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Folate absence

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https://www.readbyqxmd.com/read/29760651/human-dna-helicase-b-as-a-candidate-for-unwinding-secondary-cgg-repeat-structures-at-the-fragile-x-mental-retardation-gene
#1
Gulfem D Guler, Zev Rosenwaks, Jeannine Gerhardt
The fragile X syndrome (FXS) is caused by a CGG repeat expansion at the fragile X mental retardation ( FMR1 ) gene. FMR1 alleles with more than 200 CGG repeats bear chromosomal fragility when cells experience folate deficiency. CGG repeats were reported to be able to form secondary structures, such as hairpins, in vitro . When such secondary structures are formed, repeats can lead to replication fork stalling even in the absence of any additional perturbation. Indeed, it was recently shown that the replication forks stall at the endogenous FMR1 locus in unaffected and FXS cells, suggesting the formation of secondary repeat structures at the FMR1 gene in vivo ...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29744644/an-epigenetic-association-of-malformations-adverse-reproductive-outcomes-and-fetal-origins
#2
Mark Lubinsky
VACTERL, the prototype for associated congenital anomalies, also has connections with functional issues such as pregnancy losses, prematurity, growth delays, perinatal difficulties, and parental subfertility. This segues into a broader association with similar connections even in the absence of malformations. DNA methylation disturbances in the ovum are a likely cause, with epigenetic links to individual components and to folate effects before conception, explaining diverse fetal and placental findings and providing a link to fetal origin hypothesis-related effects...
May 9, 2018: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/29679304/analytic-approaches-for-the-treatment-of-hyperhomocysteinemia-and-its-impact-on-vascular-disease
#3
REVIEW
Soo-Sang Kang, Robert S Rosenson
Homocysteine is an intermediary metabolite in the methionine cycle. Accumulation of homocysteine is caused either by mutation of relevant genes or by nutritional depletion of related vitamin(s). This review covers the historical background of hyperhomocysteinemia in which indispensable subjects in relation to underlying pathophysiological processes are discussed with the view of metabolism and genetics of folate and methionine cycles. This review emphasizes the unique role of homocysteine that is clearly distinct from other risk factors, particularly cholesterol in the development of vascular disease...
April 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29667177/adverse-placental-effects-of-valproic-acid-studies-in-perfused-human-placentas
#4
Miriam Rubinchik-Stern, Miriam Shmuel, Jacob Bar, Michal Kovo, Sara Eyal
OBJECTIVE: In utero exposure to valproic acid (VPA) has been associated with worse pregnancy outcomes compared to all other antiepileptic drugs. We have previously shown that VPA alters the expression of placental transporters for hormones and nutrients in vitro and in pregnant mice. Here, our aim was to characterize the effects of short exposure to VPA on the expression of carriers for compounds essential for fetal development in human placentas ex vivo, under controlled conditions...
April 17, 2018: Epilepsia
https://www.readbyqxmd.com/read/29588319/improving-car-t-cell-therapy-of-solid-tumors-with-oncolytic-virus-driven-production-of-a-bispecific-t-cell-engager
#5
Anna Wing, Carlos Alberto Fajardo, Avery D Posey, Carolyn Shaw, Tong Da, Regina Young, Ramon Alemany, Carl H June, Sonia Guedan
T cells expressing chimeric antigen receptors (CARTs) have shown significant promise in clinical trials to treat hematologic malignancies, but their efficacy in solid tumors has been limited. Oncolytic viruses have the potential to act in synergy with immunotherapies due to their immunogenic oncolytic properties and the opportunity of incorporating therapeutic transgenes in their genomes. Here, we hypothesized that an oncolytic adenovirus armed with an EGFR-targeting, bispecific T-cell engager (OAd-BiTE) would improve the outcome of CART-cell therapy in solid tumors...
March 27, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29551366/dictyostelium-erk2-is-an-atypical-mapk-required-for-chemotaxis
#6
David J Schwebs, Miao Pan, Nirakar Adhikari, Nick A Kuburich, Tian Jin, Jeffrey A Hadwiger
The Dictyostelium genome encodes only two MAPKs, Erk1 and Erk2, and both are expressed during growth and development. Reduced levels of Erk2 expression have been shown previously to restrict cAMP production during development but still allow for chemotactic movement. In this study the erk2 gene was disrupted to eliminate Erk2 function. The absence of Erk2 resulted in a complete loss of folate and cAMP chemotaxis suggesting that this MAPK plays an integral role in the signaling mechanisms involved with this cellular response...
June 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29532755/homocysteine-and-hyperhomocysteinaemia
#7
Bozidarka L Zaric, Milan Obradovic, Vladan Bajic, Mohamed A Haidara, Milos Jovanovic, Esma R Isenovic
Homocysteine (Hcy) is thiol group containing the amino acid, which naturally occurs in all humans. Hcy is degraded in the body through two metabolic pathways, while a minor part is excreted through kidneys. The chemical reactions that are necessary for degradation of Hcy require the presence of the folic acid, vitamins B6 and B12. Consequently, the level of the total Hcy in the serum is influenced by the presence or absence of these vitamins. An elevated level of the Hcy, hyperhomocysteinemia (HHcy) and homocystinuria are connected with occlusive artery disease, especially in the brain, the heart, and the kidney, in addition to venous thrombosis, chronic renal failure, megaloblastic anemia, osteoporosis, depression, Alzheimer's disease, pregnancy problems, and others...
March 12, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29532515/triple-surveillance-a-proposal-for-an-integrated-strategy-to-support-and-accelerate-birth-defect-prevention
#8
Lorenzo D Botto, Pierpaolo Mastroiacovo
Preventing neural tube defects (NTDs) easily qualifies as a high-value opportunity to improve childhood survival and health: the unmet need is significant (major preventable burden), the intervention is transformative (providing sufficient folic acid), and delivery strategies (e.g., fortification) are effective in low-resource countries. Yet, NTD prevention is lagging. Can public health surveillance help fix this problem? Critics contend that surveillance is largely unnecessary, that limited resources are best spent on interventions, and that surveillance is unrealistic in developing countries...
February 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29500675/a-randomized-trial-of-a-novel-chewable-multivitamin-and-mineral-supplement-following-roux-en-y-gastric-bypass
#9
Jamie Perin, Gregory Prokopowicz, Margaret Furtado, Konstantinos Papas, Kimberley E Steele
BACKGROUND: Vitamin and mineral deficiencies are common following Roux-en-Y gastric bypass (RYGB) and can lead to significant morbidity, but little research on the efficacy of vitamin supplementation regimens exists. We compared the efficacy and tolerability of an investigational versus a standard multivitamin regimen in patients undergoing RYGB. METHODS: Fifty-six patients, aged 18 to 65, were randomized to an investigational versus a standard multivitamin. Plasma levels of vitamins A, B-12, D, E-α, E-β/γ, thiamine, folate, iron, iron-binding capacity, iron saturation, prealbumin, and parathyroid hormone (PTH) were measured at 3 and 6 months postoperatively...
March 2, 2018: Obesity Surgery
https://www.readbyqxmd.com/read/29461227/-the-differentiated-approach-to-prevention-of-neural-tube-defects-in-children
#10
N Kotova, V Maichuk, O Fedorenko
Neural tube defects occupy second place in frequency after the defects of the cardiovascular system. The folate metabolism violation and hyperhomocysteinemia in women are proved to be the leading risk factors for the NTD of the fetus. Polymorphism of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) is a genetic determinant of folate metabolism violation. Admission of folic acid in a standard dose of 0.4 mg and / or the use of fortified foods does not allow reaching the protective level of folic acid if there is a mutation of the MTHFR gene or when several risk factors combine, which requires a higher dose of folic acid...
January 2018: Georgian Medical News
https://www.readbyqxmd.com/read/29427165/association-of-mthfr-gene-polymorphisms-with-migraine-in-north-indian-population
#11
Sukhvinder Kaur, Arif Ali, Anil Kumar Pandey, Balkirat Singh
Polymorphisms in MTHFR gene are mostly associated with increased levels of homocysteine in the absence of dietary folate and are a risk factor for complex neurovascular diseases like migraine. The aim of present case-control study was to determine the association between MTHFR gene polymorphisms (C667T; rs 1801133, A1298C; rs 1801131) with migraine susceptibility. In total, 100 patients with migraine (23with MA and 77 with MO) and age-sex matched 100 healthy controls were included in this study from OPD of ESIC Medical College & Hospital, Faridabad...
April 2018: Neurological Sciences
https://www.readbyqxmd.com/read/29372898/the-folate-binding-module-of-thermus-thermophilus-cobalamin-dependent-methionine-synthase-displays-a-distinct-variation-of-the-classical-tim-barrel-a-tim-barrel-with-a-twist
#12
Kazuhiro Yamada, Markos Koutmos
Methyl transfer between methyltetrahydrofolate and corrinoid molecules is a key reaction in biology that is catalyzed by a number of enzymes in many prokaryotic and eukaryotic organisms. One classic example of such an enzyme is cobalamin-dependent methionine synthase (MS). MS is a large modular protein that utilizes an SN 2-type mechanism to catalyze the chemically challenging methyl transfer from the tertiary amine (N5) of methyltetrahydrofolate to homocysteine in order to form methionine. Despite over half a century of study, many questions remain about how folate-dependent methyltransferases, and MS in particular, function...
January 1, 2018: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/29291347/absence-of-albumin-improves-in-vitro-cellular-uptake-and-disruption-of-poloxamer-407-based-nanoparticles-inside-cancer-cells
#13
Ana Loureiro, Jennifer Noro, Ana S Abreu, Eugénia Nogueira, Diana Soares da Costa, Carla Silva, Artur Cavaco-Paulo
Novel nanoparticles based on Poloxamer 407 and vegetable oil were produced by high pressure homogenization. Functionalization of those nanoparticles was made by incorporation of folic acid (FA)-Poloxamer 407 conjugate. These nanoparticles showed suitable characteristics for intravenous therapeutic applications similarly to PEGylated albumin-based nanoparticles, previously described by our research group. Here, we found that the absence of albumin at the interface of Poloxamer 407-based nanoparticles improves the overall process of in vitro cellular uptake and nanoparticle disruption inside cancer cells (folate receptor, FR, positive cells)...
February 5, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29028357/folate-peg-nota-al-18-f-a-new-folate-based-radiotracer-for-pet-imaging-of-folate-receptor-positive-tumors
#14
Qingshou Chen, Xiangjun Meng, Paul McQuade, Daniel Rubins, Shu-An Lin, Zhizhen Zeng, Hyking Haley, Patricia Miller, Dinko González Trotter, Philip S Low
The folate receptor (FR) has been established as a promising target for imaging and therapy of cancer (FR-α), inflammation, and autoimmune diseases (FR-β). Several folate based PET radiotracers have been reported in the literature, but an18 F-labeled folate-PET imaging agent with optimal properties for clinical translation is still lacking. In the present study, we report the design and preclinical evaluation of folate-PEG12 -NOTA-Al18 F (1), a new folate-PET agent with improved potential for clinical applications...
December 4, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28960955/improving-tumor-specificity-and-anticancer-activity-of-dasatinib-by-dual-targeted-polymeric-micelles
#15
Qing Yao, Jong Hoon Choi, Zhi Dai, Jiao Wang, Dongin Kim, Xing Tang, Lin Zhu
To improve tumor targetability and drug efficacy and decrease drug resistance of dasatinib (DSB), the multifunctional micellar nanoparticles that combined the matrix metalloproteinase 2 (MMP2)-sensitive tumor (site) targeting with folate receptor-mediated tumor (cell) targeting were developed. Two major functional polymers, polyethylene glycol (5000 Da)-MMP2-sensitive peptide-phosphoethanolamine (PEG5k-pp-PE) and folic acid-polyethylene glycol (2000 Da)-phosphoethanolamine (FA-PEG2k-PE), were synthesized to construct the dual-targeted micellar nanoparticles (MMP/FR micelles)...
October 10, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28780092/whole-body-propionate-and-glucose-metabolism-of-multiparous-dairy-cows-receiving-folic-acid-and-vitamin-b12-supplements
#16
M Duplessis, H Lapierre, B Ouattara, N Bissonnette, D Pellerin, J-P Laforest, C L Girard
This study was undertaken to evaluate the effect of supplementation of folic acid and vitamin B12 on glucose and propionate metabolism. Twenty-four multiparous cows were assigned according to a complete block design in a 2 × 2 factorial arrangement to one of the following treatments: (1) saline 0.9% NaCl, (2) 320 mg of folic acid, (3) 10 mg of vitamin B12, or (4) 320 mg of folic acid and 10 mg of vitamin B12. Intramuscular injections were given weekly from 3 wk before the expected calving date until 9 wk postpartum...
August 2, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28768807/folamirs-ligand-targeted-vehicle-free-delivery-of-micrornas-for-the-treatment-of-cancer
#17
Esteban A Orellana, Srinivasarao Tenneti, Loganathan Rangasamy, L Tiffany Lyle, Philip S Low, Andrea L Kasinski
MicroRNAs are small RNAs that negatively regulate gene expression posttranscriptionally. Because changes in microRNA expression can promote or maintain disease states, microRNA-based therapeutics are being evaluated extensively. Unfortunately, the therapeutic potential of microRNA replacement is limited by deficient delivery vehicles. In this work, microRNAs are delivered in the absence of a protective vehicle. The method relies on direct attachment of microRNAs to folate (FolamiR), which mediates delivery of the conjugated microRNA into cells that overexpress the folate receptor...
August 2, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28766937/a-structural-basis-for-biguanide-activity
#18
Scott A Gabel, Michael R Duff, Lars C Pedersen, Eugene F DeRose, Juno M Krahn, Elizabeth E Howell, Robert E London
Metformin is the most commonly prescribed treatment for type II diabetes and related disorders; however, molecular insights into its mode(s) of action have been limited by an absence of structural data. Structural considerations along with a growing body of literature demonstrating its effects on one-carbon metabolism suggest the possibility of folate mimicry and anti-folate activity. Motivated by the growing recognition that anti-diabetic biguanides may act directly upon the gut microbiome, we have determined structures of the complexes formed between the anti-diabetic biguanides (phenformin, buformin, and metformin) and Escherichia coli dihydrofolate reductase (ecDHFR) based on nuclear magnetic resonance, crystallographic, and molecular modeling studies...
September 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28580921/crystal-structure-of-the-active-form-of-native-human-thymidylate-synthase-in-the-absence-of-bound-substrates
#19
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 N5 ,N10 -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
#20
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
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