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- Gupta, Dhanu, et al.
(författare)
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Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles
- 2021
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Ingår i: Nature Biomedical Engineering. - Stockholm : Karolinska Institutet, Dept of Laboratory Medicine. - 2157-846X.
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) can be functionalized to display specific protein receptors on their surface. However, surface-display technology typically labels only a small fraction of the EV population. Here, we show that the joint display of two different therapeutically relevant protein receptors on EVs can be optimized by systematically screening EV-loading protein moieties. We used cytokine-binding domains derived from tumour necrosis factor receptor 1 (TNFR1) and interleukin-6 signal transducer (IL-6ST), which can act as decoy receptors for the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-α) and IL-6, respectively. We found that the genetic engineering of EV-producing cells to express oligomerized exosomal sorting domains and the N-terminal fragment of syntenin (a cytosolic adaptor of the single transmembrane domain protein syndecan) increased the display efficiency and inhibitory activity of TNFR1 and IL-6ST and facilitated their joint display on EVs. In mouse models of systemic inflammation, neuroinflammation and intestinal inflammation, EVs displaying the cytokine decoys ameliorated the disease phenotypes with higher efficacy as compared with clinically approved biopharmaceutical agents targeting the TNF-α and IL-6 pathways.
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- Saulnier, DD, et al.
(författare)
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Staying afloat: community perspectives on health system resilience in the management of pregnancy and childbirth care during floods in Cambodia
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- Resilient health systems have the capacity to continue providing health services to meet the community’s diverse health needs following floods. This capacity is related to how the community manages its own health needs and the community and health system’s joined capacities for resilience. Yet little is known about how community participation influences health systems resilience. The purpose of this study was to understand how community management of pregnancy and childbirth care during floods is contributing to the system’s capacity to absorb, adapt or transform as viewed through a framework on health systems resilience.MethodsEight focus group discussions and 17 semi-structured interviews were conducted with community members and leaders who experienced pregnancy or childbirth during recent flooding in rural Cambodia. The data were analysed by thematic analysis and discussed in relation to the resilience framework.ResultsThe theme ‘Responsible for the status quo’ reflected the community’s responsibility to find ways to manage pregnancy and childbirth care, when neither the expectations of the health system nor the available benefits changed during floods. The theme was informed by notions on: i) developmental changes, the unpredictable nature of floods and limited support for managing care, ii) how information promoted by the public health system led to a limited decision-making space for pregnancy and childbirth care, iii) a desire for security during floods that outweighed mistrust in the public health system and iv) the limits to the coping strategies that the community prepared in case of flooding.ConclusionsThe community mainly employed absorptive strategies to manage their care during floods, relieving the burden on the health system, yet restricted support and decision-making may risk their capacity. Further involvement in decision-making for care could help improve the health system’s resilience by creating room for the community to adapt and transform when experiencing floods.
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