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31.
Claudia Giuseppina Fresta Giuseppe Caruso Annamaria Fidilio Chiara Bianca Maria Platania Nicol Musso Filippo Caraci Filippo Drago Claudio Bucolo 《International journal of molecular sciences》2020,21(23)
Activation of P2X7 signaling, due to high glucose levels, leads to blood retinal barrier (BRB) breakdown, which is a hallmark of diabetic retinopathy (DR). Furthermore, several studies report that high glucose (HG) conditions and the related activation of the P2X7 receptor (P2X7R) lead to the over-expression of pro-inflammatory markers. In order to identify novel P2X7R antagonists, we carried out virtual screening on a focused compound dataset, including indole derivatives and natural compounds such as caffeic acid phenethyl ester derivatives, flavonoids, and diterpenoids. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring and structural fingerprint clustering of docking poses from virtual screening highlighted that the diterpenoid dihydrotanshinone (DHTS) clustered with the well-known P2X7R antagonist JNJ47965567. A human-based in vitro BRB model made of retinal pericytes, astrocytes, and endothelial cells was used to assess the potential protective effect of DHTS against HG and 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP), a P2X7R agonist, insult. We found that HG/BzATP exposure generated BRB breakdown by enhancing barrier permeability (trans-endothelial electrical resistance (TEER)) and reducing the levels of ZO-1 and VE-cadherin junction proteins as well as of the Cx-43 mRNA expression levels. Furthermore, HG levels and P2X7R agonist treatment led to increased expression of pro-inflammatory mediators (TLR-4, IL-1β, IL-6, TNF-α, and IL-8) and other molecular markers (P2X7R, VEGF-A, and ICAM-1), along with enhanced production of reactive oxygen species. Treatment with DHTS preserved the BRB integrity from HG/BzATP damage. The protective effects of DHTS were also compared to the validated P2X7R antagonist, JNJ47965567. In conclusion, we provided new findings pointing out the therapeutic potential of DHTS, which is an inhibitor of P2X7R, in terms of preventing and/or counteracting the BRB dysfunctions elicited by HG conditions. 相似文献
32.
The plating of brass on steel from a tartrate based alloy bath has been studied using electrochemical methods and surface analysis techniques. The coating composition obtained using both direct current (d.c.) and pulsed current (p.c.) electrolysis was examined for a variety of temperatures, current densities and bath compositions. The dissolution process of a suitable composition of brass anodes was studied using small amounts of nitrate as depolarizing agent. Tests in a pilot plant showed that when electrolysis is carried outin continuo the coating composition remains constant with time (±1%). Tests were performed at cathode current densities of industrial interest (20–30 A dm–2). The Auger and XPS analyses combined with Ar+ etching indicated a homogeneous composition throughout the coating. 相似文献
33.
Kuwanon‐L as a New Allosteric HIV‐1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation 下载免费PDF全文
Dr. Francesca Esposito Dr. Cristina Tintori Dr. Riccardo Martini Dr. Frauke Christ Prof. Zeger Debyser Roberto Ferrarese Dr. Gianluigi Cabiddu Dr. Angela Corona Dr. Elisa Rita Ceresola Dr. Andrea Calcaterra Dr. Valentina Iovine Prof. Bruno Botta Dr. Massimo Clementi Dr. Filippo Canducci Prof. Maurizio Botta Prof. Enzo Tramontano 《Chembiochem : a European journal of chemical biology》2015,16(17):2507-2512
HIV‐1 integrase (IN) active site inhibitors are the latest class of drugs approved for HIV treatment. The selection of IN strand‐transfer drug‐resistant HIV strains in patients supports the development of new agents that are active as allosteric IN inhibitors. Here, a docking‐based virtual screening has been applied to a small library of natural ligands to identify new allosteric IN inhibitors that target the sucrose binding pocket. From theoretical studies, kuwanon‐L emerged as the most promising binder and was thus selected for biological studies. Biochemical studies showed that kuwanon‐L is able to inhibit the HIV‐1 IN catalytic activity in the absence and in the presence of LEDGF/p75 protein, the IN dimerization, and the IN/LEDGF binding. Kuwanon‐L also inhibited HIV‐1 replication in cell cultures. Overall, docking and biochemical results suggest that kuwanon‐L binds to an allosteric binding pocket and can be considered an attractive lead for the development of new allosteric IN antiviral agents. 相似文献
34.
Filippo Lococo Massimiliano Paci Cristian Rapicetta Teresa Rossi Valentina Sancisi Luca Braglia Silvio Cavuto Alessandra Bisagni Italia Bongarzone Douglas M. Noonan Adriana Albini Sally Maramotti 《International journal of molecular sciences》2015,16(8):19612-19630
Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies. 相似文献
35.
Paola Zunin Raffaella Boggia Filippo Evangelisti 《Journal of the American Oil Chemists' Society》2001,78(10):1037-1040
Cholesterol oxidation in tuna canned in brine was studied. Gas chromatography-mass spectrometry was used for the detection
of the seven major cholesterol oxidation products originating from both direct and indirect oxidation. The total amount of
cholesterol oxidation products in the analyzed samples varied considerably, ranging between 40 and 350 μg/g lipids, with the
exception of an anomalous sample, that reached a 1600 μg/g level. The lipid content ranged between 0.5 and 1 g/100 g wet product.
As most samples did not exceed 100 μg/g lipids, it is possible to assume that the total content of cholesterol oxidation products
can be kept below this value if good manufacturing conditions are used, together with a careful choice of the best tuna cuts.
The application of principal component analysis to the detected variables confirmed that 7-ketocholesterol is a useful index
of the whole oxidation process. 相似文献
36.
Dr. Riccardo Martini Dr. Francesca Esposito Dr. Angela Corona Dr. Roberto Ferrarese Dr. Elisa Rita Ceresola Dr. Laura Visconti Dr. Cristina Tintori Dr. Alessandro Barbieri Dr. Andrea Calcaterra Dr. Valentina Iovine Dr. Filippo Canducci Prof. Enzo Tramontano Prof. Maurizio Botta 《Chembiochem : a European journal of chemical biology》2017,18(4):374-377
37.
Filippo Favretto Dr. Michael Assfalg Dr. Mariana Gallo Prof. Daniel Oscar Cicero Dr. Mariapina D'Onofrio Prof. Henriette Molinari 《Chembiochem : a European journal of chemical biology》2013,14(14):1807-1819
Human liver fatty acid binding protein (hL‐FABP) has been reported to act as an intracellular shuttle of lipid molecules, thus playing a central role in systemic metabolic homeostasis. The involvement of hL‐FABP in the transport of bile salts has been postulated but scarcely investigated. Here we describe a thorough NMR investigation of glycocholate (GCA) binding to hL‐FABP. The protein molecule bound a single molecule of GCA, in contrast to the 1:2 stoichiometry observed with fatty acids. GCA was found to occupy the large internal cavity of hL‐FABP, without requiring major conformational rearrangement of the protein backbone; rather, this led to increased stability, similar to that estimated for the hL‐FABP:oleate complex. Fast‐timescale dynamics appeared not to be significantly perturbed in the presence of ligands. Slow motions (unlike for other proteins of the family) were retained or enhanced upon binding, consistent with a requirement for structural plasticity for promiscuous recognition. 相似文献
38.
Yanina Luciani Dosinda González-Mendizabal Filippo Pironti 《Chemical Engineering Communications》2013,200(12):1653-1670
In this work, solid-liquid wetting factors were determined from liquid holdup and pressure drop measurements according to the model proposed by Pironti et al. for different air-liquid systems: distilled water and CMC solutions at viscosity values of 3, 6, 9, and 12 mPa.s. The experiments were carried out at atmospheric conditions in a column of 10.2 cm internal diameter and 2 m high, packed with a cylindrical material. The superficial mass velocities varied from 0.67 to 18.6 kg/m 2 s for liquid flow and from 0.024 to 0.31 kg/m 2 s for gas flow. Under these operating conditions, regime of continuous gas flow was observed. The wetting factors obtained were in agreement with those reported by other methods, which allow us to confirm that the model used in this work is applicable to fluids of different properties at low gas velocities. 相似文献
39.
Damiano Rossi Sara Filippi Filippo Merusi Felice Giuliani Giovanni Polacco 《应用聚合物科学杂志》2013,129(6):3341-3354
Polymer modified asphalts (PMA) and warm mix asphalts (WMA) are technologies widely adopted in the paving industry. The first one is well established, while the second one is relatively new, but rapidly growing since it guarantees economic and environmental advantages. Until now PMA and WMA have been used disjointedly, but it would be useful to combine them to keep the advantages of both. One of the adopted solutions to obtain a warm effect is the addition of waxes to the asphaltic binder. Therefore, a “warm mix polymer modified asphalt” may be potentially obtained with a ternary asphalt/polymer/wax system. However, the final warm effect and performances of the binder will depend on the interactions between the three components. A preliminary investigation was done by mixing asphalt, styrene‐butadiene‐styrene block copolymer and a wax chosen among the following three categories: paraffinic, partially oxidized and maleic anhydride functionalized. The morphological and calorimetric analyses and solubility tests allowed identifying different behaviors depending on the wax type, which may preferentially interact either with the asphalt or with the polymer, thus influencing the whole binder structure. With regard to the ternary mixes, it was found that: (i) the paraffinic wax preferentially resides in the polymer‐rich phase, and slightly enhances the asphalt‐polymer compatibility; (ii) the partially oxidized wax prefers the asphaltene‐rich phase and reduces the compatibility; (iii) it is not clear where the functionalized wax is located, but it has a considerable compatibilizing effect and strongly alters the colloidal equilibrium of the asphalt‐polymer blend. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013 相似文献
40.
Densification and properties of bulk nanocrystalline functional ceramics with grain size below 50 nm
Filippo Maglia Ilenia G. Tredici Umberto Anselmi-Tamburini 《Journal of the European Ceramic Society》2013,33(6):1045-1066
The synthesis and functional characterization of dense bulk nanometric oxides are reviewed, with particular emphasis on the modifications that a grain size in the low nanometric range (10–50 nm) introduces in their physical properties. The preparation of ceramics with low porosity and extremely small grain size is particularly challenging and mostly relies on the sintering of extremely fine nanopowder. The most popular methods for the preparation of the starting nanopowders are introduced and briefly discussed as well as the most widely employed densification techniques. The role of nanostructure in controlling phase stability, electrical and thermal transport, optical and magnetic properties of nano-oxides is discussed in details. Several examples are given where bulk materials prepared with grain size equal or below 50 nm show characteristics that are either enhanced or, in some cases, completely different from those possessed by the same materials, but with larger grain sizes. 相似文献