Design, synthesis and biological activity of 6-substituted carbamoyl benzimidazoles as new nonpeptidic angiotensin II AT₁ receptor antagonists

A series of 6-substituted carbamoyl benzimidazoles were designed and synthesised as new nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed a nanomolar AT(1) receptor binding affinity for all compounds in the series, and a potent antagonistic activity in an isolated rabbit aortic strip functional assay for compounds 6f, 6g, 6h and 6k was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6g is an orally active AT(1) receptor antagonist with low toxicity.     

转Bar基因甘蓝型油菜叶片蛋白质组变化的初步分析

采取SDS-PAGE与MALDI-TOF-MS联用的方法,对抗除草剂转Bar基因T1代甘蓝型油菜与普通栽培油菜的叶片蛋白质组进行比较性研究,获得差异蛋白质组的重要信息,并初步探讨差异蛋白的主要功能,以期找到与转Bar基因油菜抗除草剂有关的蛋白质,揭示其抗性机理.双向电泳表达图谱研究表明,Bar基因的转入使得转基因油菜中的差异蛋白表达质与量发生了显著变化,共得到16个发生差异表达的蛋白质点,其中11个经质谱分析功能得到鉴定,这些鉴定出的蛋白质涉及多个生理过程,如能量与代谢、信号转导、代谢相关蛋白离子转运和防御应答等.     

亚砷酸钠对胰岛β细胞的Nrf2及其调控的抗氧化酶表达的影响

目的检测亚砷酸钠对小鼠胰岛B细胞的核转录因子Nrf2及其调控的抗氧化酶硫氧还蛋白（Srx）,y-谷氨酰半胱氨酸连接酶催化亚基（Gele）表达的影响。方法应用2、4、6、8、10t2mol／L亚砷酸钠（NaAs02）作用MIN6细胞6h,通过WesternBlot检测Nrf2蛋白表达;利用Real—timePCR检测抗氧化酶Srx、Oclc的mRNA表达。结果4／μmol／L亚砷酸钠染毒6h后,Nrf2的蛋白表达显著增高,并随着亚砷酸钠剂量的增大,Nrf2蛋白表达也随之增多。抗氧化酶Srx、GelcmRNA在2μmol／L亚砷酸钠染毒6h后开始出现明显的诱导表达,并随亚砷酸钠剂量的增加而表达增强。结论亚砷酸钠能诱导小鼠胰岛B细胞Nrf2蛋白及其调控的抗氧化酶Srx和Gclc基因的表达,并存在显著地剂量依赖性。     

shRNA抑制宫颈癌Hela细胞株HPV18 E6、E7基因表达的研究

应用短发夹RNA(Short hairpin RNA,shRNA)表达载体抑制宫颈癌Hela细胞株HPV18 E6、E7基因的表达。应用已鉴定的shRNA表达载体pHPV1、pHPV2转染Hela细胞,G418筛选阳性细胞,建立稳定转染细胞株;倒置荧光显微镜检测转染情况;提取细胞内总RNA,RT-PCR方法检测HPV18 E6、E7 mRNA;WesternBlot检测HPV18 E6、E7蛋白表达的变化;采用灰度分析软件对PCR扩增条带与蛋白质条带进行灰度分析。pHPV1实验组细胞内HPV18 E6、E7 mRNA含量分别为阴性对照组的31%、38%,E6、E7蛋白分别为阴性对照组的37%、31%;pHPV2实验组细胞内HPV18 E6、E7 mRNA含量分别为阴性对照组的54%、77%,E6、E7蛋白分别为阴性对照组的52%、83%。pHPV1、pHPV2表达载体能抑制Hela细胞HPV18 E6、E7的表达,针对外显子区434-452的pHPV1抑制作用更强。     

下丘脑室旁核注射GLP-1 对糖尿病大鼠中枢GLP-1 受体表达

目的:探讨下丘脑室旁核(hypothalamic paraventricular nucleus,PVN)注射GLP-1(胰高血糖素样肽-1)对糖尿病大鼠胃排空的影响及机制。方法:30只Wistar大鼠随机分为正常对照组(NC组)、糖尿病组(DM组)和GLP-1干预组(GLP-1组),每组各10只。DM组和GLP-1组腹腔注射链脲佐菌素,三组大鼠均PVN区埋置套管,恢复7d,GLP-1组微量注射0.5μg/0.5μl的GLP-1,NC组和DM组大鼠PVN区微量注射等体积生理盐水。甲基纤维素-酚红灌胃法检测胃排空;半定量RT-PCR检测大鼠下丘脑GLP-1RmRNA的表达。结果:DM组胃排空率较NC组明显升高(P<0.05),GLP-1组胃排空明显低于DM组(P<0.05),GLP-1组和NC组差异无统计学意义(P>0.05)。GLP-1组下丘脑GLP-1RmRNA的表达明显高于DM组和NC组(P<0.05),并与胃排空率成负相关(P<0.05)。DM组和NC组差异无统计学意义(P>0.05)。结论:PVN区注射GLP-1可以抑制糖尿病大鼠早期胃排空加速,作用机制可能和促进下丘脑GLP-1受体表达有关。     

面部念珠菌性肉芽肿1例

报道1例面部皮肤念珠菌性肉芽肿.患者女,14岁,口角糜烂10 a,面部散在斑块、结痂6 a.表现为面部大小不等圆形暗红色斑块,表面见黄褐色厚痂.额部皮损真菌镜检见大量菌丝,真菌培养鉴定为白念珠菌.组织病理见真皮浅中层弥漫性淋巴细胞、少量中性粒细胞浸润,并见多核巨细胞.PAS染色示角质层及痂皮内见大量菌丝,真皮多核巨细胞内见孢子.诊断为念珠菌性肉芽肿.给予灰黄霉素治疗2个月、卡介菌多糖核酸治疗6个月、伊曲康唑治疗7个月后,皮损减少,面部痂皮大部分脱落,目前仍在治疗中.     

两种腹膜透析手术置管术的临床对比研究

目的:探讨腹腔镜下腹膜透析置管术与手术切开腹膜透析置管术的临床对比与应用价值.方法:选择2007年3月1日至2012年3月1日在新疆维吾尔自治区人民医院肾病科收治的慢性肾功能衰竭且自愿行腹膜透析的患者96例,其中45例在局麻下行常规手术切开置管术(A组),51例行腹腔镜置管术(B组),术后均使用百特双联系统装置进行腹膜透析.并对术后导管相关性并发症、住院天数、手术费用等方面进行回顾性分析和对比.结果:A组中:导管移位3例(6.7％),网膜包裹2例(4.4％),胸膜瘘1例(2.2％),腹膜炎1例(2.2％),短期透析引流时疼痛2例(4.4％),总体导管相关并发症发生率(19.9％),手术时间为25-40 min,人均手术费用1000元,住院时间7-15天.B组中:无一例发生漂管,阴囊水肿2例(3.9％％),透析管周围渗液2例(3.9％),胸膜瘘1例(2.0％),腹壁疝2例(3.9％),腹膜炎1例(2.0％),总体导管相关并发症发生率(15.7％),手术时间为15-25min,人均费用5500元,住院时间12-25天.结论:腹腔镜置管术与手术切开置管术各有利弊,选择哪种方法要根据患者经济、身体状况、患者意愿来选择.     

Functional analysis of slow myosin heavy chain 1 and myomesin-3 in sarcomere organization in zebrafish embryonic slow muscles

Myofibrillogenesis, the process of sarcomere formation, requires close interactions of sarcomeric proteins and various components of sarcomere structures. The myosin thick filaments and M-lines are two key components of the sarcomere. It has been suggested that myomesin proteins of M-lines interact with myosin and titin proteins and keep the thick and titin filaments in order. However, the function of myomesin in myofibrillogenesis and sarcomere organization remained largely enigmatic. No knockout or knockdown animal models have been reported to elucidate the role of myomesin in sarcomere organization in vivo. In this study, by using the gene-specific knockdown approach in zebrafish embryos, we carried out a loss-of-function analysis of myomesin-3 and slow myosin heavy chain 1 (smyhc1) expressed specifically in slow muscles. We demonstrated that knockdown of smyhc1 abolished the sarcomeric localization of myomesin-3 in slow muscles. In contrast, loss of myomesin-3 had no effect on the sarcomeric organization of thick and thin filaments as well as M- and Z-line structures. Together, these studies indicate that myosin thick filaments are required for M-line organization and M-line localization of myomesin-3. In contrast, myomesin-3 is dispensable for sarcomere organization in slow muscles.     

Therapeutic effects of human amniotic epithelial cell transplantation on double-transgenic mice co-expressing APPswe and PS1ΔE9-deleted genes

Human amniotic epithelial cells (HAECs), which exhibit characteristics of embryonic and pluripotent stem cells, could be utilized for cell therapy without legal or ethical problems. Double-transgenic (TG) mice (n=20) and wild-type (WT) mice (n=20) were randomly assigned to two groups, respectively. The transplantation group was treated with HAECs and the control group with PBS. A six-radial arm water maze was used to assess spatial memory. Immunofluorescence was utilized to track HAEC survival. Immunohistochemistry was used to determine octamer-binding protein 4 (oct-4) and nanog expression in the HAECs. High-performance liquid chromatography (HPLC) was used to measure acetylcholine levels in the hippocampus. The density of cholinergic neurons in the basal forebrain and nerve fibers in the hippocampus was measured following acetylcholinesterase staining. Results showed that transplanted HAECs survived for at least eight weeks and migrated to the third ventricle without immune rejection. Graft HAECs also expressed the specific stem cell markers oct-4 and nanog. Compared with the control group, HAEC transplantation significantly ameliorated spatial memory deficits in TG mice, as well as increased acetylcholine levels and the number of hippocampal cholinergic neurites. Intracerebroventricular HAEC transplantation improved spatial memory in double-TG mice, and results suggested that increased acetylcholine levels in the hippocampus, released by surviving cholinergic neurites, were responsible for this improvement.