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https://www.readbyqxmd.com/read/28580921/crystal-structure-of-the-active-form-of-native-human-thymidylate-synthase-in-the-absence-of-bound-substrates
#1
P Deschamps, S Réty, J Bareille, N Leulliot
Human thymidylate synthase (hTS) provides the sole de novo intracellular source of thymidine 5'-monophosphate (dTMP). hTS is required for DNA replication prior to cell division, making it an attractive target for anticancer chemotherapy and drug discovery. hTS binds 2'-deoxyuridine 5'-monophosphate (dUMP) and the folate co-substrate N(5),N(10)-methylenetetrahydrofolate (meTHF) in a pocket near the catalytic residue Cys195. The catalytic loop, which is composed of amino-acid residues 181-197, can adopt two distinct conformations related by a 180° rotation...
June 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28566636/inhibition-of-methotrexate-uptake-via-organic-anion-transporters-oat1-and-oat3-by-glucuronides-of-nonsteroidal-anti-inflammatory-drugs
#2
Masahiro Iwaki, Hiroaki Shimada, Yuri Irino, Manami Take, Sachiko Egashira
Combination therapy of non-steroidal anti-inflammatory drugs (NSAIDs) and methotrexate (MTX) sometimes triggers adverse effects, such as liver injury, renal failure, gastrointestinal disorders, and myelosuppression, owing to the reduction of MTX clearance. Previous reports have suggested that NSAIDs inhibit renal MTX uptake via organic anion transporters (OATs) and reduced folate transporter (RFC)-1 and efflux via multidrug resistance-associated proteins (MRPs). Recently, our laboratory found inhibitory effects of NSAIDs-glucuronide (NSAIDs-Glu), a major metabolite of NSAIDs, on MRP-mediated MTX transport as a new site of interaction between MTX and NSAIDs...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28518056/functionally-diverse-human-t-cells-recognize-non-microbial-antigens-presented-by-mr1
#3
Marco Lepore, Artem Kalinichenko, Salvatore Calogero, Pavanish Kumar, Bhairav Paleja, Mathias Schmaler, Vipin Narang, Francesca Zolezzi, Michael Poidinger, Lucia Mori, Gennaro De Libero
MHC class I-related molecule MR1 presents riboflavin- and folate-related metabolites to mucosal-associated invariant T cells, but it is unknown whether MR1 can present alternative antigens to other T cell lineages. In healthy individuals we identified MR1-restricted T cells (named MR1T cells) displaying diverse TCRs and reacting to MR1-expressing cells in the absence of microbial ligands. Analysis of MR1T cell clones revealed specificity for distinct cell-derived antigens and alternative transcriptional strategies for metabolic programming, cell cycle control and functional polarization following antigen stimulation...
May 18, 2017: ELife
https://www.readbyqxmd.com/read/28515336/the-effects-of-micronutrient-deficiencies-on-bacterial-species-from-the-human-gut-microbiota
#4
Matthew C Hibberd, Meng Wu, Dmitry A Rodionov, Xiaoqing Li, Jiye Cheng, Nicholas W Griffin, Michael J Barratt, Richard J Giannone, Robert L Hettich, Andrei L Osterman, Jeffrey I Gordon
Vitamin and mineral (micronutrient) deficiencies afflict 2 billion people. Although the impact of these imbalances on host biology has been studied extensively, much less is known about their effects on the gut microbiota of developing or adult humans. Therefore, we established a community of cultured, sequenced human gut-derived bacterial species in gnotobiotic mice and fed the animals a defined micronutrient-sufficient diet, followed by a derivative diet devoid of vitamin A, folate, iron, or zinc, followed by return to the sufficient diet...
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28444786/targeted-photodynamic-therapy-with-a-folate-sensitizer-assembly-produced-from-mesoporous-silica
#5
Chunfang Zhou, Damien Afonso, Sabrina Valetti, Adam Feiler, Venera Cardile, Adriana C E Graziano, Sabrina Conoci, Salvatore Sortino
A mesoporous silica material prepared by using folic acid (FA) as a template enables the effective encapsulation of meso-tetrakis(4-carboxyphenyl)porphyrin (TCPP) in its interior. Combination of steady-state and time-resolved absorption and emission spectroscopy demonstrate that FA and TCPP are released from the silica material to the aqueous phase in the form of a non-covalent assembly. This assembly does not form by simple mixing of the two components in the absence of silica, suggesting the key role of the material in the assembling process...
April 26, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28443623/novel-slc25a32-mutation-in-a-patient-with-a-severe-neuromuscular-phenotype
#6
Debby M E I Hellebrekers, Suzanne C E H Sallevelt, Tom E J Theunissen, Alexandra T M Hendrickx, Ralph W Gottschalk, Janneke G J Hoeijmakers, Daphna D Habets, Jörgen Bierau, Kees G Schoonderwoerd, Hubert J M Smeets
In a 51-year-old patient of consanguineous parents with a severe neuromuscular phenotype of early-onset ataxia, myoclonia, dysarthria, muscle weakness and exercise intolerance, exome sequencing revealed a novel homozygous variant (c.-264_31delinsCTCACAAATGCTCA) in the mitochondrial FAD-transporter gene SLC25A32. Flavin adenine dinucleotide (FAD) is an essential co-factor for many mitochondrial enzymes and impaired mitochondrial FAD-transport was supported by a reduced oxidative phosphorylation complex II activity in the patient's muscle, decreased ATP production in fibroblasts, and a deficiency of mitochondrial FAD-dependent enzymes...
June 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28397463/colorectal-cancer-carcinogenesis-a-multivariate-genetic-model-in-a-cohort-of-romanian-population
#7
Lucia M Procopciuc, Gelu Osian, Mihaela Iancu
BACKGROUND: The molecular mechanism of carcinogenesis of sporadic colorectal cancer (CRC) involves genes with roles in folate metabolism, genes involved in metabolization of carcinogenic compounds from diet and tobacco smoke, and genes related to the DNA repair process. The aim of the study was to examine whether the MTHFRC677T, MTHFR- A1298C, TS-2rpt/3rpt, TS-1494del6bp, NAT2*5C-C481T, NAT2*5A-T341C, NAT2*6B-G590A, NAT2*7B-G857A, NAT2*18-A845C, GSTM1-null, XRCC1-Arg399Gln, XRCC3-Thr241Met, XPD-Lys751Gln genetic variations are associated with CRC prognosis, in the presence of environmental and demographic factors...
April 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28369746/safety-and-benefits-of-interventions-to-increase-folate-status-in-malaria-endemic-areas
#8
REVIEW
Hans Verhoef, Jacobien Veenemans, Martin N Mwangi, Andrew M Prentice
For decades, folic acid has routinely been given to prevent or treat anaemia in children, pregnant women and people with sickle cell disease. However, there is no conclusive evidence that folate deficiency anaemia constitutes a public health problem in any of these groups. Industrial flour fortification is recommended and implemented in many countries to combat neural tube defects. Dietary folates or folic acid can antagonise the action of antifolate drugs that play a critical role in the prevention and treatment of malaria...
June 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28241813/anaemia-in-hospitalised-preschool-children-from-a-rural-area-in-mozambique-a-case-control-study-in-search-for-aetiological-agents
#9
Cinta Moraleda, Ruth Aguilar, Llorenç Quintó, Tacilta Nhampossa, Montserrat Renom, Augusto Nhabomba, Sozinho Acácio, John J Aponte, Delino Nhalungo, Ariel H Achtman, Louis Schofield, Helder Martins, Eusebio Macete, Pedro L Alonso, Clara Menéndez
BACKGROUND: Young children bear the world's highest prevalence of anaemia, the majority of which is of multifactorial aetiology, which in turn hampers its successful prevention. Even moderate degrees of anaemia are associated with increased mortality and morbidity. Despite this evidence, there is a lack of effective preventive programs and absence of consensus in the safety of iron supplementation in malaria areas, which reflects the poor understanding of the contribution of different aetiologies to anaemia...
February 28, 2017: BMC Pediatrics
https://www.readbyqxmd.com/read/28178022/the-impact-of-essential-fatty-acid-b-vitamins-vitamin-c-magnesium-and-zinc-supplementation-on-stress-levels-in-women-a-systematic-review
#10
Delia McCabe, Karolina Lisy, Craig Lockwood, Marc Colbeck
BACKGROUND: Women juggling multiple roles in our complex society are increasingly experiencing psychological stress. Dietary supplementation to manage stress is widespread despite limited supporting evidence. A systematic review of the available literature was undertaken to investigate the efficacy of specific dietary supplements in managing female stress and anxiety. OBJECTIVES: To identify the impact of essential fatty acids (EFAs), B vitamins, vitamin C, magnesium and/or zinc, consumed as dietary supplements to the daily diet, on female stress and anxiety levels...
February 2017: JBI Database of Systematic Reviews and Implementation Reports
https://www.readbyqxmd.com/read/28122733/impact-of-posttranslational-modifications-of-engineered-cysteines-on-the-substituted-cysteine-accessibility-method-evidence-for-glutathionylation
#11
Rongbao Zhao, Mitra Najmi, Srinivas Aluri, I David Goldman
The substituted cysteine accessibility method (SCAM) is widely used to study the structure and function of channels, receptors and transporters. In its usual application, a cysteine residue is introduced into a protein which lacks native cysteines following which the accessibility of the residue to the aqueous compartment is assessed. Implicit, and generally assumed, is that if the cysteine-substituted residue is not available to react with sulfhydryl reagents it is not exposed to the extracellular compartment or within the aqueous translocation pathway...
April 1, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28017143/a-hr-ms-based-method-for-the-determination-of-chorismate-synthase-activity
#12
Harvinder Kour Khera, Susheel Kumar Singh, Rafia Mir, Vikram Bhardwaj, Subhash Singh
Chorismate synthase (Cs) catalyzes the last step of Shikimate pathway involving a unique biochemical reaction of anti-1,4 elimination of 3-phosphate group and the C-(6proR) hydrogen from 5-enolpyruvylshikimate-3-phosphate (EPSP) leading to the formation of chorismate, which is the common precursor for aromatic amino acid, ubiquinone, and folate biosynthesis in plants and several bacterial, fungal, and parasitic pathogens. Absence of Shikimate pathway in the vertebrate host, make Cs an appealing target for drug discovery against these pathogens...
December 22, 2016: Protein and Peptide Letters
https://www.readbyqxmd.com/read/27942180/imerslund-grasbeck-syndrome-in-a-5-year-old-iranian-boy
#13
K Goudarzipour, N Zavvar, B Behnam, M A Ahmadi
Imerslund-Grasbeck syndrome (IGS) is a rare syndrome characterized by clinical symptoms and signs of Vitamin B12 deficiency and proteinuria. Our patient was a 5-year-old boy with pallor, lack of appetite, and low weight gain. Laboratory studies showed severe macrocytic anemia, normal reticulocyte count, negative direct coombs test, normal osmotic fragility, and autohemolysis test. He has had intermittent proteinuria since 3 years ago despite normal creatinine level and absence of hematuria or hypertension. Finally, based on low level of serum B12 vitamin and normal folate level accompanied by asymptomatic proteinuria, the diagnosis of IGS was made...
November 2016: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/27902365/oral-cavities-of-healthy-infants-harbour-high-proportions-of-streptococcus-salivarius-strains-with-phenotypic-and-genotypic-resistance-to-multiple-classes-of-antibiotics
#14
Thaís H Palma, Erika N Harth-Chú, Jodie Scott, Rafael N Stipp, Heike Boisvert, Mariana F Salomão, Jéssica D Theobaldo, Rosana F Possobon, Leandro C Nascimento, Jonathan W McCafferty, Lina Faller, Margaret J Duncan, Renata O Mattos-Graner
Emerging antibiotic resistance in the oropharyngeal microbiota, of which Streptococcus salivarius is a prominent species, represents a challenge for treating paediatric populations. In this study, we investigated the role of Streptococcussalivarius as a reservoir for antibiotic resistance genes (ARG) in the oral microbiota by analysing 95 Streptococcussalivarius isolates from 22 healthy infants (2-16 months of age). MICs of penicillin G, amoxicillin, erythromycin, tetracycline, doxycycline and streptomycin were determined...
December 2016: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27747873/antioxidants-from-black-and-green-tea-from-dietary-modulation-of-oxidative-stress-to-pharmacological-mechanisms
#15
REVIEW
Ilaria Peluso, Mauro Serafini
The consumption of tea (Camellia sinensis) has been correlated with a low incidence of chronic pathologies, such as cardiovascular disease and cancer, in which oxidative stress plays a critical role. Tea catechins and theaflavins are, respectively, the bioactive phytochemicals responsible for the antioxidant activity of green tea (GT) and black tea (BT). In addition to their redox properties, tea catechins and theaflavins could have also pharmacological activities, such as the ability to lower glucose, lipid and uric acid (UA) levels...
June 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27699007/effects-of-antiepileptic-drugs-on-the-serum-folate-and-vitamin-b12-in-various-epileptic-patients
#16
Hong-Li Huang, Hao Zhou, Nuan Wang, Chun-Yu Yu
Epilepsy is a common neurodegenerative disease with an increasing morbidity. Clinical treatment of epilepsy includes symptomatic treatment, etiological treatment, surgery and prevention. The aim of the present study was to determine the effects of antiepileptic drugs (AEDs) on serum folate and vitamin B12 in various epileptic patients, and to examine the correlation between these effects and secondary cerebrovascular events. A total of 68 epileptic patients, diagnosed between May 2012 and May 2014, were included in the present study...
October 2016: Biomedical Reports
https://www.readbyqxmd.com/read/27695536/high-incidence-of-neural-tube-defects-in-northern-part-of-india
#17
Sunil Kumar Rai, Royana Singh, Sharad Pandey, Kulwant Singh, Neeraj Shinde, Sangita Rai, Rajniti Prasad, Satya Narayan Shama
BACKGROUND: In the absence of primary care and prevailing associated social stigma, many patients of neural tube defects (NTDs) from remote areas die without getting any treatment. The high number of such untreated cases and unregistered deaths in these areas made us ponders to the fact that tertiary care center-based studies do not represent the true incidence of NTDs. MATERIALS AND METHODS: We did a population-based survey for NTDs births of rural areas from Jaunpur to Ghazipur district in Eastern Uttar Pradesh...
October 2016: Asian Journal of Neurosurgery
https://www.readbyqxmd.com/read/27442079/immobilization-free-electrochemical-biosensor-for-folate-receptor-in-cancer-cells-based-on-terminal-protection
#18
Jiancong Ni, Qingxiang Wang, Weiqiang Yang, Mengmeng Zhao, Ying Zhang, Longhua Guo, Bin Qiu, Zhenyu Lin, Huang-Hao Yang
The determination of folate receptor (FR) that over expressed in vast quantity of cancerous cells frequently is significant for the clinical diagnosis and treatment of cancers. Many DNA-based electrochemical biosensors have been developed for FR detection with high selectivity and sensitivity, but most of them need complicated immobilization of DNA on the electrode surface firstly, which is tedious and therefore results in the poor reproducibility. In this study, a simple, sensitive, and selective electrochemical FR biosensor in cancer cells has been proposed, which combines the advantages of the convenient immobilization-free homogeneous indium tin oxide (ITO)-based electrochemical detection strategy and the high selectivity of the terminal protection of small molecule linked DNA...
December 15, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27431289/elevated-homocysteine-with-pseudo-homozygosity-for-mthfr677t-as-predisposing-factors-for-transient-ischemic-attacks-a-case-report
#19
A Sobczyńska-Malefora, J Cutler, Y Rahman
A 21 year old male presented with a history of intermittent, transient neurological events. A brain MRI showed an area of restricted diffusion in keeping with an infarct, and an angiogram demonstrated an intracranial stenosis in the internal carotid artery, consistent with atherosclerosis. Laboratory investigations revealed a highly elevated plasma homocysteine, with low plasma folate and 5-methyltetrahydrofolate and methionine at the lower end of the normal ranges. The homocysteine normalized following treatment with folic acid...
October 2016: Metabolic Brain Disease
https://www.readbyqxmd.com/read/27423480/pterin-sulfa-conjugates-as-dihydropteroate-synthase-inhibitors-and-antibacterial-agents
#20
Ying Zhao, William R Shadrick, Miranda J Wallace, Yinan Wu, Elizabeth C Griffith, Jianjun Qi, Mi-Kyung Yun, Stephen W White, Richard E Lee
The sulfonamide class of antibiotics has been in continuous use for over 70years. They are thought to act by directly inhibiting dihydropteroate synthase (DHPS), and also acting as prodrugs that sequester pterin pools by forming dead end pterin-sulfonamide conjugates. In this study, eight pterin-sulfonamide conjugates were synthesized using a novel synthetic strategy and their biochemical and microbiological properties were investigated. The conjugates were shown to competitively inhibit DHPS, and inhibition was enhanced by the presence of pyrophosphate that is crucial to catalysis and is known to promote an ordering of the DHPS active site...
August 15, 2016: Bioorganic & Medicinal Chemistry Letters
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