Inhibition of endothelial cell functions and of angiogenesis by the metastasis inhibitor NAMI-A

NAMI-A is a ruthenium-based compound with selective anti-metastasis activity in experimental models of solid tumours. We studied whether this activity was dependent on anti-angiogenic ability of NAMI-A. We thus investigated its in vitro effects on endothelial cell functions necessary for angiogenesis to develop, as well as its in vivo effects in the chick embryo chorioallantoic membrane model. Endothelial cell proliferation, chemotaxis, and secretion of the matrix-degrading enzyme metalloproteinase-2 were inhibited by NAMI-A in a dose-dependent manner, and without morphologic signs of cell apoptosis or necrosis. Lastly, NAMI-A displayed a dose-dependent in vivo anti-angiogenic activity in the chorioallantoic membrane model. These data suggest that the anti-angiogenic activity of NAMI-A can contribute to its anti-metastatic efficacy in mice bearing malignant solid tumours

catena-Poly[zinc-tris­(μ-dimethyl­carbamato-κ2 O:O′)-zinc-μ-(2-phenyl­benzimidazolido-κ2 N:N′]

The crystal structure of the title compound, [Zn2(C13H9N2)(C3H6NO2)3]n, displays a long chiral chain. This is composed of zinc-dimer clusters capped by dimethyl­carbamate ligands, which lie on crystallographic twofold rotation axes and are polymerically linked in one dimension by 2-phenyl­benzimidadole (2–PBImi) organic ligands. The two Zn2+ ions defining the dimetal cluster are crystallographically independent, but display very similar coordination modes and tetra­hedral geometry. As such, each Zn2+ ion is coordinated on one side by the N-donor imidazole linker, while the other three available coordination sites are fully occupied by the O atoms from the capping dimethyl­carbamates. The chirality of the chain extends along the c axis, generating a rather long 52.470 (11) Å cell axis. Inter­estingly, the chiral material crystallizes from completely achiral precursors. A twofold axis and 31 screw axis serve to generate the long asymmetric unit

Lysozyme-induced transcriptional regulation of tnf-\u3b1 pathway genes in cells of the monocyte lineage

Lysozyme is one of the most important anti-bacterial effectors in the innate immune system of animals. Besides its direct antibacterial enzymatic activity, lysozyme displays other biological properties, pointing toward a significant anti-inflammatory effect, many aspects of which are still elusive. Here we investigate the perturbation of gene expression profiles induced by lysozyme in a monocyte cell line in vitro considering a perspective as broad as the whole transcriptome profiling. The results of the RNA-seq experiment show that lysozyme induces transcriptional modulation of the TNF-\u3b1/IL-1\u3b2 pathway genes in U937 monocytes. The analysis of transcriptomic profiles with IPA\uae identified a simple but robust molecular network of genes, in which the regulation trends are fully consistent with the anti-inflammatory activity of lysozyme. This study provides the first evidence in support of the anti-inflammatory action of lysozyme on the basis of transcriptomic regulation data resulting from the broad perspective of a whole-transcriptome profiling. Such important effects can be achieved with the supplementation of relatively low concentrations of lysozyme, for a short time of exposure. These new insights allow the potential of lysozyme in pharmacological applications to be better exploited

Model-based inference from microvascular measurements: Combining experimental measurements and model predictions using a Bayesian probabilistic approach

Objective: In vivo imaging of the microcirculation and network-oriented modeling have emerged as powerful means of studying microvascular function and understanding its physiological significance. Network-oriented modeling may provide the means of summarizing vast amounts of data produced by high-throughput imaging techniques in terms of key, physiological indices. To estimate such indices with sufficient certainty, however, network-oriented analysis must be robust to the inevitable presence of uncertainty due to measurement errors as well as model errors. Methods: We propose the Bayesian probabilistic data analysis framework as a means of integrating experimental measurements and network model simulations into a combined and statistically coherent analysis. The framework naturally handles noisy measurements and provides posterior distributions of model parameters as well as physiological indices associated with uncertainty. Results: We applied the analysis framework to experimental data from three rat mesentery networks and one mouse brain cortex network. We inferred distributions for more than 500 unknown pressure and hematocrit boundary conditions. Model predictions were consistent with previous analyses, and remained robust when measurements were omitted from model calibration. Conclusion: Our Bayesian probabilistic approach may be suitable for optimizing data acquisition and for analyzing and reporting large data sets acquired as part of microvascular imaging studies

A Unified Theoretical Description of the Thermodynamical Properties of Spin Crossover with Magnetic Interactions

After the discovery of the phenomena of light-induced excited spin state trapping (LIESST), the functional properties of metal complexes have been studied intensively. Among them, cooperative phenomena involving low spin-high spin (spin-crossover) transition and magnetic ordering have attracted interests, and it has become necessary to formulate a unified description of both phenomena. In this work, we propose a model in which they can be treated simultaneously by extending the Wajnflasz-Pick model including a magnetic interaction. We found that this new model is equivalent to Blume-Emery-Griffiths (BEG) Hamiltonian with degenerate levels. This model provides a unified description of the thermodynamic properties associated with various types of systems, such as spin-crossover (SC) solids and Prussian blue analogues (PBA). Here, the high spin fraction and the magnetization are the order parameters describing the cooperative phenomena of the model. We present several typical temperature dependences of the order parameters and we determine the phase diagram of the system using the mean-field theory and Monte Carlo simulations. We found that the magnetic interaction drives the SC transition leading to re-entrant magnetic and first-order SC transitions.Comment: 30pages, 11figure

Intermittent docetaxel chemotherapy as first-line treatment for metastatic castration-resistant prostate cancer patients

Aims: The intermittent administration of chemotherapy is a means of preserving patients' quality of life (QL). The aim of this study was to verify whether the intermittent administration of docetaxel (DOC) improves the patients' QL. Patients & methods: All patients received DOC 70 mg/m every 3 weeks for eight cycles. The patients were randomized to receive DOC continuously or with a fixed 3-month interval after the first four DOC courses. Results: The study involved 148 patients. There was no difference in QL between the groups receiving intermittent or continuous treatment. Intermittence had no detrimental effects on disease control. Conclusion: Although feasible and not detrimental, our results showed that true intermittent chemotherapy in metastatic castration-resistant prostate cancer patients failed to improve the patients' QL

Effects of non‐steroidal anti‐inflammatory drugs and other eicosanoid pathway modifiers on antiviral and allergic responses. EAACI task force on eicosanoids consensus report in times of COVID‐19

Non‐steroidal anti‐inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti‐inflammatory, antipyretic, and analgesic effects are applied against symptoms of respiratory infections, including SARS‐CoV‐2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID‐19 also revealed the gaps in our understanding of their mechanism of action, selectivity, and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs‐exacerbated respiratory disease (NERD). In this context, the consensus report summarizes currently available knowledge, novel discoveries, and controversies regarding the use of NSAIDs in COVID‐19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID‐19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarize the major knowledge gaps and unmet needs in current eicosanoid research

The INFN-grid testbed

The Italian INFN-Grid Project is committed to set-up, run and manage an unprecedented nation-wide Grid infrastructure. The implementation and use of this INFN-Grid Testbed is presented and discussed. Particular care and attention are devoted to those activities, relevant for the management of the Testbed, carried out by the INFN within international Grid Projects