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51.
Adele Boccuto Filippo Dragoni Francesca Picarazzi Alessia Lai Carla Della Ventura Carla Veo Federica Giammarino Francesco Saladini Gianguglielmo Zehender Maurizio Zazzi Mattia Mori Ilaria Vicenti 《International journal of molecular sciences》2021,22(5)
The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC50) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC50 shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development. 相似文献
52.
Adele Chimento Anna Santarsiero Domenico Iacopetta Jessica Ceramella Arianna De Luca Vittoria Infantino Ortensia Ilaria Parisi Paola Avena Maria Grazia Bonomo Carmela Saturnino Maria Stefania Sinicropi Vincenzo Pezzi 《International journal of molecular sciences》2021,22(10)
Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer. 相似文献
53.
Ilaria Fraudentali Renato A. Rodrigues-Pousada Riccardo Angelini Sandip A. Ghuge Alessandra Cona 《International journal of molecular sciences》2021,22(10)
Polyamines are ubiquitous, low-molecular-weight aliphatic compounds, present in living organisms and essential for cell growth and differentiation. Copper amine oxidases (CuAOs) oxidize polyamines to aminoaldehydes releasing ammonium and hydrogen peroxide, which participates in the complex network of reactive oxygen species acting as signaling molecules involved in responses to biotic and abiotic stresses. CuAOs have been identified and characterized in different plant species, but the most extensive study on a CuAO gene family has been carried out in Arabidopsis thaliana. Growing attention has been devoted in the last years to the investigation of the CuAO expression pattern during development and in response to an array of stress and stress-related hormones, events in which recent studies have highlighted CuAOs to play a key role by modulation of a multilevel phenotypic plasticity expression. In this review, the attention will be focused on the involvement of different AtCuAOs in the IAA/JA/ABA signal transduction pathways which mediate stress-induced phenotypic plasticity events. 相似文献
54.
According to the Linear Elastic Fracture Mechanics criteria, a numerical model is developed to simulate the failure evolution
of multi-cracked finite plates by means of an incremental loading procedure. A modified crack length control scheme is used
in order to analyse such problems depending on one or more independent parameters. The aim is to provide information about
a discontinuous response, such as the snap-back instability, which can be highlighted only by a deformation controlled process.
The load vs. displacement curve, included possible snap-back branches, is numerically traced by means of a procedure based
on the Displacement Discontinuity Boundary Element Method. With reference to finite plates with ordered crack distributions
in plane strain loading conditions, the model is applied in order to analyse the effects of the crack interaction on the fracture
evolution.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
55.
Complex Price Dynamics in a Financial Market with Imitation 总被引:1,自引:0,他引:1
In this work a simple financial model with fundamentalists and imitators is being considered. In order to describe the price dynamics of the heterogeneous stock market, a synergetic approach is used and some global bifurcations arising in the model are being studied. It is shown that the fundamental equilibrium point P* may be destabilized through a subcritical Neimark–Sacker bifurcation and that two invariant closed curves, one attracting and one repelling, appear when P* is still stable. This particular bifurcation scenario allows us to show some noticeable features of the market that emerge when the imitation effect is emphasized. Among these features are, for instance, the volatility clusters associated with the presence of multistability (i.e. coexistence of attractors) and the hysteresis phenomenon. 相似文献
56.
Ionic liquids as diathermic fluids for solar trough collectors’ technology: A corrosion study 总被引:1,自引:0,他引:1
Ilaria Perissi Ugo Bardi Stefano Caporali Alessio Fossati Alessandro Lavacchi 《Solar Energy Materials & Solar Cells》2008,92(4):510-517
The AISI 304 and AISI 1018 steels (frequently used in solar collectors’ plants) in contact with four different ionic liquids (ILs) suitable as diathermic fluids, were studied. Immersion tests were performed at 220 °C (the working temperature in such plants) for 10 days. The corrosion morphologies of the steels were investigated by scanning electron microscopy coupled with energy dispersive X-ray (EDX) microanalysis and the content of metals in the solution were detected via ICP-OES. The tests showed that the most performing IL is the ethyl-dimethyl-propyl-ammonium-bis(trifluoromethylsulphonyl)imide. The corrosion properties of the two alloys in contact with such IL were investigated by means of Tafel plots and resistance polarization at room temperature in open-to-air vessels. 相似文献
57.
Protocatechuic acid activates key components of insulin signaling pathway mimicking insulin activity 下载免费PDF全文
58.
Francesco Todescato Ilaria Fortunati Samuele Gardin Eleonora Garbin Elisabetta Collini Renato Bozio Jacek J. Jasieniak Gioia Della Giustina Giovanna Brusatin Stefano Toffanin Raffaella Signorini 《Advanced functional materials》2012,22(2):337-344
The development of a solution‐deposited up‐converted distributed feedback laser prototype is presented. It employs a sol–gel silica/germania soft‐lithographed microcavity and CdSe–CdZnS–ZnS quantum dot/sol–gel zirconia composites as optical gain material. Characterization of the linear and nonlinear optical properties of quantum dots establishes their high absorption cross‐sections in the one‐ and two‐ photon absorption regimes to be 1 × 10?14 cm2 and 5 × 104 GM, respectively. In addition, ultrafast transient absorption dynamics measurements of the graded seal quantum dots reveal that the Auger recombination lifetime is 220 ps, a value two times higher than that of the corresponding CdSe core. These factors enable the use of such quantum dots as optically pumped gain media, operating in the one‐ and two‐photon absorption regime. The incorporation of CdSe–CdZnS–ZnS quantum dots within a zirconia host matrix affords a quantum‐dot ink that can be directly deposited on our soft‐lithographed distributed feedback grating to form an all‐solution‐processed microcavity laser. 相似文献
59.
Ilaria Paterni Carlotta Granchi 《Critical reviews in food science and nutrition》2017,57(16):3384-3404
Xenoestrogens are widely diffused in the environment and in food, thus a large portion of human population worldwide is exposed to them. Among alimentary xenoestrogens, phytoestrogens (PhyEs) are increasingly being consumed because of their potential health benefits, although there are also important risks associated to their ingestion. Furthermore, other xenoestrogens that may be present in food are represented by other chemicals possessing estrogenic activities, that are commonly defined as endocrine disrupting chemicals (EDCs). EDCs pose a serious health concern since they may cause a wide range of health problems, starting from pre-birth till adult lifelong exposure. We herein provide an overview of the main classes of xenoestrogens, which are classified on the basis of their origin, their structures and their occurrence in the food chain. Furthermore, their either beneficial or toxic effects on human health are discussed in this review. 相似文献
60.
Behaviormetrika - In cases where only linear relationships are suspected, Pearson’s correlation is generally used to measure the strength of the association between variables. It is... 相似文献