313 research outputs found
Novel anti-invasive properties of a Fascin1 inhibitor on colorectal cancer cells
Tumor invasion and metastasis involve processes in which actin cytoskeleton rearrangement induced by Fascin1 plays a crucial role. Indeed, Fascin1 has been found overexpressed in tumors with worse prognosis. Migrastatin and its analogues target Fascin1 and inhibit its activity. However, there is need for novel and smaller Fascin1 inhibitors. The aim of this study was to assess the effect of compound G2 in colorectal cancer cell lines and compare it to migrastatin in in vitro and in vivo assays. Molecular modeling, actin-bundling, cell viability, inmunofluorescence, migration, and invasion assays were carried out in order to test anti-migratory and anti-invasive properties of compound G2. In addition, the in vivo effect of compound G2 was evaluated in a zebrafish model of invasion. HCT-116 cells exhibited the highest Fascin1 expression from eight tested colorectal cancer cell lines. Compound G2 showed important inhibitory effects on actin bundling, filopodia formation, migration, and invasion in different cell lines. Moreover, compound G2 treatment resulted in significant reduction of invasion of DLD-1 overexpressing Fascin1 and HCT-116 in zebrafish larvae xenografts; this effect being less evident in Fascin1 known-down HCT-116 cells. This study proves, for the first time, the in vitro and in vivo anti-tumoral activity of compound G2 on colorectal cancer cells and guides to design improved compound G2-based Fascin1 inhibitors. Key messages center dot Fascin is crucial for tumor invasion and metastasis and is overexpressed in bad prognostic tumors. center dot Several adverse tumors overexpress Fascin1 and lack targeted therapy. center dot Anti-fascin G2 is for the first time evaluated in colorectal carcinoma and compared with migrastatin. center dot Filopodia formation, migration activity, and invasion in vitro and in vivo assays were performed. center dot G2 blocks actin structures, migration, and invasion of colorectal cancer cells as fascin-dependent.Peer reviewe
Free ion diffusivity and charge concentration on cross-linked Polymeric Ionic Liquid iongels films based on sulfonated zwitterion salts and Lithium ions
[EN] The properties of various mixtures of a zwitterionic ionic liquid (ZIs-1) and LiNTf 2, including their conductivity, have been studied showing how they can be adjusted through their molar composition. Conductivity tends to increase with the LiNTf2 content although it presents a minimum at the region close to the eutectic point. These mixtures also provide excellent features as liquid phases for the preparation of composite materials based on crosslinked PILs. The prepared films display excellent and tuneable properties as conducting materials, with conductivities that can be higher than 10 2 S cm 1 above 100 1C. The selected polymeric compositions show very good mechanical properties and thermal stability, even for low crosslinking degrees, along with a suitable flexibility and good transparency. The final properties of the films correlate with the composition of the monomeric mixture used and with that of the ZIs-1:LiNTf2 mixture.Financial support has been provided by MINECO (ENE/2015-69203-R and RTI2018-098233-B-C22) and Generalitat Valenciana (PROMETEO/2016/071). Technical support from the SECIC of the UJI is also acknowledged. DV thanks UNED (Costa Rica) for a predoctoral fellowship.Valverde, D.; Garcia Bernabe, A.; Andrio Balado, A.; Garcia-Verdugo, E.; Luis Lafuente, S.; Compañ Moreno, V. (2019). Free ion diffusivity and charge concentration on cross-linked Polymeric Ionic Liquid iongels films based on sulfonated zwitterion salts and Lithium ions. Physical Chemistry Chemical Physics. 21(32):17923-17932. https://doi.org/10.1039/c9cp01903kS17923179322132Etacheri, V., Marom, R., Elazari, R., Salitra, G., & Aurbach, D. (2011). Challenges in the development of advanced Li-ion batteries: a review. 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New role of the antidepressant imipramine as a Fascin1 inhibitor in colorectal cancer cells
Colorectal cancer: Antitumor antidepressant The antidepressant drug imipramine can block the activity of a protein that contributes to the progression of certain aggressive tumors. Serrated adenocarcinoma (SAC) is a form of colorectal cancer with a poor prognosis. A key factor in SAC development is the overexpression of the protein fascin1, which promotes the formation of structures that help cancer cells move around, thereby leading to metastasis. Pablo Conesa-Zamora at Santa Lucia University Hospital in Cartagena, Horacio Perez-Sanchez at the Universidad Catolica de Murcia in Guadalupe, Spain, and coworkers demonstrated that imipramine shows promise in binding to fascin1 and blocking its activity. The team analyzed over 9500 compounds as potential fascin1 blockers, identifying imipramine as a possible option. In tests on human tissues and in vivo studies using zebrafish, the drug reduced cancer invasion and metastasis. Serrated adenocarcinoma (SAC) is more invasive, has worse outcomes than conventional colorectal carcinoma (CRC), and is characterized by frequent resistance to anti-epidermal growth factor receptor (EGFR) and overexpression of fascin1, a key protein in actin bundling that plays a causative role in tumor invasion and is overexpressed in different cancer types with poor prognosis. In silico screening of 9591 compounds, including 2037 approved by the Food and Drug Administration (FDA), was performed, and selected compounds were analyzed for their fascin1 binding affinity by differential scanning fluorescence. The results were compared with migrastatin as a typical fascin1 inhibitor. In silico screening and differential scanning fluorescence yielded the FDA-approved antidepressant imipramine as the most evident potential fascin1 blocker. Biophysical and different in vitro actin-bundling assays confirm this activity. Subsequent assays investigating lamellipodia formation and migration and invasion of colorectal cancer cells in vitro using 3D human tissue demonstrated anti-fascin1 and anti-invasive activities of imipramine. Furthermore, expression profiling suggests the activity of imipramine on the actin cytoskeleton. Moreover, in vivo studies using a zebrafish invasion model showed that imipramine is tolerated, its anti-invasive and antimetastatic activities are dose-dependent, and it is associated with both constitutive and induced fascin1 expression. This is the first study that demonstrates an antitumoral role of imipramine as a fascin1 inhibitor and constitutes a foundation for a molecular targeted therapy for SAC and other fascin1-overexpressing tumors.Peer reviewe
Solid Polymer Electrolytes Based on Polylactic Acid Nanofiber Mats Coated with Polypyrrole
This is the peer reviewed version of the following article: Gisbert, F., García-Bernabé, A., Compañ, V., Martínez-Ramos, C., Monleón, M., Solid Polymer Electrolytes Based on Polylactic Acid Nanofiber Mats Coated with Polypyrrole. Macromol. Mater. Eng. 2021, 306, 2000584, which has been published in final form at https://doi.org/10.1002/mame.202000584. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] The production of electroconductive nanofiber membranes made from polylactic acid (PLA) coated with polypyrrole (PPy) is investigated, performing a scanning of different reaction parameters and studying their physicochemical and dielectric properties. Depending on PPy content, a transition between conduction mechanisms is observed, with a temperature-dependent relaxation process for samples without PPy, a temperature-independent conduction process for samples with high contents of PPy and a combination of both processes for samples with low contents of PPy. A homogeneous and continuous coating is achieved from 23 wt% PPy, observing a percolation effect around 27 wt% PPy. Higher wt% PPy allow to obtain higher conductivities, but PPy aggregates appear from 34% wt% PPy. The high conductivity values obtained for electrospun membranes both through-plane and in-plane (above 0.05 and 0.20 S cm¿1, respectively, at room temperature) for the highest wt% of PPy, their porous structure with high specific surface area and their thermal stability below 140 °C make them candidates for many potential applications as solid polymer electrolytes in, for example, batteries, supercapacitors, sensors, photosensors, or polymer electrolyte membrane fuel cells (PEMFCs). In addition, the biocompatibility of PLA-PPy membranes expand their potential applications also in the field of tissue engineering and implantable devices.The authors acknowledge financing from the Spanish Government's State Research Agency (AEI) through projects DPI2015-72863-EXP and RTI2018-095872-B-C22/ERDF. FGR acknowledges the scholarship FPU16/01833 of the Spanish Ministry of Universities. 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Scalable virtual network video-optimizer for adaptive real-time video transmission in 5G networks
Ionic Liquid Composite Polybenzimidazol Membranes for High Temperature PEMFC Applications
[EN] A series of proton exchange membranes based on polybenzimidazole (PBI) were prepared using the low cost ionic liquids (ILs) derived from 1-butyl-3-methylimidazolium (BMIM) bearing different anions as conductive fillers in the polymeric matrix with the aim of enhancing the proton conductivity of PBI membranes. The composite membranes prepared by casting method (containing 5 wt. % of IL) exhibited good thermal, dimensional, mechanical, and oxidative stability for fuel cell applications. The effects of anion, temperature on the proton conductivity of phosphoric acid-doped membranes were systematically investigated by electrochemical impedance spectroscopy. The PBI composite membranes containing 1-butyl-3-methylimidazolium-derived ionic liquids exhibited high proton conductivity of 0.098 Scm(-1) at 120 degrees C when tetrafluoroborate anion was present in the polymeric matrix. This conductivity enhancement might be attributed to the formed hydrogen-bond networks between the IL molecules and the phosphoric acid molecules distributed along the polymeric matrix.The authors acknowledge the Spanish Ministerio de Economia y Competitividad (MINECO) for the financial support under the project ENE/2015-69203-R.Escorihuela, J.; Garcia Bernabe, A.; Montero Reguera, ÁE.; Sahuquillo, O.; Giménez Torres, E.; Compañ Moreno, V. (2019). Ionic Liquid Composite Polybenzimidazol Membranes for High Temperature PEMFC Applications. Polymers. 11(4):1-14. https://doi.org/10.3390/polym1104073211411
Structural and dielectric properties of Cobaltacarborane Composite Polybenzimidazole Membranes as solid polymer electrolytes at high temperature
[EN] The conductivity of a series of composite membranes, based on polybenzimidazole (PBI) containing the metallacarborane salt M[Co(C2B9H11)(2)], M[COSANE] and tetraphenylborate, M[B(C6H5)(4)], M[TPB] both anions having the same number of atoms and the same negative charge, has been investigated. Different cations (M = H+, Li+ and Na+) have been studied and the composite membranes have been characterized by water uptake, swelling ratios, ATR FT-IR, thermogravimetric analysis and electrochemical impedance spectroscopy to explore the dielectric response and ion dynamics in composite membranes. Our results show that conductivity increases with increasing temperature and it is higher for H+ than for Li+ and Na+ for all temperatures under study. The mobility of Li+ is greater in [COSANE](-) than in [TPB](-) composite PBI@membranes while for Na+ it is the opposite. The temperature dependence of the conductivity of the composite was followed by a typical Arrhenius behaviour with two different regions: (1) between 20 and 100 degrees C, and (2) between 100 and 150 degrees C. Using the analysis of electrode polarization (EP) based on the Thrukhan theory we have calculated the ionic diffusion coefficients and the density of carriers. From the double logarithmic plot of the imaginary part of the conductivity (sigma '') versus frequency in the entire range of temperatures studied we have determined for each sample at each temperature, the frequency values of the onset (f(ON)) and full development of electrode polarization (f(MAX)), respectively, which permit us to calculate static permittivity.We gratefully acknowledge Spanish Ministerio de Economia y Competitividad (MINECO) for financial support by the ENE/2015-69203-R project and CTQ2016-75150-R project, and Generalitat de Catalunya (2014/SGR/149). I. Fuentes is enrolled in the PhD program of the UAB. The authors acknowledge Dr Oscar Sahuquillo for technical assistance in TGA.Fuentes, I.; Andrio Balado, A.; Garcia Bernabe, A.; Escorihuela Fuentes, J.; Viñas, C.; Teixidor, F.; Compañ Moreno, V. (2018). Structural and dielectric properties of Cobaltacarborane Composite Polybenzimidazole Membranes as solid polymer electrolytes at high temperature. Physical Chemistry Chemical Physics. 20(15):10173-10185. https://doi.org/10.1039/c8cp00372fS10173101852015I. E. A. Statistics, IEA, Paris, France, 2016Li, W., Dahn, J. R., & Wainwright, D. S. (1994). Rechargeable Lithium Batteries with Aqueous Electrolytes. Science, 264(5162), 1115-1118. doi:10.1126/science.264.5162.1115Lee, H., Yanilmaz, M., Toprakci, O., Fu, K., & Zhang, X. (2014). A review of recent developments in membrane separators for rechargeable lithium-ion batteries. Energy Environ. Sci., 7(12), 3857-3886. doi:10.1039/c4ee01432dAnothumakkool, B., Torris A. 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