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Patrizia Ferroni, Francesca Santilli, Francesco Cavaliere, Paola Simeone, Leopoldo Costarelli, Rossella Liani, Romina Tripaldi, Silvia Riondino, Mario Roselli, Giovanni Davi, Fiorella Guadagni
The hypothesis that increased oxidative stress in breast cancer (BC) patients could induce enhanced lipid peroxidation, which, in turn, would contribute to platelet activation and poor clinical outcome is attractive. To address this issue, we investigated pre-surgical urinary 8-iso-prostaglandin (PG)F2α (marker of in vivo oxidative stress) and 11-dehydro-thromboxane (TX)B2 (marker of in vivo platelet activation) levels in patients with primary BC (n=115) compared with control women paired for co-morbidities and their association with patients' metabolic profile and clinical prognostic factors...
October 26, 2016: International Journal of Cancer. Journal International du Cancer
Helen L MacLaughlin, Iain C Macdougall, Wendy L Hall, Tracy Dew, Konstantinos Mantzoukis, Jude A Oben
BACKGROUND: The outcomes of intragastric balloon (IGB) placement to achieve weight loss in obese patients with chronic kidney disease (CKD) have not been reported to date. This study aimed to assess the safety and efficacy of the IGB as a weight-loss treatment among this patient population. METHODS: A prospective, single-arm, 'first in CKD' interventional study was conducted in patients with a body mass index >35 kg/m2 and CKD stages 3-4, referred for weight loss...
October 27, 2016: American Journal of Nephrology
Jonathan Negrel, Francine Javelle, Dominique Morandi, Géraldine Lucchi
A Gram-negative bacterium able to grow using chlorogenic acid (5-caffeoylquinic acid) as sole carbon source has been isolated from the roots of tomato plants inoculated with the arbuscular mycorrhizal fungus Rhizophagus irregularis. An intracellular esterase exhibiting very high affinity (Km = 2 μM) for chlorogenic acid has been extracted and purified by FPLC from the chlorogenate-grown cultures of this bacterium. The molecular mass of the purified esterase determined by SDS-PAGE was 61 kDa and its isoelectric point determined by chromatofocusing was 7...
October 17, 2016: Plant Physiology and Biochemistry: PPB
Timothy J Ritchie, Simon J F Macdonald
The impact of replacing a mono-substituted benzene (phenyl) ring with thirty three aromatic and nine aliphatic heterocycles on nine ADME-related screens (solubility, lipophilicity, permeability, protein binding CYP450 inhibition and metabolic clearance) was assessed using matched molecular pair analysis. The results indicate that the influence on the ADME profile can differ significantly depending on the ring identity and importantly on the individual regioisomers that are possible for some rings. This information enables the medicinal chemist to make an informed choice about which rings and regioisomers to employ as mono-substituted benzene replacements, based upon the knowledge of how such replacements are likely to influence ADME-related parameters, for example to target higher solubility whilst avoiding CYP450 liabilities...
October 15, 2016: European Journal of Medicinal Chemistry
Julie Paoletti, Liliane Assairi, Muriel Gelin, Valérie Huteau, Marie-Anne Nahori, Olivier Dussurget, Gilles Labesse, Sylvie Pochet
Increased resistance of pathogens to existing antibiotics necessitates the search for novel targets to develop potent antimicrobials. Biosynthetic pathways of several cofactors important for bacterial growth, such as nicotinamide adenine dinucleotide phosphate (NADP), have been proposed as a promising source of antibiotic targets. Nicotinamide adenine dinucleotide kinases (NADK; EC are attractive for inhibitor development, since they catalyze the phosphorylation of NAD to NADP, which is an essential step of NADP metabolism...
October 18, 2016: European Journal of Medicinal Chemistry
Tomasz Molcan, Sylwia Swigonska, Karina Orlowska, Kamil Myszczynski, Anna Nynca, Agnieszka Sadowska, Monika Ruszkowska, Jan Pawel Jastrzebski, Renata E Ciereszko
Polychlorinated dibenzo-p-dioxins (PCDDs) are widespread by-products of human industrial activity. They accumulate in tissues of animals and humans, exerting numerous adverse effects on different systems. In living organisms, dioxins are metabolized by enzymes of the cytochrome P450 family, including CYP1A1. Particular dioxin congeners differ in their toxicity level and ability to undergo biodegradation. Since the molecular mechanisms underlying dioxin susceptibility or resistance to biodegradation are unknown, in the present study the molecular interactions between five selected dioxins and porcine CYP1A1 protein were investigated...
October 23, 2016: Chemosphere
Alexandre Fisette, Stephanie Tobin, Léa Décarie-Spain, Khalil Bouyakdan, Marie-Line Peyot, S R Murthy Madiraju, Marc Prentki, Stephanie Fulton, Thierry Alquier
α/β-Hydrolase domain 6 (ABHD6) is a monoacylglycerol hydrolase that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG). Although complete or peripheral ABHD6 loss of function is protective against diet-induced obesity and insulin resistance, the role of ABHD6 in the central control of energy balance is unknown. Using a viral-mediated knockout approach, targeted endocannabinoid measures, and pharmacology, we discovered that mice lacking ABHD6 from neurons of the ventromedial hypothalamus (VMH(KO)) have higher VMH 2-AG levels in conditions of endocannabinoid recruitment and fail to physiologically adapt to key metabolic challenges...
October 25, 2016: Cell Reports
Nuno Miguel Luis, Lifen Wang, Mauricio Ortega, Hansong Deng, Subhash D Katewa, Patrick Wai-Lun Li, Jason Karpac, Heinrich Jasper, Pankaj Kapahi
Dietary restriction (DR) is one of the most robust lifespan-extending interventions in animals. The beneficial effects of DR involve a metabolic adaptation toward increased triglyceride usage. The regulatory mechanism and the tissue specificity of this metabolic switch remain unclear. Here, we show that the IRE1/XBP1 endoplasmic reticulum (ER) stress signaling module mediates metabolic adaptation upon DR in flies by promoting triglyceride synthesis and accumulation in enterocytes (ECs) of the Drosophila midgut...
October 25, 2016: Cell Reports
Tina Bernadette Angerer, Ylva Magnusson, Goran Landberg, John Stephen Fletcher
Breast cancer is an umbrella term used to describe a collection of different diseases with broad inter- and intra-tumor heterogeneity. Understanding this variation is critical in order to develop, and precisely prescribe, new treatments. Changes in the lipid metabolism of cancerous cells can provide important indications as to the metabolic state of the cells but are difficult to investigate with conventional histological methods. Due to the introduction of new higher energy (40 kV) gas cluster ion beams (GCIBs) time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging is now capable of providing information on the distribution of hundreds of molecular species simultaneously on a cellular to sub-cellular scale...
October 26, 2016: Analytical Chemistry
Carlos Fernandez-Patron, Zamaneh Kassiri, Dickson Leung
Matrix metalloproteinase-2 (MMP-2) is a 72-kDa zinc- and calcium-dependent endopeptidase with intracellular and extracellular functions ranging from the modulation of extracellular matrix remodeling to cell growth and migration, angiogenesis, inflammation, and metabolism. An upregulation of MMP-2 activity has the potential to deregulate lipid metabolism through the cleavage of numerous metabolic mediators including plasma lipoproteins and cell surface receptors of lipoproteins. Paradoxically, MMP-2 deficiency induces inflammation and deregulates metabolism...
September 15, 2016: Comprehensive Physiology
Hiroshi Kaji
Adipose tissue has recently been reevaluated as an endocrine organ, and adipose-tissue-derived endocrine factors are termed adipokines. Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of PAs, which convert plasminogen into plasmin, a critical protease involved in fibrinolysis. PAI-1 induces fibrinogenesis by suppressing intravascular and tissue fibrinolysis. Moreover, PAI-1 exerts various cellular effects independently of fibrinolysis. Although PAI-1 is expressed in various tissues, its expression is regulated by numerous growth factors, cytokines, and hormones in a paracrine and endocrine manner...
September 15, 2016: Comprehensive Physiology
Heinrich Taegtmeyer, Truong Lam, Giovanni Davogustto
The heart is a biological pump that converts chemical to mechanical energy. This process of energy conversion is highly regulated to the extent that energy substrate metabolism matches energy use for contraction on a beat-to-beat basis. The biochemistry of cardiac metabolism includes the biochemistry of energy transfer, metabolic regulation, and transcriptional, translational as well as posttranslational control of enzymatic activities. Pathways of energy substrate metabolism in the heart are complex and dynamic, but all of them conform to the First Law of Thermodynamics...
September 15, 2016: Comprehensive Physiology
Antonia Lanni, Maria Moreno, Fernando Goglia
The hypermetabolic effects of thyroid hormones (THs), the major endocrine regulators of metabolic rate, are widely recognized. Although, the cellular mechanisms underlying these effects have been extensively investigated, much has yet to be learned about how TH regulates diverse cellular functions. THs have a profound impact on mitochondria, the organelles responsible for the majority of cellular energy production, and several studies have been devoted to understand the respective importance of the nuclear and mitochondrial pathways for organelle activity...
September 15, 2016: Comprehensive Physiology
Dara M Shearer, W Murray Thomson, Jonathan M Broadbent, Jim Mann, Richie Poulton
AIM: To examine associations between periodontitis and developmental trajectories of glycated haemoglobin (HbA1c) during the third and fourth decades in an initially healthy sample. MATERIALS AND METHODS: HbA1c data collected at ages 26, 32 and 38 in the prospective Dunedin Multidisciplinary Health and Development Study were used to assign study members (n=893) to trajectories applying group-based trajectory modelling (GBTM). The model allowed the statistical linking of baseline demographic, smoking and waist-height ratio covariates to group membership probability; and added a time-varying covariate (periodontitis) to the trajectories themselves to examine whether events that occurred during the course of the trajectory altered its course...
October 26, 2016: Journal of Clinical Periodontology
Diana Milena Sánchez-Lancheros, Luis Fernando Ospina-Giraldo, María Helena Ramírez-Hernández
Nicotinamide/nicotinate adenine dinucleotide (NAD+/NaAD) performs essential functions in cell metabolism and energy production due to its redox properties. The nicotinamide/nicotinate mononucleotide adenylyltransferase (NMNAT, EC enzyme catalyses the key step in the biosynthesis of NAD+. Previously, the enzyme NMNAT was identified in Trypanosoma cruzi (TcNMNAT), a pathogenic agent with epidemiological importance in Latin America. To continue with the functional characterisation of this enzyme, its subcellular location and its possible post-translational modifications were examined in this study...
October 24, 2016: Memórias do Instituto Oswaldo Cruz
Solveig Langsrud, Katrin Steinhauer, Sonja Lüthje, Klaus Weber, Peter Goroncy-Bermes, Askild L Holck
Preservatives are added to cosmetics to protect the consumers from infections and prevent product spoilage. The concentration of preservatives should be kept as low as possible and this can be achieved by adding potentiating agents. The aim of the study was to investigate the mechanisms behind potentiation of the bactericidal effect of a commonly used preservative, 2-phenoxyethanol (PE), by the potentiating agent ethylhexylglycerin (EHG). Sub-lethal concentrations of EHG (0.075%) and PE (0.675%) in combination led to rapid killing of E...
2016: PloS One
Han Na Kwon, Hyunjung Lim
Serum vitamin D status has been associated with prediabetes and metabolic syndrome. Evidence for the increased risk of metabolic disorders in individuals with prediabetes and a low vitamin D status is limited and uncertain. Furthermore, it has not been confirmed whether this possible relationship occurs in the Korean population. The aim of this study was to assess serum vitamin D status and to examine the relationship between serum vitamin D levels and metabolic risk factors in Korean adults with prediabetes...
2016: PloS One
Henk J van Lingen, Caroline M Plugge, James G Fadel, Ermias Kebreab, André Bannink, Jan Dijkstra
Hydrogen is a key product of rumen fermentation and has been suggested to thermodynamically control the production of the various volatile fatty acids (VFA). Previous studies, however, have not accounted for the fact that only thermodynamic near-equilibrium conditions control the magnitude of reaction rate. Furthermore, the role of NAD, which is affected by hydrogen partial pressure (PH2), has often not been considered. The aim of this study was to quantify the control of PH2 on reaction rates of specific fermentation pathways, methanogenesis and NADH oxidation in rumen microbes...
2016: PloS One
Daniella Kovacsics, Izabel Patik, Csilla Özvegy-Laczka
The in vivo fate and effectiveness of a drug depends highly on its absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Organic anion transporting polypeptides (OATPs) are membrane proteins involved in the cellular uptake of various organic compounds, including clinically used drugs. Since OATPs are significant players in drug absorption and distribution, modulation of OATP function via pharmacotherapy with OATP substrates/inhibitors, or modulation of their expression, affects drug pharmacokinetics...
October 26, 2016: Expert Opinion on Drug Metabolism & Toxicology
Eileen K Jaffe
Porphobilinogen synthase (PBGS), also known as 5-aminolevulinate dehydratase, is an essential enzyme in the biosynthesis of all tetrapyrroles, which function in respiration, photosynthesis, and methanogenesis. Throughout evolution, PBGS adapted to a diversity of cellular niches and evolved to use an unusual variety of metal ions both for catalytic function and to control protein multimerization. With regard to the active site, some PBGSs require Zn(2+); a subset of those, including human PBGS, contain a constellation of cysteine residues that acts as a sink for the environmental toxin Pb(2+)...
October 26, 2016: Accounts of Chemical Research
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