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https://www.readbyqxmd.com/read/29244873/fatty-acids-in-non-alcoholic-steatohepatitis-focus-on-pentadecanoic-acid
#1
Wonbeak Yoo, Donjeta Gjuka, Heather L Stevenson, Xiaoling Song, Hong Shen, Suk Young Yoo, Jing Wang, Michael Fallon, George N Ioannou, Stephen A Harrison, Laura Beretta
Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and ranges from isolated steatosis to NASH. To determine whether circulating fatty acids could serve as diagnostic markers of NAFLD severity and whether specific fatty acids could contribute to the pathogenesis of NASH, we analyzed two independent NAFLD patient cohorts and used the methionine- and choline-deficient diet (MCD) NASH mouse model. We identified six fatty acids that could serve as non-invasive markers of NASH in patients with NAFLD...
2017: PloS One
https://www.readbyqxmd.com/read/29243196/chronic-mild-hyperhomocysteinemia-alters-inflammatory-and-oxidative-nitrative-status-and-causes-protein-dna-damage-as-well-as-ultrastructural-changes-in-cerebral-cortex-is-acetylsalicylic-acid-neuroprotective
#2
Daniella de S Moreira, Paula W Figueiró, Cassiana Siebert, Caroline A Prezzi, Francieli Rohden, Fatima C R Guma, Vanusa Manfredini, Angela T S Wyse
Homocysteine is a sulfur-containing amino acid derived from methionine metabolism. When plasma homocysteine levels exceed 10-15 μM, there is a condition known as hyperhomocysteinemia, which occur as a result of an inborn error of methionine metabolism or by non-genetic causes. Mild hyperhomocysteinemia is considered a risk factor for development of neurodegenerative diseases. The objective of the present study was to evaluate whether acetylsalicylic acid has neuroprotective role on the effect of homocysteine on inflammatory, oxidative/nitrative stress, and morphological parameters in cerebral cortex of rats subjected to chronic mild hyperhomocysteinemia...
December 14, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29242512/synthetic-integrin-binding-immune-stimulators-target-cancer-cells-and-prevent-tumor-formation
#3
Manuel Brehs, André J G Pötgens, Julia Steitz, Karine Thewes, Janett Schwarz, Anne C Conibear, Matthias Bartneck, Frank Tacke, Christian F W Becker
Immuno-oncology approaches mainly utilize monoclonal antibodies or protein-based scaffolds that bind with high affinity to cancer cells and can generate an immune response. Peptides can also bind with high affinity to cancer cells and are intermediate in size between antibodies and small molecules. They are also synthetically accessible and therefore easily modified to optimize their stability, binding affinity and selectivity. Here we describe the design of immune system engagers (ISErs), a novel class of synthetic peptide-based compounds that bind specifically to cancer cells and stimulate the immune system...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29241413/novel-missense-mutations-in-gidb-gene-associated-with-streptomycin-resistance-in-mycobacterium-tuberculosis-insights-from-molecular-dynamics
#4
Bharati Pandey, Sonam Grover, Sukriti Goyal, Salma Jamal, Aditi Singh, Jagdeep Kaur, Abhinav Grover
Streptomycin was the first antibiotic used for the treatment of tuberculosis by inhibiting translational proof reading. Point mutation in gidB gene encoding S-adenosyl methionine (SAM)-dependent 7-methylguanosine (m7G) methyltransferase required for methylation of 16S rRNA confers streptomycin (STR) resistance. As there was no structural substantiation experimentally, gidB protein model was built by threading algorithm. In this work, molecular dynamics (MD) simulations coupled with binding free energy calculations were performed to outline the mechanism underlying high-level streptomycin resistance associated with three novel missense mutants including S70R, T146M and R187M...
December 14, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29236088/dicationic-imidazolium-based-ionic-liquid-coatings-on-zirconia-surfaces-physico-chemical-and-biological-characterization
#5
Pavan P K Sandhu, Izabelle M Gindri, Danyal A Siddiqui, Danieli C Rodrigues
In the present work, dicationic imidazolium-based ionic liquids (ILs) were investigated as multi-functional coatings on a zirconia (ZrO₂) surface to prevent biofilm formation and enhance the wear performance of zirconia while maintaining the material's compatibility with host cells. ILs containing phenylalanine and methionine were synthesized and deposited on zirconia. Intermolecular interactions driving IL deposition on zirconia were studied using X-ray photoelectron spectroscopy (XPS). Anti-biofilm activity and cell compatibility were evaluated in vitro after one and seven days, and wear performance was tested using a pin-on-disk apparatus...
December 13, 2017: Journal of Functional Biomaterials
https://www.readbyqxmd.com/read/29235426/cpda-is-involved-in-amino-acid-metabolism-in-shewanella-oneidensis-mr-1
#6
Takuya Kasai, Atsushi Kouzuma, Kazuya Watanabe
Cyclic 3',5'-adenosine monophosphate (cAMP) phosphodiesterase (CPD) is an enzyme that catalyzes the hydrolysis of cAMP, a signaling molecule affecting diverse cellular and metabolic processes in bacteria. Some CPDs are also known to function in cAMP-independent manners, while their physiological roles remain largely unknown. Here, we investigated physiological roles of CPD in Shewanella oneidensis MR-1, a model environmental bacterium, and report that CPD is involved in amino-acid metabolism. We found that a CPD-deficient mutant of MR-1 (ΔcpdA) showed decreased expression of genes for the synthesis of methionine, S-adenosylmethionine, and histidine and required these three compounds to grow in minimal media...
December 13, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29232372/attenuated-expression-of-mtr-in-both-prenatally-androgenized-mice-and-women-with-the-hyperandrogenic-phenotype-of-pcos
#7
Lei Lei, Lijun Ding, Jing Su, Mengyuan Liu, Qingqing Shi, Jianjun Zhou, Haixiang Sun, Guijun Yan
Polycystic ovary syndrome (PCOS) is a common endocrine, metabolic and heterogeneous disorder in women of reproductive age, the exact etiology of which remains unknown. To unravel the molecular mechanisms underlying the hyperandrogenic phenotype of PCOS, prenatally androgenized (PNA) mice were used to mimic this phenotype in women with PCOS. Using microarray analysis, 1188 differentially expressed genes, including 671 upregulated and 517 downregulated genes, were identified in ovaries from PNA mice. Five differentially expressed genes (Aldh1a7, Bhmt, Mtr, Nrcam, Ptprg) were validated, and decreased MTR expression was shown in ovaries of PNA mice...
2017: PloS One
https://www.readbyqxmd.com/read/29229391/hepatocyte-specific-clusterin-overexpression-attenuates-diet-induced-nonalcoholic-steatohepatitis
#8
Jin-Sung Park, Young-Jun Shim, Byeong-Ho Kang, Woon-Kyu Lee, Bon-Hong Min
Clusterin is a multifunctional glycoprotein that plays important roles and is up-regulated in liver diseases such as hepatitis and hepatocellular carcinoma. However, little is known about the significance of clusterin in the pathogenesis of non-alcoholic steatohepatitis (NASH). The aim of this study is to examine the role of clusterin in progression of steatohepatitis in mice fed a methionine and choline deficient (MCD) diet. We generated hepatocyte-specific clusterin overexpression (hCLU-tg) mice, and hCLU-tg mice showed lower levels of hepatic triglycerides, less infiltration of macrophages and reduction of TNF-α, activation of Nrf-2 than wild-type littermates fed the MCD diet...
December 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29226074/characterization-of-auxiliary-iron-sulfur-clusters-in-a-radical-s-adenosylmethionine-enzyme-pqqe-from-methylobacterium-extorquens-am1
#9
Natsaran Saichana, Katsuyuki Tanizawa, Hiroshi Ueno, Jiří Pechoušek, Petr Novák, Jitka Frébortová
PqqE is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the initial reaction of pyrroloquinoline quinone (PQQ) biosynthesis. PqqE belongs to the SPASM (subtilosin/PQQ/anaerobic sulfatase/mycofactocin maturating enzymes) subfamily of the radical SAM superfamily and contains multiple Fe-S clusters. To characterize the Fe-S clusters in PqqE from Methylobacterium extorquens AM1, Cys residues conserved in the N-terminal signature motif (CX 3 CX 2C) and the C-terminal seven-cysteine motif (CX 9-15 GX 4 CX n CX 2 CX 5 CX 3 CX n C; n = an unspecified number) were individually or simultaneously mutated into Ser...
December 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29225734/pdrg1-at-the-interface-between-intermediary-metabolism-and-oncogenesis
#10
REVIEW
María Ángeles Pajares
PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damage-regulated gene 1 (PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase II complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear...
November 26, 2017: World Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29224865/effects-of-supplementation-with-ruminally-protected-choline-on-performance-of-multiparous-holstein-cows-did-not-depend-upon-prepartum-caloric-intake
#11
M G Zenobi, R Gardinal, J E Zuniga, A L G Dias, C D Nelson, J P Driver, B A Barton, J E P Santos, C R Staples
Objectives were to evaluate the effect of prepartum energy intake on performance of dairy cows supplemented with or without ruminally protected choline (RPC; 0 or 17.3 g/d of choline chloride; 0 or 60 g/d of ReaShure, Balchem Corp., New Hampton, NY). At 47 ± 6 d before the expected calving date, 93 multiparous Holstein cows were assigned randomly to 1 of 4 dietary treatments in a 2 × 2 factorial arrangement. Cows were fed energy to excess [EXE; 1.63 Mcal of net energy for lactation/kg of dry matter (DM)] or to maintenance (MNE; 1...
December 7, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29223806/preventing-the-n-terminal-processing-of-human-interferon-%C3%AE-2b-and-its-chimeric-derivatives-expressed-in-escherichia-coli
#12
Fatima Ahsan, Qurratulann Afza Gardner, Naeem Rashid, Greg J Towers, Muhammad Akhtar
We have previously shown that human interferon α-2b (IFN) produced in Escherichia coli (E. coli) is heterogeneous at the N-terminal, with three major species (Ahsan et al., 2014). These are: (a) the direct translation product of the gene retaining the N-terminal methionine, (b) a species from which the methionyl residue has been removed by E. coli methionyl aminopeptidase to give the native interferon α-2b and (c) in which the N-terminal Cys residue of the latter contains an acetyl group. In this paper we overcome this heterogeneity, using engineered interferon derivatives with phenylalanine residue directly downstream of the N-terminal methionine (Met-Phe-IFN)...
November 23, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29222062/evolutionary-history-of-the-cobalamin-independent-methionine-synthase-gene-family-across-the-land-plants
#13
Hugo Vianna Silva Rody, Luiz Orlando de Oliveira
Plants are successful paleopolyploids. The wide diversity of land plants is driven strongly by their gene duplicates undergoing distinct evolutionary fates after duplication. We used genomic resources from 35 model plant species to unravel the evolutionary fate of gene copies (paralogs) of the cobalamin-independent methionine synthase (metE) gene family across the land plants. To explore genealogical relationships and characterize positive selection as a driving force in the evolution of metE paralogs within a single species, we carried out complementary analyses on genomic data of 32 genotypes of soybean...
December 6, 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/29221950/dha-supplementation-prevent-the-progression-of-nash-via-gpr120-signaling
#14
Kazuo Nakamoto, Koki Shimada, Shinichi Harada, Yasuko Morimoto, Akira Hirasawa, Shogo Tokuyama
Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases involving chronic accumulation of fat and inflammation, often leading to advanced fibrosis, cirrhosis and carcinoma. However, the pathological mechanism for this is unknown. GPR120/FFAR4 has been recognized as a functional fatty acid receptor and an attractive therapeutic target for metabolic diseases. In this study, we investigated the involvement of GPR120/FFAR4 in the pathogenesis of NASH. Mice fed with a 0.1% methionine and choline deficient high-fat (CDAHF) diet showed a significant increase in plasma aspartate transaminase and alanine transaminase levels, fatty deposition, inflammatory cell infiltration, and mild fibrosis...
December 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29220721/novel-effect-of-methionine-enkephalin-against-influenza-a-virus-infection-through-inhibiting-tlr7-myd88-traf6-nf-%C3%AE%C2%BAb-p65-signaling-pathway
#15
Jing Tian, Xue Jiao, Xiaonan Wang, Jin Geng, Reizhe Wang, Ning Liu, Xinhua Gao, Noreen Griffin, Fengping Shan
The morbidity and mortality associated with influenza A virus infections, have stimulated the search for novel prophylactic and therapeutic drugs. The purpose of this study was to investigate the prophylactic and therapeutic effect of synthetic methionine enkephalin (MENK) on mice infected by A/PR/8/34 influenza virus (H1N1) in vivo. The results showed that MENK could exert both prophylactic and therapeutic influences on infected mice, significantly improve the survival rate, relieve acute lung injury and decrease cytokine (IFN-α, IFN-β, TNF-α, IL-6, and IL-1β) levels...
December 5, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29219315/calculation-of-standard-reduction-potentials-of-amino-acid-radicals-and-the-effects-of-water-and-incorporation-into-peptides
#16
David M Close, Peter Wardman
Guanine (Guo) is generally accepted as the most easily-oxidized DNA base when cells are subjected to ionizing radiation; calculations of the standard reduction potential of the guanyl radical, Eo(Guo•+/Guo) are within ~ 0.1 V of experimental values in aqueous solution extrapolated to standard conditions. While a number of experimental studies have shown some amino acid radicals have redox properties at pH 7 which suggest or confirm a capacity for radical 'repair' by electron transfer from the amino acid to Guo•+ (or its deprotonated conjugate), the redox properties of the radicals of other amino acids, including methionine, lysine and cystine, are less well characterized...
December 8, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/29218642/porphyrin-polymer-nanocompartments-singlet-oxygen-generation-and-antimicrobial-activity
#17
Angelo Lanzilotto, Myrto Kyropoulou, Edwin C Constable, Catherine E Housecroft, Wolfgang P Meier, Cornelia G Palivan
A new water-soluble photocatalyst for singlet oxygen generation is presented. Its absorption extends to the red part of the spectrum, showing activity up to irradiation at 660 nm. Its efficiency has been compared to that of a commercial analogue (Rose Bengal) for the oxidation of L-methionine. The quantitative and selective oxidation was promising enough to encapsulate the photocatalyst in polymersomes. The singlet oxygen generated in this way can diffuse and remain active for the oxidation of L-methionine outside the polymeric compartment...
December 7, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/29217198/clinical-molecular-and-computational-analysis-in-two-cases-with-mitochondrial-encephalomyopathy-associated-with-suclg1-mutation-in-a-consanguineous-family
#18
Marwa Maalej, Amel Tej, Jihène Bouguila, Samia Tilouche, Senda Majdoub, Boudour Khabou, Mouna Tabbebi, Rahma Felhi, Marwa Ammar, Emna Mkaouar-Rebai, Leila Keskes, Lamia Boughamoura, Faiza Fakhfakh
Deficiency of the mitochondrial enzyme succinyl COA ligase (SUCL) is associated with encephalomyopathic mtDNA depletion syndrome and methylmalonic aciduria. This disorder is caused by mutations in both SUCL subunits genes: SUCLG1 (α subnit) and SUCLA2 (β subnit). We report here, two Tunisian patients belonging to a consanguineous family with mitochondrial encephalomyopathy, hearing loss, lactic acidosis, hypotonia, psychomotor retardation and methylmalonic aciduria. Mutational analysis of SUCLG1 gene showed, for the first time, the presence of c...
December 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29214510/myeloid-deficiency-of-ccn3-exacerbates-liver-injury-in-a-mouse-model-of-nonalcoholic-fatty-liver-disease
#19
Wenconghui Wu, Xingjian Hu, Xianming Zhou, Philip A Klenotic, Qi Zhou, Zhiyong Lin
Non-alcoholic fatty liver disease (NAFLD) is a condition in which fat accumulates in the liver of patients without a prior history of alcohol abuse. The most severe form, nonalcoholic steatohepatitis (NASH), often leads to hepatic fibrosis and cirrhosis with ensuing complications. To date, there is no pharmacologic treatment for NASH. The biological effects of CCN3, specifically its role in the regulation of inflammation, reactive oxygen species production and angiogenesis, have been recently established. Additional data suggests that CCN3 is associated with the development of tumors in the liver yet may be protective of liver fibrogenesis...
December 6, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29212039/comprehensive-mapping-of-pluripotent-stem-cell-metabolism-using-dynamic-genome-scale-network-modeling
#20
Sriram Chandrasekaran, Jin Zhang, Zhen Sun, Li Zhang, Christian A Ross, Yu-Chung Huang, John M Asara, Hu Li, George Q Daley, James J Collins
Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and self-renewal, yet systems-level understanding of stem cell metabolism has been limited by the lack of genome-scale network models. Here, we develop a systems approach to integrate time-course metabolomics data with a computational model of metabolism to analyze the metabolic state of naive and primed murine pluripotent stem cells. Using this approach, we find that one-carbon metabolism involving phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a key pathway that differs between the two states, resulting in differential sensitivity to anti-folates...
December 5, 2017: Cell Reports
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