Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach

Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.     

Saliva improves Streptococcus mitis protective effect on human gingival fibroblasts in presence of 2-hydroxyethyl-methacrylate

This study aimed to investigate the effect of saliva on Streptococcus mitis free cells and on S. mitis/human gingival fibroblasts (HGFs) co-culture model, in presence of 2-hydroxyethyl-methacrylate (HEMA). The bacterial aggregation both in the planktonic phase and on HGFs, as well as the apoptotic and necrotic eukaryotic cells amount were analyzed, in presence of saliva and/or HEMA. The aggregation test revealed a significant saliva aggregation effect on S. mitis strains compared to the untreated sample. No significant differences were recorded in the amount of culturable bacteria in all studied conditions; however, from microscopy images, the saliva/HEMA combining effect induced a significant bacterial aggregation and adhesion on HGFs. HEMA treatment decreased viable eukaryotic cell number with a parallel increment of necrotic cells, but when saliva was added to the co-culture, the viable cells percentage increased to a value comparable to the control sample.     

Influence of Nb2O5 on the varistor behavior of TiO2–Cr2O3 system

This work investigated the influence of Nb₂O₅ dopant on the varistor behavior of the ternary system (99.95 ? x)%TiO₂, 0.05 %Cr₂O₃, x%Nb₂O₅, where x = 0.10; 0.15; 0.20; 0.25 % in mol. The processing was carried out using the conventional oxide mixture method. The initial oxides were homogenized in alcoholic media in a ball mill, for 3 h, dried in oven and isostatically pressed at 210 MPa and sintered at 1,400 °C for 2 h in air atmosphere and cooled at 5 °C/min cooling rate, resulting in pellets with high densification. Electrical measurements in continuous current at different temperatures revealed that for the lowest Nb₂O₅ concentration the breakdown electric field, E_B = 4.41 V/cm and non-linear coefficient, α = 4.6 were obtained, and for the highest Nb₂O₅ concentration the breakdown electric field, E_B = 9.71 V/cm and non-linear coefficient, α = 15.3 were obtained. These low values in the breakdown electric field enable these varistor systems to be used in protection systems for low-voltage energy grids. Changes in the potential barrier present in the grain–grain boundaries could also be observed, in which the height increased and the width decreased with the increase in the dopant concentration. However, for x = 0.25 % in mol Nb₂O₅, a significant reduction in the potential barrier height and the voltage per barrier was obtained. Furthermore, the tendency to increase the volume of the unitary cell with the increase of dopant concentration, which was interrupted in the system with 0.25 % Nb₂O₅, was another evidence that suggested the occurrence of Nb₂O₅ segregation in the grain boundaries, or even that the reduction in the average grain size could possibly dilute Nb₂O₅ concentration in the grain boundaries. The average grain size was calculated through SEM micrographs and ranged from 7 to 16 μm, with larger sizes occurring for lower dopant concentrations and presenting higher porosity and lower uniformity in the grains shape.     

Investigation of Interfaces by Atom Probe Tomography

We investigated the thermodynamic and transport properties of buried interfaces with atom probe tomography. Owing to the 3D subnanometer resolution and single atom sensitivity of the method, it is possible to obtain composition profiles with high accuracy both along or normal to the interfaces. We have shown that the width of the chemical interface between the Fe and Cr system follows the Cahn–Hilliard relation with a gradient energy coefficient of 1.86 × 10^?22 J nm². Sharpening of the Ni/Cu interface as a result of kinetic control was directly observed. We investigated the grain boundary and triple junction transport in Fe/Cr and Ni/Cu. Cr segregation enthalpy into Fe triple junctions was found to be 0.076 eV, which falls in between the surface (0.159 eV) and grain boundary (0.03 eV) segregation enthalpies. In the investigated 563 K to 643 K (290 °C to 370 °C) range, Ni transport is 200 to 300 times faster in the triple junctions of Cu than in the grain boundaries. The diffusion activation enthalpy in the triple junctions is two-thirds that of the grain boundaries (0.86 and 1.24 eV, respectively). These investigations have shown that triple junctions are defects in their own right with characteristic segregation and diffusion properties: They are preferred segregation sites and can be considered as a diffusion shortcut in the grain boundary network.     

Pt–Ba–Al2O3 for NOx storage and reduction: Characterization of the dispersed species

Pt–Ba–Al₂O₃ active and selective for NO_x storage and selective reduction to N₂ has been prepared and tested. Characterization of the parent Al₂O₃, Pt–Al₂O₃ and Ba–Al₂O₃ materials, as well as of Pt–Ba–Al₂O₃ catalyst in the oxidized, reduced and sulphated state has been performed by FT-IR spectroscopy of low-temperature adsorbed carbon monoxide and of adsorbed acetonitrile. XRD, TEM and XPS analyses have also been performed. Evidence for the predominance of Ba species, which are highly dispersed on the alumina support surface, and may be carbonated or sulphated, has been provided. Competitive interaction of Pt and Ba species with the surface sites of alumina has also been found.     

Enabling Electrocatalytic Fischer–Tropsch Synthesis from Carbon Dioxide Over Copper-based Electrodes

We report on the discovery that paraffins and olefins up to C₆ hydrocarbons can be obtained in CO₂ electroreduction at room temperature and atmospheric pressure by application of a commercially available Cu-electrode (Eurofysica), provided pretreatment by electropolishing is avoided. The product distribution follows the Schultz–Flory distribution and, depending on the applied potential, the chain growth probability (α) ranges from 0.23 to 0.31, values lower than those obtained in Fischer–Tropsch synthesis over heterogeneous Co- or Fe-based catalysts.     

Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: a multicenter study

The increase of proinflammatory cytokines in vaginal secretions may serve as a surrogate marker of unwanted inflammatory reaction to microbicide products topically applied for the prevention of sexually transmitted diseases, including HIV-1. Interleukin (IL)-1beta and IL-6 have been proposed as indicators of inflammation and increased risk of HIV-1 transmission; however, the lack of information regarding detection platforms optimal for vaginal fluids and interlaboratory variation limit their use for microbicide evaluation and other clinical applications. This study examines fluid matrix variants relevant to vaginal sampling techniques and proposes a model for interlaboratory comparisons across current cytokine detection technologies. IL-1beta and IL-6 standards were measured by 12 laboratories in four countries, using 14 immunoassays and four detection platforms based on absorbance, chemiluminescence, electrochemiluminescence, and fluorescence. International reference preparations of cytokines with defined biological activity were spiked into (1) a defined medium simulating the composition of human vaginal fluid at pH 4.5 and 7.2, (2) physiologic salt solutions (phosphate-buffered saline and saline) commonly used for vaginal lavage sampling in clinical studies of cytokines, and (3) human blood serum. Assays were assessed for reproducibility, linearity, accuracy, and significantly detectable fold difference in cytokine level. Factors with significant impact on cytokine recovery were determined by Kruskal-Wallis analysis of variance with Dunn's multiple comparison test and multiple regression models. All assays showed acceptable intra-assay reproducibility; however, most were associated with significant interlaboratory variation. The smallest reliably detectable cytokine differences ( P < 0.05) derived from pooled interlaboratory data varied from 1.5- to 26-fold depending on assay, cytokine, and matrix type. IL-6 but not IL-1beta determinations were lower in both saline and phosphate-buffered saline as compared to vaginal fluid matrix, with no significant effect of pH. The (electro)chemiluminescence-based assays were most discriminative and consistently detected <2-fold differences within each matrix type. The Luminex-based assays were less discriminative with lower reproducibility between laboratories. These results suggest the need for uniform vaginal sampling techniques and a better understanding of immunoassay platform differences and cross-validation before the biological significance of cytokine variations can be validated in clinical trials. This investigation provides the first standardized analytic approach for assessing differences in mucosal cytokine levels and may improve strategies for monitoring immune responses at the vaginal mucosal interface.     

Interferometer for ground-based observations of emitted spectral radiance from the troposphere: evaluation and retrieval performance

We evaluate the spectral quality, radiometric noise, and retrieval performance of a Fourier transform infrared spectrometer, which has been developed for recording spectrally resolved observations in a region of the spectrum which is important both for the science of Earth's climate and applications, such as the remote sensing of temperature and atmospheric gas species. This spectral region extends from 100 to 1600 cm(-1) and encompasses the two fundamental, rotation and vibration, absorption bands of water vapor. The instrument is a customized version of a Bomem AERI (Atmospheric Emitted Radiance Interferometer) spectrometer, whose spectral coverage has been extended in the far infrared with the use of uncooled pyroelectric detectors. Retrieval examples for water vapor and temperature profiles are shown, which also allow us to intercompare the retrieval performance of both H(2)O vibration and rotation bands.     

Serine Hydroxymethyltransferase from the Cold Adapted Microorganism Psychromonas ingrahamii: A Low Temperature Active Enzyme with Broad Substrate Specificity

Serine hydroxymethyltransferase from the psychrophilic microorganism Psychromonas ingrahamii was expressed in Escherichia coli and purified as a His-tag fusion protein. The enzyme was characterized with respect to its spectroscopic, catalytic, and thermodynamic properties. The properties of the psychrophilic enzyme have been contrasted with the characteristics of the homologous counterpart from E. coli, which has been structurally and functionally characterized in depth and with which it shares 75% sequence identity. Spectroscopic measures confirmed that the psychrophilic enzyme displays structural properties almost identical to those of the mesophilic counterpart. At variance, the P. ingrahamii enzyme showed decreased thermostability and high specific activity at low temperature, both of which are typical features of cold adapted enzymes. Furthermore, it was a more efficient biocatalyst compared to E. coli serine hydroxymethyltransferase (SHMT) particularly for side reactions. Many β-hydroxy-α-amino acids are SHMT substrates and represent important compounds in the synthesis of pharmaceuticals, agrochemicals and food additives. Thanks to these attractive properties, this enzyme could have a significant potential for biotechnological applications.