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-functiona...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.展开更多
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 knowledg...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.展开更多
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 t...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.展开更多
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 ac...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.展开更多
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...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.展开更多
AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions. METHODS: Thirty-eight patients, with premalignant gastric lesions incl...AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions. METHODS: Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia (IM) and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1 000 mg thrice daily for 3 mo. All patients underwent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy. Folate concentrations in gastric mucosa were measured with chemiluminescent enzyme immunoassay. Epithelial apoptosis and the expression of Bcl-2 and p53 protein in gastric mucosa were detected with flow cytometric assay. RESULTS: The mean of folate concentration in gastric mucosa was 9.03±3.37 μg/g wet wt in the folic acid treatment group, which was significantly higher than 6.83±3.02 μg/g wet wt in the control group. Both the epithelial apoptosis rate and the tumor suppressor p53 expression in gastric mucosa significantly increased after folic acid treatment. In contrast, the expression of Bcl-2 oncogene protein decreased after folic acid therapy. CONCLUSION: These data indicate that folic acid may play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in the patients with premalignant lesions.展开更多
After peripheral nerve injury, intraperitoneal injection of folic acid improves axon quantity, increases axon density and improves electromyography results. However, the mechanisms for this remain unclear. This study ...After peripheral nerve injury, intraperitoneal injection of folic acid improves axon quantity, increases axon density and improves electromyography results. However, the mechanisms for this remain unclear. This study explored whether folic acid promotes peripheral nerve injury repair by affecting Schwann cell function. Primary Schwann cells were obtained from rats by in vitro separation and culture. Cell proliferation, assayed using the Cell Counting Kit-8 assay, was higher in cells cultured for 72 hours with 100 mg/L folic acid compared with the control group. Cell proliferation was also higher in the 50, 100, 150, and 200 mg/L folic acid groups compared with the control group after culture for 96 hours. Proliferation was markedly higher in the 100 mg/L folic acid group compared with the 50 mg/L folic acid group and the 40 ng/L nerve growth factor group. In Transwell assays, the number of migrated Schwann cells dramatically increased after culture with 100 and 150 mg/L folic acid compared with the control group. In nerve growth factor enzyme-linked immunosorbent assays, treatment of Schwa nn cell cultures with 50, 100, and 150 mg/L folic acid increased levels of nerve growth factor in the culture medium compared with the control group at 3 days. The nerve growth factor concentration of Schwann cell cultures treated with 100 mg/L folic acid group was remarkably higher than that in the 50 and 150 mg/L folic acid groups at 3 days. Nerve growth factor concentration in the 10, 50, and 100 mg/L folic acid groups was higher than that in the control group at 7 days. The nerve growth factor concentration in the 50 mg/L folic acid group was remarkably higher than that in the 10 and 100 mg/L folic acid groups at 7 days. In vivo, 80 μg/kg folic acid was intraperitoneally administrated for 7 consecutive days after sciatic nerve injury. Immunohistochemical staining showed that the number of Schwann cells in the folic acid group was greater than that in the control group. We suggest that folic acid may play a role in improving the repair of peripheral nerve injury by promoting the proliferation and migration of Schwann cells and the secretion of nerve growth factors.展开更多
AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenom...AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps. METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years. RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonicadenomas or advanced adenomas responded better to folic acid supplementation. CONCLUSION: High dose folic acid supplementation is associated with a signif icant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia.展开更多
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) conjugate...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.展开更多
This study evaluated the effects of palm fat powder(PFP) and coated folic acid(CFA) on growth performance, ruminal fermentation, nutrient digestibility, microbial enzyme activity, microflora, hepatic lipid content and...This study evaluated the effects of palm fat powder(PFP) and coated folic acid(CFA) on growth performance, ruminal fermentation, nutrient digestibility, microbial enzyme activity, microflora, hepatic lipid content and gene expression in dairy bulls. Forty-eight Chinese Holstein bulls((362±12.4) days of age and(483±27.1) kg of body weight(BW)) were assigned to four groups in a completely randomized design with a 2×2 factorial arrangements. Supplemental PFP(0 or 30 g PFP kg-1 dietary dry matter(DM)) and CFA(0 or 120 mg FA d-1 as CFA) were mixed into the top one-third of a total mixed ration. The study included a 20-day adaptation period and followed by a 90-day collection period. The lower(P<0.01) feed conversion ratio with PFP or CFA addition resulted from the constant DM intake and the higher(P<0.05) average daily gain. The higher(P<0.05) ruminal p H, ether extract digestibility, microbial α-amylase activity, Butyrivibrio fibrisolvens copy, and expression of peroxisome-proliferator-activated receptor α(PPARα) and carnitine palmitoyl transferase-1(CPT1), and lower ruminal total volatile fatty acids(VFA) concentration, acetate to propionate ratio, neutral detergent fibre(NDF) digestibility, copies of total protozoa and Ruminococcus flavefaciens, and expression of sterol regulatory element binding protein-1(SREBP1) and acetyl-coenzyme A carboxylase α(ACACA) were observed for PFP addition. Supplementation with CFA increased(P<0.05) ruminal total VFA concentration, acetate to propionate ratio, digestibility of DM, organic matter, crude protein and NDF, activity of cellobiase, pectinase and α-amylase, copies of selected microbial except for total protozoa, as well as expression of PPARα, but decreased(P<0.05) ruminal p H, and expression of SREBP1 and ACACA. The PFP×CFA interaction(P<0.05) was observed for ammonia N, hepatic TG content, and m RNA expression of CPT1 and FAS. There had no significant difference in hepatic TG content when CFA was supplemented in the diet without PFP addition, the lower(P=0.001) hepatic TG content was observed when CFA was supplemented in the diet with PFP addition. The higher(P<0.05) m RNA expression of CPT1, and the lower(P<0.05) m RNA expression of FAS and ammonia N concentration were observed when CFA was supplemented in diet either without or with PFP addition. The results indicated that supplementation of CFA in PFP diet was more effective on increasing hepatic CPT1 expression, and decreasing ammonia N, hepatic TG content and FAS expression than in diet without PFP. Supplementation with PFP or CFA improved growth performance of dairy bulls by promoting nutrient utilization, microbial enzyme activity, microflora, and hepatic gene expression.展开更多
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 contribu...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.展开更多
To investigate the effects of dietary supplementation with folic acid on growth performance, hepatic protein metabolism and serum biochemical indices of early-weaned intrauterine growth retardation (IUGR) piglets, 2...To investigate the effects of dietary supplementation with folic acid on growth performance, hepatic protein metabolism and serum biochemical indices of early-weaned intrauterine growth retardation (IUGR) piglets, 24 male (Durocx (LandracexYorkshire)) weaned (14-d-old) IUGR piglets were randomly divided into 3 treatments with 8 replicates of 1 piglet per replicate. The piglets in each treatment were fed basal diet supplementation with either 0 (control), 5 and 10 mg kg^-1 folic acid. The trial lasted for 21 d. Dietary folic acid supplementation reduced average daily feed intake (ADFI) (P〈0.05). In addition, the average daily gain (ADG) in 10 mg kg^-1 folic acid group was significantly decreased (P〈0.01) and the ratio of feed:gain (F/G) increased slightly (P〉0.05). Serum folic acid concentration increased (P〈0.01) with increasing folic acid inclusion, however, serum homocysteine concentration decreased significantly (P〈0.01). Enhanced serum urine nitrogen (SUN) and diminished serum total protein (TP) as well as liver TP content were observed in 10 mg kg^-1 folic acid group (/'〈0.05). Furthermore, the relative mRNA expressions of insulin-like growth factor 1 (IGF-1) and mammalian target of rapamycin (m-TOR) in liver were respectively tended to reduce (P=0.06) and significantly downregulated (P〈0.05) in 10 mg kg1 group, in compared with 5 mg kg1 group. However, when compared with control group, folic acid supplementation had no significant effect on the mRNA abundance of IGF- 1 and m-TOR. The results indicated that supplementation with 10 mg kg-I folic acid impaired growth performance and hepatic protein metabolism of early-weaned IUGR piglets while 5 mg kg-~ folic acid enriched diet exerted limited positive effects.展开更多
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 fe...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.展开更多
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 o...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.展开更多
Homocysteine (Hcy) is an intermediate product of methionine formed by its demethylation. Hcy can be metabolized via remethylation to methionine or transsulfuration to cysteine which is dependent on several enzymes and...Homocysteine (Hcy) is an intermediate product of methionine formed by its demethylation. Hcy can be metabolized via remethylation to methionine or transsulfuration to cysteine which is dependent on several enzymes and cofactors. It is deleterious to blood vessel including glomeruli. Kidney is a major organ that metabolizes Hcy. More than 80% of patients with chronic renal disease develop hyperhomocysteinemia (hHcy). Accessible data of plasma Hcy in nephritic syndrome (NS) patients are controversial with increased, decreased and unchanged values reported. In renal patients, plasma Hcy concentration can be reduced by administration of folic acid. Absolute or relative deficiencies of folate, vitamin B6, or vitamin B12 may also play a role. Therefore, plasma Hcy, folic acid, vitamin B6, and vitamin B12 in children with acute glomerulonephritis (AGN) were accessed in this study. Hcy, folic acid vitamin B12, B6 and renal function such as blood urea nitrogen (BUN), creatinine (Cr) were analyzed 12 pediatric patients with AGN and 15 age and sex matched healthy children served as controls. The results revealed that a?significant increase in plasma Hcy in children with acute AGN when compared with controls. For simple regression analysis, Hcy was positively correlated with BUN, Cr, ferritin and uric acid but negatively correlated with serum glutathione. This research indicated hHcy suggests enhanced risks for inflammation and endothelial injury,?which lead to kidney disease. Folic acid has also been shown to improve endothelial function, suggesting an alternative explanation for the effect of folic acid on endothelial function. Careful considerations of not only dietary measures are necessary but also folate and vitamin B supplementation for reducing hHcy in AGN need to be investigated.展开更多
Objective To discuss the relationship of cereb ral infarction with hyperhomocyste inemia and the relationship between hyperhomo-cysteinemia and folic acid and Vitam ine B 12 .Method We measured the concentrations of h...Objective To discuss the relationship of cereb ral infarction with hyperhomocyste inemia and the relationship between hyperhomo-cysteinemia and folic acid and Vitam ine B 12 .Method We measured the concentrations of homocysteine with FIPA(fluorescence polarization im-munoassay)and Vitamin B 12 and folic acid with chemiluminescen t competitive immunoassay in 40cere bral infarction patients and 30heal thy con-trols.Results The concentration of homocysteine i n study group was higher than the cont rols’ (P <0.01).Serum folic acid level in study grou p was lower than that in control group(P <0.05).There is negative correlation betw een plasma homocysteine and serum fo lic acid(P <0.05).Conclusions Hyperhomocysteinemia is an indepen dent risk factor of atherosclerotic cerebral infarction.One reason of i ncreased level of homocysteine in blood is that the deficiency of cofactors of enzymes involved in metabo lism process.展开更多
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 r...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.展开更多
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-methy...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.展开更多
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,m...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.展开更多
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 nanoparti...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.展开更多
基金funded by Ministry of Higher Education(MOHE),Malaysia-Prototype Development Research Grant Scheme,Grant Number PRGS/1/2020/STG05/UM/02/1.
文摘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.
文摘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.
文摘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.
基金Supported by the Natural Science Foundation of Gansu Province(No.21JR7RA361).
文摘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.
文摘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.
基金Supported by the Science and Technology Foundation of the State Railway Ministry, No. J98Z034
文摘AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions. METHODS: Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia (IM) and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1 000 mg thrice daily for 3 mo. All patients underwent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy. Folate concentrations in gastric mucosa were measured with chemiluminescent enzyme immunoassay. Epithelial apoptosis and the expression of Bcl-2 and p53 protein in gastric mucosa were detected with flow cytometric assay. RESULTS: The mean of folate concentration in gastric mucosa was 9.03±3.37 μg/g wet wt in the folic acid treatment group, which was significantly higher than 6.83±3.02 μg/g wet wt in the control group. Both the epithelial apoptosis rate and the tumor suppressor p53 expression in gastric mucosa significantly increased after folic acid treatment. In contrast, the expression of Bcl-2 oncogene protein decreased after folic acid therapy. CONCLUSION: These data indicate that folic acid may play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in the patients with premalignant lesions.
基金supported by the High Levels of Health Technical Personnel in Beijing City Health System of China,No.2013-3-050(to JZY)
文摘After peripheral nerve injury, intraperitoneal injection of folic acid improves axon quantity, increases axon density and improves electromyography results. However, the mechanisms for this remain unclear. This study explored whether folic acid promotes peripheral nerve injury repair by affecting Schwann cell function. Primary Schwann cells were obtained from rats by in vitro separation and culture. Cell proliferation, assayed using the Cell Counting Kit-8 assay, was higher in cells cultured for 72 hours with 100 mg/L folic acid compared with the control group. Cell proliferation was also higher in the 50, 100, 150, and 200 mg/L folic acid groups compared with the control group after culture for 96 hours. Proliferation was markedly higher in the 100 mg/L folic acid group compared with the 50 mg/L folic acid group and the 40 ng/L nerve growth factor group. In Transwell assays, the number of migrated Schwann cells dramatically increased after culture with 100 and 150 mg/L folic acid compared with the control group. In nerve growth factor enzyme-linked immunosorbent assays, treatment of Schwa nn cell cultures with 50, 100, and 150 mg/L folic acid increased levels of nerve growth factor in the culture medium compared with the control group at 3 days. The nerve growth factor concentration of Schwann cell cultures treated with 100 mg/L folic acid group was remarkably higher than that in the 50 and 150 mg/L folic acid groups at 3 days. Nerve growth factor concentration in the 10, 50, and 100 mg/L folic acid groups was higher than that in the control group at 7 days. The nerve growth factor concentration in the 50 mg/L folic acid group was remarkably higher than that in the 10 and 100 mg/L folic acid groups at 7 days. In vivo, 80 μg/kg folic acid was intraperitoneally administrated for 7 consecutive days after sciatic nerve injury. Immunohistochemical staining showed that the number of Schwann cells in the folic acid group was greater than that in the control group. We suggest that folic acid may play a role in improving the repair of peripheral nerve injury by promoting the proliferation and migration of Schwann cells and the secretion of nerve growth factors.
文摘AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps. METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years. RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonicadenomas or advanced adenomas responded better to folic acid supplementation. CONCLUSION: High dose folic acid supplementation is associated with a signif icant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia.
基金Projects(31201074,81371013) supported by the National Natural Science Foundation of ChinaProject(2011105102016) supported by the Key Program of Medical Health of Dongguan City,Guangdong Province,ChinaProject(2011108102026) supported by Dongguan Universities Program,China
文摘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.
基金supported by a grant from the Natural Science Funding Projects of Shanxi Province,China(201801D121241)the Animal Husbandry Dominant Key Discipline Construction Project in“1331 Project”of Shanxi Province,China。
文摘This study evaluated the effects of palm fat powder(PFP) and coated folic acid(CFA) on growth performance, ruminal fermentation, nutrient digestibility, microbial enzyme activity, microflora, hepatic lipid content and gene expression in dairy bulls. Forty-eight Chinese Holstein bulls((362±12.4) days of age and(483±27.1) kg of body weight(BW)) were assigned to four groups in a completely randomized design with a 2×2 factorial arrangements. Supplemental PFP(0 or 30 g PFP kg-1 dietary dry matter(DM)) and CFA(0 or 120 mg FA d-1 as CFA) were mixed into the top one-third of a total mixed ration. The study included a 20-day adaptation period and followed by a 90-day collection period. The lower(P<0.01) feed conversion ratio with PFP or CFA addition resulted from the constant DM intake and the higher(P<0.05) average daily gain. The higher(P<0.05) ruminal p H, ether extract digestibility, microbial α-amylase activity, Butyrivibrio fibrisolvens copy, and expression of peroxisome-proliferator-activated receptor α(PPARα) and carnitine palmitoyl transferase-1(CPT1), and lower ruminal total volatile fatty acids(VFA) concentration, acetate to propionate ratio, neutral detergent fibre(NDF) digestibility, copies of total protozoa and Ruminococcus flavefaciens, and expression of sterol regulatory element binding protein-1(SREBP1) and acetyl-coenzyme A carboxylase α(ACACA) were observed for PFP addition. Supplementation with CFA increased(P<0.05) ruminal total VFA concentration, acetate to propionate ratio, digestibility of DM, organic matter, crude protein and NDF, activity of cellobiase, pectinase and α-amylase, copies of selected microbial except for total protozoa, as well as expression of PPARα, but decreased(P<0.05) ruminal p H, and expression of SREBP1 and ACACA. The PFP×CFA interaction(P<0.05) was observed for ammonia N, hepatic TG content, and m RNA expression of CPT1 and FAS. There had no significant difference in hepatic TG content when CFA was supplemented in the diet without PFP addition, the lower(P=0.001) hepatic TG content was observed when CFA was supplemented in the diet with PFP addition. The higher(P<0.05) m RNA expression of CPT1, and the lower(P<0.05) m RNA expression of FAS and ammonia N concentration were observed when CFA was supplemented in diet either without or with PFP addition. The results indicated that supplementation of CFA in PFP diet was more effective on increasing hepatic CPT1 expression, and decreasing ammonia N, hepatic TG content and FAS expression than in diet without PFP. Supplementation with PFP or CFA improved growth performance of dairy bulls by promoting nutrient utilization, microbial enzyme activity, microflora, and hepatic gene expression.
基金supported by the Natural Science Foundation of China (No. 31272464)the Program for New Century Excellent Talents (NCET-12-0476)the Program for Shaanxi Science & Technology (2014 K01-18-02, 2015NY149, 2015KTCQ02-19)
文摘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.
基金supported by the earmarked fund for China Agriculture Research System (CARS-36)the Program for Changjiang Scholars and Innovative Research Team in University,Ministry of Education of China (IRT0555)
文摘To investigate the effects of dietary supplementation with folic acid on growth performance, hepatic protein metabolism and serum biochemical indices of early-weaned intrauterine growth retardation (IUGR) piglets, 24 male (Durocx (LandracexYorkshire)) weaned (14-d-old) IUGR piglets were randomly divided into 3 treatments with 8 replicates of 1 piglet per replicate. The piglets in each treatment were fed basal diet supplementation with either 0 (control), 5 and 10 mg kg^-1 folic acid. The trial lasted for 21 d. Dietary folic acid supplementation reduced average daily feed intake (ADFI) (P〈0.05). In addition, the average daily gain (ADG) in 10 mg kg^-1 folic acid group was significantly decreased (P〈0.01) and the ratio of feed:gain (F/G) increased slightly (P〉0.05). Serum folic acid concentration increased (P〈0.01) with increasing folic acid inclusion, however, serum homocysteine concentration decreased significantly (P〈0.01). Enhanced serum urine nitrogen (SUN) and diminished serum total protein (TP) as well as liver TP content were observed in 10 mg kg^-1 folic acid group (/'〈0.05). Furthermore, the relative mRNA expressions of insulin-like growth factor 1 (IGF-1) and mammalian target of rapamycin (m-TOR) in liver were respectively tended to reduce (P=0.06) and significantly downregulated (P〈0.05) in 10 mg kg1 group, in compared with 5 mg kg1 group. However, when compared with control group, folic acid supplementation had no significant effect on the mRNA abundance of IGF- 1 and m-TOR. The results indicated that supplementation with 10 mg kg-I folic acid impaired growth performance and hepatic protein metabolism of early-weaned IUGR piglets while 5 mg kg-~ folic acid enriched diet exerted limited positive effects.
文摘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.
基金supported by Program of Changjiang Scholars and Innovative Research Team in University of China(IRT0555-5)
文摘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.
文摘Homocysteine (Hcy) is an intermediate product of methionine formed by its demethylation. Hcy can be metabolized via remethylation to methionine or transsulfuration to cysteine which is dependent on several enzymes and cofactors. It is deleterious to blood vessel including glomeruli. Kidney is a major organ that metabolizes Hcy. More than 80% of patients with chronic renal disease develop hyperhomocysteinemia (hHcy). Accessible data of plasma Hcy in nephritic syndrome (NS) patients are controversial with increased, decreased and unchanged values reported. In renal patients, plasma Hcy concentration can be reduced by administration of folic acid. Absolute or relative deficiencies of folate, vitamin B6, or vitamin B12 may also play a role. Therefore, plasma Hcy, folic acid, vitamin B6, and vitamin B12 in children with acute glomerulonephritis (AGN) were accessed in this study. Hcy, folic acid vitamin B12, B6 and renal function such as blood urea nitrogen (BUN), creatinine (Cr) were analyzed 12 pediatric patients with AGN and 15 age and sex matched healthy children served as controls. The results revealed that a?significant increase in plasma Hcy in children with acute AGN when compared with controls. For simple regression analysis, Hcy was positively correlated with BUN, Cr, ferritin and uric acid but negatively correlated with serum glutathione. This research indicated hHcy suggests enhanced risks for inflammation and endothelial injury,?which lead to kidney disease. Folic acid has also been shown to improve endothelial function, suggesting an alternative explanation for the effect of folic acid on endothelial function. Careful considerations of not only dietary measures are necessary but also folate and vitamin B supplementation for reducing hHcy in AGN need to be investigated.
文摘Objective To discuss the relationship of cereb ral infarction with hyperhomocyste inemia and the relationship between hyperhomo-cysteinemia and folic acid and Vitam ine B 12 .Method We measured the concentrations of homocysteine with FIPA(fluorescence polarization im-munoassay)and Vitamin B 12 and folic acid with chemiluminescen t competitive immunoassay in 40cere bral infarction patients and 30heal thy con-trols.Results The concentration of homocysteine i n study group was higher than the cont rols’ (P <0.01).Serum folic acid level in study grou p was lower than that in control group(P <0.05).There is negative correlation betw een plasma homocysteine and serum fo lic acid(P <0.05).Conclusions Hyperhomocysteinemia is an indepen dent risk factor of atherosclerotic cerebral infarction.One reason of i ncreased level of homocysteine in blood is that the deficiency of cofactors of enzymes involved in metabo lism process.
文摘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.
文摘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.
基金the Nutrition Research Foundation of Chinese Nutrition Society---Research Fund of Feihe Physical Nutrition and Health(Grant No:CNS-Feihe2018B01)Nanjing medical science and technology development fund(Grant No:YKK19127).
文摘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.
基金the Post-graduate Office of Guilan University(A-384579)for supporting
文摘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.