Dendritic Cells and Cancer Immunotherapy: The Adjuvant Effect

Dendritic cells (DCs) are immune specialized cells playing a critical role in promoting immune response against antigens, and may represent important targets for therapeutic interventions in cancer. DCs can be stimulated ex vivo with pro-inflammatory molecules and loaded with tumor-specific antigen(s). Protocols describing the specific details of DCs vaccination manufacturing vary widely, but regardless of the employed protocol, the DCs vaccination safety and its ability to induce antitumor responses is clearly established. Many years of studies have focused on the ability of DCs to provide overall survival benefits at least for a selection of cancer patients. Lessons learned from early trials lead to the hypothesis that, to improve the efficacy of DCs-based immunotherapy, this should be combined with other treatments. Thus, the vaccine’s ultimate role may lie in the combinatorial approaches of DCs-based immunotherapy with chemotherapy and radiotherapy, more than in monotherapy. In this review, we address some key questions regarding the integration of DCs vaccination with multimodality therapy approaches for cancer treatment paradigms.     

Modeling and biological investigations of an unusual behavior of novel synthesized acridine-based polyamine ligands in the binding of double helix and G-quadruplex DNA

Three novel 2,7-substituted acridine derivatives were designed and synthesized to investigate the effect of this functionalization on their interaction with double-stranded and G-quadruplex DNA. Detailed investigations of their ability to bind both forms of DNA were carried out by using spectrophotometric, electrophoretic, and computational approaches. The ligands in this study are characterized by an open-chain (L1) or a macrocyclic (L2, L3) framework. The aliphatic amine groups in the macrocycles are joined by ethylene (L2) or propylene chains (L3). L1 behaved similarly to the lead compound m-AMSA, efficiently intercalating into dsDNA, but stabilizing G-quadruplex structures poorly, probably due to the modest stabilization effect exerted by its protonated polyamine chains. L2 and L3, containing small polyamine macrocyclic frameworks, are known to adopt a rather bent and rigid conformation; thus they are generally expected to be sterically impeded from recognizing dsDNA according to an intercalative binding mode. This was confirmed to be true for L3. Nevertheless, we show that L2 can give rise to efficient π-π and H-bonding interactions with dsDNA. Additionally, stacking interactions allowed L2 to stabilize the G-quadruplex structure: using the human telomeric sequence, we observed the preferential induction of tetrameric G-quadruplex forms. Thus, the presence of short ethylene spacers seems to be essential for obtaining a correct match between the binding sites of L2 and the nucleobases on both DNA forms investigated. Furthermore, current modeling methodologies, including docking and MD simulations and free energy calculations, provide structural evidence of an interaction mode for L2 that is different from that of L3; this could explain the unusual stabilizing ability of the ligands (L2>L3>L1) toward G-quadruplex that was observed in this study.     

The comprehensive in vitro evaluation of eight different calcium phosphates: Significant parameters for cell behavior

Eight different calcium phosphate nanoparticles, namely bovine bone bioapatite calcined at 500, 600, and 700°C, Mg-doped brushite, fluorinated calcium phosphate, Ca-deficient hydroxyapatite, hydroxyapatite, and tricalcium phosphate, were characterized employing physico-chemical methods. Their cytocompatibility was evaluated under human osteoblast-like cell line MG-63 culture conditions in elution media and via the direct interaction of cells with calcium phosphate nanoparticles. The main objective was to determine the correlation of the cell indices with the differently determined physical and chemical parameters of the calcium phosphates. Chemical composition, which contributes toward pH changes, and the calcium ion concentration in the medium appear to make up particularly significant factors; moreover, it was proved that the number of material types represents a further important aspect. In the case of a large number of material types, almost no correlation was determined between the analyzed parameters; however, in the case of a small number of apatite types, several positive correlations were found. It can be concluded that it is not possible to identify any monitored parameters that had a major impact on cell behavior or, at least, such an effect which can be generalized. It appears more likely that cell behavior is affected by the interplay of various parameters.     

Quantitative Assessment of Affinity Selection Performance by Using DNA-Encoded Chemical Libraries

DNA-encoded chemical libraries are often used for the discovery of ligands against protein targets of interest. These large collections of DNA-barcoded chemical compounds are typically screened by using affinity capture methodologies followed by PCR amplification and DNA sequencing procedures. However, the performance of individual steps in the selection procedures has been scarcely investigated, so far. Herein, the quantitative analysis of selection experiments, by using three ligands with different affinity to carbonic anhydrase IX as model compounds, is described. In the first set of experiments, quantitative PCR (qPCR) procedures are used to evaluate the recovery and selectivity for affinity capture procedures performed on different solid-phase supports, which are commonly used for library screening. In the second step, both qPCR and analysis of DNA sequencing results are used to assess the recovery and selectivity of individual carbonic anhydrase IX ligands in a library, containing 360 000 compounds. Collectively, this study reveals that selection procedures can be efficient for ligands with sub-micromolar dissociation constants to the target protein of interest, but also that selection performance dramatically drops if 10⁴ copies per library member are used as the input.     

Nano-to-macroporous TiO2 (anatase) by cold sintering process

Cold Sintering Process (CSP) was applied on commercial nanopowders to produce nanostructured TiO₂ anatase with nano-to-macro porosity. Nanoporous TiO₂ based materials were obtained by applying CSP at 150 °C and pressures up to 500 MPa on three TiO₂ nanopowders with different specific surface area (s.s.a. = 50, 90 and 370 m²/g), using water as transient aqueous environment. Although TiO₂ is insoluble in water, a density of 68% and s.s.a. = 117 m²/g were achieved from the powder with the highest specific surface area. A post annealing process at 500 °C increased the density up to 73% with a s.s.a. = 59 m²/g, and the crystallites dimensions passed from 110 Å in the powder to 130 Å in CSP material and 172 Å after post annealing. Finally, macroporosity was produced by using thermoplastic polymer beads as sacrificial templates within TiO₂ nanopowder during CSP, followed by a debonding at 500 °C.     

Sinanodonta woodiana (mollusca: bivalvia: unionidae): isolation and characterization of the first microsatellite markers

Sinanodonta woodiana (Lea, 1834) is a large Unionid species with a real invasion success. It colonized Europe, Central America, the Indonesian Islands and recently North America. The species life cycle involves a larval parasitic stage on freshwater fish species which contributes to the spread of the mussel. In this paper we describe, for the first time, eight polymorphic microsatellite loci for the species Sinanodonta woodiana. The genetic screening of individuals confirmed that all loci were highly polymorphic. The number of alleles per locus ranged from 7 to 14 and the observed heterozygosity ranged from 0.650 to 0.950. These loci should prove useful to study the species population genetics which could help to infer important aspects of the invasion process.     

Unified study of flow regimes and gas holdup in the presence of positive and negative surfactants in a non-uniformly aerated bubble column

In this paper, a study on the global gas holdup and hydrodynamic flow regimes developed in a partially aerated bubble column at variable air superficial velocities (U_G) in the presence of positive and negative surfactants is presented. According to the results obtained, despite the different liquid phase properties variation caused by the presence of positive (alcohols) and negative (electrolytes) surfactants, both reduce coalescence and the effect in the gas holdup (ε_G) is equivalent: it increases with the surfactant concentration (C) but only when the (C/C_t) ratio is clearly above 1, being C_t the transition concentration. Contrary to the results obtained for totally aerated bubble columns, for lower values of the (C/C_t) ratio, the holdup remains practically invariable. Considering the crucial role that C and C_t play in the resulting ε_G, a new prediction equation for ε_G accounting for the ratio (C/C_t) and U_G is presented and its performance for both types of surfactants validated. Additionally, visual and wall pressure fluctuations studies reveal that the vortical flow (VF), characterized by an oscillating bubble plume, prevails in ultrapure water (UPW) but results destabilized in the presence of surfactants. This destabilization results in an evolution to a pseudo-steady flow regime, the double cell turbulent flow regime (DCTF), characterized by a quasi-static bubble jet, located at the column centerline that determines the appearance of two static symmetrical vortices     

Influence of Laponite RD on the properties of poly(vinyl alcohol) hydrogels

Poly(vinyl alcohol) (PVA) hydrogels were prepared in the presence/absence of Laponite RD (LRD) by using glutaraldehyde (GL) as chemical crosslinker. The effect of GL concentration (CHO/OH ratio between 0.02 and 0.38) and of clay addition on the PVA hydrogel properties was investigated. The swollen hydrogels showed good transparency and flexibility. LRD incorporation into the PVA hydrogel, revealed by Fourier transform infrared spectroscopy, led to a significant increase of the roughness of the dried hydrogel surface (about two times), as established by atomic force microscopy. The swelling ability was affected in a small extent by the clay addition. The elastic modulus decreased from 4680 to 3340 Pa and from 2195 to 1603 Pa by addition of 0.5% LRD into PVA hydrogels obtained with CHO/OH ratio of 0.02 and 0.06, respectively. The LRD addition reduced the gelation time determined by in situ rheological monitoring of PVA crosslinking reaction. The experimental investigations showed that there is an optimum CHO/OH ratio of 0.02 for which the PVA/LRD hybrid hydrogel presents the properties required by a targeted application, as for example support material for wound dressings. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46661.     

Expanded Polystyrene Foam Formed from Polystyrene Beads Coated with a Nanocrystalline SiO2 Film and the Analysis of Its Moisture Adsorption and Resistance to Mechanical Stress

Conventional expanded polystyrene can absorb moisture, which significantly degrades its properties. In the present study, it was demonstrated that SiO₂ can be deposited on polystyrene beads before pre-expansion and molding steps. Under the applied test conditions, expanded polystyrene with nanocrystalline SiO₂ additives had approximately 10% lower moisture adsorption and an 8.4% better resistance to deformation. Expanded polystyrene analysis suggested that the observed improvements were caused by the hydrophobic nature of nanocrystalline SiO₂ and, even more importantly, because SiO₂ acted as an amalgamation catalyst and significantly increased adhesion between the expanded polystyrene beads during the expanded polystyrene molding process.     

Reviewing Rare Earth Succinate Frameworks from the Reticular Chemistry Point of View: Structures,Nets, Catalytic and Photoluminescence Applications

The intense development that Metal-Organic Frameworks have experienced along the last two decades, reflects the interest on these compounds as a new generation of multifunctional materials with diverse applications. The first works of Prof. Omar Yaghi devoted to obtain open frameworks by combining rigid aromatic linkers and a variety of metal centers, encouraged the creativity of the scientific community to designcoordination polymers employing aliphatic ligands as multitopic building blocks . Here, a revision of the literature dedicated to rare earth coordination networks mainly based in succinate ligand and derivatives is performed. A structural analysis of 2D and 3D frameworks based on rare earth elements and succinate, was carried out considering their inner connectivities and topologies with focus on those compounds with potential photoluminescent and catalytic technological applications. Thus, a variety of optical behaviours regarding the emission mechanisms, colours, lifetimes, quantum yields as well as chemical/thermal sensing properties are presented and compared with related phases found in literature. The catalytic performance of several rare earth-succinates in three important reactions is discussed in terms of their acidity, dimensionality and available active centers towards the formation of the desired products analysing parameters such as selectivity, yields and TOFs.