结肠癌患者血清叶酸含量分析

以放射免疫法测定36例结肠癌患者血清叶酸浓度,患者血清叶酸水平低于对照组(P＜0.05).这表明血清叶酸浓度与结肠癌的发生密切相关.调整饮食结构,改善低叶酸状态将会在预防结肠癌方面产生积极作用.     

Hyperhomocysteinemia and the response to vitamin supplementation

Summary The long-term vitamin requirements of men (n=22) with moderate hyperhomocysteinemia (plasma total homocysteine concentration > 16.3 mol/1) were investigated over a period of 48 weeks. An initial 6-week period of vitamin supplementation (1.0 mg folic acid, 10 mg pyridoxine, 0.05 mg cyanocobalamin) reduced plasma homocysteine levels 54.7% (P<0.001). However, 18 weeks after vitamin therapy was discontinued, only seven participants (subgroup A) still had plasma homocysteine levels of 16.3 mol/l or lower. The remainder of the participants (subgroup B) required a second 6-week period of vitamin therapy to normalize the elevated plasma homocysteine levels. Substitution of vitamin supplementation by dietary guidelines to increase folate intake from food products failed to maintain normal plasma homocysteine levels in participants from subgroup B. Long-term vitamin supplementation may be required in some individuals to prevent hyperhomo-cysteinemia.Abbreviations HPLC high-performance liquid chromatography - Lp(a) lipoprotein(a) - PLP pyridoxal 5-phosphate     

A1298C methylenetetrahydrofolate reductase mutation and coronary artery disease: relationships with C677T polymorphism and homocysteine/folate metabolism

5, 10-Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in homocysteine/methionine metabolism. The most-studied C677T polymorphism in the MTHFR gene results in a thermolabile variant with reduced activity, and is associated with increased levels of total plasma homocysteine, a risk factor for coronary artery disease. A new mutation in the MTHFR gene (A1298C) has also been reported to lower enzyme activity. Whether A1298C is a risk factor for coronary artery disease, separately or in combination with C677T, and/or relative to total plasma homocysteine and folate status, is unclear to date. We evaluated this hypothesis in 470 angiographically characterized subjects, 302 with coronary artery disease, and 168 with normal coronary arteries. The frequency of the 1298C allele was 0.33 and that of combined heterozygosity 0.315. No difference was found in the frequency of the genotypes or when analyzed for combined heterozygosity between patients with coronary artery disease and normals. Independent of folate status, the 1298C allele was not associated with increased total plasma homocysteine. No additional effect of A1298C on total plasma homocysteine was observed in 148 combined heterozygotes compared with 98 heterozygotes for the C677T alone. These findings do not support a major role for the A1298C mutation in homocysteine metabolism and emphasize the hypothesis that MTHFR genotypes may interfere with coronary artery disease risk only when an unbalanced nutritional status leads to raised total plasma homocysteine levels.     

人类α型叶酸受体基因的克隆及其真核表达载体的构建

目的 探讨如何以人类α型叶酸受体(FOLR-1)基因为基础构建核酸疫苗。方法 应用RT-PCR技术，从人类卵巢癌细胞系-SKOV3细胞中扩增FOLR-1基因，插入克隆载体pGEM-T Easy，经DNA自动测序仪测序证实后，以亚克隆法构建于真核表达载体pcDNA3．1( )，并使用限制性内切酶酶切鉴定。结果 从卵巢癌细胞系SKOV3中成功扩增出FOLR-1基因，并克隆人pcDNA3．1( )载体。结论 成功构建FOLR-1的重组克隆及真核表达载体，为今后利用FOLR-1进行卵巢上皮性肿瘤的免疫及导向治疗研究打下了基础。     

叶酸与宫颈癌关系的病例对照研究

目的探讨膳食叶酸、血清叶酸与宫颈癌的关系以及叶酸和人乳头瘤病毒(HPV)16在宫颈癌发生中的相互作用。方法采用以医院为基础的病例对照研究方法,对111例经病理学确诊的宫颈鳞癌新发病例和111例子宫肌瘤患者进行年龄、籍贯、居住地匹配,在收集宫颈癌相关因素的同时,采用食物频数问卷(FFQ)调查膳食叶酸摄入情况,利用特异PCR检测HPV16 DNA,血清叶酸采用RIA定量测定。结果官颈癌组HPV16感染率(61．26％)显著高于对照组(28．83％),调整OR 值4．95(95％CI:2．49-9．83);病例组膳食叶酸摄入量(5．00μg/kcal±0．41 μg／kcal)和血清叶酸水平 (1．79 ng／ml±1．42 ng／ml)均低于对照组(5．14μg／kcal±0．35μg/kcal,2．59 ng／ml±2．81 ng／ml),差异有统计学意义,特别是随着血清叶酸水平的降低,患宫颈癌的危险性增加(X2=17．37,P=0．000);血清叶酸水平较低同时伴有HPV16感染患宫颈癌的危险明显高于两者单独作用之和,交互作用检验有统计学意义(G=5．56,P=0．02)。结论叶酸缺乏可增加宫颈癌发生的危险。     

蛋氨酸合成酶还原酶基因A66G多态性与Down综合征发生的相关研究

目的:研究蛋氨酸合成酶还原酶(MTRR)基因A66G多态性与Down综合征的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法对32例DS患儿母亲及70例未生育DS患儿女性MTRR的A66G进行基因分析。比较上述各组基因型和等位基因频率分布有无差异。结果:MTRR基因A66G突变型等位基因G频率在实验组和对照组中有显著性差异,GG基因型频率分布差异有显著性(P<0·05)。AG基因型比AA基因型生育DS患儿风险高1·98倍,GG基因型比AA基因型生育DS患儿风险高5·2倍。结论:MTRR A66G基因多态性与Down综合征发生相关,AG、GG基因型增加了Down综合征的发生风险。     

叶酸受体介导99mTc标记c-erbB2癌基因反义寡核苷酸的乳腺癌细胞摄取率

目的研究叶酸受体介导的99mTc标记c-erbB2癌基因反义寡核苷酸乳腺癌细胞的摄取率.方法用双功能鳌合剂次已酰双半胱氨酸(EC)连接15mer寡脱氧核苷酸(ODN)和叶酸(FA),形成ODN-EC-FA,用99mTc标记,形成99mTc-ODN-FA.同样的方法不加叶酸,形成99mTc-ODN.加2μCi的99mTc-ODN-FA和99mTc-ODN到107cell/瓶对数生长期乳腺癌细胞MDA-MB-231,分别于20、40、60、120、180、240分钟测定细胞的摄取率.结果乳腺癌细胞对99mTc-ODN-FA的摄取率明显高于99mTc-ODN.结论叶酸配体与受体的特异结合使寡核苷酸的乳腺癌细胞摄取率明显增加.     

Association of folic acid receptor α in maternal serum with neural tube defects

Abstract

Objective: To evaluate whether serum folic receptor α levels are changed in women whose previous pregnancies were complicated with neural tube defects (NTDs).

Methods: This was a case–control study that included 41 women as the control group who had previously had at least one healthy pregnancy and 37 women as the study group who had a previous pregnancy complicated with NTDs. Blood samples were obtained from all of the participants six weeks after the termination of pregnancy or delivery of a baby. Serum folate receptor α concentrations were analyzed using a commercially available enzyme-linked immunosorbent assay (ELISA) kit.

Results: The mean concentrations of serum folate receptor α were significantly lower in the NTD cases compared to those in the control group (p?=?0.02). There was no significant difference in mean serum folate titers between the NTD cases and the control group (p?=?0.07).

Conclusion: Low serum folic acid receptor α levels in the current study did not appear to be a regulatory marker of maternal folate homeostasis per se but rather a factor that contributed to the development of NTDs.     

叶酸偶联壳聚糖纳米粒的制备

目的制备叶酸偶联的壳聚糖纳米粒。方法根据叶酸与壳聚糖的偶联比选择最佳工艺条件,通过叶酸活性酯与壳聚糖上的氨基反应,制得叶酸偶联的壳聚糖,再通过离子交联法制得叶酸偶联壳聚糖纳米粒,并测定纳米粒的粒径和表面电位。结果正交实验结果显示叶酸活性酯用量和反应温度是影响偶联比的主要因素,在叶酸活性酯与壳聚糖用量比为2∶1,反应温度50℃,反应时间2 h的条件下可得到偶联比大致为每个壳聚糖分子上偶联3个叶酸分子的叶酸偶联壳聚糖。所制得的纳米粒粒径316 nm,表面电位为(24.85±1.14)mV,透射电镜下观察其形态圆整。结论该方法可成功制备叶酸偶联壳聚糖纳米粒。     

Impact of methylenetetrahydrofolate reductase (<Emphasis Type="Italic">MTHFR</Emphasis>) codon (677) and methionine synthase (<Emphasis Type="Italic">MS</Emphasis>) codon (2756) on risk of cervical carcinogenesis in North Indian population

Cervical cancer continues to be the most common cause of death among women in developing countries. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are critical enzymes of folate metabolic pathways. In this work, we have conducted a case–control study to assess the role of these two polymorphisms in cervical cancer development. We obtained blood samples from 200 women with cervical cancer and from equal matched controls and analysed using PCR-RFLP method. We found that the methylenetetrahydrofolate reductase variant CT and CT + TT genotypes decreased cervix cancer risk, statistically significant (OR:0.30, 95% CI: 0.18–0.51, P < 0.001 for CT and OR:0.29, 95% CI: 0.18–0.49, P = 0.0000006 for CT + TT). Similarly in those patients who used oral contraceptive with variant CT genotype, there was statistically highly significant reduced risk of cervix cancer (OR:0.25, 95% CI: –0.12–0.49, P < 0.001) of methylenetetrahydrofolate reductase gene. For the methionine synthase, 2756 variant AG and AG + GG genotypes were similarly associated with highly significant reduced risk of cervix cancer (OR: 0.13, 95% CI: 0.07–0.26, P < 0.001 for AG, and OR: 0.15, 95% CI: 0.08–0.27, P < 0.001 for AG + GG) genotypes. In conclusion, our study suggested that methylenetetrahydrofolate reductase and methionine synthase polymorphisms might have protective effect on the risk of cervical cancer in the North Indian women.