Maternal dietary deficiencies in folic acid or choline worsen stroke outcomes in adult male and female mouse offspring

Maternal one-carbon metabolism plays an important role in early life programming.There is a well-established connection between the fetal environment and the health status of the offspring.Howeve r,there is a knowledge gap on how maternal nutrition impacts stro ke outcomes in offspring.The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcomes in 3-month-old offspring.Adult female mice were fed a folic acid-deficient diet,choline-deficient diet,or control diet 4 weeks before pregnancy.They we re continued on diets during pregnancy and la ctation.Male and female offspring were weaned onto a control diet and at 2 months of age were subjected to ischemic stroke within the sensorimotor cortex via photothrombotic damage.Mothers maintained on either a folic acid-deficient diet or choline-deficient diet had reduced levels of S-adenosylm ethionine in the liver and S-adenosylhomocysteine in the plasma.After ischemic stro ke,motor function was impaired in 3-month-old offspring from mothers receiving either a folic acid-deficient diet or choline-deficient diet compared to the animals receiving a control diet.In brain tissue,there was no difference in ischemic damage volume.When protein levels were assessed in ischemic brain tissue,there were lower levels of active caspase-3 and hypoxia-inducible factor 1α in males compared to females and betaine levels were reduced in offspring from the mothers receiving a choline-deficient diet.Our results demonstrate that a deficient maternal diet at critical time points in neurodevelopment results in worse stro ke outcomes.This study emphasizes the importance of maternal diet and the impact it can have on offspring health.

Therapeutic effect of folic acid combined with decitabine on diabetic mice

AIM:To evaluate the therapeutic effect of folic acid combined with decitabine on diabetic mice.METHODS:The diabetic model of db/db mice were randomly divided into model group,folic acid group,decitabine group,folic acid combined with decitabine group,and C57 mice as normal control group.The density of retinal blood vessels and retinal thickness were detected by fundus photography and optical coherence tomography,respectively.Pathological changes of retina were observed by hematoxylin-eosin(HE)staining.The homocysteine(Hcy)in serum was detected by enzyme linked immunosorbent assay(ELISA).TdT-mediated dUTP nick-end labeling(TUNEL)was used to detect apoptosis in retinal tissue.Evans blue dye was used to detect the permeability of retinal blood vessels.The platelet endothelial cell adhesion molecule-1(CD31)and vascular endothelial growth factor receptor(VEGFR)protein were detected by Western blot.The 3-nitrotyrosine(3-NT)and 4-hydroxynonanine(4-HNE)were detected by immunohistochemistry.RESULTS:The density of retinal blood vessels,retinal thickness,retinal vascular permeability and the proportion of apoptotic cells of retinal tissue in the model group increased significantly than control group(P<0.05).The Hcy in serum and the levels of CD31,VEGFR,3-NT,and 4-HNE in retinal tissue increased significantly in the model group(P<0.01).Folic acid and decitabine both reversed these changes significantly,and the combination of the folic acid and decitabine worked best.CONCLUSION:The combination of folic acid and decitabine has a more significant protective effect on the retina in diabetic mice.

Efficacy of Folinic Acid in Comparison to Folic Acid for Reducing Side Effects of Methotrexate in Children with Juvenile Idiopathic Arthritis

Background: Methotrexate (MTX) is the most effective and commonly used disease-modifying anti-rheumatic drug in the management of juvenile idiopathic arthritis. Several patients develop side effects, which may lead to low quality of life and non-compliance to MTX. To reduce MTX-induced side effects, folic acid supplementation is prescribed by most rheumatologists. Even after that, some patients have symptoms while receiving MTX. Objectives: To assess the efficacy of folinic acid in comparison to folic acid for reducing the side effects of MTX in JIA patients. Material and methods: In this prospective observational study, newly diagnosed cases of JIA who would be getting MTX were included by purposive sampling. Data were collected using a predesigned questionnaire. Among 40 patients, 20 received folinic acid (Group A), and 20 received folic acid (Group B). Disease activity levels were assessed by JADAS-27 (Juvenile Arthritis Disease Activity Score). Contents from the MISS (MTX Intolerance severity score) questionnaire were used to assess the side effects. All patients were evaluated at baseline, 6th, and 12th weeks. Results: There were significant differences in the frequency of MTX-related adverse events between folinic acid (Group A) and folic acid (Group B). Group A patients only had nausea (10% and 15% in the 6th & 12th week respectively) and vomiting (5% at both follow-ups). On the other hand, in addition to nausea (70% and 95% in the 6th & 12th week) and vomiting (20% and 90% in the 6th & 12th week), folic acid group patients had restlessness, crying, and irritability. Self-discontinuation of MTX was present in the folic acid group (5% & 10% in the 6th & 12th week). Improvement of disease activity was more in the folinic acid group. Conclusion: The folinic acid group had significantly fewer side effects. Improvement of disease activity was more and compliance was also better among them. Methotrexate (MTX) is the most effective and commonly used disease-modifying anti-rheumatic drug in the management of juvenile idiopathic arthritis. A number of patients develop side effects, which may lead to low quality of life and non-compliance to MTX. To reduce MTX induced side effects, folic acid supplementation is prescribed by most rheumatologists. Even after that, some patients have symptoms while receiving MTX.

Adherence to iron and folic acid supplementation and associated factors amongmothers receiving antenatal care in Lira district, Uganda

Background:Prenatal iron and folic acid supplementation is an economical strategy for reducing iron and folic acid deficiency anemia among expectant mothers in resource-limited countries like Uganda.This study aimed to assess the level of compliance with iron and folic acid supplementation(IFAS)and identify associated factors among mothers receiving prenatal services in Lira district,Uganda.Methods:A cross-sectional study was conducted at the antenatal clinic of Lira Regional Referral Hospital,involving 252 pregnant mothers.Adherence levels to IFAS were evaluated using a visual analogue scale,and associated factors were collected through an interviewer-administered questionnaire.The data were analyzed using SPSS software,and the results were presented in tables.Results:Only 46%of the mothers attending the antenatal clinic adhered to IFAS during the 30 days preceding the study.Participants who had good knowledge of IFAS before recruitment(odds ratio(OR)1.49,95%confidence interval(CI)1.12–1.97),utilized reminder techniques(OR 1.05,95%CI 1.02–1.09),and received support from their partners or relatives(OR 1.56,95%CI 1.07–2.29)were more likely to have good adherence.The main reasons for missing IFAS were forgetfulness and fear of taking too many tablets.Conclusions:There was a low adherence rate to IFAS among mothers attending antenatal clinics in Lira district.Further investigations are recommended to identify barriers to adherence,and comprehensive health education programs should be provided to pregnant mothers.

Folic acid supplementation attenuates hyperhomocysteinemia-induced preeclampsia-like symptoms in rats

Folic acid participates in the metabolism of homocysteine and lowers plasma homocysteine levels directly or indirectly. To establish a hyperhomocysteinemic pregnant rat model, 2 mL of DL-homocysteine was administered daily by intraperitoneal injection at a dose of 200 mg/kg from day 10 to day 19 of gestation. Folic acid was administered by intragastric administration at a dose of 20 mg/kg during the period of preeclampsia induction. Results showed that systolic blood pressure, proteinuria/creatinine ratio, and plasma homocysteine levels in the hyperhomocysteinemic pregnant rats increased significantly, and that body weight and brain weight of rat pups significantly decreased. Folic acid supplementation markedly reversed the above-mentioned abnormal changes of hyperhomocysteinemic pregnant rats and rat pups. These findings suggest that folic acid can alleviate the symptoms of hyperhomocysteinemia- induced preeclampsia in pregnant rats without influencing brain development of rat pups.

EGFR/Vimentin/Folic Acid磁球检测肺癌循环肿瘤细胞初探

背景与目的循环肿瘤细胞(circulating tumor cell, CTC)在肺癌的筛查及预后方面发挥着重要的作用,但较低的CTC分离效率和特异性对其临床应用有着明显的制约,本研究旨在探讨非小细胞肺癌(non-small cell lung cancer, NSCLC)患者CTC的新型高效分离方法,以期达到对NSCLC的早期诊断的目的。方法采用薄膜法制备表皮生长因子受体(epidermal growth factor receptor, EGFR)、波形蛋白(Vimentin)和叶酸(folic acid, FA)三种免疫脂质磁球,表征后通过细胞系进行分选方案的探索,构建对NSCLC CTC的最优分选方案,初步研究了其在临床上的应用价值。结果 EGFR、Vimentin和FA磁球磁球单独和联合使用对肺癌细胞株的平均捕获效率分别为78.0%、79.0%、82.0%和91.0%;在60例肺癌患者中,以每7.5 mL血液2个CTC为cutoff值,EGFR、Vimentin、FA磁球单独和联合使用阳性率分别为65.0%、33.3%、93.3%和100.0%,同时发现联合使用三种磁球检出的CTC数量与临床分期具有相关性(P<0.05)。结论联合使用三种磁球可以分离EGFR+、Vimentin+和FA+表达且形态完整的CTC,有利于的CTC相关下游分析,本研究提供了一种提高NSCLC CTC捕获效率的新方法,且验证了捕获的CTC计数方法可用于肺癌的辅助诊断。

Effects of folic acid on in vitro astrocytic differentiation of neural stem cells from neonatal rats

BACKGROUND： Folic acid is essential for normal functioning of the nervous system. Previous studies have focused on the effects of folic acid on astrocyte proliferation. OBJECTIVE： To explore the effects of folic acid on astrocyte differentiation of neural stem cells （NSCs） and the related mechanisms in vitro. DESIGN, TIME AND SETTING： A randomized, controlled, grouping experiment was performed in Tianjin Medical University between August 2007 and October 2008. MATERIALS： Folic acid and 5-bromo-2-deoxyuridine （BrdU） were obtained from Sigma, MO, USA. Primary antibodies [rabbit anti-rat nestin, β-tubulin-Ⅲ, glial fibrillary acidic protein, and neurogeninl （Ngnl）; mouse anti-rat BrdU and β-actin monoclonal antibodies] were purchased from Santa Cruz Biotechnology, USA. METHODS： At 6 days of NSC proliferation from 24-hour-old neonatal rats, BrdU incorporation assay was performed. Seven days after primary culture, NSCs were induced to differentiate with medium containing 5% fetal bovine serum. Cultured NSCs were assigned to three groups： control, low-dose （liquid media with 8 mg/L folic acid）, and high-dose folic acid （liquid media with 44 mg/L folic acid）. MAIN OUTCOME MEASURES： At day 7 after primary culture, the cells were identified as NSCs by immunocytochemical methods. Double-label immunofluorescence technique for glial fibrillary acidic protein/BrdU detected differentiated cells 7 days after induction. Western blot was used to analyze expression of Ngnl protein in NSCs. RESULTS： In serum-free suspension medium, neurospheres comprised a large number of Nestin-, glial fibrillary acidic protein-, β-tubulin-Ⅲ-, and BrdU-positive cells. Compared with the control group, high-dose folic acid supplementation led to an marked increase in the percentage of glial fibrillary acidic protein/BrdU-positive cells （P 〈 0.05）, and significantly decreased Ngnl protein expression （P 〈 0.05）. CONCLUSION： Folic acid promotes astrocytic differentiation of NSCs, which might be related to downregulation of Ngnl protein expression.

Folic acid-conjugated liposomal vincristine for multidrug resistant cancer therapy

We encapsulated vincristine into folic acid-conjugated PEGylated liposomes to improve the anti-tumor efficacy on multidrug resistant cancers.It was observed that the drug delivery system we constructed exhibited maximum cytotoxicity on KBv200 cells(multidrug resistant variant)compared with any other formulations.The semi-quantitative analysis of region of interest revealed that there was a great increase in area under curve(AUC)of a near-infrared fluorescein in solid tumors due to folic acid-mediated accumulation.Folic acid-conjugated PEGylated liposomes showed a significant tumor growth inhibiting effect in vitro and in vivo.TUNEL assay revealed that folic acid-conjugated PEGylated liposomes could induce cell apoptosis much more greatly than others.This study demonstrated that it had potential application prospective for the treatment of multidrug resistant cancer.

Folic Acid Self-Assembly Enabling Manganese Single-Atom Electrocatalyst for Selective Nitrogen Reduction to Ammonia

Efficient and robust single-atom catalysts(SACs)based on cheap and earth-abundant elements are highly desirable for electrochemical reduction of nitrogen to ammonia(NRR)under ambient conditions.Herein,for the first time,a Mn-N-C SAC consisting of isolated manganese atomic sites on ultrathin carbon nanosheets is developed via a template-free folic acid self-assembly strategy.The spontaneous molecular partial dissociation enables a facile fabrication process without being plagued by metal atom aggregation.Thanks to well-exposed atomic Mn active sites anchored on two-dimensional conductive carbon matrix,the catalyst exhibits excellent activity for NRR with high activity and selectivity,achieving a high Faradaic efficiency of 32.02%for ammonia synthesis at−0.45 V versus reversible hydrogen electrode.Density functional theory calculations unveil the crucial role of atomic Mn sites in promoting N_(2) adsorption,activation and selective reduction to NH_(3) by the distal mechanism.This work provides a simple synthesis process for Mn-N-C SAC and a good platform for understanding the structure-activity relationship of atomic Mn sites.

Folic acid attenuates high-fat diet-induced steatohepatitis via deacetylase SIRT1-dependent restoration of PPARα

BACKGROUND Folic acid has been shown to improve non-alcoholic steatohepatitis(NASH),but its roles in hepatic lipid metabolism,hepatic one-carbon metabolism,and gut microbiota are still unknown.AIM To demonstrate the role of folic acid in lipid metabolism and gut microbiota in NASH.METHODS Twenty-four Sprague-Dawley rats were assigned into three groups:Chow diet,high-fat diet(HFD),and HFD with folic acid administration.At the end of 16 wk,the liver histology,the expression of hepatic genes related to lipid metabolism,one-carbon metabolism,and gut microbiota structure analysis of fecal samples based on 16 S r RNA sequencing were measured to evaluate the effect of folic acid.Palmitic acid-exposed Huh7 cell line was used to evaluate the role of folic acid in hepatic lipid metabolism.RESULTS Folic acid treatment attenuated steatosis,lobular inflammation,and hepatocellular ballooning in rats with HFD-induced steatohepatitis.Genes related to lipid de novo lipogenesis,β-oxidation,and lipid uptake were improvedin HFD-fed folic acid-treated rats.Furthermore,peroxisome proliferator-activated receptor alpha(PPARα)and silence information regulation factor 1(SIRT1)were restored by folic acid in HFD-fed rats and palmitic acid-exposed Huh7 cell line.The restoration of PPARαby folic acid was blocked after transfection with SIRT1 si RNA in the Huh7 cell line.Additionally,folic acid administration ameliorated depleted hepatic one-carbon metabolism and restored the diversity of the gut microbiota in rats with HFD-induced steatohepatitis.CONCLUSION Folic acid improves hepatic lipid metabolism by upregulating PPARαlevels via a SIRT1-dependent mechanism and restores hepatic one-carbon metabolism and diversity of gut microbiota,thereby attenuating HFD-induced NASH in rats.

Effect of in ovo folic acid injection on hepatic IGF2 expression and embryo growth of broilers

Background： Insulin-like factor 2（IGF2） plays an important role in embryonic growth process by modulating intermediary metabolism and cell proliferation. Folic acid is involved in one carbon metabolism and contributes to DNA methylation which is related to gene expression. The purpose of this study was to explore whether folic acid could regulate IGF2 expression via epigenetic mechanism and further promote embryonic growth of new-hatched broilers.Methods： In the present study, 360 fertile eggs were selected and randomly assigned to four treatments. On11 embryonic day of incubation（E11）, 0, 50, 100 and 150 μg folic acid were injected into eggs respectively.After hatched, growth performance of broilers were calculated. Hepatic IGF2 expression, methylation level and chromatin structure of promoter region were analyzed.Results： Results have showed that IGF2 expression was up-regulated in 150 μg folic acid group（P 〈 0.05） and other two dose of folic acid did not affect gene expression（P 〉 0.05）. Meanwhile, methylation level of IGF2 promoter were lower in 100 and 150 μg groups, which was consistent with lower expression of DNA methyltransferase1（DNMT1）（P 〈 0.05）. What＇s more, chromatin looseness of IGF2 promoter was higher in 150 μg group than control group（P 〈 0.05）. Further, birth weight（BW）, liver and bursa index of new-hatched chickens in 150 μg folic acid group were higher than the other groups（P 〈 0.05）. There were positive correlations between hepatic IGF2 expression and BW and organs index（P 〈 0.05）.Conclusion： In conclusion, our data have demonstrated that 150 μg folic acid injection on E11 could up-regulate IGF2 expression by modulating DNA hypomethylation and improving chromatin accessibility in the gene promoter region,and ulteriorly facilitate embryonic growth and organ development of broilers.

Adsorption of Folic Acid on the Single-walled Carbon Nanotubes: AIM and NBO Analyses via DFT

In the present work, the behavior of folic acid （FA） molecule adsorbed onto single-walled carbon nanotube （SWCNT） was examined using the DFT-B3LYP/6-31G＊ level. In order to obtain information about the binding features of SWCNT as adsorbent with FA molecule, several studies, including the structural and electronic parameters and also the Atoms in Molecules （AIM） analysis, were performed. It was observed that the FA molecule via hydrogen bond prefers to adsorb on SWCNT with adsorption energy of about -18.70 kcal/mol. The molecular orbitals （HOMO and LUMO）, natural bond orbital （NBO）,analysis, and density of states （DOS） plot indicated that a charge about 0.032 [ e [ is transferred from the FA molecule to the nanotube. After solvation energy calculations, it was found that the presence of a polar solvent causes an increase in FA adsorption on the single-walled carbon nanotube. Topological features such as electron energy density （Hc） and Laplacian of the electron density （V2p~） demonstrate partial covalent nature for H（ll6）...O（10） interaction in the FA/SWCNT complex. According to the calculated results, the single-walled carbon nanotubes are expected to be a potential efficient adsorbent for the adsorption of folic acid drug and also can be used as a suitable drug delivery vehicle within biological systems.

Effects of Maternal Folic Acid Supplementation on Hepatic Apoptosis-Related Gene Expressions between Intrauterine Growth Restriction and Normal Body Weight Piglets

Intrauterine growth retardation （IU- GR） causes significantly negative effects on the meth- ylation status of genes related to cell apoptosis com- pared with normal body weight （NBW） piglets. Thus, the objective of the present study was to exam- ine the effects of maternal dietary folic acid supple- mentation on genes expression profile for hepatic ap- optosis in IUGR and NBW piglets. Twenty four York- shire gilts were allocated randomly to one of the two diets ： control （ C, folic acid 1.3 mg/kg） or folic acid supplementation （ FS, folic acid 30 mg/kg） after mat- ing. Gene expressions in liver samples were deter- mined and revealed that the mRNA expressions of p53 ,BCL-2 associated X protein （Bax）, and Cyclin- dependent kinase inhibitor 1A （CDKN1A） were up-regulated in IUGR piglets compared with NBW pig- lets fed C diets,but could be reversed by maternal fo- lic acid supplementation. The expressions of vascular endothelial growth factor （VEGF）, Serine-protein Ki- nase-Ataxia Telangiectasia Mutated （ATM） ,and Cad- herin-associated protein-beta-catenin 1 （ CTNNB1 ） were influenced by maternal folic acid supplementa- tion significantly, but were not influenced by birth weight. Expression of p53 binding protein-MDM-2 （ MDM-2 ） remained unchanged. In conclusion, these results demonstrated that maternal folic acid supple- mentation could exert positive effects on genes related to apoptosis in IUGR and NBW piglets, which might facilitate their postnatal health and growth perform- alice.

Folic acid-induced animal model of kidney disease

The kidneys are a vital organ that is vulnerable to both acute kidney injury(AKI)and chronic kidney disease(CKD)which can be caused by numerous risk factors such as ischemia,sepsis,drug toxicity and drug overdose,exposure to heavy metals,and diabetes.In spite of the advances in our understanding of the pathogenesis of AKI and CKD as well AKI transition to CKD,there is still no available therapeutics that can be used to combat kidney disease effectively,highlighting an urgent need to further study the pathological mechanisms underlying AKI,CKD,and AKI progression to CKD.In this regard,animal models of kidney disease are indispensable.This article reviews a widely used animal model of kidney disease,which is induced by folic acid(FA).While a low dose of FA is nutritionally beneficial,a high dose of FA is very toxic to the kidneys.Following a brief description of the procedure for disease induction by FA,major mechanisms of FA-induced kidney injury are then reviewed,including oxidative stress,mitochondrial abnormalities such as impaired bioenergetics and mitophagy,ferroptosis,pyroptosis,and increased expression of fibroblast growth factor 23(FGF23).Finally,application of this FA-induced kidney disease model as a platform for testing the efficacy of a variety of therapeutic approaches is also discussed.Given that this animal model is simple to create and is reproducible,it should remain useful for both studying the pathological mechanisms of kidney disease and identifying therapeutic targets to fight kidney disease.

Molecular Structure and Theoretical Thermodynamic Study of Folic Acid Based on the Computational Approach

In our previous work, we studied the interaction of folic acid, FA, molecule with single- walled carbon nanotube and the related binding energies with other related parameters. Now, in order to extend our study with respect to the other structural properties of folic acid molecule and its thermodynamic properties, we optimized the structures of both neutral and zwitteronic forms of this molecule by using the DFT/B3LYP method in the gas phase and then in different solvents. In addition, the electronic properties, such as the molecular orbital study （HOMO, LUMO, PDOS, and TDOS） and geometrical structure, were investigated by the above-mentioned method with 6-3 l G（d） basis set. The thermodynamic properties of both neutral and zwitterionic forms of the FA molecule at different temperature have been calculated. Natural bond orbital （NBO） analysis has been done to study the stability of the molecule arising from charge delocalization.

Simultaneous quantitation of folic acid and 5-methyltetrahydrofolic acid in human plasma by HPLC–MS/MS and its application to a pharmacokinetic study

A sensitive method based on high-performance liquid chromatography-tandem mass spectrometry （LC- MS/MS） has been developed for the simultaneous determination of folic acid （FA） and its active meta- bolite, 5-methyltetrahydrofolic acid （5-M-THF）, in human plasma. The analytes were extracted from plasma with methanol solution containing 10 mg/mL of 2-mercaptoethanol and 0.025% （v/v） ammonium hydroxide. FA and 5-M-THF were more stable after the addition of 2-mercaptoethanol and ammonium hydroxide in the sample preparation procedures of this study than they were in the previously published methods. Chromatographic separation was performed on a Hedera ODS-2 column using a gradient elution system of acetonitrile and 1 mM ammonium acetate buffer solution containing 0.6% formic acid as mobile phase. LC-MS/MS was carried out with an ESI ion-source and operated in the multiple reaction monitoring （MRM） mode. The assay was linear over the concentration ranges of 0.249-19.9 ng/mL for FA, and 5.05-50.5 ng/mL for 5-M-THF. The developed LC-MS/MS method offers increased sensitivity for quantification of FA and 5-M-THF in human plasma and was applicable to a pharmacokinetic study of FA and 5-M-THF.

Periconceptional Folic Acid Supplementation in Chinese Women： A Cross-sectional Study

Objective To investigate the status of folic acid （FA） supplementation and determinants of its use inpregnant Chinese women Methods In this cross-sectional study, questionnaires were used to collect information of participantsand FA supplementation. Women were recruited between 6 and 12 weeks postpartum in Tianjin, China,between July 2015 and July 2016 Results A total of 1,921 women were recruited in the study. Approximately 93.1% of the studyparticipants used FA, while 14.4% of the women taking FA from three months prior to preconception tothree months post-conception. Women who took FA for three months prior to preconception throughat least three months into their pregnancy were more likely to be between 30 and 34 years old （OR =2.91, 95% CI： 1.15, 7.33）, employed （OR = 2.07, 95% CI： 1.17, 3.67）, primigravida （OR = 5.20, 95% CI：3.02, 8.96）, married to spouses with an intermediate education level （OR = 2.92, 95% CI： 1.45, 5.89）, andearn a high family income （OR = 3.19, 95% CI： 1.57, 6.49） Conclusion The prevalence of periconceptional FA intake was far below the requirements of theNational Health and Family Planning Commission of China; therefore, knowledge of FA supplementationshould be strengthened among women who are or planning to become pregnant.

Square wave voltammetric quantification of folic acid,uric acid and ascorbic acid in biological matrix

Nowadays, modified electrodes with metal nanoparticles have appeared as an alternative for the electroanalysis of various compounds. In this study, gold nanoparticles（GNPs） were chosen as interesting metal nanoparticles for modifying carbon paste electrode（CPE）. GNPs and the gold nanoparticles-modified carbon paste electrode（GNPs/CPE） were characterized by UV–Vis spectroscopy, transmission electron microscopy（TEM） and scanning electron microscopy（SEM）. GNPs/CPE as a simple and sensitive electrode was used to study three important biological molecules： folic acid（FA）, uric acid（UA） and ascorbic acid（AA）. Square wave voltammetry（SWV） was used as an accurate technique for quantitative measurements. A good linear relation was observed between anodic peak current（ipa） and FA（5.2 × 10（-6）– 2.5 × 10（-5）M）, UA（1.2 × 10（-6）– 2.1 × 10（-5）M） and AA（1.2 × 10（-6）– 2.5 × 10（-5）M） concentrations in simultaneous determination of these molecules.

Comparative Study between the Use of Regular Folic Acid Supplement versus the Use of L-Methyl Folate in Patients with Methyl Tetrahydrofolate Reductase (MTHFR) Gene Mutation with Recurrent Pregnancy Loss

Background: Methylfolate is the active metabolite of folate that is important for DNA repair, synthetized under the effect of MTHFR (methyl-tetrahydro-folatereductase) enzyme. Patients with MTHFR gene mutation have low levels of biologically active methyfolate. Those patients have high homocysteine levels causing vasculopathy and inadequate feto-maternal circulation. Aim of the Work: To predict the potential benefit of use of methylfolate instead of use of the regular folic acid in patients with MTHFR gene mutation with history of RPL (recurrent pregnancy loss). Subjects and Methods: Study was performed on 100 women. All women had experienced at least two consecutive miscarriages first trimester abortion. All patients were positive of having MTHFR gene mutation. Patients were divided into two groups in terms of 1st trimester drug intake. The 1st group recieved a regular folic acid supplement in a dose of 5 mg per day starting from the day of positive pregnancy test till the end of the first trimester. The 2nd group recieved L-methylfolate supplement in a dose of 1000 mcg per day starting from the day of positive pregnancy test till the end of the first trimester. Then both groups were compared in terms of abortion rates, pregnancy continuation rates and the development of other major obstetric complications. Results: Patients in 1st group had no associated pregnancy related complications in 56%, PE in 14%, PROM in 18% and PTL in 12% of cases. On the other hand, patients in 2nd group had no associated pregnancy related complications in 78%, PE in 6%, PROM in 8% and PTL in 8% of cases 54% of patients on folate group ended in abortion, while only 16% of patients on methylfolate group had abortion. 24% of patients on folate group had PTL, compared to 8% of patient who had had PTL in methylfolate group. 22% of patients in the 1st group continued pregnancy to full term, while 60% of 2nd group continued pregnancy to full term. Conclusion and Recommendations: The use of methyl-folate supplement during the first trimester of in patients with history of RPL and positive MTHFR gene mutation should be a routine practice instead of the regular folate supplement as it improves pregnancy continuation rates and decreases occurrence of associated pregnancy co-morbidities as preterm labor and preeclampsia.

Adsorption Properties and Quantum Molecular Descriptors of the Folic Acid Drug Adsorbed onto Zigzag and Armchair Single Walled Carbon Nanotubes:DFT Simulations

The adsorption behavior of folic acid onto（5,0） zigzag and（5,5） armchair carbon nanotube（SWCNT） has been investigated using B3 LYP density functional at the 6-31G＊ level. The adsorption energies,molecular orbital analysis and structural changes at the adsorption site are indicative of covalent adsorption on the zigzag SWCNT surface,while the adsorption is physical on the armchair SWCNT surface. The density of states（DOS） Plot and the quantum molecular descriptors（QMD） are witness to the significant changes in the electronic properties of SWCNT systems after the attachment of adsorbed species to the tube surface. According to the calculated results,the single-walled carbon nanotubes are expected to be a potential efficient adsorbent for the adsorption of folic acid drug and also can be used as a suitable drug delivery vehicle within biological systems.