ORCID Profile
0000-0001-6636-0293
Current Organisations
Aalborg University
,
Qatar University College of Medicine
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Publisher: Springer Science and Business Media LLC
Date: 11-01-2017
DOI: 10.1038/SREP40275
Abstract: Cardiovascular disease is the leading cause of death worldwide and patients with severe symptoms undergo cardiac surgery. Even after uncomplicated surgeries, some patients experience postoperative complications such as lung injury. We hypothesized that the procedure elicits metabolic activity that can be related to the disease progression, which is commonly observed two-three days postoperatively. More than 700 blood s les were collected from 50 patients at nine time points pre-, intra-, and postoperatively. Dramatic metabolite shifts were observed during and immediately after the intervention. Prolonged surgical stress was linked to an augmented anaerobic environment. Time series analysis showed shifts in purine-, nicotinic acid-, tyrosine-, hyaluronic acid-, ketone-, fatty acid, and lipid metabolism. A characteristic ‘metabolic biosignature’ was identified correlating with the risk of developing postoperative complications two days before the first clinical signs of lung injury. Hence, this study demonstrates the link between intra- and postoperative time-dependent metabolite changes and later postoperative outcome. In addition, the results indicate that metabotyping patients’ journeys early, during or just after the end of surgery, may have potential impact in hospitals for the early diagnosis of postoperative lung injury, and for the monitoring of therapeutics targeting disease progression.
Publisher: Springer Science and Business Media LLC
Date: 16-09-2021
DOI: 10.1038/S41598-021-97969-Y
Abstract: Alzheimer’s disease (AD) is the most common form of dementia and without readily available clinical biomarkers. Blood-derived proteins are routinely used for diagnostics however, comprehensive plasma profiling is challenging due to the dynamic range in protein concentrations. Extracellular vesicles (EVs) can cross the blood–brain barrier and may provide a source for AD biomarkers. We investigated plasma-derived EV proteins for AD biomarkers from 10 AD patients, 10 Mild Cognitive Impairment (MCI) patients, and 9 healthy controls (Con) using liquid chromatography-tandem mass spectrometry (LC–MS/MS). The ultracentrifuged EVs were washed and confirmed according to the MISEV2018 guidelines. Some AD patients presented with highly elevated FXIIIA1 (log 2 FC: 4.6, p -value: 0.005) and FXIIIB (log 2 FC: 4.9, p -value: 0.018). A panel of proteins was identified discriminating Con from AD (AUC: 0.91, CI: 0.67–1.00) with ORM2 (AUC: 1.00, CI: 1.00–1.00), RBP4 (AUC: 0.99, CI: 0.95–1.00), and HYDIN (AUC: 0.89, CI: 0.72–1.00) were found especially relevant for AD. This indicates that EVs provide an easily accessible matrix for possible AD biomarkers. Some of the MCI patients, with similar protein profiles as the AD group, progressed to AD within a 2-year timespan.
Publisher: Elsevier BV
Date: 12-2021
Publisher: Elsevier BV
Date: 03-2016
Publisher: Springer Science and Business Media LLC
Date: 07-01-2022
DOI: 10.1186/S12014-021-09339-5
Abstract: Early detection of small cell lung cancer (SCLC) crucially demands highly reliable markers. Growing evidence suggests that extracellular vesicles carry tumor cell-specific cargo suitable as protein markers in cancer. Quantitative proteomic profiling of circulating microvesicles and exosomes can be a high-throughput platform for discovery of novel molecular insights and putative markers. Hence, this study aimed to investigate proteome dynamics of plasma-derived microvesicles and exosomes in newly diagnosed SCLC patients to improve early detection. Plasma-derived microvesicles and exosomes from 24 healthy controls and 24 SCLC patients were isolated from plasma by either high-speed- or ultracentrifugation. Proteins derived from these extracellular vesicles were quantified using label-free mass spectrometry and statistical analysis was carried out aiming at identifying significantly altered protein expressions between SCLC patients and healthy controls. Furthermore, significantly expressed proteins were subjected to functional enrichment analysis to identify biological pathways implicated in SCLC pathogenesis. Based on fold change (FC) ≥ 2 or ≤ 0.5 and AUC ≥ 0.70 ( p 0.05), we identified 10 common and 16 and 17 unique proteins for microvesicles and exosomes, respectively. Among these proteins, we found dysregulation of coagulation factor XIII A (Log 2 FC = − 1.1, p = 0.0003, AUC = 0.82, 95% CI: 0.69–0.96) and complement factor H-related protein 4 (Log 2 FC = 1.2, p = 0.0005, AUC = 0.82, 95% CI 0.67–0.97) in SCLC patients compared to healthy in iduals. Our data may indicate a novel tumor-suppressing role of blood coagulation and involvement of complement activation in SCLC pathogenesis. In comparing SCLC patients and healthy in iduals, several differentially expressed proteins were identified. This is the first study showing that circulating extracellular vesicles may encompass specific proteins with potential diagnostic attributes for SCLC, thereby opening new opportunities as novel non-invasive markers.
Publisher: MDPI AG
Date: 07-07-2020
DOI: 10.3390/BIOMEDICINES8070199
Abstract: Easily accessible biomarkers for Alzheimer’s dementia (AD) are lacking and established clinical markers are limited in applicability. Blood is a common biofluid for biomarker discoveries, and extracellular vesicles (EVs) may provide a matrix for exploring AD related biomarkers. Thus, we investigated proteins related to neurological and inflammatory processes in plasma and EVs. By proximity extension assay (PEA), 182 proteins were measured in plasma and EVs from patients with AD (n = 10), Mild Cognitive Impairment (MCI, n = 10), and healthy controls (n = 10). Plasma-derived EVs were enriched by 20,000× g, 1 h, 4 °C, and confirmed using nanoparticle tracking analysis (NTA), western blotting, and transmission electron microscopy with immunolabelling (IEM). Presence of CD9+ EVs was confirmed by western blotting and IEM. No group differences in particle concentration or size were detected by NTA. However, significant protein profiles were observed among subjects, particularly for EVs. Several proteins and their ratios could distinguish cognitively affected from healthy in iduals. For plasma TGF-α│CCL20 (AUC = 0.96, 95% CI = 0.88–1.00, p = 0.001) and EVs CLEC1B│CCL11 (AUC = 0.95, 95% CI = 0.86–1.00, p = 0.001) showed diagnostic capabilities. Using PEA, we identified protein profiles capable of distinguishing healthy controls from AD patients. EVs provided additional biological information related to AD not observed in plasma alone.
Publisher: Wiley
Date: 2015
DOI: 10.3402/JEV.V4.30087
Abstract: Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.
Publisher: MDPI AG
Date: 28-07-2020
Abstract: Background: Pacific Small Island Developing States (SIDS) have health care systems with a limited capacity to deal with pandemics, making them especially vulnerable to the economic and social impacts of the coronavirus (COVID-19). This paper examines the introduction, transmission, and incidence of COVID-19 into Pacific SIDS. Methods: Calculate the rate of transmission (the average number of new cases per day between the first recorded case and the most recent day) and connectivity (daily direct flights to the leading airport in each selected island group) using flight history and COVID-19 transmission data. Results: Correlational analyses show that connectivity is positively related with (a) first-case dates and (b) spread rate in Pacific SIDS. Conclusion: Connectivity plays a central role in the spread of COVID-19 in Pacific SIDS. The continued entry of people was a significant factor for spread within countries. Efforts to prevent transmission by closing borders reduced transmission but also created significant economic hardship because many Pacific SIDS rely heavily on tourism and international exchange. The findings highlight the importance of exploring the possibility that the COVID-19 spread rate may be higher than official figures indicate, and present pathways to mitigate socio-economic impacts. The practical implications of the findings reveal the vulnerability of Pacific SIDS to pandemics and the key role of connectivity in the spread of COVID-19 in the Pacific region.
Publisher: American Association for Cancer Research (AACR)
Date: 15-05-2019
DOI: 10.1158/1078-0432.CCR-18-2946
Abstract: Liquid biopsy has great potential to improve the management of brain tumor patients at high risk of surgery-associated complications. Here, the aim was to explore plasma extracellular vesicle (plEV) immunoprofiling as a tool for noninvasive diagnosis of glioma. PlEV isolation and analysis were optimized using advanced mass spectrometry, nanoparticle tracking analysis, and electron microscopy. We then established a new procedure that combines size exclusion chromatography isolation and proximity extension assay–based ultrasensitive immunoprofiling of plEV proteins that was applied on a well-defined glioma study cohort (n = 82). Among potential candidates, we for the first time identify syndecan-1 (SDC1) as a plEV constituent that can discriminate between high-grade glioblastoma multiforme (GBM, WHO grade IV) and low-grade glioma [LGG, WHO grade II area under the ROC curve (AUC): 0.81 sensitivity: 71% specificity: 91%]. These findings were independently validated by ELISA. Tumor SDC1 mRNA expression similarly discriminated between GBM and LGG in an independent glioma patient population from The Cancer Genome Atlas cohort (AUC: 0.91 sensitivity: 79% specificity: 91%). In experimental studies with GBM cells, we show that SDC1 is efficiently sorted to secreted EVs. Importantly, we found strong support of plEVSDC1 originating from GBM tumors, as plEVSDC1 correlated with SDC1 protein expression in matched patient tumors, and plEVSDC1 was decreased postoperatively depending on the extent of surgery. Our studies support the concept of circulating plEVs as a tool for noninvasive diagnosis and monitoring of gliomas and should move this field closer to the goal of improving the management of cancer patients.
Publisher: Wiley
Date: 2015
DOI: 10.3402/JEV.V4.27783
Publisher: Wiley
Date: 2016
DOI: 10.3402/JEV.V5.31242
Abstract: Understanding the pathogenic role of extracellular vesicles (EVs) in disease and their potential diagnostic and therapeutic utility is extremely reliant on in-depth quantification, measurement and identification of EV sub-populations. Quantification of EVs has presented several challenges, predominantly due to the small size of vesicles such as exosomes and the availability of various technologies to measure nanosized particles, each technology having its own limitations. A standardized methodology to measure the concentration of extracellular vesicles (EVs) has been developed and tested. The method is based on measuring the EV concentration as a function of a defined size range. Blood plasma EVs are isolated and purified using size exclusion columns (qEV) and consecutively measured with tunable resistive pulse sensing (TRPS). Six independent research groups measured liposome and EV s les with the aim to evaluate the developed methodology. Each group measured identical s les using up to 5 nanopores with 3 repeat measurements per pore. Descriptive statistics and unsupervised multivariate data analysis with principal component analysis (PCA) were used to evaluate reproducibility across the groups and to explore and visualise possible patterns and outliers in EV and liposome data sets. PCA revealed good reproducibility within and between laboratories, with few minor outlying s les. Measured mean liposome (not filtered with qEV) and EV (filtered with qEV) concentrations had coefficients of variance of 23.9% and 52.5%, respectively. The increased variance of the EV concentration measurements could be attributed to the use of qEVs and the polydisperse nature of EVs. The results of this study demonstrate the feasibility of this standardized methodology to facilitate comparable and reproducible EV concentration measurements.
Publisher: Springer Science and Business Media LLC
Date: 18-03-2016
No related grants have been discovered for Shona Pedersen.