The interleukin-6 and noradrenaline mediated inflammation-stress feedback mechanism is dysregulated in metabolic syndrome: Effect of exercise

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MS) is a metabolic disorder associated with obesity, type-II diabetes, and "low grade inflammation", with the concomitant increased risk of cardiovascular events. Removal of the inflammatory mediator signals is a promising strategy to protect against insulin resistance, obesity, and other problems associated with MS such as cardiovascular disease. The aim of the present investigation was to determine the "inflammatory and stress status" in an experimental model of MS, and to evaluate the effect of a program of habitual exercise and the resulting training-induced adaptation to the effects of a single bout of acute exercise.</p> <p>Methods</p> <p>Obese Zucker rats (fa/fa) were used as the experimental model of MS, and lean Zucker rats (Fa/fa) were used for reference values. The habitual exercise (performed by the obese rats) consisted of treadmill running: 5 days/week for 14 weeks, at 35 cm/s for 35 min in the last month. The acute exercise consisted of a single session of 25-35 min at 35 cm/s. Circulating concentrations of IL-6 (a cytokine that regulates the inflammatory and metabolic responses), CRP (a systemic inflammatory marker), and corticosterone (CTC) (the main glucocorticoid in rats) were determined by ELISA, and that of noradrenaline (NA) was determined by HPLC. Glucose was determined by standard methods.</p> <p>Results</p> <p>The genetically obese animals showed higher circulating levels of glucose, IL-6, PCR, and NA compared with the control lean animals. The habitual exercise program increased the concentration of IL-6, PCR, NA, and glucose, but decreased that of CTC. Acute exercise increased IL-6, CRP, and NA in the sedentary obese animals, but not in the trained obese animals. CTC was increased after the acute exercise in the trained animals only.</p> <p>Conclusion</p> <p>Animals with MS present a dysregulation in the feedback mechanism between IL-6 and NA which can contribute to the systemic low-grade inflammation and/or hyperglycaemia of MS. An inappropriate exercise intensity can worsen this dysregulation, contributing to the metabolic, inflammatory, and stress disorders associated with MS. Habitual exercise (i.e., training) induces a positive adaptation in the response to acute exercise.</p

Practical guide to single-protein AFM nanomechanical spectroscopy mapping: insights and pitfalls as unraveled by all-atom MD simulations on immunoglobulin G

Atomic force microscopy is an invaluable characterization tool in almost every biophysics laboratory. However, obtaining atomic/sub-nanometer resolution on single proteins has thus far remained elusive - a feat long achieved on hard substrates. In this regard, nanomechanical spectroscopy mapping may provide a viable approach to overcome this limitation. By complementing topography with mechanical properties measured locally, one may thus enhance spatial resolution at the single-protein level. In this work, we perform all-atom molecular dynamics simulations of the indentation process on a single immunoglobulin G (IgG) adsorbed on a graphene slab. Our simulations reveal three different stages as a function of strain: a noncontact regime - where the mechanical response is linked to the presence of the water environment - followed by an elastic response and a final plastic deformation regime. In the noncontact regime, we are able to identify hydrophobic/hydrophilic patches over the protein. This regime provides the most local mechanical information that allows one to discern different regions with similar height/topography and leads to the best spatial resolution. In the elastic regime, we conclude that the Young modulus is a well-defined property only within mechanically decoupled domains. This is caused by the fact that the elastic deformation is associated with a global reorganization of the domain. Differences in the mechanical response are large enough to clearly resolve domains within a single protein, such as the three subunits forming the IgG. Two events, unfolding or protein slipping, are observed in the plastic regime. Our simulations allow us to characterize these two processes and to provide a strategy to identify them in the force curves. Finally, we elaborate on possible challenges that could hamper the interpretation of such experiments/simulations and how to overcome them. All in all, our simulations provide a detailed picture of nanomechanical spectroscopy mapping on single proteins, showing its potential and the challenges that need to be overcome to unlock its full potentialJ.G.V. acknowledges funding from a Marie Sklodowska-Curie Fellowship within the Horizon 2020 framework (Grant No. DLV-795286) and the Swiss National Science Foundation (Grant No. CRSK-2 190731/1). R.P. acknowledges support from the Spanish MINECO (Grant No. MAT2017-83273-R) and from the Ministerio de Ciencia e Innovación (MICINN) through the “María de Maeztu” Programme for Units of Excellence in R&D (Grant No. CEX2018-000805-M). R.G. acknowledges funding from the MICINN (Grant No. PID2019-106801GB-I00) and Comunidad de Madrid Grant No. S2018/NMT-4443 (Tec4Bio-CM). We thankfully acknowledge the computer resources, technical expertise, and assistance provided by the Red Española de Supercomputación (RES) at the Minotauro and CTE-Power9 supercomputers (BSC, Barcelona). We thank Dr. Alejandro Martín-González for fruitful discussion

Programa de intervención psicológica en futbolistas : evaluación de habilidades psicológicas mediante el CPRD

Psychological training is a form of sports training that is gradually inserting itself into the work methods of many athletes and sports teams. We present the implementation of a psychological training programme whose goal is for athletes to learn psychological techniques and strategies and apply them to improving their psychological skills, both during training and competition; we also sought to ascertain whether there were any differences between the CPRD scores taken at the start of the intervention and those taken at the end of it. The sample consisted of 22 footballers ages 14 to 18 from a professional football club who compete in the children's and junior categories. The psychological intervention was conducted for five months through individualised (voluntary) work and group (obligatory) work. The results indicate that there were no significant differences between the initial and final scores on the different factors of the CPRD

Study of antitumor activity in breast cell lines using silver nanoparticles produced by yeast

In the present article, we describe a study of antitumor activity in breast cell lines using silver nanoparticles (Ag NPs) synthesized by a microbiological method. These Ag NPs were tested for their antitumor activity against MCF7 and T47D cancer cells and MCF10-A normal breast cell line. We analyzed cell viability, apoptosis induction and endocytosis activity of those cell lines and we observed that the effects of the biosynthesized Ag NPs were directly related with the endocytosis activity. Moreover, Ag NPs had higher inhibition efficacy in tumor lines than in normal lines of breast, which is due to the higher endocytic activity of tumor cells comparing to normal cells. In this way, we are demonstrating that biosynthesized Ag NPs can be an alternative for the treatment of tumors.Fil: Ortega, Francisco Gabriel. Universidad de Granada. Centro de Genómica e Investigación Oncológica; EspañaFil: Fernández Baldo, Martín Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Química de San Luis; ArgentinaFil: Fernández, Jorge Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Química de San Luis; ArgentinaFil: Serrano, Maria J.. Universidad de Granada. Centro de Genómica e Investigación Oncológica; EspañaFil: Sanz Ferramola, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Química de San Luis; ArgentinaFil: Diaz Mochón, Juan J.. Universidad de Granada. Centro de Genómica e Investigación Oncológica; EspañaFil: Lorente, José Antonio. Universidad de Granada. Centro de Genómica e Investigación Oncológica; EspañaFil: Raba, Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Química de San Luis; Argentin

Mediterranean-type diet and brain structural change from 73 to 76 years in a Scottish cohort

STUDY FUNDING The data were collected by a Research into Ageing programme grant; research continues as part of the Age UK–funded Disconnected Mind project. The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1), with funding from the BBSRC and Medical Research Council. Imaging and image analysis was performed at the Brain Research Imaging Centre (sbirc.ed.ac.uk/), Edinburgh, supported by the Scottish Funding Council SINAPSE Collaboration. Derivation of mean cortical thickness measures was funded by the Scottish Funding Council’s Postdoctoral and Early Career Researchers Exchange Fund awarded by SINAPSE to David Alexander Dickie. L.C.A.C. acknowledges funding from the Scottish Government's Rural and Environment Science and Analytical Services (RESAS) division.Peer reviewedPublisher PD

Simulating high-pressure surface reactions with molecular beams

Using a reactive molecular beam with high kinetic energy ($E_{kin}$) it is possible to speed gas-surface reactions involving high activation barriers ($E_{act}$), which would require elevated pressures ($P_0$) if a random gas with a Maxwell-Boltzmann distribution is used. By simply computing the number of molecules that overcome the activation barrier in a random gas at $P_0$ and in a molecular beam at $E_{kin}$=$E_{act}$, we establish an $E_{kin}$-$P_0$ equivalence curve, through which we postulate that molecular beams are ideal tools to investigate gas-surface reactions that involve high activation energies. In particular, we foresee the use of molecular beams to simulate gas surface reactions within the industrial-range ($>$ 10 bar) using surface-sensitive Ultra-High Vacuum (UHV) techniques, such as X-ray photoemission spectroscopy (XPS). To test this idea, we revisit the oxidation of the Cu(111) surface combining O$_2$ molecular beams and XPS experiments. By tuning the kinetic energy of the O$_2$ beam in the range 0.24-1 eV we achieve the same sequence of surface oxides obtained in Ambient Pressure Photoemission (AP-XPS) experiments, in which the Cu(111) surface was exposed to a random O$_2$ gas up to 1 mbar. We observe the same surface oxidation kinetics as in the random gas, but with a much lower dose, close to the expected value derived from the equivalence curve

Inflammatory biomarkers and brain health indicators in children with overweight and obesity: The ActiveBrains project

INTRODUCTION: Chronic inflammation plays an important role on the pathogenesis of several cardiovascular and metabolic diseases, as well as on brain function and behaviour. The aim of the present study was to examine the associations between inflammatory biomarkers and a wide range of brain health indicators (i.e., academic performance, executive function, behavioural and emotional functioning, and brain volume) in children with overweight/obesity. METHODS: A total of 107 children (10.0 ± 1.1 years, 41% girls) from the ActiveBrains project were included in the analysis. Five inflammatory biomarkers were analysed in plasma: white blood cell (WBC) count, interleukin-6 (IL-6), interleukin-1beta, tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). Academic performance was assessed by Woodcock-Munoz Tests of Achievement. Executive function was assessed through the Design Fluency Test for cognitive flexibility, the Stroop test for cognitive inhibition, and the Delayed Non-Match-to-Sample task for working memory. Behavioural and emotional functioning was evaluated through the Behavior Assessment System for Children (BASC) questionnaire. Total and regional brain volume was assessed by magnetic resonance imaging. RESULTS: IL-6 was inversely associated with adaptive skills (beta = -0.228; p = 0.030), while TNF-alpha was related to mathematics (beta = -0.198; p = 0.034). In addition, CRP was positively associated with externalizing (beta = 0.246; p = 0.046) and internalizing problems (beta = 0.234; p = 0.039), as well as the behavioural symptoms index (beta = 0.236; p = 0.047). However, these significant associations disappeared after multiple comparisons correction. Inflammatory biomarkers were not associated with executive function and total brain volumes. Regarding regional brain analyses, WBC was positively associated with gray matter volume in the left middle temporal gyrus (beta = 0.387; p < 0.001, k = 44), and CRP was positively associated with gray matter volume in the right superior temporal gyrus (beta = 0.439; p < 0.001, k = 29). Additionally, when adjusting by total brain volume, CRP was positively associated with gray matter volume in the right supplementary motor cortex (beta = 0.453; p < 0.001, k = 51). Moreover, both, IL-6 (beta = 0.366; p < 0.001, k = 81) and TNF-alpha (beta = 0.368; p < 0.001, k = 62) were positively associated with white matter volume around the right inferior frontal gyrus pars opercularis, while CRP was inversely associated with white matter volume around the left superior frontal gyrus (beta = -0.482; p < 0.001, k = 82). After adjusting by total brain volume, CRP was also inversely associated with white matter volume in 3 additional clusters (beta ranging from -0.473 to -0.404; p < 0.001, k = 87). CONCLUSIONS: Inflammation was slightly associated with brain health (i.e., academic performance, behavioural and emotional functioning and regional brain volume) in children with overweight or obesity. Further larger longitudinal and interventional studies are warranted to elucidate the short-term and long-term effect of systemic low-grade inflammation on children's brain health

Present status and perspective on the future use of aflatoxin biocontrol products

Aflatoxin contamination of important food and feed crops occurs frequently in warm tropical and subtropical regions. The contamination is caused mainly by Aspergillus flavus and A. parasiticus. Aflatoxin contamination negatively affects health and trade sectors and causes economic losses to agricultural industries. Many pre- and post-harvest technologies can limit aflatoxin contamination but may not always reduce aflatoxin concentrations below tolerance thresholds. However, the use of atoxigenic (non-toxin producing) isolates of A. flavus to competitively displace aflatoxin producers is a practical strategy that effectively limits aflatoxin contamination in crops from field to plate. Biocontrol products formulated with atoxigenic isolates as active ingredients have been registered for use in the US, several African nations, and one such product is in final stages of registration in Italy. Many other nations are seeking to develop biocontrol products to protect their crops. In this review article we present an overview of the biocontrol technology, explain the basis to select atoxigenic isolates as active ingredients, describe how formulations are developed and tested, and describe how a biocontrol product is used commercially. Future perspectives on formulations of aflatoxin biocontrol products, along with other important topics related to the aflatoxin biocontrol technology are also discussed.Fil: Moral, Juan. Universidad de Córdoba; EspañaFil: Garcia-Lopez, Maria Teresa. Universidad de Córdoba; EspañaFil: Camiletti, Boris Xavier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Departamento de Recursos Naturales. Cátedra de Microbiología Agrícola; ArgentinaFil: Jaime, Ramon. University of California at Davis; Estados UnidosFil: Michailides, Themis J.. University of California at Davis; Estados UnidosFil: Bandyopadhyay, Ranajit. International Institute of Tropical Agriculture; NigeriaFil: Ortega-Beltran, Alejandro. International Institute of Tropical Agriculture; Nigeri

Dietary intake of bioactive ingredients impacts liver and adipose tissue transcriptomes in a porcine model of prepubertal early obesity

Global prevalence of obesity has increased to epidemic proportions over the past 40 years, with childhood obesity reaching alarming rates. In this study, we determined changes in liver and adipose tissue transcriptomes of a porcine model for prepubertal early obesity induced by a high-calorie diet and supplemented with bioactive ingredients. A total of 43 nine-weeks-old animals distributed in four pens were fed with four different dietary treatments for 10 weeks: a conventional diet; a western-type diet; and a western-type diet with Bifidobacterium breve and rice hydrolysate, either adding or not omega-3 fatty acids. Animals fed a western-type diet increased body weight and total fat content and exhibited elevated serum concentrations of cholesterol, whereas animals supplemented with bioactive ingredients showed lower body weight gain and tended to accumulate less fat. An RNA-seq experiment was performed with a total of 20 animals (five per group). Differential expression analyses revealed an increase in lipogenesis, cholesterogenesis and inflammatory processes in animals on the western-type diet while the supplementation with bioactive ingredients induced fatty acid oxidation and cholesterol catabolism, and decreased adipogenesis and inflammation. These results reveal molecular mechanisms underlying the beneficial effects of bioactive ingredient supplementation in an obese pig model.This work was supported by CDTI (Centro para el desarrollo Tecnológico e Industrial, Spain), Project reference: IPT-20111008, and Generalitat de Catalunya grant 2017SGR1719. M. Ballester is financially supported by a Ramon y Cajal contract (RYC-2013-12573) from the Spanish Ministry of Economy and Competitiveness. We wish to thank all of the members of the IRTA institution who contributed to the generation of the animal material used in this work

Ultra-Performance Liquid Chromatography-Ion Mobility Separation-Quadruple Time-of-Flight MS (UHPLC-IMS-QTOF MS) Metabolomics for Short-Term Biomarker Discovery of Orange Intake: A Randomized, Controlled Crossover Study

A major problem with dietary assessments is their subjective nature. Untargeted metabolomics and new technologies can shed light on this issue and provide a more complete picture of dietary intake by measuring the profile of metabolites in biological samples. Oranges are one of the most consumed fruits in the world, and therefore one of the most studied for their properties. The aim of this work was the application of untargeted metabolomics approach with the novel combination of ion mobility separation coupled to high resolution mass spectrometry (IMS-HRMS) and study the advantages that this technique can bring to the area of dietary biomarker discovery, with the specific case of biomarkers associated with orange consumption (Citrus reticulata) in plasma samples taken during an acute intervention study (consisting of a randomized, controlled crossover trial in healthy individuals). A total of six markers of acute orange consumption, including betonicines and conjugated flavonoids, were identified with the experimental data and previous literature, demonstrating the advantages of ion mobility in the identification of dietary biomarkers and the benefits that an additional structural descriptor, as the collision cross section value (CCS), can provide in this area