Objective This study aimed to evaluate the associations of serum folate and/or vitamin B12 concentrations with obesity among Chinese children and adolescents.Methods A cross-sectional study was conducted including 3,0...Objective This study aimed to evaluate the associations of serum folate and/or vitamin B12 concentrations with obesity among Chinese children and adolescents.Methods A cross-sectional study was conducted including 3,079 Chinese children and adolescents,aged 6 to 17 years,from Jiangsu,China.Anthropometric indices,such as,children's body mass index(BMI),BMI z-scores,waist circumference,and waist-to-height ratio were utilized.Multivariable linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B12 levels with anthropometric indices and odds of obesity.Results We observed that serum vitamin B12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity[odds ratio(OR)=0.68;95%confidence interval(CI)=0.59,0.78]and abdominal obesity(OR=0.68;95%CI=0.60,0.77).When compared to participants with both serum vitamin levels in the two middle quartiles,those with both serum folate and vitamin B12 levels in the highest quartile were less prone to general(OR=0.31,95%CI=0.19,0.50)or abdominal obesity(OR=0.46,95%CI=0.31,0.67).Conversely,participants with vitamin B12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity(OR=2.06,95%CI=1.09,3.91).Conclusion Higher serum vitamin B12 concentrations,but not serum folate concentrations,were associated with lower odds of childhood obesity.Children and adolescents with high levels of vitamin B12 and folate were less likely to be obese.展开更多
Objective Circular RNAs(circRNAs)participate in several important pathological processes and have been used in the diagnosis and treatment of various diseases.This study aimed to investigate the role of circRNAs in ne...Objective Circular RNAs(circRNAs)participate in several important pathological processes and have been used in the diagnosis and treatment of various diseases.This study aimed to investigate the role of circRNAs in neural tube defects(NTDs).Method We characterized circRNA-associated competitive endogenous RNA(ceRNA)networks in brain tissue of low folate-induced NTDs mouse at embryonic day 13.5 by high-throughput sequencing.The expression levels of Circzfp644,miR-20-5p and Gas7 were detected by RT-PCR.Gas7 and Circzfp644functions were determined by miRNA-mimics and inhibitors in mouse teratocarcinoma cells(F9 cells),and luciferase gene reporter assay was assessed in the F9 cells.In addition,the expression levels of Circzfp644,miR-20-5p and Gas7 were determined by Nanostring in human NTDs tissues.Results We detected 57 circRNA transcripts,16 miRNAs,and 148 mRNAs that were significantly dysregulated in NTDs brain tissues compared with their expression levels in control(normal)tissues.Circzfp644 shared miRNA response elements with the growth arrest specific 7(Gas7)gene and competitively bound with miR-20-5p to increase the expression of Gas7.Downregulation of Circzfp644and Gas7 and upregulation of miR-20-5p were found in human NTD tissue.Conclusion This study provides new perspectives on the role of circRNAs in nervous system development and the pathogenesis of NTDs.展开更多
Objective This study aimed to investigate the effects of N,N-dimethylglycine(DMG) on the concentration and metabolism of plasma homocysteine(pHcy) in folate-sufficient and folate-deficient rats.Methods In this study, ...Objective This study aimed to investigate the effects of N,N-dimethylglycine(DMG) on the concentration and metabolism of plasma homocysteine(pHcy) in folate-sufficient and folate-deficient rats.Methods In this study, 0.1% DMG was supplemented in 20% casein diets that were either folatesufficient(20 C) or folate-deficient(20 CFD). Blood and liver of rats were subjected to assays of Hcy and its metabolites. Hcy and its related metabolite concentrations were determined using a liquid chromatographic system.Results Folate deprivation significantly increased pHcy concentration in rats fed 20 C diet(from 14.19 ±0.39 μmol/L to 28.49 ± 0.50 μmol/L;P < 0.05). When supplemented with DMG, pHcy concentration was significantly decreased(12.23 ± 0.18 μmol/L) in rats fed 20 C diet but significantly increased(31.56 ±0.59 μmol/L) in rats fed 20 CFD. The hepatic methionine synthase activity in the 20 CFD group was significantly lower than that in the 20 C group;enzyme activity was unaffected by DMG supplementation regardless of folate sufficiency. The activity of hepatic cystathionine β-synthase(CBS) in the 20 CFD group was decreased but not in the 20 C group;DMG supplementation enhanced hepatic CBS activity in both groups, in which the effect was significant in the 20 C group but not in the other group.Conclusion DMG supplementation exhibited hypohomocysteinemic effects under folate-sufficient conditions. By contrast, the combination of folate deficiency and DMG supplementation has deleterious effect on pHcy concentration.展开更多
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 ...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.展开更多
Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme for the critical process of one-carbon circulation,which convert5,10-methylenetetrahydrofolate to5-methyltetrahydrofolate and participate in folate and homocys...Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme for the critical process of one-carbon circulation,which convert5,10-methylenetetrahydrofolate to5-methyltetrahydrofolate and participate in folate and homocysteine conversion correlated to methyl group supply.The enzyme activity decline depends on the gene polymorphism.MTHFR impacts on the methylation process which is related to psychiatric diseases.Studies have shown association between MTHFR gene polymorphisms and mental disorders,some of which stratified by folate and cobalamin levels.In this review,we will summarize the testimony on the relationship between methylation and MTHFR polymorphism as well as the implication on psychiatric diseases by MTHFR mutation.展开更多
Objective To review the association of methylene tetrahydrofolate reductase (MTHFR) C677T mutant with coronary artery disease, as well as to highlight the results of some of these studies and to emphasize the need to ...Objective To review the association of methylene tetrahydrofolate reductase (MTHFR) C677T mutant with coronary artery disease, as well as to highlight the results of some of these studies and to emphasize the need to focus on the genetic architecture of CAD. Data SourcesData used in this article is mainly from relevant articles obtained through Pubmed, OVID and Google Scholar published from 1980 to 2008. Major studies and trials in this period were taken into account to draw accurate conclusion on the relation of those mutations in MTHFR with homocysteinemia and CAD. ResultOur analysis shows that hyperhomocysteinemia, a risk factor for occlusive arterial diseases, can be caused by disruptions of homocysteine metabolism catalyzed by MFTHR. A common alanine to valine mutation in MTHFR may contribute to mild heperhomocysteinemia in CAD. Individuals with the homozygous mutant genotype had higher plasma homocysteine, particularly when plasma folate was below the median value. ConclusionThis MTHFR mutant in the setting of insufficient folate may be a risk factor of CAD and can be regarded as a model of genetic-environmental interaction in the development of CAD.展开更多
AIM: To evaluate the associations of serum folate levelwith development, invasiveness and patient survival of gastric cancer. METHODS: In this nested case-control study, patients with newly diagnosed gastric cancer un...AIM: To evaluate the associations of serum folate levelwith development, invasiveness and patient survival of gastric cancer. METHODS: In this nested case-control study, patients with newly diagnosed gastric cancer undergoing gastrectomy were enrolled, and patients receiving chemotherapy prior to surgery, with other concurrent malignancy, or of the aboriginal and alien populations were excluded. In total, 155 gastric cancer patients and 149 healthy controls were enrolled for determination of serum folate levels and their correlation with gastric cancer. Using the median value of serum folate computed among the overall population as the cutoff value, the associations between serum folate and gastric cancer in all cases and different age and gender subgroups were analyzed by multivariate logistic regression analysis. In the patient cohort of gastric cancer, receiver-operating characteristic analyses were performed to calculate the best cutoff values of serum folate, and the associations between serum folate levels and clinicopathological features were further analyzed by multivariate regression analysis. Survival analyses were conducted using the Cox proportional hazards model.RESULTS: The mean serum folate level was significantly lower in gastric cancer patients than that in controls(3.71 ± 0.30 ng/mL vs 8.00 ± 0.54 ng/mL, P < 0.01), and folate levels were consistently lower in gastric cancer patients regardless of age and gender(all P < 0.01). Using the median serum folate value as the cutoff value, low serum folate was significantly associated with gastric cancer risk in the whole population(OR = 19.77, 95%CI: 10.54-37.06, P < 0.001) and all strata(age < 60 years OR = 17.39, 95%CI: 7.28-41.54, age ≥ 60 years(OR = 21.67, 95%CI: 8.27-56.80), males(OR = 17.95, 95%CI: 7.93-40.62), and females(OR = 20.95, 95%CI: 7.66-57.31); all P < 0.001. In the patient cohort of gastric cancer, the respective cutoff values showed that low serum folate levels were significantly associated with serosal invasion(OR = 2.54, 95%CI: 1.23-5.23), lymphatic invasion(OR = 2.23, 95%CI: 1.17-4.26), and liver metastasis(OR =6.67, 95%CI: 1.28-34.91) of gastric cancer(all P < 0.05). Serum folate level below 1.90 ng/mL was associated with poor patient survival(HR = 1.84, 95%CI: 1.04-3.27, P < 0.05) in univariate analysis.CONCLUSION: Lower serum folate levels were significantly associated with gastric cancer development and invasive phenotypes. The role of folate depletion in gastric cancer invasion warrants further study.展开更多
Objective:Nanoparticles are becoming an important method of targeted drug delivery.To evaluate the importance of folate-conjugated human serum albumin(HSA)magnetic nanoparticles(Folate-CDDP/HSA MNP),we prepared drug-l...Objective:Nanoparticles are becoming an important method of targeted drug delivery.To evaluate the importance of folate-conjugated human serum albumin(HSA)magnetic nanoparticles(Folate-CDDP/HSA MNP),we prepared drug-loaded Folate-CDDP/HSA MNPs and characterized their features.Methods:First, folate was conjugated with HSA under the effect of a condensing agent,and the conjugating rate was evaluated by a colorimetric method using 2,4,6-trinitrobenzene sulfonic acid.Second,under N 2 gas,Fe 3 O 4 magnetic nanomaterials were prepared and characterized by using transmission electron microscopy(TEM),SEM-EDS and X-ray diffraction(XRD).Finally,Folate-CDDP/HSA MNP was prepared by using a solvent evaporation technique. TEM was used to observe particle morphology.The particle size and distribution of the prepared complexes were determined by a Laser particle size analyzer.Drug loading volume and drug release were investigated by a high performance liquid chromatography method(HPLC)in vitro.Results:We successfully prepared folate-conjugated HSA and its conjugating rate was 27.26μg/mg.Under TEM,Fe 3 O 4 magnetic nanoparticles were highly electron density and had an even size distribution in the range of 10-20 nm.It was confirmed by SEM-EDS and XRD that Fe 3 O 4 magnetic nanoparticles had been successfully prepared.Under TEM,drug-loaded magnetic nanoparticles were observed,which had a round shape,similar uniform size and smooth surface.Their average size was 79 nm which was determined by laser scattering,and they exhibited magnetic responsiveness.Encapsulation efficiency was 89.75%and effective drug loading was calculated to be 15.25%.The release results in vitro showed that the half release time(t1/ 2 )of cisplatin in cisplatin Solution and Folate-CDDP/HSA MNP was 65 min and 24 h respectively, which indicated that microspheres had an obvious effect of sustained-release.Conclusion:Folate-CDDP/HSA MNPs were prepared successfully.The preparation process and related characteristics data provided a foundation for further study,including the mechanism of the nanoparticles distribution in vivo and their intake by tumor cells.展开更多
Objective:To evaluate the potency of carboxymethyl chitosan-2,2' ethylenedioxy bisethylamine-folate(CMC-EDBE-FA) on tissue injury,antioxidant status and glutathione system in tissue mitochondria and serum against ...Objective:To evaluate the potency of carboxymethyl chitosan-2,2' ethylenedioxy bisethylamine-folate(CMC-EDBE-FA) on tissue injury,antioxidant status and glutathione system in tissue mitochondria and serum against nicotine-induced oxidative stress in mice.Methods: CMC-EDBE-FA was prepared on basis of carboxymethyl chitosan tagged with folic acid by covalently linkage through 2,2' ethylenedioxy bis-ethylamine.Animals were divided into four groups,i.e.,control,nicotine(1 mg/kg bw/day),CMC-EDBE-FA(1 mg/kg bw/day) and nicotine(1 mg/kg bw/day) and CMC-EDBE-FA(1 mg/kg bw/day) for 7 days.Levels of lipid peroxidation, oxidized glutathione level,antioxidant enzyme status and DNA damage were observed and compared.Results:The significantly increase of lipid peroxidation,oxidized glutathione levels and DNA damage was observed in nicotine treated group as compared with control group;those were significantly reduced in CMC-EDBE-FA supplemented group.Moreover,significantly reduced antioxidant status in nicotine treated group was effectively ameliorated by the supplementation of CMC-EDBE-FA.Only CMC-EDBE-FA treated groups showed no significant change as compared with control group;rather than it repairs the tissue damage of nicotine treated group.Conclusions:These findings suggest that CMC-EDBE-FA is non-toxic and ameliorates nicotine-induced toxicity.展开更多
Colorectal cancer (CRC) is one of the most common malignancies and causes of cancer deaths throughout the world. Endoscopy has its functional and finan-cial limitations; therefore,chemoprevention might be crucial in r...Colorectal cancer (CRC) is one of the most common malignancies and causes of cancer deaths throughout the world. Endoscopy has its functional and finan-cial limitations; therefore,chemoprevention might be crucial in reducing the incidence of CRC. Although a number of studies have demonstrated the potential chemopreventive effects of folate (or folic acid),many challenges still remain. The relationship between fo-late intake and CRC risk is a complex association that might depend on many factors including gender,age,alcohol consumption,and smoking,all of which inter-fere with folate metabolism. The supplementary dose of fiber,the length of time required to observe the effects,and confounding factors exposed during the trial might also influence these findings. Therefore,more evidence from clinical studies is needed regarding the mechanisms that underlie the actions of bioactive food components in minimizing the risk of CRC.展开更多
Folate deficiency and its association with cancer have been studied in the literature, but its clinical impact is still unknown. Folate deficiency and its result on gastric cancer is a mysterious part of oncology, wit...Folate deficiency and its association with cancer have been studied in the literature, but its clinical impact is still unknown. Folate deficiency and its result on gastric cancer is a mysterious part of oncology, with ongoing studies hopefully clarifying its impact on gastric cancer management. Lee et al studied folate deficiency and its impact on staging and clinical results. Here we try to contribute to the field by expressing our own thoughts about the paper.展开更多
Seven varieties of Tajik legumes and two Tajik snack type ready-to-eat (RTE) whole/split chickpeas were analyzed for iron in raw and cooked legumes and for naturally occurring folate content in cooked legumes. Iron wa...Seven varieties of Tajik legumes and two Tajik snack type ready-to-eat (RTE) whole/split chickpeas were analyzed for iron in raw and cooked legumes and for naturally occurring folate content in cooked legumes. Iron was measured according to AACC method 40 - 41B. Folate contents were determined by microbiological (Lactobacillus casei subsp. Rhamnosus ATCC 7469) and high-performance liquid chromatography analysis utilizing a tri-enzyme treatment (pro-tease, α-amylase and conjugase). Folate derivatives of tetrahydrofolate, 5-formyl-tetrahydrofolate and 5-methyl- -tetrahydrofolate were identified and quantified. Iron content for Tajik legumes ranged from 5.52 to 13.27 mg/100 g for raw;2.81 to 4.12 mg/100 g for cooked and 4.37 and 4.76 mg/100 g for RTE chickpeas. The total folate content of cooked legumes ranged from 53 to 81 μg/100 g for beans;133 to 203 μg/100 g for peas, and from 39 to 22 μg/100 g for small and large lentils, respectively. The predominant form of folate in legumes was tetrahydrofolate, followed by 5-formyl-tetrahydrofolate and 5-methyl-tetrahydrofolate.展开更多
Almost all cells are easily killed by exposure to potent oxidants. Indeed, major pathogen defense mechanisms in both animal and plant kingdoms involve production of an oxidative burst, where host defense cells show an...Almost all cells are easily killed by exposure to potent oxidants. Indeed, major pathogen defense mechanisms in both animal and plant kingdoms involve production of an oxidative burst, where host defense cells show an invading pathogen with reactive oxygen species (ROS). Although cancer cells can be similarly killed by ROS, development of oxidant-producing chemotherapies has been limited by their inherent nonspecificity and potential toxicity to healthy cells. In this paper, we describe the targeting of an ROS-generating molecule selectively to tumor cells using folate as the tumor-targeting ligand. For this purpose, we exploit the ability of 9,10-phenanthraquinone (PHQ) to enhance the continuous generation of H<sub>2</sub>O<sub>2</sub> in the presence of ascorbic acid to establish a con-stitutive source of ROS within the tumor mass. We report here that incubation of folate receptor-expressing KB cells in culture with folate-PHQ plus ascorbate results in the death of the cancer cells with an IC<sub>50</sub> of ~10 nM (folate-PHQ). We also demonstrate that a cleavable spacer linking folate to PHQ is significantly inferior to a noncleavable spacer, in contrast to most other folate-targeted therapeutic agents. Unfortunately, no evidence for folate-PHQ mediated tumor regression in murine tumor models is obtained, suggesting that unanticipated impediments to generation of cytotoxic quantities of ROS in vivo are encountered. Possible mechanisms and potential solutions to these unanticipated results are offered.展开更多
Objective:To evaluate the acute toxicity of carboxymethyl chitosan-2,2' ethylenedioxy bisethylamine-folate(CMC-EDBE-FA) and as well as possible effect on microbial growth and in vitro cell cyto-toxicity.Methods:CM...Objective:To evaluate the acute toxicity of carboxymethyl chitosan-2,2' ethylenedioxy bisethylamine-folate(CMC-EDBE-FA) and as well as possible effect on microbial growth and in vitro cell cyto-toxicity.Methods:CMC-EDBE-FA was prepared on basis of carboxymethyl chitosan tagged with folic acid by covalently linkage through 2,2' elhylenedioxy bis-ethylamine. In vivo acute toxicity,in vitro cyto-toxicity and antimicrobial activity of CMC-EDBE-FA nanoparticle were determined.Results:Vancomycin exhibited the antibacterial activity against vancomycin sensitive Staphylococcus aureus,but CMC-EDBE-FA nanoparticle did not give any antibacterial activity as evidenced by minimal inhibitory concentration(MIC),minimal bactericidal concentration(MBC),disc agar diffusion(DAD) and killing kinetic assay.Further,the CMC-EDBE-FA nanoparticle showed no signs of in vivo acute toxicity up to a dose level of 1000 mg/kg p.o.,and as well as in vitro cyto-toxicity up to 230 μg/mL.Conclnsions:These findings suggest that CMC-EDBE-FA nanoparticle is expected to be safe for biomedical applications.展开更多
Objective This study aimed to investigate predictability of preconception maternal circulating folate and homocysteine concentrations,glycemic and lipid profiles to the risk of congenital heart disease(CHD)in offsprin...Objective This study aimed to investigate predictability of preconception maternal circulating folate and homocysteine concentrations,glycemic and lipid profiles to the risk of congenital heart disease(CHD)in offspring.Methods A cohort of pregnancies was derived from a single hospital where pre-and post-conceptional serum folate,homocysteine,lipids,glycemic profiling and neonatal CHD screening program were facilitated.展开更多
Hippophae rhamnoides L.is a plant of immense ethnopharmacological importance and is a known source for various valuable biochemicals and nutraceuticals.The production of folate,a vitamin involved in several vital func...Hippophae rhamnoides L.is a plant of immense ethnopharmacological importance and is a known source for various valuable biochemicals and nutraceuticals.The production of folate,a vitamin involved in several vital functions,in this plant is rather poorly understood.Herein,we investigate the hypothesis that rhizobial bacteria serve the plant in this essential vitamin’s biosynthesis.Bacterial strains of Bacillus,Azorhizobium,Frankia,Paenibacillus,Brevibacillus and Pseudomonas,were isolated from the rhizosphere of the plant.HPLC and LCMS were used to trace the production of intra and extra-cellular folate by representative rhizospheric bacterial strains in vitro.From the seventeen functionally characterized bacterial strains of the plant’s rhizosphere,thirteen produced significant amounts of folate.Azorhizobium BR5401 produced the maximum amount of folic acid(424μg/mL),and Bacillus GY779 was the only strain capable of producing both intracellular and extra-cellular folic acid.The Open Reading Frame coding for dihydroneopterin aldolase,an enzyme involved in folate biosynthesis,was found in one of the representative isolates.Our experimental findings help us to suggest that the folate synthesized by rhizobial bacteria is transported to the plant,highlighting a significant benefit of coexistence.展开更多
AIM To evaluated the association of the risk factors and polymorphisms in MTHFR C677 T, MTHFR A1298 C, MTR A2756 G and MTRR A66 G genes.METHODS Patients with cirrhosis(n = 116), hepatocellular carcinoma(HCC)(n = 71) a...AIM To evaluated the association of the risk factors and polymorphisms in MTHFR C677 T, MTHFR A1298 C, MTR A2756 G and MTRR A66 G genes.METHODS Patients with cirrhosis(n = 116), hepatocellular carcinoma(HCC)(n = 71) and controls(n = 356) were included. Polymerase chain reaction followed by enzymatic digestion and allelic discrimination technique real-time PCR techniques were used for analysis. MINITAB-14.0and SNPstats were utilized for statistical analysis. RESULTS Showed that age ≥ 46 years(OR = 10.31; 95%CI: 5.66-18.76; P < 0.001) and smoking(OR = 0.47; 95%CI: 0.28-0.78; P = 0.003) were associated with cirrhosis. Age ≥ 46 years(OR = 16.36; 95%CI: 6.68-40.05; P < 0.001) and alcohol habit(OR = 2.01; 95%CI: 1.03-3.89; P = 0.039) were associated with HCC. MTHFR A1298 C in codominant model(OR = 3.37; 95%CI: 1.52-7.50; P = 0.014), recessive model(OR = 3.04; 95%CI: 1.43-6.47; P = 0.0051) and additive model(OR = 1.71; 95%CI: 1.16-2.52; P = 0.0072) was associated with HCC, as well as MTR A2756 G in the additive model(OR = 1.68; 95%CI: 1.01-2.77; P = 0.047), and MTRR A66 G in the codominant model(OR = 3.26; 95%CI: 1.54-6.87; P < 0.001), dominant model(OR = 2.55; 95%CI: 1.24-5.25; P = 0.007) and overdominant model(OR = 3.05; 95%CI: 1.66-5.62; P < 0.001). MTR A2756 G in the additive model(OR = 1.54; 95%CI: 1.02-2.33; P = 0.042) and smokers who presented at least one polymorphic allele for MTRR A66G(OR = 1.71; 95%CI: 0.77-3.82; P = 0.0051) showed increased risk for cirrhosis. There was no association between clinical parameters and polymorphisms. CONCLUSION Age ≥ 46 years, alcohol habit and MTR A2756 G, MTHFR A1298 C and MTRR A66 G polymorphisms are associated with an increased risk of HCC development; age ≥ 46 years, tobacco habit and the MTR A2756 G polymorphism are associated with cirrhosis.展开更多
BACKGROUND Photodynamic therapy(PDT)is a minimally invasive form of cancer therapy,and the development of a novel photosensitizer(PS)with optimal properties is important for enhancing PDT efficacy.Folate receptor(FR)m...BACKGROUND Photodynamic therapy(PDT)is a minimally invasive form of cancer therapy,and the development of a novel photosensitizer(PS)with optimal properties is important for enhancing PDT efficacy.Folate receptor(FR)membrane protein is frequently overexpressed in 40%of human cancer and a good candidate for tumor-specific targeting.Specific active targeting of PS to FR can be achieved by conjugation with the folate moiety.A folate-linked,near-infrared(NIR)-sensitive probe,folate-Si-rhodamine-1(FolateSiR-1),was previously developed and is expected to be applicable to NIR-PDT.AIM To investigate the therapeutic efficacy of NIR-PDT induced by FolateSiR-1,a FRtargeted PS,in preclinical cancer models.METHODS FolateSiR-1 was developed by conjugating a folate moiety to the Si-rhodamine derivative through a negatively charged tripeptide linker.FR expression in the designated cell lines was examined by western blotting(WB).The selective binding of FolateSiR-1 to FR was confirmed in FR overexpressing KB cells(FR+)and tumors by fluorescence microscopy and in vivo fluorescence imaging.Low FR expressing OVCAR-3 and A4 cell lines were used as negative controls(FR-).The NIR light(635±3 nm)-induced phototoxic effect of FolateSiR-1 was evaluated by cell viability imaging assays.The time-dependent distribution of FolateSiR-1 and its specific accumulation in KB tumors was determined using in vivo longitudinal fluorescence imaging.The PDT effect of FolateSiR-1 was evaluated in KB tumor bearing mice divided into four experimental groups:(1)FolateSiR-1(100μmol/L)alone;(2)FolateSiR-1(100μmol/L)followed by NIR irradiation(50 J/cm2);(3)NIR irradiation(50 J/cm2)alone;and(4)no treatment.Tumor volume measurement and immunohistochemical(IHC)and histological examinations of the tumors were performed to analyze the effect of PDT.RESULTS High FR expression was observed in the KB cells by WB,but not in the OVCAR-3 and A4 cells.Substantial FR-specific binding of FolateSiR-1 was observed by in vitro and in vivo fluorescence imaging.Cell viability imaging assays showed that NIR-PDT induced cell death in KB cells.In vivo longitudinal fluorescence imaging showed rapid peak accumulation of FolateSiR-1 in the KB tumors 2 h after injection.In vivo PDT conducted at this time point caused tumor growth delay.The relative tumor volumes in the PDT group were significantly reduced compared to those in the other groups[5.81±1.74(NIR-PDT)vs 12.24±2.48(Folate-SiR-1),vs 11.84±3.67(IR),vs 12.98±2.78(Untreated),at Day 16,P<0.05].IHC analysis revealed reduced proliferation marker Ki-67-positive cells in the PDT treated tumors,and hematoxylin-eosin staining revealed features of necrotic-and apoptotic cell death.CONCLUSION FolateSiR-1 has potential for use in PDT,and FR-targeted NIR-PDT may open a new effective strategy for the treatment of FR-overexpressing tumors.展开更多
Green tea contains folate and epigallocatechin gallate (EGCg), which is suggested to be an antifolate. In this study, we examined whether green tea was a good source of folate in a folate depletion/repletion rat model...Green tea contains folate and epigallocatechin gallate (EGCg), which is suggested to be an antifolate. In this study, we examined whether green tea was a good source of folate in a folate depletion/repletion rat model. Rats fed a folate deficient diet for 4 weeks were supplied with folate for 7 days, and then folate repletion effects were evaluated in terms of increase in total folate level in plasma, liver, and bone marrow and decrease in plasma homocysteine level. In this model, the folic acid treatment effect was observed to be dose-dependent and an appropriate dose of folic acid was 40 μg/kg/day or greater. Based on this finding, green tea as well as spinach, chicken liver, and folic acid as a reference were applied to this model. Increase in tissue folate level in response to the food samples varied among tissues, with bone marrow showing the smallest response. Increase in tissue folate level was in the order of spinach > chicken liver > green tea, which produced only a slight increase in tissue folate level and further diminished bone marrow folate level. EGCg administered by intragastric gavage at an approximate dose of 8 mg/kg did not attenuate the increase in tissue folate level when repletion was performed with folic acid. These results suggested that green tea is a poor source of food folate, but EGCg in green tea at a low dose has little effect on folic acid absorption.展开更多
基金supported by the National Health Commission of the People’s Republic of China Medical Reform Major Program:China National Chronic Diseases and Nutrition Surveillance of Adults[2015-2017]Qianrang Zhu is funded by a China Scholarship Council PhD Scholarship[No.202109110099].
文摘Objective This study aimed to evaluate the associations of serum folate and/or vitamin B12 concentrations with obesity among Chinese children and adolescents.Methods A cross-sectional study was conducted including 3,079 Chinese children and adolescents,aged 6 to 17 years,from Jiangsu,China.Anthropometric indices,such as,children's body mass index(BMI),BMI z-scores,waist circumference,and waist-to-height ratio were utilized.Multivariable linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B12 levels with anthropometric indices and odds of obesity.Results We observed that serum vitamin B12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity[odds ratio(OR)=0.68;95%confidence interval(CI)=0.59,0.78]and abdominal obesity(OR=0.68;95%CI=0.60,0.77).When compared to participants with both serum vitamin levels in the two middle quartiles,those with both serum folate and vitamin B12 levels in the highest quartile were less prone to general(OR=0.31,95%CI=0.19,0.50)or abdominal obesity(OR=0.46,95%CI=0.31,0.67).Conversely,participants with vitamin B12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity(OR=2.06,95%CI=1.09,3.91).Conclusion Higher serum vitamin B12 concentrations,but not serum folate concentrations,were associated with lower odds of childhood obesity.Children and adolescents with high levels of vitamin B12 and folate were less likely to be obese.
基金supported by the National Natural Sciences [82071690,81971390]Research Foundation of Capital Institute of Pediatrics [FX-2020-05,CXYJ-2-21-09]+1 种基金Public service development and reform pilot project of Beijing Medical Research Institute [BMR2021-1]Beijing Hospitals Authority Clinical technology innovation program [XLMX 202110]。
文摘Objective Circular RNAs(circRNAs)participate in several important pathological processes and have been used in the diagnosis and treatment of various diseases.This study aimed to investigate the role of circRNAs in neural tube defects(NTDs).Method We characterized circRNA-associated competitive endogenous RNA(ceRNA)networks in brain tissue of low folate-induced NTDs mouse at embryonic day 13.5 by high-throughput sequencing.The expression levels of Circzfp644,miR-20-5p and Gas7 were detected by RT-PCR.Gas7 and Circzfp644functions were determined by miRNA-mimics and inhibitors in mouse teratocarcinoma cells(F9 cells),and luciferase gene reporter assay was assessed in the F9 cells.In addition,the expression levels of Circzfp644,miR-20-5p and Gas7 were determined by Nanostring in human NTDs tissues.Results We detected 57 circRNA transcripts,16 miRNAs,and 148 mRNAs that were significantly dysregulated in NTDs brain tissues compared with their expression levels in control(normal)tissues.Circzfp644 shared miRNA response elements with the growth arrest specific 7(Gas7)gene and competitively bound with miR-20-5p to increase the expression of Gas7.Downregulation of Circzfp644and Gas7 and upregulation of miR-20-5p were found in human NTD tissue.Conclusion This study provides new perspectives on the role of circRNAs in nervous system development and the pathogenesis of NTDs.
基金supported by the National Natural Science Foundation of China under the Grant No. 81973048a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Culture, Sports and Technology of Japan [JSPS-C-21580137]。
文摘Objective This study aimed to investigate the effects of N,N-dimethylglycine(DMG) on the concentration and metabolism of plasma homocysteine(pHcy) in folate-sufficient and folate-deficient rats.Methods In this study, 0.1% DMG was supplemented in 20% casein diets that were either folatesufficient(20 C) or folate-deficient(20 CFD). Blood and liver of rats were subjected to assays of Hcy and its metabolites. Hcy and its related metabolite concentrations were determined using a liquid chromatographic system.Results Folate deprivation significantly increased pHcy concentration in rats fed 20 C diet(from 14.19 ±0.39 μmol/L to 28.49 ± 0.50 μmol/L;P < 0.05). When supplemented with DMG, pHcy concentration was significantly decreased(12.23 ± 0.18 μmol/L) in rats fed 20 C diet but significantly increased(31.56 ±0.59 μmol/L) in rats fed 20 CFD. The hepatic methionine synthase activity in the 20 CFD group was significantly lower than that in the 20 C group;enzyme activity was unaffected by DMG supplementation regardless of folate sufficiency. The activity of hepatic cystathionine β-synthase(CBS) in the 20 CFD group was decreased but not in the 20 C group;DMG supplementation enhanced hepatic CBS activity in both groups, in which the effect was significant in the 20 C group but not in the other group.Conclusion DMG supplementation exhibited hypohomocysteinemic effects under folate-sufficient conditions. By contrast, the combination of folate deficiency and DMG supplementation has deleterious effect on pHcy concentration.
文摘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.
文摘Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme for the critical process of one-carbon circulation,which convert5,10-methylenetetrahydrofolate to5-methyltetrahydrofolate and participate in folate and homocysteine conversion correlated to methyl group supply.The enzyme activity decline depends on the gene polymorphism.MTHFR impacts on the methylation process which is related to psychiatric diseases.Studies have shown association between MTHFR gene polymorphisms and mental disorders,some of which stratified by folate and cobalamin levels.In this review,we will summarize the testimony on the relationship between methylation and MTHFR polymorphism as well as the implication on psychiatric diseases by MTHFR mutation.
文摘Objective To review the association of methylene tetrahydrofolate reductase (MTHFR) C677T mutant with coronary artery disease, as well as to highlight the results of some of these studies and to emphasize the need to focus on the genetic architecture of CAD. Data SourcesData used in this article is mainly from relevant articles obtained through Pubmed, OVID and Google Scholar published from 1980 to 2008. Major studies and trials in this period were taken into account to draw accurate conclusion on the relation of those mutations in MTHFR with homocysteinemia and CAD. ResultOur analysis shows that hyperhomocysteinemia, a risk factor for occlusive arterial diseases, can be caused by disruptions of homocysteine metabolism catalyzed by MFTHR. A common alanine to valine mutation in MTHFR may contribute to mild heperhomocysteinemia in CAD. Individuals with the homozygous mutant genotype had higher plasma homocysteine, particularly when plasma folate was below the median value. ConclusionThis MTHFR mutant in the setting of insufficient folate may be a risk factor of CAD and can be regarded as a model of genetic-environmental interaction in the development of CAD.
基金Supported by National Science Council,Executive YuanNo.NSC-96-2314-B-075A-007,No.NSC100-2628-B005002MY4,No.NSC101-2320-B-005-006-MY3 and No.NSC101-2911-I-005-301the ATU plan of the Ministry of Education,Taiwan
文摘AIM: To evaluate the associations of serum folate levelwith development, invasiveness and patient survival of gastric cancer. METHODS: In this nested case-control study, patients with newly diagnosed gastric cancer undergoing gastrectomy were enrolled, and patients receiving chemotherapy prior to surgery, with other concurrent malignancy, or of the aboriginal and alien populations were excluded. In total, 155 gastric cancer patients and 149 healthy controls were enrolled for determination of serum folate levels and their correlation with gastric cancer. Using the median value of serum folate computed among the overall population as the cutoff value, the associations between serum folate and gastric cancer in all cases and different age and gender subgroups were analyzed by multivariate logistic regression analysis. In the patient cohort of gastric cancer, receiver-operating characteristic analyses were performed to calculate the best cutoff values of serum folate, and the associations between serum folate levels and clinicopathological features were further analyzed by multivariate regression analysis. Survival analyses were conducted using the Cox proportional hazards model.RESULTS: The mean serum folate level was significantly lower in gastric cancer patients than that in controls(3.71 ± 0.30 ng/mL vs 8.00 ± 0.54 ng/mL, P < 0.01), and folate levels were consistently lower in gastric cancer patients regardless of age and gender(all P < 0.01). Using the median serum folate value as the cutoff value, low serum folate was significantly associated with gastric cancer risk in the whole population(OR = 19.77, 95%CI: 10.54-37.06, P < 0.001) and all strata(age < 60 years OR = 17.39, 95%CI: 7.28-41.54, age ≥ 60 years(OR = 21.67, 95%CI: 8.27-56.80), males(OR = 17.95, 95%CI: 7.93-40.62), and females(OR = 20.95, 95%CI: 7.66-57.31); all P < 0.001. In the patient cohort of gastric cancer, the respective cutoff values showed that low serum folate levels were significantly associated with serosal invasion(OR = 2.54, 95%CI: 1.23-5.23), lymphatic invasion(OR = 2.23, 95%CI: 1.17-4.26), and liver metastasis(OR =6.67, 95%CI: 1.28-34.91) of gastric cancer(all P < 0.05). Serum folate level below 1.90 ng/mL was associated with poor patient survival(HR = 1.84, 95%CI: 1.04-3.27, P < 0.05) in univariate analysis.CONCLUSION: Lower serum folate levels were significantly associated with gastric cancer development and invasive phenotypes. The role of folate depletion in gastric cancer invasion warrants further study.
基金supported by a grant 30872999 from the National Natural Science Foundation of Chinaa grant BK2007023 from Jiangsu Province Natural Science Foundation of China
文摘Objective:Nanoparticles are becoming an important method of targeted drug delivery.To evaluate the importance of folate-conjugated human serum albumin(HSA)magnetic nanoparticles(Folate-CDDP/HSA MNP),we prepared drug-loaded Folate-CDDP/HSA MNPs and characterized their features.Methods:First, folate was conjugated with HSA under the effect of a condensing agent,and the conjugating rate was evaluated by a colorimetric method using 2,4,6-trinitrobenzene sulfonic acid.Second,under N 2 gas,Fe 3 O 4 magnetic nanomaterials were prepared and characterized by using transmission electron microscopy(TEM),SEM-EDS and X-ray diffraction(XRD).Finally,Folate-CDDP/HSA MNP was prepared by using a solvent evaporation technique. TEM was used to observe particle morphology.The particle size and distribution of the prepared complexes were determined by a Laser particle size analyzer.Drug loading volume and drug release were investigated by a high performance liquid chromatography method(HPLC)in vitro.Results:We successfully prepared folate-conjugated HSA and its conjugating rate was 27.26μg/mg.Under TEM,Fe 3 O 4 magnetic nanoparticles were highly electron density and had an even size distribution in the range of 10-20 nm.It was confirmed by SEM-EDS and XRD that Fe 3 O 4 magnetic nanoparticles had been successfully prepared.Under TEM,drug-loaded magnetic nanoparticles were observed,which had a round shape,similar uniform size and smooth surface.Their average size was 79 nm which was determined by laser scattering,and they exhibited magnetic responsiveness.Encapsulation efficiency was 89.75%and effective drug loading was calculated to be 15.25%.The release results in vitro showed that the half release time(t1/ 2 )of cisplatin in cisplatin Solution and Folate-CDDP/HSA MNP was 65 min and 24 h respectively, which indicated that microspheres had an obvious effect of sustained-release.Conclusion:Folate-CDDP/HSA MNPs were prepared successfully.The preparation process and related characteristics data provided a foundation for further study,including the mechanism of the nanoparticles distribution in vivo and their intake by tumor cells.
文摘Objective:To evaluate the potency of carboxymethyl chitosan-2,2' ethylenedioxy bisethylamine-folate(CMC-EDBE-FA) on tissue injury,antioxidant status and glutathione system in tissue mitochondria and serum against nicotine-induced oxidative stress in mice.Methods: CMC-EDBE-FA was prepared on basis of carboxymethyl chitosan tagged with folic acid by covalently linkage through 2,2' ethylenedioxy bis-ethylamine.Animals were divided into four groups,i.e.,control,nicotine(1 mg/kg bw/day),CMC-EDBE-FA(1 mg/kg bw/day) and nicotine(1 mg/kg bw/day) and CMC-EDBE-FA(1 mg/kg bw/day) for 7 days.Levels of lipid peroxidation, oxidized glutathione level,antioxidant enzyme status and DNA damage were observed and compared.Results:The significantly increase of lipid peroxidation,oxidized glutathione levels and DNA damage was observed in nicotine treated group as compared with control group;those were significantly reduced in CMC-EDBE-FA supplemented group.Moreover,significantly reduced antioxidant status in nicotine treated group was effectively ameliorated by the supplementation of CMC-EDBE-FA.Only CMC-EDBE-FA treated groups showed no significant change as compared with control group;rather than it repairs the tissue damage of nicotine treated group.Conclusions:These findings suggest that CMC-EDBE-FA is non-toxic and ameliorates nicotine-induced toxicity.
基金Supported by Grant from the Ministry of Public Health, China, No. 200802094
文摘Colorectal cancer (CRC) is one of the most common malignancies and causes of cancer deaths throughout the world. Endoscopy has its functional and finan-cial limitations; therefore,chemoprevention might be crucial in reducing the incidence of CRC. Although a number of studies have demonstrated the potential chemopreventive effects of folate (or folic acid),many challenges still remain. The relationship between fo-late intake and CRC risk is a complex association that might depend on many factors including gender,age,alcohol consumption,and smoking,all of which inter-fere with folate metabolism. The supplementary dose of fiber,the length of time required to observe the effects,and confounding factors exposed during the trial might also influence these findings. Therefore,more evidence from clinical studies is needed regarding the mechanisms that underlie the actions of bioactive food components in minimizing the risk of CRC.
文摘Folate deficiency and its association with cancer have been studied in the literature, but its clinical impact is still unknown. Folate deficiency and its result on gastric cancer is a mysterious part of oncology, with ongoing studies hopefully clarifying its impact on gastric cancer management. Lee et al studied folate deficiency and its impact on staging and clinical results. Here we try to contribute to the field by expressing our own thoughts about the paper.
文摘Seven varieties of Tajik legumes and two Tajik snack type ready-to-eat (RTE) whole/split chickpeas were analyzed for iron in raw and cooked legumes and for naturally occurring folate content in cooked legumes. Iron was measured according to AACC method 40 - 41B. Folate contents were determined by microbiological (Lactobacillus casei subsp. Rhamnosus ATCC 7469) and high-performance liquid chromatography analysis utilizing a tri-enzyme treatment (pro-tease, α-amylase and conjugase). Folate derivatives of tetrahydrofolate, 5-formyl-tetrahydrofolate and 5-methyl- -tetrahydrofolate were identified and quantified. Iron content for Tajik legumes ranged from 5.52 to 13.27 mg/100 g for raw;2.81 to 4.12 mg/100 g for cooked and 4.37 and 4.76 mg/100 g for RTE chickpeas. The total folate content of cooked legumes ranged from 53 to 81 μg/100 g for beans;133 to 203 μg/100 g for peas, and from 39 to 22 μg/100 g for small and large lentils, respectively. The predominant form of folate in legumes was tetrahydrofolate, followed by 5-formyl-tetrahydrofolate and 5-methyl-tetrahydrofolate.
文摘Almost all cells are easily killed by exposure to potent oxidants. Indeed, major pathogen defense mechanisms in both animal and plant kingdoms involve production of an oxidative burst, where host defense cells show an invading pathogen with reactive oxygen species (ROS). Although cancer cells can be similarly killed by ROS, development of oxidant-producing chemotherapies has been limited by their inherent nonspecificity and potential toxicity to healthy cells. In this paper, we describe the targeting of an ROS-generating molecule selectively to tumor cells using folate as the tumor-targeting ligand. For this purpose, we exploit the ability of 9,10-phenanthraquinone (PHQ) to enhance the continuous generation of H<sub>2</sub>O<sub>2</sub> in the presence of ascorbic acid to establish a con-stitutive source of ROS within the tumor mass. We report here that incubation of folate receptor-expressing KB cells in culture with folate-PHQ plus ascorbate results in the death of the cancer cells with an IC<sub>50</sub> of ~10 nM (folate-PHQ). We also demonstrate that a cleavable spacer linking folate to PHQ is significantly inferior to a noncleavable spacer, in contrast to most other folate-targeted therapeutic agents. Unfortunately, no evidence for folate-PHQ mediated tumor regression in murine tumor models is obtained, suggesting that unanticipated impediments to generation of cytotoxic quantities of ROS in vivo are encountered. Possible mechanisms and potential solutions to these unanticipated results are offered.
基金financially supported by Department of Biotechnology,Government of India(grant No.BT/PR10861/NNT/28/131/2008)
文摘Objective:To evaluate the acute toxicity of carboxymethyl chitosan-2,2' ethylenedioxy bisethylamine-folate(CMC-EDBE-FA) and as well as possible effect on microbial growth and in vitro cell cyto-toxicity.Methods:CMC-EDBE-FA was prepared on basis of carboxymethyl chitosan tagged with folic acid by covalently linkage through 2,2' elhylenedioxy bis-ethylamine. In vivo acute toxicity,in vitro cyto-toxicity and antimicrobial activity of CMC-EDBE-FA nanoparticle were determined.Results:Vancomycin exhibited the antibacterial activity against vancomycin sensitive Staphylococcus aureus,but CMC-EDBE-FA nanoparticle did not give any antibacterial activity as evidenced by minimal inhibitory concentration(MIC),minimal bactericidal concentration(MBC),disc agar diffusion(DAD) and killing kinetic assay.Further,the CMC-EDBE-FA nanoparticle showed no signs of in vivo acute toxicity up to a dose level of 1000 mg/kg p.o.,and as well as in vitro cyto-toxicity up to 230 μg/mL.Conclnsions:These findings suggest that CMC-EDBE-FA nanoparticle is expected to be safe for biomedical applications.
文摘Objective This study aimed to investigate predictability of preconception maternal circulating folate and homocysteine concentrations,glycemic and lipid profiles to the risk of congenital heart disease(CHD)in offspring.Methods A cohort of pregnancies was derived from a single hospital where pre-and post-conceptional serum folate,homocysteine,lipids,glycemic profiling and neonatal CHD screening program were facilitated.
基金The authors are grateful to the Defense Research Development Organization(Project No.TC/2519/INM/-04/2012/CARS of INM 311/1.2)for the financial support and opportunity to carry out these studies.
文摘Hippophae rhamnoides L.is a plant of immense ethnopharmacological importance and is a known source for various valuable biochemicals and nutraceuticals.The production of folate,a vitamin involved in several vital functions,in this plant is rather poorly understood.Herein,we investigate the hypothesis that rhizobial bacteria serve the plant in this essential vitamin’s biosynthesis.Bacterial strains of Bacillus,Azorhizobium,Frankia,Paenibacillus,Brevibacillus and Pseudomonas,were isolated from the rhizosphere of the plant.HPLC and LCMS were used to trace the production of intra and extra-cellular folate by representative rhizospheric bacterial strains in vitro.From the seventeen functionally characterized bacterial strains of the plant’s rhizosphere,thirteen produced significant amounts of folate.Azorhizobium BR5401 produced the maximum amount of folic acid(424μg/mL),and Bacillus GY779 was the only strain capable of producing both intracellular and extra-cellular folic acid.The Open Reading Frame coding for dihydroneopterin aldolase,an enzyme involved in folate biosynthesis,was found in one of the representative isolates.Our experimental findings help us to suggest that the folate synthesized by rhizobial bacteria is transported to the plant,highlighting a significant benefit of coexistence.
基金the Faculdade de Medicina de Sao Jose do Rio Preto,FAMERP and Medical School FoundationFUNFARME for their institutional supportUPGEM-Genetics and Molecular Biology Research Unit
文摘AIM To evaluated the association of the risk factors and polymorphisms in MTHFR C677 T, MTHFR A1298 C, MTR A2756 G and MTRR A66 G genes.METHODS Patients with cirrhosis(n = 116), hepatocellular carcinoma(HCC)(n = 71) and controls(n = 356) were included. Polymerase chain reaction followed by enzymatic digestion and allelic discrimination technique real-time PCR techniques were used for analysis. MINITAB-14.0and SNPstats were utilized for statistical analysis. RESULTS Showed that age ≥ 46 years(OR = 10.31; 95%CI: 5.66-18.76; P < 0.001) and smoking(OR = 0.47; 95%CI: 0.28-0.78; P = 0.003) were associated with cirrhosis. Age ≥ 46 years(OR = 16.36; 95%CI: 6.68-40.05; P < 0.001) and alcohol habit(OR = 2.01; 95%CI: 1.03-3.89; P = 0.039) were associated with HCC. MTHFR A1298 C in codominant model(OR = 3.37; 95%CI: 1.52-7.50; P = 0.014), recessive model(OR = 3.04; 95%CI: 1.43-6.47; P = 0.0051) and additive model(OR = 1.71; 95%CI: 1.16-2.52; P = 0.0072) was associated with HCC, as well as MTR A2756 G in the additive model(OR = 1.68; 95%CI: 1.01-2.77; P = 0.047), and MTRR A66 G in the codominant model(OR = 3.26; 95%CI: 1.54-6.87; P < 0.001), dominant model(OR = 2.55; 95%CI: 1.24-5.25; P = 0.007) and overdominant model(OR = 3.05; 95%CI: 1.66-5.62; P < 0.001). MTR A2756 G in the additive model(OR = 1.54; 95%CI: 1.02-2.33; P = 0.042) and smokers who presented at least one polymorphic allele for MTRR A66G(OR = 1.71; 95%CI: 0.77-3.82; P = 0.0051) showed increased risk for cirrhosis. There was no association between clinical parameters and polymorphisms. CONCLUSION Age ≥ 46 years, alcohol habit and MTR A2756 G, MTHFR A1298 C and MTRR A66 G polymorphisms are associated with an increased risk of HCC development; age ≥ 46 years, tobacco habit and the MTR A2756 G polymorphism are associated with cirrhosis.
文摘BACKGROUND Photodynamic therapy(PDT)is a minimally invasive form of cancer therapy,and the development of a novel photosensitizer(PS)with optimal properties is important for enhancing PDT efficacy.Folate receptor(FR)membrane protein is frequently overexpressed in 40%of human cancer and a good candidate for tumor-specific targeting.Specific active targeting of PS to FR can be achieved by conjugation with the folate moiety.A folate-linked,near-infrared(NIR)-sensitive probe,folate-Si-rhodamine-1(FolateSiR-1),was previously developed and is expected to be applicable to NIR-PDT.AIM To investigate the therapeutic efficacy of NIR-PDT induced by FolateSiR-1,a FRtargeted PS,in preclinical cancer models.METHODS FolateSiR-1 was developed by conjugating a folate moiety to the Si-rhodamine derivative through a negatively charged tripeptide linker.FR expression in the designated cell lines was examined by western blotting(WB).The selective binding of FolateSiR-1 to FR was confirmed in FR overexpressing KB cells(FR+)and tumors by fluorescence microscopy and in vivo fluorescence imaging.Low FR expressing OVCAR-3 and A4 cell lines were used as negative controls(FR-).The NIR light(635±3 nm)-induced phototoxic effect of FolateSiR-1 was evaluated by cell viability imaging assays.The time-dependent distribution of FolateSiR-1 and its specific accumulation in KB tumors was determined using in vivo longitudinal fluorescence imaging.The PDT effect of FolateSiR-1 was evaluated in KB tumor bearing mice divided into four experimental groups:(1)FolateSiR-1(100μmol/L)alone;(2)FolateSiR-1(100μmol/L)followed by NIR irradiation(50 J/cm2);(3)NIR irradiation(50 J/cm2)alone;and(4)no treatment.Tumor volume measurement and immunohistochemical(IHC)and histological examinations of the tumors were performed to analyze the effect of PDT.RESULTS High FR expression was observed in the KB cells by WB,but not in the OVCAR-3 and A4 cells.Substantial FR-specific binding of FolateSiR-1 was observed by in vitro and in vivo fluorescence imaging.Cell viability imaging assays showed that NIR-PDT induced cell death in KB cells.In vivo longitudinal fluorescence imaging showed rapid peak accumulation of FolateSiR-1 in the KB tumors 2 h after injection.In vivo PDT conducted at this time point caused tumor growth delay.The relative tumor volumes in the PDT group were significantly reduced compared to those in the other groups[5.81±1.74(NIR-PDT)vs 12.24±2.48(Folate-SiR-1),vs 11.84±3.67(IR),vs 12.98±2.78(Untreated),at Day 16,P<0.05].IHC analysis revealed reduced proliferation marker Ki-67-positive cells in the PDT treated tumors,and hematoxylin-eosin staining revealed features of necrotic-and apoptotic cell death.CONCLUSION FolateSiR-1 has potential for use in PDT,and FR-targeted NIR-PDT may open a new effective strategy for the treatment of FR-overexpressing tumors.
文摘Green tea contains folate and epigallocatechin gallate (EGCg), which is suggested to be an antifolate. In this study, we examined whether green tea was a good source of folate in a folate depletion/repletion rat model. Rats fed a folate deficient diet for 4 weeks were supplied with folate for 7 days, and then folate repletion effects were evaluated in terms of increase in total folate level in plasma, liver, and bone marrow and decrease in plasma homocysteine level. In this model, the folic acid treatment effect was observed to be dose-dependent and an appropriate dose of folic acid was 40 μg/kg/day or greater. Based on this finding, green tea as well as spinach, chicken liver, and folic acid as a reference were applied to this model. Increase in tissue folate level in response to the food samples varied among tissues, with bone marrow showing the smallest response. Increase in tissue folate level was in the order of spinach > chicken liver > green tea, which produced only a slight increase in tissue folate level and further diminished bone marrow folate level. EGCg administered by intragastric gavage at an approximate dose of 8 mg/kg did not attenuate the increase in tissue folate level when repletion was performed with folic acid. These results suggested that green tea is a poor source of food folate, but EGCg in green tea at a low dose has little effect on folic acid absorption.
