乙肝后肝硬化证候的尿代谢组学研究

目的:运用代谢组学方法,探讨慢性乙型病毒性肝炎(乙肝)后肝硬化患者证候间尿代谢物的差异及其代谢模式。方法:采用GC/MS的尿液衍生化方法,分析乙肝后肝硬化患者不同证候内源性小分子代谢物,并进行单维和多维统计分析,通过与标准品的对照确认差异性代谢物。结果:在健康者与乙肝后肝硬化患者、不同中医证候的患者间,均获得了差异性尿代谢物,这些代谢物与能量代谢和氨基酸代谢等通路密切相关。其中在湿热内蕴证与肝肾阴虚证之间存在支链氨基酸的差异。结论:乙肝后肝硬化患者不同证候间存在着尿代谢物的差异,证候间可能具有不同的代谢模式。     

Transposon-based screens for cancer gene discovery in mouse models

Significant emphasis has recently been placed on the characterization of the human cancer genome. This effort has been assisted by the development of new DNA sequencing technologies that allow the genomes of individual tumors to be analyzed in much greater detail. However, the genetic complexity of human cancer has complicated the identification of driver mutations among the more abundant passenger mutations found in tumors. Recently, the Sleeping Beauty (SB) transposon system has been engineered to model cancer in mice. SB-induced tumors are produced by transposon insertional mutagenesis, thus the tagged mutations facilitate the identification of novel cancer genes. This review provides a brief summary of the SB system and its use in modeling cancer in mice.     

MK-801急性处理改变斑马鱼幼鱼自发运动和焦虑行为

 目的  在不同光照条件下,地卓西平马来酸盐(dizocilpine,MK-801)急性处理对斑马鱼幼鱼自发运动和焦虑行为的影响。方法  野生型AB品系斑马鱼幼鱼(5天和7天)暴露在不同浓度MK-801 (0、10、20、50、100、200 μmol/L)溶液中。在光照与黑暗交替条件下,记录斑马鱼幼鱼每分钟游动距离和趋触性。结果  光照条件下,MK 801急性处理能显著降低幼鱼自发运动(P<0.05);黑暗条件下,MK-801急性处理也能降低幼鱼自发运动(P<0.05),但10 μmol/L MK-801对5天幼鱼自发运动无显著影响(P>0.05);黑暗条件下,7天幼鱼在100 μmol/L MK-801作用下抗焦虑能力显著增加,5天幼鱼在20、50 μmol/L MK-801作用下有显著的抗焦虑能力(P<0.05);光照条件下,斑马鱼幼鱼的抗焦虑行为都无显著变化(P>0.05)。结论  MK-801诱导幼鱼自发运动降低;在黑暗条件下,MK-801用药组(20、50、100和200 μmol/L)的幼鱼表现出抗焦虑行为;年龄、药物剂量和光照条件共同作用影响斑马鱼幼鱼的行为模式。     

Type 2 diabetes mellitus augments Parkinson’s disease risk or the other way around: Facts,challenges and future possibilities

About 10% of the adult population is living with type 2 diabetes mellitus (T2DM) and 1% of the population over 60 years of age is suffering from Parkinson’s disease (PD). A school of thought firmly believes that T2DM, an age-related disease, augments PD risk. Such relationship is reflected from the severity of PD symptoms in drug naive subjects possessing T2DM. Onset of Parkinsonian feature in case controls possessing T2DM corroborates the role of hyperglycemia in PD. A few cohort, meta-analysis and animal studies have shown an increased PD risk owing to insulin resistance. High fat diet and role of insulin signaling in the regulation of sugar metabolism, oxidative stress, α-synuclein aggregation and accumulation, inflammatory response and mitochondrial function in PD models and sporadic PD further connect the two. Although little is reported about the implication of PD in hyperglycemia and T2DM, a few studies have also contradicted. Ameliorative effect of anti-diabetic drugs on Parkinsonian symptoms and vague outcome of anti-PD medications in T2DM patients also suggest a link. The article reviews the literature supporting augmented risk of one by the other, analysis of proof of the concept, facts, challenges, future possibilities and standpoint on the subject.     

Serum 25-hydroxyvitamin D at pregnancy and risk of breast cancer in a prospective study

BackgroundSeveral laboratory and epidemiological studies have inversely linked endogenous vitamin D and the risk of breast cancer. The acquisition of vitamin D over time on the relative risk (RR) of the disease development is not known. In a longitudinal study, we evaluated the association between vitamin D levels at pregnancy over time with the risk of breast cancer, and pregnancy-associated breast cancer.MethodThe risk for subsequent development of breast cancer associated with serum 25-hydroxyvitamin (25-OHD) levels was assessed for consecutive (1st and 2nd pregnancy) samples of 100 cases, with mean lag times (μ_t) of 7.4 and 4.6 years between sampling and the diagnosis, and matched (parity, age, year, season) controls. Pregnancy-associated breast cancer (PABC, 111 case–control pairs, μ_t = 1year) risk was also studied. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the lowest quintile as the reference.ResultsSerum 25-OHD level was not associated with an increased risk neither at the 1st nor at the 2nd pregnancy samples (OR = 1.4, 95%CI 0.6–3.4; OR 1.4, 95%CI 0.7–2.8, respectively), but was associated with an increased risk of PABC (OR = 2.7, 95%CI 1.04–6.7).ConclusionGenerally, vitamin D may not be related to breast cancer risk but the increased PABC risk fits the association of vitamin D with the most aggressive cancers, and warrants caution with vitamin D supplementation during pregnancy.     

FABP4基因与中国汉族青少年肥胖相关性研究

目的探讨血清脂肪细胞型脂肪酸结合蛋白(FABP4)水平及其基因多态性与中国汉族青少年超重肥胖的相关性。方法收集上海地区汉族青少年的血液样本,其中154名为肥胖、111名超重、120名体质量正常,采用酶联免疫吸附法测定血清FABP4水平,并采用PCR结合Sanger测序法对FABP4基因第四号外显子中的20个SNPs位点进行比对分析。结果肥胖及超重青少年血浆FABP4蛋白水平均明显高于体质量正常者,差异有统计学意义(P<0.05)。在受试女性青少年中,FABP4基因的rs16909187(A/G)和rs16909196(A/T)位点等位基因(A)分布频率在超重组中显著低于正常组;而rs1054135(A/G)位点的等位基因(G)分布频率在肥胖组中显著低于正常组,差异均有统计学意义(P<0.05)。结论超重及肥胖青少年的血清FABP4蛋白水平升高,不同体质量女性青少年FABP4基因多态性不同。     

TNNT1 myopathy with novel compound heterozygous mutations

Nemaline myopathies are clinically and genetically heterogeneous disorders caused by several different genes. One of them is TNNT1, which was initially described in Amish families and has not been reported in Asian populations. Although most TNNT1 myopathies are caused by loss-of-function mutations, several recent studies have shown that missense mutations can also be pathogenic. A 16-year-old Korean boy with progressive muscle weakness visited the Seoul National University Hospital. He showed generalized myopathy, which was predominant in the paraspinal and neck muscles. Moreover, nemaline rods were observed in a muscle biopsy. Whole-exome sequencing of DNA samples of the patient and his younger brother, who had a similar phenotype, revealed novel compound heterozygous mutations in TNNT1 (c.724G>C (p.Ala242Pro) and c.611+1G>A). Sanger sequencing of cDNA extracted from muscle samples of the patient confirmed partial or total skipping of exon 11 in the splicing variant. The impact of the missense variant on muscle integrity and locomotor activity was verified using a zebrafish loss-of-function model. Here, we reported novel familial cases of TNNT1 myopathy with intermediate clinical presentations caused by compound heterozygous mutations and demonstrated their functional defects using an animal model.