Religion and Innovation in Europe: Implications for Product Life-Cycle Management

This paper analyzes the relationship between religion and innovation in Europe. To the best knowledge of the authors, no paper has been published about the association of religion with innovation and innovative products and services, at an individual level, for all the countries that belong to the European Union. This is the main goal of our paper. The results show that the orientation of innovativeness depends on religion. This study contains a segmentation of the main religions in Europe, taking into account their innovative profile. Connecting the characteristics of the religious segments found and the innovations life-cycle concept, companies have a tool to manage different innovations’ evolutive stages taking into consideration the religion of their customers. The European policy-makers, still dominated by a traditional innovation approach, gain a demand-side perspective to improve citizen’s innovativeness awareness and acceptance. Finally, religiosity does not seem to have a very strong relationship with attitudes towards innovation once we control for religious affiliation

Melatonin as an adjuvant to antiangiogenic cancer treatments

Melatonin is a hormone with different functions, antitumor actions being one of the most studied. Among its antitumor mechanisms is its ability to inhibit angiogenesis. Melatonin shows antiangiogenic effects in several types of tumors. Combination of melatonin and chemotherapeutic agents have a synergistic effect inhibiting angiogenesis. One of the undesirable effects of chemotherapy is the induction of pro-angiogenic factors, whilst the addition of melatonin is able to overcome these undesirable effects. This protective effect of the pineal hormone against angiogenesis might be one of the mechanisms underlying its anticancer effect, explaining, at least in part, why melatonin administration increases the sensitivity of tumors to the inhibitory effects exerted by ordinary chemotherapeutic agents. Melatonin has the ability to turn cancer totally resistant to chemotherapeutic agents into a more sensitive chemotherapy state. Definitely, melatonin regulates the expression and/or activity of many factors involved in angiogenesis which levels are affected (either positively or negatively) by chemotherapeutic agents. In addition, the pineal hormone has been proposed as a radiosensitizer, increasing the oncostatic effects of radiation on tumor cells. This review serves as a synopsis of the interaction between melatonin and angiogenesis, and we will outline some antiangiogenic mechanisms through which melatonin sensitizes cancer cells to treatments, such as radiotherapy or chemotherapy.Funding: The present study was funded by grants from the Spanish Economy and Competitiveness Ministry (SAF2016-77103-P), from University of Cantabria (Proyectos Puente 2020), and from Instituto de Investigación Sanitaria Valdecilla (IDIVAL) (APG/12)

Melatonin enhances the apoptotic effects and modulates the changes in gene expression induced by docetaxel in MCF 7 human breast cancer cells

Results from clinical trials and multiple in vivo and in vitro studies point to melatonin as a promising adjuvant molecule with many beneficial effects when concomitantly administered with chemotherapy. Melatonin palliates side?effects and enhances the efficacy of chemotherapeutic agents. However, the mechanisms through which melatonin regulates molecular changes induced by chemotherapeutic agents remain largely unknown. In this study, we demonstrated that melatonin enhanced the anti-proliferative and apoptotic responses to low doses of docetaxel in breast cancer cells. Importantly, these effects were more potent when melatonin was added prior to docetaxel. Treatment with 1 µM docetaxel (equivalent to the therapeutic dosage) induced changes in gene expression profiles and melatonin modulated these changes. Specifically, docetaxel downregulated TP53, cyclin-dependent kinase inhibitor 1A (CDKN1A) and cadherin 13 (CDH13), and upregulated mucin 1 (MUC1), GATA binding protein 3 (GATA3) and c-MYC, whereas melatonin counteracted these effects. Melatonin further stimulated the expression of the pro-apoptotic BAD and BAX genes, and enhanced the inhibition of the anti-apoptotic gene BCL-2 induced by docetaxel. The findings of this study suggest that melatonin is a molecule with potential for use as an adjuvant in cancer chemotherapy, which may have implications for designing clinical trials using chemotherapeutic drugs in combination with melatonin.Acknowledgements: The present study was supported by grants from the Spanish Science Technology and Innovation Ministry (grant no. SAF2016 77103-P) and the Research Institute Valdecilla (grant no. APG/12)

Complementary actions of melatonin on angiogenic factors,the angiopoietin/Tie2 axis and VEGF, in co-cultures of human endothelial and breast cancer cells

Melatonin exerts oncostatic activity in breast cancer through antiangiogenic actions. There, the aim of the present study was to ascertain whether melatonin modulates, in a coordinated action, angiopoietin-1 (ANG-1), ANG-2, their cognate Tie2 receptor and VEGF in co-cultures of human endothelial cells (HUVECs) and breast cancer (MCF-7) cells. To accomplish this we used co-cultures of human breast cancer cells (MCF-7) or non-malignant human mammary epithelial cells (MCF?10A) with endothelial cells (HUVECs). The presence of breast cancer cells increased HUVEC proliferation and 1 mM melatonin prevented this effect. ANG-1, ANG-2 and VEGF levels in co-culture media and mRNA expression were upregulated and Tie2 mRNA expression was downregulated in the HUVECs and MCF-7. Melatonin (1 mM) downregulated ANG-1, ANG-2 and VEGF levels in the co-culture media and mRNA expression in both types of cells and upregulated Tie2 mRNA expression in HUVECs. ANG-1, ANG-2, Tie2 and VEGF mRNA expression were not modified during HUVEC/MCF-10A co-culture. Estradiol (10 nM) increased ANG-1, ANG-2 and VEGF mRNA expression in HUVECs and melatonin (1 mM) counteracted this effect. We conclude that melatonin simultaneously coordinates downregulation of angiopoietins with a reduction in VEGF, which could be an effective therapeutic strategy for blocking tumor angiogenesis.The present study was supported by grants from the Spanish Economy and Competitiveness Ministry (SAF2013-42012-P, SAF2016-77103-P), and from the Instituto de Investigación Sanitaria Valdecilla (IDIVAL) (APG/12)

Melatonin as a Radio-Sensitizer in Cancer

Radiotherapy is one of the treatments of choice in many types of cancer. Adjuvant treatments to radiotherapy try, on one hand, to enhance the response of tumor cells to radiation and, on the other hand, to reduce the side effects to normal cells. Radiosensitizers are agents that increase the effect of radiation in tumor cells by trying not to increase side effects in normal tissues. Melatonin is a hormone produced mainly by the pineal gland which has an important role in the regulation of cancer growth, especially in hormone-dependent mammary tumors. Different studies have showed that melatonin administered with radiotherapy is able to enhance its therapeutic effects and can protect normal cells against side effects of this treatment. Several mechanisms are involved in the radiosensitization induced by melatonin: increase of reactive oxygen species production, modulation of proteins involved in estrogen biosynthesis, impairment of tumor cells to DNA repair, modulation of angiogenesis, abolition of inflammation, induction of apoptosis, stimulation of preadipocytes differentiation and modulation of metabolism. At this moment, there are very few clinical trials that study the therapeutic usefulness to associate melatonin and radiotherapy in humans. All findings point to melatonin as an effective adjuvant molecule to radiotherapy in cancer treatment

Single neuron electroporation in manipulating and measuring the central nervous system

The development and application of single neuron electroporation largely advanced the use of traditional genetics in investigations of the central nervous system. This quick and accurate manipulation of the brain at individual neuron level allowed the gain and loss of functional analyses of different genes and/or proteins. This manuscript reviewed the development of the technique and discussed some technical aspects in practical manipulations. Then the manuscript summarized the potential applications with this technique. Last but not least, the technique showed prospective future when combined with other modern methods in neuroscience research

Melatonin modulation of radiation-induced molecular changes in MCF-7 human breast cancer cells

Radiation therapy is an important component of cancer treatment scheduled for cancer patients, although it can cause numerous deleterious effects. The use of adjuvant molecules aims to limit the damage in normal surrounding tissues and to enhance the effects of radiation therapy either killing tumor cells or slowing down their growth. Melatonin, an indoleamine released by the pineal gland, behaves as a radiosensitizer in breast cancer since it enhances the therapeutic effects of ionizing radiation and mitigates side effects on normal cells. However, the molecular mechanisms through which melatonin modulates the molecular changes triggered by radiotherapy remain mostly unknown. Here we report that melatonin potentiated the antiproliferative effect of radiation in MCF-7 cells. Treatment with ionizing radiation induced changes in expression of many genes. Out of a total of twenty-five genes altered by radiation, melatonin potentiated changes in thirteen of them, whereas reverted the effect in another ten cases. Among them, melatonin elevated the levels of PTEN and NME1, whereas counteracted the induction by radiation of SNAI2, ERBB2, AKT, SERPINE1, SFN, PLAU, ATM and N3RC1. We also analyzed the expression of several microRNAs and found that melatonin enhanced the effect of radiation on the levels of miR-20a, miR-19a, miR-93, miR-20b, miR-29a. Rather surprisingly, radiation induced miR-17, miR-141 and miR-15a but melatonin treatment prior to radiation counteracted this stimulatory effect. Radiation alone enhanced the expression of the cancer suppressor miR-34a, and melatonin strongly stimulated this effect. Melatonin further enhanced the radiationmediated inhibition of Akt. Finally, in an in vivo assay, melatonin restrained new vascularization in combination with ionizing radiation. Our results confirm that melatonin blocks many of the undesirable effects of ionizing radiation in MCF-7 cells and enhances changes that lead to optimed treatment resultsAcknowledgments: The present study was funded by grants from the Spanish Economy and Competitiveness Ministry (SAF2016-77103-P), from Universidad de Cantabria (Proyectos Puente 2020) with the participation of the Consejería de Universidades, Igualdad, Cultura y Deporte del Gobierno de Cantabria, and from Instituto de Investigación Sanitaria Valdecilla (IDIVAL) (APG/12)