Folic Acid-Functionalized Nanocrystalline Cellulose as a Renewable and Biocompatible Nanomaterial for Cancer-Targeting Nanoparticles

The study focuses on the development of biocompatible and stable FA-functionalized nanocrystalline cellulose(NCC)as a potential drug delivery system for targeting folate receptor-positive cancer cells.The FA-functionalized NCCs were synthesized through a series of chemical reactions,resulting in nanoparticles with favorable properties for biomedical applications.The microstructural analysis revealed that the functionalized NCCs maintained their rod-shaped morphology and displayed hydrodynamic diameters suitable for evading the mononuclear phagocytic system while being large enough to target tumor tissues.Importantly,these nanoparticles possessed a negative surface charge,enhancing their stability and repelling potential aggregation.The binding specificity of FA-functionalized NCCs to folate receptor-positive cancer cells was demonstrated through various assays.The free folic acid inhibition assay showed approximately 30%decrease in the binding of functionalized NCCs in the presence of just 5 mM free FA,confirming their selectivity for folate receptor-positive cells.Confocal microscopy further validated this specificity,as only cancer cells displayed significant binding of functionalized NCCs.Crucially,biocompatibility tests revealed that both NCCs and FA-functionalized NCCs had minimal effects on red blood cells,and they did not induce erythrocyte aggregation.Furthermore,cell viability assays demonstrated functionalized NCCs have selective cytotoxicity against colorectal cancer cells HT-29 and SW-620(68%–88%cell viability)while sparing noncancerous colon cells CCD-18Co(81%–97%cell viability).In summary,FA-functionalized NCCs exhibit promising characteristics for targeted drug delivery in cancer therapy.Their biocompatibility,stability,and selective cytotoxicity make them an attractive option for delivering therapeutic agents to folate receptor-positive cancer cells,potentially improving the effectiveness of cancer treatments while minimizing harm to healthy tissues.

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.

Prevention of neural tube defects with folic acid: The Chinese experience

Neural tube defects(NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28 th day of conception. Anencephaly and spina bifida are the two major subtypes. Fetuses with anencephaly are often stillborn or electively aborted due to prenatal diagnosis, or they die shortly after birth. Most infants with spina bifida are live-born and, with proper surgical treatment, can survive into adulthood. However, these children often have life-long physical disabilities. China has one of the highest prevalence of NTDs in the world. Inadequate dietary folate intake is believed to be the main cause of the cluster. Unlike many other countries that use staple fortification with folic acid as the public health strategy to prevent NTDs, the Chinese government provides all women who have a rural household registration and who plan to become pregnant with folic acid supplements, free of charge, through a nation-wide program started in 2009. Two to three years after the initiation of the program, the folic acid supplementation rate increased to 85% in the areas of the highest NTD prevalence. The mean plasma folate level of women during early and mid-pregnancy doubled the level before the program was introduced. However, most women began taking folic acid supplements when they knew that they were pregnant. This is too late for the protection of the embryonic neural tube. In a postprogram survey of the women who reported folic acid supplementation, less than a quarter of the women began taking supplements prior to pregnancy, indicating that the remaining three quarters of the fetuses remained unprotected during the time of neural tube formation. Therefore, staple food fortification with folic acid should be considered as a priority in the prevention of NTDs.

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.

Preparation and functional characterization of tumor-targeted folic acid-chitosan conjugated nanoparticles loaded with mitoxantrone

Folic acid conjugated chitosan was prepared by cross-linking reaction with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(EDC), and then used as a template to prepare folic acid-chitosan(FA-CS) conjugated nanoparticles and load mitoxantrone nanoparticles(FA-CSNP/MTX). Drug dissolution testing, CCK-8 method, and confocal microscopy were used to detect their controlled-release capability in different situations and the specific uptake by HONE1 cells. The experimental results show that the nanoparticles have uniform size distribution of 48-58 nm. The highest encapsulation rate of the particles on mitoxantrone hydrochloride(MTX) is(77.5±1.9)%, and the drug loading efficiency is(18.4±0.4)%. The sustained release effect, cell growth inhibition activity and targeting effect of the FA-CS/MTX nanoparticles are good in artificial gastric fluid and intestinal fluid. It is demonstrated that the FA-CSNP system is a potentially useful system for the targeted delivery of anticancer drug MTX.

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.

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.

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.

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.

The association between folic acid supplementation,maternal folate during pregnancy and intelligence development in infants:a prospective cohort study

Objective The study aimed to explore the association between folic acid supplementation,maternal nutritional levels during pregnancy and intelligence development of infants.Method This was a prospective cohort study,mothers and their offspring in Jurong Maternal and Child Health Hospital were followed up through pregnancy up to 1 year.The basic information of pregnant women was obtained through questionnaire survey,including pregnancy lifestyle,marital status,vitamin and mineral supplements during pregnancy.Blood samples of pregnant women were collected on admission,serum folate,vitamin B12 and homocysteine concentrations were determined.Maternal postpartum colostrum was collected and the concentrations of folate and vitamin B12 in colostrum were determined.Pregnant women(n=478)and their corresponding infants were followed up and the Developmental Screen Test scores were recorded at 1,3,6,8 and 12 months of age.Results Compared with the normal group,infants in the low serum folate group had a score of 0.12 points lower in the intellectual energy zone(95%CI:-0.23–-0.01,P=0.04),and infants with the high homocysteine level scored 1.30 points lower than the lower-level group(95%CI:-2.52–-0.08,P=0.04).In the colostrum low-vitamin B12 level group,infants scored 0.10 points lower(95%CI:-1.84–-0.02,P=0.02)in the social adaptation zone compared to the normal group.Conclusion In conclusion,folic acid supplementation in the pre-pregnancy supplementation group and the post-pregnancy supplementation group may be not associated with infant mental development.In addition,maternal folate and homocysteine may be related to the intellectual development of infants.The level of vitamin B_(12)in colostrum may be associated with infants’social adaptive capacity.This result may be caused by individual differences in folate and homocysteine metabolism in pregnant women.

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.

Gestational Diabetes Mellitus and Folic Acid Supplementation in Pregnant Women: A Systematic Review

Background: Gestational diabetes mellitus (GDM) is a common pregnancy disorder screened for between the 24th and 28th weeks of gestation using oral glucose tolerance test. GDM has maternal and fetal health implications. Objective: To assess the relation between folic acid supplementation in pregnant women and the risk of developing GDM. Search Strategy: The search employed topic-based strategies designed for each database in June 2020. Databases searched were Pubmed, Cochrane Library, Embase and Lebanese American University online database. Selection Criteria: Studies eligible were those targeting the association of GDM development and folic acid supplementation, including pregnant women who have developed GDM and pregnant women who were on folic acid supplementation and developed GDM. Both interventional and observational studies were included. Data Collection and Analysis: Two reviewers extracted the data independently. A third reviewer checked the data for consistency and clarity. Data extracted included the sample characteristics, sample size and outcomes. Cohen’s κ was used to assess agreement between reviewers. All tools and processes were piloted prior to use. Risk of bias was assessed using the Newcastle-Ottawa Scale. Data was presented in a tabulated form. Main Results: Six studies showed a proportional relation between folic acid intake and GDM, two reported a protective effect, and one cohort found no association. Conclusion: The inconsistent results made the formulation of a definitive conclusion difficult. Hence, larger studies are needed.

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.

Folic Acid-Polyethyleneimine-Ethosome as a Potential Tumor Targeting Carrier: Preparation, Characterization and in vitro Evaluation

A novel composite carrier of folic acid(FA)-polyethyleneimine(PEI)-ethosome(Eth)(FA-PEI-Eth)was developed for the treatment of cancers through loading and targeting delivery of multidrug(including gene and other drugs)into cancer cells.Physical and chemical property tests were done to prove the grafting of the composite.Gel retardation test was done to determine the optimal ratio of DNA@PEI complex,and cytocompatibility tests and tumor cell uptake tests were done to evaluate the efficiency of the composite.The results demonstrated that the FA-PEI-Eth could effectively deliver a gene and other drugs into tumor cells simultaneously,and suggested that this composite would be a promising carrier in tumor-targeted therapy applications.

Folic Acid Supplementation in Chinese Periconceptional Population:Results from the SPCC Study

Objective To determine the prevalence and determinants of folic acid(FA)supplementation in Chinese couples planning for pregnancy and in women during early pregnancy.Methods This was a cross-sectional study based on the Shanghai PreConception Cohort(SPCC)study.Data on FA supplementation and socio-demographic features were collected using questionnaires.Couples visiting clinics for pre-pregnancy examination and pregnant women at<14 gestational weeks were recruited in Shanghai,China,between March 2016 and September 2018.Results Among the pregnancy planners,42.4%(4,710/11,099)women and 17.1%(1,377/8,045)men used FA supplements,while 93.4%(14,585/15,615)of the pregnant women used FA supplements.FA supplement use was higher in female pregnancy planners who were older(RR:1.13,95%CI:1.08–1.18),had higher education(RR:1.71,95%CI:1.53–1.92),and were residing in urban districts(RR:1.06,95%CI:1.01–1.11)of FA supplementation;female pregnancy planners with alcohol consumption(RR:0.95,95%CI:0.90–0.99)had lower odds of FA supplementation.In early pregnancy,women with higher educational level(RR:1.04,95%CI:1.03–1.06),who underwent pre-pregnancy examination(RR:1.02,95%CI:1.01–1.03)had higher odds of using an FA supplement;older aged(RR:0.99,95%CI:0.98–0.99),and multigravida(RR:0.97,95%CI:0.96–0.98)had lower odds of FA supplementation.Conclusion Although the majority of pregnant women took FA supplements,more than half of the women planning for pregnancy did not.Urgent strategies are needed to improve pre-conception FA supplementation.

Effect of a 12-Week Dietary Intervention with Folic Acid or Folate-Enhanced Foods on Folate Status in Healthy Egyptian Women

The Egyptian government introduced wheat-flour fortification with iron and folic acid to reduce the incidence of neural tube defects, but suspended it for technical reasons. We previously developed novel legume foods with enhanced folate content. In this study, we investigated the efficacy of 12-week intervention with folate-enhanced foods versus folic acid supplement in improving folate status in Egyptian women. A randomized, parallel intervention trial with two active groups (n = 19, n = 18) and one blinded control group (n = 20) was executed over 12 weeks. Volunteers received either germinated legume foods and orange juice (≈250 μg/d folate) or folic acid supplement (500 μg/d) or apple juice (0 μg/d folate). Folate status was assessed by erythrocyte and plasma folate and total homocysteine (tHcy) at day 0, and after 8 and 12 weeks of intervention. After 12 weeks, mean plasma folate increased by 14 (P < 0.0001) and 12 (P < 0.0001) nmoL in the folic acid and food group, respectively. Erythrocyte folate concentration increased in the folic acid group from 614 to 912 (P < 0.0001) and in the food group from 631 to 914 nmoL (P < 0.0001). After 12 weeks, 90% of subjects in the folic acid group and 70% in the food group had erythrocyte folate concentrations exceeding 906 nmol/L. tHcy concentration was decreased by 20% (P = 0.007) and 18% (P = 0.006) in the folic acid and food group, respectively, but remained unchanged in the control group during intervention. Folate-enhanced foods effectively improve folate status in women of reproductive age. These foods could be used as a complement to folic acid fortification.

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。

The interaction mechanism between zein and folic acid in alkaline aqueous solutions:an experimental and molecular simulation study

Objectives:Folic acid is a vitamin that is not highly soluble in water and is sensitive to the environment.Therefore,it is important to find suitable carriers.This study aimed to exemplify the interaction of folic acid with zein in alkaline aqueous solutions and shed light on how zein can be used as a carrier for folic acid.Materials and Methods:Zein and folic acid were separately dissolved in NaOH solutions with a PH of 11.5.Zein solution and folic acid solution were combined in specific ratios.Various methods including multi-spectroscopy,dynamic light scattering,and electron microscopy combining with molecular dynamics simulations were used to study the interaction mechanism between zein and folic acid in alkaline aqueous solutions.Results:Fluorescence spectroscopy showed that the quenching of zein by folic acid was mainly static,and the main driving force behind this interaction was van der Waals forces and hydrogen bonds.The formation of zein–folic acid complexes was confirmed by ultraviolet–visible spectroscopy,Fourier transform infrared spectroscopy,and circular dichroism spectroscopy.The results also showed that the structure of zein changed when it interacted with folic acid.Dynamic light scattering analysis revealed that the addition of folic acid caused proteins to aggregate.The aggregates of the complexes had an irregular shape and were large,as observed by scanning electron microscopy and transmission electron microscopy.Molecular simulation was used to further investigate the interaction mechanisms.According to these findings,the folic acid molecule interacted with zein in a shallow recess near the protein surface.The dominant forces at play in the zein–folic acid interaction were van der Waals forces and electrostatic forces,including hydrogen bonding.Conclusion:The zein alkali-soluble system is very suitable for folic acid delivery.