Osteosarcoma Pathogenesis Leads the Way to New Target Treatments

Osteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets.     

κ-Opioid Signaling in the Lateral Hypothalamic Area Modulates Nicotine-Induced Negative Energy Balance

Several studies have reported that nicotine, the main bioactive component of tobacco, exerts a marked negative energy balance. Apart from its anorectic action, nicotine also modulates energy expenditure, by regulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. These effects are mainly controlled at the central level by modulation of hypothalamic neuropeptide systems and energy sensors, such as AMP-activated protein kinase (AMPK). In this study, we aimed to investigate the kappa opioid receptor (κOR)/dynorphin signaling in the modulation of nicotine’s effects on energy balance. We found that body weight loss after nicotine treatment is associated with a down-regulation of the κOR endogenous ligand dynorphin precursor and with a marked reduction in κOR signaling and the p70 S6 kinase/ribosomal protein S6 (S6K/rpS6) pathway in the lateral hypothalamic area (LHA). The inhibition of these pathways by nicotine was completely blunted in κOR deficient mice, after central pharmacological blockade of κOR, and in rodents where κOR was genetically knocked down specifically in the LHA. Moreover, κOR-mediated nicotine effects on body weight do not depend on orexin. These data unravel a new central regulatory pathway modulating nicotine’s effects on energy balance.     

Stem Photosynthesis—A Key Element of Grass Pea (Lathyrus sativus L.) Acclimatisation to Salinity

Grass pea (Lathyrus sativus) is a leguminous plant of outstanding tolerance to abiotic stress. The aim of the presented study was to describe the mechanism of grass pea (Lathyrus sativus L.) photosynthetic apparatus acclimatisation strategies to salinity stress. The seedlings were cultivated in a hydroponic system in media containing various concentrations of NaCl (0, 50, and 100 mM), imitating none, moderate, and severe salinity, respectively, for three weeks. In order to characterise the function and structure of the photosynthetic apparatus, Chl a fluorescence, gas exchange measurements, proteome analysis, and Fourier-transform infrared spectroscopy (FT-IR) analysis were done inter alia. Significant differences in the response of the leaf and stem photosynthetic apparatus to severe salt stress were observed. Leaves became the place of harmful ion (Na⁺) accumulation, and the efficiency of their carboxylation decreased sharply. In turn, in stems, the reconstruction of the photosynthetic apparatus (antenna and photosystem complexes) activated alternative electron transport pathways, leading to effective ATP synthesis, which is required for the efficient translocation of Na⁺ to leaves. These changes enabled efficient stem carboxylation and made them the main source of assimilates. The observed changes indicate the high plasticity of grass pea photosynthetic apparatus, providing an effective mechanism of tolerance to salinity stress.     

Gluten-free cakes with walnut flour: a technological,sensory, and microstructural approach

Walnut flour (WF), a by-product of walnut oil production, is characterised by high polyunsaturated fatty acids, proteins, and fibre contents and presents suitability for bakery products. However, when using non-traditional ingredients, it is essential to evaluate the effect on the quality properties of the final product. So, this work aimed to assess the impact of WF on the technological, physicochemical, and sensory properties of gluten-free (GF) cakes. WF was added at a flour blend (cassava (CS) and maize (MS) starches and rice flour) at 0, 10%, 15%, and 20%. The results showed that WF modified starch gelatinisation, increased amylose–lipid complex (ALC) content, and made crumbs easier to chew. Besides, the total dietary fibre (TDF) and protein content significantly increased. Cakes with 15% WF presented the highest specific volume (SV) and no differences in overall acceptability with respect to control. Hence, WF is a suitable ingredient for gluten-free bakery products.     

Tailored-Made Polydopamine Nanoparticles to Induce Ferroptosis in Breast Cancer Cells in Combination with Chemotherapy

Ferroptosis is gaining followers as mechanism of selective killing cancer cells in a non-apoptotic manner, and novel nanosystems capable of inducing this iron-dependent death are being increasingly developed. Among them, polydopamine nanoparticles (PDA NPs) are arousing interest, since they have great capability of chelating iron. In this work, PDA NPs were loaded with Fe³⁺ at different pH values to assess the importance that the pH may have in determining their therapeutic activity and selectivity. In addition, doxorubicin was also loaded to the nanoparticles to achieve a synergist effect. The in vitro assays that were performed with the BT474 and HS5 cell lines showed that, when Fe³⁺ was adsorbed in PDA NPs at pH values close to which Fe(OH)₃ begins to be formed, these nanoparticles had greater antitumor activity and selectivity despite having chelated a smaller amount of Fe³⁺. Otherwise, it was demonstrated that Fe³⁺ could be released in the late endo/lysosomes thanks to their acidic pH and their Ca²⁺ content, and that when Fe³⁺ was co-transported with doxorubicin, the therapeutic activity of PDA NPs was enhanced. Thus, reported PDA NPs loaded with both Fe³⁺ and doxorubicin may constitute a good approach to target breast tumors.     

Validation of scientific topic models using graph analysis and corpus metadata

Probabilistic topic modeling algorithms like Latent Dirichlet Allocation (LDA) have become powerful tools for the analysis of large collections of documents (such as papers, projects, or funding applications) in science, technology an innovation (STI) policy design and monitoring. However, selecting an appropriate and stable topic model for a specific application (by adjusting the hyperparameters of the algorithm) is not a trivial problem. Common validation metrics like coherence or perplexity, which are focused on the quality of topics, are not a good fit in applications where the quality of the document similarity relations inferred from the topic model is especially relevant. Relying on graph analysis techniques, the aim of our work is to state a new methodology for the selection of hyperparameters which is specifically oriented to optimize the similarity metrics emanating from the topic model. In order to do this, we propose two graph metrics: the first measures the variability of the similarity graphs that result from different runs of the algorithm for a fixed value of the hyperparameters, while the second metric measures the alignment between the graph derived from the LDA model and another obtained using metadata available for the corresponding corpus. Through experiments on various corpora related to STI, it is shown that the proposed metrics provide relevant indicators to select the number of topics and build persistent topic models that are consistent with the metadata. Their use, which can be extended to other topic models beyond LDA, could facilitate the systematic adoption of this kind of techniques in STI policy analysis and design.

     

Two-step sinter-crystallization of K2O–CaO–P2O5–SiO2 (45S5-K) bioactive glass

Bioactive glasses and glass-ceramics (GCs) effectively regenerate bone tissue, however most GCs show improved mechanical properties. In this work, we developed and tested a rarely studied bioactive glass composition (24.4K₂O-26.9CaO-46.1SiO₂-2.6P₂O₅ mol%, identified as 45S5-K) with different particle sizes and heating rates to obtain a sintered GC that combines good fracture strength, low elastic modulus, and bioactivity. We analyzed the influence of the sintering processing conditions in the elastic modulus, Vickers microhardness, density, and crystal phase formation in the GC. The best GC shows improved properties compared with its parent glass. This glass achieves a good densification degree with a two-step viscous flow sintering approach and the resulting GC shows as high bioactivity as that of the standard 45S5 Bioglass®. Furthermore, the GC elastic modulus (56 GPa) is relatively low, minimizing stress shielding. Therefore, we unveiled the glass sintering behavior with concurrent crystallization of this complex bioactive glass composition and developed a potential GC for bone regeneration.     

Increasing the photocatalytic and fungicide activities of Ag3PO4 microcrystals under visible-light irradiation

The present study reports for the first time the performance of silver phosphate (Ag₃PO₄) microcrystals as photocatalyst (degradation of Rodamine B-RhB) and antifungal agent (against Candida albicans–C. albicans) under visible-light irradiation (455 nm). Ag₃PO₄ microcrystals were synthesized by a simple co-precipitation (CP) method at room temperature. The structural and electronic properties of the as-synthetized Ag₃PO₄ have been investigated before and after 4 cycles of RhB degradation under visible light using X-ray diffraction (XRD), micro-Raman spectroscopy, UV–Vis spectrophotometer and field emission scanning electron microscopy (FE-SEM) images. The antifungal activity was analyzed in planktonic cells and 48h-biofilm of C. albicans by colony forming units (CFU) counting, confocal laser and FE-SE microscopies. Statistical analysis was carried out using SPSS software. Morphological and structural modifications of Ag₃PO₄ were observed upon recycling. After 4 recycles, the material maintained its photodegradation property; an eightfold increase in the efficiency of Ag₃PO₄ was observed in planktonic cells and a two fold increase in biofilm when irradiated under visible light. Thus, higher antifungal effectiveness against C. albicans was obtained when associated with visible-light irradiation.