Non-chromatographic preparation of a bacterially produced single-shot modular virus-like particle capsomere vaccine for avian influenza

Highly pathogenic avian influenza (HPAI) causes significant economic loss, reduced food security and poses an ongoing pandemic threat. Poultry vaccination significantly decreases these problems and recognizes that the health of humans, animals and ecosystems are connected. Low-cost manufacture of poultry vaccine matched quickly to the ever-changing circulating strain is needed for effective vaccination. Here, we re-engineered the process to manufacture bacterially synthesized modular capsomere comprising influenza M2e, previously shown to confer complete protection in challenged mice, for application in poultry. Modular capsomere was prepared using a simplified non-chromatographic salting-out precipitation method and its immunogenicity tested in vivo in poultry. Modular capsomere crudely purified by precipitation (pCapM2e) contained more contaminants than equivalent product purified by chromatography (cCapM2e). Unadjuvanted pCapM2e containing 80 EU of endotoxin per dose was inferior to highly purified and adjuvanted cCapM2e (2 EU per dose). However, addition of adjuvant to pCapM2e resulting in high immunogenicity after only a single dose of vaccination, yet without any local adverse reaction. This finding suggests a strong synergy between adjuvant, antigen and contaminants, and the possible existence of a “Goldilocks” level of contaminants, where high immunogenicity and low reactogenicity can be obtained in a single-shot vaccination. The simplified process offers potential cost and speed advantages to address the needs in influenza poultry vaccination in low-cost veterinary markets.     

Prospective associations between a dietary index based on the British Food Standard Agency nutrient profiling system and 13-year weight gain in the SU.VI.MAX cohort

Background/objectivesThe scoring of the nutritional quality of individual foods using nutrient profiling systems (NPS) has been suggested as a basis for public health preventive measures. Used for front-of-package labeling, such scoring would help consumers in making healthier food choices. An individual dietary score based on the Food Standards Agency NPS has been developed (FSA-NPS-DI), but its long term association with weight gain has not been investigated. Our objectives were to investigate long-term associations between the FSA-NPS DI and weight gain and overweight/obesity onset in a middle-aged French population.Subjects/methodsSubjects included in the French SU.VI.MAX cohort with at least three dietary records at baseline and available anthropometric measurements at baseline and at a 13-year follow-up examination were included in the study. FSA-NPS DI at baseline was computed for each subject. Association between FSA-NPS DI and weight and BMI gain were investigated with ANCOVA and associations with overweight/obesity onset with logistic regression models.ResultsHigher baseline FSA-NPS DI (reflecting a poorer diet) was associated with higher weight and BMI gain (beta Q4 versus Q1 = 0.70; (95%CI 0.01; 1.38), P for trend = 0.04). A 16% higher risk of obesity for a 1 point increase of FSA-NPS DI was observed only in men.ConclusionsOur results suggest that a shift in nutritional quality of the foods and beverages within an individual's diet, as expressed by the FSA-NPS DI would be associated with lower weight gain in the long term. Using the FSA-NPS as a basis for food labeling might therefore contribute to tackle obesity.     

东亚人群VD受体基因ApaI多态性与银屑病易感性的Meta-分析

目的采用Meta-分析的方法对东亚人群VDR基因ApaI多态性与银屑病易感性的关系进行综合评价。方法系统检索所有2012年1月前在PubMed、中国生物医学文献数据库（CBM）上发表的ApaI多态性与银屑病关联分析的文献,然后按一定的标准选择合格的研究并从每个纳入研究中提取相关信息。对于ApaI多态位点,我们进行基于等位基因、显性遗传模式和隐性遗传模式关联研究的Meta-分析。通过固定或随机效应模型计算合并的优势比（Odds ratio,OR）。通过敏感性分析确定异质性并探索其来源。用漏斗图和Egger检验检测出版偏倚。结果有4个研究符合我们的标准进入本Meta-分析。基于等位基因、显性及隐性遗传模式关联研究的Meta-分析结果显示：在东亚人群中,等位基因A不是银屑病发病的危险因素：异质性χ2=14.48,P=0.002,I2=79.3%;OR随机效应模型=1.110,95%CI=0.667～1.847,z=0.40,P=0.689;基因型AA与aa均与银屑病发病不相关：显性遗传模式,异质性χ2=13.76,P=0.003,I2=78.2%,OR随机效应模型=1.034,95%CI=0.547,1.955,z=0.10,P=0.918;隐性遗传模式,异质性χ2=10.61,P=0.014,I2=71.7%,OR随机效应模型=1.406,95%CI=0.514,3.848,z=0.66,P=0.507。敏感性分析显示来自韩国的一个研究是异质性的主要来源,当排除该研究后,同样表现了上述趋势。另外,本Meta-分析所纳入的文献均不存在显著的出版偏倚。结论在东亚人群中,维生素D受体基因ApaI位点不是银屑病的易感位点。     

Alu cell-free DNA concentration,Alu index,and LINE-1 hypomethylation as a cancer predictor

IntroductionThe liquid biopsy approach, a less-invasive diagnostic tool, enables the detection of disease-specific genetic and epigenetic aberrations. Approximately 66–69% of the human genome may be composed of transposable repetitive elements, including Alu and LINE-1. This study aimed to investigate whether Alu-derived cell-free DNA (cfDNA) concentrations, Alu index, and LINE-1 methylation could be used to distinguish patients with cancers from healthy individuals.MethodsTwo sets of primers, shorter and longer Alu fragments, were used to amplify Alu elements, followed by the quantitation of Alu DNA concentration and its integrity index. LINE-1 methylation status was then analyzed with quantitative PCR using methylation- and unmethylation-specific TaqMan probes.ResultsBoth Alu index and LINE-1 methylation level were significantly different in comparison between patients with lung or breast cancer and the healthy controls. The area under the ROC curve of the Alu index and LINE-1 hypomethylation was 0.742 and 0.848 for lung cancer, respectively, and 0.724 and 0.890 for breast cancer, respectively. However, Alu longer fragment DNA concentration was significantly correlated with Alu index in comparison to LINE-1 hypomethylation. Regression analysis suggested that the LINE-1 methylation level, rather than the Alu index, was a good discriminator for lung and breast cancers.ConclusionsThis study investigated the genome-wide Alu index and LINE-1 methylation status; their associations with cancers suggested that these combinatory panels could be implemented as a triage test to discriminate cancer patients from healthy individuals.     

Aluminum trichloride impairs bone and downregulates Wnt/β-catenin signaling pathway in young growing rats

Aluminum (Al) can accumulate in bone and cause bone diseases. Few studies have investigated molecular mechanism of Al-induced bone diseases. Thus, in this study, rats were orally exposed to 0 (control group) and 0.4 g/L aluminum trichloride (AlCl₃) (treatment group) for 30, 60, 90 or 120 days, respectively. The Al content of femora and serum, bone histological structure, bone mineral density (BMD) of the distal and proximal femoral metaphysis and Wnt/β-catenin signaling pathway (the mRNA expressions of Wnt3a, Fzd2, LRP-5, β-catenin, Tcf4, cyclin D1 and c-Myc, the protein levels of Wnt3a and β-catenin, the activities of Fzd2 and LRP-5) in rat femora were determined on day 30, 60, 90 or 120, respectively. The results showed that the Al contents of femora and serum were increased, the BMD of the distal and proximal femoral metaphysis were decreased, the femora histological structure were disrupted, the mRNA expressions of Wnt3a, Fzd2, LRP-5, β-catenin, Tcf4, cyclin D1 and c-Myc, the protein levels of Wnt3a and β-catenin, the activities of Fzd2 and LRP-5 were all decreased in the treatment group compared with the control group with time prolonged. These results indicated that AlCl₃ impaired femora by inhibiting the Wnt/β-catenin signaling pathway in young growing rats.     

3种不同来源CD146阳性间充质干细胞亚群的生物学特性比较

目的比较脐带间充质干细胞(UCMSCs)、脂肪间充质干细胞(AMSCs)以及骨髓间充质干细胞(BM-MSCs)中CD146^+细胞亚群的生物学特性。方法用磁珠分选法分选不同组织来源的间充质干细胞,获得高纯度CD146^+亚群;用流式细胞计量术分析表型;透射电子显微镜观察细胞结构;成脂诱导分化后油红O染色;RT-qPCR检测成脂相关基因LPL、C/EBPα和PPARγ表达;成骨诱导分化后ALP染色,检测成骨相关基因ALP、OPN和RUNX2表达;检测细胞干性基因及血管生成相关基因表达;检测细胞体外成管能力。结果3种组织来源CD146^+MSCs具有相似的形态,表达除CD106外相似的细胞表面标志分子。与其他两种细胞比较,CD146^+AMSCs表达更高的干性基因OCT-4、SOX2和NANOG。在相同的诱导时间,CD146^+UCMSCs成脂和成骨能力较其他两种来源的CD146^+MSCs弱。3种组织来源的CD146^+MSCs均可表达血管内皮相关刺激因子BFGF、VEGF、Ang-1和EGF,但CD146^+BM-MSCs具有更强的体外成管能力。结论3种不同来源的CD146^+MSC具有不同的生物学特性,为进一步研究不同组织来源的间充质干细胞的特定应用提供了基础。