Design,Synthesis, Radiosynthesis and Biological Evaluation of Fenretinide Analogues as Anticancer and Metabolic Syndrome-Preventive Agents

Fenretinide (4-HPR) is a synthetic derivative of all-trans-retinoic acid (ATRA) characterised by improved therapeutic properties and toxicological profile relative to ATRA. 4-HPR has been mostly investigated as an anti-cancer agent, but recent studies showed its promising therapeutic potential for preventing metabolic syndrome. Several biological targets are involved in 4-HPR's activity, leading to the potential use of this molecule for treating different pathologies. However, although 4-HPR displays quite well-understood multitarget promiscuity with regards to pharmacology, interpreting its precise physiological role remains challenging. In addition, despite promising results in vitro, the clinical efficacy of 4-HPR as a chemotherapeutic agent has not been satisfactory so far. Herein, we describe the preparation of a library of 4-HPR analogues, followed by the biological evaluation of their anti-cancer and anti-obesity/diabetic properties. The click-type analogue 3 b showed good capacity to reduce the amount of lipid accumulation in 3T3-L1 adipocytes during differentiation. Furthermore, it showed an IC₅₀ of 0.53±0.8 μM in cell viability tests on breast cancer cell line MCF-7, together with a good selectivity (SI=121) over noncancerous HEK293 cells. Thus, 3 b was selected as a potential PET tracer to study retinoids in vivo, and the radiosynthesis of [¹⁸F] 3b was successfully developed. Unfortunately, the stability of [¹⁸F] 3b turned out to be insufficient to pursue imaging studies.     

On the Viscoelastic Properties of Collagen‐Gel‐Based Lattices under Cyclic Loading: Applications for Vascular Tissue Engineering

Reconstituted collagen gels are widely used as scaffolds even though their low strength and poor elasticity limit their applications in VTE. Here, two approaches are adopted to modify their mechanical behavior: in the first, gels prepared under physiologic conditions are remodeled by cell‐mediated contraction; in the second, gels prepared in non‐physiologic conditions are chemically crosslinked. Samples are tested under cyclic loading and their viscoelastic behavior is assessed. The results show that both approaches result in lattices with adequate strength, and crosslinking significantly reduces hysteresis and permanent deformation. SEM shows that SMCs are capable of contracting and remodeling all the lattices, confirming that these are suitable supports for tissue regeneration.

     

Catalyst–support interactions and their influence in water-assisted carbon nanotube carpet growth

We report results from characterization studies focused on a diverse selection of catalyst support materials in order to understand what makes a good catalyst support during carbon nanotube (CNT) carpet growth via water-assisted chemical vapor deposition. The growth and catalyst morphological changes occurring for thin Fe layers deposited on Al₂O₃, MgO, TiN, and ZrO₂ are compared. The growth behaviors of the catalyst substrates were evidently different, with Al₂O₃/Fe supporting CNT carpet growth and showing the highest activity and longest lifetime. The TiN/Fe catalyst also supported CNT carpet growth, albeit with much lower activity, shorter lifetime, and lower CNT quality while MgO/Fe and ZrO₂/Fe did not support CNT carpet growth under standard growth conditions. Studies using a combination of atomic force microscopy and X-ray photoelectron spectroscopy revealed a general correlation between the catalyst behavior (activity and lifetime) and the 3D evolution of the catalyst for active catalysts (Al₂O₃/Fe and TiN/Fe). Analysis of inactive catalysts under standard conditions (MgO/Fe and ZrO₂/Fe) raise interesting questions related to additional chemical interactions between the substrate and catalyst that could influence nucleation and CNT growth. This work provides a step toward understanding the challenges that arise in engineering efficient CNT growth processes on a desired substrate.     

Quantifying dissipative contributions in nanoscale interactions

Imaging with nanoscale resolution has become routine practice with the use of scanning probe techniques. Nevertheless, quantification of material properties and processes has been hampered by the complexity of the tip-surface interaction and the dependency of the dynamics on operational parameters. Here, we propose a framework for the quantification of the coefficients of viscoelasticity, surface energy, surface energy hysteresis and elastic modulus. Quantification of these parameters at the nanoscale will provide a firm ground to the understanding and modelling of tribology and nanoscale sciences with true nanoscale resolution.     

Unpatterned Bioactive Poly(Butylene 1,4-Cyclohexanedicarboxylate)-Based Film Fast Induced Neuronal-Like Differentiation of Human Bone Marrow-Mesenchymal Stem Cells

Herein, we present poly(butylene 1,4-cyclohexanedicarboxylate) (PBCE) films characterized by an unpatterned microstructure and a specific hydrophobicity, capable of boosting a drastic cytoskeleton architecture remodeling, culminating with the neuronal-like differentiation of human bone marrow-mesenchymal stem cells (hBM-MSCs). We have used two different filming procedures to prepare the films, solvent casting (PBCE) and compression-moulding (PBCE*). PBCE film had a rough and porous surface with spherulite-like aggregations (Ø = 10–20 μm) and was characterized by a water contact angle = 100°. PBCE* showed a smooth and continuous surface without voids and visible spherulite-like aggregations and was more hydrophobic (WCA = 110°). Both surface characteristics were modulated through the copolymerization of different amounts of ether-oxygen-containing co-units into PBCE chemical structure. We showed that only the surface characteristics of PBCE-solvent-casted films steered hBM-MSCs toward a neuronal-like differentiation. hBM-MSCs lost their canonical mesenchymal morphology, acquired a neuronal polarized shape with a long cell protrusion (≥150 μm), expressed neuron-specific class III β-tubulin and microtubule-associated protein 2 neuronal markers, while nestin, a marker of uncommitted stem cells, was drastically silenced. These events were observed as early as 2-days after cell seeding. Of note, the phenomenon was totally absent on PBCE* film, as hBM-MSCs maintained the mesenchymal shape and behavior and did not express neuronal/glial markers.     

Imaging of KCa3.1 Channels in Tumor Cells with PET and Small-Molecule Fluorescent Probes

The Ca²⁺ activated K⁺ channel K_Ca3.1 is overexpressed in several human tumor cell lines, e. g. clear cell renal carcinoma, prostate cancer, non-small cell lung cancer. Highly aggressive cancer cells use this ion channel for key processes of the metastatic cascade such as migration, extravasation and invasion. Therefore, small molecules, which are able to image this K_Ca3.1 channel in vitro and in vivo represent valuable diagnostic and prognostic tool compounds. The [¹⁸F]fluoroethyltriazolyl substituted senicapoc was used as positron emission tomography (PET) tracer and showed promising properties for imaging of K_Ca3.1 channels in lung adenocarcinoma cells in mice. The novel senicapoc BODIPY conjugates with two F-atoms ( 9 a ) and with a F-atom and a methoxy moiety ( 9 b ) at the B-atom led to the characteristic punctate staining pattern resulting from labeling of single K_Ca3.1 channels in A549-3R cells. This punctate pattern was completely removed by preincubation with an excess of senicapoc confirming the high specificity of K_Ca3.1 labeling. Due to the methoxy moiety at the B-atom and the additional oxyethylene unit in the spacer, 9 b exhibits higher polarity, which improves solubility and handling without reduction of fluorescence quantum yield. Docking studies using a cryo-electron microscopy (EM) structure of the K_Ca3.1 channel confirmed the interaction of 9 a and 9 b with a binding pocket in the channel pore.     

Premixed metal fibre burners based on a Pd catalyst

As an alternative to previously developed catalytic FeCrAlloy fibre mat burners based on perovskite catalysts, new catalytic burners have been developed based on Pd catalyst on lantana-stabilised Al₂O₃ and different fibre structures (NIT100A, NIT100S and NIT200S by ACOTECH NV). All development steps are considered, shifting from catalyst preparation (based on combustion synthesis of γ-Al₂O₃) to the optimisation of lantana and Pd loadings, from the definitions of the best catalyst-deposition conditions (washcoating) to the catalytic burners performances, determined in an ad hoc developed combustion chamber. The results show almost half pollutants emissions and better performance compared to various non-catalytic counterparts, especially as far as CO and NO_x emissions are concerned. Some flame instability problems were though registered, especially for one of the catalytic burner mattresses employed, at low specific power inputs and excesses of air (<375 kW/m² and <12%, respectively). Further, PdO/Pd transition is shown to influence the dynamic behaviour of the catalytic burners.     

X-ray Diffraction Methodology for the Microstructural Analysis of Nanocrystalline Powders: Application to Cerium Oxide

The microstructural evolution of nanocrystalline ceria produced by sol–gel has been analyzed as a function of the calcination temperature employing a novel nondestructive method based on the modeling of the whole X-ray diffraction pattern. The results have been thoroughly verified by transmission electron microscopy. A variation both in the average size and in the distribution of the crystalline domains is evidenced. In addition, information concerning lattice defects can be inferred on a larger scale than that normally accessible by microscopy techniques.     

HA/β-TCP plasma sprayed coatings on Ti substrate for biomedical applications

The present work focuses on the fabrication of βTCP (β-tricalcium phosphate) and HA/βTCP (hydroxyapatite/β-tricalcium phosphate) composite coatings by plasma spraying. The starting powders were produced via solid-state method using 2 wt% MgO to stabilize βTCP phase. The synthesized powders were preliminarily granulated to be used by the plasma spray process. Coatings obtained on titanium substrates are uniform and well adherent but due to the high temperature and cooling rate typical for plasma spraying process, βTCP phase is almost totally transformed into the α allotrope. Thermal treatment at 800 °C allows the reconversion of the phase αTCP→ βTCP. It is therefore possible to produce coatings with tuneable dissolution properties by selecting the proper initial powder mixture and the specific thermal treatment.