The Extra Virgin Olive Oil phenolic compounds () oleacein and () oleocanthal inhibit tumor cell autophagy

Es una comunicación a congreso internacional en formato póster.Our group has recently shown that the antitumor Extra Virgin Olive Oil phenolic compounds (—)oleocanthal and (—)oleacein also behave as antiangiogenic agents. Interestingly, it has been described that phenolic compounds found in the Mediterranean diet affect the autophagy pathway. Based on this background, we studied the modulatory effects of (—)oleocanthal and (—)oleacein on tumor cell autophagy. Methodologically, the tumor cell lines MDAMB231, MCF7 and HT1080 cell lines were used in in vitro cellular and molecular studies of the autophagy flux and key mediators of this process, and High Content Screening (HCS) System using Perkin Elmer Operetta for single-cell analysis was performed in these cells. Interestingly, (—)oleocanthal and (—)oleacein repressed the autophagy flux of MDAMB231 and MCF7 submitted to autophagy inducing conditions (severe starving) at doses in the low micromolar range. In addition, key autophagy mediators, like LC3 or WIPI2 proteins, were dramatically reduced in the same settings, as seen in immunohistochemical studies. Furthermore, preliminary results of HCS in tumor cells revealed depletory effects on autophagy by using specifics dyes for this process at the single-cell level. Altogether, our results point to a drastic inhibitory effect of (—)oleocanthal and (—)oleacein on tumor cell autophagy at low doses.[Grants: PID2022-138181OB-I00, PID2019-105010RB-I00 and RTI2018-098560-BC22 (Spanish Government), UMA18-FEDERJA-220, and PY20_00257 (Andalusian Government and FEDER). Funds from BIO 267 (Andalusian Government) M.B. is supported by “Juan de la Cierva – Incorporation Program” (IJC2018-037657-I), Spanish Ministry of Science and Innovation, Spain.]. Supported with a a help from the «II Plan Propio de Investigación, Transferencia y Divulgación Científica de la UMA», Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

The synthetic molecule stauprimide impairs cell growth and migration in triple-negative breast cancer

Stauprimide, a semi-synthetic derivative of staurosporine, is known mainly for its potent differentiation-enhancing properties in embryonic stem cells. Here, we studied the effects of stauprimide in cell growth and migration of triple-negative breast cancer cells in vitro, evaluating its potential antitumoral activity in an orthotopic mouse model of breast cancer in vivo. Our results from survival curves, EdU incorporation, cell cycle analysis and annexin-V detection in MDA-MB-231 cells indicated that stauprimide inhibited cell proliferation, arresting cell cycle in G2/M without induction of apoptosis. A decrease in the migratory capability of MDA-MB-231 was also assessed in response to stauprimide. In this work we pointed to a mechanism of action of stauprimide involving the modulation of ERK1/2, Akt and p38 MAPK signalling pathways, and the downregulation of MYC in MDA-MB-231 cells. In addition, orthotopic MDA-MB-231 xenograft and 4T1 syngeneic models suggested an effect of stauprimide in vivo, increasing the necrotic core of tumors and reducing metastasis in lung and liver of mice. Together, our results point to the promising role of stauprimide as a putative therapeutic agent in triple-negative breast cancer.MRI experiments were performed in the ICTS “NANBIOSIS”, more specifically in the U28 Unit at the Andalusian Centre for Nanomedicine & Biotechnology (BIONAND). Cell cultures were performed in the Cell Culture Service at the Central Support Services of Research (SCAI) of the University of Málaga. // Partial funding for open access charge: Universidad de Málaga / CBUA

A comparative study of the antiangiogenic activity of hydroxytyrosyl alkyl ethers

Versión preprint del manuscrito de los autores, publicado finalmente en: Food Chemistry 333 (2020) 127476 con DOI: 10.1016/j.foodchem.2020.127476The phenolic compound hydroxytyrosol and its derivatives are responsible for some of the health benefits of the intake of virgin olive oil, having shown antiangiogenic properties. In this study, we explored the antiangiogenic potential of six synthetic hydroxytyrosyl alkyl ethers (HT C1, C2, C4, C6, C8 and C12). Our results showed that all compounds affected endothelial cell viability in vitro at low micromolar doses. In addition, compounds HT C1, C2, C4 and C6 inhibited endothelial cell migration and formation of tubular-like structures. In these assays, hydroxytyrosyl hexyl ether (HT C6) exhibited the most potent inhibitory activity in vitro, activating as well apoptosis in endothelial cells. Furthermore, the antiangiogenic activity of HT C6 was confirmed in vivo in the chick chorioallantoic membrane assay. Hence, we present hydroxytyrosol synthetic derivative HT C6 as a new antiangiogenic compound and as a good candidate for an antiangiogenic drug in the treatment of angiogenesisdependent diseases.This work was supported by the Spanish Ministry of Science, Innovation and Universities (grants AGL2007-66373 and PID2019- 105010RB-I00), Andalusian Government and FEDER (P12-CTS-1507, UMA18-FEDERJA-220 and funds from group BIO 267), as well as funds from the University of Málaga (“Plan Propio de Investigación y Transferencia”). The “CIBER de Enfermedades Raras” and “CIBER de Enfermedades Cardiovasculares” are initiatives from the ISCIII (Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

El Bucio : revista digital del CEP Tenerife Sur

Experiencia en el IES Los Cardones con alumnado de 3º ESO que forman parte del Proyecto CLIL/AICLE con el Huerto Escolar como eje vertebrador y trabajando de manera interdisciplinar desde diferentes materias en este nivel de la ESO. A partir de los criterios de evaluación 7 y 10 de la materia Geografía e Historia, y viendo la necesidad de que el alumnado del centro valorase la importancia de la agricultura en general, pero también entendiese las dificultades que tiene el sector primario en las Islas Canarias y de que asimilara las virtudes de la agricultura ecológica, se opta por plantar en diciembre lechugas en el huerto, y que en el tiempo que tardan en crecer, se pudiese trabajar en las materias de Inglés, Biología, Matemáticas, Educación Física y Geografía e Historia. Asignaturas que forman parte de las materias CLIL de este grupo de tercero, aspectos de salud, nutrición, dieta equilibrada, vocabulario específico, redacción correcta de recetas de cocina, estadísticas, y como no, el sector primario. Todo esto desde el bilingüismo propio del CLIL. La motivación última del alumnado es saber que esas lechugas que plantan y posteriormente recogen ellos mismos las utilizan para preparar ensaladas que se venden en el centro durante un recreo. A un precio simbólico, lo recaudado se destina al proyecto del centro dentro de la Red Canaria de Escuelas Solidarias, y por tanto, a ayudar a los demás.ES

Angioprevention of Urologic Cancers by Plant-Derived Foods.

The number of cancer cases worldwide keeps growing unstoppably, despite the undeniable advances achieved by basic research and clinical practice. Urologic tumors, including some as prevalent as prostate, bladder or kidney tumors, are no exceptions to this rule. Moreover, the fact that many of these tumors are detected in early stages lengthens the duration of their treatment, with a significant increase in health care costs. In this scenario, prevention offers the most cost-effective long-term strategy for the global control of these diseases. Although specialized diets are not the only way to decrease the chances to develop cancer, epidemiological evidence support the role of certain plant-derived foods in the prevention of urologic cancer. In many cases, these plants are rich in antiangiogenic phytochemicals, which could be responsible for their protective or angiopreventive properties. Angiogenesis inhibition may contribute to slow down the progression of the tumor at very different stages and, for this reason, angiopreventive strategies could be implemented at different levels of chemoprevention, depending on the targeted population. In this review, epidemiological evidence supporting the role of certain plant-derived foods in urologic cancer prevention are presented, with particular emphasis on their content in bioactive phytochemicals that could be used in the angioprevention of cancer

Inhibition of Endothelial Inflammatory Response by HT-C6, a Hydroxytyrosol Alkyl Ether Derivative

Hydroxytyrosol (HT) is a bioactive phenolic compound naturally present in olives and extra virgin olive oil (EVOO) which is described as an antioxidant, antitumoral and antiangiogenic molecule. Previous studies of semi-synthetic HT-derivatives presented the hydroxytyrosyl alkyl ether HT-C6 as one of the most potent derivatives studied in the context of antioxidant, anti-platelet and antiangiogenic assays, but its direct effect on inflammation was not reported. In this work, we use RT-qPCR measure of gene expression, protein analysis by Western-blot and immunofluorescence techniques, adhesion and migration functional assays and single-cell monitoring of reactive oxygen species (ROS) in order to explore in vitro the ability of HT-C6 to interfere in the inflammatory response of endothelial cells (ECs). Our results showed that HT-C6 strongly reduces the TNF-α-induced expression of vascular cell adhesion molecule 1 (VCAM1), intercellular cell adhesion molecule 1 (ICAM1), E-selectin (SELE), C-C motif chemokine ligand 2 and 5 (CCL2 and CCL5) in HUVECs, impairing the chemotactic and adhesion potential of these cells towards THP-1 monocytes in vitro. In this work, we define a mechanism of action underlying the anti-inflammatory effect of HT-C6, which involves the abrogation of nuclear factor kappa B (NF-κB) pathway activation in ECs. These results, together with the ability of HT-C6 to reduce ROS formation in ECs, point to this compound as a promising HT-derivative to be tested in the treatment of atherosclerosis

Prosthetic Valve Candida spp. Endocarditis: New Insights Into Long-term Prognosis—The ESCAPE Study

International audienceBackground: Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with international guidelines based on expert recommendations supporting the combination of surgery and subsequent azole treatment.Methods: We retrospectively analyzed PVE-C cases collected in Spain and France between 2001 and 2015, with a focus on management and outcome.Results: Forty-six cases were followed up for a median of 9 months. Twenty-two patients (48%) had a history of endocarditis, 30 cases (65%) were nosocomial or healthcare related, and 9 (20%) patients were intravenous drug users. "Induction" therapy consisted mainly of liposomal amphotericin B (L-amB)-based (n = 21) or echinocandin-based therapy (n = 13). Overall, 19 patients (41%) were operated on. Patients <66 years old and without cardiac failure were more likely to undergo cardiac surgery (adjusted odds ratios [aORs], 6.80 [95% confidence interval [CI], 1.59-29.13] and 10.92 [1.15-104.06], respectively). Surgery was not associated with better survival rates at 6 months. Patients who received L-amB alone had a better 6-month survival rate than those who received an echinocandin alone (aOR, 13.52; 95% CI, 1.03-838.10). "Maintenance" fluconazole therapy, prescribed in 21 patients for a median duration of 13 months (range, 2-84 months), led to minor adverse effects.Conclusion: L-amB induction treatment improves survival in patients with PVE-C. Medical treatment followed by long-term maintenance fluconazole may be the best treatment option for frail patients

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective