Kynurenine aminotransferase activity in human liver: identity with human hepatic C-S lyase activity and a physiological role for this enzyme

The C-S lyase enzymes are responsible for the generation of mutagenic and cytotoxic metabolites via aberrant drug-metabolising pathways in mammalian tissues. We have examined human hepatic cytosolic, mitochondrial and microsomal fractions for evidence of C-S lyase activity. The cytosolic enzyme was purified using fast protein liquid chromatography over FFQ Sepharose, Mono P and Superose 12. An homogeneous protein (monitored by SDS-PAGE) was obtained following purification, and an 11-fold increase in C-S lyase specific activity was observed. The molecular weight of the enzyme was found to be 37 kDa in denaturing conditions, 82.3 kDa in non-denaturing conditions, and the C-S lyase activity was shown to co-purify with kynurenine aminotransferase activity when the transaminase activity of the enzyme was examined with kynurenine as the substrate.     

Studies on homologous recombination in the green alga Chlamydomonas reinhardtii

The introduction of exogenous DNA into the nuclear genome of Chlamydomonas reinhardtii occurs predominantly via non-homologous (illegitimate) recombination and results in integration at apparently-random loci. Using truncated and modified versions of the C. reinhardtii ARG7 gene in a series of transformation experiments, we demonstrate that homologous recombination between introduced DNA molecules occurs readily in C. reinhardtii, requires a region of homology of no more than 230 bp, and gives rise to intact copies of ARG7 in the nuclear genome. Evidence is presented for homologous recombination between introduced ARG7 DNA and the resident copy of the gene, and for the de-novo synthesis of the ARG7 sequence during transformation.     

肝素酶和碱性成纤维细胞生长因子与非小细胞肺癌转移和预后的关系

目的 探讨肝素酶(heparanase)和碱性成纤维细胞生长因子(bFGF)在人非小细胞肺癌(NSCLC)组织中表达的临床意义及其与肺癌转移和预后的关系。方法 采用免疫组织化学、原位杂交和Western blot方法,检测115例人NSCLC石蜡切片和45例新鲜肺癌及对应癌旁正常组织中肝素酶和bFGF的表达情况。采用χ^2检验、t检验、生存曲线和Cox比例风险回归等方法分析肝素酶和bFGF分别表达及共表达的意义。结果 免疫组织化学染色证实肝素酶(91／115)和bFGF(89／115)主要表达在癌细胞质和(或)细胞膜中,在正常肺泡上皮和支气管上皮中则呈阴性表达。Western blot也证实肝素酶在肺癌中的表达明显增高(P=0．041)。统计分析结果显示：肝素酶和bFGF的表达具有明显的一致性(P：0．0001),二者单独表达和共表达均与肺癌的分期、血管侵袭、淋巴结转移、微血管密度和预后有关,其中,二者共表达时与分期和微血管密度的相关性更显著;另外,bFGF还与肺癌的分化程度有关。多因素分析结果显示,肺癌的分化程度、血管浸润、淋巴结转移和bFGF的表达可以作为判断肺癌预后的危险因素,但肝素酶不是影响预后的独立因素。结论 肝素酶和bFGF均与肺癌的转移、血管生成和预后密切相关。     

APE/Ref-1对细胞因子的调节及与肿瘤的关系

无嘌呤无嘧啶核酸内切酶(apurinic/apyrim idinicendonuclase,APE)又名氧化还原因子1(redox factor1,Ref1),是一种多功能蛋白,除了修复AP位点外,还保持很多转录因子包括AP1、NFκB、CREB、ATF、myb、Pax、HIF1α、HLF、Egr1、NF Y、p53和PEBP2等活性还原状态,对维持DNA的稳定和调节细胞因子的表达具有重要作用。APE/Ref1基因定位于人染色体14q11.212,在体内是一种广泛表达的基因,有胞质表达、胞核表达及胞质和胞核同时表达三种表达模式,与细胞的分化成熟过程有关。APE/Ref1蛋白的不正常表达、分布及功能改变与细胞凋亡、肿瘤发生、神经系统退行性疾病和老年化等病理过程密切相关。对APE1/Ref1功能的深入研究对提高肿瘤相关性疾病的诊治水平必有重大意义。     

一氧化氮和水杨酸依次介导内生真菌诱导子促进苍术细胞中苍术素生物合成的信号转导

目的 研究介导内生真菌诱导子促进苍术悬浮细胞中苍术素生物合成的信号分子及信号转导途径,并探讨诱导子对苍术素合成途径关键酶活性的影响。方法 采用植物细胞悬浮培养法,考察内生真菌诱导子处理下苍术细胞中一氧化氮（NO）、水杨酸（SA）及苍术素量的变化。结果 内生真菌诱导子通过诱导苍术细胞中一氧化氮合酶（NOS）、苯丙氨酸解氨酶（PAL）以及乙酰辅酶A羧化酶（ACC）的活性,显著促进苍术细胞的NO迸发、SA和苍术素的合成。NOS抑制剂PBITU可以阻断诱导子对NO、SA和苍术素合成的促进作用,外源NO供体SNP及外源SA单独处理也能促进苍术素的合成,说明NO和SA是参与苍术素合成的信号分子,且NOS是参与诱导子诱发苍术细胞NO迸发的主要途径。NO猝灭剂cPITO可以有效清除诱导子诱发苍术细胞的NO迸发,显著阻断诱导子对苍术细胞中SA和苍术素合成的促进作用,外源SNP可以逆转cPITO对PAL、ACC活性以及SA、苍术素合成的抑制作用,表明NO是介导内生真菌诱导子诱发苍术细胞中苍术素和SA生物合成所必需的上游信号分子。结论 NO主要通过SA信号途径介导内生真菌诱导子激活ACC,显著促进苍术细胞中苍术素的生物合成。     

Herbal medicines for the prevention of alcoholic liver disease: A review

Ethnopharmacological relevance

Long-term excess alcohol exposure leads to alcoholic liver disease (ALD)—a global health problem without effective therapeutic approach. ALD is increasingly considered as a complex and multifaceted pathological process, involving oxidative stress, inflammation and excessive fatty acid synthesis. Over the past decade, herbal medicines have attracted much attention as potential therapeutic agents in the prevention and treatment of ALD, due to their multiple targets and less toxic side effects. Several herbs, such as Cnidium monnieri (L.) Cusson (Apiaceae), Curcuma longa L. (Zingiberaceae) and Pueraria lobata (Willd.) Ohwi (Leguminosae), etc., have been shown to be quite effective and are being widely used in China today for the treatment of ALD when used alone or in combination.

Aim of the review

To review current available knowledge on herbal medicines used to prevent or treat ALD and their underlying mechanisms.

Materials and methods

We used the pre-set searching syntax and inclusion criteria to retrieve available published literature from PUBMED and Web of Science databases, all herbal medicines and their active compounds tested on ALD induced by both acute and chronic alcohol ingestion were included.

Results

A total of 40 experimental studies involving 34 herbal medicines and (or) active compounds were retrieved and reviewed. We found that all reported extracts and individual compounds from herbal medicines/natural plants could be beneficial to ALD, which might be attributed to regulate multiple critical targets involved in the pathways of oxidation, inflammation and lipid metabolism.

Conclusions

Screening chemical candidate from herbal medicine might be a promising approach to drug discovery for the prevention or treatment of ALD. However, further studies remain to be done on the systematic assessment of herbal medicines against ALD and the underlying mechanisms, as well as their quality control studies.     

63例高级别胶质瘤中IDH1和TERT突变状态的预后价值

目的:探讨异柠檬酸脱氢酶-1（IDH1）和端粒酶逆转录酶（TERT）启动子突变对高级别胶质瘤患者的预后价值。方法:选取2014年9月至2017年6月于我院行手术切除且术后病理提示为高级别胶质瘤的患者63例（WHO Ⅲ级27例，Ⅳ级36例），完善临床资料、随访资料、分子检测结果。应用Sanger测序法检测样本中IDH1和TERT启动子突变情况，根据结果将患者分为不同亚组，通过比较其生存期的差异，分析基因突变与患者预后的关系。结果:63例高级别胶质瘤中，IDH1突变型和野生型患者的中位生存期分别为24和10个月，差异有统计学意义（P＜0.01）；TERT突变型和野生型的中位生存期无明显差异（P＞0.05）。IDH1突变为高级别胶质瘤患者预后良好的因素，TERT突变不能单独提示预后，二者联合分析提示:IDH1突变／TERT突变组预后最好，IDH1野生／TERT突变组预后最差，IDH1突变／TERT野生组预后稍好于IDH1野生／TERT野生组，四组间预后有明显差异。结论:IDH1突变的高级别胶质瘤患者有较好的临床预后，在此基础上，TERT启动子突变检测有助于进一步划分其预后分层。