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https://www.readbyqxmd.com/read/30341930/zebrafish-danio-rerio-water-tank-model-for-the-investigation-of-drug-metabolism-progress-outlook-and-challenges
#1
Vinicius Figueiredo Sardela, Carina de Souza Anselmo, Isabelle Karine da Costa Nunes, Gabriel Reis Alves Carneiro, Gustavo Ramalho Cardoso Dos Santos, Aline Reis de Carvalho, Bruna de Jesus Labanca, Daniely Silva, William Dias Ribeiro, Amanda Lessa Dutra de Araujo, Monica Costa Padilha, Cleverton Kleiton Freitas de Lima, Valeria Pereira de Sousa, Francisco Radler de Aquino Neto, Henrique Marcelo Gualberto Pereira
Zebrafish (Danio rerio) water tank (ZWT) approach was investigated as an alternative model for metabolism studies based on six different experiments with four model compounds. Sibutramine was applied for the multivariate optimization of ZWT conditions, also for the comparison of the metabolism among ZWT, humans, and mice, and for the role of CYP2B6 in ZWT. After the optimization, 18 fish and 168 hours of experiments is the minimum requirement for a relevant panel of biotransformation products. A comparison among the species resulted in the observation of the same hydroxylated metabolites, with differences in metabolites' concentration ratio...
October 20, 2018: Drug Testing and Analysis
https://www.readbyqxmd.com/read/30341891/prenatal-exposure-to-valproate-induces-sex-age-and-tissue-dependent-alterations-of-cholesterol-metabolism-potential-implications-on-autism
#2
Veronica Cartocci, Claudia Tonini, Tiziana Di Pippo, Florenzia Vuono, Sara Schiavi, Maria Marino, Viviana Trezza, Valentina Pallottini
Here, we investigated the protein network regulating cholesterol metabolism in the liver and brain of adolescent and adult male and female rats prenatally exposed to valproate (VPA), a well validated experimental model of autism spectrum disorders (ASD). We were aimed at studying whether prenatal VPA exposure affected the proteins involved in cholesterol homeostasis in a sex-dependent manner. To this aim the protein network of cholesterol metabolism, in term of synthesis and plasma membrane trafficking, was analyzed by western blot in the liver and different brain areas (amygdala, cerebellum, cortex, hippocampus, nucleus accumbens, and dorsal striatum) of adolescent and adult male and female rats prenatally exposed to VPA...
October 20, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30341615/thermal-shift-and-stability-assays-of-disease-related-misfolded-proteins-using-differential-scanning-fluorimetry
#3
Tânia G Lucas, Cláudio M Gomes, Bárbara J Henriques
Systematic identification of buffer formulations and small molecule chaperones that improve the expression, stability, and storage of proteins with therapeutic interest has gained enormous importance in biochemical research as well as in biotechnology and biomedical applications. In particular, the biochemical characterization of disease-related proteins and their genetic variants that result in misfolding requires systematic determination of protein stability, screening of optimal buffer conditions for biophysical and structural studies, and in some cases, the identification of small molecule chaperones with the potential to ameliorate folding defects...
2019: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30341613/a-cell-model-for-hsp60-deficiencies-modeling-different-levels-of-chaperonopathies-leading-to-oxidative-stress-and-mitochondrial-dysfunction
#4
Cagla Cömert, Paula Fernandez-Guerra, Peter Bross
Besides providing the majority of ATP production in cells, mitochondria are also involved in many other cellular functions and are central for cellular stress signaling. Mitochondrial dysfunction induces not only inherited mitochondrial disorders but also contributes to neurodegenerative diseases, cancer, diabetes, and metabolic syndrome. The HSP60/HSP10 molecular chaperone complex facilitates folding of mitochondrial proteins and is thus an important factor for many mitochondrial functions. To model different degrees of oxidative stress and mitochondrial dysfunction we here describe a HEK293 derived Flp-In cell system with stable insertion and tunable expression of HSP60 cDNA carrying a dominant negative mutation...
2019: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30341522/characterization-of-wnt1-inducible-signaling-pathway-protein-1-in-obese-children-and-adolescents
#5
An-Ru Wang, Xue-Qin Yan, Cai Zhang, Cai-Qi Du, Wen-Jun Long, Di Zhan, Jie Ren, Xiao-Ping Luo
Wnt1-inducible signaling pathway protein-1 (WISP1), a member of the CCN family, is increasingly being recognized as a potential target for obesity and type 2 diabetes mellitus. Recent studies have shown that WISP1 can regulate low-grade inflammation in obese mice, and circulating WISP1 levels are associated with obesity and type 2 diabetes mellitus in adults. Herein, we measured serum WISP1 levels in obese youth and explored its relationships with pro-inflammatory cytokine interleukin 18 (IL-18) and other metabolic indexes...
October 2018: Current medical science
https://www.readbyqxmd.com/read/30341298/nanodiamond-autophagy-inhibitor-allosterically-improves-the-arsenical-based-therapy-of-solid-tumors
#6
Zhifen Cui, Yu Zhang, Kai Xia, Qinglong Yan, Huating Kong, Jichao Zhang, Xiaolei Zuo, Jiye Shi, Lihua Wang, Ying Zhu, Chunhai Fan
Arsenic trioxide (ATO) is a successful chemotherapeutic drug for blood cancers via selective induction of apoptosis; however its efficacy in solid tumors is limited. Here we repurpose nanodiamonds (NDs) as a safe and potent autophagic inhibitor to allosterically improve the therapeutic efficacy of ATO-based treatment in solid tumors. We find that NDs and ATO are physically separate and functionally target different cellular pathways (autophagy vs. apoptosis); whereas their metabolic coupling in human liver carcinoma cells remarkably enhances programmed cell death...
October 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/30341247/advances-in-metabolic-flux-analysis-toward-genome-scale-profiling-of-higher-organisms
#7
Georg Basler, Alisdair R Fernie, Zoran Nikoloski
Methodological and technological advances have recently paved the way for metabolic flux profiling in higher organisms, like plants. However, in comparison to omics technologies, flux profiling has yet to provide comprehensive differential flux maps at a genome-scale and in different cell types, tissues, and organs. Here we highlight the recent advances in technologies to gather metabolic labeling patterns and flux profiling approaches. We provide an opinion of how recent local flux profiling approaches can be used in conjunction with the constraint-based modelling framework to arrive at genome-scale flux maps...
October 19, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/30341080/biochemical-reconstruction-of-a-metabolic-pathway-from-a-marine-bacterium-reveals-its-mechanism-of-pectin-depolymerization
#8
Joanne K Hobbs, Andrew G Hettle, Chelsea Vickers, Alisdair B Boraston
Pectin is a complex uronic acid-containing polysaccharide typically found in plant cell walls, though forms of pectin are also found in marine diatoms and seagrasses. Genetic loci that target pectin have recently been identified in two phyla of marine bacteria. These loci appear to encode for a pectin saccharification pathway that is distinct from the canonical pathway typically associated with phytopathogenic terrestrial bacteria. However, very few components of the marine pectin metabolism pathway have been experimentally validated...
October 19, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/30341076/mutations-on-peptidoglycan-synthesis-gene-pona-improve-electro-transformation-efficiency-of-corynebacterium-glutamicum-atcc-13869
#9
Jiao Liu, Yu Wang, Yujiao Lu, Xiaomeng Ni, Xuan Guo, Jing Zhao, Jiuzhou Chen, Taiwo Dele-Osibanjo, Ping Zheng, Jibin Sun, Yanhe Ma
Corynebacterium glutamicum is frequently engineered to serve as a versatile platform and model microorganism. However, due to its complex cell wall structure, transformation of C. glutamicum with exogenous DNA is inefficient. Although efforts have been devoted to improve the transformation efficiency by using cell wall weakening agents, direct genetic engineering of cell wall synthesis for enhancing cell competency has not been explored thus far. Herein, we reported that engineering of peptidoglycan synthesis could significantly increase the transformation efficiency of C...
October 19, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/30340917/relationship-between-allostatic-load-and-clinical-outcomes-in-youth-at-ultra-high-risk-for-psychosis-in-the-neurapro-study
#10
Maximus Berger, Suzie Lavoie, Patrick D McGorry, Barnaby Nelson, Connie Markulev, Hok-Pan Yuen, Miriam Schaefer, Zoltán Sarnyai, G Paul Amminger
Individuals at ultra-high risk (UHR) for psychosis have an elevated risk of developing psychosis and other psychiatric outcomes. Risk biomarkers can assist in delineating individual risk and allow better prediction of longer-term outcomes. The aim of the present study was to examine if allostatic load (AL), a multisystem index of neuroendocrine, cardiovascular, immune and metabolic dysregulation, is associated with clinical outcomes in youth at UHR for psychosis. AL was measured in 106 participants of the NEURAPRO study (n = 70 female, n = 36 male; mean age 17...
October 16, 2018: Schizophrenia Research
https://www.readbyqxmd.com/read/30340896/discovery-of-5-2-chloro-4-1h-imidazol-1-yl-1-1-biphenyl-4-yl-1h-tetrazole-as-potent-and-orally-efficacious-s-nitrosoglutathione-reductase-gsnor-inhibitors-for-the-potential-treatment-of-copd
#11
Nagarajan Muthukaman, Sanjay Deshmukh, Shital Tondlekar, Macchindra Tambe, Dnyandeo Pisal, Neelam Sarode, Siddharth Mhatre, Samitabh Chakraborti, Daisy Shah, Vikram M Bhosale, Abhay Kulkarni, Mahamad Yunnus A Mahat, Satyawan B Jadhav, Girish S Gudi, Neelima Khairatkar-Joshi, Laxmikant A Gharat
Endogenous nitrosothiols (SNOs) including S-nitrosoglutathione (GSNO) serve as reservoir for bioavailable nitric oxide (NO) and mediate NO-based signaling, inflammatory status and smooth muscle function in the lung. GSNOR inhibition increases pulmonary GSNO and induces bronchodilation while reducing inflammation in lung diseases. In this letter, design, synthesis and structure-activity relationships (SAR) of novel imidazole-biaryl-tetrazole based GSNOR inhibitors are described. Many potent inhibitors (30, 39, 41, 42, 44, 45 and 58) were identified with low nanomolar activity (IC50 s: <15 nM) along with adequate metabolic stability...
October 10, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/30340895/plasma-citrulline-concentration-a-marker-for-intestinal-functionality-reflects-exercise-intensity-in-healthy-young-men
#12
Shirley Kartaram, Marco Mensink, Marc Teunis, Eric Schoen, Gerrit Witte, Lonneke Janssen Duijghuijsen, Martie Verschuren, Karin Mohrmann, Laura M'Rabet, Karen Knipping, Harriet Wittink, Ardy van Helvoort, Johan Garssen, Renger Witkamp, Raymond Pieters, Klaske van Norren
BACKGROUND & AIMS: Plasma citrulline concentration is considered to be a marker for enterocyte metabolic mass and to reflect its reduction as may occur during intestinal dysfunction. Strenuous exercise can act as a stressor to induce small intestinal injury. Our previous studies suggest that this comprises the intestinal ability to produce citrulline from a glutamine-rich protein bolus. In this study we investigated the effects of different exercise intensities and hydration state on citrulline and iFABP levels following a post-exercise glutamine bolus in healthy young men...
September 28, 2018: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/30340847/forecasting-life-expectancy-years-of-life-lost-and-all-cause-and-cause-specific-mortality-for-250-causes-of-death-reference-and-alternative-scenarios-for-2016-40-for-195-countries-and-territories
#13
Kyle J Foreman, Neal Marquez, Andrew Dolgert, Kai Fukutaki, Nancy Fullman, Madeline McGaughey, Martin A Pletcher, Amanda E Smith, Kendrick Tang, Chun-Wei Yuan, Jonathan C Brown, Joseph Friedman, Jiawei He, Kyle R Heuton, Mollie Holmberg, Disha J Patel, Patrick Reidy, Austin Carter, Kelly Cercy, Abigail Chapin, Dirk Douwes-Schultz, Tahvi Frank, Falko Goettsch, Patrick Y Liu, Vishnu Nandakumar, Marissa B Reitsma, Vince Reuter, Nafis Sadat, Reed J D Sorensen, Vinay Srinivasan, Rachel L Updike, Hunter York, Alan D Lopez, Rafael Lozano, Stephen S Lim, Ali H Mokdad, Stein Emil Vollset, Christopher J L Murray
BACKGROUND: Understanding potential trajectories in health and drivers of health is crucial to guiding long-term investments and policy implementation. Past work on forecasting has provided an incomplete landscape of future health scenarios, highlighting a need for a more robust modelling platform from which policy options and potential health trajectories can be assessed. This study provides a novel approach to modelling life expectancy, all-cause mortality and cause of death forecasts -and alternative future scenarios-for 250 causes of death from 2016 to 2040 in 195 countries and territories...
October 16, 2018: Lancet
https://www.readbyqxmd.com/read/30340811/melinjo-gnetum-gnemon-l-seed-extract-induces-uncoupling-protein-1-expression-in-brown-fat-and-protects-mice-against-diet-induced-obesity-inflammation-and-insulin-resistance
#14
Takeshi Yoneshiro, Ryuji Kaede, Kazuki Nagaya, Manami Saito, Julia Aoyama, Mohamed Elfeky, Yuko Okamatsu-Ogura, Kazuhiro Kimura, Akira Terao
Dietary supplementation with melinjo (Gnetum gnemon L.) seed extract (MSE) has been proposed as an anti-obesity strategy. However, it remains unclear how MSE modulates energy balance. We tested the hypothesis that dietary MSE reduces energy intake and/or increases physical activity and metabolic thermogenesis in brown and white adipose tissue (BAT and WAT) in mice. Twenty-four C57BL/6 J mice were provided with normal diet, high-fat diet (HFD), or HFD with 1% MSE added, for 17 weeks. Food intake, spontaneous locomotor activity, hepatic triglyceride (TG) content, and blood parameters were examined...
October 2018: Nutrition Research
https://www.readbyqxmd.com/read/30340512/rapid-and-pervasive-development-and-tissue-specific-homeolog-expression-partitioning-in-newly-formed-inter-subspecific-rice-segmental-allotetraploids
#15
Long Zhao, Lei Han, Chaoxia Xiao, Xiuyun Lin, Chunming Xu, Chunwu Yang
BACKGROUND: In diverse plant taxa, whole-genome duplication (WGD) events are major sources of phenotypic novelty. Studies of gene expression in synthetic polyploids have shown immediate expression and functional partitioning of duplicated genes among different tissues. Many studies of the tissue-specific homeolog expression partitioning have focused on allopolyploids that have very different parental genomes, while few studies have focused on autopolyploids or allopolyploids that have similar parental genomes...
October 19, 2018: BMC Genomics
https://www.readbyqxmd.com/read/30340503/aerobic-and-resistance-exercise-improves-physical-fitness-bone-health-and-quality-of-life-in-overweight-and-obese-breast-cancer-survivors-a-randomized-controlled-trial
#16
Christina M Dieli-Conwright, Kerry S Courneya, Wendy Demark-Wahnefried, Nathalie Sami, Kyuwan Lee, Frank C Sweeney, Christina Stewart, Thomas A Buchanan, Darcy Spicer, Debu Tripathy, Leslie Bernstein, Joanne E Mortimer
BACKGROUND: Exercise is an effective strategy to improve quality of life and physical fitness in breast cancer survivors; however, few studies have focused on the early survivorship period, minorities, physically inactive and obese women, or tested a combined exercise program and measured bone health. Here, we report the effects of a 16-week aerobic and resistance exercise intervention on patient-reported outcomes, physical fitness, and bone health in ethnically diverse, physically inactive, overweight or obese breast cancer survivors...
October 19, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/30340496/the-effect-of-cinnamon-on-polycystic-ovary-syndrome-in-a-mouse-model
#17
Lei Dou, Yahong Zheng, Lu Li, Xiaowei Gui, Yajuan Chen, Meng Yu, Yi Guo
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most prevalent cause of anovulatory infertility and hyperandrogenism. Evidence favors insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in PCOS. The use of insulin-sensitizing drugs has been shown to improve both the reproductive and the metabolic aspects of PCOS. Cinnamon has been found to have insulin sensitizing effect and improve menstrual cyclicity in women with PCOS. The aim of this study was to determine the effect and mechanism of cinnamon on PCOS using a dehydroepiandrosterone (DHEA) induced PCOS mouse model...
October 19, 2018: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/30340465/do-polymorphisms-in-protein-kinase-catalytic-subunit-alpha-1-gene-associated-with-cancer-susceptibility-a-meta-analysis-and-systematic-review
#18
Jialin Meng, Xinyao Fan, Meng Zhang, Zongyao Hao, Chaozhao Liang
BACKGROUND: Currently, several studies have demonstrated that PRKAA1 polymorphisms conduce to the development of cancer. PRKAA1 gene encodes the AMP-activated protein kinase summit-α1, and plays an important role in cell metabolism. Thus, we performed a systematic review and meta-analysis of all enrolled eligible case-control studies to obtain a precise correlation between PRKAA1 polymorphism and cancer susceptibility. METHODS: Extensive retrieve was performed in Web of Science, Google Scholar, PubMed, EMbase, CNKI and Wanfang databases up to August 26, 2018...
October 19, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/30340390/actions-of-inonotus-obliquus-against-hyperuricemia-through-xod-and-bioactives-screened-by-molecular-modeling
#19
Tianqiao Yong, Shaodan Chen, Danling Liang, Dan Zuo, Xue Diao, Chenling Deng, Yuning Wu, Huiping Hu, Yizhen Xie, Diling Chen
Inonotus obliquus is an edible mushroom and also a remedy against various diseases, especially metabolic syndrome. In this paper we report the actions of an ethanol extract of I. obliquus (IOE) against hyperuricemia in hyperuricemic mice, and the screen of bioactives. The extract (IOE) was prepared by extracting I. obliquus at 65 °C with ethanol, and characterized by HPLC. IOE at low, middle, and high doses reduced serum uric acid (SUA) of hyperuricemic mice (353 μmol/L) to 215, 174, and 152 μmol/L ( p < 0...
October 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30340338/probiotics-in-autoimmune-and-inflammatory-disorders
#20
REVIEW
Yuying Liu, Jane J Alookaran, J Marc Rhoads
Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to impact the immune system, both in vivo and in vitro. This interaction is linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on mechanistic studies in animal models. Microbial⁻immune system crosstalk has been linked to: short-chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor...
October 18, 2018: Nutrients
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