The effects of anti-sense interleukin-5 gene transferred by recombinant adeno-associated virus in allergic rats

The accumulation and infiltration of eosinophils in airways is one of the most important characteristics of asthma, and is mediated partly by secretion of IL-5 from Th2 lymphocytes. It is well known that interleukin-5 (IL-5) played an important role in the regulation of eosinophils. In this study, an anti-sense IL-5 gene transferred by recombinant adeno-associated virus (rAAV-ASIL-5) was prepared to transfect allergic rats. It was found that the expression of IL-5 protein in plasma and BALF were inhibited significantly. The rAAV-ASIL-5-mediated suppression of total cell counts in peripheral blood and BALF were also observed. Moreover, rAAV-ASIL-5 remarkably reduced the eosinophil counts in peripheral blood and BALF, as well as the expression of ECP protein in plasma and BALF. The inflammation in lungs of rAAV-ASIL-5 pretreated rats also became slighter when compared with allergic rats. Otherwise, no apparent pathological damage to vital organs of rats was found. In conclusion, recombinant adeno-associated virus-mediated delivery of anti-sense IL-5 gene inhibited the accumulation of eosinophils and the airways inflammation in rat model of allergic asthma via suppressing IL-5 expression. It suggested the feasibility of rAAV-ASIL-5 in the gene therapy for allergic asthma and other eosinophilic diseases

Association between Polymorphism of Interleukin-1beta and Interleukin-1 Receptor Antagonist Gene and Asthma Risk: A Meta-Analysis

Background. Asthma is a complex polygenic disease in which gene-environment interactions are important. A number of studies have investigated the polymorphism of IL-1β -511C/T and IL-1RA genes in relation to asthma susceptibility in different populations. However, the results of individual studies have been inconsistent. Accordingly, we conducted a comprehensive meta-analysis to investigate the association between the IL-1β -511C/T and IL-1RA polymorphism and asthma risk. Methods. Data were collected from the following electronic databases: Pub Med, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), ISI Web of Knowledge, and Google Scholar Search databases with the last report up to July 2013. Finally, 15 studies were included in our meta-analysis. We summarized the data on the association between IL-1β -511C/T and IL-1RA polymorphism and risk of asthma in the overall population and performed subgroup analyses by ethnicity, mean of age, and source of controls. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the associations between IL-1β -511C/T and IL-1RA polymorphism and asthma risk. Statistical analysis was performed with Review Manager 5.1. Results. A total of 15 case-control studies were included in the meta-analysis of IL-1β -511C/T (1,385 cases and 1,964 controls) and IL-1RA (2,800 cases and 6,359 controls) genotypes. No association was found between IL-1β -511C/T polymorphism and asthma risk (dominant model: OR=1.11, 95% CI: 0.99–1.25, P=0.07, PHeterogeneity=0.06; recessive model: OR=1.04, 95% CI: 0.91–1.20, P=0.55, PHeterogeneity=0.11). Subgroup analysis based on ethnicity (Asian and Caucasian), source of controls (population-based controls and hospital-based controls), and mean of age (adulthood and childhood) did not present any significant association. The overall results showed that the IL-1RA polymorphism was related to an increased risk of asthma (homozygote model: OR=1.32, 95% CI: 1.12–1.56, P=0.0009, PHeterogeneity=0.87; recessive model: OR=1.39, 95% CI: 1.18–1.63, P=0.0001, PHeterogeneity=0.82). Similar results were found in the subgroup analyses by ethnicity, mean of age, and source of controls. Sensitivity analysis did not perturb the results. Conclusions. This meta-analysis provided strong evidence that the IL-1RA polymorphism was a risk factor of asthma, especially in Caucasian populations. However, no association was found for IL-1β -511C/T genotype carriers. Larger scale studies are needed for confirmation

Enhancing security behaviour by supporting the user

Although the role of users in maintaining security is regularly emphasized, this is often not matched by an accompanying level of support. Indeed, users are frequently given insufficient guidance to enable effective security choices and decisions, which can lead to perceived bad behaviour as a consequence. This paper discusses the forms of support that are possible, and seeks to investigate the effect of doing so in practice. Specifically, it presents findings from two experimental studies that investigate how variations in password meter usage and feedback can positively affect the resulting password choices. The first experiment examines the difference between passwords selected by unguided users versus those receiving guidance and alternative forms of feedback (ranging from a traditional password meter through to an emoji-based approach). The findings reveal a 30% drop in weak password choices between unguided and guided usage, with the varying meters then delivering up to 10% further improvement. The second experiment then considers variations in the form of feedback message that users may receive in addition to a meter-based rating. It is shown that by providing richer information (e.g. based upon the time required to crack a password, its relative ranking against other choices, or the probability of it being cracked), users are more motivated towards making strong choices and changing initially weak ones. While the specifics of the experimental findings were focused upon passwords, the discussion also considers the benefits that may be gained by applying the same principles of nudging and guidance to other areas of security in which users are often found to have weak behaviours

An Empirical Study of Learning-Based Web Search

Although there are various approaches to facilitate the information search on the Web, most current Web search and query systems only return URLs of relevant pages. Learning-based Web search is invented targeting at processing the URLs to dig out the desired information by utilizing user feedback

Body mass index and mortality in chronic obstructive pulmonary disease: a meta-analysis.

BACKGROUND: The association between body mass index (BMI) and mortality in patients suffering from chronic obstructive pulmonary disease (COPD) has been a subject of interest for decades. However, the evidence is inadequate to draw robust conclusions because some studies were generally small or with a short follow-up. METHODS: We carried out a search in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE database for relevant studies. Relative risks (RRs) with 95% confidence interval (CI) were calculated to assess the association between BMI and mortality in patients with COPD. In addition, a baseline risk-adjusted analysis was performed to investigate the strength of this association. RESULTS: 22 studies comprising 21,150 participants were included in this analysis. Compared with patients having a normal BMI, underweight individuals were associated with higher mortality (RR = 1.34, 95% CI = 1.01-1.78), whereas overweight (RR = 0.47, 95% CI = 0.33-0.68) and obese (RR = 0.59, 95% CI = 0.38-0.91) patients were associated with lower mortality. We further performed a baseline risk-adjusted analysis and obtained statistically similar results. CONCLUSION: Our study showed that for patients with COPD being overweight or obese had a protective effect against mortality. However, the relationship between BMI and mortality in different classes of obesity needed further clarification in well-designed clinical studies

Macrophages: friend or foe in idiopathic pulmonary fibrosis?

Abstract Idiopathic pulmonary fibrosis (IPF) is a prototype of lethal, chronic, progressive interstitial lung disease of unknown etiology. Over the past decade, macrophage has been recognized to play a significant role in IPF pathogenesis. Depending on the local microenvironments, macrophages can be polarized to either classically activated (M1) or alternatively activated (M2) phenotypes. In general, M1 macrophages are responsible for wound healing after alveolar epithelial injury, while M2 macrophages are designated to resolve wound healing processes or terminate inflammatory responses in the lung. IPF is a pathological consequence resulted from altered wound healing in response to persistent lung injury. In this review, we intend to summarize the current state of knowledge regarding the process of macrophage polarization and its mediators in the pathogenesis of pulmonary fibrosis. Our goal is to update the understanding of the mechanisms underlying the initiation and progression of IPF, and by which, we expect to provide help for developing effective therapeutic strategies in clinical settings