Rice is a poor source of folate,an essential micronutrient for the body.Biofortification offers an effective way to enhance the folate content of rice and alleviate folate deficiencies in humans.In this study,we confi...Rice is a poor source of folate,an essential micronutrient for the body.Biofortification offers an effective way to enhance the folate content of rice and alleviate folate deficiencies in humans.In this study,we confirmed that OsADCS and OsGTPCHI,encoding the initial enzymes necessary for folate synthesis,positively regulate folate accumulation in knockout mutants of both japonica and indica rice backgrounds.The folate content in the low-folate japonica variety was slightly increased by the expression of the indica alleles driven by the endosperm-specific promoter.We further obtained co-expression lines by stacking OsADCS and OsGTPCHI genes;the folate accumulation in brown rice and polished rice reached 5.65μg/g and 2.95μg/g,respectively,representing 37.9-fold and 26.5-fold increases compared with the wild type.Transcriptomic analysis of rice grains from six transgenic lines showed that folate changes affected biological pathways involved in the synthesis and metabolism of rice seed storage substances,while the expression of other folate synthesis genes was weakly regulated.In addition,we identified Aus rice as a high-folate germplasm carrying superior haplotypes of OsADCS and OsGTPCHI through natural variation.This study provides an alternative and effective complementary strategy for rice biofortification,promoting the rational combination of metabolic engineering and conventional breeding to breed high-folate varieties.展开更多
Folate(FA)is an essential micronutrient of vitamin B group for growth,development,and reproduction through participating in the nucleotide synthesis and methyl donation reactions.The changes of FA level have been link...Folate(FA)is an essential micronutrient of vitamin B group for growth,development,and reproduction through participating in the nucleotide synthesis and methyl donation reactions.The changes of FA level have been linked to dietary insufficiency(e.g.,poor diet,etc.)malabsorption(e.g.,FA-associated gene mutation,etc.),increased demand(e.g.,pregnancy,etc).or medication(e.g.,antifolates drugs),or bad habits(e.g.,smoking,alcoholism,etc.).Recently,epidemiological data showed that the levels of the host FA typically changed in patients with infectious diseases.Interactions between pathogens,including bacteria,parasites and viruses,and their hosts are complex,in particular,pathogenic infection-mediated changes of the host FA levels can affect the utilization and uptake of limited FA resources of the host.Therefore,FA supplementation or the use of antifolate agents may be a potential antimicrobial strategy for managing infectious diseases.Furthermore,given that the gut microbiota is a primary source of FA in the human body,the association between gut microbiota and pathogenic infections warrants investigation.To date,little is known about how FA status and its biochemistry function affect the course of infectious diseases.In this review,we focus on the roles of FA in the interaction between the host and microbe,and briefly discuss the potential of FA and antifolates agents in the treatment of infectious diseases.展开更多
One-third of the global population is affected by micronutrient deficiency, particularly folate. Although folate synthesis has been relatively well characterized, few folate-related genes in maize have been cloned, an...One-third of the global population is affected by micronutrient deficiency, particularly folate. Although folate synthesis has been relatively well characterized, few folate-related genes in maize have been cloned, and the molecular mechanism regulating folate synthesis in maize remains unclear. In this study,transcriptome and proteome analyses of three waxy maize inbred lines with high, medium, and low folate contents were performed to identify key genes controlling folate biosynthesis. Pairwise comparisons revealed 21 differentially expressed genes and 20 differentially expressed proteins potentially associated with folate biosynthesis in the three lines. Six key folate-associated genes, Zm Mocos2, Zm GGH,Zm ADCL2, Zm CBR1, Zm SHMT, and Zm Pur H, were identified. These genes encode enzymes that potentially function in folate biosynthesis. Functional validation of one of these genes, Zm ADCL2, using an EMS mutant(Mut9264) showed that a 4-base insertion in an exon increased the folate content of fresh maize kernels 1.37-fold that of the wild type. Zm ADCL2 was considered a potential target for generating maize lines with higher folate content. KEGG enrichment analysis of differentially expressed genes and proteins showed that several pathways in addition to folate biosynthesis were likely indirectly involved in folate metabolism and content(e.g., glycine, serine, and threonine metabolism;purine metabolism;cysteine and methionine metabolism;alanine, aspartate and glutamate metabolism;glutathione metabolism;and pyruvate metabolism. The transcriptome and proteomic data generated in this study will help to clarify the mechanisms underlying folate accumulation and aid breeding efforts to biofortify maize with folate.展开更多
BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as ...BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as targeted polymerase chain reaction technology),and current findings remain inconsistent.AIM To investigate the association of folate metabolism gene polymorphisms with ASD susceptibility and symptom severity among Chinese children.METHODS Whole-exome sequencing(WES)was conducted to systematically screen for coding region variants of key genes in the folate metabolism pathway among children with ASD,focusing on identifying polymorphisms with high mutation frequencies and potential pathogenic effects.A case-control study was then conducted to explore the association of candidate folate metabolism gene polymorphisms with the susceptibility and severity of ASD.RESULTS WES was performed on 70 children with ASD,and the case-control study included 170 children with ASD and 170 healthy controls.WES revealed that 84.3%(59/70)of children with ASD carried potentially pathogenic variants enriched in folate metabolism pathways.MTHFR C677T and MTRR A66G were significantly associated with an increased risk of ASD in both codominant and dominant models(P<0.05).The dominant model of MTRR A66G was also significantly associated with higher scores in the domains of social relations,body and object use,social and adaptive skills,total scores on the Autism Behavior Checklist,as well as emotional reactivity,nonverbal communication,and activity level on the Childhood Autism Rating Scale(P<0.05).CONCLUSION Most children with ASD carry deleterious variants in folate metabolism-related pathways.MTHFR C677T and MTRR A66G mutations are significantly associated with ASD.展开更多
BACKGROUND There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus(GDM),and the correlation between genetic factors related to folic acid metabolism pathways and...BACKGROUND There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus(GDM),and the correlation between genetic factors related to folic acid metabolism pathways and GDM remains to be revealed.AIM To examine the association between single-nucleotide polymorphisms(SNPs)of enzyme genes in the folate metabolite pathway as well as that between GDM-related genes and risk for GDM.METHODS A nested case-control study was conducted with GDM cases(n=412)and healthy controls(n=412).DNA was extracted blood samples and SNPs were genotyped using Agena Bioscience’s MassARRAY gene mass spectrometry system.The associations between different SNPs of genes and the risk for GDM were estimated using logistic regression models.The generalized multi-factor dimensionality reduction(GMDR)method was used to analyze gene-gene and gene-environment interactions using the GMDR 0.9 software.RESULTS The variation allele frequency of melatonin receptor 1B(MTNR1B)rs10830963 was higher in the GDM group than in controls(P<0.05).MTNR1B rs10830963 mutant G was associated with risk for GDM[adjusted odds ratio(aOR):1.43;95%confidence interval(95%CI):1.13-1.80]in the additive model.MTNR1B rs10830963 GG+GC was significantly associated with the risk for GDM(aOR:1.65;95%CI:1.23-2.22)in the dominant model.The two-locus model of MTNR1B rs10830963 and CHEMERIN rs4721 was the best model(P<0.05)for gene-gene interactions in the GMDR results.The high-risk rs10830963×rs4721 type of interaction was a risk factor for GDM(aOR:2.09;95%CI:1.49-2.93).CONCLUSION This study does not find an association between SNPs of folate metabolic enzymes and risk for GDM.The G mutant allele of MTNR1B rs10830963 is identified as a risk factor for GDM in the additive model,and there may be gene-gene interactions between MTNR1B rs10830963 and CHEMERIN rs4721.It is conducive to studying the causes of GDM and provides a new perspective for the precise prevention of this disease.展开更多
BACKGROUND Early metastasis and recurrence are risk factors that negatively affect the prog-nosis of advanced hepatocellular carcinoma(HCC).Alpha fetoprotein(AFP)is currently the most prevalent serum biomarker for det...BACKGROUND Early metastasis and recurrence are risk factors that negatively affect the prog-nosis of advanced hepatocellular carcinoma(HCC).Alpha fetoprotein(AFP)is currently the most prevalent serum biomarker for detecting HCC and predicting tumor recurrence.However,its sensitivity and specificity are not sufficient,espe-cially in patients who are AFP negative.METHODS This work is a retrospective study that included 128 consecutive patients with benign or malignant disease of the liver from 2020 to 2021.FR+CTCs were col-lected from 3 mL of peripheral blood via immunomagnetic depletion of leuko-cytes.After ligand-target polymerase chain reaction,the number of FR+CTCs was measured.Receiver operating characteristic curves were used to determine the threshold of sensitivity and specificity of FR+CTCs.The Youden index was used to identify the optimal cutoff point and diagnostic efficiency of FR+CTCs counts.Univariate and multivariate Cox proportional hazards regression analyses were performed to evaluate the associations of biomarkers or clinical parameters with disease-free survival(DFS).RESULTS The FR+CTCs counts showed excellent diagnostic efficacy in patients with HCC,with high sensitivity(0.905)and specificity(0.773)compared with patients with benign disease.Compared with that of the AFP level,the area under the receiver operating characteristic curve of the FR+CTC count is significantly greater(0.900 compared with 0.730,P<0.05).FR+CTC levels were significantly correlated with macrovascular invasion,tumor size,tumor number,and extrahepatic tumor stage in HCC patients.FR+CTC counts were correlated with DFS in HCC patients after R0 resection.Univariate analysis of DFS revealed that the FR+CTC count,tumor number,Barcelona Clinic Liver Cancer stage and extrahepatic metastasis status were correlated with DFS.Multivariate analysis of DFS revealed that the FR+CTC count and tumor number were correlated with DFS.CONCLUSION Ligand-target polymerase chain reaction is a sensitive tool for quantifying the number of FR+CTCs in HCC patients.These findings could provide new insight for stratifying HCC patients and predicting the recurrence of HCC.展开更多
Objective:To explore the polymorphism of folate metabolism genes and its correlation with pregnancy-induced hypertension(PIH)in women of childbearing age in the Neijiang region.Methods:Forty-five pregnant women with h...Objective:To explore the polymorphism of folate metabolism genes and its correlation with pregnancy-induced hypertension(PIH)in women of childbearing age in the Neijiang region.Methods:Forty-five pregnant women with hypertension disorders who received prenatal care at the Maternal and Child Health Hospital in the Neijiang region from May 2023 to April 2025 were selected for the study and designated as the case group.Additionally,45 healthy pregnant women during the same period were selected as the control group.Venous blood samples were collected from both groups for folate metabolism gene testing,and the correlation with PIH was analyzed.Results:There were statistically significant differences in BMI index,systolic blood pressure,diastolic blood pressure,serum folate levels,Hcy levels,and vitamin B12 levels between the case group and the control group(p<0.05).The proportions of MTHFR-wild type and MTRR-wild type in the case group were lower than those in the control group,while the proportions of MTHFR-heterozygous mutant type and MTRR-heterozygous mutant type were higher in the case group(p<0.05).The Logistic regression model showed that overweight/obesity,abnormal folate levels,abnormal Hcy levels,abnormal vitamin B12 levels,MTHFR-heterozygous mutant type,and(repeated entry corrected to another relevant factor if necessary,but assuming it’s a typo and should be another mutant type or omitted for clarity,here kept as is for direct translation)MTHFR-heterozygous mutant type(note:this repetition should likely be corrected in the original text,e.g.,to MTRR-heterozygous mutant type or another relevant factor)were independent risk factors for the occurrence of HDP(p<0.05),while MTHFR-wild type and MTRR-wild type were protective factors against HDP(p<0.05).Conclusion:The polymorphism distribution of key genes involved in folate metabolism among women of childbearing age in Neijiang is significantly associated with the occurrence of Hypertensive Disorders of Pregnancy(HDP).Mutant genotypes of MTHFR and MTRR serve as independent risk factors for HDP,while the wild-type acts as a protective factor.Additionally,overweight/obesity,reduced serum folate levels,hyperhomocysteinemia,and vitamin B12 deficiency are also important risk indicators for the onset of HDP.展开更多
Surface modification may have important influences on the penetration behavior of nanoscale drug delivery system. In the present study, we mainly focused on whether cell targeting or cell penetration could affect pene...Surface modification may have important influences on the penetration behavior of nanoscale drug delivery system. In the present study, we mainly focused on whether cell targeting or cell penetration could affect penetration abilities of nanostructured lipid carriers（NLC）. Real--time penetration of folate--or cell penetrating peptide（CPP）-modified NLC was evaluated using a multicellular tumor spheroid（MTS） established by stacking culture method as an in vitro testing platform. The results suggested that CPP modification had a better penetration behavior both on penetration depth and intensity compared with folate-modified NLC at the early stage of penetration process.展开更多
Multidrug resistance （MDR） operated by P-glycoprotein （P-gp） is one of the major causes in the treatment failure of cancers. In this work, docetaxel-loaded mixed micelles comprised of 1,2-distearoyl-sn-glycero-3-p...Multidrug resistance （MDR） operated by P-glycoprotein （P-gp） is one of the major causes in the treatment failure of cancers. In this work, docetaxel-loaded mixed micelles comprised of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy （polyethylene-glycol）2000 （DSPE-PEG2000）, D-α-Tocopherylpolyethylene glycol 1000 succinate （TPGSIooo） and DSPE-PEG2000-folate were developed to overcome MDR and reduce the side effect of docetaxel in cancer therapy. The diameters of micelles ranged from 13 to 26 nm and the encapsulation efficiencies were all above 85%. The influences of DSPE-PEG2000 and TPGSIooo ratios on the micellar characteristics and anti-resistant tumors effects were evaluated. Micelles with high TPGS1000 amount showed an increased cellular uptake and stronger cytotoxicity against MDR KBv cells. Moreover, the micelles modified by targeting ligand of folic acid exhibited better antitumor effect on folate receptor over-expressing KBv cells. The study provides a method for overcoming MDR in cancer therapy.展开更多
The set of all spheres and hyperplanes in the Euclidean space Rn+1 could be identified with the Sitter space Λn+1. All the conformal properties are invariant by the Lorentz form which is natural pseudo-Riemannian met...The set of all spheres and hyperplanes in the Euclidean space Rn+1 could be identified with the Sitter space Λn+1. All the conformal properties are invariant by the Lorentz form which is natural pseudo-Riemannian metric on Λn+1. We shall study behaviour of some surfaces and foliations as their families using computation in the de Sitter space.展开更多
Objective: To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), the central enzymes in folate metabolism that affects DNA meth...Objective: To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), the central enzymes in folate metabolism that affects DNA methylation and synthesis, and the risk of Down syndrome in China. Methods: Genomic DNA was isolated from the peripheral lymphocytes of 64 mothers of children with Down syndrome and 70 age matched control subjects. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR 677C→T, MTRR 66A→G and the relationship between these genotypes and the risk of Down syndrome was analyzed. Results: The results show that the MTHFR 677C→T polymorphism is more prevalent among mothers of children with Down syndrome than among control mothers, with an odds ratio of 3.78 (95% confidence interval (CI), 1.78～8.47). In addition, the homozygous MTRR 66A→G polymorphism was independently associated with a 5.2-fold increase in estimated risk (95% CI, 1.90～14.22). The combined presence of both polymorphisms was associated with a greater risk of Down syndrome than the presence of either alone, with an odds ratio of 6.0 (95% CI, 2.058～17.496). The two polymorphisms appear to act without a multiplicative interaction. Conclusion: MTHFR and MTRR gene mutation alleles are related to Down syndrome, and CT, TT and GG gene mutation types increase the risk of Down syndrome.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
AIM: To investigate serum levels of homocysteine (Hcys) and the risk that altered levels carry for thrombosis development in ulcerative colitis (UC) patients. METHODS: 55 UC patients and 45 healthy adults were include...AIM: To investigate serum levels of homocysteine (Hcys) and the risk that altered levels carry for thrombosis development in ulcerative colitis (UC) patients. METHODS: 55 UC patients and 45 healthy adults were included. Hcys, vitamin B12 and folic acid levels were measured in both groups. Clinical history and thrombo- embolic events were investigated. RESULTS: The average Hcys level in the UC patients was 13.3 ± 1.93 μmmol/L (range 4.60-87) and was higher than the average Hcys level of the control group which was 11.2 ± 3.58 μmmol/L (range 4.00-20.8) (P < 0.001). Vitamin B12 and folic acid average values were also lower in the UC group (P < 0.001). Whenmultivariate regression analysis was performed, it was seen that folic acid deficiency was the only risk factor for hyperhomocysteinemia. Frequencies of thromboembolic complications were not statistically significantly different in UC and control groups. When those with and without a thrombosis history in the UC group were compared according to Hcys levels, it was seen that there were no statistically significant differences. A negative linear relationship was found between folic acid levels and Hcys. CONCLUSION: We could not find any correlations between Hcys levels and history of prior thromboembolic events.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 prep...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., gas, Fe：~O1 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 27.26 μg/mg. Under TEM, Fe2O4 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 Fe304 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 （ta/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
We present here the development of cholesterol(Chol)-modified dendrimer system for targeted chemotherapy of folate(FA)receptor-expressing cancer cells. In our study, poly(amidoamine)(PAMAM) dendrimers of generation 5(...We present here the development of cholesterol(Chol)-modified dendrimer system for targeted chemotherapy of folate(FA)receptor-expressing cancer cells. In our study, poly(amidoamine)(PAMAM) dendrimers of generation 5(G5) were functionalized stepby-step with Chol, fluorescein isothiocyanate(FI), and FA via a poly(ethylene glycol)(PEG) spacer(PEG-FA), and then acetamide to shield their remaining surface amines. The synthesized G5.NHAc-Chol-FI-PEG-FA(for short, G5-CFPF) dendrimers were utilized to encapsulate 10-hydroxycamptothecin(HCP), a hydrophobic anticancer drug. We find that each G5-CFPF dendrimer can encapsulate 13.8 HCP molecules. The complexes show a slower release profiles of HCP in a pH-dependent manner than the control complexes formed using the same dendrimers without Chol under the same conditions. Thanks to the targeting role played by FA, the complexes display a specific inhibition efficacy to FA receptor-expressing cervical cancer cells. The designed Chol-modified dendrimers may be adopted as a promising carrier for application in targeted cancer therapy.展开更多
One-carbon metabolism is a network of biological reactions that plays critical role in DNA methylation and DNA synthesis, and in turn, facilitates the cross-talk between genetic and epigenetic processes. Genetic polym...One-carbon metabolism is a network of biological reactions that plays critical role in DNA methylation and DNA synthesis, and in turn, facilitates the cross-talk between genetic and epigenetic processes. Genetic polymorphisms and supplies of cofactors （e.g. folate, vitamins B） involved in this pathway have been shown to influence cancer risk and even survival. In this review, we summarized the epidemiological evidence for one-carbon metabolism, from both genetics and lifestyle aspects, in relation to breast cancer risk. We also discussed this pathway in relation to breast cancer survival and the modulation of one-carbon polymorphism in chemotherapy. Emerging evidence on modulation of DNA methylation by one-carbon metabolism suggests that disruption of epigenome might have been the underlying mechanism. More results are expected and will be translated to guidance to the general population for disease prevention as well as to clinicians for treatment and management of the disease.展开更多
AIM: To determine whether Helicobacter pylori (H pylori) infection caused hyperhomocysteinemia by altering serum vitamin B_(12), serum folate and erythrocyte folate levels and whether eradication of this organism decr...AIM: To determine whether Helicobacter pylori (H pylori) infection caused hyperhomocysteinemia by altering serum vitamin B_(12), serum folate and erythrocyte folate levels and whether eradication of this organism decreased serum homocysteine level. METHODS: The study involved 73 dyspeptic H pylork positive patients, none of them had gastric mucosal atrophy based on rapid urease test and histology. Out of 73 patients, 41 (56.2%) showed a successful eradication of H pylori 4 wk after the end of treatment. In these 41 patients, fasting serum vitamin B_(12) folate and homocysteine levels, and erythrocyte folate levels before and 4 wk after H pylori eradication therapy were compared. RESULTS: The group with a successful eradication of H pylori had significantly higher serum vitamin B_(12) and erythrocyte folate levels in the post-treatment period compared to those in pre-treatment period (210±97 pg/mL vs 237±94 pg/mL,P＜0.001 and 442±212 ng/mL vs 539±304 ng/mL, P=0.024, respectively), but showed no significant change in serum folate levels (5.6±2.6 ng/mL vs 6.0+2.4 ng/mL, P=0.341). Also, the serum homocysteine levels in this group were significantly lower after therapy (13.1±5.2 μmol/L vs 11.9±6.2 μmol/L, P=0.002). Regression analysis showed that serum homocysteine level was positively correlated with age (P=0.01) and negatively with serum folate level before therapy (P=0.003). CONCLUSION: Eradication of H pylori decreases serum homocysteine even in patients who do not exhibit gastric mucosal atrophy. It appears that the level of homocysteine in serum is related to a complex interaction among serum vitamin B_(12), serum folate and erythrocyte folate levels.展开更多
Two new folate-derived analogues,named uncarophyllofolic acids A(1)and B(2),respectively,were isolated from the Uncaria rhynchophylla hook bearing stem(Gouteng in Chinese).The distinct stereochemical structures of 1 a...Two new folate-derived analogues,named uncarophyllofolic acids A(1)and B(2),respectively,were isolated from the Uncaria rhynchophylla hook bearing stem(Gouteng in Chinese).The distinct stereochemical structures of 1 and 2 were determined by spectroscopic data analysis in combination with acidic hydrolysis and Marfey’s derivatization,along with comparison of their specific rotation and Cotton effect(CE)data with those of the biogenetically related known derivatives as well as theoretical calculations of electronic circular dichroism(ECD)spectra.A plausible biosynthetic pathway of 1 and 2,associating to folate metabolism and the previously reported orychophragines A-C from Orychophragmus violaceus,is discussed.展开更多
AIM: To evaluate whether folate levels in mucosal tissue and some common methylenetetrahydrofolate reductase (MTHFR) variants are associated with the risk of gastric cancer through DNA methylation. METHODS: Real-time ...AIM: To evaluate whether folate levels in mucosal tissue and some common methylenetetrahydrofolate reductase (MTHFR) variants are associated with the risk of gastric cancer through DNA methylation. METHODS: Real-time PCR was used to study the expression of tumor related genes in 76 mucosal tissue samples from 38 patients with gastric cancer. Samples from the gastroscopic biopsy tissues of 34 patients with chronic superficial gastritis (CSG) were used as controls. Folate concentrations in these tissues were detected by the FOL ACS: 180 automated chemiluminescence system. MTHFR polymorphisms were analyzed by PCR-RFLP, and the promoter methylation of tumor-related genes was determined by methylation-specific PCR (MSP). RESULTS: Folate concentrations were significantly higher in CSG than in cancerous tissues. Decreased expression and methylation of c-myc accompanied higher folate concentrations. Promoter hypermethylation and loss of p16INK4A in samples with MTHFR 677CC were more frequent than in samples with the 677TT or 677CT genotype. And the promoter hypermethylation and loss of p21WAF1 in samples with MTHFR 677CT were more frequent than when 677CC or 677TT was present. The 677CT genotype showed a non-significant higher risk for gastric cancer as compared with the 677CC genotype. CONCLUSION: Lower folate levels in gastric mucosal tissue may confer a higher risk of gastric carcinogenesisthrough hypomethylation and overexpression of c-myc.展开更多
AIM:To evaluate joint effects of Methylentetra-hydrofolate reductase(MTHFR) C677T genotypes,and serum folate/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer...AIM:To evaluate joint effects of Methylentetra-hydrofolate reductase(MTHFR) C677T genotypes,and serum folate/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer patients. METHODS:We examined the associations between MTHFR C677T genotype,and promoter methylation of P16,hMLH1,and hMSH2 tumor-related genes among151 sporadic colorectal cancer patients. The promoter methylation of tumor-related genes was determined by methylation-specific PCR. Eighty six patients from whom fresh tumor samples were obtained and 81 controls were also examined for serum folate and vitamin B12 concentrations by a commercial radioimmunoassay kit. RESULTS:We found 29.1% of cases had tumors with at least one methylated gene promoter. In case-case comparison,we did not find a significant association between methylation in tumors and any single genotype. However,in comparison to controls with the CC genotype,an increased risk of tumor methylation was associated with the CT genotype(OR = 2.5;95% CI,1.1-5.6) . In case-case comparisons,folate/vitamin B12 levels were positively associated with tumor methylation. Adjusted odds ratios for tumor methylation in cases with high(above median) versus low(below median) serum folate/vitamin B12 levels were 4.9(95% CI,1.4-17.7) ,and 3.9(95% CI,1.1-13.9) ,respectively. The frequency of methylated tumors was significantly higher in high methyl donor than low methyl donor group,especially in those with MTHFR CT(P = 0.01) ,and CT/TT(P = 0.002) genotypes,but not in those with the CC genotype(P = 1.0) . CONCLUSION:We conclude that high concentrations of serum folate/vitamin B12 levels are associated with the risk of promoter methylation in tumor-specific genes,and this relationship is modified by MTHFR C677T genotypes.展开更多
基金supported by the Central Public-Interest Scientific Institution Basal Research Fund,China(Grant No.CPSIBRF-CNRRI-202403)。
文摘Rice is a poor source of folate,an essential micronutrient for the body.Biofortification offers an effective way to enhance the folate content of rice and alleviate folate deficiencies in humans.In this study,we confirmed that OsADCS and OsGTPCHI,encoding the initial enzymes necessary for folate synthesis,positively regulate folate accumulation in knockout mutants of both japonica and indica rice backgrounds.The folate content in the low-folate japonica variety was slightly increased by the expression of the indica alleles driven by the endosperm-specific promoter.We further obtained co-expression lines by stacking OsADCS and OsGTPCHI genes;the folate accumulation in brown rice and polished rice reached 5.65μg/g and 2.95μg/g,respectively,representing 37.9-fold and 26.5-fold increases compared with the wild type.Transcriptomic analysis of rice grains from six transgenic lines showed that folate changes affected biological pathways involved in the synthesis and metabolism of rice seed storage substances,while the expression of other folate synthesis genes was weakly regulated.In addition,we identified Aus rice as a high-folate germplasm carrying superior haplotypes of OsADCS and OsGTPCHI through natural variation.This study provides an alternative and effective complementary strategy for rice biofortification,promoting the rational combination of metabolic engineering and conventional breeding to breed high-folate varieties.
基金supported by the Natural Science Foundation of Fujian Province,China(2025J01761 to J.W.)Open Subjects for Key Laboratory of Infection and Immunity of Anhui Higher Education Institutes,Bengbu Medical University(I&I-2024-K03 to J.W.)+2 种基金The Middle-aged and Young Teachers’Educational Research Project of Fujian Province(JAT241032 to J.W.)The Research Foundation for Advanced Talents from Bengbu Medical University(bsqd2024011 to D.C.)High-Level Hospital Construction Project of Nanjing Stomatological Hospital,Affiliated Hospital of Medical School,Institute of Stomatology,Nanjing University(0224C041 to Y.Q.).
文摘Folate(FA)is an essential micronutrient of vitamin B group for growth,development,and reproduction through participating in the nucleotide synthesis and methyl donation reactions.The changes of FA level have been linked to dietary insufficiency(e.g.,poor diet,etc.)malabsorption(e.g.,FA-associated gene mutation,etc.),increased demand(e.g.,pregnancy,etc).or medication(e.g.,antifolates drugs),or bad habits(e.g.,smoking,alcoholism,etc.).Recently,epidemiological data showed that the levels of the host FA typically changed in patients with infectious diseases.Interactions between pathogens,including bacteria,parasites and viruses,and their hosts are complex,in particular,pathogenic infection-mediated changes of the host FA levels can affect the utilization and uptake of limited FA resources of the host.Therefore,FA supplementation or the use of antifolate agents may be a potential antimicrobial strategy for managing infectious diseases.Furthermore,given that the gut microbiota is a primary source of FA in the human body,the association between gut microbiota and pathogenic infections warrants investigation.To date,little is known about how FA status and its biochemistry function affect the course of infectious diseases.In this review,we focus on the roles of FA in the interaction between the host and microbe,and briefly discuss the potential of FA and antifolates agents in the treatment of infectious diseases.
基金supported by Youth Scientific Research Foundation of Beijing Academy of Agriculture and Forestry Sciences (QNJJ202208)the Collaborative Innovation Center of Beijing Academy of Agriculture and Forestry Sciences (KJCX20240408)+1 种基金Major Scientific and Technological Achievements Cultivation Project of Beijing Academy of Agriculture and Forestry SciencesNational Natural Science Foundation of China (32201815)。
文摘One-third of the global population is affected by micronutrient deficiency, particularly folate. Although folate synthesis has been relatively well characterized, few folate-related genes in maize have been cloned, and the molecular mechanism regulating folate synthesis in maize remains unclear. In this study,transcriptome and proteome analyses of three waxy maize inbred lines with high, medium, and low folate contents were performed to identify key genes controlling folate biosynthesis. Pairwise comparisons revealed 21 differentially expressed genes and 20 differentially expressed proteins potentially associated with folate biosynthesis in the three lines. Six key folate-associated genes, Zm Mocos2, Zm GGH,Zm ADCL2, Zm CBR1, Zm SHMT, and Zm Pur H, were identified. These genes encode enzymes that potentially function in folate biosynthesis. Functional validation of one of these genes, Zm ADCL2, using an EMS mutant(Mut9264) showed that a 4-base insertion in an exon increased the folate content of fresh maize kernels 1.37-fold that of the wild type. Zm ADCL2 was considered a potential target for generating maize lines with higher folate content. KEGG enrichment analysis of differentially expressed genes and proteins showed that several pathways in addition to folate biosynthesis were likely indirectly involved in folate metabolism and content(e.g., glycine, serine, and threonine metabolism;purine metabolism;cysteine and methionine metabolism;alanine, aspartate and glutamate metabolism;glutathione metabolism;and pyruvate metabolism. The transcriptome and proteomic data generated in this study will help to clarify the mechanisms underlying folate accumulation and aid breeding efforts to biofortify maize with folate.
基金Supported by the National Key Research and Development Program of China,No.2024YFC2707801the Science and Technology Innovation Commission of Shenzhen,No.JCYJ20230807143800002.
文摘BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as targeted polymerase chain reaction technology),and current findings remain inconsistent.AIM To investigate the association of folate metabolism gene polymorphisms with ASD susceptibility and symptom severity among Chinese children.METHODS Whole-exome sequencing(WES)was conducted to systematically screen for coding region variants of key genes in the folate metabolism pathway among children with ASD,focusing on identifying polymorphisms with high mutation frequencies and potential pathogenic effects.A case-control study was then conducted to explore the association of candidate folate metabolism gene polymorphisms with the susceptibility and severity of ASD.RESULTS WES was performed on 70 children with ASD,and the case-control study included 170 children with ASD and 170 healthy controls.WES revealed that 84.3%(59/70)of children with ASD carried potentially pathogenic variants enriched in folate metabolism pathways.MTHFR C677T and MTRR A66G were significantly associated with an increased risk of ASD in both codominant and dominant models(P<0.05).The dominant model of MTRR A66G was also significantly associated with higher scores in the domains of social relations,body and object use,social and adaptive skills,total scores on the Autism Behavior Checklist,as well as emotional reactivity,nonverbal communication,and activity level on the Childhood Autism Rating Scale(P<0.05).CONCLUSION Most children with ASD carry deleterious variants in folate metabolism-related pathways.MTHFR C677T and MTRR A66G mutations are significantly associated with ASD.
基金Supported by the National Key Research and Development Program of China,No.2021YFC2700700 and No.2021YFC2700704Capital’s Funds for Health Improvement and Research(CFH)in People’s Republic of China,No.2020-1-5112.
文摘BACKGROUND There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus(GDM),and the correlation between genetic factors related to folic acid metabolism pathways and GDM remains to be revealed.AIM To examine the association between single-nucleotide polymorphisms(SNPs)of enzyme genes in the folate metabolite pathway as well as that between GDM-related genes and risk for GDM.METHODS A nested case-control study was conducted with GDM cases(n=412)and healthy controls(n=412).DNA was extracted blood samples and SNPs were genotyped using Agena Bioscience’s MassARRAY gene mass spectrometry system.The associations between different SNPs of genes and the risk for GDM were estimated using logistic regression models.The generalized multi-factor dimensionality reduction(GMDR)method was used to analyze gene-gene and gene-environment interactions using the GMDR 0.9 software.RESULTS The variation allele frequency of melatonin receptor 1B(MTNR1B)rs10830963 was higher in the GDM group than in controls(P<0.05).MTNR1B rs10830963 mutant G was associated with risk for GDM[adjusted odds ratio(aOR):1.43;95%confidence interval(95%CI):1.13-1.80]in the additive model.MTNR1B rs10830963 GG+GC was significantly associated with the risk for GDM(aOR:1.65;95%CI:1.23-2.22)in the dominant model.The two-locus model of MTNR1B rs10830963 and CHEMERIN rs4721 was the best model(P<0.05)for gene-gene interactions in the GMDR results.The high-risk rs10830963×rs4721 type of interaction was a risk factor for GDM(aOR:2.09;95%CI:1.49-2.93).CONCLUSION This study does not find an association between SNPs of folate metabolic enzymes and risk for GDM.The G mutant allele of MTNR1B rs10830963 is identified as a risk factor for GDM in the additive model,and there may be gene-gene interactions between MTNR1B rs10830963 and CHEMERIN rs4721.It is conducive to studying the causes of GDM and provides a new perspective for the precise prevention of this disease.
文摘BACKGROUND Early metastasis and recurrence are risk factors that negatively affect the prog-nosis of advanced hepatocellular carcinoma(HCC).Alpha fetoprotein(AFP)is currently the most prevalent serum biomarker for detecting HCC and predicting tumor recurrence.However,its sensitivity and specificity are not sufficient,espe-cially in patients who are AFP negative.METHODS This work is a retrospective study that included 128 consecutive patients with benign or malignant disease of the liver from 2020 to 2021.FR+CTCs were col-lected from 3 mL of peripheral blood via immunomagnetic depletion of leuko-cytes.After ligand-target polymerase chain reaction,the number of FR+CTCs was measured.Receiver operating characteristic curves were used to determine the threshold of sensitivity and specificity of FR+CTCs.The Youden index was used to identify the optimal cutoff point and diagnostic efficiency of FR+CTCs counts.Univariate and multivariate Cox proportional hazards regression analyses were performed to evaluate the associations of biomarkers or clinical parameters with disease-free survival(DFS).RESULTS The FR+CTCs counts showed excellent diagnostic efficacy in patients with HCC,with high sensitivity(0.905)and specificity(0.773)compared with patients with benign disease.Compared with that of the AFP level,the area under the receiver operating characteristic curve of the FR+CTC count is significantly greater(0.900 compared with 0.730,P<0.05).FR+CTC levels were significantly correlated with macrovascular invasion,tumor size,tumor number,and extrahepatic tumor stage in HCC patients.FR+CTC counts were correlated with DFS in HCC patients after R0 resection.Univariate analysis of DFS revealed that the FR+CTC count,tumor number,Barcelona Clinic Liver Cancer stage and extrahepatic metastasis status were correlated with DFS.Multivariate analysis of DFS revealed that the FR+CTC count and tumor number were correlated with DFS.CONCLUSION Ligand-target polymerase chain reaction is a sensitive tool for quantifying the number of FR+CTCs in HCC patients.These findings could provide new insight for stratifying HCC patients and predicting the recurrence of HCC.
文摘Objective:To explore the polymorphism of folate metabolism genes and its correlation with pregnancy-induced hypertension(PIH)in women of childbearing age in the Neijiang region.Methods:Forty-five pregnant women with hypertension disorders who received prenatal care at the Maternal and Child Health Hospital in the Neijiang region from May 2023 to April 2025 were selected for the study and designated as the case group.Additionally,45 healthy pregnant women during the same period were selected as the control group.Venous blood samples were collected from both groups for folate metabolism gene testing,and the correlation with PIH was analyzed.Results:There were statistically significant differences in BMI index,systolic blood pressure,diastolic blood pressure,serum folate levels,Hcy levels,and vitamin B12 levels between the case group and the control group(p<0.05).The proportions of MTHFR-wild type and MTRR-wild type in the case group were lower than those in the control group,while the proportions of MTHFR-heterozygous mutant type and MTRR-heterozygous mutant type were higher in the case group(p<0.05).The Logistic regression model showed that overweight/obesity,abnormal folate levels,abnormal Hcy levels,abnormal vitamin B12 levels,MTHFR-heterozygous mutant type,and(repeated entry corrected to another relevant factor if necessary,but assuming it’s a typo and should be another mutant type or omitted for clarity,here kept as is for direct translation)MTHFR-heterozygous mutant type(note:this repetition should likely be corrected in the original text,e.g.,to MTRR-heterozygous mutant type or another relevant factor)were independent risk factors for the occurrence of HDP(p<0.05),while MTHFR-wild type and MTRR-wild type were protective factors against HDP(p<0.05).Conclusion:The polymorphism distribution of key genes involved in folate metabolism among women of childbearing age in Neijiang is significantly associated with the occurrence of Hypertensive Disorders of Pregnancy(HDP).Mutant genotypes of MTHFR and MTRR serve as independent risk factors for HDP,while the wild-type acts as a protective factor.Additionally,overweight/obesity,reduced serum folate levels,hyperhomocysteinemia,and vitamin B12 deficiency are also important risk indicators for the onset of HDP.
基金National key Basic Research Program(Grant No.2013CB932501)National Natural Science Foundation of China(Grant No.81273454 and 81473156)+1 种基金Beijing National Science Foundation(Grant No.7132113)Doctoral Foundation of the Ministry of Education(Grant No.20130001110055)
文摘Surface modification may have important influences on the penetration behavior of nanoscale drug delivery system. In the present study, we mainly focused on whether cell targeting or cell penetration could affect penetration abilities of nanostructured lipid carriers（NLC）. Real--time penetration of folate--or cell penetrating peptide（CPP）-modified NLC was evaluated using a multicellular tumor spheroid（MTS） established by stacking culture method as an in vitro testing platform. The results suggested that CPP modification had a better penetration behavior both on penetration depth and intensity compared with folate-modified NLC at the early stage of penetration process.
基金National Natural Science Foundation of China(Grant No.81273454 and 81473156)Beijing National Science Foundation(Grant No.7132113)+1 种基金National Key Basic Research Program(Grant No.2013CB932501)Doctoral Foundation of the Ministry of Education(Grant No.20130001110055)
文摘Multidrug resistance （MDR） operated by P-glycoprotein （P-gp） is one of the major causes in the treatment failure of cancers. In this work, docetaxel-loaded mixed micelles comprised of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy （polyethylene-glycol）2000 （DSPE-PEG2000）, D-α-Tocopherylpolyethylene glycol 1000 succinate （TPGSIooo） and DSPE-PEG2000-folate were developed to overcome MDR and reduce the side effect of docetaxel in cancer therapy. The diameters of micelles ranged from 13 to 26 nm and the encapsulation efficiencies were all above 85%. The influences of DSPE-PEG2000 and TPGSIooo ratios on the micellar characteristics and anti-resistant tumors effects were evaluated. Micelles with high TPGS1000 amount showed an increased cellular uptake and stronger cytotoxicity against MDR KBv cells. Moreover, the micelles modified by targeting ligand of folic acid exhibited better antitumor effect on folate receptor over-expressing KBv cells. The study provides a method for overcoming MDR in cancer therapy.
文摘The set of all spheres and hyperplanes in the Euclidean space Rn+1 could be identified with the Sitter space Λn+1. All the conformal properties are invariant by the Lorentz form which is natural pseudo-Riemannian metric on Λn+1. We shall study behaviour of some surfaces and foliations as their families using computation in the de Sitter space.
基金Project (No. 2003ABA148) supported by the Science Foundation of Hubei Province, China
文摘Objective: To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), the central enzymes in folate metabolism that affects DNA methylation and synthesis, and the risk of Down syndrome in China. Methods: Genomic DNA was isolated from the peripheral lymphocytes of 64 mothers of children with Down syndrome and 70 age matched control subjects. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR 677C→T, MTRR 66A→G and the relationship between these genotypes and the risk of Down syndrome was analyzed. Results: The results show that the MTHFR 677C→T polymorphism is more prevalent among mothers of children with Down syndrome than among control mothers, with an odds ratio of 3.78 (95% confidence interval (CI), 1.78～8.47). In addition, the homozygous MTRR 66A→G polymorphism was independently associated with a 5.2-fold increase in estimated risk (95% CI, 1.90～14.22). The combined presence of both polymorphisms was associated with a greater risk of Down syndrome than the presence of either alone, with an odds ratio of 6.0 (95% CI, 2.058～17.496). The two polymorphisms appear to act without a multiplicative interaction. Conclusion: MTHFR and MTRR gene mutation alleles are related to Down syndrome, and CT, TT and GG gene mutation types increase the risk of Down syndrome.
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.
文摘AIM: To investigate serum levels of homocysteine (Hcys) and the risk that altered levels carry for thrombosis development in ulcerative colitis (UC) patients. METHODS: 55 UC patients and 45 healthy adults were included. Hcys, vitamin B12 and folic acid levels were measured in both groups. Clinical history and thrombo- embolic events were investigated. RESULTS: The average Hcys level in the UC patients was 13.3 ± 1.93 μmmol/L (range 4.60-87) and was higher than the average Hcys level of the control group which was 11.2 ± 3.58 μmmol/L (range 4.00-20.8) (P < 0.001). Vitamin B12 and folic acid average values were also lower in the UC group (P < 0.001). Whenmultivariate regression analysis was performed, it was seen that folic acid deficiency was the only risk factor for hyperhomocysteinemia. Frequencies of thromboembolic complications were not statistically significantly different in UC and control groups. When those with and without a thrombosis history in the UC group were compared according to Hcys levels, it was seen that there were no statistically significant differences. A negative linear relationship was found between folic acid levels and Hcys. CONCLUSION: We could not find any correlations between Hcys levels and history of prior thromboembolic events.
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., gas, Fe：~O1 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 27.26 μg/mg. Under TEM, Fe2O4 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 Fe304 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 （ta/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.
基金financially supported by the Fundamental Research Funds for the Central Universities(for M.Shen and X.Shi)the National Natural Science Foundation of China(Nos.81761148028and 21773026)the Science and Technology Commission of Shanghai Municipality(Nos.15520711400 and 17540712000)
文摘We present here the development of cholesterol(Chol)-modified dendrimer system for targeted chemotherapy of folate(FA)receptor-expressing cancer cells. In our study, poly(amidoamine)(PAMAM) dendrimers of generation 5(G5) were functionalized stepby-step with Chol, fluorescein isothiocyanate(FI), and FA via a poly(ethylene glycol)(PEG) spacer(PEG-FA), and then acetamide to shield their remaining surface amines. The synthesized G5.NHAc-Chol-FI-PEG-FA(for short, G5-CFPF) dendrimers were utilized to encapsulate 10-hydroxycamptothecin(HCP), a hydrophobic anticancer drug. We find that each G5-CFPF dendrimer can encapsulate 13.8 HCP molecules. The complexes show a slower release profiles of HCP in a pH-dependent manner than the control complexes formed using the same dendrimers without Chol under the same conditions. Thanks to the targeting role played by FA, the complexes display a specific inhibition efficacy to FA receptor-expressing cervical cancer cells. The designed Chol-modified dendrimers may be adopted as a promising carrier for application in targeted cancer therapy.
基金supported by the grants from the National Institutes of Health (No. CA109753)the Department of Defense of USA (No. BC031746 and training award W81XWH-06-1-0298)
文摘One-carbon metabolism is a network of biological reactions that plays critical role in DNA methylation and DNA synthesis, and in turn, facilitates the cross-talk between genetic and epigenetic processes. Genetic polymorphisms and supplies of cofactors （e.g. folate, vitamins B） involved in this pathway have been shown to influence cancer risk and even survival. In this review, we summarized the epidemiological evidence for one-carbon metabolism, from both genetics and lifestyle aspects, in relation to breast cancer risk. We also discussed this pathway in relation to breast cancer survival and the modulation of one-carbon polymorphism in chemotherapy. Emerging evidence on modulation of DNA methylation by one-carbon metabolism suggests that disruption of epigenome might have been the underlying mechanism. More results are expected and will be translated to guidance to the general population for disease prevention as well as to clinicians for treatment and management of the disease.
文摘AIM: To determine whether Helicobacter pylori (H pylori) infection caused hyperhomocysteinemia by altering serum vitamin B_(12), serum folate and erythrocyte folate levels and whether eradication of this organism decreased serum homocysteine level. METHODS: The study involved 73 dyspeptic H pylork positive patients, none of them had gastric mucosal atrophy based on rapid urease test and histology. Out of 73 patients, 41 (56.2%) showed a successful eradication of H pylori 4 wk after the end of treatment. In these 41 patients, fasting serum vitamin B_(12) folate and homocysteine levels, and erythrocyte folate levels before and 4 wk after H pylori eradication therapy were compared. RESULTS: The group with a successful eradication of H pylori had significantly higher serum vitamin B_(12) and erythrocyte folate levels in the post-treatment period compared to those in pre-treatment period (210±97 pg/mL vs 237±94 pg/mL,P＜0.001 and 442±212 ng/mL vs 539±304 ng/mL, P=0.024, respectively), but showed no significant change in serum folate levels (5.6±2.6 ng/mL vs 6.0+2.4 ng/mL, P=0.341). Also, the serum homocysteine levels in this group were significantly lower after therapy (13.1±5.2 μmol/L vs 11.9±6.2 μmol/L, P=0.002). Regression analysis showed that serum homocysteine level was positively correlated with age (P=0.01) and negatively with serum folate level before therapy (P=0.003). CONCLUSION: Eradication of H pylori decreases serum homocysteine even in patients who do not exhibit gastric mucosal atrophy. It appears that the level of homocysteine in serum is related to a complex interaction among serum vitamin B_(12), serum folate and erythrocyte folate levels.
基金supported by the National Natural Sciences Foundation of China(Nos.81630094,21732008,and 81730093)CAMS Innovation Fund for Medical Science of China(Nos.2017-I2M-3-010 and 2016-I2M-1-010)the Drug Innovation Major Project(No.2018ZX09711001-001-001)
文摘Two new folate-derived analogues,named uncarophyllofolic acids A(1)and B(2),respectively,were isolated from the Uncaria rhynchophylla hook bearing stem(Gouteng in Chinese).The distinct stereochemical structures of 1 and 2 were determined by spectroscopic data analysis in combination with acidic hydrolysis and Marfey’s derivatization,along with comparison of their specific rotation and Cotton effect(CE)data with those of the biogenetically related known derivatives as well as theoretical calculations of electronic circular dichroism(ECD)spectra.A plausible biosynthetic pathway of 1 and 2,associating to folate metabolism and the previously reported orychophragines A-C from Orychophragmus violaceus,is discussed.
基金Supported by the National Basic Research Funds of China 973 Project, No. 2005CB522400 grants from the National Natural Science Foundation of China, No. 30470781 grants from Shanghai Municipal Commission for Science and Technology, No. 04DZ14006 and Doctoral Funds from the Ministry of Education of China, No. 20050266013
文摘AIM: To evaluate whether folate levels in mucosal tissue and some common methylenetetrahydrofolate reductase (MTHFR) variants are associated with the risk of gastric cancer through DNA methylation. METHODS: Real-time PCR was used to study the expression of tumor related genes in 76 mucosal tissue samples from 38 patients with gastric cancer. Samples from the gastroscopic biopsy tissues of 34 patients with chronic superficial gastritis (CSG) were used as controls. Folate concentrations in these tissues were detected by the FOL ACS: 180 automated chemiluminescence system. MTHFR polymorphisms were analyzed by PCR-RFLP, and the promoter methylation of tumor-related genes was determined by methylation-specific PCR (MSP). RESULTS: Folate concentrations were significantly higher in CSG than in cancerous tissues. Decreased expression and methylation of c-myc accompanied higher folate concentrations. Promoter hypermethylation and loss of p16INK4A in samples with MTHFR 677CC were more frequent than in samples with the 677TT or 677CT genotype. And the promoter hypermethylation and loss of p21WAF1 in samples with MTHFR 677CT were more frequent than when 677CC or 677TT was present. The 677CT genotype showed a non-significant higher risk for gastric cancer as compared with the 677CC genotype. CONCLUSION: Lower folate levels in gastric mucosal tissue may confer a higher risk of gastric carcinogenesisthrough hypomethylation and overexpression of c-myc.
基金The office of the Vice Chancellor for Research, Shiraz University of Medical Sciences, No. 83-2212 Grant from the Gastroenterohepatology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
文摘AIM:To evaluate joint effects of Methylentetra-hydrofolate reductase(MTHFR) C677T genotypes,and serum folate/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer patients. METHODS:We examined the associations between MTHFR C677T genotype,and promoter methylation of P16,hMLH1,and hMSH2 tumor-related genes among151 sporadic colorectal cancer patients. The promoter methylation of tumor-related genes was determined by methylation-specific PCR. Eighty six patients from whom fresh tumor samples were obtained and 81 controls were also examined for serum folate and vitamin B12 concentrations by a commercial radioimmunoassay kit. RESULTS:We found 29.1% of cases had tumors with at least one methylated gene promoter. In case-case comparison,we did not find a significant association between methylation in tumors and any single genotype. However,in comparison to controls with the CC genotype,an increased risk of tumor methylation was associated with the CT genotype(OR = 2.5;95% CI,1.1-5.6) . In case-case comparisons,folate/vitamin B12 levels were positively associated with tumor methylation. Adjusted odds ratios for tumor methylation in cases with high(above median) versus low(below median) serum folate/vitamin B12 levels were 4.9(95% CI,1.4-17.7) ,and 3.9(95% CI,1.1-13.9) ,respectively. The frequency of methylated tumors was significantly higher in high methyl donor than low methyl donor group,especially in those with MTHFR CT(P = 0.01) ,and CT/TT(P = 0.002) genotypes,but not in those with the CC genotype(P = 1.0) . CONCLUSION:We conclude that high concentrations of serum folate/vitamin B12 levels are associated with the risk of promoter methylation in tumor-specific genes,and this relationship is modified by MTHFR C677T genotypes.
