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

New Opportunities for Endometrial Health by Modifying Uterine Microbial Composition: Present or Future?

We acknowledge the research support by Copan Italia S.p.A Inc., and Clearblue, SPD Swiss Precision Diagnostics GmbH. This study is part of a PhD Thesis conducted at the Official Doctoral Programme in Biomedicine of the University of Granada, Spain. We are grateful to Ana Yara Postigo-Fuentes for her assistance with English language.Current knowledge suggests that the uterus harbours its own microbiota, where the microbes could influence the uterine functions in health and disease; however, the core uterine microbial composition and the host-microbial relationships remain to be fully elucidated. Different studies are indicating, based on next-generation sequencing techniques, that microbial dysbiosis could be associated with several gynaecological disorders, such as endometriosis, chronic endometritis, dysfunctional menstrual bleeding, endometrial cancer, and infertility. Treatments using antibiotics and probiotics and/or prebiotics for endometrial microbial dysbiosis are being applied. Nevertheless there is no unified protocol for assessing the endometrial dysbiosis and no optimal treatment protocol for the established dysbiosis. With this review we outline the microbes (mostly bacteria) identified in the endometrial microbiome studies, the current treatments offered for bacterial dysbiosis in the clinical setting, and the future possibilities such as pro- and prebiotics and microbial transplants for modifying uterine microbial composition.This work is supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and European Regional Development Fund (FEDER): grants RYC-2016-21199 and ENDORE SAF2017-87526-R; Programa Operativo FEDER Andalucía (B-CTS-500-UGR18) and by the University of Granada Plan Propio de Investigación 2016—Excellence actions: Unit of Excellence on Exercise and Health (UCEES)—and Plan Propio de Investigación 2018—Programa Contratos-Puente, and the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades, European Regional Development Funds (ref. SOMM17/6107/UGR). A.S.-L. is funded by the Spanish Ministry of Science, Innovation and Universities (PRE2018-0854409)

Estudio celular y molecular de los cambios gonadales y espermáticos en conejos hipercolesterolémicos. Análisis del efecto del aceite de oliva

La ingesta elevada de grasas de origen animal (“saturadas”) conlleva a un incremento de colesterol en sangre (hipercolesterolemia, HC), y es un factor de riesgo para el desarrollo de enfermedades cardiovasculares

Eradication of bovine tuberculosis at a herd-level in Madrid, Spain: study of within-herd transmission dynamics over a 12 year period

BACKGROUND Eradication of bovine tuberculosis (bTB) through the application of test-and-cull programs is a declared goal of developed countries in which the disease is still endemic. Here, longitudinal data from more than 1,700 cattle herds tested during a 12 year-period in the eradication program in the region of Madrid, Spain, were analyzed to quantify the within-herd transmission coefficient (β) depending on the herd-type (beef/dairy/bullfighting). In addition, the probability to recover the officially bTB free (OTF) status in infected herds depending on the type of herd and the diagnostic strategy implemented was assessed using Cox proportional hazard models. RESULTS Overall, dairy herds showed higher β (median 4.7) than beef or bullfighting herds (2.3 and 2.2 respectively). Introduction of interferon-gamma (IFN-γ) as an ancillary test produced an apparent increase in the β coefficient regardless of production type, likely due to an increase in diagnostic sensitivity. Time to recover OTF status was also significantly lower in dairy herds, and length of bTB episodes was significantly reduced when the IFN-γ was implemented to manage the outbreak. CONCLUSIONS Our results suggest that bTB spreads more rapidly in dairy herds compared to other herd types, a likely cause being management and demographic-related factors. However, outbreaks in dairy herds can be controlled more rapidly than in typically extensive herd types. Finally, IFN-γ proved its usefulness to rapidly eradicate bTB at a herd-level

Changes in phytoplankton population along the saline gradient of the Júcar estuary and plume

This paper presents the results of phytoplankton counts carried out with epifluorescence at five sampling stations: two in the Júcar River Estuary and the other three in the region of freshwater influence of the Júcar River. From June 2002 to July 2003, nine sampling campaigns were carried out as a part of the EU's ECOSUD project. Two of these campaigns (the 2nd and 8th) were selected for analysis. These sampling campaigns represent two different conditions: in the 2nd campaign the discharge of the Júcar River was almost null, while in the 8th campaign it was significantly higher. Along the salinity gradient, as the influence of fresh water and nutrient loads decreases, a decrease in the population density of eukaryotic phytoplankton was observed. Typical freshwater phytoplankton groups (colonial cyanobacteria and chlorophyceae) clearly decrease in density and percentage as salinity increases. In general, picocyanobacteria exhibit the opposite behavior. The behavior pattern of groups with species adapted to fresh water and seawater is less clear. The density of these groups (diatoms and prymnesiophytes) is highest in the salt-wedge area due to nutrient accumulation. However, the densities are generally higher at the freshwater stations than in the marine environment. The vertical distribution at the estuarine stations shows clear density maximums in the interface area, which seems to have two causes: the retention of senescent phytoplankton affected by saline shock in this quiescent area and the growth of phytoplankton that exploit the accumulated nutrients.González Del Rio Rams, J.; Romero Gil, I.; Falco, S.; Rodilla, M.; Sierra, JP.; Sánchez-Arcilla, A.; Mösso, C. (2007). Changes in phytoplankton population along the saline gradient of the Júcar estuary and plume. Journal of Coastal Research. SI 47:63-68. doi:10.2112/1551-5036-47.sp1.63S6368SI 4

Efecto del aceite de oliva sobre el metabolismo del colesterol en conejos hipercolesterolémicos.

El aceite de oliva, componente esencial de la Dieta Mediterránea, posee efectosbeneficiosos sobre la hipercolesterolemia, principal factor de riesgo de enfermedadescardiovasculares. La administración de una dieta grasa en conejos provoca laacumulación de colesterol en la membrana celular del espermatozoide y se correlacionacon defectos en la biogénesis del acrosoma y de la cabeza en general. Este incrementode colesterol interfiere con el normal funcionamiento de la gameta masculina y podría sercausa de infertilidad masculina. Interesantemente, la administración de aceite de oliva aestos animales mejoró los parámetros alterados por la ingesta grasa.Nuestro interés reside en estudiar la vía intracelular de colesterol en testículo deconejos bajo diferentes dietas experimentales. El efecto beneficioso del aceite de oliva anivel celular no ha sido estudiado a nivel celular/molecular

Early Post-treatment Prostate-specific Antigen at 4 Weeks and Abiraterone and Enzalutamide Treatment for Advanced Prostate Cancer: An International Collaborative Analysis.

Background Declines in prostate-specific antigen (PSA) levels at 12wk are used to evaluate treatment response in metastatic castration-resistant prostate cancer (mCRPC). PSA fall by ≥30% at 4wk (PSA4w30) has been reported to be associated with better outcome in a single-centre cohort study.Objective To evaluate clinical relevance of early PSA decline in mCRPC patients treated with next-generation hormonal treatments (NGHTs) such as abiraterone and enzalutamide.Design, setting, and participants This was a retrospective multicentre analysis. Eligible patients received NGHT for mCRPC between 6 January 2006 and 31 December 2017 in 13 cancer centres worldwide, and had PSA levels assessed at baseline and at 4 and/or 12wk after treatment. PSA response was defined as a ≥30% decline (progression as a ≥25% increase) from baseline.Outcome measurements and statistical analysis Association with overall survival (OS) was analysed using landmark multivariable Cox regression adjusting for previous chemotherapy, including cancer centre as a shared frailty term.Results and limitations We identified 1358 mCRPC patients treated with first-line NGHT (1133 had PSA available at 4wk, and 948 at both 4 and 12wk). Overall, 583 (52%) had a PSA4w30; it was associated with longer OS (median: 23; 95% confidence interval [CI]: 21-25) compared with no change (median: 17; 95% CI: 15-18) and progression (median: 13; 95% CI: 10-15). A PSA12w30 was associated with lower mortality (median OS 22 vs 14; hazard ratio=0.57; 95% CI=0.48-0.67; p<0.001). PSA4w30 strongly correlated with PSA12w30 (ρ=0.91; 95% CI=0.90-0.92; p<0.001). In total, 432/494 (87%) with a PSA4w30 achieved a PSA12w30. Overall, 11/152 (7%) patients progressing at 4wk had a PSA12w30 (1% of the overall population).Conclusions PSA changes in the first 4wk of NGHT therapies are strongly associated with clinical outcome from mCRPC and can help guide early treatment switch decisions.Patient summary Prostate-specific antigen changes at 4wk after abiraterone/enzalutamide treatment are important to determine patients' outcome and should be taken into consideration in clinical practice

Where myth and archaeology meet: Discovering the Gorgon Medusa's Lair.

Here we report the discovery of ceramic fragments that form part of a Gorgoneion, a ceramic image representation of the Gorgon Medusa. The fragments were found in a deep part of Gorham's Cave, well known to ancient mariners as a natural shrine, between the 8th and 2nd century BCE. We discuss the context of this discovery, both within the inner topography of the cave itself, and also the broader geographical context. The discovery is situated at the extreme western end of the Mediterranean Sea, where it meets the Atlantic Ocean. The location was known to ancient mariners as the northern Pillar of Herakles, which marked the end of the known world. We relate the discovery, and its geographical and chronological context, to Greek legends that situated the lair of the Gorgon sisters at a location which coincides with the physical attributes and geographical position of Gorham's Cave. We thus provide, uniquely, a geographical and archaeological context to the myth of Perseus and the slaying of the Gorgon Medusa

NKG2D expression in CD4+ T lymphocytes as a marker of senescence in the aged immune system

Human aging is characterized by changes in the immune system which have a profound impact on the T-cell compartment. These changes are more frequently found in CD8+ T cells, and there are not well-defined markers of differentiation in the CD4+ subset. Typical features of cell immunosenescence are characteristics of pathologies in which the aberrant expression of NKG2D in CD4+ T cells has been described. To evaluate a possible age-related expression of NKG2D in CD4+ T cells, we compared their percentage in peripheral blood from 100 elderly and 50 young adults. The median percentage of CD4+ NKG2D+ in elders was 5.3% (interquartile range (IR): 8.74%) versus 1.4% (IR: 1.7%) in young subjects (p < 0.3 × 10−10). CD28 expression distinguished two subsets of CD4+ NKG2D+ cells with distinct functional properties and differentiation status. CD28+ cells showed an immature phenotype associated with high frequencies of CD45RA and CD31. However, most of the NKG2D+ cells belonged to the CD28null compartment and shared their phenotypical properties. NKG2D+ cells represented a more advanced stage of maturation and exhibited greater response to CMV (5.3 ± 3.1% versus 3.4 ± 2%, p = 0.037), higher production of IFN-γ (40.56 ± 13.7% versus 24 ± 8.8%, p = 0.015), lower activation threshold and reduced TREC content. Moreover, the frequency of the CD4+ NKG2D+ subset was clearly related to the status of the T cells. Higher frequencies of the NKG2D+ subset were accompanied with a gradual decrease of NAIVE and central memory cells, but also with a higher level of more differentiated subsets of CD4+ T cells. In conclusion, CD4+ NKG2D+ represent a subset of highly differentiated T cells which characterizes the senescence of the immune system