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Metabolic modeling

Julie J Miller, Wolfgang Wick
The majority of World Health Organization grade II and grade III gliomas harbor heterozygous mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1), and tumors with an IDH wild-type status show molecular features of a glioblastoma and simply may constitute a separate disease entity. This discovery has led to a profound shift in the way that gliomas are classified and, consequently, how treatment decisions are made. We will review the current understanding of IDH- mutant gliomagenesis and the preclinical models being used to investigate the underlying biology of these tumors and to explore new therapeutic options for these patients...
February 2018: Seminars in Neurology
Brooke N Wolford, Cristen J Willer, Ida Surakka
The combination of Electronic Health Records (EHRs) with genetic data has ushered in the next wave of complex disease genetics. Population-based biobanks and other large cohorts provide sufficient sample sizes to identify novel genetic associations across the hundreds to thousands of phenotypes gleaned from EHRs. In this review we summarize the current state of these EHR-linked biobanks, explore ongoing methods development in the field, and highlight recent discoveries of genetic associations. We enumerate the many existing biobanks with EHRs linked to genetic data, many of which are available to researchers via application and contain sample sizes > 50,000...
March 14, 2018: Human Molecular Genetics
Sergio Polakof, Didier Rémond, Jérémie David, Dominique Dardevet, Isabelle Savary-Auzeloux
OBJECTIVES: High-fat high-sucrose diet (HFHS) overfeeding is one of the main factors responsible for the increased prevalence of metabolic disorders. Elevated levels of branched-chain amino acids (BCAAs) have been associated with metabolic dysfunctions, including insulin resistance (IR). The aim of this study was to elucidate whether elevated BCAA levels are the cause or the consequence of IR and to determine the mechanisms and tissues involved in such a phenotype. METHODS: We performed a 2-mo follow-up on minipigs overfed an HFHS diet and focused on kinetics fasting and postprandial (PP) BCAA levels and BCAA catabolism in key tissues...
November 27, 2017: Nutrition
Jared T Hammill, Deepak Bhasin, Daniel C Scott, Jaeki Min, Yizhe Chen, Yan Lu, Lei Yang, Ho Shin Kim, Michele C Connelly, Courtney Hammill, Gloria Holbrook, Cynthia Jeffries, Bhuvanesh Singh, Brenda A Schulman, R Kiplin Guy
We previously reported the discovery, validation, and structure-activity relationships of a series of piperidinyl ureas that potently inhibit the DCN1-UBE2M interaction. We demonstrated that compound 7 inhibits both the DCN1-UBE2M protein-protein interaction and DCN1-mediated cullin neddylation in biochemical assays and reduces levels of steady-state cullin neddylation in a squamous carcinoma cell line harboring DCN1 amplification. Although compound 7 exhibits good solubility and permeability, it is rapidly metabolized in microsomal models (CLint = 170 mL/min/kg)...
March 16, 2018: Journal of Medicinal Chemistry
Nasir Mehmood, Ranim Alayoubi, Eric Husson, Cédric Jacquard, Jochen Büchs, Catherine Sarazin, Isabelle Gosselin
Imidazolium ionic liquids (ILs) are promising solvents for lignocellulosic biomass (LCB) pretreatment and allow the achievement of higher ethanolic yields after enzymatic hydrolysis and ethanolic fermentation. However, residual ILs entrapped in pretreated biomass are often toxic for fermentative microorganisms, but interaction mechanisms between ILs and cells are still unknown. Here we studied the effects of 1-ethyl-3-methylimidazolium acetate [Emim][OAc] and 1-ethyl-3-methylimidazolium methylphosphonate [Emim][MeO(H)PO₂] on Kluyveromyces marxianus , a thermotolerant ethanologenic yeast...
March 16, 2018: International Journal of Molecular Sciences
Huaqi Zhang, Song Lin, Tianlin Gao, Feng Zhong, Jing Cai, Yongye Sun, Aiguo Ma
The associations between sarcopenia and metabolic syndrome (MetS) in non-obese middle-aged and older adults remain controversial. Thus, this meta-analysis aimed to evaluate the overall prevalence of MetS and the correlations between sarcopenia and MetS in middle-aged and older non-obese adults. We performed a systematic searched strategy using PUBMED, EMBASE and Web of Science databases for relevant observational studies investigating sarcopenia and MetS up to 11 May 2017. The polled prevalence of MetS and odds ratios with 95% confidence intervals (CI), as well as subgroup analyses were calculated using a random effects model...
March 16, 2018: Nutrients
Martin Kornecki, Jochen Strube
Productivity improvements of mammalian cell culture in the production of recombinant proteins have been made by optimizing cell lines, media, and process operation. This led to enhanced titers and process robustness without increasing the cost of the upstream processing (USP); however, a downstream bottleneck remains. In terms of process control improvement, the process analytical technology (PAT) initiative, initiated by the American Food and Drug Administration (FDA), aims to measure, analyze, monitor, and ultimately control all important attributes of a bioprocess...
March 16, 2018: Bioengineering
Michał Rurek, Magdalena Czołpińska, Tomasz Andrzej Pawłowski, Włodzimierz Krzesiński, Tomasz Spiżewski
Complex proteomic and physiological approaches for studying cold and heat stress responses in plant mitochondria are still limited. Variations in the mitochondrial proteome of cauliflower ( Brassica oleracea var. botrytis ) curds after cold and heat and after stress recovery were assayed by two-dimensional polyacrylamide gel electrophoresis (2D PAGE) in relation to mRNA abundance and respiratory parameters. Quantitative analysis of the mitochondrial proteome revealed numerous stress-affected protein spots. In cold, major downregulations in the level of photorespiratory enzymes, porine isoforms, oxidative phosphorylation (OXPHOS) and some low-abundant proteins were observed...
March 16, 2018: International Journal of Molecular Sciences
Bastian Ramms, Philip L S M Gordts
PURPOSE OF REVIEW: Apolipoprotein (apo) C-III is a key player in triglyceride-rich lipoprotein metabolism and strongly associated with elevated plasma triglyceride levels. Several new studies added important insights on apoC-III and its physiological function confirming its promise as a valid therapeutic target. RECENT FINDINGS: APOC3 is expressed in liver and intestine and regulates triglyceride-rich lipoprotein (TRL) catabolism and anabolism. The transcriptional regulation in both organs requires different regulatory elements...
March 15, 2018: Current Opinion in Lipidology
Daniela Calzia, Greta Garbarino, Federico Caicci, Mario Pestarino, Lucia Manni, Carlo Enrico Traverso, Isabella Panfoli, Simona Candiani
Previous studies on purified bovine rod outer segments (OS) disks pointed to Oxidative Phosphorylation (OXPHOS) as being the most likely mechanism involved in ATP production, as yet not fully understood, to support the first phototransduction steps. Bovine and murine rod OS disks, devoid of mitochondria, would house respiratory chain complexes I to IV and ATP synthase, similar to mitochondria. Zebrafish ( Danio rerio) is a well-suited animal model to study vertebrate embryogenesis as well as the retina, morphologically and functionally similar to its human counterpart...
March 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
María José Garcés Hernández, Miguel Klünder, Nayely Garibay Nieto, Juan Carlos López Alvarenga, Jenny Vilchis Gil, Samuel Flores Huerta, Rosa Quispe Siccha, Joselin Hernandez
OBJECTIVE: Visceral adiposity index (VAI) is a mathematical model associated with cardiometabolic risk in adults, but studies on children failed to support this association. Our group has proposed a pediatric VAI model using pediatric ranges, but it has not yet been evaluated and needs further adjustments. The objective of this study was to further adjust the proposed pediatric VAI by age, creating a new pediatric metabolic index (PMI), and assess the correlation of the PMI with insulin resistance indexes and hepatic enzymes...
March 2018: Endocrine Practice
Lars Frings, Sabine Hellwig, Tobias Bormann, Timo S Spehl, Ralph Buchert, Philipp T Meyer
PURPOSE: The value of imaging regional glucose metabolism with [18 F]FDG PET for the prediction of progression from mild cognitive impairment (MCI) to Alzheimer's dementia (AD) is controversial. The predictive value of imaging with [18 F]FDG PET was therefore tested and compared with that of imaging beta-amyloid load with [11 C]PIB PET in the same memory clinic population of MCI patients. METHODS: Thirty-nine patients with MCI who had undergone [18 F]FDG as well as [11 C]PIB PET were identified from a single-centre clinical registry...
March 15, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Rezvan Salehidoost, Asieh Mansouri, Massoud Amini, Sima Aminorroaya Yamini, Ashraf Aminorroaya
AIMS: The relationship between obesity and mortality rate among diabetic patients is a controversial topic. The aim of this study was to investigate the association between obesity and all-cause mortality risk in patients with type 2 diabetes. METHODS: In this retrospective database study, 2383 patients with type 2 diabetes, who had been registered in the Isfahan Endocrine and Metabolism Research Center, Iran, were enrolled between 1992 and 2010. The mean (SD) of diabetes duration and follow-up period was 15...
March 15, 2018: Acta Diabetologica
Mika Hilvo, Tuire Salonurmi, Aki S Havulinna, Dimple Kauhanen, Eva Ringdal Pedersen, Grethe S Tell, Klaus Meyer, Anna-Maria Teeriniemi, Tiina Laatikainen, Pekka Jousilahti, Markku J Savolainen, Ottar Nygård, Veikko Salomaa, Reijo Laaksonen
AIMS/HYPOTHESIS: Ceramide lipids have a role in the development of insulin resistance, diabetes and risk of cardiovascular disease. Here we investigated four ceramides and their ratios to find the best predictors of incident diabetes. METHODS: A validated mass-spectrometric method was applied to measure Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1) from serum or plasma samples. These ceramides were analysed in a population-based risk factor study (FINRISK 2002, n = 8045), in a cohort of participants undergoing elective coronary angiography for suspected stable angina pectoris (Western Norway Coronary Angiography Cohort [WECAC], n = 3344) and in an intervention trial investigating improved methods of lifestyle modification for individuals at high risk of the metabolic syndrome (Prevent Metabolic Syndrome [PrevMetSyn], n = 371)...
March 15, 2018: Diabetologia
Te-Sha Tsai, Sonika Tyagi, Justin C St John
STUDY QUESTION: What are the molecular differences between mitochondrial DNA (mtDNA)-deficient and mtDNA-normal oocytes and how does mitochondrial supplementation alter these? SUMMARY ANSWER: Changes to DNA methylation in a 5' cytosine-phosphate-guanine 3' (CpG) island in the mtDNA-specific replication factor (DNA polymerase gamma (POLG)) of mtDNA-deficient oocytes mediates an increase in mtDNA copy number by the 2-cell stage that positively modulates the expression of nuclear genes, which affect cellular and metabolic processes, following autologous mitochondrial supplementation...
March 13, 2018: Human Reproduction
Nicholette D Palmer, Hayrettin Okut, Fang-Chi Hsu, Maggie C Y Ng, Yii-Der Ida Chen, Mark O Goodarzi, Kent D Taylor, Jill M Norris, Carlos Lorenzo, Jerome I Rotter, Richard N Bergman, Carl D Langefeld, Lynne E Wagenknecht, Donald W Bowden
Context: Metabolomics provides a biochemical fingerprint which, when coupled with clinical phenotypes, can provide insight into physiological processes and disease. Objective: Survey metabolites associated with dynamic and basal measures of glucose homeostasis. Design: Analysis of 733 serum metabolites from the Insulin Resistance Atherosclerosis Family Study. Setting: Community-based. Participants: 1111 Mexican Americans...
March 13, 2018: Journal of Clinical Endocrinology and Metabolism
Jessica L H Walters, Geoffry N De Iuliis, Matthew D Dun, Robert John Aitken, Eileen A McLaughlin, Brett Nixon, Elizabeth G Bromfield
One of the leading causes of male infertility is defective sperm function, a pathology that commonly arises from oxidative stress in the germline. Lipid peroxidation events in the sperm plasma membrane result in the generation of cytotoxic aldehydes such as 4-hydroxynonenal (4HNE), which accentuate the production of reactive oxygen species (ROS) and cause cellular damage. One of the key enzymes involved in the metabolism of polyunsaturated fatty acids to 4HNE in somatic cells is arachidonate 15-lipoxygenase (ALOX15)...
March 13, 2018: Biology of Reproduction
Chengzhi Fang, Lili Xie, Chunmei Liu, Chunhua Fu, Wei Ye, Hong Liu, Binghong Zhang
Neonatal necrotizing enterocolitis (NEC) is a severe acquired disease that predominantly affects the small intestine of neonates. NEC is caused by a combination of metabolic products, dysfunctions of the blood vessels, mucus and other unknown factors. Berberine may induce beneficial effects on necrotic and cardiovascular diseases due to its anti-inflammatory and anti-apoptotic effects on epithelial cells. In the present study, the therapeutic effects of berberine were investigated and the potential mechanisms by which it functions within a neonatal NEC mouse model were analyzed...
April 2018: Experimental and Therapeutic Medicine
Hai-Tao Hou, Ya-Nan Wang, Shi-Ze Shao, Song Fu, Xiang-Peng Huang, Xiao-Hui Wang
Dietary calcium (Ca) supplementation has beneficial effects on bone health. However, it is not clear whether a high calcium diet (HCD) following 5/6 nephrectomy (5/6 Nx) is beneficial to bone health. The aim of the present study was to examine the effects of an HCD on bone metabolism using a chronic kidney disease (CKD) mouse model. Male C57BL/6J mice were divided into three groups: Sham group, 5/6 Nx group and 5/6 Nx + HCD group. Mice were sacrificed 12 weeks post-surgery. Calcium (Ca) and creatinine (Cr) were measured using standard colorimetric methods and picric acid methods, respectively...
April 2018: Experimental and Therapeutic Medicine
Oscar Illescas, Juan C Gomez-Verjan, Lizbeth García-Velázquez, Tzipe Govezensky, Miriam Rodriguez-Sosa
Human macrophage migration inhibitory factor (MIF) is a cytokine that plays a role in several metabolic and inflammatory processes. Single nucleotide polymorphism (SNP) -173 G/C (rs755622) on MIF gene has been associated with numerous diseases, such as arthritis and cancer. However, most of the reports concerning the association of MIF with these and other pathologies are inconsistent and remain quite controversial. Therefore, we performed a meta-analysis from 96 case-control studies on -173 G/C MIF SNP and stratified the data according to the subjects geographic localization or the disease pathophysiology, in order to determine a more meaningful significance to this SNP...
2018: Frontiers in Genetics
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