Skin sensitizing properties of the ethanolamines mono‐, di‐, and triethanolamine. Data analysis of a multicentre surveillance network (IVDK*) and review of the literature

Numerous publications address the skin sensitizing potential of the short chain alkanolamines triethanolamine (TEA), diethanolamine (DEA), monoethanolamine (MEA), which are not skin sensitizing according to animal studies. Regarding TEA, we analysed patch test data of 85 098 patients who had been tested with TEA 2.5% petrolatum by Information Network of Departments of Dermatology (IVDK) to identify particular exposures possibly associated with an elevated risk of sensitization. Altogether, 323 patients (0.4%) tested positive. The profile of patch test reactions indicates a slightly irritant potential rather than a true allergic response in many cases. Although used widely, no exposure associated with an increased risk of TEA sensitization was identified. Therefore, the risk of sensitization to TEA seems to be very low. MEA and DEA were patch tested in a much more aimed fashion in 9602 and 8791 patients, respectively when prevalence of contact allergy was 3.8% and 1.8%. MEA is the prominent allergen in metalworkers with exposure to water‐based metalworking fluids (wbMWFs); DEA is probably used in cutting fluids less frequently nowadays. Chronic damage to the skin barrier resulting from wbMWF, the alkalinity of ethanolamines (increasing from TEA to MEA), and other cofactors may contribute to a notable sensitization risk.     

AcMNPV EXON0 (AC141) which is required for the efficient egress of budded virus nucleocapsids interacts with β-tubulin

The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) encoded protein, EXON0 (AC141), is required for the efficient transport of nucleocapsids out of the nucleus for the production of budded virus (BV). To further elucidate the molecular mechanisms by which EXON0 regulates BV production, EXON0 was tagged at the N-terminus with 3× FLAG-6× His. Protein complexes were isolated by tandem affinity purification and potential EXON0 specific interacting protein partners were gel purified and identified by LC-MS/MS. This analysis showed that the cellular protein, β-tubulin, co-purified with EXON0 which was confirmed by co-immunoprecipitation. In addition, immunofluorescence showed that EXON0 and β-tubulin co-localized during virus infection. The microtubule inhibitors colchicine and nocodazole were used to treat AcMNPV infected Sf9 cells and results showed that BV production was reduced by over 85%. These data suggest that the egress of AcMNPV budded virus may be facilitated by the interaction of EXON0 with β-tubulin and microtubules.     

人参皂甙Rb1改善转基因扩张型心肌病模型小鼠的心功能和心脏重构

目的 利用cTnTR141W转基因扩张型心肌病小鼠,研究人参皂甙Rb1对遗传性扩张型心肌病心功能及心脏重构的作用及其可能机制.方法 将cTnTR141W转基因小鼠随机分为模型组和人参皂甙Rb1治疗组(70 mg/kg/d),连续给药7个月,取野生型小鼠作为对照组.心脏超声检测心脏功能及几何构型.HE染色观察心肌细胞变化.透射电镜分析心肌超微结构.RT-PCR检测心肌粘附蛋白的表达.免疫荧光激光共聚焦观察心肌粘附分子Itga8的表达与分布.结果 Rb1长期给药能显著改善该模型的心脏功能及几何构型.光镜和透射电镜观察显示Rb1能减轻心肌细胞排列紊乱及超微结构的破坏.RT-PCR结果显示,在模型中Cx40表达降低,E-cad、itga8 和itgb1bp3表达升高,但在Rb1组中接近正常水平.免疫荧光激光共聚焦结果显示Rb1可降低Itga8的表达量并调节其分布.结论 Rb1可改善扩张型心肌病模型的心功能,抑制心脏重构,其作用可能部分通过调节粘附蛋白的表达而实现的.     

miR-141在儿童急性B淋巴细胞白血病中的表达及意义

背景与目的：微小RNA(microRNA,miRNA)是一类长度为21~25 nt的内源性单链非编码RNA小分子。本研究旨在探讨miR-141在儿童急性B淋巴细胞白血病(acute lymphoblastic leukemia,ALL)中的表达及临床意义。方法：收集B细胞ALL患儿35例为B细胞ALL组,以非血液病患儿15例为对照组,采集骨髓标本,提取总RNA,采用real-time PCR检测miR-141的表达,比较各组miR-141表达差异。结果：miR-141在B细胞ALL组中的表达低于对照组(P<0.05);miR-141在治疗前的表达明显低于治疗第30天及第12周(P<0.05),治疗第30天的表达低于治疗第12周(P<0.05);≥10岁组miR-141的表达低于＜10岁组(P<0.05);低危组治疗前miR-141表达高于中、高危组(P<0.05),而中危组高于高危组(P<0.05)。结论：miR-141在儿童B细胞ALL中很可能存在抑癌作用,并是预后预测的潜在靶点。     

Resistance to HIV protease inhibitors

Summary. Resistance to the HIV-1 protease inhibitor indinavir involves the accumulation of multiple amino acid substitutions in the viral protease. A minimum of 11 amino acid positions have been identified as potential contributors to phenotypic resistance. Three or more amino acid substitutions in the protease are required before resistance becomes measurable (≥four-fold). Further losses in susceptibility follow the stepwise accumulation of additional amino acid substitutions, indicating that antiviral activity (selective pressure) is maintained despite the appearance of multiple amino acid substitutions in the viral protease. Importantly, the sequential nature of these changes indicates that the effects of these substitutions are additive, and that the evolution of resistance is driven by viral replication. This result has significant implications for therapy. It predicts that viral variants resistant to indinavir are unlikely to pre-exist in protease inhibitor-naive patients, and further, that high-level resistance can only develop if the virus is allowed to replicate in the presence of the drug. The use of indinavir in combination with other antiretroviral agents has been demonstrated to dramatically reduce the incidence of resistance mutations, suggesting that with maximal suppression of viral replication, long-term control of HIV-1 infection may be achievable. Thus, the goal of therapy must be to never to allow the virus to replicate. This can be best accomplished by initiating therapy with a maximally suppressive regimen, to reduce viral replication as much as possible, and by imposing a high genetic barrier to resistance. Previous use of other protease inhibitors or inadequate adherence to therapy may compromise the long-term benefit of indinavir by allowing the virus to gain a foothold through the development of resistance. An understanding of these issues will be critical in realizing the full potential of this potent new drug for the control of HIV-1 infection.     

The -141C Ins/Del and Taq1A polymorphism in the dopamine D2 receptor gene may confer susceptibility to schizophrenia in Asian populations

It has been reported that two single nucleotide polymorphisms (SNP) Taq1A and -141C Ins/Del in the DRD2 gene may be associated with susceptibility to schizophrenia. Due to inconclusive and mixed results, a meta-analysis was conducted to further clarify the relationship between the two SNP and schizophrenia susceptibility. A systematic literature search for the association of these two SNP with schizophrenia susceptibility was conducted using PubMed, ScienceDirect, Chinese Biomedical Literature Database, and Chinese National Knowledge Infrastructure. Odds ratios (OR) with 95% confidence intervals (CI) were used to assess the strength of the associations reported. A total of 5558 schizophrenic patients and 6792 healthy controls from 31 articles were included in this study. Evidence regarding the association between -141C Ins/Del polymorphism and schizophrenia was found in the allele frequency comparison (Ins versus Del: OR 1.29, 95% CI 1.06–1.57; p = 0.01, P_raw = 0.1, P_{False Discovery Rate} = 0.023). In ethnic subgroup analysis, the result revealed that the 141C Ins/Del polymorphism was associated with schizophrenia in all genetic models in Asians, but not in Caucasians. For Taq1A polymorphism, a significant association was found in the allele frequency (A1 versus A2: OR 0.71, 95% CI 0.52–0.98, p = 0.03). Stratification by ethnicity indicated an association between the Taq1A polymorphism and schizophrenia in Asians, but not Caucasians. The present study suggests that the -141C Ins/Del polymorphism carries a significantly increased risk of schizophrenia, while the Taq1A polymorphism carries a significantly decreased risk of schizophrenia susceptibility in Asians.     

非小细胞肺癌中miRNA-141的表达及临床意义

目的:探讨miRNA-141在非小细胞肺癌中的表达及其与临床病理特征的关系。方法:采用real time-PCR法对54例非小细胞患者,肺癌组织及正常肺组织的miRNA-141表达水平进行定量分析,结果由2-△△CT处理,并分析与临床病理资料的关系。结果:在NSCLC患者肿瘤组织中miRNA-141表达水平明显升高,其表达与临床分期、病理类型显著相关(P<0.05)。而在不同年龄、性别、肿瘤大小、吸烟史患者间差异无统计学意义(P>0.05)。结论:MiRNA-141高表达与非小细胞肺癌的临床分期、病理分型密切相关,miRNA-141有可能作为非小细胞肺癌的重要肿瘤标志物之一。