Jacksondupont4480

Microbial recognition by pattern recognition receptors (PRRs) expressed on hematopoietic stem and progenitor cells (HSPCs) not only activates myelopoiesis but also programs the function of the monocytes and macrophages they produce. For instance, changes in HSPC programming modify the ability of macrophages derived from them to produce inflammatory cytokines. While HSPCs exposed to a TLR2 agonist give rise to tolerized macrophages (lower proinflammatory cytokine production), HSPCs treated with Dectin-1 ligands produce trained macrophages (higher proinflammatory cytokine production). However, nothing is known about the impact of HSPC exposure to microbes on the function of antigen presenting cells (APCs). In this study we evaluated whether treatment of murine bone marrow HSPCs with a TLR2 or Dectin-1 ligand impacts the antigen presenting capacity of APCs derived from them in vitro. Following activation with microbial ligands or Candida albicans yeasts, APCs derived from TLR2/Dectin-1-programed HSPCs exhibit altered expression of MHCII (signal 1), co-stimulatory molecules (CD40, CD80 and CD86; signal 2) and cytokines (TNF-α, IL-6, IL-12 p40 and IL-2; signal 3). Moreover, APCs derived from TLR2/Dectin-1-programed HSPCs prime enhanced Th1 and Th17 responses, which are important for antifungal defense, in CD4 T cell cocultures. Overall, these results demonstrate for the first time that microbial detection by bone marrow HSPCs can modulate the adaptive immune response by inducing the production of APCs with an altered phenotype.Plant-based drinks represent a heterogeneous class of beverages, made from several vegetal sources, with a market rapidly expanding around the world. These beverages are mainly drunk in the replacement of milk. Thus, aims of the present study were to (i) evaluate the nutritional declaration of 330 plant-based drinks currently available on the Italian market; (ii) compare their nutrition facts based on type, presence or not of organic certification and nutrition (NC) or health claims (HC), and of specific claims ("no added sugars" and "source of calcium"); (iii) compare their nutrition composition with cow's milk. A high variability in terms of nutrient profile among products was observed. Limited difference was found between products belonging to both organic and NC categories, while products carrying HC showed lower energy, carbohydrates, sugar, and higher protein contents than the related counterparts. Compared to cow's milk, plant-based drinks showed differences in terms of nutrient profile, mostly regarding the lower protein content (except for soy drinks). Overall, due to the variability, findings from the present survey show that plant-based drinks sold in Italy cannot be considered tout court as milk substitutes and support the importance of improving knowledge towards food labeling to make conscious food choices.Despite considerable efforts in prevention and therapy, breast cancer remains a major public health concern worldwide. Numerous studies using breast cancer cell lines have shown the antiproliferative and pro-apoptotic effects of docosahexaenoic acid (DHA). Some studies have also demonstrated the inhibitory effect of DHA on the migration and invasion of breast cancer cells, making DHA a potential anti-metastatic agent. Thus, DHA has shown its potential as a chemotherapeutic adjuvant. However, the molecular mechanisms triggering DHA effects remain unclear, and the aim of this study was to provide a transcriptomic basis for further cellular and molecular investigations. Therefore, MDA-MB-231 cells were treated with 100 µM DHA for 1`2 h or 24 h before RNA-seq analysis. The results show the great impact of DHA-treatment on the transcriptome, especially after 24 h of treatment. The impact of DHA is particularly visible in genes involved in the cholesterol biosynthesis pathway that is strongly downregulated, and the endoplasmic reticulum (ER)-stress response that is, conversely, upregulated. This ER-stress and unfolded protein response could explain the pro-apoptotic effect of DHA. The expression of genes related to migration and invasion (especially SERPINE1, PLAT, and MMP11) is also impacted by DHA. In conclusion, this transcriptomic analysis supports the antiproliferative, pro-apoptotic and anti-invasive effects of DHA, and provides new avenues for understanding its molecular mechanisms.Natural killer (NK) cells are major contributors to immunosurveillance and control of tumor development by inducing apoptosis of malignant cells. Among the main mechanisms involved in NK cell-mediated cytotoxicity, the death receptor pathway and the release of granules containing perforin/granzymes stand out due to their efficacy in eliminating tumor cells. However, accumulated evidence suggest a profound immune suppression in the context of tumor progression affecting effector cells, such as NK cells, leading to decreased cytotoxicity. This diminished capability, together with the development of resistance to apoptosis by cancer cells, favor the loss of immunogenicity and promote immunosuppression, thus partially inducing NK cell-mediated killing resistance. Altered expression patterns of pro- and anti-apoptotic proteins along with genetic background comprise the main mechanisms of resistance to NK cell-related apoptosis. Herein, we summarize the main effector cytotoxic mechanisms against tumor cells, as well as the major resistance strategies acquired by tumor cells that hamper the extrinsic and intrinsic apoptotic pathways related to NK cell-mediated killing.Eight partially grouted (PG-RM) concrete masonry walls were tested to study the influence of the strength and width of blocks, the wall aspect ratio, the horizontal and vertical reinforcement ratio, and the presence of edge elements (flanges). The results were analyzed in terms of the failure mode, damage progression, shear strength, lateral stiffness degradation, equivalent viscous damping ratio, and displacement ductility. Additionally, the performances of some existing shear expressions were analyzed by comparing the measured and predicted lateral load capacity of the tested walls. Based on the results, a slight increment in the lateral stiffness was achieved when employing stronger blocks, while the shear strength remained constant. read more Besides, increasing the width of concrete blocks did not have a significant effect on the shear strength nor in the initial tangential stiffness, but it generated a softer post-peak strength degradation. Increasing the wall aspect ratio reduced the brittleness of the response and the shear strength.