基于文本挖掘技术探测胰岛淀粉样多肽的研究趋势

胰岛淀粉样多肽是2型糖尿病的重要致病原因之一.为了研究胰岛淀粉样多肽的生物学作用及其应用范围,本文拟通过文本挖掘技术来对胰岛淀粉样多肽生化用专业试剂和试剂盒检测的研究发展趋势进行探测.     

Amyloid beta soluble forms and plasminogen activation system in Alzheimer’s disease: Consequences on extracellular maturation of brain‐derived neurotrophic factor and therapeutic implications

Soluble oligomeric forms of amyloid beta (Aβ) play an important role in causing the cognitive deficits in Alzheimer’s disease (AD) by targeting and disrupting synaptic pathways. Thus, the present research is directed toward identifying the neuronal pathways targeted by soluble forms and, accordingly, develops alternative therapeutic strategies. The neurotrophin brain‐derived neurotrophic factor (BDNF) is synthesized as a precursor (pro‐BDNF) which is cleaved extracellularly by plasmin to release the mature form. The conversion from pro‐BDNF to BDNF is an important process that regulates neuronal activity and memory processes. Plasmin‐dependent maturation of BDNF in the brain is regulated by plasminogen activator inhibitor‐1 (PAI‐1), the natural inhibitor of tissue‐type plasminogen activator (tPA). Therefore, tPA/PAI‐1 system represents an important regulator of extracellular BDNF/pro‐BDNF ratio. In this review, we summarize the data on the components of the plasminogen activation system and on BDNF in AD. Moreover, we will hypothesize a possible pathogenic mechanism caused by soluble Aβ forms based on the effects on tPA/PAI‐1 system and on the consequence of an altered conversion from pro‐BDNF to the mature BDNF in the brain of AD patients. Translation into clinic may include a better characterization of the disease stage and future direction on therapeutic targets.     

Addition of Transdermal or Inhaled Long-Acting β 2-Agonists in Adult Asthmatic Patients Treated with Inhaled Corticosteroids: Switchover Study from Tulobuterol Patch to Salmeterol Dry Powder Inhaler

Sixty-four patients with persistent asthma receiving 200 to 800 μ g of fluticasone propionate daily were enrolled in this switchover study. The patients applied a tulobuterol patch 2 mg every 24 hours for 4 weeks followed by inhalation of salmeterol 100 μ g bid for 4 weeks. The mean values for morning and evening peak expiratory flow improved significantly compared with baseline during the 4 weeks of tulobuterol patch treatment. Further improvement was seen on switching to salmeterol treatment, which was significant even in the first week, and continued until the final week of the study. Use of salmeterol alone resulted in a significant increase in the percentage of forced expiratory volume in 1 second %FEV1 from baseline, with 51% of patients feeling that the treatment was effective (vs. 37% on tulobuterol). These data suggest that salmeterol can achieve better control in asthmatic patients after switching from using tulobuterol patches.     

Elimination of endoplasmic reticulum stress and cardiovascular,type 2 diabetic,and other metabolic diseases

Abstract

Multiple factors including unhealthy living habits influence the life-maintaining functions of the endoplasmic reticulum (ER) and induce ER stress and metabolic abnormalities. The ER responds to the disturbances by activating mechanisms that increase the capacity to eliminate ER stress. This article elucidates the effects of ER activation that eliminates both ER stress and associated cardiovascular, type 2 diabetic (DM2), and other metabolic diseases. ER-activating compounds eliminate ER stress by lowering elevated cholesterol, regress atherosclerosis, decrease cardiovascular mortality, reduce blood glucose and insulin, and, together with the normalization of glucose–insulin homeostasis, remove insulin resistance, pancreatic β-cell failure, and DM2. A deficient cytochrome P450 activity in hepatic ER leads to cholesterol accumulation that induces stress and xanthoma formation, whereas P450-activating therapy up-regulates apolipoprotein AI and LDLR genes, down-regulates apolipoprotein B gene, and produces an antiatherogenic plasma lipoprotein profile. The ER activation reduces the stress also by eliminating hepatic fat and converting saturated fatty acids (FAs) to unsaturated FAs. Cognitive processes require gene expression modification, and preclinical studies indicate that ER-activating therapy improves cognition. Promotion of healthy lifestyle choices and indicated therapies are key factors in the prevention and elimination of ER stress and associated global health problems.     

TAKAYASU'S DISEASE ASSOCIATED WITH GENERALISED AMYLOIDOSIS

A case of Takayasu's disease in a young Caucasian female is described. The major complications which developed over the ten year course of the disease include nephrotic syndrome, severe refractory hypertension, aortic valve regurgitation associated with aneurysmal dilatation of the ascending aorta, and recurrent congestive heart failure. Amyloid deposits have been demonstrated in the aorta, atrial appendage, aortic valve, and renal cortex.
The association of amyloidosis and Takayasu's disease is discussed. (Aust NZ J Med 1985; 15: 343–345.)     

急性肺损伤小鼠血糖水平与支气管肺泡灌洗液中TNF-α、IL-1β的关系

目的：观察脂多糖（LPS）所致急性肺损伤小鼠血糖、支气管肺泡灌洗液（βALF）中TNF—OL、IL-1β的变化规律,并初步探讨它们间的关系。方法：雄性βALβ／c小鼠45只,随机分为正常对照组、麻醉对照组、LPS组（气管内给予LPS1mg／kg）,每组15只。分别于处理后1、3、6、12、24h采血,检测血糖;获取各组小鼠βALF,采用ELISA法检测其中TNF—a和IL-1β的浓度。数据结果用统计学软件SPSS17．0进行分析。结果：与正常对照组及麻醉对照组比较,LPS组小鼠血糖明显升高,12h时与正常对照组比较仍有统计学意义（P〈0．05）;βALF中TNF-α及IL-1β浓度均明显升高,24h时与正常对照组比较仍有统计学意义（P〈0．05）。LPS组小鼠血糖水平与相应时间段βALF中TNF—d浓度呈正相关（L=0．738,P〈0．05）;与相应时间段βALF中IL-1β浓度呈正相关（0=0．618,P〈0．05）。结论：LPS诱导的急性肺损伤血糖、TNF-α、IL-1β均明显升高,且血糖水平与TNF-α、IL一1β浓度有相关性。     

记忆力减退 精神行为异常 四肢抽搐

正病例摘要患者男性,74岁。因记忆力减退7年、行为异常2年、四肢抽搐4 d,于2014年10月22日入院。患者系财务工作者,自7年前开始出现严重记忆力减退,如工作中不记得他人交代的事情,经反复提示亦无任何印象,需依靠便条、日记等方法协助记事;此后6个月逐渐出现重复询问同样问题,有时晨起刷牙5～6次,自觉记忆力有问题,于2007年10月     

Deficits in hippocampal‐dependent transfer generalization learning accompany synaptic dysfunction in a mouse model of amyloidosis

Elevated β‐amyloid and impaired synaptic function in hippocampus are among the earliest manifestations of Alzheimer's disease (AD). Most cognitive assessments employed in both humans and animal models, however, are insensitive to this early disease pathology. One critical aspect of hippocampal function is its role in episodic memory, which involves the binding of temporally coincident sensory information (e.g., sights, smells, and sounds) to create a representation of a specific learning epoch. Flexible associations can be formed among these distinct sensory stimuli that enable the “transfer” of new learning across a wide variety of contexts. The current studies employed a mouse analog of an associative “transfer learning” task that has previously been used to identify risk for prodromal AD in humans. The rodent version of the task assesses the transfer of learning about stimulus features relevant to a food reward across a series of compound discrimination problems. The relevant feature that predicts the food reward is unchanged across problems, but an irrelevant feature (i.e., the context) is altered. Experiment 1 demonstrated that C57BL6/J mice with bilateral ibotenic acid lesions of hippocampus were able to discriminate between two stimuli on par with control mice; however, lesioned mice were unable to transfer or apply this learning to new problem configurations. Experiment 2 used the APP_swePS1 mouse model of amyloidosis to show that robust impairments in transfer learning are evident in mice with subtle β‐amyloid‐induced synaptic deficits in the hippocampus. Finally, Experiment 3 confirmed that the same transfer learning impairments observed in APPswePS1 mice were also evident in the Tg‐SwDI mouse, a second model of amyloidosis. Together, these data show that the ability to generalize learned associations to new contexts is disrupted even in the presence of subtle hippocampal dysfunction and suggest that, across species, this aspect of hippocampal‐dependent learning may be useful for early identification of AD‐like pathology. © 2015 Wiley Periodicals, Inc.