Aerobic Cytotoxicity of Aromatic N-Oxides: The Role of NAD(P)H:Quinone Oxidoreductase (NQO1)

Derivatives of tirapazamine and other heteroaromatic N-oxides (ArN→O) exhibit tumoricidal, antibacterial, and antiprotozoal activities, which are typically attributed to bioreductive activation and free radical generation. In this work, we aimed to clarify the role of NAD(P)H:quinone oxidoreductase (NQO1) in ArN→O aerobic cytotoxicity. We synthesized 9 representatives of ArN→O with uncharacterized redox properties and examined their single-electron reduction by rat NADPH:cytochrome P-450 reductase (P-450R) and Plasmodium falciparum ferredoxin:NADP⁺ oxidoreductase (PfFNR), and by rat NQO1. NQO1 catalyzed both redox cycling and the formation of stable reduction products of ArN→O. The reactivity of ArN→O in NQO1-catalyzed reactions did not correlate with the geometric average of their activity towards P-450R- and PfFNR, which was taken for the parameter of their redox cycling efficacy. The cytotoxicity of compounds in murine hepatoma MH22a cells was decreased by antioxidants and the inhibitor of NQO1, dicoumarol. The multiparameter regression analysis of the data of this and a previous study (DOI: 10.3390/ijms20184602) shows that the cytotoxicity of ArN→O (n = 18) in MH22a and human colon carcinoma HCT-116 cells increases with the geometric average of their reactivity towards P-450R and PfFNR, and with their reactivity towards NQO1. These data demonstrate that NQO1 is a potentially important target of action of heteroaromatic N-oxides.     

Rapid MALDI-TOF-MS Detection of Anthocyanins in Wine and Grape Using Different Matrices

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) as a new valuable technique has been used for qualitative screening of anthocyanins in wine and grape samples from Vranec and Merlot variety. For that purpose, different MALDI matrices have been tested, such as α-cyano-4-hydroxycinnamic acid, sinapic acid, 2,5-dihydroxybenzoic acid (2,5-DHB), and C₇₀ fullerene. It was observed that 2,5-DHB was superior with respect to all the matrices used in the study. Furthermore, fullerene was, for the first time, tested and used as a possible matrix for MALDI-TOF-MS identification of anthocyanins in wine and grape samples. The results obtained showed identification of aglycone forms of anthocyanins only, since the higher laser energy applied for ionization of the fullerene molecules led to great deal of fragmentation of the sugar moiety from glucosides, acetylglucoside, and p-coumaroylglucoside groups from the corresponding anthocyanin molecules. Additionally, liquid chromatography/electrospray ionization mass spectrometry has also been applied for anthocyanin characterization.     

A 5-component mathematical model for salt-induced hypertension in Dahl-S and Dahl-R rats

Salt-induced hypertension has been demonstrated in a variety of species including rats, monkeys, chimpanzees and humans. Until recently, the multiple phases of this blood pressure increase due to high salt intake had not been closely studied. This work builds upon a recent study, which developed a grey-box multi-component model of salt-induced hypertension in the Dahl-S rat. The previous 3-component model has been extended here to include additional model dynamics to improve the model fit and add new important elements to the model response. The model was optimised using numerical techniques with experimental data from 4 different protocols with Dahl-S, Dahl-R and FF2 hybrid rats. Results show a marked improvement over the previous model and confirm the merit of the 5-component model structure. A comparison between the model dynamics for different rat strains has also been included.     

YB-1 Is Altered in Pregnancy-Associated Disorders and Affects Trophoblast in Vitro Properties via Alternation of Multiple Molecular Traits

Cold shock Y-box binding protein-1 (YB-1) coordinates several molecular processes between the nucleus and the cytoplasm and plays a crucial role in cell function. Moreover, it is involved in cancer progression, invasion, and metastasis. As trophoblast cells share similar characteristics with cancer cells, we hypothesized that YB-1 might also be necessary for trophoblast functionality. In samples of patients with intrauterine growth restriction, YB-1 mRNA levels were decreased, while they were increased in preeclampsia and unchanged in spontaneous abortions when compared to normal pregnant controls. Studies with overexpression and downregulation of YB-1 were performed to assess the key trophoblast processes in two trophoblast cell lines HTR8/SVneo and JEG3. Overexpression of YB-1 or exposure of trophoblast cells to recombinant YB-1 caused enhanced proliferation, while knockdown of YB-1 lead to proliferative disadvantage in JEG3 or HTR8/SVneo cells. The invasion and migration properties were affected at different degrees among the trophoblast cell lines. Trophoblast expression of genes mediating migration, invasion, apoptosis, and inflammation was altered upon YB-1 downregulation. Moreover, IL-6 secretion was excessively increased in HTR8/SVneo. Ultimately, YB-1 directly binds to NF-κB enhancer mark in HTR8/SVneo cells. Our data show that YB-1 protein is important for trophoblast cell functioning and, when downregulated, leads to trophoblast disadvantage that at least in part is mediated by NF-κB.     

New urethane oligodimethacrylates with quaternary alkylammonium for formulating dental composites

The aim of this study was to prepare urethane dimethacrylates containing quaternary alkyl (C16, C12) ammonium and polyethylene glycol short sequences (Mn, 400 g/mol) and to investigate their behaviour in some experimental formulations in order to evaluate their potential applicability in the dental composites field. The structure of urethane dimethacrylates has been confirmed by ¹H (¹³C) NMR and FTIR spectra, as well as by electrospray ionization tandem mass spectroscopy, and gel permeation chromatography measurements. The effects of the cationic macromers on the properties of the filled/non-filled composites were examined through FTIR, photoDSC, and specific measurements as volumetric polymerization shrinkage, water sorption/solubility, contact angle, mechanical parameters, and morphology. The monomer compositions based on cationic dimethacrylate (6.88–27.52 wt%), BisGMA-analogue (48.18–68.82 wt%) and TEGDMA (23.3 wt%) showed a good photoreactivity in terms of double bond conversion (DC, 50.07–68.81 %) and polymerization rate (R_p, 0.099–0.141 s^?1) measured by photoDSC compared to a control sample (BisGMA-1/TEGDMA: DC, 45.91 %; R_p, 0.162 s^?1), while the polymerization shrinkage increased in acceptable limits (5.37–7.74 vol%). The mechanical properties (compressive, flexural and diametral tensile strength) of the composite resin incorporating 70 wt% silanized zirconium silicate micro/nanopowder can be modulated by the initial co-monomer concentrations.     

Atmospheric corrosion of magnesium alloys AZ31 and AZ61 under continuous condensation conditions

This paper studies the corrosion rate of magnesium alloys AZ31 and AZ61 exposed in humid air under continuous condensation conditions. The shape of the gravimetric curves for corrosion progress suggests that the process is controlled by factors related with the corrosion product layer growing on the metallic surface according to gravimetric results there is an initial period in which only a small part of the corroded metal is incorporated in the corrosion product layer, but after longer testing times the proportion of metal that comes to form part of this layer tends to increase very significantly.     

Physiological requirements for growth and competitiveness of Dekkera bruxellensis under oxygen-limited or anaerobic conditions

The effect of glucose and oxygen limitation on the growth and fermentation performances of Dekkera bruxellensis was investigated in order to understand which factors favour its propagation in ethanol or wine plants. Although D. bruxellensis has been described as a facultative anaerobe, no growth was observed in mineral medium under complete anaerobiosis while growth was retarded under severe oxygen limitation. In a continuous culture with no gas inflow, glucose was not completely consumed, most probably due to oxygen limitation. When an air/nitrogen mixture (O₂‐content ca. 5%) was sparged to the culture, growth became glucose‐limited. In co‐cultivations with Saccharomyces cerevisiae, ethanol yields/g consumed sugar were not affected by the co‐cultures as compared to the pure cultures. However, different population responses were observed in both systems. In oxygen‐limited cultivation, glucose was depleted within 24 h after challenging with S. cerevisiae and both yeast populations were maintained at a stable level. In contrast, the S. cerevisiae population constantly decreased to about 1% of its initial cell number in the sparged glucose‐limited fermentation, whereas the D. bruxellensis population remained constant. To identify the requirements of D. bruxellensis for anaerobic growth, the yeast was cultivated in several nitrogen sources and with the addition of amino acids. Yeast extract and most of the supplied amino acids supported anaerobic growth, which points towards a higher nutrient demand for D. bruxellensis compared to S. cerevisiae in anaerobic conditions. Copyright © 2012 John Wiley & Sons, Ltd.     

The influence of the deposition time on morphological and optical properties of Cu x S films deposited on polypropylene substrate

Copper sulfide (Cu _x S) films deposited on polypropylene substrate were obtained by chemical bath deposition (CBD) method. The influence of the deposition time on the morphology of Cu _x S films was studied by means of scanning electron microscopy. We have found that the average particles dimension increased from 37 to 49 nm with the increase of deposition time from 20 to 30 minutes. The study of optical properties of the copper sulfide films was carried out based on optical transmission spectra recorded in the 400–1000 nm wavelength range. The optical constants, such as refractive index, extinction coefficient and dielectric constant as well as electrical and optical conductivity of Cu _x S films were calculated. The obtained values are in accordance with the ones reported in the literature:We have shown that both, morphological and optical properties of Cu _x S films are strongly affected by the deposition time.