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| 2. |
- Lener, Thomas, et al.
(författare)
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Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper.
- 2015
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Ingår i: Journal of extracellular vesicles. - : Wiley. - 2001-3078. ; 4
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Tidskriftsartikel (refereegranskat)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.
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| 3. |
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| 4. |
- Shao, WG, et al.
(författare)
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The SysteMHC Atlas project
- 2018
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Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 46:D1, s. D1237-D1247
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Noguera-Salva, M. A., et al.
(författare)
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Role of the C-terminal basic amino acids and the lipid anchor of the G gamma(2) protein in membrane interactions and cell localization
- 2017
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Ingår i: Biochimica Et Biophysica Acta-Biomembranes. - : Elsevier BV. - 0005-2736. ; 1859:9, s. 1536-1547
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Tidskriftsartikel (refereegranskat)abstract
- Heterotrimeric G proteins are peripheral membrane proteins that frequently localize to the plasma membrane where their presence in molar excess over G protein coupled receptors permits signal amplification. Their distribution is regulated by protein-lipid interactions, which has a clear influence on their activity. G beta gamma dimer drives the interaction between G protein heterotrimers with cell membranes. We focused our study on the role of the C-terminal region of the G gamma(2) protein in G protein interactions with cell membranes. The G gamma(2) subunit is modified at cysteine (Cys) 68 by the addition of an isoprenyl lipid, which is followed by the proteolytic removal of the last three residues that leaves an isoprenylated and carboxyl methylated Cys-68 as the terminal amino acid. The role of Cys isoprenylation of the CAAX box has been defined for other proteins, yet the importance of proteolysis and carboxyl methylation of isoprenylated proteins is less clear. Here, we showed that not only geranylgeranylation but also proteolysis and carboxyl methylation are essential for the correct localization of G gamma(2) in the plasma membrane. Moreover, we showed the importance of electrostatic interactions between the inner leaflet of the plasma membrane and the positively charged C-terminal domain of the G gamma(2) subunit (amino acids Arg-62, Lys-64 and Lys-65) as a second signal to reach the plasma membrane. Indeed, single or multiple point mutations at G gamma(2) C-terminal amino acids have a significant effect on G gamma(2) protein-plasma membrane interactions and its localization to charged Ld (liquid disordered) membrane microdomains. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escriba. (C) 2017 Published by Elsevier B.V.
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| 6. |
- Yáñez-Mó, María, et al.
(författare)
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Biological properties of extracellular vesicles and their physiological functions.
- 2015
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Ingår i: Journal of extracellular vesicles. - : Wiley. - 2001-3078. ; 4
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Forskningsöversikt (refereegranskat)abstract
- In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
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| 7. |
- Sanchez, Jaime S., et al.
(författare)
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Versatile electrochemical manufacturing of mixed metal sulfide/N-doped rGO composites as bifunctional catalysts for high power rechargeable Zn–air batteries
- 2024
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Ingår i: Journal of Materials Chemistry A. - 2050-7488 .- 2050-7496. ; In Press
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Tidskriftsartikel (refereegranskat)abstract
- The development of rechargeable zinc–air batteries requires air cathodes capable of performing both the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) with high performance and an extended operational lifespan. Here, we present a cost-effective and versatile electrochemical method for the direct assembly of such electrocatalysts, consisting of nitrogen-doped reduced graphene oxide (NrGO) and mixed transition metal sulfides (NiCoMnSx or NCMS). To this end, we use a small electric bias to electro-deposit both NrGO and NCMS directly on conductive graphene foam, resulting in a perfect porous network and two interpenetrated paths for the easy transport of electrons and ions. The NCMS/ NrGO composite shows one of the highest limiting currents reported so far for a non-noble metal catalyst. Additionally, it exhibits outstanding bifunctional performance for the ORR/OER, superior to both mixed transition metal compounds and noble metals from previous reports. Thus, it serves as a highly efficient air cathode for practical zinc–air batteries featuring high power densities (124 mW cm−2) and long catalyst durability (1560 cycles, around 260 h). We attribute the excellent performance to the synergistic effect between hetero-structured metallic sites and nitrogen dopants. Our approach can be used for preparing efficient zinc–air cathodes on conductive 3D carbon substrates with arbitrary shapes and good performance.
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