Obatoclax and Paclitaxel Synergistically Induce Apoptosis and Overcome Paclitaxel Resistance in Urothelial Cancer Cells

Paclitaxel is a treatment option for advanced or metastatic bladder cancer after the failure of first-line cisplatin and gemcitabine, although resistance limits its clinical benefits. Mcl-1 is an anti-apoptotic protein that promotes resistance to paclitaxel in different tumors. Obatoclax, a BH3 mimetic of the Bcl-2 family of proteins, antagonizes Mcl-1 and hence may reverse paclitaxel resistance in Mcl-1-overexpressing tumors. In this study, paclitaxel-sensitive 5637 and -resistant HT1197 bladder cancer cells were treated with paclitaxel, obatoclax, or combinations of both. Apoptosis, cell cycle, and autophagy were measured by Western blot, flow cytometry, and fluorescence microscopy. Moreover, Mcl-1 expression was analyzed by immunohistochemistry in bladder carcinoma tissues. Our results confirmed that paclitaxel alone induced Mcl-1 downregulation and apoptosis in 5637, but not in HT1197 cells; however, combinations of obatoclax and paclitaxel sensitized HT1197 cells to the treatment. In obatoclax-treated 5637 and obatoclax + paclitaxel-treated HT1197 cells, the blockade of the autophagic flux correlated with apoptosis and was associated with caspase-dependent cleavage of beclin-1. Obatoclax alone delayed the cell cycle in 5637, but not in HT1197 cells, whereas combinations of both retarded the cell cycle and reduced mitotic slippage. In conclusion, obatoclax sensitizes HT1197 cells to paclitaxel-induced apoptosis through the blockade of the autophagic flux and effects on the cell cycle. Furthermore, Mcl-1 is overexpressed in many invasive bladder carcinomas, and it is related to tumor progression, so Mcl-1 expression may be of predictive value in bladder cancer.España, Sistema Público Andaluz Biobanco y ISCIII-Red de Biobancos PT17/0015/004

Frying edible vegetable oil quality from street-food vendors in a Metropolitan area in the Central Highlands of Mexico

Vegetable oil deterioration during frying is a health problem because of oil degradation compounds and recycled oil practices are related to disturb oil quality. Frying food street-vendors are an important part of endemic market type Tianguis at the Metropolitan areas in the Central Highlands of Mexico. The main objective of this research was to evaluate frying edible vegetable oil quality from frying by street-food vendors in a Metropolitan area in the Central Highlands of Mexico. A behaviour questionary registered fresh and recycling oil addition, frying temperature and method in real operation conditions for three working days. Free fatty acid, colour, p-Anisidine, peroxide, and TOTOX indexes were observed in the vendors by triplicate. Free fatty acids and peroxide values in two vendors exceeded the NMX-F-223-SCFI-2011 values. Physicochemical variables revealed oil oxidation deterioration. Not so high temperatures were registered, and continually fresh oil addition was suggested as mitigating or masking edible oil of thermal oxidation and its degradation agents during the observed time. Thermal oxidation could be lower than in controlled conditions as in many reports due to vendor operations studied as a real approximation that suggested less oil degradation. Present results could be evidence for government intervention in the regulation needsCONACY

Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties

The Wnt/β-catenin pathway plays an important role in tumor progression and chemother apy resistance and seems to be essential for the maintenance of cancer stem cells (CSC) in several tumor types. However, the interplay of these factors has not been fully addressed in bladder cancer. Here, our goal was to analyze the role of the Wnt/β-catenin pathway in paclitaxel resistance and to study the therapeutic efficacy of its inhibition in bladder cancer cells, as well as to determine its influence in the maintenance of the CSC-like phenotype in bladder cancer. Our results show that paclitaxel-resistant HT1197 cells have hyperactivation of the Wnt/β-catenin pathway and increased CSC-like properties compared with paclitaxel-sensitive 5637 cells. Paclitaxel sensitivity diminishes in 5637 cells after β-catenin overexpression or when they are grown as tumorspheres, enriched for the CSC-like phenotype. Additionally, downregulation of β-catenin or inhibition with XAV939 sensitizes HT1197 cells to paclitaxel. Moreover, a subset of muscle-invasive bladder carcinomas shows aberrant expression of β-catenin that associates with positive expression of the CSC marker ALDH1A1. In conclusion, we demonstrate that Wnt/β-catenin signaling contributes to paclitaxel resistance in bladder cancer cells with CSC-like properties.Instituto de Salud Carlos III FIS-PI17/1240Instituto de Salud Carlos III FIS-PI20/1641Ministry of Economy, Industry and Competitiveness SAF2017-87358-C2-1-R and -2-RMinisterio de Ciencia e Innovación PID2020-118774RB-C21 and -C22Consejería de Salud y Familias PI-0213-2020Consejería de Salud y Familias OH-0017-201

Effect of temperature and reaction time of the synthesis of nanocrystalline brucite

Mg(OH)2 nanoparticles has been successfully synthesized by means of the hydrothermal method. The effect of the reaction time and the synthesis temperature on the nanoparticles obtained has also been studied. The physic-chemical properties of the synthesized brucite samples have been characterized by X-Ray-diffraction (XRD), scanning electron microscopy/energy dispersive X-rays analysis (SEM/EDX), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), thermogravimetry/ differential scanning Calorimetry (TG-DSC) and in situ high-temperature X-ray diffraction (XRD). The influence of the synthesis parameters in the brucite samples has been discussed in detail. Furthermore, it has been shown that the increase of temperature from 180 to 200ºC improves the crystallinity degree of Mg(OH)2 nanostructured particles and also, promotes the formation of plates with bigger uniform size. As well, the increase in the time reaction induces the formation of bigger size brucite plates. So, this hydrothermal method has been shown to be a really promising method for the large scale production.Peer Reviewe

Downregulation of protein tyrosine phosphatase PTPL1 alters cell cycle and upregulates invasion-related genes in prostate cancer cells

The final publication is available at link.springer.comPTPL1, a non-receptor type protein tyrosine phosphatase, has been involved in the regulation of apoptosis and invasiveness of various tumour cell types, but its role in prostate cancer remained to be investigated. We report here that downregulation of PTPL1 by small interfering RNA in PC3 cells decreases cell proliferation and concomitantly reduces the expression of cell cycle-related proteins such as cyclins E and B1, PCNA, PTTG1 and phospho-histone H3. PTPL1 downregulation also increases the invasion ability of PC3 cells through Matrigel coated membranes. cDNA array of PTPL1-silenced PC3 cells versus control cells showed an upregulation of invasion-related genes such as uPA, uPAR, tPA, PAI-1, integrin α6 and osteopontin. This increased expression was also confirmed in PTPL1-silenced DU145 prostate cancer cells by quantitative real time PCR and western blot. These findings suggest that PTPL1 is an important mediator of central cellular processes such as proliferation and invasion. © 2012 Springer Science+Business Media B.V.This work was supported by Grants from the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III, Spain (FIS PI10/02026 and SAF2008-05046-C02-02), ISCIIIRETIC-RD06/0020-FEDER, Consejería de Salud (PI-2009-0589, AI-2010-003 to M.A.J.), and Consejería de Innovación, Ciencia y Empresa (CTS-6243), Junta de Andalucía (06/189, PI-2009-0589, and AI-2010-003 to M. A. J.). C. C. was supported by a pre-doctoral Grant from the Spanish Ministerio de Educación (F.P.I.: BES200612419) co-financiated by Fondo Social Europeo. C. S. was supported by a contract from Instituto de Salud Carlos III/FIS and Fundación Progreso y Salud, Consejería de Salud, Junta de Andalucía, Miguel Servet Program.Peer Reviewe

Experimental and quantum chemical studies of a novel synthetic prenylated chalcone

BACKGROUND: Chalcones are ubiquitous natural compounds with a wide variety of reported biological activities, including antitumoral, antiviral and antimicrobial effects. Furthermore, chalcones are being studied for its potential use in organic electroluminescent devices; therefore the description of their spectroscopic properties is important to elucidate the structure of these molecules. One of the main techniques available for structure elucidation is the use of Nuclear Magnetic Resonance Spectroscopy (NMR). Accordingly, the prediction of the NMR spectra in this kind of molecules is necessary to gather information about the influence of substituents on their spectra. RESULTS: A novel substituted chalcone has been synthetized. In order to identify the functional groups present in the new synthesized compound and confirm its chemical structure, experimental and theoretical (1)H-NMR and (13)C-NMR spectra were analyzed. The theoretical molecular structure and NMR spectra were calculated at both the Hartree-Fock and Density Functional (meta: TPSS; hybrid: B3LYP and PBE1PBE; hybrid meta GGA: M05-2X and M06-2X) levels of theory in combination with a 6-311++G(d,p) basis set. The structural parameters showed that the best method for geometry optimization was DFT:M06-2X/6-311++G(d,p), whereas the calculated bond angles and bond distances match experimental values of similar chalcone derivatives. The NMR calculations were carried out using the Gauge-Independent Atomic Orbital (GIAO) formalism in a DFT:M06-2X/6-311++G(d,p) optimized geometry. CONCLUSION: Considering all HF and DFT methods with GIAO calculations, TPSS and PBE1PBE were the most accurate methods used for calculation of (1)H-NMR and (13)C-NMR chemical shifts, which was almost similar to the B3LYP functional, followed in order by HF, M05-2X and M06-2X methods. All calculations were done using the Gaussian 09 software package. Theoretical calculations can be used to predict and confirm the structure of substituted chalcones with good correlation with the experimental data

Influence of TFAP2B and KCTD15 genetic variability on personality dimensions in anorexia and bulimia nervosa

INTRODUCCIÓN: TFAP2B y KCTD15 son genes relacionados con la obesidad que interactúan para regular el comportamiento de alimentación. Nuestra hipótesis es que la variabilidad en estos loci, aislada o en combinación, también podría estar relacionada con el riesgo de trastornos de la alimentación (DE) y / o rasgos psicológicos asociados. MÉTODOS: Seleccionamos a 425 participantes (169 pacientes con DE, 75 sujetos obesos y 181 controles) para 10 polimorfismos de nucleótido único (SNP) clínicamente relevantes y marcados en KCTD15 y TFAP2B por la plataforma Sequenom MassARRAY y la secuenciación directa. La evaluación psicométrica se realizó con los inventarios de EDI-2 y SCL-90R. RESULTADOS: El alelo variante KCTD15 rs287103 T se asoció con un mayor riesgo de bulimia nerviosa (BN) (OR = 4.34 [1.47–29.52]; p = .003) y con puntuaciones de escalas psicopatológicas de estos pacientes. El haplotipo * 6 en KCTD15 fue más frecuente en los controles (OR = 0,40 [0,20-0,80], p = .009 para la anorexia nerviosa), mientras que el haplotipo * 4 en TFAP2B afectó las tres escalas del inventario SCL ‐ 90R en pacientes BN (p ≤ .01). Los análisis de epistasis revelaron interacciones relevantes con el índice de masa corporal de los pacientes con BN (p <.001). Los perfiles genéticos en pacientes obesos no difirieron significativamente de los encontrados en pacientes con DE. CONCLUSIONES: Este es el primer estudio que evalúa el papel combinado de los genes TFAP2B y KCTD15 en la DE. Nuestros hallazgos preliminares sugieren que la interacción de la variabilidad genética en estos loci podría influir en el riesgo de disfunción eréctil y / o parámetros antropométricos y psicológicos.INTRODUCTION: TFAP2B and KCTD15 are obesity‐related genes that interact to regulate feeding behavior. We hypothesize that variability in these loci, isolated or in combination, could also be related to the risk of eating disorders (ED) and/or associated psychological traits. METHODS: We screened 425 participants (169 ED patients, 75 obese subjects, and 181 controls) for 10 clinically relevant and tag single‐nucleotide polymorphisms (SNPs) in KCTD15 and TFAP2B by the Sequenom MassARRAY platform and direct sequencing. Psychometric evaluation was performed with EDI‐2 and SCL‐90R inventories. RESULTS: The KCTD15 rs287103 T variant allele was associated with increased risk of bulimia nervosa (BN) (OR = 4.34 [1.47–29.52]; p = .003) and with scores of psychopathological scales of these patients. Haplotype *6 in KCTD15 was more frequent in controls (OR = 0.40 [0.20–0.80], p = .009 for anorexia nervosa), while haplotype *4 in TFAP2B affected all three scales of the SCL‐90R inventory in BN patients (p ≤ .01). Epistasis analyses revealed relevant interactions with body mass index of BN patients (p < .001). Genetic profiles in obese patients did not significantly differ from those found in ED patients. CONCLUSIONS: This is the first study that evaluates the combined role of TFAP2B and KCTD15 genes in ED. Our preliminary findings suggest that the interaction of genetic variability in these loci could influence the risk for ED and/or anthropometric and psychological parameters.• Alicia Koplowitz Foundation • Junta de Extremadura. Ayuda GR15012 • Fundação para a Ciência e a Tecnologia (Portugal). Beca postdoctoral SFRH/BPD/109043/2015, para David dos Santos AlbuquerquepeerReviewe

Pre-history of the botellón: an anthology of moments of collective consumption of alcohol in Granada

El botellón es un fenómeno social muy reciente y dinámico, que alude a una forma de ocio entre los jóvenes basada en el consumo colectivo de alcohol en espacios públicos. El fenómeno puede explicarse entre otros factores por la función social de la bebida, y la tradición que el beber tiene en la cultura mediterránea, donde no hay fiesta sin alcohol. Este trabajo se pregunta qué hay de cierto en la idea de que el consumo colectivo de alcohol ha estado siempre presente en el cotidiano de las personas, y para responder a la cuestión nos planteamos hacer un estudio descriptivo sobre fuentes históricas y literarias de la ciudad de Granada en busca de lo que denominamos la pre-historia del botellón. Guiados por el enfoque arqueológico de Foucault, se muestra una selección antológica de textos, seleccionados entre fuentes literarias, crónicas históricas, narrativas, etnografías y fuentes orales, con una dimensión temporal muy amplia, abarcando desde fuentes medievales a testimonios de nuestros días, que tienen en común la plasmación de discursos en torno al beber en la ciudad de Granada.The botellón is a very recent and dynamic social phenomenon making reference to leisurely activity based on the collective consumption of alcohol in public spaces. Among other factors, the phenomenon can be explained by the social role that drinking plays and by the tradition that drinking has in our Mediterranean culture, where there is no party without alcohol. This work addresses the idea that collective consumption of alcohol has always been present in people's daily life and asks whether this perception is true. To answer this question we propose to carry out a descriptive study on historic and literary sources about the city of Granada searching for what we have called the "pre-history" of the botellón. Guided by Foucault's archaeological approach we show an anthology selection of texts chosen from among literary sources, historical chronicles, ethnographies, and oral sources. These sources have a very broad temporal dimension spanning from medieval sources to current testimonies, and what they all have in common is the reflection of discourses about drinking in the city of Granada