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Takeharu Shiroki, Misa Yokoyama, Nobuhiro Tanuma, Ryuhei Maejima, Keiichi Tamai, Kazunori Yamaguchi, Tomoyuki Oikawa, Tetsuya Noguchi, Koh Miura, Tsuneaki Fujiya, Hiroshi Shima, Ikuro Sato, Naoko Murata-Kamiya, Masanori Hatakeyama, Katsunori Iijima, Tooru Shimosegawa, Kennichi Satoh
Recent studies have indicated that an increased expression of the M2 isoform of pyruvate kinase (PKM2) is involved in glycolysis and in tumor development. However, little is known about the role of PKM2 in gastric cancer (GC). Therefore, we examined the expression and function of PKM2 in human GC. We evaluated PKM1 and PKM2 expression by quantitative RT-PCR in gastric tissues from 10 patients who underwent gastric endoscopic submucosal dissection (ESD), 80 patients who underwent gastrectomy, and 7 healthy volunteers, and analyzed the correlation with clinicopathological variables...
February 24, 2017: Cancer Science
Matthew E Welsch, Anna Kaplan, Jennifer M Chambers, Michael E Stokes, Pieter H Bos, Arie Zask, Yan Zhang, Marta Sanchez-Martin, Michael A Badgley, Christine S Huang, Timothy H Tran, Hemanth Akkiraju, Lewis M Brown, Renu Nandakumar, Serge Cremers, Wan Seok Yang, Liang Tong, Kenneth P Olive, Adolfo Ferrando, Brent R Stockwell
Design of small molecules that disrupt protein-protein interactions, including the interaction of RAS proteins and their effectors, may provide chemical probes and therapeutic agents. We describe here the synthesis and testing of potential small-molecule pan-RAS ligands, which were designed to interact with adjacent sites on the surface of oncogenic KRAS. One compound, termed 3144, was found to bind to RAS proteins using microscale thermophoresis, nuclear magnetic resonance spectroscopy, and isothermal titration calorimetry and to exhibit lethality in cells partially dependent on expression of RAS proteins...
February 23, 2017: Cell
Christoffer Clemmensen, Timo D Müller, Stephen C Woods, Hans-Rudolf Berthoud, Randy J Seeley, Matthias H Tschöp
Because human energy metabolism evolved to favor adiposity over leanness, the availability of palatable, easily attainable, and calorically dense foods has led to unprecedented levels of obesity and its associated metabolic co-morbidities that appear resistant to traditional lifestyle interventions. However, recent progress identifying the molecular signaling pathways through which the brain and the gastrointestinal system communicate to govern energy homeostasis, combined with emerging insights on the molecular mechanisms underlying successful bariatric surgery, gives reason to be optimistic that novel precision medicines that mimic, enhance, and/or modulate gut-brain signaling can have unprecedented potential for stopping the obesity and type 2 diabetes pandemics...
February 23, 2017: Cell
Salvatore Petta, Mohammed Eslam, Luca Valenti, Elisabetta Bugianesi, Marco Barbara, Calogero Cammà, Marianna Porzio, Chiara Rosso, Silvia Fargion, Jacob George, Antonio Craxì
BACKGROUND/AIMS: Metabolic syndrome (MS) and its individual components are associated with the severity and progression of nonalcoholic fatty liver disease (NAFLD). We sought to evaluate the relationship between MS components and the risk of severe hepatic fibrosis in NAFLD patients discriminated by age. METHODS: We considered 863 consecutive patients with biopsy-proven NAFLD, who had been fully evaluated for components of metabolic syndnrome (MS). RESULTS: Multivariate logistic regression analysis showed that F3-F4 was associated with visceral obesity, IFG/diabetes, and low HDL cholesterol, but not triglycerides >150 or arterial hypertension...
February 24, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
Reinhold Feldmann, Eva Wolfgart, Josef Weglage, Frank Rutsch
AIM: Sapropterin causes reductions in blood phenylalanine concentrations in sensitive patients with phenylketonuria (PKU),. We examined whether the subsequent relaxation of dietary restrictions influenced the quality of life (QoL) of patients and parents. METHODS: The study cohort comprised 112 patients with PKU followed at the metabolic centre at Münster University Children's Hospital, Germany, from 2012 to 2015. A sapropterin response was defined as a ≥30% reduction in blood phenylalanine levels...
February 24, 2017: Acta Paediatrica
Terez Shea-Donohue, Bolin Qin, Allen Smith
Nutritional immunology, immunometabolism, and identification of novel immunotherapeutic targets, are areas of active investigation in parasitology. There is a well-documented crosstalk among immune cells and cells in metabolically active tissues that is important for homeostasis. The numbers and function of these cells are altered by obesity leading to inflammation. A variety of helminths spend some part of their life cycle in the gastrointestinal tract and even entirely enteral nematode infections exert beneficial effects on glucose and lipid metabolism...
February 24, 2017: Parasite Immunology
Julita Sadowska, Andrzej K Gębczyński, Marek Konarzewski
Factors affecting contribution of spontaneous physical activity (SPA; activity associated with everyday tasks) to energy balance of humans are not well understood, as it is not clear whether low activity is related to dietary habits, precedes obesity or is a result of thereof. In particular, human studies on SPA and basal metabolic rates (BMR, accounting for >50% of human energy budget) and their associations with diet composition, metabolic thrift and obesity are equivocal. To clarify these ambiguities we used a unique animal model-mice selected for divergent BMR rates (the H-BMR and L-BMR line type) presenting a 50% between-line type difference in the primary selected trait...
2017: PloS One
Pentti Kuusela, Mayank Saraswat, Sakari Joenväärä, Johanna Kaartinen, Asko Järvinen, Risto Renkonen
Blood culture is the primary diagnostic test performed in a suspicion of bloodstream infection to detect the presence of microorganisms and direct the treatment. However, blood culture is slow and time consuming method to detect blood stream infections or separate septic and/or bacteremic patients from others with less serious febrile disease. Plasma proteomics, despite its challenges, remains an important source for early biomarkers for systemic diseases and might show changes before direct evidence from bacteria can be obtained...
2017: PloS One
Satoshi Kato, Hideki Murakami, Anri Inaki, Takafumi Mochizuki, Satoru Demura, Junsuke Nakase, Katsuhito Yoshioka, Noriaki Yokogawa, Takashi Igarashi, Naoki Takahashi, Noritaka Yonezawa, Seigo Kinuya, Hiroyuki Tsuchiya
BACKGROUND: Exercise is one of the few treatments that provide significant improvements in chronic low back pain (CLBP). We developed an innovative exercise device for abdominal trunk muscles. This device can be used in a sitting or standing position and contains a built-in system to measure abdominal trunk muscle strength. We examined whether subjects can adequately use the device to perform the exercises and measure their abdominal trunk muscle strength. METHODS: We collected data on the body height, body weight, body mass index, and girth of 30 healthy male volunteers, and measured their grip power and trunk extensor muscle strength using a dynamometer...
2017: PloS One
Ruixue Li, Dandan Chen, Taichu Wang, Yizhen Wan, Rongfang Li, Rongjun Fang, Yuting Wang, Fei Hu, Hong Zhou, Long Li, Weiguo Zhao
MicroRNAs (miRNAs) play important regulatory roles by targeting mRNAs for cleavage or translational repression. Identification of miRNA targets is essential to better understanding the roles of miRNAs. miRNA targets have not been well characterized in mulberry (Morus alba). To anatomize miRNA guided gene regulation under drought stress, transcriptome-wide high throughput degradome sequencing was used in this study to directly detect drought stress responsive miRNA targets in mulberry. A drought library (DL) and a contrast library (CL) were constructed to capture the cleaved mRNAs for sequencing...
2017: PloS One
Francesco Gianfagna, Claudio Grippi, Wolfgang Ahrens, Mark E S Bailey, Claudia Börnhorst, Stefan De Henauw, Ronja Foraita, Anna C Koni, Vittorio Krogh, Staffan Mårild, Dénes Molnár, Luis Moreno, Yannis Pitsiladis, Paola Russo, Alfonso Siani, Michael Tornaritis, Toomas Veidebaum, Licia Iacoviello
BACKGROUND AND AIMS: Neuromedin U (NMU) is a hypothalamic neuropeptide with important roles in several metabolic processes, recently suggested as potential therapeutic target for obesity. We analysed the associations between NMU gene variants and haplotypes and body mass index (BMI) in a large sample of European children. METHODS AND RESULTS: From a large European multi-center study on childhood obesity, 4,528 children (2.0-9.9 years, mean age 6.0±1.8 SD; boys 52...
2017: PloS One
Jo E Lewis, John M Brameld, Phil Hill, Cristina Cocco, Barbara Noli, Gian-Luca Ferri, Perry Barrett, Francis J P Ebling, Preeti H Jethwa
VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological effects of VGF-derived peptides...
2017: PloS One
Fuat Arikan, Tamara Martínez-Valverde, Ángela Sánchez-Guerrero, Mireia Campos, Marielle Esteves, Dario Gandara, Ramon Torné, Lidia Castro, Antoni Dalmau, Joan Tibau, Juan Sahuquillo
BACKGROUND AND PURPOSE: Interspecies variability and poor clinical translation from rodent studies indicate that large gyrencephalic animal stroke models are urgently needed. We present a proof-of-principle study describing an alternative animal model of malignant infarction of the middle cerebral artery (MCA) in the common pig and illustrate some of its potential applications. We report on metabolic patterns, ionic profile, brain partial pressure of oxygen (PtiO2), expression of sulfonylurea receptor 1 (SUR1), and the transient receptor potential melastatin 4 (TRPM4)...
2017: PloS One
Jae Uk Chong, Ho Kyoung Hwang, Jin Ho Lee, Mijin Yun, Chang Moo Kang, Woo Jung Lee
PURPOSE: To investigate the association between clinical PET (positron emission tomography) type and oncologic outcome in resectable pancreatic cancer. METHODS: Between January 2008 and October 2012, patients who underwent potentially curative resection for resectable pancreatic ductal adenocarcinoma without neoadjuvant treatment were retrospectively investigated. Clinical PET type was defined as follows: pancreatic cancer with similar 18FDG uptake to renal calyx was determined as kidney-type (K-type), and relatively lower 18FDG uptake than that of renal calyx was regarded as Non-K type...
2017: PloS One
Livvi Li Wei Sim, Kenneth Hon Kim Ban, Tin Wee Tan, Sunil Kumar Sethi, Tze Ping Loh
Management of complex chronic diseases such as diabetes requires the assimilation and interpretation of multiple laboratory test results. Traditional electronic health records tend to display laboratory results in a piecemeal and segregated fashion. This makes the assembly and interpretation of results related to diabetes care challenging. We developed a diabetes-specific clinical decision support system (Diabetes Dashboard) interface for displaying glycemic, lipid and renal function results, in an integrated form with decision support capabilities, based on local clinical practice guidelines...
2017: PloS One
Marisa Simon, Fahmi Mesmar, Luisa Helguero, Cecilia Williams
Triple-negative breast cancer (TNBC) is an aggressive, highly recurrent breast cancer subtype, affecting approximately one-fifth of all breast cancer patients. Subpopulations of treatment-resistant cancer stem cells within the tumors are considered to contribute to disease recurrence. A potential druggable target for such cells is the maternal embryonic leucine-zipper kinase (MELK). MELK expression is upregulated in mammary stem cells and in undifferentiated cancers, where it correlates with poor prognosis and potentially mediates treatment resistance...
2017: PloS One
Kazunari Ozasa, June Won, Simon Song, Shun Tamaki, Takahiro Ishikawa, Mizuo Maeda
The adaptation to a strong light is one of the essential characteristics of green algae, yet lacking relatively the information about the photophobic responses of Eukaryotic microalgae. We investigated the photophobic step-up responses of Euglena gracilis over a time course of several hours with alternated repetition of blue-light pulse illumination and spatially patterned blue-light illumination. Four distinctive photophobic motions in response to strong blue light were identified in a trace image analysis, namely on-site rotation, running and tumbling, continuous circular swimming, and unaffected straightforward swimming...
2017: PloS One
Jose V Die, Ransom L Baldwin, Lisa J Rowland, Robert Li, Sunghee Oh, Congjun Li, Erin E Connor, Maria-Jose Ranilla
The rumen is lined on the luminal side by a stratified squamous epithelium that is responsible for not only absorption, but also transport, extensive short-chain fatty acid (SCFA) metabolism and protection. Butyrate has been demonstrated to initiate the differentiation of the tissue following introduction of solid feed to the weaning neonate as well as affecting the metabolism of other nutrients and absorption of nutrients in in vitro experiments. The objective of the present study was to validate expression stability of eight putative reference genes bovine rumen, considering the intrinsic heterogeneity of bovine rumen with regard to different luminal characteristics due to direct infusion of butyrate to double the intra-ruminal content of the rumen liquor...
2017: PloS One
Xiaoli Xu, Xianmei Liu, Jinhua Long, Zuquan Hu, Qinni Zheng, Chunlin Zhang, Long Li, Yun Wang, Yi Jia, Wei Qiu, Jing Zhou, Weijuan Yao, Zhu Zeng
Interlukin-10 (IL-10) is an immunomodulatory cytokine which predominantly induces immune-tolerance. It has been also identified as a major cytokine in the tumor microenvironment that markedly mediates tumor immune escape. Previous studies on the roles of IL-10 in tumor immunosuppression mainly focus on its biochemical effects. But the effects of IL-10 on the biophysical characteristics of immune cells are ill-defined. Dendritic cells (DCs) are the most potent antigen-presenting cells and play a key role in the anti-tumor immune response...
2017: PloS One
Susanne Blöß, Christian Klemann, Ann-Katrin Rother, Sandra Mehmecke, Ulrike Schumacher, Urs Mücke, Martin Mücke, Christiane Stieber, Frank Klawonn, Xiaowei Kortum, Werner Lechner, Lorenz Grigull
BACKGROUND: Worldwide approximately 7,000 rare diseases have been identified. Accordingly, 4 million individuals live with a rare disease in Germany. The mean time to diagnosis is about 6 years and patients receive several incorrect diagnoses during this time. A multiplicity of factors renders diagnosing a rare disease extremely difficult. Detection of shared phenomena among individuals with different rare diseases could assist the diagnostic process. In order to explore the demand for diagnostic support and to obtain the commonalities among patients, a nationwide Delphi survey of centers for rare diseases and patient groups was conducted...
2017: PloS One
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