An update on PTEN modulators – a patent review

ABSTRACT

Introduction: A multitude of cellular and physiological functions have been attributed to the biological activity of PTEN (Phosphatase and tensin homolog) such as inhibiting angiogenesis, promoting apoptosis, preventing cell proliferation, and maintaining cellular homeostasis. Based on whether cell growth is needed to be initiated or to be inhibited, enhancing PTEN expression or seeking to inhibit it was pursued.

Areas covered: Here the authors provide recent updates to their previous publication on ‘PTEN modulators: A patent review’, and discuss on new specificities that affirm the therapeutic potential of PTEN in promoting neuro-regeneration, stem cell regeneration, autophagy, bone and cartilage regeneration. Also, targeting PTEN appears to be effective in developing new treatment strategies for Parkinson’s disease, Alzheimer’s disease, macular degeneration, immune disorders, asthma, arthritis, lupus, Crohn’s disease, and several cancer types.

Expert opinion: PTEN mainly inhibits the PI3k/Akt pathway. However, the PI3k/Akt pathway can be activated by other signaling proteins. Thus, novel treatment strategies that can regulate PTEN alone, or combinational treatment approaches that can induce PTEN and simultaneously affect downstream mediators in the PI3K/Akt pathway, are needed, which were not investigated in detail. Commercial interests associated with molecules that regulate PTEN are discussed here, along with limitations and new possibilities to improve them.     

进口散装废金属原料及其船舶携带媒介生物调查研究

目的通过对进口散装废金属原料及其船舶媒介生物的调查,为开展口岸媒介生物防治提供科学依据。方法按照《国境口岸及出入境交通工具医学媒介生物监测规定》方法,选取210批次散装废金属原料,以及767艘次装运废金属原料船舶进行医学媒介生物调查,并对调查数据进行统计分析。结果在进口散装废金属原料中未截获医学媒介生物,运载船舶发现医学媒介107艘次,阳性率13.95%;在103艘船舶(13.42%)上发现2种蝇类,共1 174只;在4艘船舶上发现蟑螂,共265只,阳性率0.52%;鼠类、蚊类、蚤类未发现。结论使用目前常规媒介监测手段难以发现进口散装废金属原料携带医学媒介情况。装载散装废金属原料船舶有较高的医学媒介生物携带率,需要加强对该类船舶的卫生检疫工作。     

Effectiveness of a multiple intervention strategy for the control of the tiger mosquito (Aedes albopictus) in Spain

This study was undertaken to evaluate the effectiveness of four complementary and combined strategies to minimize the presence of the invasive mosquito Aedes albopictus, firmly established in Sant Cugat del Vallès, Catalonia, Spain. A quasi-experimental design including six neighbourhoods was performed in 2008-2009. The abundance of mosquitoes was monitored through ovitraps. The multiple intervention strategy consisted of four actions: source reduction; larvicide treatments (Bacillus thuringiensis israelensis and diflubenzuron); adulticide treatments (alfacipermetrin); and cleaning up uncontrolled landfills. The results showed the number of eggs significantly reduced in the areas with intervention. In 2008, the accumulate median of eggs was 175 and 272 in the intervention and control areas, respectively. In 2009, these medians were 884 and 1668 eggs. In total, 3104 households were visited and 683 people were interviewed. During inspections inside the houses, the cooperation of citizens in 2009 was 16% higher than that in 2008 (95% CI 13-19%). These findings suggest that the strategy was effective in reducing the number of eggs. Citizen cooperation, an essential factor for success, was observed through a high level of collaboration by the home owners, who allowed entry into their private dwellings. This study could be a model for controlling the populations of Ae. albopictus in the Mediterranean region.     

Attenuation and immunogenicity of host-range extended modified vaccinia virus Ankara recombinants

Modified vaccinia virus Ankara (MVA) is being widely investigated as a safe smallpox vaccine and as an expression vector to produce vaccines against other infectious diseases and cancer. MVA was isolated following more than 500 passages in chick embryo fibroblasts and suffered several major deletions and numerous small mutations resulting in replication defects in human and most other mammalian cells as well as severe attenuation of pathogenicity. Due to the host range restriction, primary chick embryo fibroblasts are routinely used for production of MVA-based vaccines. While a replication defect undoubtedly contributes to safety of MVA, it is worth considering whether host range and attenuation are partially separable properties. Marker rescue transfection experiments resulted in the creation of recombinant MVAs with extended mammalian cell host range. Here, we characterize two host-range extended rMVAs and show that they (i) have acquired the ability to stably replicate in Vero cells, which are frequently used as a cell substrate for vaccine manufacture, (ii) are severely attenuated in immunocompetent and immunodeficient mouse strains following intranasal infection, (iii) are more pathogenic than MVA but less pathogenic than the ACAM2000 vaccine strain at high intracranial doses, (iv) do not form lesions upon tail scratch in mice in contrast to ACAM2000 and (v) induce protective humoral and cell-mediated immune responses similar to MVA. The extended host range of rMVAs may be useful for vaccine production.     

船舶外来医学媒介生物传入风险分析初探

目的探讨船舶外来医学媒介生物传入的风险评估方法。方法通过建立医学媒介风险logistic回归模型,同时采用层次聚类分析以实例数据进行医学媒介风险预测,与医学媒介实际检出情况进行比对,以受试者工作特征曲线（ROC曲线）比较2种方法的预测效果。结果船员国籍、本地季节和历史医学媒介疫情是外来医学媒介生物传入的危险因素。医学媒介风险logistic回归模型的预测灵敏度为50%,特异度为77%;层次聚类分析法灵敏度为11%,特异度为93%;以ROC曲线比较2种方法的预测效果,其ROC曲线下面积AUC分别为0.64和0.52,Logistic回归模型预测效果略高于层次聚类分析。结论2种预测方法（AUC）均在0.7以下,准确性不高,为国际航行船舶外来媒介生物风险评估及预警系统的建立提供一种思路。     

2006-2009年常州口岸输入性医学媒介生物分析

目的通过对2006-2009年常州口岸截获输入性医学媒介生物的情况进行分析,为该口岸更好的防范外来医学媒介生物提供参考。方法利用统计学方法对常州口岸输入性医学媒介生物的批次、种类、截获时间、货物种类等资料进行统计分析。结果在2006-2009年共截获输入性医学媒介生物307批次54543只,蝇类、蜚蠊占绝对优势,并呈现一定的季节消长趋势。结论常州口岸存在医学媒介生物传入的风险,应加强检验检疫监管和查验力度,做好医学媒介生物监测和控制工作。     

结核分枝杆菌早期分泌蛋白CFP-10的原核表达

目的 构建结核分枝杆菌(MTB)早期分泌蛋白CFP-10原核表达载体并进行诱导表达.方法 通过PCR技术从结核分枝杆菌H37 Rv基因组中扩增出lhp基因片段,目的基因片段克隆至表达载体pET-32a(+),构建pET-32a-CFP-10重组表达质粒,将其转化E.coli BL21(DE3),经IPTG诱导表达.结果 成功地构建原核表达载体pET-32a-CFP-10,以重组体转化E.coli BL21(DE3),成功进行诱导表达.结论 成功构建CFP10的原核表达质粒,高效表达目的蛋白CFP-10,为进一步研究其免疫学功能奠定了基础.     

病媒生物化学防治安全风险及其控制措施探讨

病媒生物化学防治安全风险主要是对人体、环境、非靶标生物及植物的危害,其影响因素包括防治药物的性质、施药设备的性能和从业人员的个人素质等。为将其有效控制,应重点考虑：合理选用药物和剂型;做好药物的运输和保管工作;按规范要求配制与施用药物;做好作业人员个人防护;保护作业环境及非靶标生物;提高从业人员专业素质。     

国境口岸医学媒介生物监测与可持续控制策略的探讨

为了进一步强化医学媒介生物监测和防治工作,本文从国境口岸医学媒介生物监测与控制工作现状入手,对国境口岸医学媒介生物监测与可持续控制策略进行了探讨,为制订医学媒介生物防治方案提供依据,并在工作中逐步细化、丰富、完善相关工作。