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11.
Myriam Gonzlez María Ovejero-Snchez Alba Vicente-Blzquez Raquel lvarez Ana B. Herrero Manuel Medarde Rogelio Gonzlez-Sarmiento Rafael Pelez 《International journal of molecular sciences》2021,22(4)
Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers. 相似文献
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Lorena Rodríguez-López Myriam Rincón-Fontán Xanel Vecino Ana B. Moldes Jose M. Cruz 《Journal of surfactants and detergents》2020,23(1):79-90
Over the last few years, the global biosurfactant market has raised due to the increasing awareness among consumers, for the use of biological or bio-based products. Because of their composition, it can be speculated that these are more biocompatible and more biodegradable than their chemical homologous. However, at the moment, no studies exist in the literature about the biodegradability of biosurfactants. In this work, a biosurfactant contained in a crude extract, obtained from a corn wet-milling industry stream that ferments spontaneously in the presence of lactic acid bacteria, was subjected to a biodegradation study, without addition of external microbial biomass, under different conditions of temperature (5–45 °C), biodegradation time (15–55 days), and pH (5–7). For that, a Box–Behnken factorial design was applied, which allowed to predict the percentage of biodegradation for the biosurfactant contained in the crude extract, between the range of the independent variables selected in the study, obtaining biodegradation values between 3 and 80%. The percentage of biodegradation for the biosurfactant was calculated based on the increase in the surface tension of samples of the crude extract. Furthermore, it was also possible to predict the variation in t1/2 for the biosurfactant (time to achieve the 50% of biodegradation) under different conditions. 相似文献
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Rock joints infilled with sediments can strongly influence the strength of rock mass. As infilled joints often exist under unsaturated condition, this study investigated the influence of matric suction of infill on the overall joint shear strength. A novel technique that allows direct measurement of matric suction of infill using high capacity tensiometers (HCTs) during direct shear of infilled joints under constant normal stiffness (CNS) is described. The CNS apparatus was modified to accommodate the HCT and the procedure is explained in detail. Joint specimens were simulated by gypsum plaster using three-dimensional (3D) printed surface moulds, and filled with kaolin and sand mixture prepared at different water contents. Shear behaviours of both planar infilled joints and rough joints having joint roughness coefficients (JRCs) of 8–10 and 18–20 with the ratios of infill thickness to asperity height (t/a) equal to 0.5 were investigated. Matric suction shows predominantly unimodal behaviour during shearing of both planar and rough joints, which is closely associated with the variation of unloading rate and volumetric changes of the infill material. As expected, two-peak behaviour was observed for the rough joints and both peaks increased with the increase of infill matric suction. The results suggest that the contribution of matric suction of infill on the joint peak normalised shear stress is relatively independent of the joint roughness. 相似文献
16.
Juana Maria de Lourdes Medina-Contreras Patrick Mailloux-Salinas Juventino III Colado-Velazquez Norma Leticia Gomez Viquez Gómez-Viquez Rodrigo Velázquez-Espejel Ana del Carmen Susunaga-Notario David Julian Arias-Chávez Guadalupe Bravo 《Journal of the science of food and agriculture》2020,100(7):3212-3219
17.
Ana Rita Gomes Nasim Bahram Sangani Tiago G. Fernandes M. Margarida Diogo Leopold M. G. Curfs Chris P. Reutelingsperger 《International journal of molecular sciences》2020,21(24)
The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics. 相似文献
18.
Maja D. Markovic Vesna V. Panic Sanja I. Seslija Ana D. Milivojevic Pavle M. Spasojevic Nevenka M. Boskovic-Vragolovic Rada V. Pjanovic 《Polymer Engineering and Science》2020,60(8):2008-2022
Carriers for targeted delivery and controlled release of poorly water-soluble active substances (PWSAS) are facing three challenges: (a) the encapsulation issues, (b) limitations of PWSAS water solubility, and (c) burst drug release which can be pharmacologically dangerous and economically inefficient. The present study brings a novel strategy for encapsulation and controlled release of PWSAS—caffeine in concentrations which are higher than its maximal water solubility without the possibility of burst effect. The modification of hydrophilic carrier based on poly(methacylic acid) was done using casein and liposomes. To further increase the maximal caffeine loading inside the carrier nicotinamide was used. The release study of the encapsulated PWSAS was elaborated with respect to morphology of the carriers and interactions that could be established between its structural components. The carriers swelling and the release of caffeine and nicotinamide were also investigated depending on caffeine concentration, the presence of different liposomal formulations and the volume ratio of liposomal formulation, in three media with different pH simulating the path of the carrier through the human gastrointestinal tract. The synthesized carriers are promising candidates for encapsulation of PWSAS in concentrations which are higher than its maximal water solubility and for the targeted delivery of those dosages. 相似文献
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Paola Cristina Cajas Daza Rodrigo Arbey Muñoz Meneses Ana Candida Martins Rodrigues Cosme Roberto Moreira da Silva 《Ceramics International》2018,44(12):13699-13705
Doped CeGdO and codoped CeGdOSmO compositions were synthesized, giving rise to nanoparticulate powders. Ionic conductivities at bulk and grain boundaries of the sintered samples were determined, exhibiting increased conductivity in the samaria-codoped samples. Scanning electron microscopy (SEM) showed a significant reduction in the grain size of samaria-codoped electrolytes. This reduced grain size of the codoped samples caused a reduction in Schottky barrier height, increasing oxygen vacancy concentration in the space-charge layer of the grain boundary and culminating in greater ionic conductivity in the boundary region. For the gadolinium doped samples, high resolution transmission electron microscopy images at grains showed the presence of large cluster of defects (nanodomains), hindering the movement of charge carriers and reducing ionic conductivity. However, the samaria-codoped system displayed better homogeneity at atomic level, resulting in reduced oxygen vacancy ordering and, consequently, smaller nanodomains and higher bulk (grain) conductivity. The reduced grain sizes and smaller nanodomains caused by codoping favor the ionic conductivity of ceria-based ceramics, doped with gadolinia and codoped with samaria. 相似文献