Quercetin Administration Suppresses the Cytokine Storm in Myeloid and Plasmacytoid Dendritic Cells

Dendritic cells (DCs) can be divided by lineage into myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs). They both are present in mucosal tissues and regulate the immune response by secreting chemokines and cytokines. Inflammatory bowel diseases (IBDs) are characterized by a leaky intestinal barrier and the consequent translocation of bacterial lipopolysaccharide (LPS) to the basolateral side. This results in DCs activation, but the response of pDCs is still poorly characterized. In the present study, we compared mDCs and pDCs responses to LPS administration. We present a broad panel of DCs secreted factors, including cytokines, chemokines, and growth factors. Our recent studies demonstrated the anti-inflammatory effects of quercetin administration, but to date, there is no evidence about quercetin’s effects on pDCs. The results of the present study demonstrate that pDCs can respond to LPS and that quercetin exposure modulates soluble factors release through the same molecular pathway used by mDCs (Slpi, Hmox1, and AP-1).     

Inhibition of the FGF/FGFR System Induces Apoptosis in Lung Cancer Cells via c-Myc Downregulation and Oxidative Stress

Lung cancer represents an extremely diffused neoplastic disorder with different histological/molecular features. Among the different lung tumors, non-small-cell lung cancer (NSCLC) is the most represented histotype, characterized by various molecular markers, including the expression/overexpression of the fibroblast growth factor receptor-1 (FGFR1). Thus, FGF/FGFR blockade by tyrosine kinase inhibitors (TKi) or FGF-ligand inhibitors may represent a promising therapeutic approach in lung cancers. In this study we demonstrate the potential therapeutic benefit of targeting the FGF/FGFR system in FGF-dependent lung tumor cells using FGF trapping (NSC12) or TKi (erdafitinib) approaches. The results show that inhibition of FGF/FGFR by NSC12 or erdafitinib induces apoptosis in FGF-dependent human squamous cell carcinoma NCI-H1581 and NCI-H520 cells. Induction of oxidative stress is the main mechanism responsible for the therapeutic/pro-apoptotic effect exerted by both NSC12 and erdafitinib, with apoptosis being abolished by antioxidant treatments. Finally, reduction of c-Myc protein levels appears to strictly determine the onset of oxidative stress and the therapeutic response to FGF/FGFR inhibition, indicating c-Myc as a key downstream effector of FGF/FGFR signaling in FGF-dependent lung cancers.     

Thermal behavior and structural study of ZrO2/poly(ε-caprolactone) hybrids synthesized via sol-gel route

The thermal behavior of pure ZrO₂ and four ZrO₂-based organic-inorganic hybrids (OIHs) containing increasing amount (6, 12, 24 and 50?wt%) of poly(ε-caprolactone) (PCL) (named Z, ZP6, ZP12, ZP24 and ZP50 respectively) has been studied by simultaneous thermogravimetry (TG) and differential scanning calorimetry (DSC). The FTIR analysis of the gas mixture evolved at defined temperatures from the samples submitted to the TG experiments identified the mechanism of each thermally activated process. The obtained results suggest that the inorganic matrix of the OIHs prepared by this method exerts a stabilizing effect on the polymer, in particular for poor-PCL hybrid materials. In fact, the different thermal behavior of the ZP50 sample suggests that the polymer is not entirely bonded to the -OH groups of the zirconia matrix due to their saturation. For this reason a part of PCL is not affected by the stabilizing effect of the matrix and is subjected to thermal degradation. Finally, by observing their thermal behavior it was possible to select the most suitable temperatures for thermal pretreatment: 400, 600 and 1000?°C. The structural analysis by X-ray diffraction (XRD) revealed that at 400?°C the materials are amorphous, while at 600?°C they are mostly tetragonal, and the content of the tetragonal phase decreases with increasing the amount of PCL in the OIHs. All the materials treated at 1000?°C are monoclinic, but their crystallinity decreases with increasing the PCL content.     

SKPFM investigations of intermetallic compounds of innovative Er‐ and Zr‐containing Al–Si–Mg alloys and their influence on corrosion localization in saline solution

The paper aims at characterizing the influence of intermetallic compounds on the corrosion localization of innovative Al–Si–Mg Er‐ and Zr‐containing casting alloys. Samples of the investigated materials were studied by means of optical and scanning electron microscope micrographs, immersion tests, and scanning Kelvin probe force microscope (SKPFM) analyses in the T6 temper. Combination of immersion tests and SKPFM analyses allowed to identify those classes of intermetallic compounds promoting localization of the corrosion process. It was found that intermetallic compounds richer in Fe were the most critical for corrosion localization; furthermore, additions of Er caused a marked decrease of the potential difference of intermetallic compounds with respect to the Al matrix and a consequent less intense microgalvanic coupling, which translates into slower corrosion kinetics. Further, Zr additions slightly increased the potential difference of intermetallic compounds with the Al matrix, promoting a faster corrosion process.     

Optimized production of a high-performance hybrid biomaterial: biomineralized spider silk for bone tissue engineering

Silks have been widely used as biomaterials due to their biocompatibility, biodegradability, and excellent mechanical properties. In the present work, native spider silk was used as organic template for controlled nucleation of hydroxyapatite (HA) nano-coating that can act as biomimetic interface. Different bio-inspired neutralization methods and process parameters were evaluated to optimize the silk functionalization. The morphology and chemical composition were investigated by scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analysis and mechanical properties were studied through tensile tests. Results showed that the optimized protocol enabled a controlled and homogeneous nucleation of apatite nano-crystals while maintaining silk mechanical performances after mineralization. This study reports the optimization of a simple and effective bio-inspired nucleation process for precise nucleation of HA onto spider silk templates, suitable to develop high-performance hybrid interfaces for bone tissue engineering. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48739.     

SGLT2is and Renal Protection: From Biological Mechanisms to Real-World Clinical Benefits

In recent years, following the publication of results from several RCTs, first on cardiovascular and more recently on renal outcomes, SGLT2is have become the standard of care to prevent diabetic kidney disease and slow its progression. This narrative review focuses on biological mechanisms, both renal and extrarenal, underlying kidney protection with SGLT2is. Furthermore, data from cardiovascular as well as renal outcome trials, mostly conducted in diabetic patients, are presented and discussed to provide an overview of current uses as well as the future therapeutic potential of these drugs.     

A2B Adenosine Receptors: When Outsiders May Become an Attractive Target to Treat Brain Ischemia or Demyelination

Adenosine is a signaling molecule, which, by activating its receptors, acts as an important player after cerebral ischemia. Here, we review data in the literature describing A_2BR-mediated effects in models of cerebral ischemia obtained in vivo by the occlusion of the middle cerebral artery (MCAo) or in vitro by oxygen-glucose deprivation (OGD) in hippocampal slices. Adenosine plays an apparently contradictory role in this receptor subtype depending on whether it is activated on neuro-glial cells or peripheral blood vessels and/or inflammatory cells after ischemia. Indeed, A_2BRs participate in the early glutamate-mediated excitotoxicity responsible for neuronal and synaptic loss in the CA1 hippocampus. On the contrary, later after ischemia, the same receptors have a protective role in tissue damage and functional impairments, reducing inflammatory cell infiltration and neuroinflammation by central and/or peripheral mechanisms. Of note, demyelination following brain ischemia, or autoimmune neuroinflammatory reactions, are also profoundly affected by A_2BRs since they are expressed by oligodendroglia where their activation inhibits cell maturation and expression of myelin-related proteins. In conclusion, data in the literature indicate the A_2BRs as putative therapeutic targets for the still unmet treatment of stroke or demyelinating diseases.