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metabolic models

Leizhen Duan, Zonggui Xue, Huanwen Ji, Dongdong Zhang, Yan Wang
BACKGROUND AND OBJECTIVE: CYP2R1 is a key gene in the vitamin D metabolic pathway. It has been suggested that CYP2R1 gene variants in European populations are associated with concentrations of 25(OH)D, a biomarker of vitamin D levels and status in peripheral blood. However, a comprehensive meta-analysis of this effect including different ethnicities has never been conducted. The objective of this meta-analysis was to evaluate the association between CYP2R1 gene variants and 25(OH)D levels and vitamin D status...
August 15, 2018: Gene
Xilin Li, Zemin Wang, James E Klaunig
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the western countries. The histological spectrum of NAFLD includes simple steatosis, steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. Nuclear receptors are a large group of ligand-dependent transcription factors that sense the environmental and endogenous changes and regulate numerous physiological and pathological processes. Accumulating evidence has suggested that a dysregulation of nuclear receptors in NAFLD may effect on the metabolism of endogenous and exogenous chemicals in the liver...
August 15, 2018: Toxicology
Gustavo Roberto Thomé, Vitor Antunes Oliveira, Maria Rosa Chitolina Schetinger, Rogério Aquino Saraiva, Diego Souza, Oscar Endrigo Dorneles Rodrigues, João Batista Teixeira Rocha, Rafael Porto Ineu, Maria Ester Pereira
The present study evaluated the neuroprotective effects of one selenium-containing AZT derivative compound (S1073) in memory and learning impairment caused by Intracerebroventricular-streptozotocin (ICV-STZ). ICV-STZ in mice causes impairment of energy metabolism with oxidative damage and cholinergic dysfunction, and provides a relevant model for sporadic dementia of Alzheimer's type (AD). Acetylcolinesterase (AChE), Catalase (CAT), dichlorofluorescein oxidation (DCFH), TBARS and thiol content were measured...
August 15, 2018: Chemico-biological Interactions
Estelle Lowry, Nina Rautio, Ville Karhunen, Jouko Miettunen, Leena Ala-Mursula, Juha Auvinen, Sirkka Keinänen-Kiukaanniemi, Katri Puukka, Inga Prokopenko, Karl-Heinz Herzig, Alexandra Lewin, Sylvain Sebert, Marjo-Riitta Järvelin
BACKGROUND: The prevention of the risk of type 2 diabetes (T2D) is complicated by multidimensional interplays between biological and psychosocial factors acting at the individual level. To address the challenge we took a systematic approach, to explore the bio-psychosocial predictors of blood glucose in mid-age. METHODS: Based on the 31-year and 46-year follow-ups (5,078 participants, 43% male) of Northern Finland Birth Cohort 1966, we used a systematic strategy to select bio-psychosocial variables at 31 years to enable a data-driven approach...
August 17, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Se-Hyung Kim, Ji-Young Byeon, Young-Hoon Kim, Choong-Min Lee, Yun Jeong Lee, Choon-Gon Jang, Seok-Yong Lee
Atomoxetine is a norepinephrine reuptake inhibitor indicated in the treatment of attention-deficit/hyperactivity disorder. It is primarily metabolized by CYP2D6 to its equipotent metabolite, 4-hydroxyatomoxetine, which promptly undergoes further glucuronidation to an inactive 4-HAT-O-glucuronide. Clinical trials have shown that decreased CYP2D6 activity leads to substantially elevated atomoxetine exposure and increase in adverse reactions. The aim of this study was to to develop a pharmacologically based pharmacokinetic (PBPK) model of atomoxetine in different CYP2D6 genotypes...
August 17, 2018: Scientific Reports
Marina Campos Rocha, Krissia Franco de Godoy, Renata Bannitz-Fernandes, João H T Marilhano Fabri, Mayra M Ferrari Barbosa, Patrícia Alves de Castro, Fausto Almeida, Gustavo Henrique Goldman, Anderson Ferreira da Cunha, Luis E S Netto, Marcos Antonio de Oliveira, Iran Malavazi
Standing among the front defense strategies against pathogens, host phagocytic cells release various oxidants. Therefore, pathogens have to cope with stressful conditions at the site of infection. Peroxiredoxins (Prx) are highly reactive and abundant peroxidases that can support virulence and persistence of pathogens in distinct hosts. Here, we revealed that the opportunistic human pathogen A. fumigatus presents three 1-Cys Prx (Prx6 subfamily), which is unprecedented. We showed that PrxB and PrxC were in mitochondria, while Prx1 was in cytosol...
August 17, 2018: Scientific Reports
Sarah A Pötgens, Hélène Brossel, Martina Sboarina, Emilie Catry, Patrice D Cani, Audrey M Neyrinck, Nathalie M Delzenne, Laure B Bindels
Cancer cachexia is a complex multi-organ syndrome characterized by body weight loss, weakness, muscle atrophy and fat depletion. With a prevalence of 1 million people in Europe and only limited therapeutic options, there is a high medical need for new approaches to treat cachexia. Our latest results highlighted microbial dysbiosis, characterized by a bloom in Enterobacteriaceae and altered gut barrier function in preclinical models of cancer cachexia. They also demonstrated the potential of targeting the gut microbial dysbiosis in this pathology...
August 17, 2018: Scientific Reports
Theresa Maria Rottmann, Carolin Fritz, Norbert Sauer, Ruth Stadler
Pollen tube growth requires a high amount of metabolic energy and precise targeting towards the ovules. Sugars, especially glucose, can serve as nutrient and as signaling molecules. Unexpectedly, in vitro assays revealed an inhibitory effect of glucose on pollen tube elongation, contradicting the hypothesis that monosaccharide uptake is a source of nutrition for growing pollen tubes. Measurements with FRET-based nanosensors revealed that glucose is taken up into pollen tubes and that the intracellular concentration is in the low micromolar range...
August 17, 2018: Plant Cell
Carlos B Hirschberg
Defects in protein glycosylation can have a dramatic impact on eukaryotic cells and is associated with mental and developmental pathologies in humans. The studies outlined below illustrate how a basic biochemical problem in the mechanisms of protein glycosylation, specifically substrate transporters of nucleotide sugars, including ATP and 3'-phosphoadenyl-5'-phosphosulfate (PAPS), in the membrane of the Golgi apparatus and endoplasmic reticulum, expanded into diverse biological systems from mammals, including humans, to yeast, roundworms, and protozoa...
August 17, 2018: Journal of Biological Chemistry
Hong Xue, Guangyuan Zhang, Aron M Geurts, Kristie Usa, David M Jensen, Yong Liu, Michael E Widlansky, Mingyu Liang
BACKGROUND: miR-29 is a master regulator of extracellular matrix genes, but conflicting data on its anti-fibrotic effect have been reported. miR-29 improves nitric oxide (NO) production in arterioles by targeting Lypla1. Mir29b1 targeted mutation exacerbates hypertension in a model derived from the Dahl salt-sensitive rat. We examined the effect of Mir29b1 mutation on tissue fibrosis and NO levels with a focus on kidney regions. METHODS: Mir29b1 targeted mutant rats on the genetic background of SS-Chr13BN rats were studied...
August 14, 2018: EBioMedicine
Jing Li, Xiaoxu Huo, Yun-Feng Cao, Sai-Nan Li, Zuo Du, Ping Shao, Junhong Leng, Cuiping Zhang, Xiao-Yu Sun, Ronald C W Ma, Zhong-Ze Fang, XilinYang
BACKGROUND: Bile acid metabolism plays an important role in metabolism but it is uncertain whether bile acid metabolites in early pregnancy are associated with risk of gestational diabetes mellitus (GDM). METHODS: We organized a 1:1 case-control study nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in China: 243 women with GDM were matched with 243 non-GDM controls on age (±1 year). Conditional logistic regression and restricted cubic spline were used to examine full-range associations of bile acid metabolites with GDM...
August 14, 2018: EBioMedicine
Wen-Li Sun, Nan Wang, Yan Xu
OBJECTIVE: To investigate how miR-302b affect the calcium-phosphorus metabolism and vascular calcification (VC) of rats with chronic renal failure (CRF) via the regulation of bone morphogentic proteins 2/Runt-related transcription factor 3/Osterix (BMP-2/Runx2/Osterix) signaling pathway. METHODS: SD rats were selected to establish CRF rat models and assigned into Sham, CRF, CRF + miR-302b, and CRF + miR-NC groups. The biochemical indexes of rats were detected at 8th and 12th week...
August 10, 2018: Archives of Medical Research
Gregory Knell, Qing Li, Kelley Pettee Gabriel, Kerem Shuval
More than two-thirds of American adults are overweight or obese, with many attempting to lose weight to avoid adverse health outcomes and improve well-being. Achieving long-term weight loss (LTWL) success, defined as reaching at least a 5% to 10% weight loss goal, is challenging, yet important for overall metabolic health. It is currently unclear whether achieving higher thresholds of LTWL is associated with improved health. Therefore, the purpose of this study was to examine the association between LTWL thresholds (5%-9...
August 10, 2018: Mayo Clinic Proceedings
Elizabeth J Mayer-Davis, David M Maahs, Michael Seid, Jamie Crandell, Franziska K Bishop, Kimberly A Driscoll, Christine M Hunter, Jessica C Kichler, Debra Standiford, Joan M Thomas
BACKGROUND: Adolescents with type 1 diabetes commonly have poor glycaemic control. We aimed to test the efficacy of a newly developed adaptive behavioral intervention (Flexible Lifestyles Empowering Change; FLEX) on metabolic and psychosocial outcomes in adolescents with type 1 diabetes. METHODS: Young people (13-16 years, type 1 diabetes duration >1 year, HbA1c of 64-119 mmol/mol [8·0-13·0%], and without other serious medical conditions or pregnancy) from two clinical sites (Colorado and Ohio, USA) were eligible for enrolment...
September 2018: Lancet Child & Adolescent Health
Jia Tao, Min Zhang, Zhijie Wen, Baoxue Wang, Lei Zhang, Yu Ou, Xu Tang, Xiaoping Yu, Qinglin Jiang
OBJECTIVES: Pulmonary fibrosis is strongly correlated with inflammation factors, cytokine, and collagen secretion, whereby discoidin domain receptor 1 (DDR1) signaling plays an important role. EP300 is defined as an acetyltransferase that can acetylate histone and has been broadly studied in several chronic diseases, including cancer, inflammation and fibrosis. This study aimed to investigate the relationship between p300 and DDR1 in the pathological processes of pulmonary fibrosis. MATERIALS AND METHODS: Transcriptome analysis of single cell RNA-sequencing for idiopathic pulmonary fibrosis (IPF) bronchial epithelial cells demonstrated that both DDR1 and EP300 were up-regulated and involved in the regulation of autophagy, cellular response to organonitrogen compounds, and collagen metabolic pathways, respectively...
July 30, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Britta Wilms, Rahel Keppler, Barbara Ernst, Sebastian M Schmid, Martin Thurnheer, Bernd Schultes
BACKGROUND: Even subjects with severe obesity show a wide range of metabolic health states, with some showing marked alterations in glucose and lipid metabolism whereas others do not. In severely obese women, we could recently show that the degree of cardiorespiratory fitness is, independently of body mass and age, associated with several markers of glucose and lipid metabolism. AIMS: In our retrospective study on a clinical data set, we questioned whether such an association also exists in severely obese men...
August 17, 2018: Experimental and Clinical Endocrinology & Diabetes
Masaru Ishida, Shigeru Miyagawa, Atsuhiro Saito, Satsuki Fukushima, Akima Harada, Emiko Ito, Fumiya Ohashi, Tadashi Watabe, Jun Hatazawa, Katsuhisa Matsuura, Yoshiki Sawa
BACKGROUND: Somatic stem cell (SC) therapy can improve cardiac performance following ischemic injury. In this study, we investigated whether induced pluripotent SC-derived cardiomyocytes (iPS-CMs) are more effective than somatic SCs, such as skeletal myoblasts (SM) and mesenchymal (M)SCs, in promoting functional recovery upon transplantation in a porcine model of myocardial infarction (MI). METHODS: Myocardial injury was induced by ameroid ring placement in immunosuppressed female mini-pigs; after 1 month, epicardial cell transplantation was performed with iPS-CMs (n = 7), SMs (n = 7), and MSCs (n = 7)...
August 17, 2018: Transplantation
Kennosuke Yorifuji, Yuko Uemura, Shinji Horibata, Goh Tsuji, Yoko Suzuki, Kazuya Miyagawa, Kazuhiko Nakayama, Ken-Ichi Hirata, Shunichi Kumagai, Noriaki Emoto
Bosentan, an endothelin receptor antagonist, has been widely used as a first-line drug for the treatment of pulmonary arterial hypertension (PAH). In addition, bosentan is approved for patients with digital ulcers related to systemic sclerosis. Liver dysfunction is a major adverse effect of bosentan and may lead to discontinuation of therapy. The purpose of this study was to identify genomic biomarkers to predict bosentan-induced liver injury. A total of 69 PAH patients were recruited into the study. An exploratory analysis of 1,936 single-nucleotide polymorphisms (SNPs) in 231 genes involved in absorption, distribution, metabolism, and elimination of multiple medications using Affimetrix DMET™ (Drug Metabolism Enzymes and Transporters) chips was performed...
August 14, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Leônidas Graças Mendes-Junior, Leandro Ceotto Freitas-Lima, Janaína Ribeiro Oliveira, Marcos B Melo, Carlos Eduardo Mendes D'Angelis, Jonh David Feltenberger, Igor Viana Brandi, Bruna Mara Aparecida Carvalho, André Luiz Sena Guimarães, Alfredo Maurício Batista De Paula, Carlos Eduardo Mendes D'Angelis, Maria José Campagnole-Santos, Robson Augusto Souza Santos, Valdir Andrade Braga, Sérgio Henrique Sousa Santos
Diabetic cardiomyopathy (DC) describes diabetes-associated changes in the structure and function of myocardium that are not directly linked to other factors such as hypertension. Currently there are some models of DC; however, they take a large time period to mimic key features. In the present study, we investigated the effects of a short-term high-fat/high salt diet (HFHS) treatment on myocardial function and structure, and vascular reactivity in C57BL/6 male mice. After 14 weeks HFHS induced hypertension (MAP = 144...
August 14, 2018: Life Sciences
Qianwen Wang, Zhong Zuo
In parallel with the blood-brain barrier (BBB), transporters and enzymes on the blood-cerebrospinal fluid barrier (BCSFB) serve as the first barrier for drug brain uptake. In addition, their expressions on the brain parenchyma are considered as the secondary barrier for central nervous system (CNS) drug delivery. Currently, a lack of information on transporters and enzymes expressed on both BCSFB and brain parenchyma is the major cause of failure in CNS drug development. Areas covered: Transporters and enzymes expressed on BCSFB as well as brain parenchyma and their impact on drug brain uptake was highlighted and compared with that on BBB...
August 17, 2018: Expert Opinion on Drug Metabolism & Toxicology
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