KEGG数据库在生物合成研究中的应用

KEGG(Kyoto Encyclopedia of Genes and Genomes)提供了一个操作平台,即以基因组信息(GENES)和化学物质信息(LIGAND)为构建模块,通过代谢网络(PATHWAY)将基因组和生物系统联系起来,然后根据功能等级进行归纳分类(BRITE)。KEGG还为各种组学研究提供相关软件,用于代谢途径重建、遗传分析和化合物比对。作为一个综合数据库,KEGG不仅指导生物燃料、药物和新材料等生物基化学品的合成,而且致力于研究日趋严重的环境问题。系统介绍了KEGG数据库的结构、功能及其相关工具的最新进展,并展望在生物合成中的应用前景。     

Intratesticular hypertonic sodium chloride solution treatment as a method of chemical castration in cattle

Castration of male calves is necessary for trading to facilitate handling and prevent reproduction. However, some methods of castration are traumatic and lead to economic losses because of infection and myiasis. The objective of the present study was to evaluate the efficiency of intratesticular injection (ITI) of hypertonic sodium chloride (NaCl; 20%) solution in male calf castration during the first weeks of life. Forty male calves were allocated to one of the following experimental groups: negative control—surgically castrated immediately after birth; positive control —intact males; G1—ITI from 1- to 5-day old; G2—ITI from 15- to 20-day old; and G3—ITI from 25- to 30-day old. Intratesticular injection induced coagulative necrosis of Leydig cells and seminiferous tubules leading to extensive fibrosis. Testosterone secretion and testicular development were severely impaired in 12-month-old animals from G1 and G2 groups (P < 0.05), in which no testicular structure and sperm cells were observed during breeding soundness evaluation. Rectal and scrotal temperatures were not affected by different procedures. In conclusion, ITI of hypertonic NaCl solution induces sterility and completely suppresses testosterone secretion when performed during the first 20 days of life.     

Glutathione and cysteine enhance porcine preimplantation embryo development in vitro after intracytoplasmic sperm injection

Because intracytoplasmic sperm injection (ICSI) had been introduced to animal science, not only reproductive biology of domestic animals, but also medicine to treat infertility has been developed. This assisted reproductive technology is beneficial for generating transgenic animals, especially pigs, because polyspermy is the greatest hurdle in porcine IVF when researchers make highly qualified preimplantation embryos. However, ICSI-derived embryos expressed high level of reactive oxygen species (ROS), which are known to cause serious dysfunction during preimplantation development. The objective of this study was to investigate the developmental competence, ROS level, and apoptosis index when glutathione (GSH) or cysteine was supplemented into the in vitro culture medium for ICSI-derived porcine embryos. First, we evaluated the effect of different concentrations of GSH or cysteine on developmental ability of porcine ICSI-derived embryos. The cleavage rate (79.6%) and the blastocyst formation rate (20.9%) were significantly improved in culture medium supplemented with 1 mmol/L GSH compared with other concentrations or no supplementation. Also, 1.71 mmol/L cysteine showed a significantly higher proportion of cleavage (80.7%) and blastocyst formation (22.5%) than other cysteine-supplemented groups. Next, we confirmed that intracellular ROS level was significantly reduced in the group of blastocysts cultured with GSH or cysteine after ICSI compared with the no supplementation group. Finally, we found that terminal uridine nick-end labeling index, fragmentation, and total apoptosis were significantly decreased and the total cell number was significantly increased in blastocysts when ICSI-derived embryos were cultured with supplementation of 1.71 mmol/L cysteine or 1 mmol/L GSH. Taken together, these results strongly indicate that GSH or cysteine can improve the developmental competence of porcine ICSI-derived embryos by reducing intracellular ROS level and the apoptosis index.     

丹参多酚酸盐联合凯时注射液治疗慢性肾功能哀竭的临床疗效观察

目的：观察丹参多酚酸盐联合凯时注射液治疗慢性肾功能哀竭（CRF）的临床疗效,探讨提高CRF临床疗效的措施。方法：选择2010年5月至2012年11月我院收治的CRF患者94例,在患者知情同意的前提下,将其随机均分为对照组（n=47例）和观察组（n=47例）,对照组给予常规治疗措施,观察组在以上治疗基础上加用丹参多酚酸盐联合凯时注射液治疗,治疗4周后比较两组患者肾功能指标、临床疗效及不良反应的发生情况。结果：治疗前,两组患者的BUN、Scr和Ccr比较,差异无统计学意义（均P〉0．05）;治疗4周后,两组的BUN、Scr水平均较治疗前显著下降,Ccr水平较治疗前显著升高,且观察组BUN、Scr水平明显低于对照组,而Ccr水平明显高于对照组,差异均具有统计学意义（均P〈0．05）。两组的临床总有效率分别为76．6％和91．5％,观察组显著高于对照组,差异具有统计学意义（均P〈0．05）。治疗过程中,两组不良反应的发生率比较差异无统计学意义（P〉0．05）。结论：丹参多酚酸盐联合凯时注射液辅助治疗CRF可提高临床疗效,且安全性高。     

静注人免疫球蛋白中白喉抗体效价对其Fc段生物学活性检测结果影响的分析

目的分析静注人免疫球蛋白(IVIG)中白喉抗体效价对其Fc段生物学活性检测的影响。方法检测20批IVIG的白喉抗体效价水平和Fc段生物学活性结果,进一步探讨白喉抗体效价与Fc段生物学活性的关系。结果20批IVIG中白喉抗体效价水平均符合中国药典的要求,在3~60 HAU/g之间,其中有两批IVIG的白喉抗体效价水平相对较高,其他18批IVIG的白喉抗体效价水平变化趋势不明显。20批IVIG的Fc段生物学活性均较高,在60%~140%之间。白喉抗体效价水平高者,其Fc段生物学活性并非高,反之亦然。结论 IVIG的Fc段生物学活性与其白喉抗体效价水平无明显的相关性。     

Ultrasound Imaging-guided Intracardiac Injection to Develop a Mouse Model of Breast Cancer Brain Metastases Followed by Longitudinal MRI

Breast cancer brain metastasis, occurring in 30% of breast cancer patients at stage IV, is associated with high mortality. The median survival is only 6 months. It is critical to have suitable animal models to mimic the hemodynamic spread of the metastatic cells in the clinical scenario. Here, we are introducing the use of small animal ultrasound imaging to guide an accurate injection of brain tropical breast cancer cells into the left ventricle of athymic nude mice. Longitudinal MRI is used to assessing intracranial initiation and growth of brain metastases. Ultrasound-guided intracardiac injection ensures not only an accurate injection and hereby a higher successful rate but also significantly decreased mortality rate, as compared to our previous manual procedure. In vivo high resolution MRI allows the visualization of hyperintense multifocal lesions, as small as 310 µm in diameter on T₂-weighted images at 3 weeks post injection. Follow-up MRI reveals intracranial tumor growth and increased number of metastases that distribute throughout the whole brain.     

EU-OPENSCREEN—chemical tools for the study of plant biology and resistance mechanisms

EU-OPENSCREEN is an academic research infrastructure initiative in Europe for enabling researchers in all life sciences to take advantage of chemical biology approaches to their projects. In a collaborative effort of national networks in 16 European countries, EU-OPENSCREEN will develop novel chemical compounds with external users to address questions in, among other fields, systems and network biology (directed and selective perturbation of signalling pathways), structural biology (compound-target interactions at atomic resolution), pharmacology (early drug discovery and toxicology) and plant biology (response of wild or crop plants to environmental and agricultural substances). EU-OPENSCREEN supports all stages of a tool development project, including assay adaptation, high-throughput screening and chemical optimisation of the ‘hit’ compounds. All tool compounds and data will be made available to the scientific community. EU-OPENSCREEN integrates high-capacity screening platforms throughout Europe, which share a rationally selected compound collection comprising up to 300,000 (commercial and proprietary compounds collected from European chemists). By testing systematically this chemical collection in hundreds of assays originating from very different biological themes, the screening process generates enormous amounts of information about the biological activities of the substances and thereby steadily enriches our understanding of how and where they act.     

英夫利西单抗联合复合益生菌对炎症性肠病患者肠黏膜屏障、炎症因子、细胞免疫功能及骨代谢指标的影响

摘要 目的：探讨英夫利西单抗联合复合益生菌对炎症性肠病（IBD）患者肠黏膜屏障、细胞免疫功能及骨代谢指标的影响。方法：研究对象选取2017年3月~2019年12月期间来我院诊治的290例IBD患者,信封抽签法分为对照组和研究组,各145例。研究组采用英夫利西单抗联合复合益生菌治疗,对照组采用英夫利西单抗治疗,比较两组患者疗效、肠黏膜屏障功能、T细胞亚群、骨代谢指标及炎症因子水平,并记录两组治疗期间不良反应情况。结果：对照组治疗2疗程后的临床总有效率为71.72%（104/145）,低于研究组的86.21%（125/145）（P<0.05）。治疗1疗程后、治疗2疗程后,两组患者的C反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）、骨钙素（BGP）、Ｉ-型胶原Ｃ末端肽（CTX）、CD8⁺及尿乳果糖/甘露醇比值均较治疗前降低,治疗2疗程后上述指标水平低于治疗1疗程后,且研究组低于对照组（P<0.05）。治疗1疗程后、治疗2疗程后,两组的CD4⁺、CD4⁺/ CD8⁺较治疗前升高,治疗2疗程后上述指标水平高于治疗1疗程后,且研究组高于对照组（P<0.05）。两组不良反应发生率对比无统计学差异（P>0.05）。结论：英夫利西单抗联合复合益生菌治疗IBD患者,可减轻患者的炎症反应,提高患者的免疫功能,改善其肠黏膜屏障和骨代谢指标,且安全性较好。     

牛肺磷脂注射液在呼吸窘迫综合征患儿正压通气中的应用

目的:探讨牛肺磷脂注射液联合呼吸机鼻塞式持续正压通气治疗新生儿呼吸窘迫综合征的疗效。方法:98例呼吸窘迫综合征新生儿为研究对象,随机数字法分为两组。对照组应用呼吸机鼻塞式持续正压通气治疗,研究组应用牛肺磷脂注射液联合治疗。结果:研究组有效率高于对照组(P<0.05);治疗前两组患儿的动脉血气指标无明显差异,治疗后,研究组12 h及24 h后的PaO₂、血pH水平高于对照组,PaCO₂水平低于对照组,两组差异有统计学意义(P<0.05);治疗前两组患儿的胸部X线情况对比无明显差异,治疗后,研究组胸部X线各项情况的改善均优于对照组,两组差异有统计学意义(P<0.05);研究组用机时间、住院时间均短于对照组(P<0.05);研究组并发症的发生率低于对照组,两组差异有统计学意义(P<0.05)。结论:牛肺磷脂注射液联合呼吸机鼻塞式持续正压通气治疗新生儿呼吸窘迫综合征效果理想,能够改善患儿的动脉血气指标,提高治疗的效果,缩短患儿的用机及住院时间。