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Title:
Mechanisms of risk reduction in the clinical practice of Alzheimer's disease prevention
Authors:
Schelke, Matthew W.; Attia, Peter; Palenchar, Daniel J.; Kaplan, Bob; Mureb, Monica; Ganzer, Christine A.; Scheyer, Olivia; Rahman, Aneela; Kachko, Robert; Krikorian, Robert; Mosconi, Lisa; Isaacson, Richard S.
Abstract:
Abstract: Alzheimer's disease (AD) is a neurodegenerative dementia that affects nearly 50 million people worldwide and is a major source of morbidity, mortality, and healthcare expenditure. While there have been many attempts to develop disease-modifying therapies for late-onset AD, none have so far shown efficacy in humans. However, the long latency between the initial neuronal changes and onset of symptoms, the ability to identify patients at risk based on family history and genetic markers, and the emergence of AD biomarkers for preclinical disease suggests that early risk-reducing interventions may be able to decrease the incidence of, delay or prevent AD. In this review, we discuss six mechanisms—dysregulation of glucose metabolism, inflammation, oxidative stress, trophic factor release, amyloid burden, and calcium toxicity—involved in AD pathogenesis that offer promising targets for risk-reducing interventions. In addition, we offer a blueprint for a multi-modality AD risk reduction program that can be clinically implemented with the current state of knowledge. Focused risk reduction aimed at particular pathological factors may transform AD to a preventable disorder in select cases.
Published:
2018
Title:
Medium Chain Triglycerides enhances exercise endurance through the increased mitochondrial biogenesis and metabolism
Authors:
Wang, Ying; Liu, Zhenzhen; Han, Yi; Xu, Jiping; Huang, Wen; Li, Zhaoshen
Abstract:
Medium Chain Triglycerides (MCT) is a dietary supplement and usually used along with medications for treating food absorption disorders including diarrhea, steatorrhea and liver disease. It has been shown that MCT plays a role in lowering weight, and decreasing metabolic syndrome, abdominal obesity and inflammation. However, it is still unknown whether MCT enhances exercise endurance. Here, we demonstrated that MCT containing diet improves high temperature induced exercise performance impairment. We found that MCT up-regulates the expression and protein levels of genes involved in mitochondrial biogenesis and metabolism. Further investigation demonstrated that the increased mitochondrial biogenesis and metabolism is mediated through the activation of Akt and AMPK signaling pathways and inhibition of TGF-β signaling pathway. Collectively, our findings indicate a beneficial effect of dietary MCT in exercise performance through the increase of mitochondrial biogenesis and metabolism.
Published:
2018
Title:
Metabonomics Profiling Reveals Biochemical Pathways Associated with Pulmonary Arterial Hypertension in Broiler Chickens
Authors:
Shao, F.-J.; Ying, Y.-T.; Tan, X.; Zhang, Q.-Y.; Liao, W.-T.
Abstract:
Pulmonary arterial hypertension (PAH) is the major cause of death in fast growing meat-type chickens (broiler chickens). At present, the underlying mechanisms that give rise to PAH are not fully understood. To identify the metabonomics profiles characterizing the process, we conducted a comprehensive gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling of lung tissues from PAH broilers and age-matched controls. PAH was induced by excess salt in drinking water. Medial hypertrophy of pulmonary arteries was present in PAH birds as compared with controls. The metabonomics profiles of lung tissues well distinguished PAH broilers from control subjects. Significant changes in the levels of 41 metabolites were detected in PAH vs normal birds. Aside from the metabolic alterations indicating a status of oxidative stress and inflammation, evidence of reduced cellular uptake of arginine due to increased lysine biosynthesis and of a shift of arginine metabolism to arginase pathway were observed. In addition, PAH birds showed increased biosynthesis of fatty acids, which may be associated with excessive proliferation of vascular cells during pulmonary vascular remodeling. Furthermore, we observed significant changes in pentose phosphate pathway and increased aminomalonic acid in PAH broilers. These results provide additional biochemical insights into the pathogenesis of the PAH. Our data may lead to the development of new strategies to control PAH in broilers. © Copyright 2018 American Chemical Society.
Published:
2018
Title:
Metabotypes Related to Meat and Vegetable Intake Reflect Microbial, Lipid and Amino Acid Metabolism in Healthy People
Authors:
Wei, R.; Ross, A.B.; Su, M.; Wang, J.; Guiraud, S.-P.; Draper, C.F.; Beaumont, M.; Jia, W.; Martin, F.-P.
Abstract:
Scope: The objective of this study is to develop a new methodology to identify the relationship between dietary patterns and metabolites indicative of food intake and metabolism. Methods and results: Plasma and urine samples from healthy Swiss subjects (n = 89) collected over two time points are analyzed for a panel of host–microbial metabolites using GC– and LC–MS. Dietary intake is evaluated using a validated food frequency questionnaire. Dietary pattern clusters and relationships with metabolites are determined using Non-Negative Matrix Factorization (NNMF) and Sparse Generalized Canonical Correlation Analysis (SGCCA). Use of NNMF allows detection of latent diet clusters in this population, which describes a high intake of meat or vegetables. SGCCA associates these clusters to i) diet-host microbial and lipid associated bile acid metabolism, and ii) essential amino acid metabolism. Conclusion: This novel application of NNMF and SGCCA allows detection of distinct metabotypes for meat and vegetable dietary patterns in a heterogeneous population. As many of the metabolites associated with meat or vegetable intake are the result of host–microbiota interactions, the findings support a role for microbiota mediating the metabolic imprinting of different dietary choices. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Published:
2018
Title:
Methods for trustworthy nutritional recommendations NutriRECS (Nutritional Recommendations and accessible Evidence summaries Composed of Systematic reviews): A protocol
Authors:
Johnston, Bradley C.; Alonso-Coello, Pablo; Bala, Malgorzata M.; Zeraatkar, Dena; Rabassa, Montserrat; Valli, Claudia; Marshall, Catherine; El Dib, Regina; Vernooij, Robin W.M.; Vandvik, Per O.; Guyatt, Gordon H.
Abstract:
Background: Recent systematic reviews and editorials suggest that many organizations that produce nutritional guideline recommendations do not adhere to internationally recognized standards set forth by the Institute of Medicine (IoM), Guidelines International Network (GIN), Appraisal of Guidelines Research and Evaluation (AGREE), and Grading Recommendations, Assessment, Development and Evaluation (GRADE). Methods: The potential solution is an independent group with content expertise and skilled in the methodology of systematic reviews and practice guidelines to produce trustworthy guideline recommendations, recommendations that are supported by publication in a top tier journal. The BMJ Rapid Recommendations project has recently demonstrated the feasibility and utility of this approach. Here, we are proposing trustworthy nutritional guideline recommendations based on internationally accepted guideline development standards, recommendations that will be informed by rigorous and novel systematic reviews of the benefits and harms associated with nutritional exposures, as well as studies on the values and preferences related to dietary behaviors among members of the international community. Discussion: Adhering to international guideline standards, conducting high quality systematic reviews, and actively assessing the values and preferences of key stakeholders is expected to improve the quality of nutritional guidelines and their relevance to end-users, particularly patients and community members. We will send our work for peer review, and if found acceptable, we will publish our nutritional recommendations in top-tier general medicine journals.
Published:
2018
Title:
MicroRNAs from plants to animals, do they define a new messenger for communication?
Authors:
Li, Zhiqing; Xu, Ruodan; Li, Ning
Abstract:
MicroRNAs (miRNAs), a class of single-stranded non-coding RNA of about 22 nucleotides, are potent regulators of gene expression existing in both plants and animals. Recent studies showed that plant miRNAs could enter mammalian bloodstream via gastrointestinal tract, through which access a variety of tissues and cells of recipients to exert therapeutic effects. This intriguing phenomenon indicates that miRNAs of diet/plant origin may act as a new class of bioactive ingredients communicating with mammalian systems. In this review, in order to pinpoint the reason underlying discrepancies of miRNAs transmission from diet/plant to animals, the pathways that generate miRNAs and machineries involved in the functions of miRNAs in both kingdoms were outlined and compared. Then, the current controversies concerning cross-kingdom regulations and the potential mechanisms responsible for absorption and transfer of diet/plant-derived miRNAs were interpreted. Furthermore, the hormone-like action of miRNAs and the intricate interplay between miRNAs and hormones were implicated. Finally, how these findings may impact nutrition and medicine were briefly discussed.
Published:
2018
Title:
Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
Authors:
Théry, Clotilde; Witwer, Kenneth W.; Aikawa, Elena; Alcaraz, Maria Jose; Anderson, Johnathon D.; Andriantsitohaina, Ramaroson; Antoniou, Anna; Arab, Tanina; Archer, Fabienne; Atkin-Smith, Georgia K.; Ayre, D. Craig; Bach, Jean-Marie; Bachurski, Daniel; Baharvand, Hossein; Balaj, Leonora; Baldacchino, Shawn; Bauer, Natalie N.; Baxter, Amy A.; Bebawy, Mary; Beckham, Carla; Bedina Zavec, Apolonija; Benmoussa, Abderrahim; Berardi, Anna C.; Bergese, Paolo; Bielska, Ewa; Blenkiron, Cherie; Bobis-Wozowicz, Sylwia; Boilard, Eric; Boireau, Wilfrid; Bongiovanni, Antonella; Borràs, Francesc E.; Bosch, Steffi; Boulanger, Chantal M.; Breakefield, Xandra; Breglio, Andrew M.; Brennan, Meadhbh Á; Brigstock, David R.; Brisson, Alain; Broekman, Marike Ld; Bromberg, Jacqueline F.; Bryl-Górecka, Paulina; Buch, Shilpa; Buck, Amy H.; Burger, Dylan; Busatto, Sara; Buschmann, Dominik; Bussolati, Benedetta; Buzás, Edit I.; Byrd, James Bryan; Camussi, Giovanni; Carter, David Rf; Caruso, Sarah; Chamley, Lawrence W.; Chang, Yu-Ting; Chen, Chihchen; Chen, Shuai; Cheng, Lesley; Chin, Andrew R.; Clayton, Aled; Clerici, Stefano P.; Cocks, Alex; Cocucci, Emanuele; Coffey, Robert J.; Cordeiro-da-Silva, Anabela; Couch, Yvonne; Coumans, Frank Aw; Coyle, Beth; Crescitelli, Rossella; Criado, Miria Ferreira; D'Souza-Schorey, Crislyn; Das, Saumya; Datta Chaudhuri, Amrita; de Candia, Paola; De Santana, Eliezer F.; De Wever, Olivier; Del Portillo, Hernando A.; Demaret, Tanguy; Deville, Sarah; Devitt, Andrew; Dhondt, Bert; Di Vizio, Dolores; Dieterich, Lothar C.; Dolo, Vincenza; Dominguez Rubio, Ana Paula; Dominici, Massimo; Dourado, Mauricio R.; Driedonks, Tom Ap; Duarte, Filipe V.; Duncan, Heather M.; Eichenberger, Ramon M.; Ekström, Karin; El Andaloussi, Samir; Elie-Caille, Celine; Erdbrügger, Uta; Falcón-Pérez, Juan M.; Fatima, Farah; Fish, Jason E.; Flores-Bellver, Miguel; Försönits, András; Frelet-Barrand, Annie; Fricke, Fabia; Fuhrmann, Gregor; Gabrielsson, Susanne; Gámez-Valero, Ana; Gardiner, Chris; Gärtner, Kathrin; Gaudin, Raphael; Gho, Yong Song; Giebel, Bernd; Gilbert, Caroline; Gimona, Mario; Giusti, Ilaria; Goberdhan, Deborah Ci; Görgens, André; Gorski, Sharon M.; Greening, David W.; Gross, Julia Christina; Gualerzi, Alice; Gupta, Gopal N.; Gustafson, Dakota; Handberg, Aase; Haraszti, Reka A.; Harrison, Paul; Hegyesi, Hargita; Hendrix, An; Hill, Andrew F.; Hochberg, Fred H.; Hoffmann, Karl F.; Holder, Beth; Holthofer, Harry; Hosseinkhani, Baharak; Hu, Guoku; Huang, Yiyao; Huber, Veronica; Hunt, Stuart; Ibrahim, Ahmed Gamal-Eldin; Ikezu, Tsuneya; Inal, Jameel M.; Isin, Mustafa; Ivanova, Alena; Jackson, Hannah K.; Jacobsen, Soren; Jay, Steven M.; Jayachandran, Muthuvel; Jenster, Guido; Jiang, Lanzhou; Johnson, Suzanne M.; Jones, Jennifer C.; Jong, Ambrose; Jovanovic-Talisman, Tijana; Jung, Stephanie; Kalluri, Raghu; Kano, Shin-Ichi; Kaur, Sukhbir; Kawamura, Yumi; Keller, Evan T.; Khamari, Delaram; Khomyakova, Elena; Khvorova, Anastasia; Kierulf, Peter; Kim, Kwang Pyo; Kislinger, Thomas; Klingeborn, Mikael; Klinke, David J.; Kornek, Miroslaw; Kosanović, Maja M.; Kovács, Árpád Ferenc; Krämer-Albers, Eva-Maria; Krasemann, Susanne; Krause, Mirja; Kurochkin, Igor V.; Kusuma, Gina D.; Kuypers, Sören; Laitinen, Saara; Langevin, Scott M.; Languino, Lucia R.; Lannigan, Joanne; Lässer, Cecilia; Laurent, Louise C.; Lavieu, Gregory; Lázaro-Ibáñez, Elisa; Le Lay, Soazig; Lee, Myung-Shin; Lee, Yi Xin Fiona; Lemos, Debora S.; Lenassi, Metka; Leszczynska, Aleksandra; Li, Isaac Ts; Liao, Ke; Libregts, Sten F.; Ligeti, Erzsebet; Lim, Rebecca; Lim, Sai Kiang; Linē, Aija; Linnemannstöns, Karen; Llorente, Alicia; Lombard, Catherine A.; Lorenowicz, Magdalena J.; Lörincz, Ákos M.; Lötvall, Jan; Lovett, Jason; Lowry, Michelle C.; Loyer, Xavier; Lu, Quan; Lukomska, Barbara; Lunavat, Taral R.; Maas, Sybren Ln; Malhi, Harmeet; Marcilla, Antonio; Mariani, Jacopo; Mariscal, Javier; Martens-Uzunova, Elena S.; Martin-Jaular, Lorena; Martinez, M. Carmen; Martins, Vilma Regina; Mathieu, Mathilde; Mathivanan, Suresh; Maugeri, Marco; McGinnis, Lynda K.; McVey, Mark J.; Meckes, David G.; Meehan, Katie L.; Mertens, Inge; Minciacchi, Valentina R.; Möller, Andreas; Møller Jørgensen, Malene; Morales-Kastresana, Aizea; Morhayim, Jess; Mullier, François; Muraca, Maurizio; Musante, Luca; Mussack, Veronika; Muth, Dillon C.; Myburgh, Kathryn H.; Najrana, Tanbir; Nawaz, Muhammad; Nazarenko, Irina; Nejsum, Peter; Neri, Christian; Neri, Tommaso; Nieuwland, Rienk; Nimrichter, Leonardo; Nolan, John P.; Nolte-'t Hoen, Esther Nm; Noren Hooten, Nicole; O'Driscoll, Lorraine; O'Grady, Tina; O'Loghlen, Ana; Ochiya, Takahiro; Olivier, Martin; Ortiz, Alberto; Ortiz, Luis A.; Osteikoetxea, Xabier; Østergaard, Ole; Ostrowski, Matias; Park, Jaesung; Pegtel, D. Michiel; Peinado, Hector; Perut, Francesca; Pfaffl, Michael W.; Phinney, Donald G.; Pieters, Bartijn Ch; Pink, Ryan C.; Pisetsky, David S.; Pogge von Strandmann, Elke; Polakovicova, Iva; Poon, Ivan Kh; Powell, Bonita H.; Prada, Ilaria; Pulliam, Lynn; Quesenberry, Peter; Radeghieri, Annalisa; Raffai, Robert L.; Raimondo, Stefania; Rak, Janusz; Ramirez, Marcel I.; Raposo, Graça; Rayyan, Morsi S.; Regev-Rudzki, Neta; Ricklefs, Franz L.; Robbins, Paul D.; Roberts, David D.; Rodrigues, Silvia C.; Rohde, Eva; Rome, Sophie; Rouschop, Kasper Ma; Rughetti, Aurelia; Russell, Ashley E.; Saá, Paula; Sahoo, Susmita; Salas-Huenuleo, Edison; Sánchez, Catherine; Saugstad, Julie A.; Saul, Meike J.; Schiffelers, Raymond M.; Schneider, Raphael; Schøyen, Tine Hiorth; Scott, Aaron; Shahaj, Eriomina; Sharma, Shivani; Shatnyeva, Olga; Shekari, Faezeh; Shelke, Ganesh Vilas; Shetty, Ashok K.; Shiba, Kiyotaka; Siljander, Pia R.-M.; Silva, Andreia M.; Skowronek, Agata; Snyder, Orman L.; Soares, Rodrigo Pedro; Sódar, Barbara W.; Soekmadji, Carolina; Sotillo, Javier; Stahl, Philip D.; Stoorvogel, Willem; Stott, Shannon L.; Strasser, Erwin F.; Swift, Simon; Tahara, Hidetoshi; Tewari, Muneesh; Timms, Kate; Tiwari, Swasti; Tixeira, Rochelle; Tkach, Mercedes; Toh, Wei Seong; Tomasini, Richard; Torrecilhas, Ana Claudia; Tosar, Juan Pablo; Toxavidis, Vasilis; Urbanelli, Lorena; Vader, Pieter; van Balkom, Bas Wm; van der Grein, Susanne G.; Van Deun, Jan; van Herwijnen, Martijn Jc; Van Keuren-Jensen, Kendall; van Niel, Guillaume; van Royen, Martin E.; van Wijnen, Andre J.; Vasconcelos, M. Helena; Vechetti, Ivan J.; Veit, Tiago D.; Vella, Laura J.; Velot, Émilie; Verweij, Frederik J.; Vestad, Beate; Viñas, Jose L.; Visnovitz, Tamás; Vukman, Krisztina V.; Wahlgren, Jessica; Watson, Dionysios C.; Wauben, Marca Hm; Weaver, Alissa; Webber, Jason P.; Weber, Viktoria; Wehman, Ann M.; Weiss, Daniel J.; Welsh, Joshua A.; Wendt, Sebastian; Wheelock, Asa M.; Wiener, Zoltán; Witte, Leonie; Wolfram, Joy; Xagorari, Angeliki; Xander, Patricia; Xu, Jing; Yan, Xiaomei; Yáñez-Mó, María; Yin, Hang; Yuana, Yuana; Zappulli, Valentina; Zarubova, Jana; Žėkas, Vytautas; Zhang, Jian-Ye; Zhao, Zezhou; Zheng, Lei; Zheutlin, Alexander R.; Zickler, Antje M.; Zimmermann, Pascale; Zivkovic, Angela M.; Zocco, Davide; Zuba-Surma, Ewa K.
Abstract:
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Published:
2018
Title:
Model-driven discovery of long-chain fatty acid metabolic reprogramming in heterogeneous prostate cancer cells
Authors:
Marín de Mas, Igor; Aguilar, Esther; Zodda, Erika; Balcells, Cristina; Marin, Silvia; Dallmann, Guido; Thomson, Timothy M.; Papp, Balázs; Cascante, Marta
Abstract:
Epithelial-mesenchymal-transition promotes intra-tumoral heterogeneity, by enhancing tumor cell invasiveness and promoting drug resistance. We integrated transcriptomic data for two clonal subpopulations from a prostate cancer cell line (PC-3) into a genome-scale metabolic network model to explore their metabolic differences and potential vulnerabilities. In this dual cell model, PC-3/S cells express Epithelial-mesenchymal-transition markers and display high invasiveness and low metastatic potential, while PC-3/M cells present the opposite phenotype and higher proliferative rate. Model-driven analysis and experimental validations unveiled a marked metabolic reprogramming in long-chain fatty acids metabolism. While PC-3/M cells showed an enhanced entry of long-chain fatty acids into the mitochondria, PC-3/S cells used long-chain fatty acids as precursors of eicosanoid metabolism. We suggest that this metabolic reprogramming endows PC-3/M cells with augmented energy metabolism for fast proliferation and PC-3/S cells with increased eicosanoid production impacting angiogenesis, cell adhesion and invasion. PC-3/S metabolism also promotes the accumulation of docosahexaenoic acid, a long-chain fatty acid with antiproliferative effects. The potential therapeutic significance of our model was supported by a differential sensitivity of PC-3/M cells to etomoxir, an inhibitor of long-chain fatty acid transport to the mitochondria.
Published:
2018
Title:
Modifiable “predictors” of zinc status in toddlers
Authors:
Daniels, L.; Williams, S.M.; Gibson, R.S.; Taylor, R.W.; Samman, S.; Heath, A.-L.M.
Abstract:
Suboptimal zinc status is common in very young children and likely associated with increased risk of infection and detrimental effects on growth. No studies have determined potentially modifiable “predictors” of zinc status in toddlers from high-income countries. This cross-sectional analysis of 115 toddlers from the Baby-Led Introduction to SolidS (BLISS) study used weighed diet records (three non-consecutive days) to assess dietary intake, and a venous blood sample (trace-element free techniques) to assess plasma zinc, at 12 months of age. “Predictors” of plasma zinc were determined by univariate analysis and multiple regression. Mean (SD) plasma zinc was 9.7 (1.5) µmol/L, 60% were below the IZiNCG reference limit of
Published:
2018
Title:
Molecular and Cellular Requirements for the Assembly of Tertiary Lymphoid Structures
Authors:
Mueller, C. G.; Nayar, S.; Campos, J.; Barone, F.
Abstract:
Published:
2018
Title:
More sugar? No, thank you! The elusive nature of low carbohydrate diets
Authors:
Giugliano, Dario; Maiorino, Maria Ida; Bellastella, Giuseppe; Esposito, Katherine
Abstract:
In the past decades, dietary guidelines focused on reducing saturated fat as the primary strategy for cardiovascular disease prevention, neglecting the many other potential effects of diet on health, in particular the harmful effects of sugar. A greater intake of soft drinks (sugar-sweetened beverages), for example, is associated with a 44% increased prevalence of metabolic syndrome, a higher risk of obesity, and a 26% increased risk of developing diabetes mellitus. Carbohydrates comprise around 55% of the typical western diet, ranging from 200 to 350 g/day in relation to a person's overall caloric intake. For long-term weight gain, food rich in refined grains, starches, and sugar appear to be major culprits. Low-carbohydrate diets restrict daily carbohydrates between 20 and 50 g, as in clinical ketogenic diets. The results of controlled trials show that people on ketogenic diets (a diet with no more than 50 g carbohydrates/day) tend to lose more weight than people on low-fat diets. Moreover, there is no good evidence for recommending low-fat diets, as low-carbohydrate diets lead to significantly greater weight loss (1.15 kg) than did low-fat interventions. However, the magnitude of such a benefit is small. As the quality of ingested carbohydrates seems more important than the quantity for health outcomes, people with metabolic disorders should avoid or substantially reduce low-fiber, rapidly digested, refined grains, starches, and added sugars. So, the consumption of the right carbohydrates (high-fiber, slowly digested, and whole grains), in a moderately lower amount (between 40 and 50% of daily energy content), is compatible with a state of good health and may represent a scientifically-based and palatable choice for people with metabolic disorders.
Published:
2018
Title:
Multiple Symmetric Lipomatosis (Madelung Disease) in a Large Canadian Family With the Mitochondrial MTTK c.8344A\textgreaterG Variant
Authors:
Perera, Uththara; Kennedy, Brooke A.; Hegele, Robert A.
Abstract:
Background. Multiple symmetric lipomatosis (MSL), also known as Madelung disease, is a rare adult-onset disorder characterized by benign lipomatosis usually localized to the nuchal and upper thoracic region. A subset of these patients has germline variants in mitochondrial DNA. Methods. Three siblings of Northern European descent with MSL were assessed initially and provided whole blood for DNA analysis. Family history revealed several additional affected siblings who were dispersed across Canada. Targeted histories were obtained from 6 additional affected family members by telephone interviews using a standardized questionnaire, and genomic DNA was obtained from saliva. Sequencing of mitochondrial DNA was performed. Genetic analysis. Eight affected individuals who were studied each had the MTTK gene c.8344A\textgreaterG variant. None of the affected individuals had epilepsy, ataxia, or myopathy. Conclusion. In this extended Canadian family, the rare MTTK c.8344A\textgreaterG variant was linked with Madelung disease in multiple family members. Knowing the likely basis of MSL in this family may help with diagnosis, genetic counseling, monitoring for associated phenotypes, and potential future targeted interventions.
Published:
2018
Title:
NMR-based metabolomics: Quality and authenticity of milk and meat
Authors:
Bertram, H.C.
Abstract:
Animal-based products constitute an important part of our diet, and NMR-based metabolomics has been established as a useful tool in the analysis of dairy products and meat-based food products. In cow milk, NMR-based metabolomics has gained important insight into the associations between metabolic/health status of the cow and the milk metabolite profile, and also the heritability of individual milk metabolites have been established through NMR-based metabolomics analyses. In processed milk such as UHT milk, NMR-based metabolomics can probe storage-induced chemical changes including formation of amino acids as a result of proteolysis, and in fermented dairy products, NMR-based metabolomics is recently established as a useful tool to study the fermentation process and elucidate synergistic and symbiotic microbial interactions. Based on correlation analyses between the cheese metabolome and sensory properties of soft cheese, specific metabolites of importance for cheese aroma have been identified. On meat, NMR metabolomics has been used to elucidate the associations between postmortem metabolism and subsequent meat quality development, where lactate and energy-rich phosphorous-containing metabolites are essential. Furthermore, NMR metabolomics has been applied to examine how the meat metabolite profile varies between species and breeds and as function of slaughter age and aging. In processed meat, NMR metabolomics of lipophilic meat extracts has been demonstrated to hold a promise for discrimination of nonirradiated and irradiated products. Overall, NMR-based metabolomics is found useful in a variety of applications on animal-based foods. © Springer International Publishing AG, part of Springer Nature 2018.
Published:
2018
Title:
Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study
Authors:
Burisch, Johan; Kiudelis, Gediminas; Kupcinskas, Limas; Kievit, Hendrika Adriana Linda; Andersen, Karina Winther; Andersen, Vibeke; Salupere, Riina; Pedersen, Natalia; Kjeldsen, Jens; D'Incà, Renata; Valpiani, Daniela; Schwartz, Doron; Odes, Selwyn; Olsen, Jóngerð; Nielsen, Kári Rubek; Vegh, Zsuzsanna; Lakatos, Peter Laszlo; Toca, Alina; Turcan, Svetlana; Katsanos, Konstantinos H.; Christodoulou, Dimitrios K.; Fumery, Mathurin; Gower-Rousseau, Corinne; Chetcuti Zammit, Stefania; Ellul, Pierre; Eriksson, Carl; Halfvarson, Jonas; Magro, Fernando Jose; Duricova, Dana; Bortlik, Martin; Fernandez, Alberto; Hernández, Vicent; Myers, Sally; Sebastian, Shaji; Oksanen, Pia; Collin, Pekka; Goldis, Adrian; Misra, Ravi; Arebi, Naila; Kaimakliotis, Ioannis P.; Nikuina, Inna; Belousova, Elena; Brinar, Marko; Cukovic-Cavka, Silvija; Langholz, Ebbe; Munkholm, Pia; Epi-IBD group
Abstract:
OBJECTIVE: The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn's disease (CD). DESIGN: Patients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis. RESULTS: In total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P
Published:
2018
Title:
Neuronal autophagy and intercellular regulation of homeostasis in the brain
Authors:
Kulkarni, Aditi; Chen, Jessica; Maday, Sandra
Abstract:
Neurons are particularly dependent on robust quality control pathways to maintain cellular homeostasis and functionality throughout their extended lifetime. Failure to regulate protein and organelle integrity is linked to devastating neurodegenerative diseases. Autophagy is a lysosomal degradation pathway that maintains homeostasis by recycling damaged or aged cellular components. Autophagy has important functions in development of the nervous system, as well as in neuronal function and survival. In fact, defects in autophagy underlie neurodegeneration in mice and humans. Here, we review the compartment-specific dynamics and functions for autophagy in neurons. Emerging evidence suggests novel pathways for the intercellular coordination of quality control pathways between neurons and glia to maintain homeostasis in the brain.
Published:
2018
Title:
Night shift work increases the risks of multiple primary cancers in women: A systematic review and meta-analysis of 61 articles
Authors:
Yuan, Xia; Zhu, Chenjing; Wang, Manni; Mo, Fei; Du, Wei; Ma, Xuelei
Abstract:
© 2018 American Association for Cancer Research. A growing number of studies have examined associations between night shift work and the risks of common cancers among women, with varying conclusions. We did a metaanalysis to identify whether long-term night shift work increased the risks of common cancers in women. We enrolled 61 articles involving 114,628 cases and 3,909,152 participants fromEurope, North America, Asia, and Australia. Risk estimates were performed with a random-effect model or a fixed-effect model. Subgroup analyses and meta-regression analyses about breast cancer were conducted to explore possible sources of heterogeneity. In addition, we carried out a dose-response analysis to quantitatively estimate the accumulative effect of night shift work on the risk of breast cancer. A positive relationship was revealed between long-term night shift work and the risks of breast [OR = 1.316; 95% confidence interval (CI), 1.196-1.448], digestive system (OR = 1.177; 95% CI, 1.065- 1.301), and skin cancer (OR = 1.408; 95% CI, 1.024-1.934). For every 5 years of night shift work, the risk of breast cancer in women was increased by 3.3% (OR = 1.033; 95% CI, 1.012- 1.056). Concerning the group of nurses, long-term night shift work presented potential carcinogenic effect in breast cancer (OR = 1.577; 95% CI, 1.235-2.014), digestive system cancer (OR = 1.350; 95% CI, 1.030-1.770), and lung cancer (OR = 1.280; 95% CI, 1.070-1.531). This systematic review confirmed the positive association between night shift work and the risks of several common cancers in women. We identified that cancer risk of women increased with accumulating years of night shift work, which might help establish and implement effective measures to protect female night shifters.
Published:
2018
Title:
Non-invasive continuous real-time in vivo analysis of microbial hydrogen production shows adaptation to fermentable carbohydrates in mice
Authors:
Fernández-Calleja, José M. S.; Konstanti, Prokopis; Swarts, Hans J. M.; Bouwman, Lianne M. S.; Garcia-Campayo, Vicenta; Billecke, Nils; Oosting, Annemarie; Smidt, Hauke; Keijer, Jaap; van Schothorst, Evert M.
Abstract:
Real time in vivo methods are needed to better understand the interplay between diet and the gastrointestinal microbiota. Therefore, a rodent indirect calorimetry system was equipped with hydrogen (H2) and methane (CH4) sensors. H2 production was readily detected in C57BL/6J mice and followed a circadian rhythm. H2 production was increased within 12 hours after first exposure to a lowly-digestible starch diet (LDD) compared to a highly-digestible starch diet (HDD). Marked differences were observed in the faecal microbiota of animals fed the LDD and HDD diets. H2 was identified as a key variable explaining the variation in microbial communities, with specific taxa (including Bacteroides and Parasutterella) correlating with H2 production upon LDD-feeding. CH4 production was undetectable which was in line with absence of CH4 producers in the gut. We conclude that real-time in vivo monitoring of gases provides a non-invasive time-resolved system to explore the interplay between nutrition and gut microbes in a mouse model, and demonstrates potential for translation to other animal models and human studies.
Published:
2018
Title:
Nontoxic Targeting of Energy Metabolism in Preclinical VM-M3 Experimental Glioblastoma
Authors:
Augur, Zachary M.; Doyle, Catherine M.; Li, Mingyi; Mukherjee, Purna; Seyfried, Thomas N.
Abstract:
Introduction: Temozolomide (TMZ) is part of the standard of care for treating glioblastoma multiforme (GBM), an aggressive primary brain tumor. New approaches are needed to enhance therapeutic efficacy and reduce toxicity. GBM tumor cells are dependent on glucose and glutamine while relying heavily on aerobic fermentation for energy metabolism. Restricted availability of glucose and glutamine may therefore reduce disease progression. Calorically restricted ketogenic diets (KD-R), which reduce glucose and elevate ketone bodies, offer a promising alternative in targeting energy metabolism because cancer cells cannot effectively burn ketones due to defects in the number, structure, and function of mitochondria. Similarly, oxaloacetate, which participates in the deamination of glutamate, has the potential to reduce the negative effects of excess glutamate found in many brain tumors, while hyperbaric oxygen therapy can reverse the hypoxic phenotype of tumors and reduce growth. We hypothesize that the combinatorial therapy of KD-R, hyperbaric oxygen, and oxaloacetate, could reduce or eliminate the need for TMZ in GBM patients. Methods: Our proposed approach for inhibiting tumor metabolism involved various combinations of the KD-R, oxaloacetate (2 mg/g), hyperbaric oxygen, and TMZ (20 mg/kg). This combinatorial therapy was tested on adult VM/Dk mice bearing the VM-M3/Fluc preclinical GBM model grown orthotopically. After 14 days, tumor growth was quantified via bioluminescence. A survival study was performed and the data were analyzed and portrayed in a Kaplan Meier plot. Preliminary dosage studies were used and strict diet and drug administration was maintained throughout the study. Results: The therapeutic effect of all treatments was powerful when administered under KD-R. The most promising survival advantage was seen in the two groups receiving oxaloacetate without TMZ. The survival of mice receiving TMZ was diminished due to its apparent toxicity. Among all groups, those receiving TMZ had the most significant reduction in tumor growth. The most powerful therapeutic effect was evident with combinations of these therapies. Conclusion: This study provides evidence for a potentially novel therapeutic regimen of hyperbaric oxygen, oxaloacetate, and the KD-R for managing growth and progression of VM-M3/Fluc GBM.
Published:
2018
Title:
Nutrimetabolomics: integrating metabolomics in nutrition to disentangle intake of animal-based foods
Authors:
Bertram, Hanne Christine; Jakobsen, Louise Margrethe Arildsen
Abstract:
Food intake and metabolization of foods is a complex and multi-facetted process that encompasses the introduction of new metabolite compounds in our body, initiation or alterations in endogenous metabolic processes and biochemical pathways, and likely also involving the activity of the gut microbial community that we host. The explorative nature of metabolomics makes it a superior tool for examining the whole response to food intake in a more thorough way and has led to the introduction of the term nutrimetabolomics. Protein derived from animal sources constitutes an important part of our diet, and there is therefore an interest in understanding how these animal-derived dietary sources influence us metabolically. This review aims to illuminate how the introduction of nutrimetabolomics has contributed to gain novel insight into metabolic and nutritional aspects related to intake of animal-based foods.
Published:
2018
Title:
Nutrition and prevention of cognitive impairment
Authors:
Scarmeas, N.; Anastasiou, C.A.; Yannakoulia, M.
Abstract:
Nutrition is an important lifestyle factor that can modify the risk of future cognitive impairment and dementia. Some, but not conclusive, evidence (mostly from observational studies and infrequently from clinical trials) exists of a protective association between certain nutrients (eg, folate, flavonoids, vitamin D, and certain lipids) or food groups (eg, seafood, vegetables, and fruits, and potentially moderate alcohol and caffeine consumption) and cognitive outcomes in older people. For some nutrients and food groups, protection might be greater in individuals with either deficiencies in certain nutrients or a genetic predisposition to cognitive impairment. Identification of potentially different associations between such subgroups should be a priority for future research. At present, evidence of an association between nutrition and cognitive outcomes is somehow stronger for healthy dietary patterns, such as the Mediterranean-type diet, than for individual nutrients and food groups, possibly because of the cumulative beneficial effects of the many ingredients in these diets. Multidomain interventions (including a nutrition component) might also hold some promise for the prevention of cognitive impairment and dementia, but their effectiveness is still uncertain. Use of advanced technologies for nutrition assessment (eg, metabolomics and innovative methods of dietary intake assessment) and recently identified biomarkers of nutrition and neurobiological outcomes will be important to achieve this goal. © 2018 Elsevier Ltd
Published:
2018
Title:
Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health
Authors:
Miller, Vincent J.; Villamena, Frederick A.; Volek, Jeff S.
Abstract:
Impaired mitochondrial function often results in excessive production of reactive oxygen species (ROS) and is involved in the etiology of many chronic diseases, including cardiovascular disease, diabetes, neurodegenerative disorders, and cancer. Moderate levels of mitochondrial ROS, however, can protect against chronic disease by inducing upregulation of mitochondrial capacity and endogenous antioxidant defense. This phenomenon, referred to as mitohormesis, is induced through increased reliance on mitochondrial respiration, which can occur through diet or exercise. Nutritional ketosis is a safe and physiological metabolic state induced through a ketogenic diet low in carbohydrate and moderate in protein. Such a diet increases reliance on mitochondrial respiration and may, therefore, induce mitohormesis. Furthermore, the ketone β -hydroxybutyrate (BHB), which is elevated during nutritional ketosis to levels no greater than those resulting from fasting, acts as a signaling molecule in addition to its traditionally known role as an energy substrate. BHB signaling induces adaptations similar to mitohormesis, thereby expanding the potential benefit of nutritional ketosis beyond carbohydrate restriction. This review describes the evidence supporting enhancement of mitochondrial function and endogenous antioxidant defense in response to nutritional ketosis, as well as the potential mechanisms leading to these adaptations.
Published:
2018
Title:
Nutritional Ketosis for Weight Management and Reversal of Metabolic Syndrome
Authors:
Gershuni, Victoria M.; Yan, Stephanie L.; Medici, Valentina
Abstract:
PURPOSE OF REVIEW: The goal of this paper is to review current literature on nutritional ketosis within the context of weight management and metabolic syndrome, namely, insulin resistance, lipid profile, cardiovascular disease risk, and development of non-alcoholic fatty liver disease. We provide background on the mechanism of ketogenesis and describe nutritional ketosis. RECENT FINDINGS: Nutritional ketosis has been found to improve metabolic and inflammatory markers, including lipids, HbA1c, high-sensitivity CRP, fasting insulin and glucose levels, and aid in weight management. We discuss these findings and elaborate on potential mechanisms of ketones for promoting weight loss, decreasing hunger, and increasing satiety. Humans have evolved with the capacity for metabolic flexibility and the ability to use ketones for fuel. During states of low dietary carbohydrate intake, insulin levels remain low and ketogenesis takes place. These conditions promote breakdown of excess fat stores, sparing of lean muscle, and improvement in insulin sensitivity.
Published:
2018
Title:
Nutritionally recommended food for semi- to strict vegetarian diets based on large-scale nutrient composition data
Authors:
Kim, Seunghyeon; Fenech, Michael F.; Kim, Pan-Jun
Abstract:
Diet design for vegetarian health is challenging due to the limited food repertoire of vegetarians. This challenge can be partially overcome by quantitative, data-driven approaches that utilise massive nutritional information collected for many different foods. Based on large-scale data of foods' nutrient compositions, the recent concept of nutritional fitness helps quantify a nutrient balance within each food with regard to satisfying daily nutritional requirements. Nutritional fitness offers prioritisation of recommended foods using the foods' occurrence in nutritionally adequate food combinations. Here, we systematically identify nutritionally recommendable foods for semi- to strict vegetarian diets through the computation of nutritional fitness. Along with commonly recommendable foods across different diets, our analysis reveals favourable foods specific to each diet, such as immature lima beans for a vegan diet as an amino acid and choline source, and mushrooms for ovo-lacto vegetarian and vegan diets as a vitamin D source. Furthermore, we find that selenium and other essential micronutrients can be subject to deficiency in plant-based diets, and suggest nutritionally-desirable dietary patterns. We extend our analysis to two hypothetical scenarios of highly personalised, plant-based methionine-restricted diets. Our nutrient-profiling approach may provide a useful guide for designing different types of personalised vegetarian diets.
Published:
2018
Title:
O-GlcNAcylation of RACK1 promotes hepatocellular carcinogenesis
Authors:
Duan, Fangfang; Wu, Hao; Jia, Dongwei; Wu, Weicheng; Ren, Shifang; Wang, Lan; Song, Shushu; Guo, Xinying; Liu, Fenglin; Ruan, Yuanyuan; Gu, Jianxin
Abstract:
BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis. Nevertheless, whether and how these two pathways are interlinked remain unknown. Our previous study indicated that ribosomal receptor for activated C-kinase 1 (RACK1) promoted chemoresistance and growth in hepatocellular carcinoma (HCC). The aim of this study is to examine the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis. METHODS: The site(s) of RACK1 for O-GlcNAcylation was mapped by mass spectrometry analysis. HCC cell lines were employed to examine the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells in vitro. Transgenic knock-in mice were used to detect the role of RACK1 O-GlcNAcylation in modulating HCC tumorigenesis in vivo. The correlation of RACK1 O-GlcNAcylation with tumor progression and relapse were analyzed in clinical HCC samples. RESULTS: We found that ribosomal RACK1 was highly modified by O-GlcNAc at Ser122. O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells. Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model. Increased RACK1 O-GlcNAcylation was also observed in HCC patient samples and correlated with tumor development and recurrence after chemotherapy. CONCLUSIONS: These findings demonstrate that RACK1 acts as key mediator linking O-GlcNAc metabolism to cap-dependent translation during HCC tumorigenesis. Targeting RACK1 O-GlcNAcylation provides promising options for HCC treatment. LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma. Increased O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 is positively correlated with tumor growth, metastasis and recurrence in patients with hepatocellular carcinoma.
Published:
2018
Title:
Omega‐6 fats for the primary and secondary prevention of cardiovascular disease
Authors:
Hooper, Lee; Al‐Khudairy, Lena; Abdelhamid, Asmaa S.; Rees, Karen; Brainard, Julii S.; Brown, Tracey J.; Ajabnoor, Sarah M.; O'Brien, Alex T.; Winstanley, Lauren E.; Donaldson, Daisy H.; Song, Fujian; Deane, Katherine HO
Abstract:
Published:
2018
Title:
Paleoecology of the Serengeti during the Oldowan-Acheulean transition at Olduvai Gorge, Tanzania: The mammal and fish evidence
Authors:
Bibi, Faysal; Pante, Michael; Souron, Antoine; Stewart, Kathlyn; Varela, Sara; Werdelin, Lars; Boisserie, Jean-Renaud; Fortelius, Mikael; Hlusko, Leslea; Njau, Jackson; de la Torre, Ignacio
Abstract:
Eight years of excavation work by the Olduvai Geochronology and Archaeology Project (OGAP) has produced a rich vertebrate fauna from several sites within Bed II, Olduvai Gorge, Tanzania. Study of these as well as recently re-organized collections from Mary Leakey's 1972 HWK EE excavations here provides a synthetic view of the faunal community of Olduvai during Middle Bed II at ∼1.7-1.4 Ma, an interval that captures the local transition from Oldowan to Acheulean technology. We expand the faunal list for this interval, name a new bovid species, clarify the evolution of several mammalian lineages, and record new local first and last appearances. Compositions of the fish and large mammal assemblages support previous indications for the dominance of open and seasonal grassland habitats at the margins of an alkaline lake. Fish diversity is low and dominated by cichlids, which indicates strongly saline conditions. The taphonomy of the fish assemblages supports reconstructions of fluctuating lake levels with mass die-offs in evaporating pools. The mammals are dominated by grazing bovids and equids. Habitats remained consistently dry and open throughout the entire Bed II sequence, with no major turnover or paleoecological changes taking place. Rather, wooded and wet habitats had already given way to drier and more open habitats by the top of Bed I, at 1.85-1.80 Ma. This ecological change is close to the age of the Oldowan-Acheulean transition in Kenya and Ethiopia, but precedes the local transition in Middle Bed II. The Middle Bed II large mammal community is much richer in species and includes a much larger number of large-bodied species (>300 kg) than the modern Serengeti. This reflects the severity of Pleistocene extinctions on African large mammals, with the loss of large species fitting a pattern typical of defaunation or 'downsizing' by human disturbance. However, trophic network (food web) analyses show that the Middle Bed II community was robust, and comparisons with the Serengeti community indicate that the fundamental structure of food webs remained intact despite Pleistocene extinctions. The presence of a generalized meat-eating hominin in the Middle Bed II community would have increased competition among carnivores and vulnerability among herbivores, but the high generality and interconnectedness of the Middle Bed II food web suggests this community was buffered against extinctions caused by trophic interactions.
Published:
2018
Title:
Paradox of hypercholesterolaemia in highly trained, keto-adapted athletes
Authors:
Creighton, Brent C.; Hyde, Parker Neil; Maresh, Carl M.; Kraemer, William J.; Phinney, Stephen D.; Volek, Jeff S.
Abstract:
Objective A growing number of ultra-endurance athletes have switched to a very low-carbohydrate/high-fat eating pattern. We compared markers of cholesterol and the lipoprotein profile in a group of elite ultra-runners consuming a high-carbohydrate (HC) or low-carbohydrate (LC) diet. Methods Fasting blood was obtained from competitive male ultra-endurance runners habitually consuming a very low-carbohydrate (LC; n=10) or high-carbohydrate (HC; n=10) diet to determine blood cholesterol profile, lipoprotein particle distribution and sterol biomarkers of cholesterol balance. Results Plasma total cholesterol, low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) cholesterol were all significantly greater (p\textless0.000) in the LC group (65%, 83% and 60%, respectively). There were also significant differences in lipoprotein particle distribution as evidenced by a greater size and concentration of large HDL and LDL particles, and total LDL particle concentration was significantly greater in the LC group, but they had significantly fewer small LDL particles. Conclusion Ultra-endurance athletes habitually consuming a very low-carbohydrate/high-fat diet for over a year showed unique cholesterol profiles characterised by consistently higher plasma LDL-C and HDL-C, less small LDL particles, and lipoprotein profiles consistent with higher insulin sensitivity. There may be a functional purpose to the expansion of the circulating cholesterol pool to meet the heightened demand for lipid transport in highly trained, keto-adapted athletes.
Published:
2018
Title:
Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin/kexin type 9 antibody treatment
Authors:
Stiekema, Lotte C A; Stroes, Erik S G; Verweij, Simone L; Kassahun, Helina; Chen, Lisa; Wasserman, Scott M; Sabatine, Marc S; Mani, Venkatesh; Fayad, Zahi A
Abstract:
Aims Subjects with lipoprotein(a) [Lp(a)] elevation have increased arterial wall inflammation and cardiovascular risk. In patients at increased cardiovascular risk, arterial wall inflammation is reduced following lipid-lowering therapy by statin treatment or lipoprotein apheresis. However, it is unknown whether lipid-lowering treatment in elevated Lp(a) subjects alters arterial wall inflammation. We evaluated whether evolocumab, which lowers both low-density lipoprotein cholesterol (LDL-C) and Lp(a), attenuates arterial wall inflammation in patients with elevated Lp(a). Methods and results In this multicentre, randomized, double-blind, placebo-controlled study, 129 patients {median [interquartile range (IQR)]: age 60.0 [54.0-67.0] years, Lp(a) 200.0 [155.5-301.5] nmol/L [80.0 (62.5-121.0) mg/dL]; mean [standard deviation (SD)] LDL-C 3.7 [1.0] mmol/L [144.0 (39.7) mg/dL]; National Cholesterol Education Program high risk, 25.6%} were randomized to monthly subcutaneous evolocumab 420 mg or placebo. Compared with placebo, evolocumab reduced LDL-C by 60.7% [95% confidence interval (CI) 65.8-55.5] and Lp(a) by 13.9% (95% CI 19.3-8.5). Among evolocumab-treated patients, the Week 16 mean (SD) LDL-C level was 1.6 (0.7) mmol/L [60.1 (28.1) mg/dL], and the median (IQR) Lp(a) level was 188.0 (140.0-268.0) nmol/L [75.2 (56.0-107.2) mg/dL]. Arterial wall inflammation [most diseased segment target-to-background ratio (MDS TBR)] in the index vessel (left carotid, right carotid, or thoracic aorta) was assessed by 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography. Week 16 index vessel MDS TBR was not significantly altered with evolocumab (-8.3%) vs. placebo (-5.3%) [treatment difference -3.0% (95% CI -7.4% to 1.4%); P = 0.18]. Conclusion Evolocumab treatment in patients with median baseline Lp(a) 200.0 nmol/L led to a large reduction in LDL-C and a small reduction in Lp(a), resulting in persistent elevated Lp(a) levels. The latter may have contributed to the unaltered arterial wall inflammation.
Published:
2018
Title:
Perspectives in the Use of Peptidomics in Ham
Authors:
Gallego, M.; Mora, L.; Toldrá, F.
Abstract:
The use of proteomics in food science has permitted both a better characterization of the food products and the control of their final quality despite the fact that food systems are under continuous changes during processing and consumption. Ham is a very popular meat product frequently consumed in Mediterranean countries after a dry-curing processing that results in the generation of large amounts of peptides that contribute to its texture, flavor, and final quality. Proteolysis is the main biochemical mechanism occurring throughout the dry-cured ham processing and a better knowledge of this phenomenon is essential to give an extra value to the product and produce regular batches. In this regard, peptidomics has become an important tool for the characterization of dry-cured hams in order to identify and quantify bioactive peptides and potential biomarkers, study their stability under processing conditions or gastrointestinal digestion, and search for post-translational modifications that could affect the quality of dry-cured hams. This manuscript is reviewing from the first uses of comparative proteomics in dry-cured ham approaches to the most modern peptidomic studies and their contribution to the advance in meat science. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Published:
2018
Title:
Plant-based diets and cardiovascular health
Authors:
Satija, Ambika; Hu, Frank B.
Abstract:
Plant-based diets, defined in terms of low frequency of animal food consumption, have been increasingly recommended for their health benefits. Numerous studies have found plant-based diets, especially when rich in high quality plant foods such as whole grains, fruits, vegetables, and nuts, to be associated with lower risk of cardiovascular outcomes and intermediate risk factors. This review summarizes the current evidence base examining the associations of plant-based diets with cardiovascular endpoints, and discusses the potential biological mechanisms underlying their health effects, practical recommendations and applications of this research, and directions for future research. Healthful plant-based diets should be recommended as an environmentally sustainable dietary option for improved cardiovascular health.
Published:
2018
Title:
Plant-based diets for children as a means of improving adult cardiometabolic health
Authors:
Desmond, Malgorzata A.; Sobiecki, Jakub; Fewtrell, Mary; Wells, Jonathan C. K.
Abstract:
Cardiovascular disease (CVD) is the largest contributor to global mortality, and this trend is expected to continue. Although mortality rates have been falling, adverse developments in obesity and diabetes threaten to reverse this. It has been estimated that the only viable strategy to reduce the epidemic is to focus on population-wide risk factor reduction. Primordial prevention, a strategy aimed at avoiding the development of risk factors before the disease onset, has been shown to reduce the CVD epidemic substantially. Plant-based diets appear beneficial for prevention of cardiometabolic diseases, with adult vegetarians and vegans having lower CVD risk than omnivores. Atherosclerosis starts in childhood and progresses in relation to classical CVD risk factors, which, along with dietary habits, track to adulthood. Based on this evidence, it is proposed that plant-based diets in childhood could promote cardiometabolic health in adults and thereby reduce CVD and promote longevity and health. However, the need for additional research to establish the safety of predominantly or exclusively plant-based diets in children is noted.
Published:
2018
Title:
Plasma metabolites associated with healthy Nordic dietary indexes and risk of type 2 diabetes - A nested case-control study in a Swedish population
Authors:
Shi, L.; Brunius, C.; Johansson, I.; Bergdahl, I.A.; Lindahl, B.; Hanhineva, K.; Landberg, R.
Abstract:
Background: Epidemiologic evidence on the association of a healthy Nordic diet and future type 2 diabetes (T2D) is limited. Exploring metabolites as biomarkers of healthy Nordic dietary patterns may facilitate investigation of associations between such patterns and T2D. Objectives: We aimed to identify metabolites related to a priori-defined healthy Nordic dietary indexes, the Baltic Sea Diet Score (BSDS) and Healthy Nordic Food Index (HNFI), and evaluate associations with the T2D risk in a case-control study nested in a Swedish population-based prospective cohort. Design: Plasma samples from 421 case-control pairs at baseline and samples from a subset of 151 healthy controls at a 10-y follow-up were analyzed with the use of untargeted liquid chromatography-mass spectrometry metabolomics. Index-related metabolites were identified through the use of random forest modelling followed by partial correlation analysis adjustment for lifestyle confounders. Metabolite patterns were derived via principal component analysis (PCA). ORs of T2D were estimated via conditional logistic regression. Reproducibility of metabolites was assessed by intraclass correlation (ICC) in healthy controls. Associations were also assessed for 10 metabolites previously identified as linking a healthy Nordic diet with T2D. Results: In total, 31 metabolites were associated with BSDS and/or HNFI (-0.19 ≤ r ≤ 0.21, 0.10 ≤ ICC ≤ 0.59). Two PCs were determined from index-related metabolites: PC1 strongly correlated to the indexes (r = 0.27 for BSDS, r = 0.25 for HNFI, ICC = 0.45) but showed no association with T2D risk. PC2 was weakly associated with the indexes, but more strongly with foods not part of the indexes, e.g., pizza, sausages, and hamburgers. PC2 was also significantly associated with T2D risk. Predefined metabolites were confirmed to be reflective of consumption of whole grains, fish, or vegetables, but not related to T2D risk. Conclusions: Our study did not support an association between healthy Nordic dietary indexes and T2D. However, foods such as hamburger, sausage, and pizza not covered by the indexes appeared to be more important for T2D risk in the current population. © 2018 American Society for Nutrition.
Published:
2018
Title:
Postprandial Metabolism and Appetite Do Not Differ between Lean Adults that Eat Breakfast or Morning Fast for 6 Weeks
Authors:
Chowdhury, Enhad A.; Richardson, Judith D.; Tsintzas, Kostas; Thompson, Dylan; Betts, James A.
Abstract:
Background: It remains unknown whether sustained daily feeding-fasting patterns modify the acute response to specific feedings on a given day. Objective: We conducted a randomized controlled trial to establish if daily breakfast consumption or fasting until noon modifies the acute metabolic and appetitive responses to a fixed breakfast and ad libitum lunch. Methods: With the use of a parallel group design, we randomly assigned 31 healthy, lean men and women (22-56 y) to 6 wk of either consuming ≥700 kcal of self-selected items before 1100 or fasting (0 kcal) until 1200 daily. Following 48 h of diet and physical activity standardization, we examined metabolic and appetite responses to a standardized breakfast and ad libitum lunch before and after the intervention. Data were analyzed using 3- and 2-way ANCOVA. Results: Systemic concentrations of energy balance regulatory hormones total and acylated ghrelin, leptin, and peptide tyrosine-tyrosine) responded similarly to breakfast and lunch before and after 6 wk of either morning fasting or regular breakfast, with the exception of a tendency for increased glucagon-like peptide-1 concentrations from baseline to follow-up in the Breakfast Group compared with a decrease over that period in the Fasting Group [P = 0.06, partial eta squared value (ƞ2) = 0.16]. Subjective appetite sensations also did not differ over the course of the day, and ad libitum energy intake at lunch was not systematically affected by either intervention, decreasing by 27 kcal (95% CI: -203, 149 kcal) with fasting and by 77 kcal (95% CI: -210, 56 kcal) with breakfast. Similarly, glycemic, insulinemic, lipemic, and thermogenic responses to breakfast and lunch were very stable at baseline and follow-up and, thus, did not differ between treatment groups. Conclusions: Our results indicate that a sustained period of either extended morning fasting or eating a daily breakfast has minimal effect upon acute metabolic and appetite responses in lean adults. This trial was registered at www.isrctn.org as ISRCTN31521726.
Published:
2018
Title:
Precision Medicine for Alzheimer's Disease Prevention
Authors:
Scheyer, Olivia; Mosconi, Lisa; Berkowitz, Cara; Hristov, Hollie; Rahman, Aneela; Isaacson, Richard
Abstract:
Precision medicine is an approach to medical treatment and prevention that takes into account individual variability in genes, environment, and lifestyle and allows for personalization that is based on factors that may affect the response to treatment. Several genetic and epigenetic risk factors have been shown to increase susceptibility to late-onset Alzheimer's disease (AD). As such, it may be beneficial to integrate genetic risk factors into the AD prevention approach, which in the past has primarily been focused on universal risk-reduction strategies for the general population rather than individualized interventions in a targeted fashion. This review discusses examples of a “one-size-fits-all” versus clinical precision medicine AD prevention strategy, in which the precision medicine approach considers two genes that can be commercially sequenced for polymorphisms associated with AD, apolipoprotein E (APOE), and methylenetetrahydrofolate reductase (MTHFR). Comparing these two distinct approaches provides support for a clinical precision medicine prevention strategy, which may ultimately lead to more favorable patient outcomes as the interventions are targeted to address individualized risks.
Published:
2018
Title:
Primate Diet
Authors:
Lambert, Joanna E.
Abstract:
Published:
2018
Title:
Protocols for Migration and Invasion Studies in Prostate Cancer
Authors:
van de Merbel, Arjanneke F.; van der Horst, Geertje; Buijs, Jeroen T.; van der Pluijm, Gabri
Abstract:
Prostate cancer is the most common malignancy diagnosed in men in the western world. The development of distant metastases and therapy resistance are major clinical problems in the management of prostate cancer patients. In order for prostate cancer to metastasize to distant sites in the human body, prostate cancer cells have to migrate and invade neighboring tissue. Cancer cells can acquire a migratory and invasive phenotype in several ways, including single cell and collective migration. As a requisite for migration, epithelial prostate cancer cells often need to acquire a motile, mesenchymal-like phenotype. This way prostate cancer cells often lose polarity and epithelial characteristics (e.g., expression of E-cadherin homotypic adhesion receptor), and acquire mesenchymal phenotype (for example, cytoskeletal rearrangements, enhanced expression of proteolytic enzymes and other repertory of integrins). This process is referred to as epithelial-to-mesenchymal transition (EMT). Cellular invasion, one of the hallmarks of cancer, is characterized by the movement of cells through a three-dimensional matrix, resulting in remodeling of the cellular environment. Cellular invasion requires adhesion, proteolysis of the extracellular matrix, and migration of cells. Studying the migratory and invasive ability of cells in vitro represents a useful tool to assess the aggressiveness of solid cancers, including those of the prostate.This chapter provides a comprehensive description of the Transwell migration assay, a commonly used technique to investigate the migratory behavior of prostate cancer cells in vitro. Furthermore, we will provide an overview of the adaptations to the Transwell migration protocol to study the invasive capacity of prostate cancer cells, i.e., the Transwell invasion assay. Finally, we will present a detailed description of the procedures required to stain the Transwell filter inserts and quantify the migration and/or invasion.
Published:
2018
Title:
RNA-Seq reveals differentially expressed genes affecting polyunsaturated fatty acids percentage in the Huangshan Black chicken population
Authors:
Yang, S.; Wang, Y.; Wang, L.; Shi, Z.; Ou, X.; Wu, D.; Zhang, X.; Hu, H.; Yuan, J.; Wang, W.; Cao, F.; Liu, G.
Abstract:
Fatty acids metabolic products determine meat quality in chickens. Identifying genes associated with fatty acids composition could provide valuable information for the complex genetic networks of genes with underlying variations in fatty acids synthesis. RNA sequencing (RNA-Seq) was conducted to explore the chicken transcriptome from the thigh muscle tissue of 6 Huangshan Black Chickens with 3 extremely high and low phenotypic values for percentage of polyunsaturated fatty acids (PUFAs). In total, we obtained 41,139,108–44,901,729 uniquely mapped reads, which covered 74.15% of the current annotated transcripts including 18964 mRNA transcripts, across all the six thigh muscle tissue samples. Of these, we revealed 274 differentially expressed genes (DEGs) with a highly significant correlation with polyunsaturated fatty acids percentage between the comparison groups based on the ratio of PUFA/SFA. Gene ontology and pathway analysis indicated that the DEGs were enriched in particular biological processes affecting fatty acids metabolism, biosynthe-sis of unsaturated fatty acids (USFAs), and cell junction-related pathways. Integrated interpretation of differential gene expression and formerly reported quantitative trait loci (QTL) demonstrated that FADS2, DCN, FRZB, OGN, PRKAG3, LHFP, CHCHD10, CYTL1, FBLN5, and ADGRD1 are the most promising candidate genes affecting polyunsaturated fatty acids percentage. © 2018 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Published:
2018
Title:
Reduced salt intake for heart failure: A systematic review
Authors:
Mahtani, Kamal R.; Heneghan, Carl; Onakpoya, Igho; Tierney, Stephanie; Aronson, Jeffrey K.; Roberts, Nia; Hobbs, F. D.Richard; Nunan, David
Abstract:
\textlessh3\textgreaterImportance\textless/h3\textgreater\textlessp\textgreaterRecent estimates suggest that more than 26 million people worldwide have heart failure. The syndrome is associated with major symptoms, significantly increased mortality, and extensive use of health care. Evidence-based treatments influence all these outcomes in a proportion of patients with heart failure. Current management also often includes advice to reduce dietary salt intake, although the benefits are uncertain.\textless/p\textgreater\textlessh3\textgreaterObjective\textless/h3\textgreater\textlessp\textgreaterTo systematically review randomized clinical trials of reduced dietary salt in adult inpatients or outpatients with heart failure.\textless/p\textgreater\textlessh3\textgreaterEvidence Review\textless/h3\textgreater\textlessp\textgreaterSeveral bibliographic databases were systematically searched, including the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and CINAHL. The methodologic quality of the studies was evaluated, and data associated with primary outcomes of interest (cardiovascular-associated mortality, all-cause mortality, and adverse events, such as stroke and myocardial infarction) and secondary outcomes (hospitalization, length of inpatient stay, change in New York Heart Association [NYHA] functional class, adherence to dietary low-salt intake, and changes in blood pressure) were extracted.\textless/p\textgreater\textlessh3\textgreaterFindings\textless/h3\textgreater\textlessp\textgreaterOf 2655 retrieved references, 9 studies involving 479 unique participants were included in the analysis. None of the studies included more than 100 participants. The risks of bias in the 9 studies were variable. None of the included studies provided sufficient data on the primary outcomes of interest. For the secondary outcomes of interest, 2 outpatient-based studies reported that NYHA functional class was not improved by restriction of salt intake, whereas 2 studies reported significant improvements in NYHA functional class.\textless/p\textgreater\textlessh3\textgreaterConclusions and Relevance\textless/h3\textgreater\textlessp\textgreaterLimited evidence of clinical improvement was available among outpatients who reduced dietary salt intake, and evidence was inconclusive for inpatients. Overall, a paucity of robust high-quality evidence to support or refute current guidance was available. This review suggests that well-designed, adequately powered studies are needed to reduce uncertainty about the use of this intervention.\textless/p\textgreater\textlessh3\textgreaterProtocol Registration\textless/h3\textgreater\textlessp\textgreaterPROSPERO Identifier:CRD42015019504\textless/p\textgreater
Published:
2018
Title:
Regulation of immunophenotype modulation of monocytes-macrophages from M1 into M2 by prostate cancer cell-culture supernatant via transcription factor STAT3
Authors:
Solís-Martínez, R.; Cancino-Marentes, M.; Hernández-Flores, G.; Ortiz-Lazareno, P.; Mandujano-Álvarez, G.; Cruz-Gálvez, C.; Sierra-Díaz, E.; Rodríguez-Padilla, C.; Jave-Suárez, L. F.; Aguilar-Lemarroy, A.; Bravo-Cuellar, A.
Abstract:
BACKGROUND: Transcription factor STAT3 has a prominent innate immunity effect on cancer progression. We determined the regulation of STAT3 in the immunophenotype modulation of macrophages from M1 into M2 induced by the cell-culture supernatant of the Prostate-Cancer line PC3. METHODS: Monocytes-macrophages from healthy donors were cultured in the supernatant of PC3 cells, membrane proteins, and intracytoplasmic and phosphorylated STAT3 were measured using flow cytometry, while cytokines and growth factors were studied using luminescence. Cytotoxicity and nitric oxide were evaluated via colorimetric assays. RESULTS: The supernatant of PC3 prostate-tumor cells effectively induced macrophages toward an M2 profile, and the expression of phosphorylated STAT3 in the monocytes-macrophages notably increased, and mainly related to IL-10. In the group of monocytes-macrophages treated with a STAT3 inhibitor, the macrophages were induced toward an M1 phenotype. CONCLUSIONS: In this study, we showed that the secretion profile of PC3 prostate-cancer cells induces a change in macrophage phenotype from M1 into M2, and that the phenomenon is related to phosphorylation of transcription factor STAT3 and IL-10.
Published:
2018
Title:
Relapse Prevention in Ulcerative Colitis by Plant-Based Diet Through Educational Hospitalization: A Single-Group Trial
Authors:
Chiba, Mitsuro; Nakane, Kunio; Tsuji, Tsuyotoshi; Tsuda, Satoko; Ishii, Hajime; Ohno, Hideo; Watanabe, Kenta; Ito, Mai; Komatsu, Masafumi; Yamada, Koko; Sugawara, Takeshi
Abstract:
CONTEXT: No known published study has focused on a plant-based diet (PBD) in the treatment of ulcerative colitis (UC). OBJECTIVE: To investigate relapse prevention in UC after consumption of a PBD during educational hospitalization in Japan. DESIGN: Prospective study of patients with mild UC or UC in remission who did not need immediate treatment. A PBD and dietary guidance were provided during a two-week hospitalization. MAIN OUTCOME MEASURES: The primary end point was relapse (a flare-up that required more aggressive treatment) during the follow-up period. Kaplan-Meier analysis was used to calculate the cumulative relapse rate. Secondary end points were immediate improvement in symptoms or laboratory data during hospitalization and a chronologic change in the PBD score, which evaluated adherence to the PBD. RESULTS: Sixty cases were studied: 29 initial episode cases and 31 relapse cases. Of these, 31 involved proctitis; 7, left-sided colitis; and 22, extensive colitis. Thirty-seven patients were receiving medication; 23 were not. The median age was 34 years; median follow-up was 3 years 6 months. Eight cases relapsed during follow-up. The cumulative relapse rates at 1, 2, 3, 4, and 5 years of follow-up were 2%, 4%, 7%, 19%, and 19%, respectively. Most patients (77%) experienced some improvement such as disappearance or decrease of bloody stool during hospitalization. The short- and long-term PBD scores after the hospitalization were higher than baseline PBD scores. CONCLUSION: Relapse rates after educational hospitalization providing a PBD were far lower than those reported with medication. Educational hospitalization is effective at inducing habitual dietary changes.
Published:
2018
Title:
Relationship Between Fish Consumption and Disease Activity in Rheumatoid Arthritis
Authors:
Tedeschi, Sara K.; Bathon, Joan M.; Giles, Jon T.; Lin, Tzu-Chieh; Yoshida, Kazuki; Solomon, Daniel H.
Abstract:
Objective To assess whether more frequent fish consumption is associated with lower rheumatoid arthritis (RA) disease activity scores among participants in an RA cohort. Methods We conducted a cross-sectional analysis using baseline data from participants in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis cohort study. Frequency of fish consumption was assessed by a baseline food frequency questionnaire assessing usual diet in the past year. Multivariable, total energy–adjusted linear regression models provided effect estimates and 95% confidence intervals (95% CIs) for frequency of fish consumption (i.e., never to <1 time/month, 1 time/month to <1 time/week, 1 time/week, and ≥2 times/week) on baseline Disease Activity Score in 28 joints (DAS28) using the C-reactive protein (CRP) level. We also estimated the difference in DAS28-CRP associated with increasing fish consumption by 1 serving per week. Results Among 176 participants, the median DAS28-CRP score was 3.5 (interquartile range 2.9–4.3). In an adjusted linear regression model, subjects consuming fish ≥2 times/week had a significantly lower DAS28-CRP compared with subjects who ate fish never to
Published:
2018
Title:
Rethinking the evolution of the human foot: insights from experimental research
Authors:
Holowka, Nicholas B.; Lieberman, Daniel E.
Abstract:
Adaptive explanations for modern human foot anatomy have long fascinated evolutionary biologists because of the dramatic differences between our feet and those of our closest living relatives, the great apes. Morphological features, including hallucal opposability, toe length and the longitudinal arch, have traditionally been used to dichotomize human and great ape feet as being adapted for bipedal walking and arboreal locomotion, respectively. However, recent biomechanical models of human foot function and experimental investigations of great ape locomotion have undermined this simple dichotomy. Here, we review this research, focusing on the biomechanics of foot strike, push-off and elastic energy storage in the foot, and show that humans and great apes share some underappreciated, surprising similarities in foot function, such as use of plantigrady and ability to stiffen the midfoot. We also show that several unique features of the human foot, including a spring-like longitudinal arch and short toes, are likely adaptations to long distance running. We use this framework to interpret the fossil record and argue that the human foot passed through three evolutionary stages: first, a great ape-like foot adapted for arboreal locomotion but with some adaptations for bipedal walking; second, a foot adapted for effective bipedal walking but retaining some arboreal grasping adaptations; and third, a human-like foot adapted for enhanced economy during long-distance walking and running that had lost its prehensility. Based on this scenario, we suggest that selection for bipedal running played a major role in the loss of arboreal adaptations.
Published:
2018
Title:
Rethinking the evolution of the human foot: insights from experimental research
Authors:
Holowka, Nicholas B.; Lieberman, Daniel E.
Abstract:
Adaptive explanations for modern human foot anatomy have long fascinated evolutionary biologists because of the dramatic differences between our feet and those of our closest living relatives, the great apes. Morphological features, including hallucal opposability, toe length and the longitudinal arch, have traditionally been used to dichotomize human and great ape feet as being adapted for bipedal walking and arboreal locomotion, respectively. However, recent biomechanical models of human foot function and experimental investigations of great ape locomotion have undermined this simple dichotomy. Here, we review this research, focusing on the biomechanics of foot strike, push-off and elastic energy storage in the foot, and show that humans and great apes share some underappreciated, surprising similarities in foot function, such as use of plantigrady and ability to stiffen the midfoot. We also show that several unique features of the human foot, including a spring-like longitudinal arch and short toes, are likely adaptations to long distance running. We use this framework to interpret the fossil record and argue that the human foot passed through three evolutionary stages: first, a great ape-like foot adapted for arboreal locomotion but with some adaptations for bipedal walking; second, a foot adapted for effective bipedal walking but retaining some arboreal grasping adaptations; and third, a human-like foot adapted for enhanced economy during long-distance walking and running that had lost its prehensility. Based on this scenario, we suggest that selection for bipedal running played a major role in the loss of arboreal adaptations.
Published:
2018
Title:
Risk factors for type 2 diabetes mellitus: An exposure-wide umbrella review of meta-analyses
Authors:
Bellou, V.; Belbasis, L.; Tzoulaki, I.; Evangelou, E.
Abstract:
Background Type 2 diabetes mellitus (T2DM) is a global epidemic associated with increased health expenditure, and low quality of life. Many non-genetic risk factors have been suggested, but their overall epidemiological credibility has not been assessed. Methods We searched PubMed to capture all meta-analyses and Mendelian randomization studies for risk factors of T2DM. For each association, we estimated the summary effect size, its 95% confidence and prediction interval, and the I2 metric. We examined the presence of small-study effects and excess significance bias. We assessed the epidemiological credibility through a set of predefined criteria. Results We captured 86 eligible papers (142 associations) covering a wide range of biomarkers, medical conditions, and dietary, lifestyle, environmental and psychosocial factors. Adi-posity, low hip circumference, serum biomarkers (increased level of alanine aminotransferase, gamma-glutamyl transferase, uric acid and C-reactive protein, and decreased level of adiponectin and vitamin D), an unhealthy dietary pattern (increased consumption of processed meat and sugar-sweetened beverages, decreased intake of whole grains, coffee and heme iron, and low adherence to a healthy dietary pattern), low level of education and conscientiousness, decreased physical activity, high sedentary time and duration of television watching, low alcohol drinking, smoking, air pollution, and some medical conditions (high systolic blood pressure, late menarche age, gestational diabetes, metabolic syndrome, preterm birth) presented robust evidence for increased risk of T2DM. Conclusions A healthy lifestyle pattern could lead to decreased risk for T2DM. Future randomized clinical trials should focus on identifying efficient strategies to modify harmful daily habits and predisposing dietary patterns. © 2018 Bellou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Published:
2018
Title:
Role of advanced glycation end products in carcinogenesis and their therapeutic implications
Authors:
Schröter, D.; Höhn, A.
Abstract:
Aging is one of the biggest risk factors for the major prevalent diseases such as cardiovascular diseases, neurodegeneration and cancer, but due to the complex and multifactorial nature of the aging process, the molecular mechanisms underlying age-related diseases are not yet fully understood. Research has been intensive in the last years aiming to characterize the pathophysiology of aging and develop therapies to fight age-related diseases. In this context advanced glycation end products (AGEs) have received attention. AGEs, when accumulated in tissues, significantly increase the level of inflammation in the body which has long been associated with the development of cancer. Here we discuss the classical settings promoting AGE formation, as well as reduction strategies, occurrence and relevance of AGEs in cancer tissues and the role of AGE-interaction with the receptor for advanced glycation end products (RAGE) in cancer initiation and progression. © 2018 Bentham Science Publishers.
Published:
2018
Title:
Rumen and plasma metabolomics profiling by UHPLC-QTOF/MS revealed metabolic alterations associated with a high-corn diet in beef steers
Authors:
Yang, Y.; Dong, G.; Wang, Z.; Wang, J.; Zhang, Z.; Liu, J.
Abstract:
High-grain diets are strongly associated with metabolic disorders in beef steers. Metabolomics can be used to explore the relationship between diet and metabolic changes, but no study has reported rumen and plasma metabolomics profiling associated with increasing dietary corn proportions in the diet of beef steers. Therefore, 12 steers paired according to similar body weights and body condition scores were randomly allocated to one of two diets: a low-corn (28.76%) diet (LCD) with a 40:60 ratio of concentrate to roughage and a high-corn (48.76%) diet (HCD) with a 60:40 ratio of concentrate to roughage. Metabolomics profiling by ultra-high-performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF/MS) showed that steers fed the HCD had increased rumen and plasma carbohydrate metabolites and amino acids, which contributed to the growth of the beef steers. However, the rumen acidity and ruminal and plasma lipopolysaccharide (LPS) concentrations significantly increased with the increase amounts of corn in the diet. In total, 717 rumen metabolites and 386 plasma metabolites were identified. By multivariate analysis, 144 rumen and 56 plasma metabolites were further identified that were significantly different between the two groups (P 1). The differential metabolites in the rumen and plasma were associated with different metabolic pathways, and phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism were common key metabolic pathways for the two biofluids. In conclusion, the high-corn diet improved the growth performance of beef steers but decreased the ruminal pH and increased the LPS and harmful metabolites in the rumen and blood, which has implications for the incidence of metabolic diseases. The identified differential metabolites in both the rumen and plasma and the related metabolic pathways may contribute to the exploration of potential biomarkers for high-corn diet-based metabolic diseases. © 2018 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Published:
2018
Title:
SGLT-2 Inhibitors and Cardiovascular Protection: Lessons and Gaps in Understanding the Current Outcome Trials and Possible Benefits of Combining SGLT-2 Inhibitors With GLP-1 Agonists
Authors:
Abdelgadir, Elamin; Rashid, Fauzia; Bashier, Alaaeldin; Ali, Razan
Abstract:
Landmark trials on diabetes control have shown variable results in terms of cardiovascular benefits, with the majority showing a favorable effect of glycemic control on microvascular and, more recently, macrovascular complications. However, some trials pointed out a CV hazard with tight diabetes mellitus (DM) control. Most of those trials were assessing the impact of glycemic control, more than evaluating the effect of a certain medication. In the last decade, food and drugs administration (FDA) has mandated that all new hypoglycemic agents run a CV outcome trial (CVOT) for safety in order to grant and sustain approval. The most stunning results came from relatively new agents in the field of diabetes management, sodium-glucose cotrans-porter-2 inhibitors (SGLT2i) and the glucagon-like peptide-1 agonists (GLP-1 agonists), details of these CVOTs will be addressed later in this document. SGLT2i effect on the cardiovascular system remains an area of extensive research. We aimed in this review to summarize what is the current evidence of cardiovascular protection upon using SGLT2i. Moreover, we wanted to raise a point that may be strongly adopted in the future, combining SGLT2i plus GLP-1 agonists, having a cardiovascular privilege in both molecules.
Published:
2018
Title:
Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension
Authors:
Chakraborty, Saroj; Galla, Sarah; Cheng, Xi; Yeo, Ji Youn; Mell, Blair; Singh, Vishal; Yeoh, Beng San; Saha, Piu; Mathew, Anna V.; Vijay-Kumar, Matam; Joe, Bina
Abstract:
Dietary salt reduction and exercise are lifestyle modifications for salt-sensitive hypertensives. While exercise has prominent metabolic effects, salt has an adverse effect on metabolic syndrome, of which hypertension is a hallmark. We hypothesized that dietary salt impacts metabolism in a salt-sensitive model of hypertension. An untargeted metabolomic approach demonstrates lower circulating levels of the ketone body, beta-hydroxybutyrate (βOHB), in high salt-fed hypertensive rats. Despite the high salt intake, specific rescue of βOHB levels by nutritional supplementation of its precursor, 1,3-butanediol, attenuates hypertension and protects kidney function. This beneficial effect of βOHB was likely independent of gut-microbiotal and Th17-mediated effects of salt and instead facilitated by βOHB inhibiting the renal Nlrp3 inflammasome. The juxtaposed effects of dietary salt and exercise on salt-sensitive hypertension, which decrease and increase βOHB respectively, indicate that nutritional supplementation of a precursor of βOHB provides a similar benefit to salt-sensitive hypertension as exercise. Chakraborty et al. report a link between dietary salt, a ketone, and experimental hypertension. Intake of a high salt diet lowers the ketone body beta-hydroxybutyrate (βOHB), produced by the liver, which functions to prevent Nlrp3-mediated kidney inflammation. Rescuing βOHB by nutritional supplementation of its precursor attenuates hypertension.
Published:
2018
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