Fondos de inversión en renta variable, un estudio práctico del caso BBVA.

Los fondos de inversión son uno de los instrumentos de ahorro más populares, es por ello que su evolución ha ido en sentido creciente. En los fondos de inversión intervienen 5 elementos: los Partícipes, la Sociedad Gestora, la Entidad Depositaria, las Participaciones del fondo de inversión y, la Comisión Nacional del Mercado de Valores (CNMV). Según la vocación inversora del fondo, es decir, según en qué activos se invierte, se distinguen fondos de renta fija, de renta variable, de renta mixta, globales, garantizados, por compartimentos, y, otros fondos. A la hora de la colocación del ahorro en los fondos de inversión, hay que soportar unos gastos conocidos como comisiones, y, además, en el momento en el que el partícipe retira el dinero, el resultado obtenido debe integrarse en la base imponible del IRPF tributando en función del valor inicial de la inversión. Con los fondos de inversión también se puede proceder a la realización de operaciones,tales como la suscripción y reembolso de participaciones y, los traspasos. Para conocer más a fondo los fondos de inversión, es necesario analizar la relación rentabilidad-riesgo a través de las conocidas medidas de eficiencia de gestión: Alfa Jensen, Ratio Sharpe e Índice Treynor

Development of in vitro and in vivo tools to evaluate the antiangiogenic potential of melatonin to neutralize the angiogenic effects of VEGF and breast cancer cells: CAM assay and 3D endothelial cell spheroids

Melatonin is a molecule with different antitumor actions in breast cancer and has been described as an inhibitor of vascular endothelial growth factor (VEGF). Despite the recognition of the key role exerted by VEGF in tumor angiogenesis, limitations arise when developing models to test new antiangiogenic molecules. Thus, the aim of this study was to develop rapid, economic, high capacity and easy handling angiogenesis assays to test the antiangiogenic effects of melatonin and demonstrate its most effective dose to neutralize and interfere with the angiogenic sprouting effect induced by VEGF and MCF-7. To perform this, 3D endothelial cell (HUVEC) spheroids and a chicken embryo chorioallantoic membrane (CAM) assay were used. The results showed that VEGF and MCF-7 were able to stimulate the sprouting of the new vessels in 3D endothelial spheroids and the CAM assay, and that melatonin had an inhibitory effect on angiogenesis. Specifically, as the 1 mM pharmacological dose was the only effective dose able to inhibit the formation of ramifications around the alginate in the CAM assay model, this inhibition was shown to occur in a dose-dependent manner. Taken together, these techniques represent novel tools for the development of antiangiogenic molecules such as melatonin, with possible implications for the therapy of breast cancer.Funding: This work was funded in part by PE-0106–2019 from the Consejería de Salud de la Junta de Andalucía, C19047–2018 from Fundación Unicaja and UMA18-FEDERJA-042 from UMA-FEDER & ALIANZA MIXTA ANDALUCÍA-ROCHE. Alicia González González is a recipient of a postdoctoral grant Margarita Salas (RMS-08) from European Union-NextGenerationEU, Spanish Ministry of Universities and Recovery Transformation and Resilience Plan, through a call from University of Cantabria. Aurora Laborda Illanes is a recipient of a predoctoral grant, PFIS-ISCIII (FI19–00112), co-funded by the Fondo Social Europeo (FSE). Lidia Sanchez Alcoholado is a recipient of a postdoctoral grant (RH-0026–2021) from the Consejería de Salud y Familia (co-funded by the Fondo Europeo de Andalucía 2014–2020, Andalucía, Spain). Daniel Castellano Castillo is a recipient of a postdoctoral grant Sara Borrell (CD21/00164) from Instituto de Salud Carlos III

A Promising Challenge in the Link between Melatonin and Breast Cancer: Exploring the Microbiome-Gut-Brain Axis

In this chapter, we describe the possible link between gut microbiota, melatonin, and breast cancer disease. It is widely described that changes in melatonin production due to circadian disruption is one of the causes of breast cancer. In addition, recently it is described that dysbiosis caused by changes in the gut microbiota composition could be as well constitute an important factor to induce breast cancer. The dysbiosis process, in turn, induces the stimulation of kynurenine pathway, leading to reduced circulating melatonin levels. Therefore, in this chapter we deep into the relationship between circadian disruption, dysbiosis, and breast cancer disease. This constitutes an important step in the therapeutic approach and prevention of this pathology

The Role of the Gut Microbiome in Colorectal Cancer Development and Therapy Response

Colorectal cancer (CRC) is the third most common cancer worldwide and the leading cause of cancer-related deaths. Recently, several studies have demonstrated that gut microbiota can alter CRC susceptibility and progression by modulating mechanisms such as inflammation and DNA damage, and by producing metabolites involved in tumor progression or suppression. Dysbiosis of gut microbiota has been observed in patients with CRC, with a decrease in commensal bacterial species (butyrate-producing bacteria) and an enrichment of detrimental bacterial populations (pro-inflammatory opportunistic pathogens). CRC is characterized by altered production of bacterial metabolites directly involved in cancer metabolism including short-chain fatty acids and polyamines. Emerging evidence suggests that diet has an important impact on the risk of CRC development. The intake of high-fiber diets and the supplementation of diet with polyunsaturated fatty acids, polyphenols and probiotics, which are known to regulate gut microbiota, could be not only a potential mechanism for the reduction of CRC risk in a primary prevention setting, but may also be important to enhance the response to cancer therapy when used as adjuvant to conventional treatment for CRC. Therefore, a personalized modulation of the pattern of gut microbiome by diet may be a promising approach to prevent the development and progression of CRC and to improve the efficacy of antitumoral therapy.This work was supported by PI15/00256 from the Institute of Health “Carlos III” (ISCIII), co-funded by the Fondo Europeo de Desarrollo Regional-FEDER. Maria Isabel Queipo-Ortuño was supported by the “Miguel Servet Type II” program (CPI13/00003, ISCIII, Spain; co-funded by the Fondo Europeo de Desarrollo Regional-FEDER), and by the “Nicolas Monardes” research program of the Consejería de Salud (C-0030-2018, Junta de Andalucía, Spain. Bruno Ramos Molina was supported by a “Miguel Servet Type I” program (CP19/00098, ISCIII, Spain; co-funded by the Fondo Europeo de Desarrollo Regional-FEDER). Lidia Sanchez-Alcoholado was recipient of a predoctoral grant (PE-0106-2019) from the Consejería de Salud y Familia (co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Andalucia, Spain). Aurora Laborda-Illanes was recipient of a predoctoral grant PFIS-ISCIII (FI19-00112) co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Madrid, Spain.Ye

A New Paradigm in the Relationship between Melatonin and Breast Cancer: Gut Microbiota Identified as a Potential Regulatory Agent.

In this review we summarize a possible connection between gut microbiota, melatonin production, and breast cancer. An imbalance in gut bacterial population composition (dysbiosis), or changes in the production of melatonin (circadian disruption) alters estrogen levels. On the one hand, this may be due to the bacterial composition of estrobolome, since bacteria with β-glucuronidase activity favour estrogens in a deconjugated state, which may ultimately lead to pathologies, including breast cancer. On the other hand, it has been shown that these changes in intestinal microbiota stimulate the kynurenine pathway, moving tryptophan away from the melatonergic pathway, thereby reducing circulating melatonin levels. Due to the fact that melatonin has antiestrogenic properties, it affects active and inactive estrogen levels. These changes increase the risk of developing breast cancer. Additionally, melatonin stimulates the differentiation of preadipocytes into adipocytes, which have low estrogen levels due to the fact that adipocytes do not express aromatase. Consequently, melatonin also reduces the risk of breast cancer. However, more studies are needed to determine the relationship between microbiota, melatonin, and breast cancer, in addition to clinical trials to confirm the sensitizing effects of melatonin to chemotherapy and radiotherapy, and its ability to ameliorate or prevent the side effects of these therapies

Breast and Gut Microbiota Action Mechanisms in Breast Cancer Pathogenesis and Treatment

In breast cancer (BC) the employment of sequencing technologies for metagenomic analyses has allowed not only the description of the overall metagenomic landscape but also the specific microbial changes and their functional implications. Most of the available data suggest that BC is related to bacterial dysbiosis in both the gut microenvironment and breast tissue. It is hypothesized that changes in the composition and functions of several breast and gut bacterial taxa may contribute to BC development and progression through several pathways. One of the most prominent roles of gut microbiota is the regulation of steroid-hormone metabolism, such as estrogens, a component playing an important role as risk factor in BC development, especially in postmenopausal women. On the other hand, breast and gut resident microbiota are the link in the reciprocal interactions between cancer cells and their local environment, since microbiota are capable of modulating mucosal and systemic immune responses. Several in vivo and in vitro studies show remarkable evidence that diet, probiotics and prebiotics could exert important anticarcinogenic effects in BC. Moreover, gut microbiota have an important role in the metabolism of chemotherapeutic drugs and in the activity of immunogenic chemotherapies since they are a potential dominant mediator in the response to cancer therapy. Then, the microbiome impact in BC is multi-factorial, and the gut and breast tissue bacteria population could be important in regulating the local immune system, in tumor formation and progression and in therapy response and/or resistance.This work was supported in part by PE-0106-2019 from the Consejería de Salud de la Junta de Andalucía, C19047-2018 from Fundación Unicaja and UMA18-FEDERJA-042 from UMA-FEDER. Maria Isabel Queipo-Ortuño is recipient of a “Miguel Servet Type II” program (CPI13/00003) from ISCIII, co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Madrid, Spain and also belongs to the regional “Nicolas Monardes” research program of the Consejería de Salud (C-0030-2018, Junta de Andalucía, Spain. Aurora Laborda-Illanes was recipient of a predoctoral grant PFIS-ISCIII (FI19-00112) co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Madrid, Spain. Lidia Sanchez-Alcoholado was recipient of a predoctoral grant (PE-0106-2019) from the Consejería de Salud y Familia (co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Andalucia, Spain).Ye

Gut Microbiota-Mediated Inflammation and Gut Permeability in Patients with Obesity and Colorectal Cancer

Obesity is considered an important factor that increases the risk of colorectal cancer (CRC). So far, the association of gut microbiota with both obesity and cancer has been described independently. Nevertheless, a specific obesity-related microbial profile linked to CRC development has not been identified. The aim of this study was to determine the gut microbiota composition in fecal samples from CRC patients with (OB-CRC) and without obesity (L-CRC) compared to the microbiota profile present in non-obese healthy controls (L-HC), in order to unravel the possible relationship between gut microbiota and microbial-derived metabolite trimethylamine N-oxide (TMAO), the inflammatory status, and the intestinal permeability in the context of obesity-associated CRC. The presence of obesity does not induce significant changes in the diversity and richness of intestinal bacteria of CRC patients. Nevertheless, OB-CRC patients display a specific gut microbiota profile characterized by a reduction in butyrate-producing bacteria and an overabundance of opportunistic pathogens, which in turn could be responsible, at least in part, for the higher levels of proinflammatory cytokine IL-1β, the deleterious bacterial metabolite TMAO, and gut permeability found in these patients. These results suggest a possible role of obesity-related gut microbiota in the development of CRC, which could give new clues for the design of new diagnostic tools for CRC prevention.This work was supported by PI15/00256 from the Institute of Health “Carlos III” (ISCIII), co-funded by the Fondo Europeo de Desarrollo Regional-FEDER. Maria Isabel Queipo-Ortuño was supported by the “Miguel Servet Type II” program (CPI13/00003, ISCIII, Spain; co-funded by the Fondo Europeo de Desarrollo Regional-FEDER), and by the “Nicolas Monardes” research program of the Consejería de Salud (C-0030-2018, Junta de Andalucía, Spain. Bruno Ramos Molina was supported by the “Miguel Servet Type I” program (CP19/00098, ISCIII, Spain; co-funded by the Fondo Europeo de Desarrollo Regional-FEDER). Lidia Sanchez-Alcoholado was recipient of a predoctoral grant (PE-0106-2019) from the Consejería de Salud y Familia (co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Andalucia, Spain). Aurora Laborda-Illanes was recipient of a predoctoral grant PFIS-ISCIII (FI19-00112) co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Madrid, Spain.Ye

Relationships of Gut Microbiota Composition, Short-Chain Fatty Acids and Polyamines with the Pathological Response to Neoadjuvant Radiochemotherapy in Colorectal Cancer Patients.

Emerging evidence has suggested that dysbiosis of the gut microbiota may influence the drug efficacy of colorectal cancer (CRC) patients during cancer treatment by modulating drug metabolism and the host immune response. Moreover, gut microbiota can produce metabolites that may influence tumor proliferation and therapy responsiveness. In this study we have investigated the potential contribution of the gut microbiota and microbial-derived metabolites such as short chain fatty acids and polyamines to neoadjuvant radiochemotherapy (RCT) outcome in CRC patients. First, we established a profile for healthy gut microbiota by comparing the microbial diversity and composition between CRC patients and healthy controls. Second, our metagenomic analysis revealed that the gut microbiota composition of CRC patients was relatively stable over treatment time with neoadjuvant RCT. Nevertheless, treated patients who achieved clinical benefits from RTC (responders, R) had significantly higher microbial diversity and richness compared to non-responder patients (NR). Importantly, the fecal microbiota of the R was enriched in butyrate-producing bacteria and had significantly higher levels of acetic, butyric, isobutyric, and hexanoic acids than NR. In addition, NR patients exhibited higher serum levels of spermine and acetyl polyamines (oncometabolites related to CRC) as well as zonulin (gut permeability marker), and their gut microbiota was abundant in pro-inflammatory species. Finally, we identified a baseline consortium of five bacterial species that could potentially predict CRC treatment outcome. Overall, our results suggest that the gut microbiota may have an important role in the response to cancer therapies in CRC patients