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https://www.readbyqxmd.com/read/28815411/synthesis-characterization-and-molecular-docking-studies-of-thiouracil-derivatives-as-potent-thymidylate-synthase-inhibitors-and-potential-anticancer-agents
#1
Abeer M El-Naggar, Mohsen M Abou-El-Regal, Souad A El-Metwally, Farag F Sherbiny, Ibrahim H Eissa
Thymidylate synthase (TS), one of folate-dependent enzymes, is a key and well-recognized target for anticancer agents. In this study, a series of 6-aryl-5-cyano thiouracil derivatives were designed and synthesized in accordance with essential pharmacophoric features of known TS inhibitors. Nineteen compounds were screened in vitro for their anti-proliferative activities toward HePG-2, MCF-7, HCT-116, and PC-3 cell lines. Compounds [Formula: see text], [Formula: see text], and 24 exhibited high anti-proliferative activity, comparable to that of 5-fluorouracil...
August 16, 2017: Molecular Diversity
https://www.readbyqxmd.com/read/28815233/the-protective-effect-of-acerola-malpighia-emarginata-against-oxidative-damage-in-human-dermal-fibroblasts-through-the-improvement-of-antioxidant-enzyme-activity-and-mitochondrial-functionality
#2
José M Alvarez-Suarez, Francesca Giampieri, Massimiliano Gasparrini, Luca Mazzoni, Celestino Santos-Buelga, Ana M González-Paramás, Tamara Y Forbes-Hernández, Sadia Afrin, Timothy Páez-Watson, José L Quiles, Maurizio Battino
Acerola fruits (Malpighia emarginata DC.) from the central region of Cuba were analyzed to determine their chemical composition and protective capacity against oxidative damage using an in vitro human dermal fibroblast (HDFa) model. The chemical composition analyses showed a high content of vitamin C, total polyphenols, β-carotene and folates in the acerola fruit. From the HPLC-DAD/ESI-MS(n) analyses, two anthocyanins (cyanidin 3-O-rhamnoside and pelargonidin 3-O-rhamnoside), three hydroxycinnamoyl derivatives (caffeoyl hexoside, dihydrocaffeoylquinic acid and coumaroyl hexoside) and fifteen flavonols (mostly glycosylated forms of quercetin and kaempferol) were detected...
August 17, 2017: Food & Function
https://www.readbyqxmd.com/read/28814982/cord-blood-dna-methylation-and-adiposity-measures-in-early-and-mid-childhood
#3
Jacob K Kresovich, Yinan Zheng, Andres Cardenas, Brian T Joyce, Sheryl L Rifas-Shiman, Emily Oken, Matthew W Gillman, Marie-France Hivert, Andrea A Baccarelli, Lifang Hou
BACKGROUND: Excess adiposity in childhood is associated with numerous adverse health outcomes. As this condition is difficult to treat once present, identification of risk early in life can help inform and implement strategies to prevent the onset of the condition. We performed an epigenome-wide association study to prospectively investigate the relationship between cord blood DNA methylation and adiposity measurements in childhood. METHODS: We measured genome-wide DNA methylation from 478 children in cord blood and measured overall and central adiposity via skinfold caliper measurements in early (range 3...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28814397/association-of-tcn2-rs1801198-c-776g-c-polymorphism-with-markers-of-one-carbon-metabolism-and-related-diseases-a-systematic-review-and-meta-analysis-of-genetic-association-studies
#4
Abderrahim Oussalah, Julien Levy, Pierre Filhine-Trésarrieu, Fares Namour, Jean-Louis Guéant
Background: Vitamin B-12 (cobalamin) deficiency may produce severe neurologic and hematologic manifestations. Approximately 20-25% of circulating cobalamin binds to transcobalamin 2 (TCN2), which is referred to as active vitamin B-12. The G allele of the TCN2 c.776G>C (rs1801198) polymorphism has been associated with a lower plasma concentration of holotranscobalamin. However, genotype association studies on rs1801198 have led to conflicting results regarding its influence on one-carbon metabolism (OCM) markers or its association with pathologic conditions...
August 16, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28814349/breakfast-consumption-and-nutrient-intakes-in-4-18-year-olds-uk-national-diet-and-nutrition-survey-rolling-programme-2008-2012
#5
Janine D Coulthard, Luigi Palla, Gerda K Pot
Although breakfast consumption is widely considered to be an important component of a healthy lifestyle, few UK studies have examined differences in nutrient intakes between breakfast consumers and breakfast skippers among children and adolescents. We investigated associations between breakfast skipping in 4-18-year-olds and their nutrient intakes using data from the UK's National Diet and Nutrition Survey Rolling Programme. Dietary data were derived from 4-d estimated food diaries of 802 children aged 4-10 years and 884 children aged 11-18 years (1686 in total)...
August 17, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28813411/mammals-divert-endogenous-genotoxic-formaldehyde-into-one-carbon-metabolism
#6
Guillermo Burgos-Barragan, Niek Wit, Johannes Meiser, Felix A Dingler, Matthias Pietzke, Lee Mulderrig, Lucas B Pontel, Ivan V Rosado, Thomas F Brewer, Rebecca L Cordell, Paul S Monks, Christopher J Chang, Alexei Vazquez, Ketan J Patel
The folate-driven one-carbon (1C) cycle is a fundamental metabolic hub in cells that enables the synthesis of nucleotides and amino acids and epigenetic modifications. This cycle might also release formaldehyde, a potent protein and DNA crosslinking agent that organisms produce in substantial quantities. Here we show that supplementation with tetrahydrofolate, the essential cofactor of this cycle, and other oxidation-prone folate derivatives kills human, mouse and chicken cells that cannot detoxify formaldehyde or that lack DNA crosslink repair...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28811683/methylenetetrahydrofolate-reductase-c677t-polymorphism-and-risk-for-male-infertility-in-asian-population
#7
Vandana Rai, Pradeep Kumar
Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of folate pathway and required for DNA synthesis and methylation. MTHFE C677T polymorphisms is reported as risk factors for various diseases and disorders like birth defects, metabolic, neurological, psychiatric disorders, and cancers. Several studies have investigated association between the MTHFR C677T polymorphism and male infertility. To assess the risk associated with MTHFR C677T polymorphism in Asian population, a meta-analysis was performed...
July 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28809784/folate-receptor-positive-gynecological-cancer-cells-in-vitro-and-in-vivo-characterization
#8
Klaudia Siwowska, Raffaella M Schmid, Susan Cohrs, Roger Schibli, Cristina Müller
The folate receptor (FR) is expressed in a variety of gynecological cancer types. It has been widely used for tumor targeting with folic acid conjugates of diagnostic and therapeutic probes. The cervical KB tumor cells have evolved as the standard model for preclinical investigations of folate-based (radio) conjugates. In this study, a panel of FR-expressing human cancer cell lines-including cervical (HeLa, KB, KB-V1), ovarian (IGROV-1, SKOV-3, SKOV-3.ip), choriocarcinoma (JAR, BeWo) and endometrial (EFE-184) tumor cells-was investigated in vitro and for their ability to grow as xenografts in mice...
August 15, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28809400/prenatal-one-carbon-metabolism-dysregulation-programs-schizophrenia-like-deficits
#9
A Alachkar, L Wang, R Yoshimura, A R Hamzeh, Z Wang, N Sanathara, S M Lee, X Xu, G W Abbott, O Civelli
The methionine-folate cycle-dependent one-carbon metabolism is implicated in the pathophysiology of schizophrenia. Since schizophrenia is a developmental disorder, we examined the effects that perturbation of the one-carbon metabolism during gestation has on mice progeny. Pregnant mice were administered methionine equivalent to double their daily intake during the last week of gestation. Their progeny (MET mice) exhibited schizophrenia-like social deficits, cognitive impairments and elevated stereotypy, decreased neurogenesis and synaptic plasticity, and abnormally reduced local excitatory synaptic connections in CA1 neurons...
August 15, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28807232/ovarian-cancer-novel-molecular-aspects-for-clinical-assessment
#10
REVIEW
Raffaele Palmirotta, Erica Silvestris, Stella D'Oronzo, Angela Cardascia, Franco Silvestris
Ovarian cancer is a very heterogeneous tumor which has been traditionally characterized according to the different histological subtypes and differentiation degree. In recent years, innovative molecular screening biotechnologies have allowed to identify further subtypes of this cancer based on gene expression profiles, mutational features, and epigenetic factors. These novel classification systems emphasizing the molecular signatures within the broad spectrum of ovarian cancer have not only allowed a more precise prognostic prediction, but also proper therapeutic strategies for specific subgroups of patients...
September 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28805741/alcohol-and-cancer-mechanisms-and-therapies
#11
REVIEW
Anuradha Ratna, Pranoti Mandrekar
Several scientific and clinical studies have shown an association between chronic alcohol consumption and the occurrence of cancer in humans. The mechanism for alcohol-induced carcinogenesis has not been fully understood, although plausible events include genotoxic effects of acetaldehyde, cytochrome P450 2E1 (CYP2E1)-mediated generation of reactive oxygen species, aberrant metabolism of folate and retinoids, increased estrogen, and genetic polymorphisms. Here, we summarize the impact of alcohol drinking on the risk of cancer development and potential underlying molecular mechanisms...
August 14, 2017: Biomolecules
https://www.readbyqxmd.com/read/28805734/grain-foods-are-contributors-of-nutrient-density-for-american-adults-and-help-close-nutrient-recommendation-gaps-data-from-the-national-health-and-nutrition-examination-survey-2009-2012
#12
Yanni Papanikolaou, Victor L Fulgoni
The 2015-2020 Dietary Guidelines for Americans (2015-2020 DGA) maintains recommendations for increased consumption of whole grains while limiting intake of enriched/refined grains. A variety of enriched grains are sources of several shortfall nutrients identified by 2015-2020 DGA, including dietary fiber, folate, iron, and magnesium. The purpose of this study was to determine food sources of energy and nutrients for free-living U.S. adults using data from the National Health and Nutrition Examination Survey, 2009-2012...
August 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28803010/short-communication-apparent-ruminal-synthesis-of-b-vitamins-in-lactating-dairy-cows-fed-saccharomyces-cerevisiae-fermentation-product
#13
D S Castagnino, Y Ying, M S Allen, R Gervais, P Y Chouinard, C L Girard
Apparent ruminal synthesis and duodenal flow of thiamin, riboflavin, niacin, vitamin B6, folates, and vitamin B12 were evaluated in an experiment using 15 ruminally and duodenally cannulated lactating Holstein cows fed a basal diet, according to a crossover design, supplemented or not with 56 g/d of Saccharomyces cerevisiae fermentation product. Duration of the treatment period was 28 d. The basal ration had 28% neutral detergent fber, 30% starch and 16.5% crude protein; forages were corn silage (67% of forage dry matter) and alfalfa silage (33% of forage dry matter)...
August 9, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28802835/residues-in-the-eighth-transmembrane-domain-of-the-proton-coupled-folate-transporter-slc46a1-play-an-important-role-in-defining-the-aqueous-translocation-pathway-and-in-folate-substrate-binding
#14
Srinivas Aluri, Rongbao Zhao, Andras Fiser, I David Goldman
The proton-coupled folate transporter (PCFT-SLC46A1) is required for intestinal folate absorption and folate transport across the choroid plexus. This report addresses the structure/function of the 8th transmembrane helix. Based upon biotinylation of cysteine-substituted residues by MTSEA-biotin, 14 contiguous exofacial residues to Leu316 were accessible to the extracellular compartment of the 23 residues in this helix (Leu303-Leu325). Pemetrexed blocked biotinylation of six Cys-substituted residues deep within the helix implicating an important role for this region in folate binding...
August 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28799782/effects-of-nutrient-and-bioactive-food-components-on-alzheimer-s-disease-and-epigenetic
#15
Elİf Celİk, Nevİn Sanlİer
Alzheimer's disease (AD) is the most common form of dementia in the elderly and is a chronic neurodegenerative disease that is becoming widespread. For this reason, in recent years factors affecting the development, progression and cognitive function of the AD have been emphasized. Nutrients and other bioactive nutrients are among the factors that are effective in AD. In particular, vitamins A, C and E, vitamins B1, B6 and B12, folate, magnesium, choline, inositol, anthocyanins, isoflavones etc. nutrients and bioactive nutrients are known to be effective in the development of AD...
August 11, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28799495/a-nanotechnology-based-strategy-to-increase-the-efficiency-of-cancer-diagnosis-and-therapy-folate-conjugated-gold-nanoparticles
#16
Jaber Beik, Sara Khademi, Neda Attaran, Saeed Sarkar, Ali Shakeri-Zadeh, Habib Ghaznavi, Hossein Ghadiri
BACKGROUND: Gold nanoparticle (AuNP), owing to its elegant physicochemical properties, has been recently introduced as a promising theranostic nanoparticle. Folic acid is a necessary vitamin for cell proliferation and cancer cells highly require such an essential molecule to be replicated. Accordingly, surface functionalization of AuNP with folic acid may offer great potentials for development of a new nanotechnology based strategy to increase the efficiency of cancer diagnosis and therapy...
August 10, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28799141/trace-element-and-vitamin-concentrations-in-paediatric-dialysis-patients
#17
Triona Joyce, Frances Court Brown, Dean Wallace, Christopher J D Reid, Manish D Sinha
BACKGROUND: There are few recent data regarding blood micronutrient concentrations and supplementation in children on maintenance dialysis. We investigated micronutrient concentrations following dialysis commencement. METHODS: Retrospective review, including all children on maintenance dialysis (peritoneal dialysis, PD; intermittent haemodialysis, IHD), for nutritional blood concentrations measured over the first 12 months. Patients received pyridoxine and Dialyvit® daily with planned 3-monthly micronutrient concentration monitoring including selenium, manganese, copper, zinc, folate and vitamins A, D, B12 and E...
August 10, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28799108/an-lc-ms-chemical-derivatization-method-for-the-measurement-of-five-different-one-carbon-states-of-cellular-tetrahydrofolate
#18
Li Chen, Gregory S Ducker, Wenyun Lu, Xin Teng, Joshua D Rabinowitz
The cofactor tetrahydrofolate (THF) is used to reduce, oxidize, and transfer one-carbon (1C) units required for the synthesis of nucleotides, glycine, and methionine. Measurement of intracellular THF species is complicated by their chemical instability, signal dilution caused by variable polyglutamation, and the potential for interconversion among these species. Here, we describe a method using negative mode liquid chromatography-mass spectrometry (LC-MS) to measure intracellular folate species from mammalian cells...
August 10, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28797054/large-scale-wheat-flour-folic-acid-fortification-program-increases-plasma-folate-levels-among-women-of-reproductive-age-in-urban-tanzania
#19
Ramadhani A Noor, Ajibola I Abioye, Nzovu Ulenga, Salum Msham, George Kaishozi, Nilupa S Gunaratna, Ramadhani Mwiru, Erin Smith, Christina Nyhus Dhillon, Donna Spiegelman, Wafaie Fawzi
There is widespread vitamin and mineral deficiency problem in Tanzania with known deficiencies of at least vitamin A, iron, folate and zinc, resulting in lasting negative consequences especially on maternal health, cognitive development and thus the nation's economic potential. Folate deficiency is associated with significant adverse health effects among women of reproductive age, including a higher risk of neural tube defects. Several countries, including Tanzania, have implemented mandatory fortification of wheat and maize flour but evidence on the effectiveness of these programs in developing countries remains limited...
2017: PloS One
https://www.readbyqxmd.com/read/28796944/effect-of-freezing-thermal-pasteurization-and-hydrostatic-pressure-on-fractionation-and-folate-recovery-in-egg-yolk
#20
Nassim Naderi, Yves Pouliot, James D House, Alain Doyen
In this study, the impact of pasteurization and freezing of raw material, as performed at a commercial scale, on egg yolk fractionation and folate recovery was assessed. Freezing induced denaturation of the lipoproteins in egg yolk which prevented further fractionation of the yolk. Thermal pasteurization of egg yolk at 61.1ºC for 3.5 min as well as high hydrostatic pressure (HHP) treatment (400 MPa for 5 min) did not change (p<0.05) the composition of egg yolk or yolk fractions after their recovery by centrifugation...
August 10, 2017: Journal of Agricultural and Food Chemistry
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