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1.
《Vaccine》2019,37(31):4302-4309
Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted. 相似文献
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Hui Fan Xianzhen Jin Chunyan Liao Lina Qiao Wei Zhao 《Pathology, research and practice》2019,215(11):152667
MicroRNAs (miRNAs) have been found to be aberrantly expressed and exert essential roles in the tumorigenesis and progression of gastric cancer (GC). miR-301b-3p has been recognized as a cancer-related miRNA in lung cancer, bladder cancer and hepatocellular carcinoma. However, the function of miR-301b-3p in GC progression and its underlying mechanism have not been studied yet. In this study, we found that miR-301b-3p expression was up-regulated in GC tissues compared to adjacent noncancerous tissues. Furthermore, the elevated levels of miR-301b-3p were detected in GC cell lines (SGC-7901, AGS, MKN-45 and MGC-803) as compared with GES-1 cells. Interestingly, GC tissues from patients with tumor size ≥ 5 cm and advanced tumor stages showed obvious higher levels of miR-301b-3p compared to matched controls. Functionally, miR-301b-3p knockdown prominently inhibited cell proliferation, and induced cell cycle arrest at G1 phase and apoptosis in MGC-803 cells. Meanwhile, ectopic expression of miR-301b-3p conversely regulated these biological behaviors of MKN-45 cells. Next, we found that miR-301b-3p knockdown increased, whereas miR-301b-3p overexpression reduced the expression of zinc finger and BTB domain containing 4 (ZBTB4) in GC cells. Accordingly, luciferase reporter assay identified ZBTB4 as a direct target of miR-301b-3p. ZBTB4 overexpression markedly restrained the growth of MGC-803 cells. More importantly, ZBTB4 silencing partially reversed miR-301b-3p knockdown-induced tumor suppressive effects on MGC-803 cells. In conclusion, we firstly revealed that miR-301-3p was highly expressed in GC and contributed to tumor progression via attenuating ZBTB4, which might provide a novel molecular-targeted strategy for GC treatment. 相似文献
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José Herrera-Rodriguez Aurora Signorazzi Marijke Holtrop Jacqueline de Vries-Idema Anke Huckriede 《Vaccine》2019,37(12):1630-1637
The vast majority of commercially available inactivated influenza vaccines are produced from egg-grown or cell-grown live influenza virus. The first step in the production process is virus inactivation with β-propiolactone (BPL) or formaldehyde (FA). Recommendations for production of inactivated vaccines merely define the maximal concentration for both reagents, leaving the optimization of the process to the manufacturers. We assessed the effect of inactivation with BPL and FA on 5 different influenza virus strains. The properties of the viral formulation, such as successful inactivation, preservation of hemagglutinin (HA) binding ability, fusion capacity and the potential to stimulate a Toll-like receptor 7 (TLR7) reporter cell line were then assessed and compared to the properties of the untreated virus. Inactivation with BPL resulted in undetectable infectivity levels, while FA-treated virus retained very low infectious titers. Hemagglutination and fusion ability were highly affected by those treatments that conferred higher inactivation, with BPL-treated virus binding and fusing at a lower degree compared to FA-inactivated samples. On the other hand, BPL-inactivated virus induced higher levels of activation of TLR7 than FA-inactivated virus. The alterations caused by BPL or FA treatments were virus strain dependent. This data shows that the inactivation procedures should be tailored on the virus strain, and that many other elements beside the concentration of the inactivating agent, such as incubation time and temperature, buffer and virus concentration, have to be defined to achieve a functional product. 相似文献
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目的探讨乙肝病毒核心蛋白(hepatitis B virus C protein,HBC)对唾液酸酶1(neuraminidase 1,NEU1)及相关基因表达的影响。方法通过脂质体将pcDNA3.1和pcDNA3.1-HBC质粒分别转染HepG2细胞和Huh7细胞,采用Quantitative real-time-PCR(q-PCR)及Western blot检测NEU1的表达;PCR扩增NEU1基因并与pcDNA3.1载体质粒连接,构建NEU1过表达质粒pcDNA3.1-NEU1;将pcDNA3.1-NEU1和对照质粒分别转染HepG2细胞,收集细胞,进行转录组测序,获得差异表达基因,用q-PCR对差异表达基因进行验证;将pcDNA3.1-HBC和对照质粒转入肝癌细胞,q-PCR检测HBC对NEU1相关的差异表达基因的影响;在HBC阳性肝癌细胞,利用NEU1的小干扰质粒抑制其表达,q-PCR检测HBC是否通过NEU1调控相关基因的表达。结果与对照组肝癌细胞相比,转染HBC质粒的肝癌细胞NEU1表达显著上调;PCR鉴定pcDNA3.1-NEU1插入片段正确,重组质粒构建成功;转录组测序显示,与对照组比较,过表达NEU1的HepG2细胞有8个基因表达显著不同,其中6种基因表达上调,2种基因表达下调;q-PCR检测转录组测序获得的差异表达基因与转录组测序的结果一致;与对照肝癌细胞相比,NEU1相关的上调差异表达基因在HBC阳性肝癌细胞中高表达,且干扰NEU1表达后以上基因在HBC阳性肝癌细胞中表达下调;与NEU1相关的下调差异表达基因在HBC基因组中低表达,且干扰NEU1表达后相关基因在HBC阳性肝癌细胞中表达上调。结论HBC能够通过NEU1调控肝癌细胞中相关基因的表达。 相似文献
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Chih-Hsueh Yang Duen-Huey Tan Wei-Li Hsu Ting-Ting Jong Chi-Luan Wen Shih-Lan Hsu Poa-Chun Chang 《Journal of ethnopharmacology》2014