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81.
pH‐Cleavable Nucleoside Lipids: A New Paradigm for Controlling the Stability of Lipid‐Based Delivery Systems 下载免费PDF全文
Dr. Khalid Oumzil Sébastien Benizri Giovanni Tonelli Dr. Cathy Staedel Ananda Appavoo Max Chaffanet Laurence Navailles Prof. Philippe Barthélémy 《ChemMedChem》2015,10(11):1797-1801
Lipid‐based delivery systems are an established technology with considerable clinical acceptance and several applications in human. Herein, we report the design, synthesis and evaluation of novel orthoester nucleoside lipids (ONLs) for the modulation of liposome stability. The ONLs contain head groups with 3′‐orthoester nucleoside derivatives featuring positive or negative charges. The insertion of the orthoester function in the NL structures allows the formation of pH‐sensitive liposomes. ONL‐based liposomes can be hydrolyzed to provide nontoxic products, including nucleoside derivatives and hexadecanol. To allow the release to be tunable at different hydrolysis rates, the charge of the polar head structure is modulated, and the head group can be released at a biologically relevant pH. Crucially, when ONLs are mixed with natural phosphocholine lipids (PC), the resultant liposome evolves toward the formation of a hexadecanol/PC lamellar system. Biological evaluation shows that stable nucleic acid lipid particles (SNALPs) formulated with ONLs and siRNAs can effectively enter into tumor cells and release their nucleic acid payload in response to an intracellular acidic environment. This results in a much higher antitumor activity than conventional SNALPs. The ability to use pH‐cleavable nucleolipids to control the stability of lipid‐based delivery systems represents a promising approach for the intracellular delivery of drug cargos. 相似文献
82.
Carlotta Lassandro Giuseppe Banderali Giovanni Radaelli Elisa Borghi Francesca Moretti Elvira Verduci 《International journal of molecular sciences》2015,16(8):19989-20000
Prevalence of metabolic syndrome is increasing in the pediatric population. Considering the different existing criteria to define metabolic syndrome, the use of the International Diabetes Federation (IDF) criteria has been suggested in children. Docosahexaenoic acid (DHA) has been associated with beneficial effects on health. The evidence about the relationship of DHA status in blood and components of the metabolic syndrome is unclear. This review discusses the possible association between DHA content in plasma and erythrocytes and components of the metabolic syndrome included in the IDF criteria (obesity, alteration of glucose metabolism, blood lipid profile, and blood pressure) and non-alcoholic fatty liver disease in obese children. The current evidence is inconsistent and no definitive conclusion can be drawn in the pediatric population. Well-designed longitudinal and powered trials need to clarify the possible association between blood DHA status and metabolic syndrome. 相似文献
83.
Alfonso Policicchio Raffaele Filosa Salvatore Abate Giovanni Desiderio Elio Colavita 《Journal of Porous Materials》2017,24(4):905-922
The aim of this comprehensive review on materials for methane storage application is to understand which are the best conditions and the best materials for their use for the implementation of storage tank. The research was focused on two different families of samples that up to now appear like the most promising. In particular, Activated carbon and metal organic framework were analyzed and an overall picture was extrapolated. Analysis of the structural parameters and adsorption capacities were evaluated and relation between them were obtained. A comparison of values available in literature was done and, when possible, laboratory tests were performed. The presented results allow to identify potential materials with high specific storage capacity and to verify their performances in optimized conditions. This work represents the starting point for a real and efficient method to the methane storage as a starting point for the development of Adsorbed Natural Gas technology for static and/or automotive applications. 相似文献
84.
Dr. Cristina Tintori Ilaria Laurenzana Francesco La Rocca Dr. Federico Falchi Prof. Fabio Carraro Alba Ruiz Prof. José A. Esté Miroslava Kissova Dr. Emmanuele Crespan Prof. Giovanni Maga Prof. Mariangela Biava Dr. Chiara Brullo Prof. Silvia Schenone Prof. Maurizio Botta 《ChemMedChem》2013,8(8):1353-1360
Hematopoietic cell kinase (Hck) is a member of the Src family of non‐receptor protein tyrosine kinases. High levels of Hck are associated with drug resistance in chronic myeloid leukemia. Furthermore, Hck activity has been connected with HIV‐1. Herein, structure‐based drug design efforts were aimed at identifying novel Hck inhibitors. First, an in‐house library of pyrazolo[3,4‐d]pyrimidine derivatives, which were previously shown to be dual Abl and c‐Src inhibitors, was analyzed by docking studies within the ATP binding site of Hck to select the best candidates to be tested in a cell‐free assay. Next, the same computational protocol was applied to screen a database of commercially available compounds. As a result, most of the selected compounds were found active against Hck, with Ki values ranging from 0.14 to 18.4 μM , confirming the suitability of the computational approach adopted. Furthermore, selected compounds showed an interesting antiproliferative activity profile against the human leukemia cell line KU‐812, and one compound was found to block HIV‐1 replication at sub‐toxic concentrations. 相似文献
85.
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
86.
Antonio Mancini Sebastiano Raimondo Chantal Di Segni Mariasara Persano Giovanni Gadotti Andrea Silvestrini Roberto Festa Luca Tiano Alfredo Pontecorvi Elisabetta Meucci 《International journal of molecular sciences》2013,14(12):23893-23909
In previous works we demonstrated an inverse correlation between plasma Coenzyme Q10 (CoQ10) and thyroid hormones; in fact, CoQ10 levels in hyperthyroid patients were found among the lowest detected in human diseases. On the contrary, CoQ10 is elevated in hypothyroid subjects, also in subclinical conditions, suggesting the usefulness of this index in assessing metabolic status in thyroid disorders. A Low-T3 syndrome is a condition observed in several chronic diseases: it is considered an adaptation mechanism, where there is a reduction in pro-hormone T4 conversion. Low T3-Syndrome is not usually considered to be corrected with replacement therapy. We review the role of thyroid hormones in regulation of antioxidant systems, also presenting data on total antioxidant capacity and Coenzyme Q10. Published studies suggest that oxidative stress could be involved in the clinical course of different heart diseases; our data could support the rationale of replacement therapy in low-T3 conditions. 相似文献
87.
Elena Vismara Antonio Valerio Alessia Coletti Giangiacomo Torri Sabrina Bertini Giorgio Eisele Rosalba Gornati Giovanni Bernardini 《International journal of molecular sciences》2013,14(7):13463-13481
Heparin has been conjugated to Fe3O4, Co3O4, and NiO nanoparticles (NPs) through electrostatic interactions, producing colloidal suspensions of hybrid metal oxide heparin NPs that are stable in water. Negative zeta potentials and retention of heparin’s ability to capture toluidine blue indicate that heparin’s negative charges are exposed on the surface of the coated NPs. IR results confirmed the formation of nanohybrids as did NMR experiments, which were also interpreted on the basis of toluidine blue tests. Transmission electron microscopy results revealed that the heparin coating does not modify the shape or dimension of the NPs. Dynamic light scattering and negative zeta potential measurements confirmed that heparin surface functionalisation is an effective strategy to prevent NP aggregation. 相似文献
88.
Daniela Erriquez Giovanni Perini Alessandra Ferlini 《International journal of molecular sciences》2013,14(10):19681-19704
ncRNAs are the most recently identified class of regulatory RNAs with vital functions in gene expression regulation and cell development. Among the variety of roles they play, their involvement in human diseases has opened new avenues of research towards the discovery and development of novel therapeutic approaches. Important data come from the field of hereditary muscle dystrophies, like Duchenne muscle dystrophy and Myotonic dystrophies, rare diseases affecting 1 in 7000–15,000 newborns and is characterized by severe to mild muscle weakness associated with cardiac involvement. Novel therapeutic approaches are now ongoing for these diseases, also based on splicing modulation. In this review we provide an overview about ncRNAs and their behavior in muscular dystrophy and explore their links with diagnosis, prognosis and treatments, highlighting the role of regulatory RNAs in these pathologies. 相似文献
89.
Isodiana Crupi Stefano Boscarino Giacomo Torrisi Giorgia Scapellato Salvatore Mirabella Giovanni Piccitto Francesca Simone Antonio Terrasi 《Nanoscale research letters》2013,8(1):392
Laser irradiation of ZnO:Al/Ag/ZnO:Al transparent contacts is investigated for segmentation purposes. The quality of the irradiated areas has been experimentally evaluated by separation resistance measurements, and the results are complemented with a thermal model used for numerical simulations of the laser process. The presence of the Ag interlayer plays two key effects on the laser scribing process by increasing the maximum temperature reached in the structure and accelerating the cool down process. These evidences can promote the use of ultra-thin ZnO:Al/Ag/ZnO:Al electrode in large-area products, such as for solar modules. 相似文献
90.
Giada Arena Giuseppe Barreca Luca Carcone Elena Cini Giovanni Marras Hans G. Nedden Marcello Rasparini Stephen Roseblade Adele Russo Maurizio Taddei Antonio Zanotti‐Gerosa 《Advanced Synthesis \u0026amp; Catalysis》2013,355(8):1449-1454
The novel rhodium complex [Rh(S)‐Phanephos(cod)]‐catalyzed hydrogenation of disubstituted (E)‐enol acetate carboxylic acids is reported. The catalytic cycle works under 30 bar of hydrogen under conventional heating giving different 3‐acetoxy‐2,3‐disubstituted carboxylic acids with ee ≥90%. Hydrogenation occurred also under microwave dielectric heating without eroding the enantioselectivity but improving the overall efficiency of the process. With microwaves, hydrogen pressure and reaction time required for complete hydrogenation dropped to 5 bar and 30 min, respectively. The best performance of this catalyst under microwave irradiation was TON 100, TOF 196 h−1 with ee 99% on a 6‐g scale. 相似文献