Fibroblastic niches prime T cell alloimmunity through Delta-like Notch ligands.

Alloimmune T cell responses induce graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (allo-BMT). Although Notch signaling mediated by Delta-like 1/4 (DLL1/4) Notch ligands has emerged as a major regulator of GVHD pathogenesis, little is known about the timing of essential Notch signals and the cellular source of Notch ligands after allo-BMT. Here, we have shown that critical DLL1/4-mediated Notch signals are delivered to donor T cells during a short 48-hour window after transplantation in a mouse allo-BMT model. Stromal, but not hematopoietic, cells were the essential source of Notch ligands during in vivo priming of alloreactive T cells. GVHD could be prevented by selective inactivation of Dll1 and Dll4 in subsets of fibroblastic stromal cells that were derived from chemokine Ccl19-expressing host cells, including fibroblastic reticular cells and follicular dendritic cells. However, neither T cell recruitment into secondary lymphoid organs nor initial T cell activation was affected by Dll1/4 loss. Thus, we have uncovered a pathogenic function for fibroblastic stromal cells in alloimmune reactivity that can be dissociated from their homeostatic functions. Our results reveal what we believe to be a previously unrecognized Notch-mediated immunopathogenic role for stromal cell niches in secondary lymphoid organs after allo-BMT and define a framework of early cellular and molecular interactions that regulate T cell alloimmunity

SEM-EDS characterization of natural products on corrosion inhibition of Al-Mg-Si alloy

The corrosion resistance of aluminum and its alloys is the subject of tremendous technological importance due to their increased industrial applications. The corrosion protections and the mechanism of corrosion inhibitions of natural products for an Al-Mg-Si alloy in seawater were investigated at room temperature. The surface morphology was studied by means of macro scale electrochemical techniques and localized microscopic methods, i.e., Scanning electron microscope (SEM) with associated elemental analysis by energy dispersive spectrometer (EDS). SEM examinations provided morphological characterization of the surface of Al-Mg-Si alloy sample before and after immersion in seawater; meanwhile surface analytical techniques by the EDS allowed us to investigate detail the chemical composition of aluminum oxide layers. The experiments were performed with Al-Mg-Si alloy, immersed in a 5 L beaker containing seawater with and without the natural products for 60 days at room temperature. The SEM results indicate that the natural products (natural honey, vanillin, and tapioca starch) absolutely inhibited the corrosion products on the specimen surfaces. They also protected the passive film from dissolution in seawater. The EDS spectrums were determined that carbonaceous, carbonyl, methoxy and hydroxyl groups as functional groups of natural products in inhibition mechanism

Expression of mitochondrial TSPO and FAM173B is associated with inflammation and symptoms in patients with painful knee osteoarthritis

Objectives To characterize the expression profiles of two nuclear-encoded mitochondrial genes previously associated with chronic pain, the translocator protein (TSPO) and family with sequence similarity 173B (FAM173B), in different knee compartments from patients with painful knee OA. Also, to examine their association with the joint expression of inflammatory cytokines/chemokines and clinical symptoms. Methods The study was performed on 40 knee OA patients and 19 postmortem (PM) controls from which we collected the knee tissues: articular cartilage (AC), synovial membrane (SM) and subchondral bone (SB). Quantitative real-time polymerase chain reaction was used to determine the relative mRNA levels of TSPO, FAM173B, and inflammatory mediators IL6, IL8, IL10, IL12, MCP1, CCL11 and CCL17. OA patients rated their pain intensity (visual analogue scale), severity of knee-related outcomes (KOOS) and pain sensitivity assessed by pressure algometry. Results The gene expression of TSPO in SM was elevated in OA patients compared with control subjects while there were no group differences in AC and SB. Expression of FAM173B was reduced in SM but elevated in SB in OA patients compared with controls. The expression of TSPO and FAM173B in SM and SB was associated with the expression of inflammatory substances, but not in AC. Synovial expression of TSPO correlated with lower pain intensity and FAM173B with increased pressure pain sensitivity in OA. Conclusion Our results suggest that altered expression of TSPO and FAM173B is associated with joint expression of inflammatory mediators and with clinical symptoms indicating the relevance for the pathophysiology of knee OA

Phyllostachys Pubescens: From Traditional to Functional Food: Phyllostachys pubescens as functional food

9siBamboo shoot (Phyllostachys pubescens) is mainly cultivated in China and Japan. It represents a reservoir of micro and macronutrients and contains a high amount of proteins, essential amino acids, phenolic acids, sterols, and fibers. Thank to these compounds, several beneficial health effects have been attributed to the bamboo shoot. This review is aimed at discussing a collection of research papers on Bamboo shoot in pharmaceutical and food fields. A particular focus is addressed to the chemical profile, the different biological activities, the different uses, the traditional recipes, the methods of conservation and the treatments of the shoot. To the best of our knowledge, this is the first example of a comprehensive review that is focused exclusively on the applications of the shoot of bamboo Phyllostachys pubescens in different fields.nonenoneCurci F.; Cavalluzzi M.M.; Milani G.; Clodoveo M.L.; Radojcic Redovnikovic I.; Cellamare S.; Franchini C.; Mandracchia D.; Corbo F.Curci, F.; Cavalluzzi, M. M.; Milani, G.; Clodoveo, M. L.; Radojcic Redovnikovic, I.; Cellamare, S.; Franchini, C.; Mandracchia, D.; Corbo, F

Signatures of immune dysfunction predict outcomes and define checkpoint blockade-unresponsive microenvironments in acute myeloid leukemia

Background and methods: The functional and transcriptional features of immune effector senescence and their influence on therapeutic response were investigated in independent AML clinical cohorts comprising 1,896 patients treated with chemotherapy and/or immune checkpoint blockade (ICB). Results: We show that senescent-like bone marrow CD8+ T cells were impaired in killing autologous AML blasts, and that their proportion negatively correlated with overall survival (OS). We defined new immune effector dysfunction (IED) signatures using two gene expression profiling platforms and report that IED scores correlated with adverse-risk molecular lesions, stemness, and poor outcomes as a potentially more powerful predictor of OS than 2017-ELN risk or leukemia stem cell (LSC17) scores. IED expression signatures also identified an ICB-unresponsive tumor microenvironment and predicted significantly worse OS. Conclusion: The newly described IED scores provided improved AML risk stratification and could facilitate the delivery of personalized immunotherapies to patients who are most likely to benefit