HIV gp120 interactions with coreceptors: insights from studies with CCR5-based peptides

Human immunodeficiency virus enters cells by a direct fusion mechanism triggered by sequential binding of the gp120 subunit of the envelope glycoprotein, first to CD4, then to the coreceptor CCR5 or CXCR4. The coreceptors are chemokine receptors, members of the superfamily of G protein-coupled receptors that are characterized by 7 transmembrane domains. gp120 is presumed to interact with the extracellular portion, which consists of the N-terminal segment and three extracellular loops. Synthetic peptides based on these regions have proven to be valuable probes for elucidating the molecular details of the complex gp120-coreceptor interactions.     

Congestive heart failure: new paradigms and therapeutic targets

Congestive heart failure is a major clinical and public health challenge. With increased aging, and advanced care of almost all other cardiac diseases, myocardial failure has become the single most common reason for hospitalization for patients older than 65. Conventional wisdom addressed heart failure as a hemodynamic perturbation consisting of congestion and limited cardiac output. Efforts intuitively focused on augmenting systolic function and clearing excessive pulmonary and systemic edema. Despite symptomatic improvement, mortality and functional deterioration continued unabated. Afterload reducing therapy emerged as an effective modality of improving cardiac function. Selective targeting of renin-angiotensin-aldosterone system (RAAS) was shown to be superior to alternative nonhormone-based approaches. These clinical observations gave impetus to the neurohumoral paradigm of heart failure. Whereas attention to the congestive aspects of heart failure remains an essential component of therapy, it is by no means sufficient to neutralize the complex and interactive pathogenic mechanisms which underlie this syndrome. Particularly relevant, is the asymptomatic stage of ventricular dysfunction which portend significant future structural and functional deterioration. Mounting evidence confirm the benefit of ACEI and ARB in attenuating ventricular remodeling and improving survival. This paper aims at reviewing the evidence which has led to the strongly held paradigm of neurohormonal basis of heart failure. Appropriate and evidence based therapeutic strategies are presented.     

细胞组学与药理毒理学研究新机遇

细胞组学是基于单细胞分析的科学,能在生命活动最小单位的活细胞水平,反映细胞在外环境调控下,与细胞动力学和组织功能相关的基因组学、蛋白组学,旨在测定单细胞的分子表型。结合数据模式分析,通过特定的模拟临床疾病细胞模型图像分析、流式细胞术等高内涵筛选,提供复杂疾病治疗相关的生物信息。通过分析正常与病理情况下基因、蛋白和分子信号通路的差异起源,经过整合与相互关联、相互作用的基因、蛋白和多重代谢反应的网络系统研究,可发现假设的药物作用的靶点,并预测临床可能遇到的不良反应。利用上述概念构建的“工作模型”,与先进的测试手段和信息工具综合而成的细胞组学,可望给药理毒理学研究带来新机遇。     

虚拟筛选技术与新药开发

计算机模拟与化学合成、生物测试的结合构成了后基因组时代新药研究的新策略。从已有的化合物,包括合成化合物和天然产物中寻找药物或先导化合物,是药物发现的一个重要途径[1]。到目前为止,人们只是针对大约500种疾病治疗靶点,筛选     

Autoimmune hepatitis: new paradigms in the pathogenesis, diagnosis, and management Hepatol Int

一、临床表现自身免疫性肝炎(autoimmune hepatis,AIH)的临床表现复杂多样、缺乏特异性,多见于女性(70％),各年龄段、各种族均可发病.2型AIH常见于儿童,约20％成人患者60岁后发病,发病率为0.1‰～0.2‰,常合并其他自身免疫性疾病.少数可能发生暴发性肝炎和肝功能衰竭,部分患者尤其是老年人可能无症状.急性AIH的临床表现为黄疸、关节疼痛、食欲不振和乏力,肝组织活检可能是急性肝炎的表现;部分临床表现为急性肝炎的症状,但肝活检则为纤维化或肝硬化等慢性肝病的表现.AIH也可能隐匿起病,仅进展到失代偿期肝硬化后才有临床表现,常见于老年人.越来越多的AIH是因体检或其他疾病就诊时发现肝脏生化指标异常而诊断的.体格检查可能正常,也可能出现肝肿大、脾肿大、黄疸等慢性肝病表现.     

河南省2012—2014年新报告艾滋病病毒感染者中新发感染情况分析

目的了解河南省2012—2014年新报告艾滋病病毒感染者中新发感染的情况。方法通过中国法定传染病监测信息网络直报系统子平台《艾滋病综合防治数据信息管理系统》对河南省2012年7月1日至2014年6月30日新上报的HIV-1感染者进行信息整理并进行HIV-1 BED新发感染检测。结果共筛选到4 267例新报告HIV-1感染者,并进行样本收集、信息整理和相关检测。4 267例新报告HIV-1感染者中1 146例被判定为BED阳性,总的新发感染比例为26.86%,2012年下半年、2013年上半年、2013年下半年和2014年上半年的新发感染比例分别为27.60%、25.24%、28.40%、26.33%。4 267例新报告HIV-1感染者中抗-HCV阳性率为13.19%,563例HIV/HCV共感染者中BED阳性者有86例,新发感染比例为15.28%。抗-HCV阴性、报告地区为安阳市以及文化程度在大专及以上的新报告HIV-1感染者人群中新发感染比例较高。结论 2012—2014年河南省新报告HIV-1感染者人数增加,特定人群的新发感染比例较高。     

Diabetes-induced osteoarthritis: from a new paradigm to a new phenotype

Several epidemiological and experimental data support the hypothesis that diabetes could be an independent risk factor for osteoarthritis (OA), at least in some patients, leading to the concept of a diabetes-induced OA phenotype. If confirmed, this new paradigm will have a dramatic impact on prevention of OA initiation and progression.     

2009-2011年青海地区男男性行为者HIV-1新发感染率调查

目的了解青海省男男性行为者(Men have sex with men,MSM)人群HIV新发感染情况。方法此次对青海省2009-2011年连续3年第二季度MSM人群进行横断面调查,采用ELISA和WB对采集的国家哨点MSM人群监测样本进行初筛与确证实验,再对血清学确认为HIV-1阳性的样本进行BED HIV-1捕获酶联法(BED方法)检测,从而估算新发感染情况。结果在1 382份样本中筛出128份HIV-1阳性样本,实际进行BED检测113例,判定为新近感染者59例。3年新发感染率分别为8.14%、9.77%、11.13%。结论青海地区2009-2011年MSM人群HIV新发感染率维持在较高水平,其中2011年超过10%,提示该人群存在HIV感染高水平流行,并可能成为向主流人群蔓延的桥梁人群,应采取有效措施控制艾滋病在MSM人群中的广泛传播,进一步阻断疫情向一般人群蔓延。