Can we eradicate viral pathogens? Alizon, Samuel; Turner, Paul E.
Journal of evolutionary biology,
December 2021, 2021-12-00, 20211201, 2021-12, Letnik:
34, Številka:
12
Journal Article
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The COVID-19 pandemic has led to a resurgence of the debate on whether host-parasite interactions should evolve towards avirulence. In this review, we first show that SARS-CoV-2 virulence is ...evolving, before explaining why some expect the mortality caused by the epidemic to converge towards that of human seasonal alphacoronaviruses. Leaning on existing theory, we then include viral evolution into the picture and discuss hypotheses explaining why the virulence has increased since the beginning of the pandemic. Finally, we mention some potential scenarios for the future.
The ease with which bacteria can evolve resistance to phages is a key consideration for development of phage therapy. Here, we review recent work on the different evolutionary and ecological ...approaches to mitigate the problem. The approaches are broadly categorised into two areas: Minimising evolved phage resistance; and Directing phage-resistance evolution towards therapeutically beneficial outcomes.
Three-dimensional (3D) bioprinting has emerged to create novel cell-based therapies for regenerative medicine applications. Vascularized networks within engineered constructs are required, and toward ...this end, we report a promising strategy using core-shell (c/s) extrusion 3D-bioprinting technology that employs biomimetic biomaterials to construct regenerative, prevascularized scaffolds for wound care. A custom-designed cell-responsive bioink consisting of a 13% (w/v) cell-laden gelatin methacryloyl (GelMA) shell surrounding a peptide-functionalized, succinylated chitosan (C)/dextran aldehyde (D) cell-laden core was successfully bioprinted resulting in organized microdesigns exhibiting excellent cell viability and subsequent vessel formation. Our templating strategy takes advantage of GelMA’s intrinsic thermoreversible properties of low degree of acryloyl functionalization used in combination with a lightly, chemically cross-linked peptide-CD core to serve as temporal structural supports that stabilize during extrusion onto a cooled platform. Mechanical integrity was further strengthened layer-by-layer via GelMA UV photo-cross-linking. We report the first example of GelMA used in combination with a peptide-CD bioink to c/s 3D-bioprint regenerative, prevascularized constructs for wound care. Particular cell adhesion and proteolytic peptide-CD functionalized pair combinations, P15/MMP-2 and P15/cRGD, were found to significantly increase growth of human bone-marrow-derived mesenchymal stems cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs). The constructs delivered two cell types: hBMSCs in the shell bioink and HUVECs within the core bioink. Cord-like, natural microvascularization was shown with endothelial cell marker expression as confirmed by immunofluorescence (IF) staining exhibiting tubelike structures. In addition, in vitro skin wound healing activity of the construct showed a ∼twofold rate of wound closure. Overall, c/s 3D-bioprinted, peptide-CD/GelMA constructs provided the appropriate microenvironment for in vitro stem and endothelial cell viability, delivery, and differentiation. We foresee these custom constructs as representing a fundamental step toward engineering larger scale regenerative, prevascularized tissues.
Biomaterials-based approaches to harnessing the immune and inflammatory responses to potentiate wound healing hold important promise. Bone fracture healing is characterized by an acute inflammatory ...phase, followed by a transition to a regenerative and repair phase. In this study, we developed genipin-crosslinked gelatin microspheres designed to be preferentially degraded by inflammatory (M1) macrophages. Highly crosslinked (>90%) microspheres allowed efficient incorporation of bioactive bone morphogenetic protein 2 (BMP2), a potent stimulator of osteogenesis in progenitor cells, via electrostatic interactions. Release of BMP2 was directly correlated with degradation of the gelatin matrix. Exposure of microspheres to polarized murine macrophages showed that degradation was significantly higher in the presence of M1 macrophages, relative to alternatively activated (M2) macrophages and unpolarized controls. Microsphere degradation in the presence of non-inflammatory cells resulted in very low degradation rates. The expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMP (TIMPs) by macrophages were consistent with the observed phenotype-dependent degradation rates. Indirect co-culture of BMP2-loaded microspheres and macrophages with isolated adipose-derived mesenchymal stem cells (MSC) showed that M1 macrophages produced the strongest osteogenic response, comparable to direct supplementation of the culture medium with BMP2. Controlled release systems that are synchronized with the inflammatory response have the potential to provide better spatiotemporal control of growth factor delivery and therefore may improve the outcomes of recalcitrant wounds.
PURPOSE OF REVIEWThe observed increase in incidence of allergic disease in many regions over the past 3 decades has intensified interest in understanding the epidemiology of severe allergic ...reactions. We discuss the issues in collecting and interpreting these data and highlight current deficiencies in the current methods of data gathering.
RECENT FINDINGSAnaphylaxis, as measured by hospital admission rates, is not uncommon and has increased in the United Kingdom, the United States, Canada, and Australia over the last 10–20 years. All large datasets are hampered by a large proportion of uncoded, ‘unspecified’ causes of anaphylaxis. Fatal anaphylaxis remains a rare event, but appears to be increasing for medication in Australia, Canada, and the United States. The rate of fatal food anaphylaxis is stable in the United Kingdom and the United States, but has increased in Australia. The age distribution for fatal food anaphylaxis is different to other causes, with data suggesting an age-related predisposition to fatal outcomes in teenagers and adults to the fourth decade of life.
SUMMARYThe increasing rates of food and medication allergy (the latter exacerbated by an ageing population) has significant implications for future fatality trends. An improved ability to accurately gather and analyse population-level anaphylaxis data in a harmonized fashion is required, so as to ultimately minimize risk and improve management.
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