ORCID Profile
0000-0002-9888-1955
Current Organisations
Aalborg University
,
Aalborg Universitet
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Publisher: SAGE Publications
Date: 17-07-2017
Abstract: Preterm infants are highly susceptible to late-onset sepsis (LOS) and necrotizing enterocolitis (NEC), but disease pathogenesis and specific diagnostic markers are lacking. Circulating cell-free DNA (cfDNA) and immune cell-derived proteins are involved in multiple immune diseases in adults but have not been investigated in preterm neonates. We explored the relation of circulating neutrophil-associated proteins and cfDNA to LOS and/or NEC. Using a clinically relevant preterm pig model of spontaneous LOS and NEC development, we investigated neutrophil-associated proteins and cfDNA in plasma, together with cytokines in gut tissues. The changes in cfDNA levels were further studied in preterm pigs and neonatal mice with induced sepsis, and in preterm infants with or without LOS and/or NEC. Fifteen of 114 preterm pigs spontaneously developed both LOS and NEC, and they showed increased intestinal levels of IL-6 and IL-1β and plasma levels of cfDNA, neutrophil-associated proteins, and proteins involved in platelet-neutrophil interaction during systemic inflammation. The abundance of neutrophil-associated proteins highly correlated with cfDNA levels. Further, Staphylococcus epidermidis challenge of neonatal mice and preterm pigs increased plasma cfDNA levels and bacterial accumulation in the spleen. In infants, plasma cfDNA levels were elevated at LOS diagnosis and 1–6 d before NEC. In conclusion, elevated levels of plasma cfDNA and neutrophil proteins are associated with LOS and NEC diagnosis.
Publisher: Wiley
Date: 02-2016
Publisher: Wiley
Date: 08-2021
DOI: 10.1002/JEV2.12131
Abstract: Emerging evidence suggests that immune cells not only communicate with each other through cytokines, chemokines, and cell surface receptors, but also by releasing small membranous structures known as extracellular vesicles (EVs). EVs carry a variety of different molecules that can be taken up by recipient cells. Parasitic worms are well known for their immunomodulatory properties, but whether they can affect immune responses by altering EV‐driven communication between host immune cells remains unclear. Here we provide evidence that stimulation of bone marrow‐derived macrophages (BMDMs) with soluble products of Trichuris suis (TSPs), leads to the release of EVs with anti‐inflammatory properties. Specifically, we found that EVs from TSP‐pulsed BMDMs, but not those from unstimulated BMDMs can suppress TNFα and IL‐6 release in LPS‐stimulated BMDMs and BMDCs. However, no polarization toward M1 or M2 was observed in macrophages exposed to EVs. Moreover, EVs enhanced reactive oxygen species (ROS) production in the exposed BMDMs, which was associated with a deregulated redox homeostasis as revealed by pathway analysis of transcriptomic data. Proteomic analysis identified cytochrome p450 (CYP450) as a potential source of ROS in EVs from TSP‐pulsed BMDMs. Finally, pharmacological inhibition of CYP450 activity could suppress ROS production in those BMDMs. In summary, we find that TSPs can modulate immune responses not only via direct interactions but also indirectly by eliciting the release of EVs from BMDMs that exert anti‐inflammatory effects on recipient cells.
Publisher: Wiley
Date: 14-02-2019
Publisher: Springer Science and Business Media LLC
Date: 02-12-2012
DOI: 10.1007/S10532-012-9610-5
Abstract: Ibuprofen is the third most consumed pharmaceutical drug in the world. Several isolates have been shown to degrade ibuprofen, but very little is known about the biochemistry of this process. This study investigates the degradation of ibuprofen by Patulibacter sp. strain I11 by quantitative proteomics using a metabolic labelling strategy. The whole-genome of Patulibacter sp. strain I11 was sequenced to provide a species-specific protein platform for optimal protein identification. The bacterial proteomes of actively ibuprofen-degrading cells and cells grown in the absence of ibuprofen was identified and quantified by gel based shotgun-proteomics. In total 251 unique proteins were quantitated using this approach. Biological process and pathway analysis indicated a number of proteins that were up-regulated in response to active degradation of ibuprofen, some of them are known to be involved in the degradation of aromatic compounds. Data analysis revealed that several of these proteins are likely involved in ibuprofen degradation by Patulibacter sp. strain I11.
Publisher: Wiley
Date: 2015
DOI: 10.3402/JEV.V4.27783
Publisher: MDPI AG
Date: 14-07-2020
DOI: 10.3390/BIOMEDICINES8070213
Abstract: In the last two decades, extracellular vesicles (EVs) from the three domains of life, Archaea, Bacteria and Eukaryotes, have gained increasing scientific attention. As such, the role of EVs in host-pathogen communication and immune modulation are being intensely investigated. Pivotal to EV research is the determination of how and where EVs are taken up by recipient cells and organs in vivo, which requires suitable tracking strategies including labelling. Labelling of EVs is often performed post-isolation which increases risks of non-specific labelling and the introduction of labelling artefacts. Here we exploited the inability of helminths to de novo synthesise fatty acids to enable labelling of EVs by whole organism uptake of fluorescent lipid analogues and the subsequent incorporation in EVs. We showed uptake of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(lissamine rhodamine B sulfonyl) (DOPE-Rho) in Anisakis spp. and Trichuris suis larvae. EVs isolated from the supernatant of Anisakis spp. labelled with DOPE-Rho were characterised to assess the effects of labelling on size, structure and fluorescence of EVs. Fluorescent EVs were successfully taken up by the human macrophage cell line THP-1. This study, therefore, presents a novel staining method that can be utilized by the EV field in parasitology and potentially across multiple species.
Publisher: Wiley
Date: 12-2017
Publisher: Oxford University Press (OUP)
Date: 10-11-2014
DOI: 10.1093/BIOINFORMATICS/BTU741
Abstract: Motivation: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for EV-related publications and vesicular components are currently challenging. Results: We present an improved version of EVpedia, a public database for EVs research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools and a personalized function. EVpedia includes 6879 publications, 172 080 vesicular components from 263 high-throughput datasets, and has been accessed more than 65 000 times from more than 750 cities. In addition, about 350 members from 73 international research groups have participated in developing EVpedia. This free web-based database might serve as a useful resource to stimulate the emerging field of EV research. Availability and implementation: The web site was implemented in PHP, Java, MySQL and Apache, and is freely available at evpedia.info. Contact: ysgho@postech.ac.kr
Publisher: Public Library of Science (PLoS)
Date: 18-12-2012
Publisher: Wiley
Date: 04-2019
Abstract: Issues associated with upscaling exosome production for therapeutic use may be overcome through utilizing artificial exosomes. Cell-derived mimetic nanovesicles (M-NVs) are a potentially promising alternative to exosomes for clinical applicability, demonstrating higher yield without incumbent production and isolation issues. Although several studies have shown that M-NVs have similar morphology, size and therapeutic potential compared to exosomes, comprehensive characterization and to what extent M-NVs components mimic exosomes remain elusive. M-NVs were generated through the extrusion of cells and proteomic profiling demonstrated an enrichment of proteins associated with membrane and cytosolic components. The proteomic data herein reveal a subset of proteins that are highly abundant in M-NVs in comparison to exosomes. M-NVs contain proteins that largely represent the parental cell proteome, whereas the profile of exosomal proteins highlight their endosomally derived origin. This advantage of M-NVs alleviates the necessity of endosomal sorting of endogenous therapeutic proteins or RNA into exosomes. This study also highlights differences in protein post-translational modifications among M-NVs, as distinct from exosomes. Overall this study provides key insights into defining the proteome composition of M-NVs as a distinct from exosomes, and the potential advantage of M-NVs as an alternative nanocarrier when spontaneous endosomal sorting of therapeutics are limited.
No related grants have been discovered for Allan Stensballe.