Tangential Flow Filtration for Highly Efficient Concentration of Extracellular Vesicles from Large Volumes of Fluid

Concentration of extracellular vesicles (EVs) from biological fluids in a scalable and reproducible manner represents a major challenge. This study reports the use of tangential flow filtration (TFF) for the highly efficient isolation of EVs from large volumes of samples. When compared to ultracentrifugation (UC), which is the most widely used method to concentrate EVs, TFF is a more efficient, scalable, and gentler method. Comparative assessment of TFF and UC of conditioned cell culture media revealed that the former concentrates EVs of comparable physicochemical characteristics, but with higher yield, less single macromolecules and aggregates (<15 nm in size), and improved batch-to-batch consistency in half the processing time (1 h). The TFF protocol was then successfully implemented on fluids derived from patient lipoaspirate. EVs from adipose tissue are of high clinical relevance, as they are expected to mirror the regenerative properties of the parent cells

Validated respiratory drug deposition predictions from 2D and 3D medical images with statistical shape models and convolutional neural networks

For the one billion sufferers of respiratory disease, managing their disease with inhalers crucially influences their quality of life. Generic treatment plans could be improved with the aid of computational models that account for patient-specific features such as breathing pattern, lung pathology and morphology. Therefore, we aim to develop and validate an automated computational framework for patient-specific deposition modelling. To that end, an image processing approach is proposed that could produce 3D patient respiratory geometries from 2D chest X-rays and 3D CT images. We evaluated the airway and lung morphology produced by our image processing framework, and assessed deposition compared to in vivo data. The 2D-to-3D image processing reproduces airway diameter to 9% median error compared to ground truth segmentations, but is sensitive to outliers of up to 33% due to lung outline noise. Predicted regional deposition gave 5% median error compared to in vivo measurements. The proposed framework is capable of providing patient-specific deposition measurements for varying treatments, to determine which treatment would best satisfy the needs imposed by each patient (such as disease and lung/airway morphology). Integration of patient-specific modelling into clinical practice as an additional decision-making tool could optimise treatment plans and lower the burden of respiratory diseases.</p

Polyethylene glycol (PEG)-dendron phospholipids as innovative constructs for the preparation of super stealth liposomes for anticancer therapy

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Targeting the thyroid gland with thyroid-stimulating hormone (TSH)-nanoliposomes

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Regenerative medicine therapy: adipose derived extracellular vesicles in viral myocarditis

Objective: Myocarditis, inflammation of the heart muscle, is an autoimmune heart disease that can be caused by viruses, bacteria and toxins. Myocarditis can lead to dilated cardiomyopathy (DCM) and heart failure. Currently there are no disease-specific therapies for treating myocarditis or preventing progression to DCM. Adipose Extracellular Vesicles (AEVs) are lipid bilayer nanoparticles that are released into the outside environment of adipocytes and provide promising regenerative potential for inflammatory diseases like myocarditis. Methods: Lipoaspirate was obtained from women and men and AEVs isolated from the lipoaspirate using tangential flow filtration. We injected wild type male BALB/c mice with 250uL AEVs (1×10^10 EV/mL) intraperitoneally or sucrose control on day -1, 0, 1 with viral infection on day 0. Mice were harvested on day 10 post infection at the peak of myocarditis. Results: We found that male mice treated with AEVs from a female patient had a significantly higher body weight (p=0.0003), less calcification in the gut (p=0.001) and less myocardial inflammation (p=0.007) than controls. Mouse hearts analyzed by qRT-PCR revealed that AEV treated mice had significantly lower relative gene expression of cell markers for total immune cells (CD45, p=0.002), macrophages (CD11b, p=0.002, F4/80, p=0.0004); specifically M2 macrophages (Chi313, p=0.003), as well as CD3+ (p=0.007) and CD4+ T cells (p=0.01) than controls. Additionally, we found that mice treated with AEVs from a male patient also had significantly less myocardial inflammation (p=0.01). Conclusion: AEVs could provide an innovative therapy to reduce cardiac inflammation and decrease the risk of developing DCM following myocarditis

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors

Subnormal plasma levels of high-density lipoprotein cholesterol (HDL-C) constitute a major cardiovascular risk factor; raising low HDL-C levels may therefore reduce the residual cardiovascular risk that frequently presents in dyslipidaemic subjects despite statin therapy. Cholesteryl ester transfer protein (CETP), a key modulator not only of the intravascular metabolism of HDL and apolipoprotein (apo) A-I but also of triglyceride (TG)-rich particles and low-density lipoprotein (LDL), mediates the transfer of cholesteryl esters from HDL to pro-atherogenic apoB-lipoproteins, with heterotransfer of TG mainly from very low-density lipoprotein to HDL. Cholesteryl ester transfer protein activity is elevated in the dyslipidaemias of metabolic disease involving insulin resistance and moderate to marked hypertriglyceridaemia, and is intimately associated with premature atherosclerosis and high cardiovascular risk. Cholesteryl ester transfer protein inhibition therefore presents a preferential target for elevation of HDL-C and reduction in atherosclerosis. This review appraises recent evidence for a central role of CETP in the action of current lipid-modulating agents with HDL-raising potential, i.e. statins, fibrates, and niacin, and compares their mechanisms of action with those of pharmacological agents under development which directly inhibit CETP. New CETP inhibitors, such as dalcetrapib and anacetrapib, are targeted to normalize HDL/apoA-I levels and anti-atherogenic activities of HDL particles. Further studies of these CETP inhibitors, in particular in long-term, large-scale outcome trials, will provide essential information on their safety and efficacy in reducing residual cardiovascular risk

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Differences in the Aerobic Capacity of Flight Muscles between Butterfly Populations and Species with Dissimilar Flight Abilities

Habitat loss and climate change are rapidly converting natural habitats and thereby increasing the significance of dispersal capacity for vulnerable species. Flight is necessary for dispersal in many insects, and differences in dispersal capacity may reflect dissimilarities in flight muscle aerobic capacity. In a large metapopulation of the Glanville fritillary butterfly in the Åland Islands in Finland, adults disperse frequently between small local populations. Individuals found in newly established populations have higher flight metabolic rates and field-measured dispersal distances than butterflies in old populations. To assess possible differences in flight muscle aerobic capacity among Glanville fritillary populations, enzyme activities and tissue concentrations of the mitochondrial protein Cytochrome-c Oxidase (CytOx) were measured and compared with four other species of Nymphalid butterflies. Flight muscle structure and mitochondrial density were also examined in the Glanville fritillary and a long-distance migrant, the red admiral. Glanville fritillaries from new populations had significantly higher aerobic capacities than individuals from old populations. Comparing the different species, strong-flying butterfly species had higher flight muscle CytOx content and enzymatic activity than short-distance fliers, and mitochondria were larger and more numerous in the flight muscle of the red admiral than the Glanville fritillary. These results suggest that superior dispersal capacity of butterflies in new populations of the Glanville fritillary is due in part to greater aerobic capacity, though this species has a low aerobic capacity in general when compared with known strong fliers. Low aerobic capacity may limit dispersal ability of the Glanville fritillary.Peer reviewe