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Amino Acid Therapy

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https://www.readbyqxmd.com/read/28105853/identification-of-potential-molecular-associations-between-chikungunya-virus-non-structural-protein-2-and-human-host-proteins
#1
J Rana, S Gulati, S Rajasekharan, A Gupta, V Chaudhary, S Gupta
Chikungunya virus (CHIKV) non-structural protein 2 (nsP2) is considered to be the master regulator of viral RNA replication and host responses generated during viral infection. This protein has two main functional domains: an N-terminal domain which exhibits NTPase, RNA triphosphatase and helicase activities and a C-terminal protease domain. Understanding how CHIKV nsP2 interacts with its host proteins is essential for elucidating all the required processes for viral replication and pathogenesis along with the identification of potential targets for antiviral therapy...
January 19, 2017: Acta Virologica
https://www.readbyqxmd.com/read/28104899/amino-acid-based-material-for-the-complementary-therapy-of-decubitus-ulcers
#2
Frederico Nogueira, Isabel C Gouveia
Chronic wounds, pressure sores, lesions and infections of microbial origin in bedridden, paralyzed or malnutrition patients remain the object of study of many researchers. There are several intrinsic and extrinsic factors involved in the development of these disorders, which are related to the patient's immune system, making it unable to respond effectively to the treatment of the wound. These factors can be properly controlled, giving particular importance to the ethiology and stage of the wound, as well as the time periods corresponding to the replacement of the dressings...
January 20, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28102733/plk1-polo-like-kinase-1-inhibits-mtor-complex-1-and-promotes-autophagy
#3
Stefanie Ruf, Alexander Martin Heberle, Miriam Langelaar-Makkinje, Sara Gelino, Deepti Wilkinson, Carolin Gerbeth, Jennifer Jasmin Schwarz, Birgit Holzwarth, Bettina Warscheid, Chris Meisinger, Marcel A T M van Vugt, Ralf Baumeister, Malene Hansen, Kathrin Thedieck
Mechanistic target of rapamycin complex 1 (MTORC1) and PLK1 (polo like kinase 1) are major drivers of cancer cell growth and proliferation, and inhibitors of both protein kinases are currently being investigated in clinical studies. To date, MTORC1's and PLK1's functions are mostly studied separately, and reports on their mutual crosstalk are scarce. Here, we identify PLK1 as a physical MTORC1 interactor in human cancer cells. PLK1 inhibition enhances MTORC1 activity under nutrient sufficiency and in starved cells, and PLK1 directly phosphorylates the MTORC1 component RPTOR/RAPTOR in vitro...
January 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28100850/molecular-characteristic-and-physiological-role-of-dopa-decarboxylase
#4
Joanna Guenter, Robert Lenartowski
The enzyme DOPA decarboxylase (aromatic-L-amino-acid decarboxylase, DDC) plays an important role in the dopaminergic system and participates in the uptake and decarboxylation of amine precursors in the peripheral tissues. Apart from catecholamines, DDC catalyses the biosynthesis of serotonin and trace amines. It has been shown that the DDC amino acid sequence is highly evolutionarily conserved across many species. The activity of holoenzyme is regulated by stimulation/blockade of membrane receptors, phosphorylation of serine residues, and DDC interaction with regulatory proteins...
December 31, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28099989/effects-of-a-dietary-ketone-ester-on-hippocampal-glycolytic-and-tca-cycle-intermediates-and-amino-acids-in-a-3xtgad-mouse-model-of-alzheimer-s-disease
#5
Robert J Pawlosky, Martin F Kemper, Yoshihero Kashiwaya, M Todd King, Mark P Mattson, Richard L Veech
In patients with Alzheimer's disease (AD) and in a triple transgenic (3xTgAD) mouse model of AD low glucose metabolism in the brain precedes loss of memory and cognitive decline. The metabolism of ketones in the brain by-passes glycolysis and therefore may correct several deficiencies that are associated with glucose hypometabolism. A dietary supplement composed of an ester of D-β-hydroxybutyrate and R-1,3 butane diol referred to as ketone ester (KE) was incorporated into a rodent diet and fed to 3xTgAD mice for 8 months...
January 18, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28099515/polymorphisms-and-mutational-covariation-associated-with-death-in-a-prospective-cohort-of-hiv-aids-patients-receiving-long-term-art-in-china
#6
Pengtao Liu, Yi Feng, Jianjun Wu, Suian Tian, Bin Su, Zhe Wang, Lingjie Liao, Hui Xing, Yinghui You, Yiming Shao, Yuhua Ruan
BACKGROUND: HIV drug resistance is associated with faster clinical progression of AIDS. However, the effect of significant polymorphisms and mutational covariation on mortality among HIV/AIDS patients receiving long-term antiretroviral therapy (ART), have rarely been studied. METHODS: In this prospective cohort study from December 2003 to December 2014, we present a new computational modelling approach based on bioinformatics-based models and several statistical methods to elucidate the molecular mechanisms involved in the acquisition of polymorphisms and mutations on death in HIV/AIDS patients receiving long-term ART in China...
2017: PloS One
https://www.readbyqxmd.com/read/28096461/differential-contribution-of-transmembrane-domains-iv-v-vi-and-vii-to-human-angiotensin-ii-type-1-receptor-homomer-formation
#7
Brent M Young, Elaine Nguyen, Matthew A J Chedrawe, Jan K Rainey, Denis J Dupré
G protein-coupled receptors (GPCRs) play an important role in drug therapy, and represent one of the largest families of drug targets. The angiotensin II type 1 receptor (AT1R) is notable as it has a central role in the treatment of cardiovascular disease. Blockade of AT1R signaling has been shown to alleviate hypertension and improve outcomes in patients with heart failure. Despite this, it has become apparent that our initial understanding of AT1R signaling is over-simplified. There is considerable evidence to suggest that AT1R signaling is highly modified in the presence of receptor-receptor interactions, but there is very little structural data available to explain this phenomenon even with the recent elucidation of the AT1R crystal structure...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28089773/mitochondrial-diseases-yeast-as-a-model-for-the-study-of-suppressors
#8
Silvia Francisci, Arianna Montanari
Mitochondrial (mt) tRNA gene mutations are an important cause of human morbidity and are associated with different syndromes. We have previously shown that the mitochondrial protein synthesis elongation factor EF-Tu and isolated sequences from the carboxy-terminal domain of yeast and human mt leucyl-tRNA synthetases (LeuRS), have a wide range of suppression capability among different yeast mt tRNA mutants having defective respiratory phenotype. Here we show that the rescuing capability can be restricted to a specific sequence of six amino acids from the carboxy-terminal domain of mt LeuRS...
January 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28089735/effects-of-simvastatin-on-cat-1-mediated-arginine-transport-and-no-level-under-high-glucose-conditions-in-conditionally-immortalized-rat-inner-blood-retinal-barrier-cell-lines-tr-ibrb
#9
Temdara Tun, Young-Sook Kang
OBJECTIVE: Hyperglycemia causes the breakdown of the blood-retinal barrier by impairing endothelial nitric oxide synthase (eNOS) function. Statins have many pleiotropic effects such as improving endothelial barrier permeability and increasing eNOS mRNA stability. The objective of this study was to determine effect of simvastatin on l-arginine transport and NO production under high-glucose conditions in conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB). METHODS: Changes in l-arginine transport uptake and, expression levels of cationic amino acid transporter 1 (CAT-1) and eNOS mRNA were investigated after pre-treatment with simvastatin and NOS inhibitors (l-NMMA and l-NAME) under high-glucose conditions using TR-iBRB, an in vitro model of iBRB...
January 12, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28088904/fc-fusion-proteins-in-therapy-an-updated-view
#10
Reza Jafari, Naime Majidi Zolbanin, Houshang Rafatpanah, Jafar Majidi, Tohid Kazemi
Fc-fusion proteins are composed of Fc region of IgG antibody (Hinge-CH2-CH3) and a desired linked protein. Fc region of Fc-fusion proteins can bind to neonatal Fc receptor (FcRn) thereby rescuing it from degradation. The first therapeutic Fc-fusion protein was introduced for treatment of AIDS. The molecular designing is the first stage in production of Fc-fusion proteins. The amino acid residues in the Fc region and linked protein are very important in the bioactivity and affinity of the fusion proteins. Although, therapeutic monoclonal antibodies are the top selling biologics but the application of therapeutic Fc-fusion proteins in clinic is in progress and among of these medications Etanercept is the most effective in therapy...
January 13, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28088504/novel-insights-into-the-transport-mechanism-of-the-human-amino-acid-transporter-lat1-slc7a5-probing-critical-residues-for-substrate-translocation
#11
Lara Napolitano, Michele Galluccio, Mariafrancesca Scalise, Chiara Parravicini, Luca Palazzolo, Ivano Eberini, Cesare Indiveri
BACKGROUND: LAT1 (SLC7A5) is the transport competent unit of the heterodimer formed with the glycoprotein CD98 (SLC3A2). It catalyzes antiport of His and some neutral amino acids such as Ile, Leu, Val, Cys, Met, Gln and Phe thus being involved in amino acid metabolism. Interestingly, LAT1 is over-expressed in many human cancers that are characterized by increased demand of amino acids. Therefore LAT1 was recently acknowledged as a novel target for cancer therapy. However, knowledge on molecular mechanism of LAT1 transport is still scarce...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28087643/tumor-brca1-reversion-mutation-arising-during-neoadjuvant-platinum-based-chemotherapy-in-triple-negative-breast-cancer-is-associated-with-therapy-resistance
#12
Anosheh Afghahi, Kirsten M Timms, Shaveta Vinayak, Kristin C Jensen, Allison W Kurian, Robert W Carlson, Pei-Jen Chang, Elizabeth A Schackmann, Anne-Renee Hartman, James M Ford, Melinda L Telli
BACKGROUND: In germline BRCA1 or BRCA2 (BRCA1/2) mutation carriers, restoration of tumor BRCA1/2 function by a secondary mutation is recognized as a mechanism of resistance to platinum and PARP inhibitors, primarily in ovarian cancer. We evaluated this mechanism of resistance in newly diagnosed BRCA1/2-mutant breast cancer patients with poor response to neoadjuvant platinum-based therapy. METHODS: PrECOG 0105 was a phase II neoadjuvant study of gemcitabine, carboplatin and iniparib in patients with stage I-IIIA triple-negative or BRCA1/2 mutation-associated breast cancer (n=80)...
January 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28087278/prolyl-trna-synthetase-inhibition-promotes-cell-death-in-sk-mel-2%C3%A2-cells-through-gcn2-atf4-pathway-activation
#13
Takeo Arita, Megumi Morimoto, Yukiko Yamamoto, Hitoshi Miyashita, Satoshi Kitazawa, Takaharu Hirayama, Sou Sakamoto, Kazumasa Miyamoto, Ryutaro Adachi, Misa Iwatani, Takahito Hara
Protein translation is highly activated in cancer tissues through oncogenic mutations and amplifications, and this can support survival and aberrant proliferation. Therefore, blocking translation could be a promising way to block cancer progression. The process of charging a cognate amino acid to tRNA, a crucial step in protein synthesis, is mediated by tRNA synthetases such as prolyl tRNA synthetase (PRS). Interestingly, unlike pan-translation inhibitors, we demonstrated that a novel small molecule PRS inhibitor (T-3861174) induced cell death in several tumor cell lines including SK-MEL-2 without complete suppression of translation...
January 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28073960/ligand-characterization-of-cyp4b1-isoforms-modified-for-high-level-expression-in-escherichia-coli-and-hepg2-cells
#14
Katharina Roellecke, Vera D Jäger, Veselin H Gyurov, John P Kowalski, Stephanie Mielke, Allan E Rettie, Helmut Hanenberg, Constanze Wiek, Marco Girhard
Human CYP4B1, a cytochrome P450 monooxygenase predominantly expressed in the lung, inefficiently metabolizes classical CYP4B1 substrates, such as the naturally occurring furan pro-toxin 4-ipomeanol (4-IPO). Highly active animal forms of the enzyme convert 4-IPO to reactive alkylating metabolite(s) that bind(s) to cellular macromolecules. By substitution of 13 amino acids, we restored the enzymatic activity of human CYP4B1 toward 4-IPO and this modified cDNA is potentially valuable as a suicide gene for adoptive T-cell therapies...
January 10, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28070986/predicting-severity-of-disease-causing-variants
#15
Abhishek Niroula, Mauno Vihinen
Most diseases, including those of genetic origin, express a continuum of severity. Clinical interventions for numerous diseases are based on the severity of the phenotype. Predicting severity due to genetic variants could facilitate diagnosis and choice of therapy. Although computational predictions have been used as evidence for classifying the disease-relevance of genetic variants, special tools for predicting disease severity in large scale are missing. Here, we manually curated a dataset containing variants leading to severe and less severe phenotypes and studied the abilities of variation impact predictors to distinguish between them...
January 9, 2017: Human Mutation
https://www.readbyqxmd.com/read/28070831/the-prolyl-oligopeptidase-inhibitor-suam-14746-attenuates-the-proliferation-of-human-breast-cancer-cell-lines-in-vitro
#16
Satoshi Tanaka, Kanayo Suzuki, Minoru Sakaguchi
BACKGROUND: Prolyl oligopeptidase (POP, EC 3.4.1.26) is a serine peptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We previously reported that POP inhibition suppressed the growth of NB-1 human neuroblastomas cells and KATO III human gastric cancer cells. POP activity is commonly elevated in many cancers, which includes breast cancer. However, the effect of POP inhibition as a candidate breast cancer therapy is unknown. METHODS: The effects of POP inhibition and knockdown on the proliferation of cultured human estrogen receptor-positive (ER+) MCF7 and T47D, and ER-negative (ER-) MDA-MB-231 breast cancer cell lines and the MCF12A non-tumorigenic epithelial cell line were tested by analyzing their influence on cell proliferation (WST-1 assay), cell viability (trypan blue exclusion assay), and cell cycle arrest (cell cycle analysis, cell cycle regulator proteins expression)...
January 9, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28069647/ribosomal-mutations-conferring-macrolide-resistance-in-legionella-pneumophila
#17
Ghislaine Descours, Christophe Ginevra, Nathalie Jacotin, Françoise Forey, Joëlle Chastang, Elisabeth Kay, Jerome Etienne, Gérard Lina, Patricia Doublet, Sophie Jarraud
OBJECTIVES: Monitoring the emergence of antibiotic resistance is a recent issue in the treatment of Legionnaires' disease. Macrolides are recommended as first-line therapy but resistance mechanisms have not been studied in Legionella species. Our aim was to determine the molecular basis of macrolide resistance in L. pneumophila METHODS: Twelve independent lineages were propagated under erythromycin or azithromycin pressure towards a high-level macrolide resistance from a common susceptible L...
January 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28068987/effects-of-acetyl-dl-leucine-on-cerebellar-ataxia-alcat-trial-study-protocol-for-a-multicenter-multinational-randomized-double-blind-placebo-controlled-crossover-phase-iii-trial
#18
Katharina Feil, Christine Adrion, Julian Teufel, Sylvia Bösch, Jens Claassen, Ilaria Giordano, Holger Hengel, Heike Jacobi, Thomas Klockgether, Thomas Klopstock, Wolfgang Nachbauer, Ludger Schöls, Claudia Stendel, Ellen Uslar, Bart van de Warrenburg, Ingrid Berger, Ivonne Naumann, Otmar Bayer, Hans-Helge Müller, Ulrich Mansmann, Michael Strupp
BACKGROUND: Cerebellar ataxia (CA) is a frequent and often disabling condition that impairs motor functioning and impacts on quality of life (QoL). No medication has yet been proven effective for the symptomatic or even causative treatment of hereditary or non-hereditary, non-acquired CA. So far, the only treatment recommendation is physiotherapy. Therefore, new therapeutic options are needed. Based on three observational studies, the primary objective of the acetyl-DL-leucine on ataxia (ALCAT) trial is to examine the efficacy and tolerability of a symptomatic therapy with acetyl-DL-leucine compared to placebo on motor function measured by the Scale for the Assessment and Rating of Ataxia (SARA) in patients with CA...
January 10, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28067632/hcv-genotype-1-subtypes-and-resistance-associated-substitutions-in-drug-naive-and-in-direct-acting-antiviral-treatment-failure-patients
#19
Yael Gozlan, Ziv Ben-Ari, Roy Moscona, Rachel Shirazi, Avia Rakovsky, Arij Kabat, Ella Veizman, Tania Berdichevski, Peretz Weiss, Oranit Cohen-Ezra, Yoav Lurie, Inna Gafanovich, Marius Braun, Michal Cohen-Naftaly, Amir Shlomai, Oren Shibolet, Ehud Zigmond, Eli Zuckerman, Michal Carmiel-Haggai, Assy Nimer, Rawi Hazzan, Yaakov Maor, Yona Kitay-Cohen, Yonat Shemer, Zipi Kra-Oz, Lisita Schreiber, Ofer Peleg, Ella Mendelson, Orna Mor
BACKGROUND: Direct-acting antiviral (DAA) treatment regimens and response rates of patients with hepatitis C virus (HCV) genotype 1 (GT1) are currently considered subtype-dependent. Identification of clinically relevant resistance-associated substitutions (RASs) in the NS3 and NS5A proteins at baseline and in DAA failures, may also impact clinical decisions. METHODS: In a multicenter cohort study (n=308), NS3 or NS5B sequencing (n=248) was used to discriminate between GT1 subtypes...
January 9, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28064504/development-of-l-tyrosine-based-enzyme-responsive-amphiphilic-poly-ester-urethane-nanocarriers-for-multiple-drug-delivery-to-cancer-cells
#20
Rajendra Aluri, Manickam Jayakannan
New classes of enzymatic-biodegradable amphiphilic poly(ester-urethane)s were designed and developed from l-tyrosine amino acid resources and their self-assembled nanoparticles were employed as multiple drug delivery vehicles in cancer therapy. The amine and carboxylic acid functional groups in l-tyrosine were converted into dual functional ester-urethane monomers and they were subjected to solvent free melt polycondensation with hydrophilic polyethylene glycols to produce comb-type poly(ester-urethane)s. The phenolic unit in the l-tyrosine was anchored with hydrophobic alkyl side chain to bring appropriate amphiphilicity in the polymer geometry to self-assemble them as stable nanoscaffolds in aqueous medium...
January 9, 2017: Biomacromolecules
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