Immunological implications of diverse production approaches for Chikungunya virus-like particle vaccines

Chikungunya virus (CHIKV), an arbovirus from the Alphavirus genus, causes sporadic outbreaks and epidemics and can cause acute febrile illness accompanied by severe long-term arthralgias. Over 20 CHIKV vaccine candidates have been developed over the last two decades, utilizing a wide range of vaccine platforms, including virus-like particles (VLP). A CHIKV VLP vaccine candidate is among three candidates in late-stage clinical testing and has potentially promising data in nonclinical and clinical studies exploring safety and vaccine immunogenicity. Despite the consistency of the CHIKV VLP structure, vaccine candidates vary significantly in protein sequence identity, structural protein expression cassettes and their mode of production. Here, we explore the impact of CHIKV VLP coding sequence variation and the chosen expression platform, which affect VLP expression yields, antigenicity and overall vaccine immunogenicity. Additionally, we explore the potential of the CHIKV VLP platform to be modified to elicit protection against other pathogens.     

Decreased expression of Neurensin-2 correlates with poor prognosis in hepatocellular carcinoma

AIM： To investigate the expression of Neurensin-2 （NRSN2） in hepatocellular carcinoma （HCC） and its prognostic values in predicting survival. METHODS： The expression and prognostic significance of NRSN2 in HCC was examined by performing immunohistochemical analysis using a total of 110 HCC clinical tissue samples, and Western blotting analysis to further confirm the result. RESULTS： Decreased NRSN2 expression was shown in 70.9% cases. Loss of NRSN2 expression in HCC was significantly related to tumor size （P = 0.006）. Larger tumor size was related to negative expression of NRSN2. Patients showing negative NRSN2 expression had a significantly shorter overall survival than those with positive expression （P = 0.008）. Multivariate Cox regression analysis indicated that NRSN2 expression level was an independent factor of survival （P = 0.013）. Western blotting analysis further confirmed decreased expression of NRSN2 in tumor tissues compared with non-tumorous tissues. CONCLUSION： Our study indicated that NRSIV2 could be a tumor suppressor gene for HCC and a candidate biomarker for long-term survival in HCC.     

脂联素受体的表达与调节

脂联素受体1在骨骼肌中有丰富表达,而脂联素受体2主要在肝中表达。另外,两种脂联素受体也在胰岛β细胞、脂肪组织、单核细胞、巨噬细胞、成骨细胞、心肌组织和胎盘组织中表达。生长激素、胰岛素以及过氧化物酶体增殖物活化受体(PPAR)α、PPARγ和肝X受体激动剂等可影响脂联素受体的表达。研究脂联素受体在不同组织、细胞中的表达与调节可了解其组织特异性作用。     

朱震亨从脾胃病探析误诊误治

[目的] 通过探析《局方发挥》之脾胃病误诊误治,以期指导与改进现代医家临床治疗。[方法] 对《局方发挥》之脾胃病误诊误治进行整理分析,揭示朱震亨从脾胃病探析误诊误治的特色。[结果] 朱震亨从脾胃病论误诊误治的特色:1)《和剂局方》具有误导性脾胃病治疗的中医知识,导致当时医者与患者误诊误治脾胃病。2)《和剂局方》引起的脾胃病误诊误治问题,主要可分成两类:辨证失误和治法失误。3)辨证失误所导致的误诊误治包括忽视审证求因、认为“诸寒为病”、误辨寒热虚实等。4)治法失误包括“一方通治诸病”、滥用辛香燥热药组方、利用砒丹巴硇行积垢、修改汤剂为丸剂、用峻剂盲目祛邪及错误滋补等。[结论] 朱震亨在《局方发挥》指出当时脾胃病的误诊误治问题,显示出了其独特见解,对现代医家治疗脾胃病,具有一定的指导作用与参考价值。     

miRNA-449a在肺癌组织中的表达及其检测意义

目的探讨miRNA-449a在肺癌组织中的表达及其临床应用价值。方法收集右江族医学院附属医院2011年1月1日~2013年6月30日收治的58例肺癌患者为研究对象,采用反转录荧光定量聚合酶链式反应(RT-PCR)检测miRNA-449a在肺癌组织和癌旁正常组织中的表达量,分析miRNA-449a与临床病理特征的关系,并采用荧光电子显微镜观察miRNA-449a模拟物对体外培养肺癌细胞株95D细胞凋亡的影响。结果鳞癌组和腺癌组miRNA-449a平均表达量均明显低于癌旁正常对照组(LSD-t=6.712,P=0.000;LSD-t=4.572,P=0.000),其相对表达量与瘤体大小(u=78.412,P=0.012)有关,与患者年龄(u=920.000,P=0.615)、性别(u=800.000,P=0.215)、病理类型(χ2=4.221,P=0.155)和临床分期(u=754.000,P=0.009)无关。与阴性对照组比较,miRNA-449a模拟物可明显促进肺癌细胞的凋亡,且呈剂量依赖性。结论 miRNA-449a在肺癌组织中呈低表达,可诱导肺癌细胞凋亡,发挥抑癌基因的作用,可能成为肺癌早期诊断与治疗的新分子靶标。     

甲状腺肿瘤组织中VEGF、p73蛋白表达情况及相互关系研究

目的 探析甲状腺肿瘤组织中血管内皮生长因子(VEGF)、肿瘤抑制因子(p73)的表达及其相关性.方法 选取某院2013年1月至2014年1月收治的60例甲状腺癌和60例甲状腺腺瘤患者作为观察对象,并将同期60例健康人群作为对照,采用免疫组化(SP)法检测组织中VEGF和p73的表达,并采用Pearson相关分析研究组织中VEGF和p73的相关性.结果 甲状腺癌组组织中VEGF阳性表达率86.7％(52/60)显著高于甲状腺腺瘤组71.7％(43/60),高于正常对照组0％,差异均有统计学意义(P＜0.05);甲状腺癌组组织中p73阳性表达率93.3％(56/60)显著高于甲状腺腺瘤组80.0％(48/60),高于正常对照组0％,差异均有统计学意义(P＜0.05).甲状腺组织中VEGF和p73呈正相关,在甲状腺癌组织中相关系数r=0.723,P＜0.05,在甲状腺腺瘤组织中相关系数r=0.542,P＜0.05.结论 甲状腺肿瘤患者组织中VEGF和p73蛋白表达均显著升高,且二者呈正相关.     

Preliminary evaluation of [18F]AlF-NOTA-MAL-Cys39-exendin-4 in insulinoma with PET

Background: High expression of glucagon-like peptide-1 receptor (GLP-1R) in insulinoma supplies a potential drug target for tumor imaging. Exendin-4 can specifically bind to GLP-1R as an agonist and its analogs are extensively used in receptor imaging studies.

Purpose: A new GLP-1R imaging agent, [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4, was designed and prepared for insulinoma imaging.

Methods: Cys³⁹-exendin-4 was conjugated with NOTA-MAL, then the compound was radiolabeled with [¹⁸F]AlF complex to obtained [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4. The tumor-targeting characters of the tracer were evaluated in INS-1 cells and BALB/c nude mice models.

Results: [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4 can be efficiently produced with a yield of 17.5?±?3.2% (non-decay corrected) and radiochemical purity of >95%. The IC₅₀ value of displacement [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4 with Cys³⁹-exendin-4 was 13.52?±?1.36?nM. PET images showed excellent tumor visualization with high uptake (9.15?±?1.6%ID/g at 30?min and 7.74?±?0.87%ID/g at 60?min). The tumor to muscle, pancreas and liver ratios were 63.25, 3.85 and 7.29 at 60?min after injection. GLP-1R binding specificity was demonstrated by co-injection with an excess of unlabeled Cys³⁹-exendin-4 and the tumor uptake was found to be reduced significantly.

Conclusion: [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4 shows favorable characteristics for insulinoma imaging and may be translated to clinical studies.