为探究des(rhamnosyl)verbascoside体外抗乙型肝炎病毒(HBV)的活性作用和机制,本研究以des(rhamnosyl)verbascoside为实验药物对HepG2.2.15细胞进行干预,实验分为药物干预组和对照组,采用串联质谱标签(Tandem Mass Tag,TMT)蛋白质组学...为探究des(rhamnosyl)verbascoside体外抗乙型肝炎病毒(HBV)的活性作用和机制,本研究以des(rhamnosyl)verbascoside为实验药物对HepG2.2.15细胞进行干预,实验分为药物干预组和对照组,采用串联质谱标签(Tandem Mass Tag,TMT)蛋白质组学方法对提取的总蛋白进行分析。结果表明,共筛选得到300个差异表达蛋白,其中有109个上调蛋白,191个下调蛋白。基因本体论(Gene Ontology,GO)分析结果显示,差异蛋白主要参与DNA复制(DNA replication)、鞘糖脂代谢(Glycosphingolipid metabolic process)、细胞增殖(Cell proliferation)、寡糖分解代谢(Oligosaccharide catabolic process)等生物学过程,以及DNA聚合酶活性(DNA polymerase activity)、丝氨酸型羧肽酶活性(Serine type carboxypeptidase activity)、DNA引物酶活性(DNA primase activity)等分子功能。京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析结果显示,差异蛋白主要参与细胞代谢(Metabolism)、遗传信息传导(Genetic information processing)、生物系统通路(Organismal systems)等相关信号通路。亚细胞定位分析表明,差异蛋白大多定位在细胞质和细胞核。本研究共筛选出13个与抗HBV密切相关的蛋白。通过定量蛋白组学初步揭示des(rhamnosyl)verbascoside可能通过增加HGF、SORT1、MAN2B1,减少PRIM1、PRIM2、POLA1、POLD3、POLD2、POLD1、POLE、ERCC2、LAMC1、SDC1等蛋白表达来起到体外抗HBV的作用。展开更多
[Objectives]This study was conducted to explore rapid and large-scale screening and detection of peste des petits ruminants(PPR),so as to provide important technical means for prevention,control and purification of PP...[Objectives]This study was conducted to explore rapid and large-scale screening and detection of peste des petits ruminants(PPR),so as to provide important technical means for prevention,control and purification of PPR.[Methods]Soluble N protein and NH fusion protein were successfully obtained in an Escherichia coli expression system by optimizing E.coli codon and expression conditions.Furthermore,based on purified soluble N protein and NH fusion protein,a double-antigen sandwich time-resolved fluorescence immunoassay method for detection of peste des petits ruminants virus(PPRV)was established.[Results]The method has high sensitivity and specificity and can specifically detect the antibody against PPRV in sheep serum,and it has no cross reaction with other related diseases.The method was used to detect 292 clinical samples,and compared with French IDVET competition ELISA kit.The coincidence rates of positive samples and negative samples from the two kinds of test kits were 92.47%and 97.26%,respectively,and the overall coincidence rate was 94.86%.The intra-group and inter-group coefficients of variation in the repeatability test were less than 10%.[Conclusions]Compared with the traditional ELISA method,the double-antigen sandwich time-resolved fluorescence immunoassay for detection of PPRV has equivalent sensitivity and specificity,and simple and rapid operation,and thus high application and popularization value.展开更多
Background:Desmoid tumors are rare,locally aggressive,highly recurrent soft-tissue tumors without approved treatments.Methods:We conducted a phase 3,international,double-blind,randomized,placebo-controlled trial of ni...Background:Desmoid tumors are rare,locally aggressive,highly recurrent soft-tissue tumors without approved treatments.Methods:We conducted a phase 3,international,double-blind,randomized,placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors,version 1.1.Patients were assigned in a 1:1 ratio to receive the oralγ-secretase inhibitor nirogacestat(150 mg)or placebo twice daily.The primary end point was progression-free survival.展开更多
文摘为探究des(rhamnosyl)verbascoside体外抗乙型肝炎病毒(HBV)的活性作用和机制,本研究以des(rhamnosyl)verbascoside为实验药物对HepG2.2.15细胞进行干预,实验分为药物干预组和对照组,采用串联质谱标签(Tandem Mass Tag,TMT)蛋白质组学方法对提取的总蛋白进行分析。结果表明,共筛选得到300个差异表达蛋白,其中有109个上调蛋白,191个下调蛋白。基因本体论(Gene Ontology,GO)分析结果显示,差异蛋白主要参与DNA复制(DNA replication)、鞘糖脂代谢(Glycosphingolipid metabolic process)、细胞增殖(Cell proliferation)、寡糖分解代谢(Oligosaccharide catabolic process)等生物学过程,以及DNA聚合酶活性(DNA polymerase activity)、丝氨酸型羧肽酶活性(Serine type carboxypeptidase activity)、DNA引物酶活性(DNA primase activity)等分子功能。京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析结果显示,差异蛋白主要参与细胞代谢(Metabolism)、遗传信息传导(Genetic information processing)、生物系统通路(Organismal systems)等相关信号通路。亚细胞定位分析表明,差异蛋白大多定位在细胞质和细胞核。本研究共筛选出13个与抗HBV密切相关的蛋白。通过定量蛋白组学初步揭示des(rhamnosyl)verbascoside可能通过增加HGF、SORT1、MAN2B1,减少PRIM1、PRIM2、POLA1、POLD3、POLD2、POLD1、POLE、ERCC2、LAMC1、SDC1等蛋白表达来起到体外抗HBV的作用。
基金Supported by National Key R&D Program for the Prevention and Control of Major Exotic Animal Diseases(2022YFD1800500)National Mutton Sheep Industrial Technology System(CARS39)+2 种基金Key Research and Development Program of Shandong Province(Major Science and Technology Innovation Project)(2021CXGC011306)Scientific Research Project of General Administration of Customs(2024HK033)Scientific Research Project of Jinan Customs(2023JK005).
文摘[Objectives]This study was conducted to explore rapid and large-scale screening and detection of peste des petits ruminants(PPR),so as to provide important technical means for prevention,control and purification of PPR.[Methods]Soluble N protein and NH fusion protein were successfully obtained in an Escherichia coli expression system by optimizing E.coli codon and expression conditions.Furthermore,based on purified soluble N protein and NH fusion protein,a double-antigen sandwich time-resolved fluorescence immunoassay method for detection of peste des petits ruminants virus(PPRV)was established.[Results]The method has high sensitivity and specificity and can specifically detect the antibody against PPRV in sheep serum,and it has no cross reaction with other related diseases.The method was used to detect 292 clinical samples,and compared with French IDVET competition ELISA kit.The coincidence rates of positive samples and negative samples from the two kinds of test kits were 92.47%and 97.26%,respectively,and the overall coincidence rate was 94.86%.The intra-group and inter-group coefficients of variation in the repeatability test were less than 10%.[Conclusions]Compared with the traditional ELISA method,the double-antigen sandwich time-resolved fluorescence immunoassay for detection of PPRV has equivalent sensitivity and specificity,and simple and rapid operation,and thus high application and popularization value.
文摘Background:Desmoid tumors are rare,locally aggressive,highly recurrent soft-tissue tumors without approved treatments.Methods:We conducted a phase 3,international,double-blind,randomized,placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors,version 1.1.Patients were assigned in a 1:1 ratio to receive the oralγ-secretase inhibitor nirogacestat(150 mg)or placebo twice daily.The primary end point was progression-free survival.
