肺纤维化初期肺动脉高压大鼠肺动脉反应性的变化

目的：观察肺纤维化初期肺动脉高压大鼠肺动脉血管反应性的变化。方法：66只雄性SD大鼠,随机分为博莱霉素（BLM）组和手术对照（Sham）组。BLM组为气管内一次性滴注BLM（5 mg/kg）;Sham组为气管内滴注等容量的生理盐水（NS）。应用离体血管张力检测技术测定大鼠肺动脉血管反应性变化;用HE显示肺动脉壁病理形态学变化;Masson染色检测肺纤维化程度;右心漂浮导管技术测定大鼠平均肺动脉压。结果：①BLM组大鼠的肺动脉血管（保留内皮和去内皮）对苯肾上腺素（PE）的收缩反应均弱于Sham组（P均〈0.05）。②BLM组大鼠肺动脉血管（保留内皮）对氯化乙酰胆碱（Ach）的舒张反应明显弱于Sham组（P〈0.01）。③Sham组有内皮的肺动脉血管对L-NAME和PE联合作用的收缩反应明显强于PE单独作用（P〈0.01）,而BLM组有内皮肺动脉血管对L-NAME和PE联合作用的收缩反应与对PE单独作用比,其差异无统计学意义（P〉0.05）。④BLM组肺动脉内皮细胞脱落。⑤BLM组大鼠肺组织呈现纤维增生初期的病理特征,且大鼠的平均肺动脉压明显高于Sham组（P〈0.05）。结论：肺纤维化形成初期肺动脉高压大鼠肺动脉血管反应性出现异常。     

Mechanistic findings of green tea as cancer preventive for humans

Based on our initial work with green tea, in which repeated topical applications of (-)-epigallocatechin gallate (EGCG), the main green tea polyphenol, inhibited tumor promotion in a two-stage carcinogenesis experiment on mouse skin (Phytother Res 1, 44-47, 1987), numerous scientists have since provided so much additional evidence of the benefits of drinking green tea that it is now an acknowledged cancer preventive in Japan, and will possibly soon be recognized as such in other countries. Our work has so far produced several important results with EGCG and green tea: a wide range of target organs in animal experiments for cancer prevention, wide bioavailability of 3H-EGCG in various organs of mice, delayed cancer onset of patients with a history of consuming over 10 cups of green tea per day, and absence of any severe adverse effects among volunteers who took 15 green tea tablets per day (2.25 g green tea extracts, 337.5 mg EGCG, and 135 mg caffeine) for 6 months. This paper introduces three new findings: 1) EGCG interacted with the phospholipid bilayer membrane resulting in confirmation of the sealing effect of EGCG; 2) EGCG inhibited TNF-alpha gene expression in the cells and TNF-alpha release from the cells; 3) high consumption of green tea was closely associated with decreased numbers of axillary lymph node metastases among premenopausal Stage I and II breast cancer patients, and with increased expression of progesterone and estrogen receptors among postmenopausal ones. These results provide new insights into our understanding of the mechanisms of action of tea polyphenols and green tea extract as a cancer preventive.     

Ethacrynic-acid-induced glutathione depletion and oxidative stress in normal and Mrp2-deficient rat liver

Oxidative stress in the liver is sometimes accompanied by cholestasis. We investigated the localization and role of multidrug-resistance-associated protein (Mrp) 2, a biliary transporter involved in bile-salt-independent bile flow, under ethacrynic acid (EA)-induced acute oxidative stress. Normal Sprague-Dawley rat (SDR) and Mrp2-deficient Eisai hyperbilirubinemic rat (EHBR) livers were perfused with 500 microM EA. The release of glutamic pyruvic transaminase (GPT) and thiobarbituric-acid-reactive substances (TBARS) from EHBR liver was markedly delayed compared with that from SDR liver. This is mainly due to the higher basal level of glutathione (GSH) in EHBR liver (59.1 +/- 0.3 nmol/mg protein) compared with SDR liver (39.7 +/- 1.5 nmol/mg protein). EA similarly induced a rapid reduction in GSH followed by mitochondrial permeability transition in the isolated mitochondria from both SDR and EHBR. Internalization of Mrp2 was detected before nonspecific disruption of the canalicular membrane and GPT release in SDR liver perfused with 100 microM EA. SDR liver preperfused with hyperosmolar buffer (405 mosmol/L) for 30 min induced internalization of Mrp2 without changing the basal GSH level, while elimination of hepatic GSH by 300 microM EA perfusion was significantly delayed thereafter. Concomitantly, hepatotoxicity assessed by the release of GPT and TBARS was also significantly attenuated under hyperosmolar conditions. In conclusion, preserved cytosolic and intramitochondrial GSH is the key factor involved in the acute hepatotoxicity induced by EA and its susceptibility could be altered by the presence of Mrp2.     

口服草原兔尾鼠卵透明带3纳米乳剂DNA疫苗免疫效果研究

用免疫不育疫苗控制有害动物的数量成为动物种群数量控制的一个有效措施,对于大多数动物来说．口服饵料发送系统是最好的选择。但是口服疫苗容易产生耐受,且生物利用度低,利用多聚物包裹口服疫苗是一种打破口服耐受．提高其生物利用度的新途径。本文以纳米乳剂作为草原兔尾鼠卵透明带3（Lugurus zone pellucida 3,LZP3）DNA疫苗的发送载体,探讨通过口服途径增强小鼠的免疫效果和抗生育率。用纳米乳剂包裹lzp3 DNA疫苗后,采用强阴离子交换色谱法测定纳米乳剂的包封率．将制备好的质粒纳米乳剂lzp3 DNA疫苗通过口服饵料免疫小鼠,检测到免疫后小鼠的体内产生了特异性的抗LZP3的IgG和IgA。对免疫后小鼠进行抗生育实验,分析生育后免疫小鼠的卵巢病理切片。研究结果表明,用质粒纳米乳剂如p3DNA疫苗通过口服途径免疫．在小鼠的血清和粘液中检测到了特异性的抗LZP3的IgG和IgA,同时也产生了相应的抗生育作用．表明纳米乳剂作为口服不育疫苗的发送载体是可行的,为草原兔尾鼠鼠害的防治提供了理论基础．     

Triterpenoid saponins from Fatsia japonica

Five triterpenoid saponins isolated from the flowers, the mature fruits and the leaves of Fatsia japonica were identified as 3-O-[β-d-glucopyranosyl(1→4)-β-d-glucopyranosyl]-hederagenin (1), 3-O-[β-d-glucopyranosyl-(1→4)-α-l-arabinopyranosyl]-oleanolic acid (2), 3-O-[α-l-arabinopyranosyl]-hederagenin (3), 3-O-[β-d-glucopyranosyl]-hederagenin (4) and 3-O-[β-d-glucopyranosyl(1→4)-α-l-arabinopyranosyl]-hederagenin (5). The saponins 1 and 2 are new, naturally occurring, triterpenoid saponins. The distribution of the five saponins in three parts of the plant was investigated. Saponins 2, 3 and 5 were present in the flowers, saponins 1, 3, 4 and 5 were in the mature fruits and saponins 2, 3, 4 and 5 were in the leaves.     

细菌漆酶的生物信息学分析

漆酶是一种含铜的多酚氧化酶。本研究利用生物信息学分析工具对细菌的漆酶蛋白序列的基本性质、保守结构域、系统发育树以及结构等进行了分析。所分析细菌主要分布在变形菌门、放线菌和厚壁菌门。细菌漆酶的物理化学性质相似,但不同细菌来源的漆酶之间序列相似性较低,但其仍然具有容易识别的保守结构域特征。二级结构及三级结构具有明显的相似性。细菌漆酶的生物信息分析为其功能研究及在其他微生物中研究该类酶提供了基础。     

Systematic analysis of multigene predictors in gastric cancer exploiting gene expression signature

Gastric cancer (GC) is the second most common cause of cancer death worldwide but could be more curable if diagnosed at an earlier stage. At present, the capability to predict the efficaciousness of molecular diagnosis for GC for each patient remains elusive. The purpose of this study was to identify tumor biomarkers through systems analysis of multigene predictors exploiting the available data resource. In this study, we investigated the top 10% overexpressed genes in GC from five data sets of the Oncomine platform, with 265 GC samples versus 174 normal gastric mucosa samples. Sixteen candidate genes were identified as predictors of GC, of which 14 genes were verified through the comparison of expression levels in specimens from normal (chronic gastritis, 21 samples) and GC groups (38 samples). In addition, unique molecular portraits of diffuse adenocarcinoma (DA), intestinal adenocarcinoma (IA), and mixed adenocarcinoma (MA) were studied through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, where DA showed higher extracellular matrix alteration while IA and MA showed higher cell-cycle alteration than other types. We also found that the elevated expressions of genes during GC progression were independent of gene mutations, and high core-binding factor subunit β expression is correlated with a high overall survival rate in GC patients. Our research may provide an efficient clinical diagnosis of GC at an early stage with high accuracy and thus help improve the overall survival rate through early therapeutic interventions.