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Metabolic modeling

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https://www.readbyqxmd.com/read/27926952/growth-hormone-treatment-increases-plasma-irisin-concentration-in-patients-with-turner-syndrome
#1
B Wikiera, K Zawadzka, Ł Łaczmański, N Słoka, M Bolanowski, A Basiak, A Noczyńska, J Daroszewski
Irisin (Ir) deficiency may be a contributing factor in metabolic disease. This study aimed to investigate the effect of supraphysiological doses of recombinant human growth hormone (rhGH) on Ir plasma concentration in relation to metabolic disorders, including obesity and other components of metabolic syndrome. We studied 36 girls with Turner syndrome (mean age 8.2 years) treated with rhGH (0.05 mg/kg/day). Anthropometric data and fasting blood levels [e. g., Ir, insulin, glucose, glycated hemoglobin (HbA1c), IGF-1, IGFBP-3, cholesterol, insulin resistance (HOMA-IR), and β-cell function (HOMA-β)] were analyzed prior to and following rhGH therapy [mean (SD) follow-up of 1...
December 7, 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/27926861/immunometabolic-pathways-in-bcg-induced-trained-immunity
#2
Rob J W Arts, Agostinho Carvalho, Claudia La Rocca, Carla Palma, Fernando Rodrigues, Ricardo Silvestre, Johanneke Kleinnijenhuis, Ekta Lachmandas, Luís G Gonçalves, Ana Belinha, Cristina Cunha, Marije Oosting, Leo A B Joosten, Giuseppe Matarese, Reinout van Crevel, Mihai G Netea
The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity. Here, we show that BCG induction of trained immunity in monocytes is accompanied by a strong increase in glycolysis and, to a lesser extent, glutamine metabolism, both in an in-vitro model and after vaccination of mice and humans...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926859/rapamycin-reverses-metabolic-deficits-in-lamin-a-c-deficient-mice
#3
Chen-Yu Liao, Sydney S Anderson, Nicole H Chicoine, Jarrott R Mayfield, Emmeline C Academia, Joy A Wilson, Chalermkwan Pongkietisak, Morgan A Thompson, Earl P Lagmay, Delana M Miller, Yueh-Mei Hsu, Mark A McCormick, Monique N O'Leary, Brian K Kennedy
The role of the mTOR inhibitor, rapamycin, in regulation of adiposity remains controversial. Here, we evaluate mTOR signaling in lipid metabolism in adipose tissues of Lmna(-/-) mice, a mouse model for dilated cardiomyopathy and muscular dystrophy. Lifespan extension by rapamycin is associated with increased body weight and fat content, two phenotypes we link to suppression of elevated energy expenditure. In both white and brown adipose tissue of Lmna(-/-) mice, we find that rapamycin inhibits mTORC1 but not mTORC2, leading to suppression of elevated lipolysis and restoration of thermogenic protein UCP1 levels, respectively...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926818/disruption-of-miaa-provides-insights-into-the-regulation-of-phenazine-biosynthesis-under-suboptimal-growth-conditions-in-pseudomonas-chlororaphis-30-84
#4
Jun Myoung Yu, Donping Wang, Leland S Pierson, Elizabeth A Pierson
Many products of secondary metabolism are activated by quorum sensing (QS), yet even at cell densities sufficient for QS, their production may be repressed under suboptimal growth conditions via mechanisms that still require elucidation. For many beneficial plant-associated bacteria, secondary metabolites such as phenazines are important for their competitive survival and plant-protective activities. Previous work established that phenazine biosynthesis in Pseudomonas chlororaphis 30-84 is regulated by the PhzR/PhzI QS system, which in turn is regulated by transcriptional regulator Pip, two-component system RpeA/RpeB, and stationary-phase/stress sigma factor RpoS...
December 7, 2016: Microbiology
https://www.readbyqxmd.com/read/27926487/egf-induces-epithelial-mesenchymal-transition-and-cancer-stem-like-cell-properties-in-human-oral-cancer-cells-via-promoting-warburg-effect
#5
Qilin Xu, Qunzhou Zhang, Yasutaka Ishida, Souren Hajjar, Xudong Tang, Haoran Shi, Chi V Dang, Anh D Le
"Warburg effect", the enhanced glycolysis or aerobic glycolysis, confers cancer cells the ability to survive and proliferate even under stressed conditions. In this study, we explored the role of epidermal growth factor (EGF) in orchestrating Warburg effect, the epithelial-mesenchymal transition (EMT) process, and the acquisition of cancer stem-like cell properties in human oral squamous cell carcinoma (OSCC) cells. Our results showed that EGF induces EMT process in OSCC cells, which correlates with the acquisition of cancer stem-like properties, including the enrichment of CD44+/CD24- population of cancer cells and an increased expression of CSC-related genes, aldehyde dehydrogenase-1 (ALDH1) and Bmi-1...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925773/post-translational-modifications-of-lipid-activated-nuclear-receptors-focus-on-metabolism
#6
Natalia Becares Salles, Matthew C Gage, Inés Pineda-Torra
Post-translational modifications (PTM) occur to nearly all proteins, are catalysed by specific enzymes and are subjected to tight regulation. They have been shown to be a powerful means by which the function of proteins can be modified resulting in diverse effects. Technological advances such as the increased sensitivity of mass spectrometry-based techniques and availability of mutant animal models have enhanced our understanding of the complexities of their regulation and the effect they have on protein function...
December 7, 2016: Endocrinology
https://www.readbyqxmd.com/read/27925692/a-method-to-generate-and-analyze-modified-myristoylated-proteins
#7
Huanyao Gao, Wei Sun, Zhiquan Song, Yanbao Yu, Li Wang, Xian Chen, Qisheng Zhang
Covalent lipid modification of proteins is essential to their cellular localizations and functions. Engineered lipid motif coupled with bio-orthogonal chemistry has been utilized to identify myristoylated or palmitoylated proteins in cells. However, whether modified proteins have similar properties as endogenous ones has not been well investigated mainly due to lack of methods to generate and analyze purified proteins. We have developed a method that utilizes metabolic interference and mass spectrometry to produce and analyze modified, myristoylated small GTPase ADP-ribosylation factor 1 (Arf1)...
December 7, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27925683/inorganic-polyphosphate-a-key-modulator-of-inflammation
#8
REVIEW
Seyed Mahdi Hassanian, Amir Avan, Abdolreza Ardeshirylajimi
Inorganic polyphosphate (PolyP) is a molecule with prothrombotic and proinflammatory properties in blood. PolyP activates the NF-κB signaling pathway, increases the expression of cell surface adhesion molecules and disrupts the vascular barrier integrity of endothelial cells. PolyP-induced NF-κB activation and vascular hyperpermeability are regulated by the mTORC1 and mTORC2 pathways, respectively. Through interaction with RAGE and P2Y1 receptors, PolyP dramatically amplifies the proinflammatory responses of nuclear proteins...
December 7, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27925481/mitochondrial-ros-uncoupled-from-atp-synthesis-determine-endothelial-activation-for-both-physiological-recruitment-of-patrolling-cells-and-pathological-recruitment-of-inflammatory-cells
#9
Xinyuan Li, Pu Fang, William Y Yang, Kylie Chan, Muriel Lavallee, Keman Xu, Tracy Gao, Hong Wang, Xiaofeng Yang
Mitochondrial reactive oxygen species (mtROS) are signaling molecules, which drive inflammatory cytokine production and T cell activation. In addition, cardiovascular diseases, cancers, and autoimmune diseases all share a common feature of increased mtROS level. Both mtROS and ATP are produced as a result of electron transport chain activity, but it remains enigmatic whether mtROS could be generated independently from ATP synthesis. A recent study shed light on this important question and found that, during endothelial cell (EC) activation, mtROS could be upregulated in a proton leak-coupled, but ATP synthesis-uncoupled manner...
November 5, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27925440/enhancing-bioactive-properties-of-silk-fibroin-with-diatom-particles-for-bone-tissue-engineering-applications
#10
Thi Duy Hanh Le, Volha Liaudanskaya, Walter Bonani, Claudio Migliaresi, Antonella Motta
Many studies have highlighted the role of silicon in human bone formation and maintenance. Silicon, in fact, is considered to nucleate the precipitation of hydroxyapatite and to reduce the bone resorption. For this reason, we have combined silk fibroin with silicon releasing diatom particles, as potential material for bone tissue engineering applications. Sponges of fibroin loaded with different amounts and sizes of diatom particles were prepared by solvent casting-particulate leaching method, and their morphology, porosity and mechanical properties were evaluated...
December 7, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27925359/effect-of-aerobic-exercise-intervention-on-markers-of-insulin-resistance-in-breast-cancer-women
#11
E Bruno, E Roveda, J Vitale, A Montaruli, F Berrino, A Villarini, E Venturelli, G Gargano, L Galasso, A Caumo, F Carandente, P Pasanisi
Insulin may affect breast cancer (BC) risk and prognosis. Exercise reduces insulin in obese BC survivors. We designed a randomised controlled trial to test the effect of an aerobic exercise intervention (AEI) on insulin parameters and body composition in non-obese BC women without insulin resistance. Thirty-eight BC women were randomised into an intervention group (IG = 18) or control group (CG = 20). IG participated in a structured AEI for 3 months, while CG received only the Word Cancer Research Fund/American Institute Cancer Research (WCRF/AICR) recommendation to be physically active...
December 7, 2016: European Journal of Cancer Care
https://www.readbyqxmd.com/read/27925282/hypobaric-hypoxia-regulates-brain-iron-homeostasis-in-rats
#12
Yaru Li, Peng Yu, Shi-Yang Chang, Qiong Wu, Panpan Yu, Congcong Xie, Wenyue Wu, Baolu Zhao, Guofen Gao, Yan-Zhong Chang
Disruption of iron homeostasis in brain has been found to be closely involved in several neurodegenerative diseases. Recent studies have reported that appropriate intermittent hypobaric hypoxia played a protective role in brain injury caused by acute hypoxia. However, the mechanisms of this protective effect have not been fully understood. In this study, Sprague-Dawley rat models were developed by hypobaric hypoxia treatment in an altitude chamber, and the iron level and iron related protein levels were determined in rat brain after four weeks of treatment...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27925239/physiologically-based-pharmacokinetic-modeling-revealed-minimal-codeine-intestinal-metabolism-in-first-pass-removal-in-rats
#13
Keumhan Noh, Shu Chen, Qi J Yang, K Sandy Pang
The physiologically-based model with segregated flow to the intestine (SFM-PBPK; partial, lower flow to enterocyte region vs. greater flow to serosal region) was found to describe first-pass glucuronidation of morphine (M) to morphine-3β-glucuronide (MG) in rats after intraduodenal (ID) and intravenous (IV) administration better than the traditional model (TM), for which a single intestinal flow perfused the whole of the intestinal tissue. The SFM described a greater extent of intestinal M glucuronidation for ID vs...
December 7, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27925234/puerarin-offsets-the-anticoagulation-effect-of-warfarin-in-rats-by-inducing-rcyps-upregulating-vitamin-k-epoxide-reductase-and-inhibiting-thrombomodulin
#14
Beikang Ge, Zhen Zhang, Teddy Taining Lam, Zhong Zuo
PURPOSE: The current study was conducted to investigate the potential pharmacokinetic and pharmacodynamic interactions between warfarin and puerarin which is the most abundant component in Pueraria lobata (Gegen). In vivo and ex vivo rat models were used to reveal the underlying mechanisms of such interactions. METHODS: Apart from one control group, five groups of Sprague-Dawley rats were treated with warfarin, oral puerarin, oral puerarin with warfarin, intravenous puerarin, intravenous puerarin with warfarin...
December 7, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27925207/acetate-metabolism-does-not-reflect-astrocytic-activity-contributes-directly-to-gaba-synthesis-and-is-increased-by-silent-information-regulator-1-activation
#15
Benjamin D Rowlands, Matthias Klugmann, Caroline D Rae
[(13) C]acetate is known to label metabolites preferentially in astrocytes rather than neurons and it has consequently been used as a marker for astrocytic activity. Recent discoveries suggest that control of acetate metabolism and its contributions to the synthesis of metabolites in brain is not as simple as first thought. Here, using a Guinea pig brain cortical tissue slice model metabolizing [1-(13) C]D-glucose and [1,2-(13) C]acetate, we investigated control of acetate metabolism and the degree to which it reflects astrocytic activity...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27924915/serum-uric-acid-is-independently-and-linearly-associated-with-risk-of-nonalcoholic-fatty-liver-disease-in-obese-chinese-adults
#16
Chang-Qin Liu, Chun-Mei He, Ning Chen, Dongmei Wang, Xiulin Shi, Yongwen Liu, Xin Zeng, Bing Yan, Suhuan Liu, Shuyu Yang, Xiaoying Li, Xuejun Li, Zhibin Li
The present study aimed to explore the independent association and potential pathways between serum uric acid (SUA) and nonalcoholic fatty liver disease (NAFLD). 1365 community-living obese Chinese adults who received hepatic ultrasonography scanning were included. The prevalence rates of NAFLD were 71.5% for men and 53.8% for women. Compared with controls, NAFLD subjects showed significantly increased SUA levels (333.3 ± 84.9 v.s. 383.4 ± 93.7 μmol/L) and prevalence rate of hyperuricemia (HUA) (25...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924806/abdominal-fat-distribution-differently-affects-muscle-strength-of-the-upper-and-lower-extremities-in-women
#17
L Otten, A Bosy-Westphal, J Ordemann, E Rothkegel, N Stobäus, U Elbelt, K Norman
BACKGROUND/OBJECTIVES: In obese subjects, reduced muscle mass and strength are associated with impaired functional and metabolic capacity. We therefore investigated the association between abdominal fat distribution, fat mass index and maximum muscle strength of upper and lower extremities in obese patients. SUBJECTS/METHODS: One hundred and fifty five outpatients with a body mass index (BMI)⩾30 kg/m(2) (105 women; 45.1±14.6 years; BMI 43.5±8.2 kg/m(2)) were included in the study...
December 7, 2016: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/27924717/effects-of-benzo-a-pyrene-aromatic-amines-and-a-combination-of-both-on-cyp1a1-activities-in-rt-4-human-bladder-papilloma-cells
#18
Sabine Plöttner, Lilian Annika Bastian, Heiko Udo Käfferlein, Thomas Brüning
The interaction of arylamines and polycyclic aromatic hydrocarbons (PAH) is of particular interest in the etiology of bladder cancer. The aim of this study was to (1) examine the metabolic capacity of RT-4 human bladder papilloma cells and (2) investigate the influence of aromatic amines on the induction of cytochrome P-450 1A1 (CYP1A1) activity and their effects on benzo[a]pyrene (BaP)-induced CYP1A1 activities. Cells were incubated for 24 h with different concentrations of BaP, 1- or 2-naphthylamine (NA), 2-, 3-, or 4-aminobiphenyl (ABP), and binary mixtures consisting of 1 µM BaP and different concentrations of each arylamine...
2016: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/27924615/a-model-for-predicting-the-interindividual-variability-of-drug-drug-interactions
#19
M Tod, L Bourguignon, N Bleyzac, S Goutelle
Pharmacokinetic drug-drug interactions are frequently characterized and quantified by an AUC ratio (Rauc). The typical value of the AUC ratio in case of cytochrome-mediated interactions may be predicted by several approaches, based on in vitro or in vivo data. Prediction of the interindividual variability of Rauc would help to anticipate more completely the consequences of a drug-drug interaction. We propose and evaluate a simple approach for predicting the standard deviation (sd) of Ln(Rauc), a metric close to the interindividual coefficient of variation of Rauc...
December 6, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27924154/early-diagnosis-of-brain-metastases-using-a-biofluids-metabolomics-approach-in-mice
#20
James R Larkin, Alex M Dickens, Timothy D W Claridge, Claire Bristow, Kleopatra Andreou, Daniel C Anthony, Nicola R Sibson
Over 20% of cancer patients will develop brain metastases. Prognosis is currently extremely poor, largely owing to late-stage diagnosis. We hypothesized that biofluid metabolomics could detect tumours at the micrometastatic stage, prior to the current clinical gold-standard of blood-brain barrier breakdown. Metastatic mammary carcinoma cells (4T1-GFP) were injected into BALB/c mice via intracerebral, intracardiac or intravenous routes to induce differing cerebral and systemic tumour burdens. B16F10 melanoma and MDA231BR-GFP human breast carcinoma cells were used for additional modelling...
2016: Theranostics
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