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https://www.readbyqxmd.com/read/28926911/enhanced-biosynthesis-of-3-4-dihydroxybutyric-acid-by-engineered-escherichia-coli-in-a-dual-substrate-system
#1
Haijun Gao, Yu Gao, Runan Dong
3,4-Dihydroxybutyric acid (3,4-DHBA), a versatile platform four carbon (C4) chemical, can be used as a precursor in the production of many commercially important chemicals. Here, a dual-substrate biosynthesis system was developed for 3,4-DHBA production via a synthetic pathway established in an engineered Escherichia coli, and using xylose as a synthetic substrate and glucose as a cell growth substrate. The deletion of genes xylA, yjhH and yagE and others encoding for alcohol dehydrogenases in E. coli is essential for the production of 3,4-DHBA...
September 5, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28925872/abdominal-aorta-aneurysm-aaa-is-there-a-role-for-prevention-and-therapy-using-antioxidants
#2
Joël Pincemail, Jean-Olivier Defraigne, Audrey Courtois, Adelin Albert, Jean-Paul Cheramy-Bien, Natzi Sakalihasan
Abdominal aortic aneurysm (AAA) is a degenerative disease that cause mortality in people aged > 65 years. Increased reactive oxygen species (ROS) and oxidative stress seems to play a pivotal role in AAA pathogenesis. Several sources of ROS have been identified in aortic tissues using experimental models: inflammation, increased activity of NAD(P)H or NOX, over-expression of inducible nitric oxide synthase (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), platelets activation and iron release from hemoglobin...
September 18, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28925274/-a-case-report-of-peritoneal-tuberculosis-the-diagnostic-role-of-pet-ct-and-laparoscopy
#3
H Macháčková, R Pilka, S Losse, M Žurková, V Lošťáková, T Tichý, Y Lovečková
OBJECTIVE: We present a case of peritoneal tuberculosis of young woman with focus on difficult diagnosis of this low incidence disease in developed countries. DESIGN: Case report. SETTING: Department of Gynaecology and Obstetrics, Faculty Hospital, Olomouc. Department of Obstetric and Gynaecology, Nový Jičín Hospital. Department of Pulmonary Diseases and Tuberculosis, Faculty Hospital, Olomouc. Department of Pathology nad Molecular Medicine, Faculty Hospital, Olomouc...
2017: Ceská Gynekologie
https://www.readbyqxmd.com/read/28923965/sirt7-promotes-adipogenesis-in-the-mouse-by-inhibiting-autocatalytic-activation-of-sirt1
#4
Jian Fang, Alessandro Ianni, Christian Smolka, Olesya Vakhrusheva, Hendrik Nolte, Marcus Krüger, Astrid Wietelmann, Nicolas G Simonet, Juan M Adrian-Segarra, Alejandro Vaquero, Thomas Braun, Eva Bober
Sirtuins (Sirt1-Sirt7) are NAD(+)-dependent protein deacetylases/ADP ribosyltransferases, which play decisive roles in chromatin silencing, cell cycle regulation, cellular differentiation, and metabolism. Different sirtuins control similar cellular processes, suggesting a coordinated mode of action but information about potential cross-regulatory interactions within the sirtuin family is still limited. Here, we demonstrate that Sirt1 requires autodeacetylation to efficiently deacetylate targets such as p53, H3K9, and H4K16...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923648/octreotide-ameliorates-renal-ischemia-reperfusion-injury-via-antioxidation-and-anti-inflammation
#5
Z Xu, K Zhao, P Han, X Qi, W Zhang, T Niu
Oxidative stress, calcium overload, inflammation, cellular necrosis, and apoptosis are implicated in renal ischemic/reperfusion injury (RIRI). Because octreotide (OCT) is protective in retinal IRI, the effect of OCT on mouse RIRI and the mechanisms involved were investigated. The RIRI model was induced in male C57BL/6 mice, and the mice were then treated with saline or OCT. Serum and kidneys were subjected to periodic acid-Schiff staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923496/deficiency-of-the-mitochondrial-nad-kinase-causes-stress-induced-hepatic-steatosis-in-mice
#6
Kezhong Zhang, Hyunbae Kim, Zhiyao Fu, Yining Qiu, Zhao Yang, Jiemei Wang, Deqiang Zhang, Xin Tong, Lei Yin, Jing Li, Jianmei Wu, Nathan R Qi, Sander M Houten, Ren Zhang
BACKGROUND & AIMS: The mitochondrial nicotinamide adenine dinucleotide (NAD) kinase (NADK2, also called MNADK) catalyzes phosphorylation of NAD to yield NADP. Little is known about the functions of mitochondrial NADP and MNADK in liver physiology and pathology. We investigated the effects of reduced mitochondrial NADP by deleting MNADK in mice. METHODS: We generated MNADK-knockout (KO) mice on a C57BL/6NTac background; mice with a wild-type Mnadk gene were used as controls...
September 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28923345/sirt1-is-a-transcriptional-enhancer-of-the-glucocorticoid-receptor-acting-independently-to-its-deacetylase-activity
#7
Shigeru Suzuki, James R Iben, Steven L Coon, Tomoshige Kino
Glucocorticoids have strong effects on diverse human activities through the glucocorticoid receptor (GR). Sirtuin 1 (SIRT1) is a NAD(+)-dependent histone deacetylase and promotes longevity by influencing intermediary metabolism and other regulatory activities including mitochondrial function. In this study, we examined the effects of SIRT1 on GR-mediated transcriptional activity. We found that SIRT1 enhanced GR-induced transcriptional activity on exogenous and endogenous glucocorticoid-responsive genes, whereas knockdown of SIRT1 attenuated it...
September 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28922779/targeting-the-myofibroblastic-cancer-associated-fibroblast-phenotype-through-inhibition-of-nox4
#8
Christopher J Hanley, Massimiliano Mellone, Kirsty Ford, Steve M Thirdborough, Toby Mellows, Steven J Frampton, David M Smith, Elena Harden, Cedric Szyndralewiez, Marc Bullock, Fergus Noble, Karwan A Moutasim, Emma V King, Pandurangan Vijayanand, Alex H Mirnezami, Timothy J Underwood, Christian H Ottensmeier, Gareth J Thomas
Background: Cancer-associated fibroblasts (CAFs) are tumor-promoting and correlate with poor survival in many cancers, which has led to their emergence as potential therapeutic targets. However, effective methods to manipulate these cells clinically have yet to be developed. Methods: CAF accumulation and prognostic significance in head and neck cancer (oral, n = 260; oropharyngeal, n = 271), and colorectal cancer (n = 56) was analyzed using immunohistochemistry...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922724/oyster-ostrea-plicatula-gmelin-polysaccharides-intervention-ameliorates-cyclophosphamide-induced-genotoxicity-and-hepatotoxicity-in-mice-via-the-nrf2-are-pathway
#9
Shuting Lin, Gengxin Hao, Min Long, Fei Lai, Qingqin Li, Yongmei Xiong, Yan Tian, Dong Lai
In this study, we explored the protective effects of oyster (Ostrea plicatula Gmelin) polysaccharides (OPS) against genotoxicity and liver injury induced by cyclophosphamide (CP) in BALB/c mice. OPS was administered to mice at doses of 100 and 200mg/kg for 7 consecutive days, then 50mg/kg CP was injected via abdomen. Then mice were sacrificed and samples were collected. Bone marrow micronuclei (MN) and polychromatic erythrocytes (PCE): normochromatic erythrocytes (NCE) ratio were calculated to evaluate CP induced genetic toxicity...
September 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28922594/dose-dependent-response-to-3-nitrobenzanthrone-exposure-in-human-urothelial-cancer-cells
#10
Mario Pink, Nisha Verma, Anna Zerries, Simone Schmitz-Spanke
A product of incomplete combustion of diesel fuel, 3-nitrobenzanthrone (3-NBA), has been classified as a cancer-causing substance. It first gained attention as a potential urinary bladder carcinogen due to the presence of its metabolite in urine and formation of DNA adducts. The aim of the present study was to characterise the dose-response relationship of 3-NBA in human urothelial cancer cell line (RT4) exposed to concentrations ranging from 0.0003 µM (environmentally relevant) to 80 µM by utilising toxicological and metabolomic approaches...
September 18, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28921510/development-of-a-formaldehyde-biosensor-with-application-to-synthetic-methylotrophy
#11
Benjamin M Woolston, Timothy Roth, Ishwar Kohale, David Liu, Gregory Stephanopoulos
Formaldehyde is a prevalent environmental toxin and a key intermediate in single carbon metabolism. The ability to monitor formaldehyde concentration is therefore of interest for both environmental monitoring and for metabolic engineering of native and synthetic methylotrophs, but current methods suffer from low sensitivity, complex workflows, or require expensive analytical equipment. Here we develop a formaldehyde biosensor based on the FrmR repressor protein and cognate promoter of E. coli. Optimization of the native repressor binding site and regulatory architecture enabled detection at levels as low as 1 µM...
September 16, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28921162/a-bionanohybrid-znal-nads-ecological-pesticide-as-a-treatment-for-soft-rot-disease-in-potato-solanum-tuberosum-l
#12
Erika Elizabeth Morales-Irigoyen, Yolanda de Las Mercedes Gómez-Y-Gómez, Jorge Luis Flores-Moreno, Marina Olivia Franco-Hernández
Pectobacterium carotovorum (Pc) is a phytopathogenic strain that causes soft rot disease in potato (Solanum tuberosum L.), resulting in postharvest losses. Chemical control is effective for managing this disease, but overdoses cause adverse effects. Because farmers insist on using chemical agents for crop protection, it is necessary to develop more effective pesticides in which the active compound released can be regulated. In this context, we proposed the synthesis of ZnAl-NADS, in which nalidixic acid sodium salt (NADS) is linked to a ZnAl-NO3 layered double hydroxide (LDH) host as a nanocarrier...
September 18, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28919418/the-nampt-e2f2-sirt1-axis-promotes-proliferation-and-inhibits-p53-dependent-apoptosis-in-human-melanoma-cells
#13
Hailong Zhao, Weiwei Tang, Xiaowen Chen, Siyu Wang, Xianyan Wang, Haiyan Xu, Lijuan Li
Melanoma is the most common primary malignant neoplasm in adults, causing more deaths than any other skin cancer, necessitating the development of new target-based approaches. Current evidence suggests SIRT1, the mammalian nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase, and nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting NAD(+) biosynthetic enzyme, together comprise a novel systemic regulatory network to play a pivotal role in cell proliferation and apoptosis. Nevertheless, how the regulation of this cofactor interfaces with signal transduction network remains poorly understood in melanoma...
September 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28919254/palmitic-acid-stimulates-energy-metabolism-and-inhibits-insulin-pi3k-akt-signaling-in-differentiated-human-neuroblastoma-cells-the-role-of-mtor-activation-and-mitochondrial-ros-production
#14
Erika Calvo-Ochoa, Karina Sánchez-Alegría, Cecilia Gómez-Inclán, Patricia Ferrera, Clorinda Arias
The high consumption of saturated lipids has been largely associated with the increasing prevalence of metabolic diseases. In particular, saturated fatty acids such as palmitic acid (PA) have been implicated in the development of insulin resistance in peripheral tissues. However, how neurons develop insulin resistance in response to lipid overload is not fully understood. Here, we used cultured rat cortical neurons and differentiated human neuroblastoma cells to demonstrate that PA blocks insulin-induced metabolic activation, inhibits the activation of the insulin/PI3K/Akt pathway and activates mTOR kinase downstream of Akt...
September 15, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28918750/expression-purification-and-activity-of-acthis-a-thiazole-biosynthesis-enzyme-from-acremonium-chrysogenum
#15
Zhihui Song, Jie Pan, Liping Xie, Guihua Gong, Shu Han, Wei Zhang, Youjia Hu
Thiamine pyrophosphate is an essential coenzyme in all organisms. Its biosynthesis involves independent syntheses of the precursors, pyrimidine and thiazole, which are then coupled. In our previous study with overexpressed and silent mutants of ActhiS (thiazole biosynthesis enzyme from Acremonium chrysogenum), we found that the enzyme level correlated with intracellular thiamine content in A. chrysogenum. However, the exact structure and function of ActhiS remain unclear. In this study, the enzyme-bound ligand was characterized as the ADP adduct of 5-(2-hydroxyethyl)-4-methylthiazole-2-carboxylic acid (ADT) using HPLC and (1)H NMR...
July 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28917714/mitochondria-in-the-nervous-system-from-health-to-disease-part-i
#16
EDITORIAL
Brian M Polster, Maria Teresa Carrì, Philip M Beart
In Part I of this Special Issue on "Mitochondria in the Nervous System: From Health to Disease", the editors bring together contributions from experts in brain mitochondrial research to provide an up-to-date overview of mitochondrial functioning in physiology and pathology. The issue provides cutting edge reviews on classical areas of mitochondrial biology that include energy substrate utilization, calcium handling, mitochondria-endoplasmic reticulum communication, and cell death regulation. Additional reviews and original research articles touch upon key mitochondrial defects seen across multiple neurodegenerative conditions, including fragmentation, loss of respiratory capacity, calcium overload, elevated reactive oxygen species generation, perturbed NAD(+) metabolism, altered protein acetylation, and compromised mitophagy...
September 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28916726/the-nqo1-bioactivatable-drug-%C3%AE-lapachone-alters-the-redox-state-of-nqo1-pancreatic-cancer-cells-causing-perturbation-in-central-carbon-metabolism
#17
Molly A Silvers, Stanislaw Deja, Naveen Singh, Robert A Egnatchik, Jessica Sudderth, Xiuquan Luo, Muhammad S Beg, Shawn C Burgess, Ralph J DeBerardinis, David A Boothman, Matthew E Merritt
Many cancer treatments, such as those for managing recalcitrant tumors like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlighting the need for more tumor-selective chemotherapies. β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide, then peroxide formation, which damages DNA and causes hyperactivation of poly (ADP-ribose) polymerase (PARP), resulting in extensive NAD+/ATP depletion...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916720/glucose-availability-controls-adipogenesis-in-mouse-3t3-l1-adipocytes-via-upregulation-of-nicotinamide-metabolism
#18
Robert M Jackson, Beth A Griesel, Jami M Gurley, Luke I Szweda, Ann Louise Olson
Expansion of adipose tissue in response to a positive energy balance underlies obesity and occurs through both hypertrophy of existing cells and increased differentiation of adipocyte precursors (hyperplasia). To better understand the nutrient signals that promote adipocyte differentiation, we investigated the role of glucose availability in regulating adipocyte differentiation and maturation. 3T3-L1 preadipocytes were grown and differentiated in media containing a standard differentiation hormone cocktail and either 4 or 25mM glucose...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916476/pharmacologic-ascorbate-induces-neuroblastoma-cell-death-by-hydrogen-peroxide-mediated-dna-damage-and-reduction-in-cancer-cell-glycolysis
#19
Enlong Ma, Ping Chen, Heather M Wilkins, Tao Wang, Russell H Swerdlow, Qi Chen
An ascorbate-mediated production of oxidative stress has been shown to retard tumor growth. Subsequent glycolysis inhibition has been suggested. Here, we further define the mechanisms relevant to this observation. Ascorbate was cytotoxic to human neuroblastoma cells through the production of H2O2, which led to ATP depletion, inhibited GAPDH, and non-apoptotic and non-autophagic cell death. The mechanism of cytotoxicity is different when PARP-dependent DNA repair machinery is active or inhibited. Ascorbate-generated H2O2 damaged DNA, activated PARP, depleted NAD+, and reduced glycolysis flux...
September 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28915567/melatonin-inhibits-sirt1-dependent-nampt-and-nfat5-signaling-in-chondrocytes-to-attenuate-osteoarthritis
#20
Jia Yi Guo, Feng Li, Yong Bing Wen, Hong Xun Cui, Ma Long Guo, Lin Zhang, Yun Fei Zhang, Yan Jin Guo, Yan Xing Guo
Osteoarthritis (OA) is a degenerative joint disease mainly characterized by cartilage degradation. Interleukin-1β (IL-1β) contributes to OA pathogenesis by enhancing oxidative stress and inflammation. Melatonin reportedly elicits potent protection against OA. However, the role of melatonin and underlying mechanism in IL-1β-stimulated chondrocytes remain largely unclear. In this study, we found that melatonin inhibited IL-1β-induced toxicity and sirtuin 1 (Sirt1) enhancement in human chondrocytes. Melatonin reduced the IL-1β-increased nicotinamide phosphoribosyltransferase (NAMPT) expression and the NAD(+) level in chondrocytes in a Sirt1-dependent manner...
August 22, 2017: Oncotarget
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