Synthesis and In Vitro Studies of Photoactivatable Semisquaraine-type Pt(II) Complexes

Altres ajuts: acord transformatiu CRUE-CSICThe synthesis, full characterization, photochemical properties, and cytotoxic activity toward cisplatin-resistant cancer cell lines of new semisquaraine-type Pt(II) complexes are presented. The synthesis of eight semisquaraine-type ligands has been carried out by means of an innovative, straightforward methodology. A thorough structural NMR and X-ray diffraction analysis of the new ligands and complexes has been done. Density functional theory calculations have allowed to assign the trans configuration of the platinum center. Through the structural modification of the ligands, it has been possible to synthesize some complexes, which have turned out to be photoactive at wavelengths that allow their activation in cell cultures and, importantly, two of them show remarkable solubility in biological media. Photodegradation processes have been studied in depth, including the structural identification of photoproducts, thus justifying the changes observed after irradiation. From biological assessment, complexes C7 and C8 have been demonstrated to behave as promising photoactivatable compounds in the assayed cancer cell lines. Upon photoactivation, both complexes are capable of inducing a higher cytotoxic effect on the tested cells compared with nonphotoactivated compounds. Among the observed results, it is remarkable to note that C7 showed a PI > 50 in HeLa cells, and C8 showed a PI > 40 in A2780 cells, being also effective over cisplatin-resistant A2780cis cells (PI = 7 and PI = 4, respectively). The mechanism of action of these complexes has been studied, revealing that these photoactivated platinum complexes would actually present a combined mode of action, a therapeutically potential advantage. The synthesis, full characterization, photochemical properties, and cytotoxic activity toward cisplatin-resistant cancer cell lines of new semisquaraine-type Pt(II) complexes are presented. Eight semisquaraine-type ligands and their corresponding Pt(II) complexes have been studied. These complexes have turned out to be photoactive at wavelengths that allow their activation in cell cultures. Two of them display remarkable solubility in biological media showing a promising behavior as photoactivatable compounds against several cancer cell lines

Resistin Regulates Pituitary Lipid Metabolism and Inflammation In Vivo and In Vitro

The adipokine resistin is an insulin-antagonizing factor that also plays a regulatory role in inflammation, immunity, food intake, and gonadal function and also regulates growth hormone (GH) secretion in rat adenopituitary cells cultures with the adipokine. Although adipose tissue is the primary source of resistin, it is also expressed in other tissues, including the pituitary. The aim of this study is to investigate the possible action of resistin on the lipid metabolism in the pituitary gland in vivo (rats in two different nutritional status, fed and fast, treated with resistin on acute and a chronic way) and in vitro (adenopituitary cell cultures treated with the adipokine). Here, by a combination of in vivo and in vitro experimental models, we demonstrated that central acute and chronic administration of resistin enhance mRNA levels of the lipid metabolic enzymes which participated on lipolysis and moreover inhibiting mRNA levels of the lipid metabolic enzymes involved in lipogenesis. Taken together, our results demonstrate for the first time that resistin has a regulatory role on lipid metabolism in the pituitary gland providing a novel insight in relation to the mechanism by which this adipokine can participate in the integrated control of lipid metabolism.Sara Borrell Postdoctoral program; BFU 2011 and CIBER Obesidad y Nutricion (Instituto de Salud Carlos Tercero (ISCIII), Ministerio de Ciencia e Innovacion). Juan de la Cierva Program (Ministerio de Educacion y Ciencia)S

Modulation of Pore Shape and Adsorption Selectivity by Ligand Functionalization in a Series of “rob”-like Flexible Metal-Organic Frameworks

We report the synthesis of a new family of four new isoreticular metal–organic frameworks (MOFs) based on Cu–Cu paddle-wheel building units. The four MOFs contain 1D microchannels modulated by chemical functionalisation of a dicarboxylate ligand or the use of different bis-4,40-pyridyl-like connectors behaving as ancillary linkers. A deep analysis of their CO2, H2 and CH4 adsorption properties, combining both experimental and grand canonical Monte Carlo isotherms as well as in situ synchrotron X-ray diffraction, shows variable adsorption behaviour towards the studied gases, with some materials acting as molecular sieves with virtually infinite selectivity.This work was supported by the Junta de Andalucía (FQM-1484), Red Guipuzcoana de Ciencia, Tecnolgía e Innovación (OF188/2017) and University of the Basque Country (GIU14/01, GIU17/013, EHUA16/32). The authors acknowledge technical and human support provided by SGIker of UPV/EHU and European funding (ERDF and ESF). D. F.-J. thanks the Royal Society for funding through a University Research Fellowship and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (NanoMOFdeli), ERC-2016-COG 726380

Implantación de metodologías de aprendizaje y evaluación continua en la docencia de la Edafología en el ámbito de la ingeniería agronómica

[SPA] El objetivo fundamental de este trabajo es la evaluación de la implantación de metodologías de enseñanza-aprendizaje en la materia de Edafología en diferentes grados del ámbito agronómico y analizar los resultados académicos obtenidos en cada uno de los grados. El Grupo de Innovación edu-SOIL (UPM) aprovechando los recursos de las TIC, con materiales interactivos de consulta y apoyo de Webquest para elaborar un trabajo de curso, ha establecido un proceso de enseñanza aprendizaje acorde con los sistemas metodológicos previstos en el EEES. Se presentan en el trabajo, además de una breve recopilación de la metodología aplicada, la evolución de las tasas de eficiencia y éxito a lo largo de 2-3 años desde la implantación de los planes de estudio. Se pone de manifiesto la influencia de la estructura de cada plan de estudios en los resultados alcanzados así como la influencia del número de ECTS en la impartición de la materia. [ENG] The main objective of this study was to evaluate the implementation of teaching-learning methodologies in the field of Soil Science in different degrees of the agronomic ambits and to analyze the results obtained in each degree. The edu-SOIL Innovation Group (UPM) taking advantage of TIC resources, using interactive course material and using a Webquest for a class project has established a process of teaching and learning in line with the methodological systems under the European system. This work presents a brief description of the methodology used along with the evolution of efficiency and success rates over 2-3 years since the implementation of the curriculum. The study shows the influence of the structure of each curriculum in the results achieved and also the effect of the number of ECTS in teaching the subject

Inhibition of ATG3 ameliorates liver steatosis by increasing mitochondrial function

Non-alcoholic fatty liver disease (NAFLD) is a major health threat in both developed and developing countries and is a precursor of the more advanced liver diseases, including non-alcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. Currently, understanding the multiple and complex molecular pathways implicated in NAFLD onset and progression is a major priority. The transcription factor p63, which belongs to a family comprising p53, p63, and p73,1 is one of many factors that contributes to the development of liver steatosis. The role of p63 as a tumor suppressor and in cell maintenance and renewal is well studied, but we have recently reported that it is also relevant in the control of lipid metabolism.2 p63 encodes multiple isoforms that can be grouped into 2 categories; isoforms with an acidic transactivation domain (TA) and those without this domain (domain negative). The TAp63α isoform is elevated in the liver of animal models of NAFLD as well as in liver biopsies from obese patients with NAFLD. Furthermore, downregulation of p63α in the liver attenuates liver steatosis in diet-induced obese (DIO) mice, while the activation of TAp63α increases hepatic fat content, mediated by the activation of IKKβ and endoplasmic reticulum stress.2 A specialized form of autophagy that degrades lipid droplets, termed “lipophagy”, is a major pathway of lipid mobilization in hepatocytes. Lipophagy is elevated in hepatoma cells upon exposure to free fatty acids,3 and reduces the fatty acid load in mouse hepatocytes.4 Its impairment has been associated with the development of fatty liver and insulin resistance3,5; in contrast, the autophagic flux is increased during the activation of hepatic stellate cells.6 In the present study, we used an unbiased proteomics approach to gain insight into novel proteins modulating lipid metabolism in the liver of mice with genetic knockdown or overexpression of TAp63α. We found that autophagy-related gene 3 (ATG3) was upregulated by TAp63α activation and downregulated after p63α inhibition. ATG3 is elevated in several animal models of NAFLD and in the liver of patients with NAFLD. Genetic overexpression of ATG3 increased the lipid load in hepatocytes, while its repression alleviated TAp63α- and diet-induced steatosis. ATG3 exerted its role in lipid metabolism by regulating SIRT1 and mitochondrial function. Collectively, these findings identify ATG3 as a novel factor implicated in the development of steatosisThis work has been supported by grants from FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación (PA: RTI2018-095134-B-100; DS and LH: SAF2017-83813-C3-1-R; MLMC: RTC2019-007125-1; CD: BFU2017-87721; ML: RTI2018–101840-B-I00; GS; PID2019-104399RB-I00; RN: RTI2018-099413-B-I00 and RED2018-102379-T; MLMC: SAF2017-87301-R; TCD: RTI2018-096759-A-100), FEDER/Instituto de Salud Carlos III (AGR: PI19/00123), Xunta de Galicia (ML: 2016-PG068; RN: 2015-CP080 and 2016-PG057), Fundación BBVA (RN, GS and MLM), Proyectos Investigación en Salud (MLMC: DTS20/00138), Sistema Universitario Vasco (PA: IT971-16); Fundación Atresmedia (ML and RN), Fundación La Caixa (M.L., R.N. and M.C.), Gilead Sciences International Research Scholars Program in Liver Disease (MVR), Marató TV3 Foundation (DS: 201627), Government of Catalonia (DS: 2017SGR278) and European Foundation for the Study of Diabetes (RN and GS). This research also received funding from the European Community’s H2020 Framework Programme (ERC Synergy Grant-2019-WATCH- 810331, to RN, VP and MS). Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Hepáticas y Digestivas (CIBERehd) and CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem). CIBERobn, CIBERehd and CIBERdem are initiatives of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644)S

Management of acute diverticulitis with pericolic free gas (ADIFAS). an international multicenter observational study

Background: There are no specific recommendations regarding the optimal management of this group of patients. The World Society of Emergency Surgery suggested a nonoperative strategy with antibiotic therapy, but this was a weak recommendation. This study aims to identify the optimal management of patients with acute diverticulitis (AD) presenting with pericolic free air with or without pericolic fluid. Methods: A multicenter, prospective, international study of patients diagnosed with AD and pericolic-free air with or without pericolic free fluid at a computed tomography (CT) scan between May 2020 and June 2021 was included. Patients were excluded if they had intra-abdominal distant free air, an abscess, generalized peritonitis, or less than a 1-year follow-up. The primary outcome was the rate of failure of nonoperative management within the index admission. Secondary outcomes included the rate of failure of nonoperative management within the first year and risk factors for failure. Results: A total of 810 patients were recruited across 69 European and South American centers; 744 patients (92%) were treated nonoperatively, and 66 (8%) underwent immediate surgery. Baseline characteristics were similar between groups. Hinchey II-IV on diagnostic imaging was the only independent risk factor for surgical intervention during index admission (odds ratios: 12.5, 95% CI: 2.4-64, P =0.003). Among patients treated nonoperatively, at index admission, 697 (94%) patients were discharged without any complications, 35 (4.7%) required emergency surgery, and 12 (1.6%) percutaneous drainage. Free pericolic fluid on CT scan was associated with a higher risk of failure of nonoperative management (odds ratios: 4.9, 95% CI: 1.2-19.9, P =0.023), with 88% of success compared to 96% without free fluid ( P <0.001). The rate of treatment failure with nonoperative management during the first year of follow-up was 16.5%. Conclusion: Patients with AD presenting with pericolic free gas can be successfully managed nonoperatively in the vast majority of cases. Patients with both free pericolic gas and free pericolic fluid on a CT scan are at a higher risk of failing nonoperative management and require closer observation

Creencias y actitudes del alumnado universitario hacia la violencia de género

Introducción: La violencia de género es un grave problema de salud pública que requiere la intervención, entre otros, de personal sanitario. Los profesionales señalan la falta de conocimientos como una de las dificultades para afrontarlo. Se han puesto de manifiesto actitudes y percepciones erróneas en el alumnado universitario debido a una formación inadecuada o insuficiente. Nuestro objetivo ha sido evaluar las creencias y actitudes sobre la violencia de género en estudiantes de la Universidad de Santiago de Compostela. Material y métodos: Un total de 491 estudiantes de medicina, enfermería, derecho y criminología de la Universidad de Santiago de Compostela completaron un cuestionario de 30 preguntas, voluntario y anónimo. Resultados: La mayoría de los participantes en la encuesta (70,9%) eran mujeres, con una edad media de 22,7 años. Aunque el 53,6% del alumnado había recibido formación previa, los datos muestran que los estudiantes tienen algunas ideas equivocadas sobre la violencia de género. Casi el 96% considera que es un problema importante en nuestra sociedad y cree que debe mejorarse la atención a las víctimas. Cerca del 90% se mostró en contra de que se considerase un asunto privado, apoyando la denuncia de estos casos por parte del personal sanitario. Conclusiones: Se muestra la necesidad de ofrecer más oportunidades educativas sobre la violencia de género, sobre todo entre el alumnado de aquellas profesiones implicadas en el abordaje de este problema. Una correcta preparación de los futuros profesionales mejorará la detección precoz y el tratamiento de las víctimas.Introduction: Gender violence is a major public health problem that requires the intervention of health personnel, among others. Professionals indicate that lack of knowledge is one of the main difficulties of facing this problem. The attitudes and misperceptions among university students might be due to inadequate or insufficient training. The aim of this study was to evaluate the beliefs and attitudes towards gender violence among students of the University of Santiago de Compostela. Material and methods: A total of 491 undergraduate students (Medicine, Nursing, Criminology and Law) of the University of Santiago de Compostela completed an anonymous 30-item questionnaire. Results: Most (70.9%) participants in the survey were women, with a mean age of 22.7 years. Although 53.6% of students had received previous training, data show that they have some misperceptions on gender violence. Nearly 96% consider it as an important problem in our society, and believe that attention to the victims has to be improved. Almost 90% of respondents disagreed about considering it a private matter, supporting the legal complaint by health personnel. Conclusions: Data shows the necessity to offer more educational opportunities on gender violence, especially to students of those professions involved in this problem. An appropriate education of the future professionals would improve the detection and treatment of the victims

Factors Affecting Fatty Acid Composition of Holstein Cow’s Milk

Milk fatty acid composition has gained the interest of both manufacturers and consumers during recent years. The present paper aimed to perform an analysis of C14:0, C16:0, C18:0, C18:1, saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA) and short chain fatty acid (SCFA) concentration in cow’s milk in relation to the type of ration, parity, lactation phase and season. Cows’ milk from animals being fed total mixed rations, including corn silage, had higher C14:0, C16:0 and SFA concentrations than those being fed pasture-based rations but lower concentrations of C18:0 and PUFA. Comparing to 1st parity cows, 2nd and 3rd parity animals had higher SFA and SCFA concentrations in milk. With respect to spring, C14:0, C16:0 and SFA concentrations increased in summer, autumn and winter while MUFA, PUFA and SCFA concentrations decreased. Considering the lactation phase, C14:0, C16:0 and SFA concentrations decreased in fresh cows with ketosis comparing to healthy fresh cows and increased in peak, mid and late lactation. C18:0, C18:1 and MUFA follow the opposite trend. The milk fatty acid profile varies significantly through the studied effects. The fact that the fatty acid profile is associated with animal health, organoleptic properties of milk or even methane production highlights the importance of studying factors that affect its variation

Factors Affecting Fatty Acid Composition of Holstein Cow’s Milk

Milk fatty acid composition has gained the interest of both manufacturers and consumers during recent years. The present paper aimed to perform an analysis of C14:0, C16:0, C18:0, C18:1, saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA) and short chain fatty acid (SCFA) concentration in cow’s milk in relation to the type of ration, parity, lactation phase and season. Cows’ milk from animals being fed total mixed rations, including corn silage, had higher C14:0, C16:0 and SFA concentrations than those being fed pasture-based rations but lower concentrations of C18:0 and PUFA. Comparing to 1st parity cows, 2nd and 3rd parity animals had higher SFA and SCFA concentrations in milk. With respect to spring, C14:0, C16:0 and SFA concentrations increased in summer, autumn and winter while MUFA, PUFA and SCFA concentrations decreased. Considering the lactation phase, C14:0, C16:0 and SFA concentrations decreased in fresh cows with ketosis comparing to healthy fresh cows and increased in peak, mid and late lactation. C18:0, C18:1 and MUFA follow the opposite trend. The milk fatty acid profile varies significantly through the studied effects. The fact that the fatty acid profile is associated with animal health, organoleptic properties of milk or even methane production highlights the importance of studying factors that affect its variation

AMPK-dependent mechanisms but not hypothalamic lipid signaling mediates GH-secretory responses to GHRH and ghrelin

This work has been supported by grants from Ministerio de Ciencia e Innovación (CD: BFU2017-87721; MT-S: BFU2017-83934-P; ML: RTI2018-101840-B-I00); “la Caixa” Foundation (ID 100010434), under the agreement LCF/PR/HR19/52160022 (ML)), Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición (CIBERobn). CIBERobn is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain supported by FEDER funds. Financial support from the Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2019-2022-ED431G 2019/02) and the European Union (European Regional Development Fund-ERDF), is gratefully acknowledged. The research leading to these results has also received funding from the European Community’s Seventh Framework Program under grant agreements (FP7/2007-2013: n° 245009: NeuroFAST).GH (growth hormone) secretion/action is modulated by alterations in energy homeostasis, such as malnutrition and obesity. Recent data have uncovered the mechanism by which hypothalamic neurons sense nutrient bioavailability, with a relevant contribution of AMPK (AMP-activated protein kinase) and mTOR (mammalian Target of Rapamycin), as sensors of cellular energy status. However, whether central AMPK-mediated lipid signaling and mTOR participate in the regulation of pituitary GH secretion remains unexplored. We provide herein evidence for the involvement of hypothalamic AMPK signaling, but not hypothalamic lipid metabolism or CPT-1 (carnitine palmitoyltransferase I) activity, in the regulation of GH stimulatory responses to the two major elicitors of GH release in vivo, namely GHRH (growth hormone–releasing hormone) and ghrelin. This effect appeared to be GH-specific, as blocking of hypothalamic AMPK failed to influence GnRH (gonadotropin-releasing hormone)-induced LH (luteinizing hormone) secretion. Additionally, central mTOR inactivation did not alter GH responses to GHRH or ghrelin, nor this blockade affected LH responses to GnRH in vivo. In sum, we document here for the first time the indispensable and specific role of preserved central AMPK, but not mTOR, signaling, through a non-canonical lipid signaling pathway, for proper GH responses to GHRH and ghrelin in vivo.Depto. de Genética, Fisiología y MicrobiologíaFac. de Ciencias BiológicasTRUEpu