Synthesis and Biological Evaluation of Tripartin,a Putative KDM4 Natural Product Inhibitor,and 1‐Dichloromethylinden‐1‐ol Analogues

The natural product tripartin has been reported to inhibit the N‐methyl‐lysine histone demethylase KDM4A. A synthesis of tripartin starting from 3,5‐dimethoxyphenylacrylic acid was developed, and the enantiomers were separated by chiral HPLC. We observed that both tripartin enantiomers manifested an apparent increase in H3K9me3 levels when dosed in cells, as measured by western blot analysis. Thus, there is no enantiomeric discrimination toward this natural product in terms of its effects on cellular histone methylation status. Interestingly, tripartin did not inhibit isolated KDM4A–E under our assay conditions (IC₅₀>100 μm ). Tripartin analogues with a dichloromethylcarbinol group derived from the indanone scaffold were synthesized and found to be inactive against isolated recombinant KDM4 enzymes and in cell‐based assays. Although the precise cellular mode of action of tripartin is unclear, our evidence suggests that it may affect histone methylation status via a mechanism other than direct inhibition of the KDM4 histone demethylases.     

Supported Gold Nanoparticles for Furfural Valorization in the Future Bio-based Industry

Gold nanoparticles prepared by sol immobilization using PVA as protecting agent were supported over different oxides (CeO₂, ZrO₂ and TiO₂). The activity of the gold catalysts was tested in the oxidative esterification of furfural by an efficient and sustainable process. The samples supported on ceria and zirconia (AuCe and AuZr) have shown complete conversion and selectivity under mild reaction conditions. The catalytic performances are better than those obtained with the reference commercial AuTiWGC. The DR UV–Vis spectroscopic results indicate that gold nanoparticles that give rise to similar plasmonic band, as in the case of AuCe and AuZr, are very active and highly selective. The extent of crystallinity of the gold particles seems to have no influence on the activity of the sol immobilized catalysts. The null selectivity of the catalyst supported on titania is probably due to the presence of residual sulphate groups. The effect of the oxygen pressure on the furfural conversion is almost negligible for all the samples and, despite of the oxygen pressure lowering, it is possible to obtain always high conversion and selectivity. The selectivity of the process is unaffected by using air instead of oxygen, even at very low pressures. On the contrary, the presence of PVA seems to influence the conversion when working in air at low pressures, due to a dilution effect of the oxidant atmosphere. This is confirmed by the results obtained for a sample synthesized by deposition precipitation of gold on zirconia, where the high metal dispersion and the absence of the protecting agent allowed to reach high conversion even in low air pressure.     

Enhanced models for privacy and utility in continuous-time diffusion networks

International Journal of Information Security - Controlling the propagation of information in social networks is a problem of growing importance. On one hand, users wish to freely communicate and...     

Oncolytic Virotherapy and Microenvironment in Multiple Myeloma

Multiple myeloma (MM) is a hematologic malignancy characterized by the accumulation of bone marrow (BM) clonal plasma cells, which are strictly dependent on the microenvironment. Despite the improvement of MM survival with the use of new drugs, MM patients still relapse and become always refractory to the treatment. The development of new therapeutic strategies targeting both tumor and microenvironment cells are necessary. Oncolytic virotherapy represent a promising approach in cancer treatment due to tumor-specific oncolysis and activation of the immune system. Different types of human viruses were checked in preclinical MM models, and the use of several viruses are currently investigated in clinical trials in MM patients. More recently, the use of alternative non-human viruses has been also highlighted in preclinical studies. This strategy could avoid the antiviral immune response of the patients against human viruses due to vaccination or natural infections, which could invalid the efficiency of virotherapy approach. In this review, we explored the effects of the main oncolytic viruses, which act through both direct and indirect mechanisms targeting myeloma and microenvironment cells inducing an anti-MM response. The efficacy of the oncolytic virus-therapy in combination with other anti-MM drugs targeting the microenvironment has been also discussed.     

A First Phenotypic and Functional Characterization of Placental Extracellular Vesicles from Women with Multiple Sclerosis

Pregnancy is a unique situation of physiological immunomodulation, as well as a strong Multiple Sclerosis (MS) disease modulator whose mechanisms are still unclear. Both maternal (decidua) and fetal (trophoblast) placental cells secrete extracellular vesicles (EVs), which are known to mediate cellular communication and modulate the maternal immune response. Their contribution to the MS disease course during pregnancy, however, is unexplored. Here, we provide a first phenotypic and functional characterization of EVs isolated from cultures of term placenta samples of women with MS, differentiating between decidua and trophoblast. In particular, we analyzed the expression profile of 37 surface proteins and tested the functional role of placental EVs on mono-cultures of CD14⁺ monocytes and co-cultures of CD4⁺ T and regulatory T (Treg) cells. Results indicated that placental EVs are enriched for surface markers typical of stem/progenitor cells, and that conditioning with EVs from samples of women with MS is associated to a moderate decrease in the expression of proinflammatory cytokines by activated monocytes and in the proliferation rate of activated T cells co-cultured with Tregs. Overall, our findings suggest an immunomodulatory potential of placental EVs from women with MS and set the stage for a promising research field aiming at elucidating their role in MS remission.     

Long-Term Shaping of Corticostriatal Synaptic Activity by Acute Fasting

Food restriction is a robust nongenic, nonsurgical and nonpharmacologic intervention known to improve health and extend lifespan in various species. Food is considered the most essential and frequently consumed natural reward, and current observations have demonstrated homeostatic responses and neuroadaptations to sustained intermittent or chronic deprivation. Results obtained to date indicate that food deprivation affects glutamatergic synapses, favoring the insertion of GluA2-lacking α-Ammino-3-idrossi-5-Metil-4-idrossazol-Propionic Acid receptors (AMPARs) in postsynaptic membranes. Despite an increasing number of studies pointing towards specific changes in response to dietary restrictions in brain regions, such as the nucleus accumbens and hippocampus, none have investigated the long-term effects of such practice in the dorsal striatum. This basal ganglia nucleus is involved in habit formation and in eating behavior, especially that based on dopaminergic control of motivation for food in both humans and animals. Here, we explored whether we could retrieve long-term signs of changes in AMPARs subunit composition in dorsal striatal neurons of mice acutely deprived for 12 hours/day for two consecutive days by analyzing glutamatergic neurotransmission and the principal forms of dopamine and glutamate-dependent synaptic plasticity. Overall, our data show that a moderate food deprivation in experimental animals is a salient event mirrored by a series of neuroadaptations and suggest that dietary restriction may be determinant in shaping striatal synaptic plasticity in the physiological state.     

Metabolomic profiling of food matrices: Preliminary identification of potential markers of microbial contamination

The research aimed to generate an early warning system highlighting in real-time bacterial contamination of meat matrices and providing information which could support companies in accepting or rejecting batches. Current microorganisms’ detection methods rely on techniques (plate counting), which provide retrospective values for microbial contamination. The purpose of this research was to evaluate the ability of the headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC/MS) methodologies to detect volatile organic carbons (VOCs), which may be associated to a peculiar microbiological contamination of food. The disposal of fast headspace gas chromatography-mass spectrometry (HS-SPME-GC/MS) able to accurately and rapidly (30 min per sample) detect pathogens in raw meat could replace the traditional and time-consuming (3 to 4 days) standardized microbiological analysis required by regulations. Experiments focused on qualitative and quantitative evaluations of VOCs produced by Salmonella Typhimurium, Campylobacter jejuni, and Staphylococcus aureus in different types of raw meat (beef, pork, chicken). HS-SPME-GC/MS allowed to use smaller sample volumes compared to traditional methods with no sample processing and the potentiality for its application on various food matrices for the detection of a wide variety of pathogens. Data analysis showed the identification of unique VOCs’ profiles being possible markers of meat contamination due to their association to specific pathogens. The identification of VOCs markers in association to selected bacterial pathogens and their metabolites could support the rapid determination of specific meat samples contamination. Further research is required to outline-specific metabolic profiles for each microorganism responsible of meat contamination and prevent false positives.     

Analytical screening of marine algal toxins for seafood safety assessment in a protected Mediterranean shallow water environment

Microalgal species growing in marine and aquaculture environments can be responsible for harmful events because of their ability to produce potent natural toxins that can accumulate in edible mollusc species. Their consumption can cause severe illness and even be lethal. The European Union provides comprehensive regulations covering various general food safety aspects to manage the risk of contamination in shellfish farms. Many analytical methods have been proposed to evaluate algal toxins presence in the environment and in food products, for conducting surveillance studies of the main molluscs production sites and, where necessary, immediate monitoring of possible contamination of shellfish. In this work, a one-year analytical surveillance study was carried out to verify the possible presence of algal biotoxins in molluscs from a Mediterranean breeding area. Water and molluscs were sampled from a district of the North-East coast of Sicily, consisting of a unique brackish ecosystem of two lakes connected to each other and to the sea by narrow canals. Water samples were collected to investigate phytoplankton i by microscope analysis to assess the presence of potentially toxin-producing species, such as Pseudo-nitzschia spp, Alexandrium spp and Gonyaulax spinifera, although the presence of toxic phytoplankton has never reached alert levels. Mussels and clams samples were submitted to analysis of paralytic shellfish poisoning toxins, amnesic shellfish poisoning toxins and lipophilic toxins by liquid chromatography-based methods Only a few yessotoxins were detected, having concentrations always below the regulation limits. An existing liquid chromatography-tandem mass spectrometry-based multiresidue method for lipophilic biotoxins was adopted and extended to cover emerging biotoxins such as cyclic imines. The performance of the analytical method for Gymnodimine A and Spirolide 13-desMeC was assessed, obtaining respective quantitation limits of 20 and 10 µg kg^?1, a precision always lower than 13% and trueness in the 81–120% range. Method applicability was confirmed using certified materials and a naturally contaminated sample.