Resiquimod-Mediated Activation of Plasmacytoid Dendritic Cells Is Amplified in Multiple Sclerosis

Background: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. The cause of multiple sclerosis is unknown but there are several evidences that associate the genetic basis of the disease with environmental causes. An important association between viral infection and development of MS is clearly demonstrated. Viruses have a strong impact on innate immune cells. In particular, myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), are able to respond to viruses and to activate the adaptive immune response. Methods: In this study we mimic viral infection using synthetic single-strand RNA, Resiquimod, and we compared the response of both DC subsets derived from healthy donors and MS patients by characterizing the expression of costimulatory molecules on the DC surface. Results: We found that pDCs from MS patients express higher levels of OX40-L, HLA-DR, and CD86 than healthy donors. Moreover, we found that blood cells from MS patients and healthy donors upon Resiquimod-stimulation are enriched in a subpopulation of pDCs, characterized by a high amount of costimulatory molecules. Conclusion: Overall, these results indicate that activation of pDCs is enhanced in MS, likely due to a latent viral infection, and that costimulatory molecules expressed on pDCs could mediate a protective response against the viral trigger of autoimmunity

Microwave Assisted Extraction of Raw Alginate as a Sustainable and Cost-Effective Method to Treat Beach-Accumulated Sargassum Algae

This paper highlights the potential of Sargassum algae, recovered from raw beach seaweed wastes, as a valid source of valuable sodium alginate. Alginate is a biodegradable, highly attractive polysaccharide widely used in food, pharmaceuticals, and biomedicine applications. The aim of this work is to employ a new eco-sustainable and cost-effective extractive method to obtain alginate as a raw material from pollutant organic Sargassum seaweeds. Algae were exposed to microwave pre-treatment under static and dynamic conditions, and three different extractive protocols were followed: (a) conventional, (b) hot water and (c) alkaline method. All samples were characterized by GPC, SEM, FTIR/ATR and TGA. It was found that alginate’s best performances were obtained by the microwave dynamic pre-treatment method followed by alkaline extractive protocol. Nevertheless, the microwave pre-treatment of algae allowed the easiest breaking of their cell walls and the following fast releasing of sodium alginate. The authors demonstrated that microwave-enhanced extraction is an effective way to obtain sodium alginate from Sargassum-stranded seaweed waste materials in a cost-effective and eco-sustainable approach. They also assessed their applications as mulching films for agricultural applications

Distinct Expression of Inflammatory Features in T Helper 17 Cells from Multiple Sclerosis Patients

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). T helper (Th) 17 lymphocytes play a role in the pathogenesis of MS. Indeed, Th17 cells are abundant in the cerebrospinal fluid and peripheral blood of MS patients and promote pathogenesis in the mouse model of MS. To gain insight into the function of Th17 cells in MS, we tested whether Th17 cells polarized from naïve CD4 T cells of healthy donors and MS patients display different features. To this end, we analysed several parameters that typify the Th17 profile during the differentiation process of naïve CD4 T cells obtained from relapsing-remitting (RR)-MS patients (n = 31) and healthy donors (HD) (n = 28). Analysis of an array of cytokines produced by Th17 cells revealed that expression of interleukin (IL)-21, tumour necrosis factor (TNF)-β, IL-2 and IL-1R1 is significantly increased in Th17 cells derived from MS patients compared to healthy donor-derived cells. Interestingly, IL-1R1 expression is also increased in Th17 cells circulating in the blood of MS patients compared to healthy donors. Since IL-2, IL-21, TNF-β, and IL-1R1 play a crucial role in the activation of immune cells, our data indicate that high expression of these molecules in Th17 cells from MS patients could be related to their high inflammatory status

Induction of transforming growth factor beta receptors following focal ischemia in the rat brain

Transforming growth factor-βs (TGF-βs) regulate cellular proliferation, differentiation, and survival. TGF-βs bind to type I (TGF-βRI) and II receptors (TGF-βRII), which are transmembrane kinase receptors, and an accessory type III receptor (TGF-βRIII). TGF-β may utilize another type I receptor, activin-like kinase receptor (Alk1). TGF-β is neuroprotective in the middle cerebral artery occlusion (MCAO) model of stroke. Recently, we reported the expression pattern of TGF-β1-3 after MCAO. To establish how TGF-βs exert their actions following MCAO, the present study describes the induction of TGF-βRI, RII, RIII and Alk1 at 24 h, 72 h and 1 mo after transient 1 h MCAO as well as following 24 h permanent MCAO using in situ hybridization histochemistry. In intact brain, only TGF-βRI had significant expression: neurons in cortical layer IV contained TGF-βRI. At 24 h after the occlusion, no TGF-β receptors showed induction. At 72 h following MCAO, all four types of TGF-β receptors were induced in the infarct area, while TGF-βRI and RII also appeared in the penumbra. Most cells with elevated TGF-βRI mRNA levels were microglia. TGF-βRII co-localized with both microglial and endothelial markers while TGF-βRIII and Alk1 were present predominantly in endothels. All four TGF-β receptors were induced within the lesion 1 mo after the occlusion. In particular, TGF-βRIII was further induced as compared to 72 h after MCAO. At this time point, TGF-βRIII signal was predominantly not associated with blood vessels suggesting its microglial location. These data suggest that TGF-β receptors are induced after MCAO in a timely and spatially regulated fashion. TGF-β receptor expression is preceded by increased TGF-β expression. TGF-βRI and RII are likely to be co-expressed in microglial cells while Alk1, TGF-βRII, and RIII in endothels within the infarct where TGF-β1 may be their ligand. At later time points, TGF-βRIII may also appear in glial cells to potentially affect signal transduction via TGF-βRI and RII

Modeling and experimental validation of mass transfer from carbonated beverages in polyethylene terephthalate bottles

Mass transfer and related shelf life assessment is an important issue in the beverage industry. Product change due to mass transfer is at stake and, with it, its consumer value and consideration. Carbonation loss takes place at the product/package interface, and to the environment through the package itself. In this paper a joint experimental/computational approach has been exploited: the CO2 loss through the polyethylene terephthalate barrier has been computed by means of a multidimensional finite element code, while actual measurements have been carried out to validate the computations. Residual carbonation histories are validated and presented for a variety of thermal regimes and for two different bottles carrying the same capacity. The paper highlights on the combination of bottle weight, initial carbonation and storage temperature, indicating the operational set for the longest shelf life within the explored cases. Lighter bottles can be used with no inference on shelf life, while the carbonic loss depends non-linearly on initial carbonation and temperature increment. The associated concentration maps help infer on the importance of polyethylene terephthalate thickness uniformity. It is then demonstrated that the model carries the flexibility of a general tool, applicable to any carbonated beverage at any storage condition

THE DESIGN OF URBAN QUALITY: INNOVATIVE COMMUNITY FACILITIES IN SUPPORT OF STRATEGIES OF URBAN RENEWAL. A METHODOLOGICAL PROPOSAL

Given the central role that services are taking over the quality of life of communities, they have to be reorganized from the point of view of efficiency, considering a supply and a demand in continuous interaction and evolution, and integrating the endowment of areas and public facilities with the actual provided services. The aim of this research is the definition of a methodology of planning and locating community facilities and services that might give support to the decision-making processes for the assets of urban planning, in order to improve urban quality and collective well-being. The methodology is divided into three phases, so that it can be integrated into urban planning. It is characterized by a preliminary, structural and executive phase, to which different results correspond. The proposed methodology considers the concept of performance at each phase, and this allows the orientation of the policies of urban regeneration and densification, by stimulating the reuse of parts of the urban tissue. Moreover, the tools and techniques of the methodology presuppose an advanced data management. Finally, the participative processes, as integrative steps of the methodology, help the dynamic aspects connected with the planning

Modeling and validation of local acrylamide formation in a model food during frying

Acrylamide formation in a food model during frying can be analyzed in space and time with a traditional heat and mass transfer approach. In this paper a joint simulation/experiment approach has been exploited: the computational fluid dynamics has been coupled to chemical kinetics, to describe concentration and temperature fields in a food substrate, subject to interdependent and non-uniform heat and mass transfer, while validating measurements have been performed by high performance liquid chromatography. A multi-objective SIMPLEX optimization has been finally employed for the overall model tuning, incorporating all phenomenological variations. The numerical results confirmed that the acrylamide formation is non-linearly dependent on the operating thermal regime, in general more than doubling its average levels when the process temperature is increased by 10% only. Based on the proposed acrylamide maps, a maximum concentration locus is found on the product’s upper corner, depending on the specific transport ensemble and therefore on the local process conditions. For potato frying at an initial temperature of 190 °C, the maximum local acrylamide level after 4 min (almost 4x10-2 mg/g) is almost four times the one obtained when frying at 170 °C, while scaling only linearly with process duration