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Title:

The role of fatty acid β-oxidation in lymphangiogenesis

Authors:

Wong, Brian W.; Wang, Xingwu; Zecchin, Annalisa; Thienpont, Bernard; Cornelissen, Ivo; Kalucka, Joanna; García-Caballero, Melissa; Missiaen, Rindert; Huang, Hongling; Brüning, Ulrike; Blacher, Silvia; Vinckier, Stefan; Goveia, Jermaine; Knobloch, Marlen; Zhao, Hui; Dierkes, Cathrin; Shi, Chenyan; Hägerling, René; Moral-Dardé, Veronica; Wyns, Sabine; Lippens, Martin; Jessberger, Sebastian; Fendt, Sarah-Maria; Luttun, Aernout; Noel, Agnès; Kiefer, Friedemann; Ghesquière, Bart; Moons, Lieve; Schoonjans, Luc; Dewerchin, Mieke; Eelen, Guy; Lambrechts, Diether; Carmeliet, Peter

Abstract:

The lymphangiogenic factor PROX1 transcriptionally upregulates CPT1A, a rate-controlling enzyme in fatty acid β-oxidation, and this co-regulates lymphatic endothelial cell differentiation by epigenetic control of lymphatic gene expression, demonstrating a role for metabolism in developmental biology.

Published:

2017-02

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Title:

Time-restricted feeding in young men performing resistance training: A randomized controlled trial†

Authors:

Tinsley, Grant M.; Forsse, Jeffrey S.; Butler, Natalie K.; Paoli, Antonio; Bane, Annie A.; La Bounty, Paul M.; Morgan, Grant B.; Grandjean, Peter W.

Abstract:

A randomized controlled trial was conducted to examine eight weeks of resistance training (RT) with and without time- restricted feeding (TRF) in order to assess nutrient intake and changes in body composition and muscular strength in young recreationally active males. The TRF programme consisted of consuming all calories within a four-hour period of time for four days per week, but included no limitations on quantities or types of foods consumed. The RT programme was performed three days per week and consisted of alternating upper and lower body workouts. For each exercise, four sets leading to muscular failure between 8 and 12 repetitions were employed. Research visits were conducted at baseline, four, and eight weeks after study commencement. Measurements of total body composition by dual-energy X-ray absorptiometry and muscle cross-sectional area by ultrasound were obtained. Upper and lower body strength and endurance were assessed, and four-day dietary records were collected. TRF reduced energy intake by ∼650 kcal per day of TRF, but did not affect total body composition within the duration of the study. Cross-sectional area of the biceps brachii and rectus femoris increased in both groups. Effect size data indicate a gain in lean soft tissue in the group that performed RT without TRF (+2.3 kg, d=0.25). Upper and lower body strength and lower body muscular endurance increased in both groups, but effect sizes demonstrate greater improvements in the TRF group. Overall, TRF reduced energy intake and did not adversely affect lean mass retention or muscular improvements with short-term RT in young males.

Published:

2017-02

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Title:

Validating inflammatory bowel disease (IBD) in the Swedish National Patient Register and the Swedish Quality Register for IBD (SWIBREG)

Authors:

Jakobsson, Gustav L.; Sternegård, Emil; Olén, Ola; Myrelid, Pär; Ljung, Rickard; Strid, Hans; Halfvarson, Jonas; Ludvigsson, Jonas F.

Abstract:

BACKGROUND: Both the Swedish National Patient Register (NPR) and the Swedish Quality Register for inflammatory bowel disease (IBD, SWIBREG) are important sources of research data and information. However, the validity of a diagnosis of IBD in these registers is unknown. METHODS: Medical charts of 129 randomly selected patients from the NPR and 165 patients registered both in SWIBREG and the NPR were reviewed. Patients were classified according to standardized criteria for ulcerative colitis (UC), Crohn's disease (CD), or IBD unclassified (IBD-U). Positive predictive values (PPVs) for UC, CD, IBD-U (only SWIBREG), or having any form of IBD were then calculated. RESULTS: For cases with ≥2 diagnoses of IBD in the NPR (hospitalizations or non-primary care outpatient visits), the PPV was 93% (95% CI: 87-97) for any IBD, 79% (66-88) for UC and 72% (60-82) for CD. In UC patients with ≥2 UC diagnoses but never a CD diagnosis, the PPV increased to 90% (77-97). The PPV for CD in patients with ≥2 CD diagnoses but never a UC diagnosis was 81% (67-91)). Combining data from SWIBREG (≥1 record) and the NPR (≥1 record), the PPV was 99% for any IBD (97-100), 96% (89-99) for UC, and 90% (82-96) for CD. CONCLUSION: The validity of the UC, CD, and IBD diagnoses is high in the NPR but even higher when cases were identified both in SWIBREG and the NPR. These results underline the need for a well-functioning Swedish Quality Register for IBD as a complement to the NPR.

Published:

2017-02

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Title:

Adaptive responses of neuronal mitochondria to bioenergetic challenges: Roles in neuroplasticity and disease resistance

Authors:

Raefsky, Sophia M.; Mattson, Mark P.

Abstract:

An important concept in neurobiology is “neurons that fire together, wire together” which means that the formation and maintenance of synapses is promoted by activation of those synapses. Very similar to the effects of the stress of exercise on muscle cells, emerging findings suggest that neurons respond to activity by activating signaling pathways (e.g., Ca2+, CREB, PGC-1α, NF-κB) that stimulate mitochondrial biogenesis and cellular stress resistance. These pathways are also activated by aerobic exercise and food deprivation, two bioenergetic challenges of fundamental importance in the evolution of the brains of all mammals, including humans. The metabolic ‘switch' in fuel source from liver glycogen store-derived glucose to adipose cell-derived fatty acids and their ketone metabolites during fasting and sustained exercise, appears to be a pivotal trigger of both brain-intrinsic and peripheral organ-derived signals that enhance learning and memory and underlying synaptic plasticity and neurogenesis. Brain-intrinsic extracellular signals include the excitatory neurotransmitter glutamate and the neurotrophic factor BDNF, and peripheral signals may include the liver-derived ketone 3-hydroxybutyrate and the muscle cell-derived protein irisin. Emerging findings suggest that fasting, exercise and an intellectually challenging lifestyle can protect neurons against the dysfunction and degeneration that they would otherwise suffer in acute brain injuries (stroke and head trauma) and neurodegenerative disorders including Alzheimer's, Parkinson's and Huntington's disease. Among the prominent intracellular responses of neurons to these bioenergetic challenges are up-regulation of antioxidant defenses, autophagy/mitophagy and DNA repair. A better understanding of such fundamental hormesis-based adaptive neuronal response mechanisms is expected to result in the development and implementation of novel interventions to promote optimal brain function and healthy brain aging.

Published:

2017-01

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Title:

Association of desaturase activity and C-reactive protein in European children

Authors:

Wolters, Maike; Börnhorst, Claudia; Schwarz, Heike; Risé, Patrizia; Galli, Claudio; Moreno, Luis A.; Pala, Valeria; Russo, Paola; Veidebaum, Toomas; Tornaritis, Michael; Fraterman, Arno; De Henauw, Stefaan; Eiben, Gabriele; Lissner, Lauren; Molnár, Dénes; Ahrens, Wolfgang

Abstract:

Desaturase enzymes influence the fatty acid (FA) composition of body tissues and their activity affects the conversion rate of saturated to monounsaturated FA and of polyunsaturated FA (PUFA) to long-chain PUFA. Desaturase activity has further been shown to be associated with inflammation. We investigate the association between delta-9 (D9D), delta-6 (D6D) and delta-5 desaturase (D5D) activity and high-sensitive C-reactive protein (CRP) in young children.

Published:

2017-01

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Title:

Biogenetic and morphofunctional heterogeneity of mitochondria: the case of synaptic mitochondria

Authors:

Fedorovich, Sergei V.; Waseem, Tatyana V.; Puchkova, Ludmila V.

Abstract:

\textlessp\textgreaterThe mitochondria of different cells are different in their morphological and biochemical properties. These organelles generate free radicals during activity, leading inevitably to mitochondrial DNA damage. It is not clear how this problem is addressed in long-lived cells, such as neurons. We propose the hypothesis that mitochondria within the same cell also differ in lifespan and ability to divide. According to our suggestion, cells have a pool of ‘stem' mitochondria with low metabolic activity and a pool of ‘differentiated' mitochondria with significantly shorter lifespans and high metabolic activity. We consider synaptic mitochondria as a possible example of ‘differentiated' mitochondria. They are significantly smaller than mitochondria from the cell body, and they are different in key enzyme activity levels, proteome, and lipidome. Synaptic mitochondria are more sensitive to different damaging factors. It has been established that neurons have a sorting mechanism that sends mitochondria with high membrane potential to presynaptic endings. This review describes the properties of synaptic mitochondria and their role in the regulation of synaptic transmission.\textless/p\textgreater

Published:

2017-01

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Title:

Comparison of the meat metabolite composition of Linwu and Pekin ducks using 600 MHz 1H nuclear magnetic resonance spectroscopy

Authors:

Wang, Xiangrong; Fang, Chengkun; He, Jianhua; Dai, Qiuzhong; Fang, Rejun

Abstract:

In an effort to further understand of the differences of meat flavor and texture between Linwu ducks and Pekin ducks at market age, we investigated the meat metabolite composition of the two breeds of ducks using 600 MHz 1H nuclear magnetic resonance (NMR) spectroscopy. Comprehensive multivariate data analysis including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal projection to latent structure-discriminant analysis (OPLS-DA) were applied to analyze the 1H-NMR profiling data to identify the distinguishing metabolites of breast meat between two breeds of ducks. Compared with 42-d-old Pekin duck meat, breast from 72-d-old Linwu duck has higher concentration of anserine, carnosine, homocarnosine, and nicotinamide, but significantly lower concentration of succinate, creatine, and myo-inositol. These results contribute to a better understanding of the differences in meat metabolite composition between 72-d-old Linwu and 42-d-old Pekin ducks, which could be used to help assess the quality of duck meat as a food. Copyright © 2016 Poultry Science Association Inc.

Published:

2017-01

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Title:

Dissection of individual prostate lobes in mouse models of prostate cancer to obtain high quality RNA

Authors:

Zingiryan, Areg; Farina, Nicholas H; Finstad, Kristiaan H; Stein, Janet L; Lian, Jane B; Stein, Gary S

Abstract:

Genetically engineered mouse models of prostate cancer allow for study of disease progression from localized tumor formation through distal metastasis. The anatomy of the mouse prostate differs dramatically from the human prostate, being composed of four lobe pairs (anterior, dorsal, lateral, and ventral), making the identification and dissection technically challenging. Although the entire murine prostate and surrounding tissue, including urethra, bladder, seminal vesicles, and associated adipose tissue, can be quickly dissected for en bloc analysis, it is necessary to isolate individual prostate lobes for gene expression studies elucidating the molecular mechanisms of prostate cancer. The procedure as described here includes full color images, allowing the researcher to appreciate the unique prostate morphology and tissue manipulation required to harvest individual prostate lobes. Along with removing all extraneous tissue, the procedure allows for direct comparison of the different prostate lobes by established downstream techniques. Importantly, high quality RNA required for next-generation gene expression analysis can only consistently be obtained from ventral and lateral lobes. Finally, preclinical studies using prostate targeted therapies can be monitored specifically in individual prostate lobes on the histological and gene expression studies.

Published:

2017-01

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Title:

Effect of classic ketogenic diet treatment on lipoprotein subfractions in children and adolescents with refractory epilepsy

Authors:

Azevedo de Lima, Patricia; Baldini Prudencio, Mariana; Murakami, Daniela Kawamoto; Pereira de Brito Sampaio, Leticia; Figueiredo Neto, Antonio Martins; Teixeira Damasceno, Nagila Raquel

Abstract:

CONCLUSIONS: KD treatment promotes negative changes in lipoprotein size and phenotype, contributing to atherogenic risk in these patients. Copyright A© 2016 Elsevier Inc. All rights reserved.

Published:

2017-01

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Title:

Genetics of Mitochondrial Disease

Authors:

Saneto, Russell P.

Abstract:

Mitochondria are intracellular organelles responsible for adenosine triphosphate production. The strict control of intracellular energy needs require proper mitochondrial functioning. The mitochondria are under dual controls of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Mitochondrial dysfunction can arise from changes in either mtDNA or nDNA genes regulating function. There are an estimated ∼1500 proteins in the mitoproteome, whereas the mtDNA genome has 37 proteins. There are, to date, ∼275 genes shown to give rise to disease. The unique physiology of mitochondrial functioning contributes to diverse gene expression. The onset and range of phenotypic expression of disease is diverse, with onset from neonatal to seventh decade of life. The range of dysfunction is heterogeneous, ranging from single organ to multisystem involvement. The complexity of disease expression has severely limited gene discovery. Combining phenotypes with improvements in gene sequencing strategies are improving the diagnosis process. This chapter focuses on the interplay of the unique physiology and gene discovery in the current knowledge of genetically derived mitochondrial disease.

Published:

2017-01

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Title:

Glucomannan- and glucomannan plus spirulina-enriched pork affect liver fatty acid profile, LDL receptor expression and antioxidant status in Zucker fa/fa rats fed atherogenic diets

Authors:

González-Torres, Laura; Matos, Cátia; Vázquez-Velasco, Miguel; Santos-López, Jorge A.; Sánchez-Martínez, Iria; García–Fernández, Camino; Bastida, Sara; Benedí, Juana; Sánchez-Muniz, Francisco J.

Abstract:

We evaluated the effects of glucomannan or glucomannan plus spirulina-restructured pork (RP) on liver fatty acid profile, desaturase/elongase enzyme activities and oxidative status of Zucker fa/fa rats for seven weeks. Control (C), glucomannan (G) and glucomannan/spirulina (GS)-RP; HC (cholesterol-enriched control), HG and HGS (cholesterol-enriched glucomannan and glucomannan/spirulina-RP) experimental diets were tested. Increased metabolic syndrome markers were found in C, G and GS rats. Cholesterol feeding increased liver size, fat, and cholesterol and reduced antioxidant enzyme levels and expressions. Cholesterolemia was lower in HG and HGS than in HC. GS vs. G showed higher stearic but lower oleic levels. SFA and PUFA decreased while MUFA increased by cholesterol feeding. The arachidonic/linoleic and docosahexaenoic/alpha-linolenic ratios were lower in HC, HG, and HGS vs. C, G, and GS, respectively, suggesting a delta-6-elongase-desaturase system inhibition. Moreover, cholesterol feeding, mainly in HGS, decreased low-density-lipoprotein receptor expression and the delta-5-desaturase activity and increased the delta-9-desaturase activity. In conclusion, the liver production of highly unsaturated fatty acids was limited to decrease their oxidation in presence of hypercholesterolaemia. Glucomannan or glucomannan/spirulina-RP has added new attributes to their functional properties in meat, partially arresting the negative effects induced by high-fat-high-cholesterol feeding on the liver fatty acid and antioxidant statuses.

Published:

2017-01

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Title:

Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance

Authors:

Lotta, Luca A.; Gulati, Pawan; Day, Felix R.; Payne, Felicity; Ongen, Halit; van de Bunt, Martijn; Gaulton, Kyle J.; Eicher, John D.; Sharp, Stephen J.; Luan, Jian’an; De Lucia Rolfe, Emanuella; Stewart, Isobel D.; Wheeler, Eleanor; Willems, Sara M.; Adams, Claire; Yaghootkar, Hanieh; Forouhi, Nita G.; Khaw, Kay-Tee; Johnson, Andrew D.; Semple, Robert K.; Frayling, Timothy; Perry, John R. B.; Dermitzakis, Emmanouil; McCarthy, Mark I.; Barroso, Inês; Wareham, Nicholas J.; Savage, David B.; Langenberg, Claudia; O’Rahilly, Stephen; Scott, Robert A.

Abstract:

Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin adjusted for BMI, lower HDL cholesterol and higher triglycerides) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy-type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms between common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognised molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important aetiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

Published:

2017-01

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Title:

Lipoprotein-X in cholestatic patients causes xanthomas and promotes foam cell formation in human macrophages

Authors:

Suzuki, Luka; Hirayama, Satoshi; Fukui, Mariko; Sasaki, Makoto; Hiroi, Sadayuki; Ayaori, Makoto; Terai, Shuji; Tozuka, Minoru; Watada, Hirotaka; Miida, Takashi

Abstract:

Published:

2017-01

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Title:

Mitochondria-Associated Membranes Response to Nutrient Availability and Role in Metabolic Diseases

Authors:

Theurey, Pierre; Rieusset, Jennifer

Abstract:

Metabolic diseases are associated with nutrient excess and metabolic inflexibility. Mitochondria and endoplasmic reticulum are important organelles and nutrient sensors, and their dysfunction has been extensively and independently implicated in metabolic diseases. Both organelles interact at sites known as mitochondria-associated membranes (MAMs), in order to exchange metabolites and calcium. Recent evidence indicates that MAM could be a hub of hepatic insulin signaling and nutrient sensing. In this review, we discuss the roles organelle function and communication play in the cell's adaptation to nutrient availability, in both physiology and metabolic diseases. We highlight how dynamic regulation of MAM affects mitochondria physiology and adaptation of cellular metabolism to nutrient availability, and how chronic MAM disruption participates in the metabolic inflexibility associated with metabolic disorders.

Published:

2017-01

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Title:

β-Hydroxybutyrate in the Brain: One Molecule, Multiple Mechanisms

Authors:

Achanta, Lavanya B.; Rae, Caroline D.

Abstract:

© 2016 Springer Science+Business Media New Yorkβ-Hydroxybutyrate (βOHB), a ketone body, is oxidised as a brain fuel. Although its contribution to energy metabolism in the healthy brain is minimal, it is an interesting metabolite which is not only oxidised but also has other direct and collateral effects which make it a molecule of interest for therapeutic purposes. In brain βOHB can be produced in astrocytes from oxidation of fatty acids or catabolism of amino acids and is metabolised in the mitochondria of all brain cell types although uptake across the blood brain barrier is a metabolic control point. βOHB possesses an intrinsic high heat of combustion, making it an efficient mitochondrial fuel, where it can alter the NAD+/NADH and Q/QH2 couples and reduce production of mitochondrial reactive oxygen species. It can directly interact as a signalling molecule influencing opening of K+ channels and regulation of Ca2+ channels. βOHB is an inhibitor of histone deacetylases resulting in upregulation of genes involved in protection against oxidative stress and regulation of metabolism. It interacts with an inflammasome in immune cells to reduce production of inflammatory cytokines and reduce inflammation. Use of βOHB as an efficient neurotherapeutic relies on increasing blood βOHB levels so as to encourage entry of βOHB to the brain. While use of βOHB as a sole therapeutic is currently limited, with employment of a ketogenic diet a more widely used approach, recent development and testing of esterified forms of βOHB have shown great promise, with the approach elevating plasma βOHB while allowing consumption of normal diet. An improved understanding of the mechanisms by which βOHB acts will allow better design of both diet and supplemental interventions.

Published:

2017-01

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Title:

A global approach to rare diseases research and orphan products development: The international rare diseases research consortium (IRDiRC)

Authors:

Cutillo, Christine M.; Austin, Christopher P.; Groft, Stephen C.

Abstract:

Rare diseases present unique challenges to researchers due to the global distribution of patients, complexity and low prevalence of each disease, and limited availability of data. They are also overwhelming and costly for patients, their families, communities, and society. As such, global integration of rare diseases research is necessary to accelerate the understanding, diagnosis, and treatment of rare disorders. The International Rare Diseases Research Consortium (IRDiRC) was born out of that need for a coordinated international community. IRDiRC was launched in 2011 to facilitate cooperation and collaboration on a global scale among the many stakeholders active in rare diseases research to stimulate better coordination, and thereby maximize output of rare diseases research efforts around the world. Members include funders, academic researchers, companies, and patient advocacy organizations all of whom share the common goals and principles of IRDiRC. The overarching objectives of the Consortium are to contribute to the development of 200 new therapies and a means to diagnose most rare diseases, by 2020. As IRDiRC approaches the end of its fifth year, these initial objectives have been largely achieved and new partners from across the globe are joining. This presents the Consortium with the exciting opportunity to set new and even more ambitious goals for the next phase with the ultimate goal of improved health through faster and better diagnostic capabilities and novel therapies for people living with rare diseases and conditions throughout the world.

Published:

2017

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Title:

A high-fat high-sugar diet-induced impairment in place-recognition memory is reversible and training-dependent

Authors:

Tran, Dominic M. D.; Westbrook, R. Frederick

Abstract:

A high-fat high-sugar (HFHS) diet is associated with cognitive deficits in people and produces spatial learning and memory deficits in rodents. Notable, such diets rapidly impair place-, but not object-recognition memory in rats within one week of exposure. Three experiments examined whether this impairment was reversed by removal of the diet, or prevented by pre-diet training. Experiment 1 showed that rats switched from HFHS to chow recovered from the place-recognition impairment that they displayed while on HFHS. Experiment 2 showed that control rats ("Untrained") who were exposed to an empty testing arena while on chow, were impaired in place-recognition when switched to HFHS and tested for the first time. However, rats tested ("Trained") on the place and object task while on chow, were protected from the diet-induce deficit and maintained good place-recognition when switched to HFHS. Experiment 3 examined the conditions of this protection effect by training rats in a square arena while on chow, and testing them in a rectangular arena while on HFHS. We have previously demonstrated that chow rats, but not HFHS rats, show geometry-based reorientation on a rectangular arena place-recognition task (Tran & Westbrook, 2015). Experiment 3 assessed whether rats switched to the HFHS diet after training on the place and object tasks in a square area, would show geometry-based reorientation in a rectangular arena. The protective benefit of training was replicated in the square arena, but both Untrained and Trained HFHS failed to show geometry-based reorientation in the rectangular arena. These findings are discussed in relation to the specificity of the training effect, the role of the hippocampus in diet-induced deficits, and their implications for dietary effects on cognition in people.

Published:

2017

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Title:

A proposal for a study on treatment selection and lifestyle recommendations in chronic inflammatory diseases: A danish multidisciplinary collaboration on prognostic factors and personalised medicine

Authors:

Andersen, V.; Holmskov, U.; Bek Sørensen, S.; Jawhara, M.; Andersen, K.W.; Bygum, A.; Hvid, L.; Grauslund, J.; Wied, J.; Glerup, H.; Fredberg, U.; Villadsen, J.A.; Kjær, S.G.; Fallingborg, J.; Moghadd, S.A.G.R.; Knudsen, T.; Brodersen, J.; Frøjk, J.; Dahlerup, J.F.; Nielsen, O.H.; Christensen, R.; Bo Bojesen, A.; Sorensen, G.L.; Thiel, S.; Færgeman, N.J.; Brandslund, I.; Stensballe, A.; Schmidt, E.B.; Franke, A.; Ellinghaus, D.; Rosenstiel, P.; Raes, J.; Heitmann, B.; Boye, M.; Nielsen, C.L.; Werner, L.; Kjeldsen, J.; Ellingsen, T.

Abstract:

Chronic inflammatory diseases (CIDs), including Crohn’s disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

Published:

2017

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Title:

A scheme for a flexible classification of dietary and health biomarkers

Authors:

Gao, Qian; Praticò, Giulia; Scalbert, Augustin; Vergères, Guy; Kolehmainen, Marjukka; Manach, Claudine; Brennan, Lorraine; Afman, Lydia A.; Wishart, David S.; Andres-Lacueva, Cristina; Garcia-Aloy, Mar; Verhagen, Hans; Feskens, Edith J. M.; Dragsted, Lars O.

Abstract:

Biomarkers are an efficient means to examine intakes or exposures and their biological effects and to assess system susceptibility. Aided by novel profiling technologies, the biomarker research field is undergoing rapid development and new putative biomarkers are continuously emerging in the scientific literature. However, the existing concepts for classification of biomarkers in the dietary and health area may be ambiguous, leading to uncertainty about their application. In order to better understand the potential of biomarkers and to communicate their use and application, it is imperative to have a solid scheme for biomarker classification that will provide a well-defined ontology for the field. In this manuscript, we provide an improved scheme for biomarker classification based on their intended use rather than the technology or outcomes (six subclasses are suggested: food compound intake biomarkers (FCIBs), food or food component intake biomarkers (FIBs), dietary pattern biomarkers (DPBs), food compound status biomarkers (FCSBs), effect biomarkers, physiological or health state biomarkers). The application of this scheme is described in detail for the dietary and health area and is compared with previous biomarker classification for this field of research.

Published:

2017

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Title:

A very low calorie ketogenic diet improves weight loss and quality of life in patients with adjustable gastric banding

Authors:

Taus, Marina; Fumelli, Daniele; Busni, Debora; Borroni, Francesca; Sebastianelli, Sonia; Nicolai, Giulia; Nicolai, Albano

Abstract:

BACKGROUND: Often, in severe obesity, diet and physical activity are not enough to achieve a healthy BMI. Bariatric surgical approach, in particular laparoscopic adjustable gastric banding (LAGB), has encouraging results in terms of weight loss and resolution of obesity-related comorbidities. However, several months after LAGB, some patients are enable to lose weight anymore and don't tolerate a further calibration because of its collateral effects (excessive sense of fullness, heartburn, regurgitation and vomiting). AIM: The aim of this study is to identify the potential role of high protein-low carbohydrate ketogenic diet (KD) in managing weight loss in patients who underwent gastric banding and didn't lose weight anymore. METHODS: 50 patients underwent LAGB between January 2010 and December 2013. In twenty patients (GROUP A) we observed a stop in weight loss so we divided this patients into two groups. One group (group A1: 10 patients) continued to follow a LCD low calorie diet and underwent a further calibration; the other group (group A2: 10 patients) started to follow a KD for the next 8 weeks. RESULTS: Both group resumed a significant weight loss, however group A1 patients reported collateral effects due to calibration and a higher Impact of Weight on Quality of Life - Lite (IWQOL-Lite) that correlates with a lower quality of life than patients following KD. CONCLUSIONS: KD can improve the weight loss and quality of life in patients who underwent LAGB and failed at losing more weight allowing a weight loss comparable to that obtained with a further calibration and it is useful to avoid drastic calibrations and their collateral effects. KEY WORDS: Laparoscopic adjustable gastric binding, Quality of life, Very low calory ketogenic binding.

Published:

2017

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Title:

A “healthy diet-optimal sleep” lifestyle pattern is inversely associated with liver stiffness and insulin resistance in patients with nonalcoholic fatty liver disease

Authors:

Katsagoni, C.N.; Papatheodoridis, G.V.; Papageorgiou, M.-V.; Ioannidou, P.; Deutsch, M.; Alexopoulou, A.; Papadopoulos, N.; Fragopoulou, E.; Kontogianni, M.D.

Abstract:

Several lifestyle habits have been described as risk factors for nonalcoholic fatty liver disease (NAFLD). Given that both healthy and unhealthy habits tend to cluster, the aim of this study was to identify lifestyle patterns and explore their potential associations with clinical characteristics of individuals with NAFLD. One hundred and thirty-six consecutive patients with ultrasound-proven NAFLD were included. Diet and physical activity level were assessed through appropriate questionnaires. Habitual night sleep hours and duration of midday naps were recorded. Optimal sleep duration was defined as sleep hours ≥ 7 and ≤ 9 h/day. Lifestyle patterns were identified using principal component analysis. Eight components were derived explaining 67% of total variation of lifestyle characteristics. Lifestyle pattern 3, namely high consumption of low-fat dairy products, vegetables, fish, and optimal sleep duration was negatively associated with insulin resistance (β = −1.66, P = 0.008) and liver stiffness (β = −1.62, P = 0.05) after controlling for age, sex, body mass index, energy intake, smoking habits, adiponectin, and tumor necrosis factor-. Lifestyle pattern 1, namely high consumption of full-fat dairy products, refined cereals, potatoes, red meat, and high television viewing time was positively associated with insulin resistance (β = 1.66, P = 0.005), although this association was weakened after adjusting for adiponectin and tumor necrosis factor-α. A “healthy diet-optimal sleep” lifestyle pattern was beneficially associated with insulin resistance and liver stiffness in NAFLD patients independent of body weight status and energy intake. © 2017, Canadian Science Publishing. All rights reserved.

Published:

2017

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Title:

AMPK signalling in health and disease

Authors:

Carling, David

Abstract:

In eukaryotic cells AMP-activated protein kinase (AMPK) plays a major role in regulating cellular energy balance. AMPK responds to changes in intracellular adenine nucleotide levels, being activated by an increase in AMP/ADP relative to ATP. Activation of AMPK increases the rate of catabolic (ATP-generating) pathways and decreases the rate of anabolic (ATP-utilising) pathways. In addition to its role in maintaining intracellular energy balance, AMPK regulates whole body energy metabolism. Given its key role in controlling energy homeostasis, AMPK has attracted widespread interest as a potential therapeutic target for metabolic diseases, including type 2 diabetes and, more recently, cancer. Here I review the regulation of AMPK and its potential as a target for therapeutic intervention in human disease.

Published:

2017

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Title:

AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance

Authors:

Garcia, Daniel; Shaw, Reuben J

Abstract:

AMPK is a highly conserved master regulator of metabolism, which restores energy balance during metabolic stress both at the cellular and physiological levels. The identification of numerous AMPK targets has helped explain how AMPK restores energy homeostasis. Recent advancements illustrate novel mechanisms of AMPK regulation, including changes in subcellular localization and phosphorylation by non-canonical up-stream kinases. Notably, the therapeutic potential of AMPK is widely recognized and heavily pursued for treatment of metabolic diseases such as diabetes, but also obesity, inflammation, and cancer. Moreover, the recently solved crystal structure of AMPK has shed light both into how nucleotides activate AMPK and, importantly, also into the sites bound by small molecule activators, thus providing a path for improved drugs. Introduction Maintenance of energy homeostasis and the execution of adap-tive responses during periods of low nutrients are critical func-tions of all cells. The main sensor of cellular energy status in effec-tively all eukaryotic cells is the AMP-activated protein kinase (AMPK), which is highly conserved across all eukaryotic species. In general, AMPK is activated in response to energy stress by sensing increases in AMP:ATP and ADP:ATP ratios and restores energy balance by inhibiting anabolic processes that consume ATP, while promoting catabolic processes that generate ATP. Moreover, the activity of AMPK is extensively regulated by multiple upstream signals, thus making AMPK a central node exploited by cells to coordinate their metabolism with specific energy demands. Importantly, the primordial role of AMPK as an energy sensor has been co-opted in higher eukaryotes, such as mammals, to also coordinate growth and metabolism both in specialized tissues and at the whole-body level. Therefore, this ability of AMPK to reprogram metabolism is heavily pursued as a therapeutic avenue for the treatment of several metabolic diseases, especially diabetes, but also for obesity, inflammation, and cancer. Here we review recent advances in our under-standing of AMPK structure, its complex upstream regulation, and downstream effects and provide perspective on novel ap-proaches for the therapeutic activation of AMPK. The AMPK Trimeric Complex AMPK exists as a trimeric complex consisting of a catalytic sub-unit (a subunit) and two regulatory subunits (b and g subunits). In mammals, the a subunit is encoded by two isoforms, and the b and g subunits are encoded by two and three isoforms,

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2017

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Activation of RAGE/STAT3 pathway by methylglyoxal contributes to spinal central sensitization and persistent pain induced by bortezomib

Authors:

Wei, Jia-You; Liu, Cui-Cui; Ouyang, Han-Dong; Ma, Chao; Xie, Man-Xiu; Liu, Meng; Lei, Wan-Long; Ding, Huan-Huan; Wu, Shao-Ling; Xin, Wen-Jun

Abstract:

Bortezomib is a first-line chemotherapeutic drug widely used for multiple myeloma and other nonsolid malignancies. Although bortezomib-induced persistent pain is easily diagnosed in clinic, the pathogenic mechanism remains unclear. Here, we studied this issue with use of a rat model of systemic intraperitoneal administration of bortezomib for consecutive 5days. Consisted with our previous study, we found that bortezomib treatment markedly induced mechanical allodynia in rats. Furthermore, we first found that bortezomib treatment significantly induced the upregulation of methylglyoxal in spinal dorsal horn of rats. Spinal local application of methylglyoxal also induced mechanical allodynia and central sensitization in normal rats. Moreover, administration of bortezomib upregulated the expression of receptors for advanced glycation end products (RAGE) and phosphorylated STAT3 (p-STAT3) in dorsal horn. Importantly, intrathecal injection of metformin, a known scavenger of methylglyoxal, significantly attenuated the upregulation of methylglyoxal and RAGE in dorsal horn, central sensitization and mechanical allodynia induced by bortezomib treatment, and blockage of RAGE also prevented the upregulation of p-STAT3, central sensitization and mechanical allodynia induced by bortezomib treatment. In addition, inhibition of STAT3 activity by S3I-201 attenuated bortezomib-induced mechanical allodynia and central sensitization. Local knockdown of STAT3 also ameliorated the mechanical allodynia induced by bortezomib administration. Our results suggest that accumulation of methylglyoxal may activate the RAGE/STAT3 signaling pathway in dorsal horn, and contributes to the spinal central sensitization and persistent pain induced by bortezomib treatment.

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2017

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Additional commentary on deception in statin research

Authors:

Diamond, David M.; Ravnskov, Uffe

Abstract:

Response to: Ferenci T. Absolute risk reduction may depend on the duration of the follow-up. Expert Rev Clin Pharmacol. 2017;10(12):1409-1410.

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2017

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An automated ranking platform for machine learning regression models for meat spoilage prediction using multi-spectral imaging and metabolic profiling

Authors:

Estelles-Lopez, Lucia; Ropodi, Athina; Pavlidis, Dimitris; Fotopoulou, Jenny; Gkousari, Christina; Peyrodie, Audrey; Panagou, Efstathios; Nychas, George-John; Mohareb, Fady

Abstract:

Over the past decade, analytical approaches based on vibrational spectroscopy, hyperspectral/multispectral imagining and biomimetic sensors started gaining popularity as rapid and efficient methods for assessing food quality, safety and authentication; as a sensible alternative to the expensive and time-consuming conventional microbiological techniques. Due to the multi-dimensional nature of the data generated from such analyses, the output needs to be coupled with a suitable statistical approach or machine-learning algorithms before the results can be interpreted. Choosing the optimum pattern recognition or machine learning approach for a given analytical platform is often challenging and involves a comparative analysis between various algorithms in order to achieve the best possible prediction accuracy. In this work, "MeatReg", a web-based application is presented, able to automate the procedure of identifying the best machine learning method for comparing data from several analytical techniques, to predict the counts of microorganisms responsible of meat spoilage regardless of the packaging system applied. In particularly up to 7 regression methods were applied and these are ordinary least squares regression, stepwise linear regression, partial least square regression, principal component regression, support vector regression, random forest and k-nearest neighbours. MeatReg" was tested with minced beef samples stored under aerobic and modified atmosphere packaging and analysed with electronic nose, HPLC, FT-IR, GC-MS and Multispectral imaging instrument. Population of total viable count, lactic acid bacteria, pseudomonads, Enterobacteriaceae and B. thermosphacta, were predicted. As a result, recommendations of which analytical platforms are suitable to predict each type of bacteria and which machine learning methods to use in each case were obtained. The developed system is accessible via the link: www.sorfml.com. Copyright © 2017 Elsevier Ltd. All rights reserved.

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2017

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Animal Proteins as Important Contributors to a Healthy Human Diet

Authors:

Elmadfa, I.; Meyer, A.L.

Abstract:

Adequate protein intake is critical for health and development. Generally, protein of animal origin is of higher quality for humans owing to its amino acid pattern and good digestibility. When administered in mixtures it can enhance the quality of plant proteins, but its availability is often low in low-income communities, especially in young children, the elderly, and pregnant and lactating women, who have increased requirements and in whom high-quality protein also stimulates (bone) growth and maintenance. Although high protein intake was associated with increased type 2 diabetes mellitus risk, milk and seafood are good sources of branched chain amino acids and taurine, which act beneficially on glucose metabolism and blood pressure. However, high consumption of protein-rich animal food is also associated with adverse health effects and higher risk for noncommunicable diseases, partly related to other components of these foods, like saturated fatty acids and potential carcinogens in processed meat but also the atherogenic methionine metabolite homocysteine. In moderation, however, animal proteins are especially important for health maintenance in vulnerable persons. Copyright ©2017 by Annual Reviews. All rights reserved.

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2017

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Annals and Analytics: The Practice of History in the Age of Big Data

Authors:

Ruis, A. R.; Shaffer, David Williamson

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2017

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Anserine/carnosine supplementation suppresses the expression of the inflammatory chemokine CCL24 in peripheral blood mononuclear cells from elderly people

Authors:

Katakura, Y.; Totsuka, M.; Imabayashi, E.; Matsuda, H.; Hisatsune, T.

Abstract:

Our goal was to determine whether anserine/carnosine supplementation (ACS) suppresses chemokine levels in elderly people. In a double-blind randomized controlled trial, volunteers were assigned to the ACS or placebo group (1:1). Sixty healthy elderly volunteers (active, n = 30; placebo, n = 30) completed the study. The ACS group was administered 1.0 g of anserine/carnosine (3:1) for 3 months. A microarray analysis and subsequent quantitative real-time polymerase chain reaction (qRT-PCR) analysis of peripheral blood mononuclear cells (PBMCs) showed decreased expression of CCL24, an inflammatory chemokine (p < 0.05). Verbal memory, assessed using the Wechsler memory scale–logical memory, was preserved in the ACS group. An age-restricted sub-analysis showed significant verbal memory preservaation by ACS in participants who were in their 60s (active, n = 12; placebo, n = 9; p = 0.048) and 70s (active, n = 7; placebo, n = 11; p = 0.017). The suppression of CCL24 expression was greatest in people who were in their 70s (p < 0.01). There was a significant correlation between the preservation of verbal memory and suppression of CCL24 expression in the group that was in the 70s (Poisson correlation, r = 0.46, p

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2017

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Application of nutrigenomics in small ruminants: Lactation, growth, and beyond

Authors:

Osorio, J.S.; Vailati-Riboni, M.; Palladino, A.; Luo, J.; Loor, J.J.

Abstract:

Ruminants have a very special niche in the animal kingdom, and are the most important livestock species providing milk, meat, and wool for humans from consumption of highly-fibrous feedstuffs. Cattle, goat and sheep have been widely-used for years as models to study ruminal fermentation and the mechanisms whereby tissues utilize nutrients for milk synthesis, growth, wool accretion, and reproduction. The advent of high-throughput technologies to study an animal's genome, proteome, and metabolome (i.e., “omics” tools) offered ruminant scientists the opportunity to study multiple levels of biological information to better understand the whole animal response to nutrition, environment, physiological state, and their interactions. The omics revolution gave rise to the field of nutrigenomics, i.e. the study of the genome-wide influences of nutrition through alteration in mRNA, protein, and metabolite expression or abundance. This field of research is relatively new in ruminants, and particularly sheep and goats. Dietary compounds affect gene expression directly or indirectly via interactions with transcription factors including ligand-dependent nuclear receptors. New knowledge generated through the application of functional analyses of transcriptomic, proteomic, and metabolomic data sets in goat and sheep is discussed. © 2017 Elsevier B.V.

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2017

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Applications of prebiotics in food industry: A review

Authors:

Singla, V.; Chakkaravarthi, S.

Abstract:

Benefits of prebiotics for stimulating a healthy intestinal tract are well known. From suppression of pathogens to proliferation of indigenous bacteria of intestines, prebiotics have it all. Since the research on the scope of prebiotics is expanding, new applications are coming up every day thus upgrading the choices consumer has for a healthy living. Incorporation of prebiotics in a wide range of products that food industry offers on shelf is an innovative way to replace fat and sugars along with enhancing the mouthfeel by providing better tongue lubrication. In some cases, the thermal stability of the product is improved along with other sensory, textural and physiological benefits. This paper gives an overview of the various prebiotics available from different sources and their applications in various segments of food industry, notably dairy, beverage, processed fruit-vegetable, bakery, confectionary, extruded snack, sweetener, infant formula, pet food and livestock industry. The effects observed on addition of various prebiotics are also elaborated. © 2017, © The Author(s) 2017.

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2017

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Are we Genetically Adapted to the Neolithic Diet?

Authors:

Hale, Nicola E.

Abstract:

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2017

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Association between self-reported vegetarian diet and the irritable bowel syndrome in the French NutriNet cohort

Authors:

Buscail, Camille; Sabate, Jean-Marc; Bouchoucha, Michel; Torres, Marion J.; Allès, Benjamin; Hercberg, Serge; Benamouzig, Robert; Julia, Chantal

Abstract:

BACKGROUND: There is growing interest in using diet counselling in the management of patients with irritable bowel syndrome (IBS). Among new emerging diets, vegetarian diets (VD) seem to be experiencing an important popularity, partly because of their alleged health benefits. A recent study performed among a rural Indian population showed that predominant VD could be associated with IBS. OBJECTIVE: This cross-sectional study aimed at assessing the association between the VD and IBS, among a large French cohort, the NutriNet-santé study. METHODS: Subjects participating in the NutriNet-Santé cohort study completed a questionnaire based on Rome III criteria (N = 41,682). Anthropometrics, socio-demographical and lifestyle data, including VD, were collected prior to the completion of Rome III questionnaire via self-administered questionnaires. Association between VD and IBS and its subtypes was investigated through multivariate logistic regression. RESULTS: The included subjects were mainly women (78.0%) and the mean age was 49.8±14.3 years. Among these individuals, 2,264 (5.4%) presented an IBS, and 805 (1.9%) reported a VD. Overall, VD was not associated with IBS or subtypes. A stable VD (i.e. self-declared at least three times) was associated with IBS (aOR 2.60 95%CI [1.37-4.91]), IBS mixed (aOR 2.97 95%CI [1.20-7.36]) and IBS diarrhoea (aOR 2.77 95%CI [1.01-7.59]). CONCLUSIONS: This study suggests that a long term VD could be associated with IBS. Nevertheless, further studies are needed to confirm these results, and investigate the multiple aspects of the vegetarian diet, possibly related to the IBS.

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2017

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Associations between food consumption patterns and saliva composition: Specificities of eating difficulties children

Authors:

Morzel, M.; Truntzer, C.; Neyraud, E.; Brignot, H.; Ducoroy, P.; Lucchi, G.; Canlet, C.; Gaillard, S.; Nicod, F.; Nicklaus, S.; Peretti, N.; Feron, G.

Abstract:

Identifying objective markers of diet would be beneficial to research fields such as nutritional epidemiology. As a preliminary study on the validity of using saliva for this purpose, and in order to explore the relationship between saliva and diet, we focused on clearly contrasted groups of children: children with eating difficulties (ED) receiving at least 50% of their energy intake through artificial nutrition vs healthy controls (C). Saliva of ED and C children was analyzed by various methods (targeted biochemical analyses, 2-D electrophoresis coupled to MS, 1H NMR) and their diet was characterized using food frequency questionnaires, considering 148 food items grouped into 13 categories. Complete datasets were obtained for 16 ED and 16 C subjects (median age 4.7 y and 5.0 y, respectively) and the statistical link between salivary and dietary characteristics was studied by Multiple Factor Analysis (MFA). Overall, ED children showed as expected lower consumption frequency scores and higher food selectivity. The two groups of children differed in “diet/saliva” associations. Some distinctive salivary variables were common to both groups of children. For example, carbonic anhydrase 6 and the consumption frequency of biscuits & sweets and drinks were positively associated with the MFA axis 1 in C children, but oppositely associated in ED children. Specifically for ED children, abundant salivary proteins (cystatins, amylase, amylase fragments) and some metabolites (amino acids, galactose, lactate) correlated with axis 1, together with the consumption frequency of sauces & seasonings, bread & cereal products, ready-to-eat meals, fish, biscuits & sweets, drinks and potatoes. Specifically for C children, several proteins (serum albumin, haptoglobin, Igκ, apolipoprotein A-1, α-1 antitrypsin) correlated with axis 1, together with the consumption frequency of biscuits & sweets, milk & dairy products, drinks, fruit, meat and vegetables. This study demonstrates that the qualitative aspect of diet is linked to saliva composition, and that the associations between dietary consumption and salivary composition differ between groups of subjects with contrasted diets. © 2017 Elsevier Inc.

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2017

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Associations of current diet with plasma and urine TMAO in the KarMeN study: direct and indirect contributions

Authors:

Kruger, Ralf; Merz, Benedikt; Rist, Manuela J.; Ferrario, Paola G.; Bub, Achim; Kulling, Sabine E.; Watzl, Bernhard

Abstract:

CONCLUSION: Meat and fish consumption differentially affects TMAO concentrations in body fluids. Only a small fraction of variance is explained by current diet. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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2017

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Bariatric surgery versus lifestyle interventions for severe obesity: 5-year changes in body weight, risk factors and comorbidities

Authors:

Øvrebø, B.; Strømmen, M.; Kulseng, B.; Martins, C.

Abstract:

Changes in body weight (BW), risk factors and comorbidities 5 years after Roux-en-Y gastric bypass (RYGB) or different lifestyle interventions are compared. A total of 209 (75% women) severe obese adults were non-randomly allocated to: (A) RYGB (n = 58), (B) weight loss (WL) camp (n = 30), (C) residential intermittent programme (n = 64) or (D) hospital outpatient programme (n = 57). Body weight, risk factors and comorbidities were assessed at baseline, 1 and 5 years. A total of 89 and 54% completed the 1- and 5-year follow-up. The RYGB group experienced more WL at 5 years (−23.9%, 95% CI [−27.7, −20.0]) compared with lifestyle groups: (B) (−9.2%, 95% CI [−16.9, −1.5]), (C) (−4.1%, 95% CI [−8.0, −0.1]) and (D) (−4.1 kg, 95% CI [−10.0, 1.8]) (all P < 0.001). No differences were observed between lifestyle groups, although groups B and C had significant WL after 5 years (all P < 0.05). Plasma glucose and high-density lipoprotein cholesterol were improved in the RYGB group at 5 years compared with lifestyle groups (all P < 0.05). More patients in the RYGB group experienced remission of hypertension (P

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2017

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Title:

Bead Based Multiplex Assay for Analysis of Tear Cytokine Profiles

Authors:

Balne, Praveen Kumar; Au, Veonice Bijin; Tong, Louis; Ghosh, Arkasubhra; Agrawal, Mukesh; Connolly, John; Agrawal, Rupesh

Abstract:

Tear film is a complex mixture of lipids, proteins and minerals which covers the external surface of the eye, thereby providing lubrication, nutrition and protection to the underlying cells. Analysis of tears is an emerging area for the identification of biomarkers for the prediction, diagnosis, and prognosis of various ocular diseases. Tears are easily accessible and their collection is non-invasive. Therefore, advancing technologies are gaining prominence for identification of multiple analytes in tears to study changes in protein or metabolite composition and its association with pathological conditions. Tear cytokines are ideal biomarkers for studying the health of the ocular surface and also help in understanding the mechanisms of different ocular surface disorders like dry eye disease and vernal conjunctivitis. Bead based multiplex assays have the capability of detecting multiple analytes in a small amount of sample with a higher sensitivity. Here we describe a standardized protocol of tear sample collection, extraction and analysis of cytokine profiling using a bead based multiplex assay.

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2017

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Biological Activities of Extracellular Vesicles and Their Cargos from Bovine and Human Milk in Humans and Implications for Infants

Authors:

Zempleni, Janos; Aguilar-Lozano, Ana; Sadri, Mahrou; Sukreet, Sonal; Manca, Sonia; Wu, Di; Zhou, Fang; Mutai, Ezra

Abstract:

Extracellular vesicles (EVs) in milk harbor a variety of compounds, including lipids, proteins, noncoding RNAs, and mRNAs. Among the various classes of EVs, exosomes are of particular interest, because cargo sorting in exosomes is a regulated, nonrandom process and exosomes play essential roles in cell-to-cell communication. Encapsulation in exosomes confers protection against enzymatic and nonenzymatic degradation of cargos and provides a pathway for cellular uptake of cargos by endocytosis of exosomes. Compelling evidence suggests that exosomes in bovine milk are transported by intestinal cells, vascular endothelial cells, and macrophages in human and rodent cell cultures, and bovine-milk exosomes are delivered to peripheral tissues in mice. Evidence also suggests that cargos in bovine-milk exosomes, in particular RNAs, are delivered to circulating immune cells in humans. Some microRNAs and mRNAs in bovine-milk exosomes may regulate the expression of human genes and be translated into protein, respectively. Some exosome cargos are quantitatively minor in the diet compared with endogenous synthesis. However, noncanonical pathways have been identified through which low concentrations of dietary microRNAs may alter gene expression, such as the accumulation of exosomes in the immune cell microenvironment and the binding of microRNAs to Toll-like receptors. Phenotypes observed in infant-feeding studies include higher Mental Developmental Index, Psychomotor Development Index, and Preschool Language Scale-3 scores in breastfed infants than in those fed various formulas. In mice, supplementation with plant-derived MIR-2911 improved the antiviral response compared with controls. Porcine-milk exosomes promote the proliferation of intestinal cells in mice. This article discusses the above-mentioned advances in research concerning milk exosomes and their cargos in human nutrition. Implications for infant nutrition are emphasized, where permitted, but data in infants are limited.

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2017

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Biological impact of advanced glycation endproducts on estrogen receptor-positive MCF-7 breast cancer cells

Authors:

Matou-Nasri, Sabine; Sharaf, Hana; Wang, Qiuyu; Almobadel, Nasser; Rabhan, Zaki; Al-Eidi, Hamad; Yahya, Wesam Bin; Trivilegio, Thadeo; Ali, Rizwan; Al-Shanti, Nasser; Ahmed, Nessar

Abstract:

Diabetes mellitus potentiates the risk of breast cancer. We have previously described the pro-tumorigenic effects of advanced glycation endproducts (AGEs) on estrogen receptor (ER)-negative MDA-MB-231 breast cancer cell line mediated through the receptor for AGEs (RAGE). However, a predominant association between women with ER-positive breast cancer and type 2 diabetes mellitus has been reported. Therefore, we have investigated the biological impact of AGEs on ER-positive human breast cancer cell line MCF-7 using in vitro cell-based assays including cell count, migration, and invasion assays. Western blot, FACS analyses and quantitative real time-PCR were also performed. We found that AGEs at 50-100μg/mL increased MCF-7 cell proliferation and cell migration associated with an enhancement of pro-matrix metalloproteinase (MMP)-9 activity, without affecting their poor invasiveness. However, 200μg/mL AGEs inhibited MCF-7 cell proliferation through induction of apoptosis indicated by caspase-3 cleavage detected using Western blotting. A phospho-protein array analysis revealed that AGEs mainly induce the phosphorylation of extracellular-signal regulated kinase (ERK)1/2 and cAMP response element binding protein-1 (CREB1), both signaling molecules considered as key regulators of AGEs pro-tumorigenic effects. We also showed that AGEs up-regulate RAGE and ER expression at the protein and transcript levels in MCF-7 cells, in a RAGE-dependent manner after blockade of AGEs/RAGE interaction using neutralizing anti-RAGE antibody. Throughout the study, BSA had no effect on cellular processes. These findings pave the way for future studies investigating whether the exposure of AGEs-treated ER-positive breast cancer cells to estrogen could lead to a potentiation of breast cancer development and progression.

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2017

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Title:

Blocking AGE-RAGE Signaling Improved Functional Disorders of Macrophages in Diabetic Wound

Authors:

Wang, Qi; Zhu, Guanya; Cao, Xiaozan; Dong, Jiaoyun; Song, Fei; Niu, Yiwen

Abstract:

Advanced glycosylation end products (AGEs) accumulate in diabetic wounds. Interactions between AGEs and their receptor (RAGE) leads to dermatologic problems in diabetes. Macrophage, which plays important roles in wound healing, highly expresses RAGE. Therefore, we investigated whether RAGE-expressing macrophages might be responsible for impaired wound healing on diabetes. We used anti-RAGE antibody applied topically on diabetic wounds. After confirming that wound healing was improved in anti-RAGE antibody group compared with normal mice, our results showed that macrophages appeared insufficient in the early stage and fading away slowly in the later proliferative phase compared with the control group, which was ameliorated in anti-RAGE antibody-applied wounds. Blocking AGE-RAGE signaling also increased neutrophils phagocytized by macrophages and promoted the phenotypic switch of macrophages from proinflammatory to prohealing activities. In vitro, phagocytosis of THP-1 (M0) and lipopolysaccharide- (LPS-) induced (M1) macrophages was impaired by treatment with AGEs, while IL-4- and IL-13-induced (M2) macrophages was not. Finally, AGEs increased the proinflammatory response of M1 macrophages, while inhibiting the polarization and anti-inflammatory functions of M2 macrophages. In conclusion, inhibition of AGE-RAGE signaling improved functional disorders of macrophages in the early inflammatory phase, which promoted the healing of wounds in diabetic mice.

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2017

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Title:

Blood lipid metabolites and meat lipid peroxidation responses of broiler chickens to dietary lecithinized palm oil

Authors:

Gheisari, A.; Fosoul, S.S.A.S.; Pourali, S.; Esfahani, E.N.; Mohammadrezaei, M.

Abstract:

This trial was conducted to investigate the effects of supplementing saturated and unsaturated fat sources on serum metabolites and meat physiochemical parameters in the diets of broiler chickens. A total of 360 day-old male broiler chicks (Ross 308) were used in a completely randomized design with five treatments and six replicates of 14 chicks. The assay diets were developed by applying a basal diet with no supplemented fat and the addition of soybean oil (SO), lecithinized palm oil (LPO), a 50: 50 mix of SO and LPO (ESL), and 75: 25 mix of SO and LPO (HSL) ratios to the basal diet. The inclusion levels of experimental fats were 2% and 4% in the starter and growing periods, respectively. Blood samples were collected from broilers to evaluate serum biochemical metabolites on day 41. Thigh meat samples were provided and analysed after 1, 5 and 10 days' storage to evaluate lipid peroxidation at the end of the experiment. Fat and protein contents of thigh muscle and abdominal fat weight were measured and reported. Chickens fed LPO had greater serum triacylglycerol and very low density lipoprotein concentrations compared with those that received other dietary treatments (P < 0.05). The fat content of the meat was higher in birds supplemented with SO, LPO and ESL than control (P < 0.05). After 5 and 10 days of storage, the values of thiobarbituric acid reactive substance were lower in meat of broilers receiving LPO than SO and HSL (P

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2017

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Title:

Body composition, pre‐diabetes and cardiovascular disease risk in early schizophrenia

Authors:

Strassnig, Martin; Clarke, Jennifer; Mann, Steve; Remington, Gary; Ganguli, Rohan

Abstract:

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2017

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Title:

Brain metabolism in health, aging, and neurodegeneration

Authors:

Camandola, Simonetta; Mattson, Mark P

Abstract:

Published 2017. This article is a U.S. Government work and is in the public domain in the USA Brain cells normally respond adaptively to bioenergetic challenges resulting from ongoing activity in neuronal circuits, and from environmental energetic stressors such as food deprivation and physical exertion. At the cellular level, such adaptive responses include the “strengthening” of existing synapses, the formation of new synapses, and the production of new neurons from stem cells. At the molecular level, bioenergetic challenges result in the activation of transcription factors that induce the expression of proteins that bolster the resistance of neurons to the kinds of metabolic, oxidative, excitotoxic, and proteotoxic stresses involved in the pathogenesis of brain disorders including stroke, and Alzheimer's and Parkinson's diseases. Emerging findings suggest that lifestyles that include intermittent bioenergetic challenges, most notably exercise and dietary energy restriction, can increase the likelihood that the brain will function optimally and in the absence of disease throughout life. Here, we provide an overview of cellular and molecular mechanisms that regulate brain energy metabolism, how such mechanisms are altered during aging and in neurodegenerative disorders, and the potential applications to brain health and disease of interventions that engage pathways involved in neuronal adaptations to metabolic stress.

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2017

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Title:

Bridging the gap between health and social care for rare diseases: Key issues and innovative solutions

Authors:

Castro, Raquel; Senecat, Juliette; de Chalendar, Myriam; Vajda, Ildikó; Dan, Dorica; Boncz, Béata

Abstract:

Bridging the gaps between health and social care for rare diseases is not only necessary but crucial to increase the life expectancy, quality of life and autonomy of people living with a rare disease, supporting them in the full realisation of their fundamental human rights.The complexity of rare diseases, their strong relation to disability and the current unmet social and daily life needs of people living with a rare disease must not be underestimated and require urgent attention from all stakeholders involved in care provision, from healthcare to social and community services.The Commission Expert Group Recommendations to Support the Incorporation of Rare Diseases into Social Services and Policies, adopted unanimously in April 2016, by the representatives of European Member States and the other rare disease stakeholders, clearly set the tone for the need to promote measures that facilitate multidisciplinary, holistic, continuous, person-centred and participative care provision to people living with rare diseases.These recommendations, sided by other recent policy developments at European and national levels, represent an important policy step into approaching rare diseases' complex challenges in regards to holistic care provision.Innovative approaches aiming at bridging the gap between health, social and community service and support providers are currently being developed and tested in different European countries: standards of care, networks of expertise, case management services, one-stop-shop services, amongst others.These ongoing pilot approaches, presented in this chapter, have the power to inspire future policies and the effective and efficient implementation of holistic care pathways for people living with a rare disease, bringing about significant changes for patients, carers, care providers, competent authorities and the society at large.Nonetheless, the challenges to fully address this issue remain numerous and other key issues will also need to be taken into account when moving forward with the implementation of measures that aim at bridging the gaps between care providers and providing holistic care to people living with a rare disease.

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2017

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Title:

CANVAS Programme Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes.

Authors:

Neal, Bruce; Perkovic, Vlado; Mahaffey, Kenneth W.; de Zeeuw, Dick; Fulcher, Greg; Erondu, Ngozi; Shaw, Wayne; Law, Gordon; Desai, Mehul; Matthews, David

Abstract:

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2017

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Title:

Caffeine intake increases plasma ketones: An acute metabolic study in humans

Authors:

Vandenberghe, Camille; St-Pierre, Valérie; Courchesne-Loyer, Alexandre; Hennebelle, Marie; Castellano, Christian Alexandre; Cunnane, Stephen C.

Abstract:

Brain glucose uptake declines during aging and is significantly impaired in Alzheimer's disease. Ketones are the main alternative brain fuel to glucose so they represent a potential approach to compensate for the brain glucose reduction. Caffeine is of interest as a potential ketogenic agent owing to its actions on lipolysis and lipid oxidation but whether it is ketogenic in humans is unknown. This study aimed to evaluate the acute ketogenic effect of 2 doses of caffeine (2.5; 5.0 mg/kg) in 10 healthy adults. Caffeine given at breakfast significantly stimulated ketone production in a dose-dependent manner (+88%; +116%) and also raised plasma free fatty acids. Whether caffeine has long-term ketogenic effects or could enhance the ketogenic effect of medium chain triglycerides remains to be determined.

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2017

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Changes of thyroid hormonal status in patients receiving ketogenic diet due to intractable epilepsy

Authors:

Kose Engin; Guzel Orkide; Demir Korcan; Arslan Nur

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2017

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Title:

Choline Theft—An Inside Job

Authors:

Mora-Ortiz, M.; Claus, S.P.

Abstract:

Choline is a crucial methyl donor necessary for epigenetic regulation. In this issue of Cell Host & Microbe, Romano et al. (2017) demonstrate that choline-utilizing gut bacteria compete with their host for this essential resource, calling for a systematic consideration of gut microbial composition for personalized diet recommendations. Choline is a crucial methyl donor necessary for epigenetic regulation. In this issue of Cell Host & Microbe, Romano et al. (2017) demonstrate that choline-utilizing gut bacteria compete with their host for this essential resource, calling for a systematic consideration of gut microbial composition for personalized diet recommendations. © 2017

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2017

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Title:

Chronic Diseases and Lifestyle Biomarkers Identification by Metabolomics

Authors:

Mastrangelo, Annalaura; Barbas, Coral

Abstract:

Chronic diseases, also known as noncommunicable diseases (NCDs), are complex disorders that last for long periods of time and progress slowly. They currently account for the major cause of death worldwide with an alarming increase in rate both in developed and developing countries. In this chapter, the principal metabolomic-based investigations on chronic diseases (cardiovascular diseases, diabetes, and respiratory chronic diseases) and their major risk factors (particularly overweight/obesity) are described by focusing both on metabolites and metabolic pathways. Additional information on the contribution of metabolomics strategies in the ambit of the biomarker discovery for NCDs is also provided by exploring the major prospective studies of the last years (i.e., Framingham Heart Study, EPIC, MONICA, KORA, FINRIK, ECLIPSE). The metabolic signature of diseases, which arises from the metabolomic-based investigation, is therefore depicted in the chapter by pointing out the potential of metabolomics to explain the pathophysiological mechanisms underlying a disease, as well as to propose new therapeutic targets for alternative treatments.

Published:

2017

Marble Surface

Title:

Climate change mitigation opportunities based on carbon footprint estimates of dietary patterns in Peru

Authors:

Vázquez-Rowe, Ian; Larrea-Gallegos, Gustavo; Villanueva-Rey, Pedro; Gilardino, Alessandro

Abstract:

Food consumption accounts for an important proportion of the world GHG emissions per capita. Previous studies have delved into the nature of dietary patterns, showing that GHG reductions can be achieved in diets if certain foods are consumed rather than other, more GHG intensive products. For instance, vegetarian and low-meat diets have proved to be less carbon intensive than diets that are based on ruminant meat. These environmental patterns, increasingly analyzed in developed nations, are yet to be assessed in countries liked Peru where food purchase represents a relatively high percentage of the average household expenditure, ranging from 38% to 51% of the same. Therefore, food consumption can be identified as a potential way to reduce GHG emissions in Peru. However, the Peruvian government lacks a specific strategy to mitigate emissions in this sector, despite the recent ratification of the Paris Accord. In view of this, the main objective of this study is to analyze the environmental impacts of a set of 47 Peruvian food diet profiles, including geographical and socioeconomic scenarios. In order to do this, Life Cycle Assessment was used as the methodological framework to obtain the overall impacts of the components in the dietary patterns observed and primary data linked to the composition of diets were collected from the Peruvian National Institute for Statistics (INEI). Life cycle inventories for the different products that are part of the Peruvian diet were obtained from a set of previous scientific articles and reports regarding food production. Results were computed using the IPCC 2013 assessment method to estimate GHG emissions. Despite variations in GHG emissions from a geographical perspective, no significant differences were observed between cities located in the three Peruvian natural regions (i.e., coast, Andes and Amazon basin). In contrast, there appears to be a strong, positive correlation between GHG emissions and social expenditure or academic status. When compared to GHG emissions computed in the literature for developed nations, where the average caloric intake is substantially higher, diet-related emissions in Peru were in the low range. Our results could be used as a baseline for policy support to align nutritional and health policies in Peru with the need to reduce the environmental impacts linked to food production.

Published:

2017

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