Cáncer, inflamación y depresión: alteraciones conductuales, inmunitarias y neuroquímicas producidas por el desarrollo de melanoma B16 en ratones macho

275 p.Existe una gran cantidad de datos en el ámbito de la Psiconeuroinmunología que evidencian que la activación del sistema inmunitario provoca una respuesta sistémica de inflamación que contribuye al desarrollo de síntomas depresivos. El objetivo de este trabajo es estudiar los cambios inmunitarios, fisiológicos y conductuales asociados al desarrollo tumoral de melanoma B16, y determinar si una situación de estrés agudo, altera dichos cambios. Para ello se han utilizando dos cepas de ratones macho (OF1 y C57/BL6) y se han llevado a cabo tres experimentos. La conducta ha sido analizada mediante diferentes pruebas conductuales validadas específicamente para evaluar conductas de tipo depresivo. También se han analizado diferentes parámetros inmunitarios y neuroquímicos como posibles responsables de los efectos que el desarrollo de melanoma B16 produce sobre la conducta.Los resultados obtenidos demuestran que el desarrollo tumoral de melanoma B16 produce conducta depresiva, caracterizada por la manifestación de anhedonia y el incremento de la inmovilidad. Además, se ha observado un aumento de la expresión de citocinas proinflamatorias (IL-6, TNF-¿, IL-1ß e IFN-¿) y de la expresión del enzima IDO, así como una reducción de la actividad monoaminérgica en cerebro. La activación del enzima IDO y/o la reducción del cofactor BH4 podrían ser los mecanismos mediante los cuales las citocinas proinflamatorias alteran la actividad monoaminérgica y posiblemente también la glutamatérgica, para producir conductas depresivas durante el desarrollo tumoral de melanoma B16.27

Graphic proposals for scientific divulgation at Geopark of Las Loras: some examples of structural and karstic geomorphology

RESUMEN El objetivo de este Trabajo Fin de Máster es la elaboración de propuestas gráficas, con una finalidad didáctica y divulgativa, de algunos caracteres geomorfológicos del Geoparque de Las Loras. La importancia del patrimonio geológico y geomorfológico es patente por el interés que, desde antiguo, han despertado las formas de relieve estructural de este espacio, especialmente sus sinclinales colgados que forman amplias mesas que dominan el conjunto y las amplias depresiones diapíricas en las que se ha centrado el poblamiento y los usos agrícolas del suelo. Además de este predominio geomorfológico de lo estructural, también las formas del relieve se han modelado por medio de la karstificación, dando lugar a importantes complejos kársticos subterráneos y superficiales. Este trabajo se ha centrado en el estudio de algunas formas exokársticas menores, quizás las menos espectaculares o llamativas, pero sí ampliamente extendidas por el conjunto de Las Loras, los lapiaces. Con el fin de facilitar el desarrollo del objetivo trazado, la finalidad didáctica y divulgativa, se han elaborado propuestas gráficas que ayuden a comprender las formas y los hechos geomorfológicos, tales como cartografía geomorfológica, bloques-diagrama y un estudio de detalle de lapiaces para las loras de Las Tuerces, Rebolledo de la Torre y Peña Amaya.ABSTRACT The Master´s Final Project goal is the elaboration of graphic proposals, with a didactic and informative purpose, of some Geopark of Las Loras´s geomorphological characters. The importance of the geological and geomorphological heritage is evident as since ancient times, forms of structural relief have awakened in this space, especially its hanging synclines forming large tables that dominate the whole and the wide diapiric depressions in which settlement and agricultural land uses have been centered. Besides this structural geomorphological predominance, the relief forms have been also modelled by karstification, giving rise to important underground and superficial karstic complexes. This work focuses on the study of some minor exokarst forms, perhaps the less spectacular or striking ones, but widely spread accross all loras, the karren. In order to facilitate the development of the outlined goal, the didactic and informative purpose, graphic proposals have been prepared to help to understand the geomorphological forms and facts, such as geomorphological cartography, block-diagrams and a detailed study of karren about the loras de Las Tuerces, Rebolledo de la Torre and Peña Amaya.Máster en Recursos Territoriales y Estrategias de Ordenació

Cáncer, inflamación y depresión: alteraciones conductuales, inmunitarias y neuroquímicas producidas por el desarrollo de melanoma B16 en ratones macho

275 p.Existe una gran cantidad de datos en el ámbito de la Psiconeuroinmunología que evidencian que la activación del sistema inmunitario provoca una respuesta sistémica de inflamación que contribuye al desarrollo de síntomas depresivos. El objetivo de este trabajo es estudiar los cambios inmunitarios, fisiológicos y conductuales asociados al desarrollo tumoral de melanoma B16, y determinar si una situación de estrés agudo, altera dichos cambios. Para ello se han utilizando dos cepas de ratones macho (OF1 y C57/BL6) y se han llevado a cabo tres experimentos. La conducta ha sido analizada mediante diferentes pruebas conductuales validadas específicamente para evaluar conductas de tipo depresivo. También se han analizado diferentes parámetros inmunitarios y neuroquímicos como posibles responsables de los efectos que el desarrollo de melanoma B16 produce sobre la conducta.Los resultados obtenidos demuestran que el desarrollo tumoral de melanoma B16 produce conducta depresiva, caracterizada por la manifestación de anhedonia y el incremento de la inmovilidad. Además, se ha observado un aumento de la expresión de citocinas proinflamatorias (IL-6, TNF-¿, IL-1ß e IFN-¿) y de la expresión del enzima IDO, así como una reducción de la actividad monoaminérgica en cerebro. La activación del enzima IDO y/o la reducción del cofactor BH4 podrían ser los mecanismos mediante los cuales las citocinas proinflamatorias alteran la actividad monoaminérgica y posiblemente también la glutamatérgica, para producir conductas depresivas durante el desarrollo tumoral de melanoma B16.27

Antifungal activity of chitosan oligomers-amino acid conjugate complexes against Fusarium culmorum in spelt (Triticum spelta L.)

Fusarium head blight (FHB) is a complex disease of cereals caused by Fusarium species, which causes severe damages in terms of yield quality and quantity worldwide, and which produces mycotoxin contamination, posing a serious threat to public health. In the study presented herein, the antifungal activity against Fusarium culmorum of chitosan oligomers (COS)–amino acid conjugate complexes was investigated both in vitro and in vivo. The amino acids assayed were cysteine, glycine, proline and tyrosine. In vitro tests showed an enhancement of mycelial growth inhibition, with EC50 and EC90 effective concentration values ranging from 320 to 948 µg·mL−1 and from 1107 to 1407 µg·mL−1 respectively, for the conjugate complexes, as a result of the synergistic behavior between COS and the amino acids, tentatively ascribed to enhanced cell membrane damage originating from lipid peroxidation. Tests on colonies showed a maximum percentage reduction in the number of colonies at 1500 µg·mL−1 concentration, while grain tests were found to inhibit fungal growth, reducing deoxynivalenol content by 89%. The formulation that showed the best performance, i.e., the conjugate complex based on COS and tyrosine, was further investigated in a small-scale field trial with artificially inoculated spelt (Triticum spelta L.), and as a seed treatment to inhibit fungal growth in spelt seedlings. The field experiment showed that the chosen formulation induced a decrease in disease severity, with a control efficacy of 83.5%, while the seed tests showed that the treatment did not affect the percentage of germination and resulted in a lower incidence of root rot caused by the pathogen, albeit with a lower control efficacy (50%). Consequently, the reported conjugate complexes hold enough promise for crop protection applications to deserve further examination in larger field trials, with other Fusarium spp. pathogens and/or Triticum species

Antifungal activity against Fusarium culmorum of stevioside, Silybum marianum seed extracts, and their conjugate complexes

Fusarium head blight (FHB) is a disease that poses a major challenge in cereal production that has important food and feed safety implications due to trichothecene contamination. In this study, the effect of stevioside—a glycoside found in the leaves of candyleaf (Stevia rebaudiana Bertoni)—was evaluated in vitro against Fusarium culmorum (W.G. Smith) Sacc., alone and in combination (in a 1:1 molar ratio) with polyphenols obtained from milk thistle seeds (Silybum marianum (L.) Gaertn). Different concentrations, ranging from 32 to 512 µg·mL−1, were assayed, finding EC50 and EC90 inhibitory concentrations of 156 and 221 µg·mL−1, respectively, for the treatment based only on stevioside, and EC50 and EC90 values of 123 and 160 µg·mL−1, respectively, for the treatment based on the stevioside–polyphenol conjugate complexes. Colony formation inhibition results were consistent, reaching full inhibition at 256 µg·mL−1. Given that synergistic behavior was observed for this latter formulation (SF = 1.43, according to Wadley’s method), it was further assessed for grain protection at storage, mostly directed against mycotoxin contamination caused by the aforementioned phytopathogen, confirming that it could inhibit fungal growth and avoid trichothecene contamination. Moreover, seed tests showed that the treatment did not affect the percentage of germination, and it resulted in a lower incidence of root rot caused by the pathogen in Kamut and winter wheat seedlings. Hence, the application of these stevioside–S. marianum seed extract conjugate complexes may be put forward as a promising and environmentally friendly treatment for the protection of cereal crops and stored grain against FHB

In vitro antifungal activity of chitosan-polyphenol conjugates against Phytophthora cinnamomi

Producción CientíficaPhytophthora cinnamomi is responsible for radical rot in a wide range of hosts, resulting in large economic and ecological losses worldwide. In Spain, it is responsible for diseases such as the oak decline or the chestnut blight. In this study, different polyphenol-stevioside inclusion compounds dispersed in a hydroalcoholic solution of chitosan oligomers have been investigated, with a view to their application as natural bioactive complexes to replace conventional systemic fungicides against this fungus. The polyphenols tested in vitro were curcumin, ferulic acid, gallic acid and silymarin. Three concentrations (125, 250 and 500 µg·mL−1) were assayed, with and without silver nanoparticles (AgNPs), and notable differences were found in the inhibition of mycelium growth, with EC50 and EC90 values ranging from 171 to 373.6 µg·mL−1, and from 446.2 to 963.7 µg·mL−1, respectively. The results obtained showed that the addition of AgNPs, despite their antimicrobial activity, did not always lead to synergies. In the case of P. cinnamomi, an unexpected antagonistic behavior was found for two of the polyphenols (curcumin and silymarin), while an additive behavior for ferulic acid and a synergistic behavior for gallic acid were attained. In view of their inhibitory power, the preparations based on ferulic acid with AgNPs and on silymarin without AgNPs are proposed for applications in crop and forests protection against P. cinnamomi.Junta de Castilla y León - Fondo Europeo de Desarrollo Regional (project VA258P18)Universidad de Zaragoza (project UZ2019-TEC-07

Chronic social instability stress down-regulates IL-10 and up-regulates CX3CR1 in tumor-bearing and non-tumor-bearing female mice

Extensive literature has reported a link between stress and tumor progression, and between both of these factors and mental health. Despite the higher incidence of affective disorders in females and the neurochemical dif-ferences according to sex, female populations have been understudied. The aim of this study was therefore to analyze the effect of stress on tumor development in female OF1 mice. For this purpose, subjects were inoculated with B16F10 melanoma cells and exposed to the Chronic Social Instability Stress (CSIS) model. Behavioral, neurochemical and neuroendocrine parameters were analyzed. Female mice exposed to CSIS exhibited reduced body weight and increased arousal, but there was no evidence of depressive behavior or anxiety. Exposure to CSIS did not affect either corticosterone levels or tumor development, although it did provoke an imbalance in cerebral inflammatory cytokines, decreasing IL-10 expression (IL-6/IL-10 and TNF-alpha/IL-10); chemokines, increasing CX3CR1 expression (CX3CL1/CX3CR1); and glucocorticoid receptors, decreasing GR expression (MR/ GR). In contrast, tumor development did not alter body weight and, although it did alter behavior, it did so to a much lesser extent. Tumor inoculation did not affect corticosterone levels, but increased the MR/GR ratio in the hippocampus and provoked an imbalance in cerebral inflammatory cytokines and chemokines, although differently from stress. These results underscore the need for experimental approaches that allow us to take sex differences into account when exploring this issue, since these results appear to indicate that the female response to stress is mediated by mechanisms different from those often proposed in relation to male mice.This study was supported by the Spanish Ministry of Science, Innovation RTI2018–098264-B-I00 (MCIU/AEI/FEDER, UE), the UPV/EHU GIU18/103 and the PIBA 2019–22 Project Grants

Do prepubertal hormones, 2D:4D index and psychosocial context jointly explain 11-year-old preadolescents' involvement in bullying?

[EN] Background: Bullying is a type of aggressive behavior that occurs repeatedly and intentionally in school environments and where there is a power imbalance. The main objective of this study was to analyze the association that hormones and the psychosocial context jointly have with bullying behavior. Method: Participants were 302 11-year-old preadolescents from the Gipuzkoan cohort of the INMA Project. Bullying was assessed using the Olweus Bully/victim Questionnaire. Prenatal sexual hormones were assessed by calculating 2D:4D ratio and in order to measure prepubertal testosterone and cortisol levels saliva samples were collected within a week of each other. Additionally, various psychosocial factors were evaluated: executive function, family context, school environment and social context. To analyze our complex hypothesis, six metamodels were tested using structural equation modeling. Results: In relation to victims, results showed that victimization was related to worse school environment' perception in boys, and higher stress and conflict in the family in girls. In the case of their involvement in bullying as a bully, lower salivary cortisol levels, worse school environment' perception and lower peers and social support was related to being more frequently involved as a bully in boys, while having more family stress and conflict was related with being a bully in girls. Conclusions: This approach makes it possible not only to explore the different biological and psychosocial factors affect bullying behavior, but also to explore associations between the predictor variables.This study was funded by grants from Instituto de Salud Carlos III (FIS-PI06/0867, FIS-PI09/00090, FIS-PI13/02187, FIS-PI18/01142, FIS-PI18/01237 incl FEDER funds) CIBERESP, Department of Health of the Basque Government (2005111093, 2009111069, 2013111089, 2015111065 and 2018111086), and the Provincial Government of Gipuzkoa (DFG06/002, DFG08/001 and DFG15/221 and DFG 89/17) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). IB would like to thank the Department of Education, Language Policy and Culture of the Government of the Basque Country for a predoctoral research training grant

Efficient microwave-assisted acid hydrolysis of lignocellulosic materials into total reducing sugars in ionic liquids

Different types of lignocellulosic materials (carnauba leaves, macauba shell and pine nut shell) and native cellulose have been studied for the production of total reducing sugars (TRS) through microwave-assisted acid-catalyzed hydrolysis in ionic liquids (ILs). Four reaction media have been assessed: two deep eutectic solvents (DES), choline chloride-oxalic acid (ChCl/ox) and choline chloride-urea (ChCl/urea), and two conventional ionic liquids, tetraethylammonium chloride (TEAC) and tetraethylammonium bromide (TEAB). Five acids (H2SO4, HCl, HNO3, H3PO4andp-toluensulfonic acid) have been evaluated in varying concentrations (5-30%) and time intervals (0-60 min), at different temperatures (100-140°C). Significant TRS production yields (as high as 83.7% in ChCl/ox for carnauba leaves) have been attained for both DES in combination with HNO3 10%, at 120°C for 30 min, with the additional advantage of low furfural and HMF by-products generation

Reactivity and Applications of Singlet Oxygen Molecule

Reactive oxygen species (ROS) are molecules produced in living organisms, in the environment, and in various chemical reactions. The main species include, among others, singlet oxygen (1O2), the superoxide anion radical (•O2−), the hydroxyl radical (HO•), and the hydroperoxyl radical (HOO•). In general, the reactivity of 1O2 is lower than that of HO• but even higher than that of •O2−. Singlet oxygen is the lowest energy excited state of molecular oxygen, but it is also a highly reactive species, which can initiate oxidation reactions of biomolecules such as amino acids, proteins, nucleic acids, and lipids, either by a direct reaction or by the induction of ROS. Singlet oxygen is a highly reactive electrophilic species that reacts with electron-rich molecules and is related to several types of pathologies. To inhibit the oxidation of biomolecules with this species, some substances act as antioxidants by performing a quenching effect. In this chapter, aspects such as its physicochemical properties, methods of generation and detection, as well as the reactivity of this molecule are detailed