Growth inhibition of human colon carcinoma cells by combinations of anti-epidermal growth factor-related growth factor antisense oligonucleotides

To gain insight into the factors controlling the maintenance or loss of T cell self tolerance we produced beef insulin (BI)-transgenic BALB/c mice. Transgenic mice express BI under control of the human insulin promoter and secrete physiological amounts of beef insulin. Although these mice are tolerant to BI, as evidenced by the lack of insulin-specific IgG antibody production following intraperitoneal immunization, tolerance is not complete. Footpad immunization results in a weak antigen-specific T cell proliferative response, indicating the presence of self-reactive BI-specific T cell in the periphery. These T cells are functional in vivo, providing support for IgG1, IgG2a, and IgG2b BI-specific antibody production, but require higher higher concentrations of antigen than nontransgenic T cells (both in vivo and following recall responses in vitro) to become activated. In vitro, BI-specific T cell proliferation in BI-transgenic mice can be largely restored by addition of interleukin-2, indicating that a significant component of T cell tolerance is mediated by anergy. To characterize the autoreactive T cells that become activated when tolerance is broken, BI-specific T cell hybridomas were generated from transgenic mice and compared to a panel of hybridomas previously derived from nontransgenic BALB/c mice. The majority of BI-transgenic hybridomas recognized the immunodominant A1-14 beef insulin peptide but with lower avidity than BALB/c hybridomas. Consistent with this, none of the dominant T cell receptor rearrangements found in the BALB/c BI-specific T cell receptor repertoire were found in the transgenic hybridomas. These results indicate that, despite evidence for clonal inactivation of many BI-specific T cells in BI-transgenic mice, loss of tolerance results from activation of low-affinity antigen-specific T cells that appear to have escaped this process.     

Volatile species in halide-activated diffusion coating packs

An atmospheric pressure sampling mass spectrometer was used to identify the vapor species generated in a halide-activated, cementation pack. Pack powder mixtures containing a Cr-Al binary masteralloy powder, an NH₄Cl activator salt, and either ZrO₂ or Y₂O₃ (or neither) were analyzed at 1000°C. Both equilibrium calculations for the pack and mass spectrometer results indicated that volatile AlCl_x and CrCl_y species were generated by the pack powder mixture; in packs containing the reactive element oxide, volatile ZrCl_z and YCl_w species were formed by the conversion of their oxide sources.     

A review on ochratoxin A occurrence and effects of processing of cereal and cereal derived food products

Ochratoxin A (OTA) continues to grab global attention and concern for the hazard and impact that embody for both human and animals, based on its toxicity and occurrence. Despite OTA has been described in a myriad of foodstuffs, cereal and its derivatives remain the major contributors to OTA exposure. For that reason, a critical review on OTA occurrence reported by recent studies worldwide focusing on unprocessed and processed cereal foodstuffs is made in this work. Special attention is drawn to the major cereal derived products, namely flour, bread, breakfast cereals, baby/infant foods and the inherently involved technological food processing methods and its influence on the redistribution and chemical modification of OTA.     

Adiponectin and Leptin Exert Antagonizing Effects on HUVEC Tube Formation and Migration Modulating the Expression of CXCL1, VEGF,MMP-2 and MMP-9

Adiponectin and leptin are two abundant adipokines with different properties but both described such as potent factors regulating angiogenesis. AdipoRon is a small-molecule that, binding to AdipoRs receptors, acts as an adiponectin agonist. Here, we investigated the effects of AdipoRon and leptin on viability, migration and tube formation on a human in vitro model, the human umbilical vein endothelial cells (HUVEC) focusing on the expression of the main endothelial angiogenic factors: hypoxia-inducible factor 1-alpha (HIF-1α), C-X-C motif chemokine ligand 1 (CXCL1), vascular endothelial growth factor A (VEGF-A), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9). Treatments with VEGF-A were used as positive control. Our data revealed that, at 24 h treatment, proliferation of HUVEC endothelial cells was not influenced by AdipoRon or leptin administration; after 48 h longer exposure time, the viability was negatively influenced by AdipoRon while leptin treatment and the combination of AdipoRon+leptin produced no effects. In addition, AdipoRon induced a significant increase in complete tubular structures together with induction of cell migration while, on the contrary, leptin did not induce tube formation and inhibited cell migration; interestingly, the co-treatment with both AdipoRon and leptin determined a significant decrease of the tubular structures and cell migration indicating that leptin antagonizes AdipoRon effects. Finally, we found that the effects induced by AdipoRon administration are accompanied by an increase in the expression of CXCL1, VEGF-A, MMP-2 and MMP-9. In conclusion, our data sustain the active role of adiponectin and leptin in linking adipose tissue with the vascular endothelium encouraging the further deepening of the role of adipokines in new vessel’s formation, to candidate them as therapeutic targets.     

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).     

Toward a better understanding of multifunctional cement-based materials: The impact of graphite nanoplatelets (GNPs)

The impact of graphite nanoplatelets (GNPs) on the physical and mechanical properties of cementitious nanocomposites was investigated. A market-available premixed mortar was modified with 0.01% by weight of cement of commercial GNPs characterized by two distinctively different aspect ratios.The rheological behavior of the GNP-modified fresh admixtures was thoroughly evaluated. Hardened cementitious nanocomposites were investigated in terms of density, microstructure (Scanning Electron Microscopy, SEM and micro–Computed Tomography, μ-CT), mechanical properties (three-point bending and compression tests), and physical properties (electrochemical impedance spectroscopy, EIS and thermal conductivity measurements). At 28 days, all GNP-modified mortars showed about 12% increased density. Mortars reinforced with high aspect ratio GNPs exhibited the highest compressive and flexural strength: about 14% and 4% improvements compared to control sample, respectively. Conversely, low aspect ratio GNPs led to cementitious nanocomposites characterized by 36% decreased electrical resistivity combined with 60% increased thermal conductivity with respect to the control sample.     

Microbial communities and malt quality of durum wheat used in brewing

Durum wheat (Triticum durum Desf.) has potential as an adjunct in brewing given its agronomic, chemical and technological properties. The aim of this work were to identify the cultivable microflora and evaluate the technological quality of the durum wheat variety ‘Senatore Cappelli’ grown and used by a craft brewery in Sardinia, Italy. The isolated bacterial strains were mainly rhizospheric (Kocuria rizophila, Microbacterium aerolatum and Bacillus pumilus) and associated with the microbiota of wheat (Staphylococcus spp.). None have been reported previously as spoilage species in brewing. The dominant yeast genera were Cryptococcus spp. and Rhodotorula spp., followed by Saccharomyces cerevisiae. The dominant filamentous fungus genera were Alternaria and Rhizopus. Low levels of mycotoxigenic Fusarium spp., Aspergillus spp. and Penicillium spp. were isolated. However, the levels of deoxynivalenol, T2‐HT2, fumonisin, aflatoxin and ochratoxin detected in the malt and grain were below the thresholds defined by European law. Malt obtained from raw grain showed interesting technological properties, but required specific malting parameters different from those of common wheat and barley. These data suggest that the use of locally grown durum wheat in brewing can increase sustainability and reduce costs, while reinforcing the link with the terroir and promoting reduced mycotoxin levels. © 2019 The Institute of Brewing & Distilling     

Notch Signaling Regulation in Autoinflammatory Diseases

Notch pathway is a highly conserved intracellular signaling route that modulates a vast variety of cellular processes including proliferation, differentiation, migration, cell fate and death. Recently, the presence of a strict crosstalk between Notch signaling and inflammation has been described, although the precise molecular mechanisms underlying this interplay have not yet been fully unravelled. Disruptions in Notch cascade, due both to direct mutations and/or to an altered regulation in the core components of Notch signaling, might lead to hypo- or hyperactivation of Notch target genes and signaling molecules, ultimately contributing to the onset of autoinflammatory diseases. To date, alterations in Notch signaling have been reported as associated with three autoinflammatory disorders, therefore, suggesting a possible role of Notch in the pathogenesis of the following diseases: hidradenitis suppurativa (HS), Behçet disease (BD), and giant cell arteritis (GCA). In this review, we aim at better characterizing the interplay between Notch and autoinflammatory diseases, trying to identify the role of this signaling route in the context of these disorders.     

Improved Biocompatibility of Amino‐Functionalized Graphene Oxide in Caenorhabditis elegans

Graphene oxide (GO) holds high promise for diagnostic and therapeutic applications in nanomedicine but reportedly displays immunotoxicity, underlining the need for developing functionalized GO with improved biocompatibility. This study describes adverse effects of GO and amino‐functionalized GO (GONH₂) during Caenorhabditis elegans development and ageing upon acute or chronic exposure. Chronic GO treatment throughout the C. elegans development causes decreased fecundity and a reduction of animal size, while acute treatment does not lead to any measurable physiological decline. However, RNA‐Sequencing data reveal that acute GO exposure induces innate immune gene expression. The p38 MAP kinase, PMK‐1, which is a well‐established master regulator of innate immunity, protects C. elegans from chronic GO toxicity, as pmk‐1 mutants show reduced tissue‐functionality and facultative vivipary. In a direct comparison, GONH₂ exposure does not cause detrimental effects in the wild type or in pmk‐1 mutants, and the innate immune response is considerably less pronounced. This work establishes enhanced biocompatibility of amino‐functionalized GO in a whole‐organism, emphasizing its potential as a biomedical nanomaterial.