Adipose Stromal/Stem Cell-Derived Extracellular Vesicles: Potential Next-Generation Anti-Obesity Agents

Over the last decade, several compounds have been identified for the treatment of obesity. However, due to the complexity of the disease, many pharmacological interventions have raised concerns about their efficacy and safety. Therefore, it is important to discover new factors involved in the induction/progression of obesity. Adipose stromal/stem cells (ASCs), which are mostly isolated from subcutaneous adipose tissue, are the primary cells contributing to the expansion of fat mass. Like other cells, ASCs release nanoparticles known as extracellular vesicles (EVs), which are being actively studied for their potential applications in a variety of diseases. Here, we focused on the importance of the con-tribution of ASC-derived EVs in the regulation of metabolic processes. In addition, we outlined the advantages/disadvantages of the use of EVs as potential next-generation anti-obesity agents

Unexpected stability of aqueous dispersions of raspberry-like colloids

Aqueous colloidal suspensions, both man-made and natural, are part of our everyday life. The applicability of colloidal suspensions, however, is highly limited by the range of conditions over which they are stable. Here, we report a novel type of highly monodisperse ‘raspberry’ colloids, which are prepared in a single-step synthesis that relies on simultaneous dispersion and emulsion polymerisation. The resulting raspberry colloids behave almost like hard spheres. In aqueous solutions such prepared raspberries show unprecedented stability against aggregation over large variations of added salt concentrations without addition of surfactants or other stabilisers. We present simple DLVO-calculations performed on raspberries and smooth colloids showing that this stability results from our raspberries’ unique morphology preventing salt-induced colloidal aggregation, which extends our understanding of colloidal stability against salting. Our calculations are supported by salting experiments using a variety of salts and differently sized colloids with varying ‘roughness’. Further, the raspberies’ stability facilitates the formation of superspheres and thin films in which the raspberry colloids self-assemble into hexagonally close-packed photonic crystals with exquisite reproducibility.Y.L. thanks the CSC Cambridge scholarship for financial support. A.C. thanks D. Frenkel for discussions and acknowledges the ETN-COLLDENSE (H2020-MCSA-ITN-2014, Grant No. 642774). S.V. acknowledges the BBSRC David Phillips fellowship (BB/K014617/1), the European Research Council (ERC-2014-STG H2020 639088) and B. Frka-Petesic for discussions. G.G. thanks the Engineering and Physical Sciences Research Council (EPSRC, 1525292), V.E.J. the European Commission (Marie Curie Fellowship LODIS, 701455), J.L. the Marie Curie FP7 SASSYPOL ITN (607602) and M.K. EPSRC (EP/L027151/1) for financial support. E.E., Y.L. and S.V. thank the Winton Programme for the Physics of Sustainability

Guanosine-mediated anxiolytic-like effect: Interplay with adenosine a1 and a2a receptors

Acute or chronic administration of guanosine (GUO) induces anxiolytic-like effects, for which the adenosine (ADO) system involvement has been postulated yet without a direct experimental evidence. Thus, we aimed to investigate whether adenosine receptors (ARs) are involved in the GUO-mediated anxiolytic-like effect, evaluated by three anxiety-related paradigms in rats. First, we confirmed that acute treatment with GUO exerts an anxiolytic-like effect. Subsequently, we investigated the effects of pretreatment with ADO or A1R (CPA, CCPA) or A2AR (CGS21680) agonists 10 min prior to GUO on a GUO-induced anxiolytic-like effect. All the combined treatments blocked the GUO anxiolytic-like effect, whereas when administered alone, each compound was ineffective as compared to the control group. Interestingly, the pretreatment with nonselective antagonist caffeine or selective A1R (DPCPX) or A2AR (ZM241385) antagonists did not modify the GUO-induced anxiolytic-like effect. Finally, binding assay performed in hippocampal membranes showed that [3H]GUO binding became saturable at 100–300 nM, suggesting the existence of a putative GUO binding site. In competition experiments, ADO showed a potency order similar to GUO in displacing [3H]GUO binding, whereas AR selective agonists, CPA and CGS21680, partially displaced [3H]GUO binding, but the sum of the two effects was able to displace [3H]GUO binding to the same extent of ADO alone. Overall, our results strengthen previous data supporting GUO-mediated anxiolytic-like effects, add new evidence that these effects are blocked by A1R and A2AR agonists and pave, although they do not elucidate the mechanism of GUO and ADO receptor interaction, for a better characterization of GUO binding sites in ARs

Changes in matrix extracellular phosphoglycoprotein expression before and during in vitro osteogenic differentiation of human dental papilla mesenchymal cells.

The purpose of this study is to characterise the expression of matrix extracellular phosphoglycoprotein (MEPE) in cultured mesenchymal cells isolated from human dental papilla (PaMCs) of impacted third molars either before or during differentiation of these cells into osteo/odontoblasts. PaMCs, like mesenchymal cells deriving from human dental pulp (DPMCs), resulted positive for a number of mesenchymal markers including CD146 and STRO-1. During the first week in culture they showed a faster proliferation rate than DPMCs, coupled to an earlier down-regulation of MEPE. Also when the cells were further cultured in osteogenic medium (containing β-glycerophosphate, ascorbic acid and dexamethasone) for 40 days, MEPE down-regulation coupled to an increased expression of osteogenic markers, such as osteocalcin and alkaline phosphatase, occurred earlier in PaMCs than in DPMCs. Thus, our data, indicating that also in PaMCs MEPE expression is higher when cells proliferate, whereas it is downregulated as cells differentiated, are in favour of a role of MEPE as an early regulator of odontogenic differentiation. We also confirm the superior proliferative potential of PaMCs in comparison with DPMCs, coupled to a more rapid induction of osteogenic differentiation. Therefore, these cells represent an optimal source to be conveniently used for dental tissue engineering and tooth regeneration

Guanosine effect on cholesterol efflux and apolipoprotein E expression in astrocytes

The main source of cholesterol in the central nervous system (CNS) is represented by glial cells, mainly astrocytes, which also synthesise and secrete apolipoproteins, in particular apolipoprotein E (ApoE), the major apolipoprotein in the brain, thus generating cholesterol-rich high density lipoproteins (HDLs). This cholesterol trafficking, even though still poorly known, is considered to play a key role in different aspects of neuronal plasticity and in the stabilisation of synaptic transmission. Moreover, cell cholesterol depletion has recently been linked to a reduction in amyloid beta formation. Here we demonstrate that guanosine, which we previously reported to exert several neuroprotective effects, was able to increase cholesterol efflux from astrocytes and C6 rat glioma cells in the absence of exogenously added acceptors. In this effect the phosphoinositide 3 kinase/extracellular signal-regulated kinase 1/2 (PI3K/ERK1/2) pathway seems to play a pivotal role. Guanosine was also able to increase the expression of ApoE in astrocytes, whereas it did not modify the levels of ATP-binding cassette protein A1 (ABCA1), considered the main cholesterol transporter in the CNS. Given the emerging role of cholesterol balance in neuronal repair, these effects provide evidence for a role of guanosine as a potential pharmacological tool in the modulation of cholesterol homeostasis in the brain

The epidemiology of mumps in Italy

In Italy, although vaccination has been recommended for a number of years, vaccination coverage for mumps is still sub-optimal. The objective of the present study was to evaluate the seroprevalence of mumps antibodies in the Italian population, stratified by age, gender and geographical area. The proportion of individuals positive for mumps antibodies remained stable in the age classes 0-11 months and 1 year (25.4% and 30.8%, respectively) and showed a continuous increase after the second year of life. The percentage of susceptible individuals was higher than 20% in persons 2-14 years of age and exceeded 10% in persons 15-39 years of age. No statistically significant differences were observed by gender or geographical area. Comparison between these results and the data obtained from a 1996 survey showed a statistically significant increase in seroprevalence in the age class 2-4 years. No changes were observed in the other age-groups. The results of this study confirm that the efforts made in recent years to improve vaccination coverage within the second year of life should be strengthened. \ua9 2008 Elsevier Ltd. All rights reserved

The epidemiology of Varicella Zoster Virus infection in Italy

<p>Abstract</p> <p>Background</p> <p>The epidemiological importance of varicella and zoster and the availability of an efficacious and safe vaccine have led to an important international debate regarding the suitability of mass vaccination. The objective of the study was to describe the epidemiology of varicella and zoster in Italy and to determine whether there have been changes with respect to observations provided by an analogous study conducted 8 years ago, in order to define the most appropriate vaccination strategy.</p> <p>Methods</p> <p>A number of data sources were evaluated, a cross-sectional population-based seroprevalence study was conducted on samples collected in 2004, and the results were compared with data obtained in 1996.</p> <p>Results</p> <p>The data from active and passive surveillance systems confirm that varicella is a widespread infectious disease which mainly affects children. VZV seroprevalence did not substantially differ from that found in the previous study. The sero-epidemiological profile in Italy is different from that in other European countries. In particular, the percentage of susceptible adolescents is at least nearly twice as high as in other European countries and in the age group 20–39 yrs, approximately 9% of individuals are susceptible to VZV.</p> <p>Conclusion</p> <p>The results of this study can contribute to evaluating the options for varicella vaccination. It is possible that in a few years, in all Italian Regions, there will exist the conditions necessary for implementing a mass vaccination campaign and that the large-scale availability of MMRV tetravalent vaccines will facilitate mass vaccination.</p

Exploring the Diversity of Plant DNA Viruses and Their Satellites Using Vector-Enabled Metagenomics on Whiteflies

Current knowledge of plant virus diversity is biased towards agents of visible and economically important diseases. Less is known about viruses that have not caused major diseases in crops, or viruses from native vegetation, which are a reservoir of biodiversity that can contribute to viral emergence. Discovery of these plant viruses is hindered by the traditional approach of sampling individual symptomatic plants. Since many damaging plant viruses are transmitted by insect vectors, we have developed “vector-enabled metagenomics” (VEM) to investigate the diversity of plant viruses. VEM involves sampling of insect vectors (in this case, whiteflies) from plants, followed by purification of viral particles and metagenomic sequencing. The VEM approach exploits the natural ability of highly mobile adult whiteflies to integrate viruses from many plants over time and space, and leverages the capability of metagenomics for discovering novel viruses. This study utilized VEM to describe the DNA viral community from whiteflies (Bemisia tabaci) collected from two important agricultural regions in Florida, USA. VEM successfully characterized the active and abundant viruses that produce disease symptoms in crops, as well as the less abundant viruses infecting adjacent native vegetation. PCR assays designed from the metagenomic sequences enabled the complete sequencing of four novel begomovirus genome components, as well as the first discovery of plant virus satellites in North America. One of the novel begomoviruses was subsequently identified in symptomatic Chenopodium ambrosiodes from the same field site, validating VEM as an effective method for proactive monitoring of plant viruses without a priori knowledge of the pathogens. This study demonstrates the power of VEM for describing the circulating viral community in a given region, which will enhance our understanding of plant viral diversity, and facilitate emerging plant virus surveillance and management of viral diseases