The PVT1 lncRNA has recently been involved in tumorigenesis by affecting the protein stability of the MYC proto-oncogene. Both MYC and PVT1 reside in a well-known cancer-risk locus and enhanced levels of their products have been reported in different human cancers. Nonetheless, the extension and relevance of the MYC-PVT1 deregulation in tumorigenesis has not yet been systematically addressed.Here we performed a pan-cancer analysis of matched copy number, transcriptomic, methylation, proteomic and clinicopathological profiles for almost 7000 patients from 17 different cancers represented in the TCGA cohorts. Among all cancers types, kidney renal clear cell carcinoma (KIRC) showed the strongest upregulation of PVT1 and increased levels of both MYC and PVT1 correlated with the clinical outcome. PVT1 misregulation in KIRC is mostly associated to promoter hypomethylation rather than locus amplification. Furthermore, we found an association between MYC levels and PVT1 expression, which impacted on MYC-target genes.Collectively, our study discloses the role of PVT1 as a novel prognostic factor and as a molecular target for novel therapeutic interventions in renal carcinoma.

Dendritic cells (DCs) hold promise for anti-cancer immunotherapy. However, clinically, their efficiency is limited and novel strategies to improve DC-mediated anti-tumor responses are needed. Human DCs display high content of sialic acids, which inhibits their maturation and co-stimulation capacity. Here, we aimed to understand whether exogenous desialylation of DCs improves their anti-tumor immunity. Compared to fully sialylated DCs, desialylated human DCs loaded with tumor-antigens showed enhanced ability to induce autologous T cells to proliferate, to secrete Th1 cytokines, and to specifically induce tumor cell apoptosis. Desialylated DCs showed an increased expression of MHC-I and -II, co-stimulatory molecules and an augmented secretion of IL-12. Desialylated HLA-A*02:01 DCs pulsed with gp100 peptides displayed enhanced peptide presentation through MHC-I, resulting in higher activation ofgp100280–288 specific CD8+ cytotoxic T cells. Desialylated murine DCs also exhibited increased MHC and co-stimulatory molecules and higher antigen cross-presentation via MHC-I. These DCs showed higher ability to activate antigen-specific CD4+ and CD8+ T cells, and to specifically induce tumor cell apoptosis. Collectively, our data demonstrates that desialylation improves DCs’ ability to elicit T cell-mediated anti-tumor activity, due to increased MHC-I expression and higher antigen presentation via MHC-I. Sialidase treatment of DCs may represent a technology to improve the efficacy of antigen loaded-DC-based vaccines for anti-cancer immunotherapy.

Mammalian aldehyde oxidases (AOXs; EC1.2.3.1) are a group of conserved proteins belonging to the family of molybdo-flavoenzymes along with the structurally related xanthine dehydrogenase enzyme. AOXs are characterized by broad substrate specificity, oxidizing not only aromatic and aliphatic aldehydes into the corresponding carboxylic acids, but also hydroxylating a series of heteroaromatic rings. The number of AOX isoenzymes expressed in different vertebrate species is variable. The two extremes are represented by humans, which express a single enzyme (AOX1) in many organs and mice or rats which are characterized by tissue-specific expression of four isoforms (AOX1, AOX2, AOX3, and AOX4). In vertebrates each AOX isoenzyme is the product of a distinct gene consisting of 35 highly conserved exons. The extant species-specific complement of AOX isoenzymes is the result of a complex evolutionary process consisting of a first phase characterized by a series of asynchronous gene duplications and a second phase where the pseudogenization and gene deletion events prevail. In the last few years remarkable advances in the elucidation of the structural characteristics and the catalytic mechanisms of mammalian AOXs have been made thanks to the successful crystallization of human AOX1 and mouse AOX3. Much less is known about the physiological function and physiological substrates of human AOX1 and other mammalian AOX isoenzymes, although the importance of these proteins in xenobiotic metabolism is fairly well established and their relevance in drug development is increasing. This review article provides an overview and a discussion of the current knowledge on mammalian AOX.

The adsorption of triclosan as model system was studied to qualify activated carbon sorbents recycled from gas masks (civilian gas mask GP5). The triclosan equilibrium concentration was measured spectrophotometrically, the morphology of the activated carbon characterized by scanning electron microscopy, and the amount of the adsorbed triclosan on the activated carbon quantified by a mass balance method. Experimental isotherms were fitted by Langmuir, Freundlich and Sips adsorption models. It was obtained that the contact time is a crucial sorption parameter that provides information on the optimum adsorption efficiency. It was shown that the maximum efficiency of GP5 (88%) is obtained after 10days of adsorption at a maximal concentration of triclosan and carbon loading 1mg/l. No significant adsorption efficiency differences were measured after 5 and 10days of adsorption. The non-linear Sips isotherm, a combined Freundlich–Langmuir model, provides suitable fitting results. The observed remarkable adsorption capacity of activated carbon (GP5) towards triclosan adsorption (∼85mg/g) makes it a viable solution for wastewater treatment.

RNAi has always captivated scientists due to its tremendous power to modulate the phenotype of living organisms. This natural and powerful biological mechanism can now be harnessed to downregulate specific gene expression in diseased cells, opening up endless opportunities. Since most of the conventional siRNA delivery methods are limited by a narrow therapeutic index and significant side and off-target effects, we are now in the dawn of a new age in gene therapy driven by nanotechnology vehicles for RNAi therapeutics. Here, we outlook the {"}do's and dont's{"} of the inorganic RNAi nanomaterials developed in the last 15 years and the different strategies employed are compared and scrutinized, offering important suggestions for the next 15. (C) 2015 Elsevier Ltd. All rights reserved.

Chitin, the second most abundant polymer in nature, is a renewable, nontoxic, biodegradable, and antibacterial polysaccharide. This semicrystalline biopolymer exhibits hierarchical structure from nano to micro-scale and is responsible for interesting living tissue properties. Recently, the scientific interest in chitin nanofibrils for applications in biomedical and tissue engineering fields has increased due to their particular capabilities such as matrix reinforcements, bioactivity and morphology similar to natural tissues. This chapter is focused on composite materials reinforced with chitin nanofibrils and their biomedical applications.

X-ray intensity ratios, such as the Kα2/Kα1 ratio, are parameters with a large application in atomic physics and related scientific and technological areas. D.

A MATLAB/SIMULINK software simulation model (structure and component blocks) has been constructed in order to view and analyze the potential of the PSD (Position Sensitive Detector) array concept technology before it is further expanded or developed. This simulation allows changing most of its parameters, such as the number of elements in the PSD array, the direction of vision, the viewing/scanning angle, the object rotation, translation, sample/scan/simulation time, etc. In addition, results show for the first time the possibility of scanning an object in 3D when using an a-Si:H thin film 128 PSD array sensor and hardware/software system. Moreover, this sensor technology is able to perform these scans and render 3D objects at high speeds and high resolutions when using a sheet-of-light laser within a triangulation platform. As shown by the simulation, a substantial enhancement in 3D object profile image quality and realism can be achieved by increasing the number of elements of the PSD array sensor as well as by achieving an optimal position response from the sensor since clearly the definition of the 3D object profile depends on the correct and accurate position response of each detector as well as on the size of the PSD array.