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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.
21

EVALUATION OF LYMPHATIC AND GLYMPHATIC ASSOCIATED EXTRACELLULAR VESICLE BIOMARKERS FOR SPORT-RELATED CONCUSSION

Rath, Meghan, 0000-0002-0952-8261 January 2022 (has links)
Purpose: Interdisciplinary research in epidemiology, neurology, neuroscience, and sports medicine commonly highlight the dangerous short- and long-term sequelae of sport-related concussions (SRC). Despite advancements in clinical evaluation and recognition, many SRCs are not properly diagnosed and managed, leaving many athletes in danger of acute and chronic neurological deficits. Epidemiological studies suggest the prevalence of chronic traumatic encephalopathy (CTE) is three times, and Alzheimer's disease is four times greater in former athletes with a history of SRC than non-athletes. The underlying mechanisms linking SRC and contact-sport participation to neurodegeneration are not fully understood. Herein, I hypothesized that transient insufficiency of the lymphatic and glymphatic clearance systems in the central nervous system (CNS) could play a crucial role in the SRC-mediated neurological conditions. Therefore, this study aimed to examine the differences in plasma levels of extracellular vesicles (EV) that are associated with the lymphatic and glymphatic clearance systems of the CNS among athletes following sport-related head impacts. Participants: Plasma EV concentrations were analyzed in collegiate athletes (controls n=29, SRC n=19) with and without SRC. In a parallel study, fourteen college-aged soccer players participated in a laboratory-based, repetitive subconcussion paradigm. All participants provided written informed consent, and the study was approved by institutional review board at Temple University. Methods: We evaluated EVs containing markers associated with the CNS lymphatic and glymphatic systems, including lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), astrocyte-specific glial fibrillary acidic protein (GFAP), aquaporin 4 (AQP4), and the platelet and endothelial cell adhesion molecule 1(PECAM-1 or CD31). Tetraspanin-28 (CD81) was used as an EV-specific marker. Blood samples from athlete controls were collected once during preseason baseline assessments. Samples from athletes with SRC were collected within 72 hours of injury. Whole blood was double-centrifuged to obtain platelet-poor plasma, snap-frozen in liquid nitrogen, and stored at -80°C until analyzed. Quantification of plasma EVs was performed using spectral flow cytometry. Mann-Whitney U tests were used for group comparisons of single and double-positive EV concentrations, and receiver-operating characteristic curve (ROC) and area under the curve (AUC) analyses assessed diagnostic efficacy. Within-group changes in plasma EVs following repetitive, subconcussive head impacts were assessed with Friedman's test using Dunn's correction for multiple comparisons. Results: Among athletes with SRC, plasma concentrations of LYVE1+EVs and CD31+EVs were significantly elevated within 72 hours of injury compared to controls (LYVE1+EVs, p < 0.0001; CD31+EVs, p = 0.005). ROC analysis revealed plasma concentrations of LYVE1+EVs demonstrated significant diagnostic accuracy to differentiate athletes with SRC from athlete controls (AUC: 0.971, 95% C.I. = 0.933-1.000, p < 0.0001). Notably, concentrations of LYVE1+/CD81+ double-positive EVs, CD31+/CD81+ double-positive EVs, and GFAP+/CD81+ double-positive EVs were significantly higher among athletes with SRC within 72 hours of injury compared to control athletes (p < 0.0001; p = 0.0002; p < 0.0001, respectively). Plasma AQP4+/GFAP+ double-positive EVs and AQP4+/CD81+ double-positive EVs were not. However, plasma concentrations of GFAP+/CD81+ double-positive EVs and AQP4+/GFAP+ double-positive EVs were significantly elevated after repetitive, subconcussive head impacts (p < 0.0001 and p = 0.004, respectively). Conclusion: Plasma concentrations of double-positive EVs, including LYVE1+/CD81+EVs, CD31+/CD81+EVs, and GFAP+/CD81+EVs, may be promising biomarkers for acute SRC. EVs associated with the glymphatic system, GFAP+/CD81+EVs and AQP4+/GFAP+EVs, were significantly elevated after repetitive subconcussive head impacts. The differences observed in EV responses to SRC and subconcussion may provide novel mechanistic insights about sport-associated neurodegeneration for current and future athletes. / Kinesiology
22

To determine the role of the Platelet activating factor - receptor in FOLFIRINOX therapy-mediated microvesicles particle generation

Awasthi, Krishna 08 May 2023 (has links)
No description available.
23

The Modulatory Role of Circulating Microvesicles in Endothelial Progenitor Cell Function Is Altered in T2DM.

Ammar, Hala Mustafa 30 May 2014 (has links)
No description available.
24

Extracellular Microvesicles as a Novel Biomarker for Wound Healing

Mari, Walid Omran, Dr. 23 May 2017 (has links)
No description available.
25

Usage of Extracellular Microvesicles as Novel and Promising Therapeutic Tool in Wound Healing

Alsabri, Sami Gamaleddin F. January 2017 (has links)
No description available.
26

Characterization of Histone H1 and Extracellular Vesicles by Mass Spectrometry

Harshman, Sean William January 2013 (has links)
No description available.
27

Regulation of the tumour suppressor PTEN through exosomes

Gabriel, Kathleen 10 1900 (has links)
<p>PTEN is a potent tumour suppressor protein. Aggressive and metastatic prostate cancer (PC) is associated with a reduction or loss of PTEN expression. PTEN reduction often occurs without gene mutations, and its downregulation is not fully understood. Herein, we show that PTEN is incorporated in the cargo of exosomes derived from cancer cells, and this is an exclusive characteristic of cancer cells; normal cells do not incorporate PTEN in their exosomes. We found that this process is affected by the expression of oncogenes, with activation of oncogenic molecules leading to increased PTEN incorporation into exosomes. PTEN expressed in exosomes can be transferred to other cells that have a reduction or loss of PTEN expression. The transferred PTEN is active, as cells showed a substantial increase in phosphatase activity upon treatment with PTEN-bearing exosomes. PTEN transferred through exosomes is also competent to confer tumour-suppression activity to acceptor cells. After incubation with PTEN-bearing exosomes, recipient cells exhibited decreased AKT phosphorylation, changes in the expression of cell cycle mediators indicating cell cycle arrest, and decreased proliferation. These data suggest that exosomal PTEN may be able to compensate for PTEN loss in cancer cells, by transferring the active protein to cancer cells where it can then perform its role as a tumour suppressor.</p> / Master of Science (MSc)
28

The study of exosomes and microvesicles secreted from breast cancer cell lines

Zheng, Ying January 2012 (has links)
Exosomes are small secreted vesicles of endocytic origin with a size range of 50-150 nm. They are secreted by many cell types and display multiple biological functions including immune-activation, immune-suppression, antigen presentation, and the shuttling of mRNA and miRNA, as well as other cargo. We have characterised the exosomes secreted from two breast cancer cell lines, MDA-MB-231 and MCF7. Exosomes secreted from both cell lines display typical markers including ALIX, Tsg101, CD9 and CD63, and were capable of inducing apoptosis of the Jurkat T cell line, indicating the potential immune-suppressive function of such tumour-derived exosomes. To further investigate the biological potential of exosomes, we loaded purified exosomes with gene specific siRNAs using electroporation, and observed the targeted inhibition of both a known component of the exosome pathway, Rab27a, and also the arthritis associated gene ERAP1, demonstrating the potential novel use of exosomes as therapeutic gene delivery vectors. We have also shown that exosomes derived from MDA-MB-231 cells and the parental cells have different lipid composition, as analysed by lipidomics study. Nanoparticle tracking analysis (NTA), which allows the rapid detection of size and concentration of nanoparticles within the size range 10 nm-1000 nm was tested for its ability to accurately measure size and concentration of exosomes and microvesicles under different conditions. NTA was capable of detecting apoptotic vesicles induced by Taxol and Curcumin treatment. Immunodepletion was used to determine the percentage of CD9 and CD63 positive vesicles. Our data suggest that NTA is a useful technique for measuring size and concentration of exosomes and microvesicles. We hypothesized that NTA could assist in the screening of agents that interfere or promote exosome release. NTA was therefore used to detect increases in exosomes secretion induced by Tamoxifen and Thimerosal treatment, and to monitor the inhibition of exosome secretion from MDA-MB-231 breast cancer cells expressing inhibitory RNA targeted for Rab27a, a component of the exosome pathway. Increases in exosome release induced by Tamoxifen and Thimerosal was detected by NTA and a significant reduction in the release of exosomes by inhibition of Rab27a expression was also observed. Treatment with the known exosomal pathway inhibitor DMA also reduced exosome release, establishing the principle of NTA as a screening technique. We further compared the siRNA targeted cells for their ability to migrate, invade and form anchorage-independent colonies, which were all significantly reduced. Supplementation with MDA-MB-231 derived exosomes restored the ability to form colonies, suggesting exosomes may contribute to metastatic lesion formation. These data suggest that the exosomal pathway is a valid target to disrupt the behaviour of tumour cells and NTA can be used to monitor its activity.
29

Effet de la radiothérapie sur la libération de microvésicules tumorales par des cellules de glioblastome / Impact of radiotherapy on the release of tumor microvesicles by glioblastoma cells

Ding, Haixia 10 December 2014 (has links)
Dans le glioblastome (GBM), la radiothérapie est un outil thérapeutique essentiel. Néanmoins, la récidive post-irradiation est quasiment inévitable, en raison de l’émergence d'une sous-population de cellules cancéreuses particulièrement radiorésistantes présentant une meilleure capacité proliférative, invasive et pro-angiogénique. Notre étude in vitro a cherché à déterminer comment les cellules cancéreuses survivantes à l’irradiation pouvaient affecter la fonction des cellules tumorales voisines et les cellules endothéliales non irradiées, en focalisant notre attention sur l’échange des signaux intercellulaires, à savoir, les facteurs solubles et les microvésicules tumorales (TMVs). La radiothérapie induit principalement un ralentissement de la prolifération des cellules de glioblastome (T98G et U87) et une mort cellulaire retardée (clonogénique) de 50-60%, sans engendrer d’apoptose. Grâce au suivi de la croissance cellulaire à long terme (via le système xCELLigence) et un test de blessure, nous avons confirmé que les cellules de glioblastome survivantes après irradiation libèrent des signaux qui peuvent modifier les fonctions de cellules endothéliales HUVEC et de cellules tumorales non-irradiées. Outre la sécrétion de certains facteurs solubles connus (VEGF, uPA), nous avons pu objectiver, en utilisant la microscopie électronique à balayage, le Nanoparticle Tracking Analysis (NTA), la libération de microvésicules tumorales (TMVs), dont la taille était globalement inférieure à 500 nm. Par NTA et cytométrie en flux, nous avons montré que cette libération de TMVs (exosome + "shedding vesicles"), peut être significativement stimulée par l’irradiation dans les 2 lignées, de façon temps-dépendant. D’après nos analyses protéomiques, les facteurs solubles tels que le VEGF ou l’IL-8, connus pour être des facteurs pro-angiogéniques, contribueraient plutôt à favoriser la survie, voire la prolifération, des cellules HUVEC, tandis que les TMVs libérées après irradiation, ont significativement modifié la capacité de migration des HUVEC et des cellules tumorales non-irradiées. Les propriétés pro-migratoires des TMVs pourraient en ce sens, contribuer aux processus de récidive dans les glioblastomes après irradiation / Radiation therapy is a major therapeutic tool for glioblastoma (GBM). However, the post-radiation recurrence is almost inevitable, due to the emergence of a subpopulation of radioresistant cancer cells with greater proliferative, invasive, and proangiogenic capacities. The objective of this study was to investigate in vitro how irradiated cancer cells affect the function of untreated neighboring tumor cells and endothelial cells, focusing on signals exchange initiated by irradiation, such as soluble factors and tumor microvesicles (TMVs). Radiotherapy has slowed down the proliferation of GBM cells (T98G, U87) and induced mitotic death of 50-60%, without significant apoptosis. Through long-term monitoring of cell growth (xCELLigence) and wound-healing assay, we have confirmed that surviving GBM cells after irradiation release signals that can change the functions of endothelial cells HUVEC and non-irradiated tumor cells. In addition to the secretion of known soluble factors (VEGF, uPA), we were able to show using scanning electron microscopy and the Nanoparticle Tracking Analysis (NTA), the release of tumor microvesicles (TMVS), whose size was generally less than 500 nm. By NTA and flow cytometry, we have shown that the release of TMVs (exosome + "shedding vesicles") can be significantly stimulated by irradiation in two lines, in a time-dependent manner. According to the proteomics analysis, soluble factors such as VEGF or IL-8, well known as pro-angiogenic factors, rather contribute to promote the survival or proliferation of HUVEC, while the released TMVs after irradiation, significantly altered the migration abilities of non-irradiated HUVEC and tumor cells. The pro-migratory properties of TMVs could thus contribute to glioblastoma recurrence after irradiation
30

About hyaluronan in the hypertrophic heart : studies on coordinated regulation of extracellular matrix signalling

Hellman, Urban January 2010 (has links)
Background. Myocardial hypertrophy is a risk factor for cardiovascular morbidity and mortality. Independent of underlying disease, the cardiac muscle strives in different ways to compensate for an increased workload. This remodelling of the heart includes changes in the extracellular matrix which will affect systolic and diastolic cardiac function. Furthermore, signal transduction, molecular diffusion and microcirculation will be affected in the hypertrophic process. One important extracellular component is the glycosaminoglycan hyaluronan. It has been shown to play a major role in other conditions that feature cellular growth and proliferation, such as wound healing and malignancies. The aim of this thesis was to investigate hyaluronan and its role in both an experimental rat model of cardiac hypertrophy as well as in cultured mouse cardiomyocytes and fibroblasts. Methods. Cardiac hypertrophy was induced in rats by aortic ligation. Hyaluronan concentration was measured and expression of genes coding for hyaluronan synthases were quantified after 1, 6 and 42 days after operation, in cardiac tissue from the left ventricular wall. Localization of hyaluronan and its receptor CD44 was studied histochemically. Hyaluronan synthesis was correlated to gene transcription using microarray gene expression analysis. Cultures of cardiomyocytes and fibroblasts were stimulated with growth factors. Hyaluronan concentration was measured and expression of genes coding for hyaluronan synthases were detected. Hyaluronan size was measured and crosstalk between cardiomyocytes and fibroblasts was investigated. Results. Increased concentration of hyaluronan in hypertrophied cardiac tissue was observed together with an up-regulation of two hyaluronan synthase genes. Hyaluronan was detected in the myocardium and in the adventitia of cardiac arteries whereas CD44 staining was mainly found in and around the adventitia. Hyaluronan synthesis correlated to the expression of genes, regulated by transcription factors known to initiate cardiac hypertrophy. Stimulation of cardiomyocytes by PDGF-BB induced synthesis of hyaluronan. Cardiomyocytes also secreted a factor into culture media that after transfer to fibroblasts initiated an increased synthesis of hyaluronan. When stimulated with hyaluronan of different sizes, a change in cardiomyocyte gene expression was observed. Different growth factors induced production of different sizes of hyaluronan in fibroblasts. The main synthase detected was hyaluronan synthase-2. Cardiomyocytes were also shown to secrete microvesicles containing both DNA and RNA. Isolated microvesicles incubated with fibroblasts were observed by confocal microscopy to be internalized into fibroblasts. Altered gene expression was observed in microvesicle stimulated fibroblasts. Conclusion. This study shows that increased hyaluronan synthesis in cardiac tissue during hypertrophic development is a part of the extracellular matrix remodelling. Cell cultures revealed the ability of cardiomyocytes to both synthesize hyaluronan and to convey signals to fibroblasts, causing them to increase hyaluronan synthesis. Cardiomyocytes are likely to express receptors for hyaluronan, which mediate intracellular signalling causing the observed altered gene expression in cardiomyocytes stimulated with hyaluronan. This demonstrates the extensive involvement of hyaluronan in cardiac hypertrophy.

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