta, Ana Isabel January 2022 (has links)
No description available.
39

Perfil de miRNAs intracelulares e liberados via vesículas extracelulares na diferenciação neural de células-tronco pluripotentes. / Intracellular and extracellular vesicles miRNAs profile during neural differentiation of pluripotent stem cells.

Cruz, Lilian 05 April 2017 (has links)
As células-tronco processam e são sensíveis a múltiplos sinais dentro de seu microambiente, os quais podem exercer influências que regulam seu destino e sua função de forma espaço temporal. Neste contexto, células podem exercer seu papel biológico por transferir informação genética e alterar expressão gênica de alvos celulares através de vesículas extracelulares (VEs). MicroRNAs (miRNAs), uma classe de pequenos RNAs não codificantes, podem ser encontrados nestas vesículas e são considerados moléculas efetivas no controle do neurodesenvolvimento por regular genes chaves em tempo controlado. Pouco se sabe sobre como a diferenciação influencia o conteúdo de miRNAs liberados via VEs revelando o papel dos mesmos no microambiente de cada etapa do comprometimento neural. Assim, a proposta deste estudo foi analisar o perfil de miRNAs intracelulares e presentes em VEs envolvidos na diferenciação neural dopaminérgica de células-tronco pluripotentes e identificar os possíveis alvos regulados pelos mesmos como mecanismo de estabelecimento de um destino neural específico. / Stem cells sense and process multiple signals in their microenvironment, which can exert influences that regulate cell fate and function in a time spatial manner. In this context, the stem cells can exert their biological role transferring genetic information and altering the genetic expression of target cells through extracellular vesicles (EVs). MicroRNAs (miRNAs), a class of small non coding RNAs, can be found in those EVs and are considered effective molecules in the control of neurodevelopment and differentiation by regulating key genes in a time specific manner. However, little is known about how the cell differentiation influences the miRNAs content released through EVs, and how these molecules function in the microenvironment of each phase of neural commitment. Thus, the purpose of this study was to analyze the intracellular and EVs miRNAs profiles involved in the dopaminergic differentiation of pluripotent stem cells in attempt to identify possible targets regulated by miRNAs as a mechanism of specific neural fate decision.
40

Comprehensive molecular characterization of extracellular vesicles : an approach to resolve their biogenetic and functional diversity / Caractérisation moléculaire comparative des vésicules extracellulaires : une approche pour résoudre leur diversité biogénétique et fonctionnelle

Kowal, Joanna 30 March 2016 (has links)
Les vésicules extracellulaires (EVs) participent à la communication intercellulaire. Dans la littérature actuelle, elles sont divisées en deux classes principales selon leur origine intracellulaire. En premier lieu, les exosomes sont formés à l'intérieur des endosomes multivésiculaires et sont libérés lors de la fusion de ces compartiments avec la membrane plasmique (MP). La taille des exosomes est contrôlée au cours de leur biogenèse et varie de 50 à 150 nm. Deuxièmement, les EVs sont formées par bourgeonnement direct et sécrétion à partir de la MP. Ces EVs sont plus hétérogènes et leur taille varie de 50 à 1000 nm. Malgré le fait que la nature hétérogène de EVs soit clairement documentée dans la littérature, la composition en protéines et les mécanismes exacts de la biogenèse des différentes EVs restent un sujet de débat en cours. Le but principal de ce travail était de redéfinir autant de sous-types différents d’EVs que possible, en trouvant des marqueurs protéiques spécifiques, et d'étudier les outils possibles pour affecter spécifiquement leur sécrétion. Dans ce projet, nous avons mis en place plusieurs outils utiles pour la caractérisation d’EVs. Tout d'abord, mes principaux efforts ont été concentrés sur la mise en place de plusieurs protocoles d'isolation et d'analyse d’EVs. Cela a conduit à la production d'une cartographie des protéines vésiculaires, qui si elle est appliquée pour caractériser les EVs, permettra de mieux les identifier par leur composition. Deuxièmement, j'ai étudié la façon dont la sécrétion de ces sous-populations d’EVs peut être modulée par l'inhibition de quelques protéines de la famille RAB et par certaines drogues. Enfin, grâce à une collaboration établie au sein de l'unité, j'ai eu l'occasion de participer à une comparaison des propriétés fonctionnelles entre les EVs et les virus sécrétés simultanément par les cellules infectées. Mes résultats confirment l'hypothèse selon laquelle l'origine intracellulaire des EVs sera reflétée dans leur composition. Les résultats présentés confirment la coexistence de plusieurs classes d'EVs et donnent un aperçu sur les moyens de les caractériser dans une préparation d’EVs donnée. En outre, nous fournissons un exemple de l'application de notre ensemble de protéines dans les études portant sur la biogenèse des EVs. / Extracellular vesicles (EVs) are participating in intercellular communication. Classically, in the current literature, they are divided into two main classes depending on their intracellular origin. Firstly, exosomes are formed within multivesicular endosomes and released upon fusion of these compartments with plasma membrane. The size of exosomes is controlled during their biogenesis and ranges from 50 to 150 nm. Secondly, EVs are formed by direct budding and pinching off from the plasma membrane. These EVs are more heterogeneous and their size varies from 50 to 1000 nm. Despite the fact that a heterogeneous nature of EVs is clearly documented in the literature, the exact protein content and biogenesis mechanisms of different EVs remain a matter of on-going debate. The principal goal of this work was to re-define as many different subtypes of EVs as possible, by finding specific protein markers, and investigate possible tools to affect specifically their secretion. In this project, we set up several tools useful for EV characterization. Firstly, my main efforts were concentrated on establishment of several protocols to isolate and analyse EVs. This led to the foundation of a vesicle protein cartography, which if applied to characterize EVs, will allow better understanding of the composition of the studied EVs. Secondly, I investigated how secretion of these EV subpopulations might be modulated by inhibition of a few RAB proteins and by some drugs. Finally, thanks to a collaboration established within the unit, I had the opportunity to participate in a comparison of the functional properties between EVs and viruses secreted simultaneously by infected cells. My results confirmed the hypothesis that the intracellular origin of EVs will be reflected in their composition. The results presented in this study point at the coexistence of several EV classes and provide insights on how to demonstrate their presence in a given EV preparation. In addition, we provide an example of the application of our set of proteins in studies addressing EV biogenesis.

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