Modification of Amorphous Mesoporous Zirconia Nanoparticles with Bisphosphonic Acids: A Straightforward Approach for Tailoring the Surface Properties of the Nanoparticles

The use of readily prepared bisphosphonic acids obtained in few steps through a thio-Michael addition of commercially available thiols on tetraethyl vinylidenebisphosphonate enables the straightforward surface modification of amorphous mesoporous zirconia nanoparticles. Simple stirring of the zirconia nanoparticles in a buffered aqueous solution of the proper bisphosphonic acid leads to the surface functionalization of the nanoparticles with different kinds of functional groups, charge and hydrophobic properties. Formation of both chemisorbed and physisorbed layers of the bisphosphonic acid take place, observing after extensive washing a grafting density of 1.1 molecules/nm2 with negligible release in neutral or acidic pH conditions, demonstrating stronger loading compared to monophosphonate derivatives. The modified nanoparticles were characterized by IR, XPS, ζ-potential analysis to investigate the loading of the bisphosphonic acid, FE-SEM to investigate the size and morphologies of the nanoparticles and 31P and 1H MAS NMR to investigate the coordination motif of the phosphonate units on the surface. All these analytical techniques demonstrated the strong affinity of the bisphosphonic moiety for the Zr(IV) metal centers. The functionalization with bisphosphonic acids represents a straightforward covalent approach for tailoring the superficial properties of zirconia nanoparticles, much straightforward compared the classic use of trisalkoxysilane or trichlorosilane reagents typically employed for the functionalization of silica and metal oxide nanoparticles. Extension of the use of bisphosphonates to other metal oxide nanoparticles is advisable

The lactonase BxdA mediates metabolic specialisation of maize root bacteria to benzoxazinoids.

Root exudates contain specialised metabolites that shape the plant's root microbiome. How host-specific microbes cope with these bioactive compounds, and how this ability affects root microbiomes, remains largely unknown. We investigated how maize root bacteria metabolise benzoxazinoids, the main specialised metabolites of maize. Diverse and abundant bacteria metabolised the major compound in the maize rhizosphere MBOA (6-methoxybenzoxazolin-2(3H)-one) and formed AMPO (2-amino-7-methoxy-phenoxazin-3-one). AMPO forming bacteria were enriched in the rhizosphere of benzoxazinoid-producing maize and could use MBOA as carbon source. We identified a gene cluster associated with AMPO formation in microbacteria. The first gene in this cluster, bxdA encodes a lactonase that converts MBOA to AMPO in vitro. A deletion mutant of the homologous bxdA genes in the genus Sphingobium, did not form AMPO nor was it able to use MBOA as a carbon source. BxdA was identified in different genera of maize root bacteria. Here we show that plant-specialised metabolites select for metabolisation-competent root bacteria. BxdA represents a benzoxazinoid metabolisation gene whose carriers successfully colonize the maize rhizosphere and thereby shape the plant's chemical environmental footprint

Epigenetics Offer New Horizons for Colorectal Cancer Prevention

In recent years, colorectal cancer (CRC) incidence has been increasing to become a major cause of morbidity and mortality worldwide from cancers, with high rates in westernized societies and increasing rates in developing countries. Epigenetic modifications including changes in DNA methylation, histone modifications, and non-coding RNAs play a critical role in carcinogenesis. Epidemiological data suggest that, in comparison to other cancers, these alterations are particularly common within the gastrointestinal tract. To explain these observations, environmental factors and especially diet were suggested to both prevent and induce CRC. Epigenetic alterations are, in contrast to genetic modifications, potentially reversible, making the use of dietary agents a promising approach in CRC for the development of chemopreventive strategies targeting epigenetic mechanisms. This review focuses on CRC-related epigenetic alterations as a rationale for various levels of prevention strategies and their potential modulation by natural dietary compounds

Reutilization and stabilization of wastes by the production of glass foams

Glass foams are known to represent highly valuable products for thermal and acoustic insulation, often produced by employing wastes. Although the usage of recycled glass is widely reported for developing the glass matrix, little research has been due to the usage of wastes for the foaming reaction. In this work the cellular structure is achieved after oxidation of SiC-based wastes coming from the polishing of glass articles. The foamed recycled soda-lime glass incorporated the residues from oxidation and provided a reasonably good chemical stability. The addition of MnO2 to the starting mixtures of wastes led to a certain improvement of the oxidation of SiC, and a complex effect on the correlation between density and mechanical strength. For selected additions, a more homogeneous foaming was found to provide a stronger cellular structure

In vitro undetectable PT and Fibrinogen (and in vivo?)

A 81 aged woman came to E.R. of Trieste University Hospital with a traumatic head injury. Blood cells count, liver enzymes and other parameters were normal, but with a photometric clot detection method PT and PT-derived Fibrinogen were undetectable, Fibrinogen-Clauss gave different results (157 to 357 mg/dL) and aPTT-Ratio was normal (0.96). When the instrument detection performance was improved, PT was normal and PT-derived Fibrinogen detectable, but Fibrinogen-Clauss was still very unsteady (352/294/558 mg/dL). When a mixing test was performed with normal pool plasma, PT was corrected, PT-derived Fibrinogen was very low (80 mg/dL) and Fibrinogen-Clauss resulted 360 mg/dL. Fibrinogen-Antigen was 368 mg/dL by a nephelometric immunoassay. In another Lab with a different optical analyzer, PT and aPTT yielded the same results, Fibrinogen-Clauss was 557 mg/dL with 35 IU/ml Thrombin reagent (and a very steep clot formation curve), but 113 mg/dL with 15 IU/ml Thrombin reagent (and a normal curve). With an electromechanical clot detection method, PT-INR and aPTT-Ratio were normal (0.88 and 0.96 respectively), Fibrinogen-Clauss was normal (400 mg/dL) but unsteady. However in a few days our patient healed up perfectly; she declared that her sister had the same performance when she was referred to another Hospital for a check-up, nonetheless they never had any severe bleeding in their life. Samples from our patient\u2019s son and daughter were taken and resulted completely normal for coagulation tests. We hypothetized: 1) a too fast Thrombin formation and/or Fibrinogen consumption, as shown by steep coagulation curves without a stable plateau; 2) an excessive thrombin formation, (in preliminary studies, however, G20210A mutation was absent and F1+2 were normal); 3) a dysfibrinogenemia, (to be studied). Further studies for Endogenous Thrombin Potential about thrombin ipothesis and for genetical pattern about fibrinogen molecule are needed to clarify this case

Grp94 acts as a mediator of curcumin-induced anti-oxidant defence in myogenic cells.

Curcumin is a non-toxic polyphenol with pleiotropic activities and limited bioavailability. We investigated whether a brief exposure to low doses of curcumin would induce in the myogenic C2C12 cell line an endoplasmic reticulum (ER) stress response and protect against oxidative stress. A 3-hr curcumin administration (5\u201310 \u3bcM) increased protein levels of the ER chaperone Grp94, without affecting those of Grp78, calreticulin and haeme-oxygenase-1 (HO-1). Exposure of cells to hydrogen peroxide 24 hrs after the curcumin treatment decreased caspase-12 activation, total protein oxidation and translocation of NF-\u3baB to the nucleus, compared with untreated cells. Grp94 overexpression, achieved by means of either stable or transient trasfection, induced comparable cytoprotective effects to hydrogen peroxide. The delayed cytoprotection induced by curcumin acted through Grp94, because the curcumin-induced increase in Grp94 expression was hampered by either stable or transient transfection with antisense cDNA; in these latter cells, the extent of total protein oxidation, as well as the translocation of NF-\u3baB to the nucleus, and the percentage of apoptotic cells were comparable to those observed in both curcumin-untreated wild-type and empty vector transfected cells. Defining the mechanism(s) by which Grp94 exerts its antioxidant defence, the determination of cytosolic calcium levels in C2C12 cells by fura-2 showed a significantly reduced amount of releasable calcium from intracellular stores, both in conditions of Grp94 overexpression and after curcumin pre-treatment. Therefore, a brief exposure to curcumin induces a delayed cytoprotection against oxidative stress in myogenic cells by increasing Grp94 protein level, which acts as a regulator of calcium homeostasis

Intravenous immunoglobulin in immune neutropenia.

6nonenoneVENTURA A.; FLOREAN P; PASCONE R; PERINI R; POCECCO M; LEPORE L.Ventura, Alessandro; Florean, P; Pascone, R; Perini, R; Pocecco, M; Lepore, L

A method for reproducible measurements of serum BDNF: comparison of the performance of six commercial assays

Brain-Derived Neurotrophic Factor (BDNF) has attracted increasing interest as potential biomarker to support the diagnosis or monitor the efficacy of therapies in brain disorders. Circulating BDNF can be measured in serum, plasma or whole blood. However, the use of BDNF as biomarker is limited by the poor reproducibility of results, likely due to the variety of methods used for sample collection and BDNF analysis. To overcome these limitations, using sera from 40 healthy adults, we compared the performance of five ELISA kits (Aviscera-Bioscience, Biosensis, Millipore-ChemiKineTM, Promega-Emax®, R&D-System-Quantikine;®) and one multiplexing assay (Millipore-Milliplex®). All kits showed 100% sample recovery and comparable range. However, they exhibited very different inter-assay variations from 5% to 20%. Inter-assay variations were higher than those declared by the manufacturers with only one exception which also had the best overall performance. Dot-blot analysis revealed that two kits selectively recognize mature BDNF, while the others reacted with both pro-BDNF and mature BDNF. In conclusion, we identified two assays to obtain reliable measurements of human serum BDNF, suitable for future clinical applications