中度高海拔地区人群血清叶酸与EPO的关系探讨

目的探讨中度高海拔地区人群叶酸营养水平与促红细胞生成素的关系。方法以2014年1月至2014年8月来自云南省弥勒市三个镇(海拔1 000 m)的健康人群485例为研究对象,进行问卷调查、体格检查,同时进行血常规、血清促红细胞生成素(EPO)、血脂四项以及血清叶酸检测,按照血清叶酸浓度将研究对象分为高、中、低血清叶酸组,运用多变量一般线性模型以及Spearman秩相关分析,分析叶酸和EPO之间的关联性。结果中度高海拔地区人群,在低、中、高血清叶酸浓度组间,血清EPO水平不同,差异具有统计学意义(P0.05);LDL-C在三组间差异也具有统计学意义(P0.05);而RBC,Hb,TC,TG,HDL-C水平在三组间的差异无统计学意义(P0.05);血清叶酸浓度与EPO呈正相关关系(rs=0.731,P0.001),与Hb呈负相关关系(rs=-0.101、P0.05),与RBC的相关系数无统计学意义。结论中度高海拔人群的血清叶酸浓度与血清EPO明显相关,血清叶酸浓度高者其血清EPO也较高,提示保持良好的叶酸营养状况有益于中度高海拔地区人群维持血清高EPO水平。     

Voluntary fortification of breakfast cereals with folic acid: contribution to dietary intake in Australia

Ready-to-eat breakfast cereals have been voluntarily fortified with folic acid since 1995, with the purpose of reducing the prevalence of neural tube defects in utero. Using data from the recent Australian Health Survey, this study aimed to estimate folate intake from one serving of breakfast cereals (median amount). Various commercial brands were purchased in 2002 (n?=?19) and in 2014 (n?=?14); folate was determined by microbiological assay and high-pressure liquid chromatography (HPLC). Total folate (μg/100?g) in 2002 and 2014 selections were 144–633 and 147–564, respectively, and mostly comparable to nutrition labels. Folic acid (2014 selection) using HPLC, ranged from 85 to 411?μg/100?g. Intake of 51?g cereals/serving by individuals ≥2 years could contribute 75–288?μg dietary folate equivalent. It seems that folic acid intake among children (2–3 years) exceeds the recommended dietary intake, when certain brands of breakfast cereals are consumed. Accordingly, the benefits and potential detrimental effects of the voluntary fortification need to be further explored.     

叶酸受体靶向伊马替尼pH敏感脂质体的制备工艺及质量评价研究

摘 要 目的：运用改良的硫酸铵梯度法制备叶酸受体靶向伊马替尼pH敏感脂质体（FSLI）,并评价其质量。方法: 采用改良的硫酸铵梯度法制备FSLI,以包封率为指标进行制备工艺的优化;采用琼脂糖凝胶CL 4B柱分离脂质体和游离药,HPLC法测定FSLI的包封率;运用Zeta PALS粒径电位分析仪测定脂质体的平均粒径及Zeta电位,透射电镜观察脂质体的形态;运用动态透析法考察FSLI在不同pH环境中的药物释放情况,并考察FSLI在不同pH、37℃水浴中的粒径随时间的变化情况。结果: 制得的FSLI为圆形或类圆形的大单室脂质体,平均粒径为（155.2±1.92）nm,Zeta电位为 （29.36±3.21）mV,平均包封率为（90.7±1.70）%。FSLI在pH 7.4的中性环境中,药物释放缓慢,24 h累积释放度为2.76%,而在pH 5.5的酸性环境中,药物释放显著加快,24 h累计释放度均达到93.2%,表现出非常强的pH敏感性能。FSLI在pH 7.4的中性环境中不具有融合性能,而在pH 5.5的酸性环境中,粒径迅速增大,脂质体发生融合。结论:采用改良硫酸铵梯度法制备的FSLI,能获得较高的包封率,并具有良好的pH敏感性能。     

血浆同型半胱氨酸与叶酸、维生素B12及还原酶的关系

目的　探讨叶酸、维生素B1 2 (VB1 2 )、血浆总同型半胱氨酸 (tHcy)、5 ,10 亚甲基四氢叶酸还原酶 (MTHFR)活性及其热敏感性基因型间的相互关系。方法　研究对象为 3 4例生育神经管畸形(NTDs)儿的母亲及 4 2例生育正常儿的母亲 ,检测指标包括tHcy、红细胞叶酸、血清叶酸和VB1 2 、MTHFR酶活性及热敏感性基因型。结果　tHcy、红细胞叶酸、血清叶酸在病例组与对照组间差异无统计学意义 ;NTDs患儿母亲VB1 2 显著低于正常儿母亲 ;tHcy与红细胞叶酸呈显著负相关 ;MTHFR热敏感性基因纯合突变组tHcy显著高于杂合突变和纯合野生组 ;血清维生素水平在MTHFR各基因型间差异无显著性 ;叶酸较低组tHcy略高于叶酸较高组 ,并与MTHFR酶活性呈显著负相关。结论　体内tHcy增高与MTHFR热敏感性基因纯合突变、酶活性下降有关 ;体内叶酸水平高低影响tHcy与MTHFR酶活性相关性。     

The effect of C677T mutation of methylene tetrahydrofolate reductase gene and plasma folate level on hyperhomocysteinemia in patients with meningomyelocele

To evaluate the relationship between genotypes of methylene tetrahydrofolate reductase (MTHFR), and plasma folate and homocysteine (Hcy) levels in meningomyelocele, 21 Korean patients, 47 of their family members, and 43 healthy controls were recruited. The presence of C677T mutation in the MTHFR gene and plasma concentrations of folate/Hcy were investigated. The genotype frequency of C677T mutation was not higher in study groups (patients and family members). The plasma folate concentration showed no difference either between the study and the control groups or among MTHFR-genotypic groups. The plasma Hcy concentration in homozygotes in the study group was higher than that in the control group, and higher than that in heterozygotes when plasma folate levels were low (P=0.006). Although neither MTHFR genotype nor plasma folate/Hcy level plays a definite part on its own, they seem to have an additive effect on the occurrence of meningomyelocele. Our results support folate supplementation for the prevention of hyperhomo- cysteinemia and meningomyelocele. Received: 11 November 1999 Revised: 3 April 2000     

Maternal metabolic profile predicts high or low risk of an autism pregnancy outcome

BackgroundCurrently there is no test for pregnant mothers that can predict the probability of having a child that will be diagnosed with autism spectrum disorder (ASD). Recent estimates indicate that if a mother has previously had a child with ASD, the risk of having a second child with ASD is ∼18.7% (High Risk) whereas the risk of ASD in the general population is ∼1.7% (Low Risk).MethodsIn this study, metabolites of the folate-dependent transmethylation and transsulfuration biochemical pathways of pregnant mothers were measured to determine whether or not the risk of having a child with autism could be predicted by her metabolic profile. Pregnant mothers who have had a child with autism before were separated into two groups based on the diagnosis of their child whether the child had autism (ASD) or not (TD). Then these mothers were compared to a group of control mothers who have not had a child with autism before. A total of 107 mothers were in the High Risk category and 25 mothers in the Low Risk category. The High Risk category was further separated into 29 mothers in the ASD group and 78 mothers in the TD group.ResultsThe metabolic results indicated that among High Risk mothers, it was not possible to predict an autism pregnancy outcome. However, the metabolic profile was able to predict with approximately 90% sensitivity and specificity whether a mother fell into the High Risk group (18.7% risk) or Low Risk group (1.7% risk).ConclusionsBased upon these measurements it is not possible to determine during a pregnancy if a child will be diagnosed with ASD by age 3. However, differences in the folate-dependent transmethylation and transsulfuration metabolites are indicative of the risk level (High Risk of 18.7% vs. Low Risk of 1.7%) of the mother for having a child with ASD.     

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

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

Preparation, therapeutic efficacy and intratumoral localization of targeted daunorubicin liposomes conjugating folate-PEG-CHEMS

Folate polyethylene glycol-cholesterol hemisuccinate (folate-PEG-CHEMS) is a novel folate ligand firstly synthesized by our group and demonstrated good stability and potential targeting results on KB cells in vitro. The current study further explored endocytosis mechanisms of liposomes via folate receptor on L1210JF cells and assessed targeted therapeutic efficacy of folate-PEG-CHEMS anchored liposomes loading daunorubicin (F-L-DNR) in vivo. Folate-PEG-CHEMS was synthesized by a modified method. The liposome properties, cell cytotoxicity, intracellular and intratumoral localization, and therapeutic efficacy on a murine tumor model bearing L1210JF cells were evaluated. High encapsulation efficiency (95.1% ± 1.5%) and appropriate particle size (76.0 ± 35.5 nm) and zeta potential (−12.83 ± 1.36 mV) were achieved for F-L-DNR. IC₅₀ of F-L-DNR on L1210JF cells was 2-3-folds lower than that of non-targeted liposomal daunorubicin (L-DNR). Anticancer efficacy on L1210JF tumor model indicated that mice survival time of F-L-DNR group at doses of 5 mg/kg and 10 mg/kg was significantly longer than that of L-DNR or free DNR. Confocal fluorescence photographs of F-L-DNR indicated enhanced endocytosis of liposomes via folate receptor on L1210JF cells, prolonged retaining time in tumors and improved drug release in the tumor site at 24 h post intravenous injection of F-L-DNR. In conclusion, folate-PEG-CHEMS is an effective ligand for folate-targeted daunorubicin liposomes to achieve increased drug release in tumor and therapeutic efficacy.     

Characterization of the human folate receptor alpha via novel antibody-based probes

Folate receptor alpha (FRA) is a cell surface protein whose aberrant expression in malignant cells has resulted in its pursuit as a therapeutic target and marker for diagnosis of cancer. The development of immune-based reagents that can reproducibly detect FRA from patient tissue processed by varying methods has been difficult due to the complex post-translational structure of the protein whereby most reagents developed to date are highly structure-sensitive and have resulted in equivocal expression results across independent studies. The aim of the present study was to generate novel monoclonal antibodies (mAbs) using modified full length FRA protein as immunogen in order to develop a panel of mAbs to various, non-overlapping epitopes that may serve as diagnostic reagents able to robustly detect FRA-positive disease. Here we report the development of a panel of FRA-specific mAbs that are able to specifically detect FRA using an array of diagnostic platforms and methods. In addition, the methods used to develop these mAbs and their diverse binding properties provide additional information on the three dimensional structure of FRA in its native cell surface configuration.     

叶酸受体α在卵巢上皮性肿瘤中的表达

目的 探讨卵巢上皮性肿瘤中叶酸受体(FR)α的表达及其临床病理学意义.方法 制备包括86例卵巢癌及29例卵巢交界性肿瘤的组织芯片,采用免疫组织化学EnVision法检测上述肿瘤组织中FRα的表达情况,同时采用即时PCR检测40例新鲜冷冻卵巢癌组织以及14例卵巢交界性肿瘤组织中FRα mRNA的表达情况.分析卵巢上皮性肿瘤中FRα表达水平与肿瘤的组织类型、不同发病模式以及临床分期的关系.结果 免疫组织化学染色结果显示,86例卵巢癌中有40例(46.5%)对FRα呈明确阳性反应,其中浆液性癌阳性表达率最高,为62.7%(32/51),高于其他组织类型的癌(P=0.000).按照卵巢癌发病模式区分,Ⅱ型卵巢癌FRα的表达明显高于Ⅰ型卵巢癌,差异具有统计学意义(P=0.001).卵巢癌组FRα表达阳性率高于交界性肿瘤(46.5%∶27.6%),但差异无统计学意义(P=0.074).卵巢癌组FRα的表达与临床分期无相关性(P=0.498).相似的结果也见于采用即时PCR检测FRα mRNA的表达情况:卵巢癌组FRα mRNA表达值高于交界性肿瘤组(P=0.000),在交界性肿瘤中,浆液型mRNA表达值高于黏液型,差异具有统计学意义(P=0.007).结论 卵巢上皮性肿瘤中FRα呈高表达,特别是在恶性肿瘤和浆液性肿瘤中.