University of Florence

About: University of Florence is a education organization based out in Florence, Toscana, Italy. It is known for research contribution in the topics: Population & Carbonic anhydrase. The organization has 27292 authors who have published 79599 publications receiving 2341684 citations. The organization is also known as: Università degli studi di Firenze & Universita degli studi di Firenze.

Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis

Abstract: Background We wondered whether short-term coseasonal sublingual immunotherapy (SLIT) can reduce the development of asthma in children with hay fever in an open randomized study. Objective We sought to determine whether SLIT is as effective as subcutaneous immunotherapy in reducing hay fever symptoms and the development of asthma in children with hay fever. Methods One hundred thirteen children aged 5 to 14 years (mean age, 7.7 years) with hay fever limited to grass pollen and no other clinically important allergies were randomized in an open study involving 6 Italian pediatric allergy centers to receive specific SLIT for 3 years or standard symptomatic therapy. All of the subjects had hay fever symptoms, but at the time of study entry, none reported seasonal asthma with more than 3 episodes per season. Symptomatic treatment was limited to cetirizine, loratadine, nasal budesonide, and salbutamol on demand. The hay fever and asthma symptoms were quantified clinically. Results The actively treated children used less medication in the second and third years of therapy, and their symptom scores tended to be lower. From the second year of immunotherapy, subjective evaluation of overall allergy symptoms was favorable in the actively treated children. Development of asthma after 3 years was 3.8 times more frequent (95% confidence limits, 1.5-10.0) in the control subjects. Conclusions Three years of coseasonal SLIT improves seasonal allergic rhinitis symptoms and reduces the development of seasonal asthma in children with hay fever.

Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression

Abstract: Several recent papers have now provided compelling experimental evidence that the progression of tumours towards a malignant phenotype does not depend exclusively on the cell-autonomous properties of cancer cells themselves but is also deeply influenced by tumour stroma reactivity, thereby undergoing a strict environmental control. Tumour microenvironmental elements include structural components such as the extracellular matrix or hypoxia as well as stromal cells, either resident cells or recruited from circulating precursors, as macrophages and other inflammatory cells, endothelial cells and cancer-associated fibroblasts (CAFs). All these elements synergistically play a specific role in cancer progression. This review summarizes our current knowledge on the role of CAFs in tumour progression, with a particular focus on the biunivocal interplay between CAFs and cancer cells leading to the activation of the epithelial–mesenchymal transition programme and the achievement of stem cell traits, as well as to the metabolic reprogramming of both stromal and cancer cells. Recent advances on the role of CAFs in the preparation of metastatic niche, as well as the controversial origin of CAFs, are discussed in light of the new emerging therapeutic implications of targeting CAFs.

Toll-Like Receptors 3 and 4 Are Expressed by Human Bone Marrow-Derived Mesenchymal Stem Cells and Can Inhibit Their T-Cell Modulatory Activity by Impairing Notch Signaling

Abstract: Bone marrow (BM)-derived mesenchymal stem cells (MSCs) are multipotent, nonhemopoietic progenitors that also possess regulatory activity on immune effector cells through different mechanisms. We demonstrate that human BM-derived MSCs expressed high levels of Toll-like receptors (TLRs) 3 and 4, which are both functional, as shown by the ability of their ligands to induce nuclear factor kappaB (NF-kappaB) activity, as well as the production of interleukin (IL)-6, IL-8, and CXCL10. Of note, ligation of TLR3 and TLR4 on MSCs also inhibited the ability of these cells to suppress the proliferation of T cells, without influencing their immunophenotype or differentiation potential. The TLR triggering effects appeared to be related to the impairment of MSC signaling to Notch receptors in T cells. Indeed, MSCs expressed the Notch ligand Jagged-1, and TLR3 or TLR4 ligation resulted in its strong downregulation. Moreover, anti-Jagged-1 neutralizing antibody and N[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of Notch signaling, hampered the suppressive activity of MSCs on T-cell proliferation. These data suggest that TLR3 and TLR4 expression on MSCs may provide an effective mechanism to block the immunosuppressive activity of MSCs and therefore to restore an efficient T-cell response in the course of dangerous infections, such as those sustained by double-stranded RNA viruses or Gram-negative bacteria, respectively.