Neutralizing antibodies are considered to be an important protective parameter used in HIV-1 vaccine evaluation. However, the exact role that neutralizing antibodies plays in controlling the disease progression of HIV...Neutralizing antibodies are considered to be an important protective parameter used in HIV-1 vaccine evaluation. However, the exact role that neutralizing antibodies plays in controlling the disease progression of HIV-1 infected peoples is still undetermined. In this paper, we compared the protective function of the neutralizing antibody response in the plasma from LTNP and TP against clade B and clade C pseudoviruses. No difference in the neutralizing activities between the plasma from LTNP and TP was found, which was consistent with the most recent reports. In addition, no correlations between the titer or breadth and CD4+ or viral load in HIV-1 infected individuals were found. The protective roles played by neutralizing antibodies in controlling disease progression of HIV-1 infected people need to be considered in a new viewpoint.展开更多
目的:了解中国HIV感染长期不进展者(Long-Term Non-Progressor,LTNP)T细胞表面IL-7(Interleukin-7,IL-7)受体的表达,分析其与疾病进展的关系。方法:收集LTNP组、HIV组、AIDS组及健康对照组(每组各20例)的抗凝全血,用流式细胞仪检测IL-7...目的:了解中国HIV感染长期不进展者(Long-Term Non-Progressor,LTNP)T细胞表面IL-7(Interleukin-7,IL-7)受体的表达,分析其与疾病进展的关系。方法:收集LTNP组、HIV组、AIDS组及健康对照组(每组各20例)的抗凝全血,用流式细胞仪检测IL-7受体的表达,并分析IL-7受体表达与血浆中IL-7水平的相关性。结果:LTNP组CD4+T、CD8+T、中枢记忆T细胞(Central memory T cells,Tcm)、效应记忆性T细胞(Effector memory T cells,Tem)表面IL-7受体表达水平明显高于无症状HIV感染组(HIV组)、AIDS病人组(AIDS组)(P<0.05),LTNP组初始T细胞(Na ve T cells,Na ve)、终末分化效应记忆型T细胞(Terminallydifferentiated effector memory T cells,Tem/td)表面IL-7受体表达水平与HIV组、AIDS组间差异无统计学意义。HIV/AIDS患者IL-7受体在CD4+T和CD8+T细胞上表达的百分率与血浆IL-7水平呈明显负相关(P<0.05),与CD4+T细胞数量呈明显的正相关(P<0.05),与病毒载量呈明显负相关(P<0.05)。结论:外周血T细胞表面IL-7受体表达与HIV疾病进展密切相关,LTNP组T细胞保持较高水平的IL-7受体表达,可能是保护因素之一。展开更多
Patients with extensive ulcerative colitis(UC) of more than eight years duration have an increased risk of colorectal cancer. Molecular biomarkers for dysplasia and cancer could have a great clinical value in managing...Patients with extensive ulcerative colitis(UC) of more than eight years duration have an increased risk of colorectal cancer. Molecular biomarkers for dysplasia and cancer could have a great clinical value in managing cancer risk in these UC patients. Using a wide range of molecular techniques- including cutting-edge OMICS technologies- recent studies have identified clinically relevant biomarker candidates from a variety of biosamples, including colonic biopsies, blood, stool, and urine. While the challenge remains to validate these candidate biomarkers in multi-center studies and with larger patient cohorts, it is certain that accurate biomarkers of colitis-associated neoplasia would improve clinical management of neoplastic risk in UC patients. This review highlights the ongoing avenues of research in biomarker development for colitis-associated colorectal cancer.展开更多
目的分析感染艾滋病病毒1型(HIV-1)后长期无进展者体内病毒的序列特征,探讨影响艾滋病疾病进程的病毒学因素。方法HIV-1病毒载量用HIV-1 Monitor Version 1.5版本试剂在AmplicorCobas上检测;CD4+T淋巴细胞计数用multitest四色试剂在FASC...目的分析感染艾滋病病毒1型(HIV-1)后长期无进展者体内病毒的序列特征,探讨影响艾滋病疾病进程的病毒学因素。方法HIV-1病毒载量用HIV-1 Monitor Version 1.5版本试剂在AmplicorCobas上检测;CD4+T淋巴细胞计数用multitest四色试剂在FASCalibur上进行计数;HIV-1近全长序列用三对引物扩增后进行测序,用ContigExpress软件进行序列编辑和拼接;HIV-1亚型用在线的REGA HIV-1Subtyping Tool-Version 3.0软件分析;HIV-1的溯源用BEAST软件包,采用贝叶斯马尔可夫链-蒙特卡罗(MCMC)算法构建系统进化树,推断该HIV-1毒株在中国最初的流行时间和地区;将HIV-1各蛋白的序列提交到至SWISS-MODEL蛋白质同源建模数据库(http://swissmodel.expasy.org/interactive),构建蛋白质结构。结果该感染者在潜伏期体内的病毒载量处于较低水平(4.32×103拷贝/mL),外周血中CD4+T淋巴细胞在感染10年后仍然高于500个/μL,该感染者感染的病毒为B亚型,最初于1992年左右在我国河南省流行。该病毒编码的Vpu与参考株HBX2编码的Vpu蛋白相比,结构存在显著的差异,这种差异可能影响该蛋白的功能。结论该感染者为长期无进展者,Vpu蛋白功能的部分丧失可能与疾病的长期无进展有关。展开更多
Human immunodeficiency virus(HIV)-infected individuals exhibit remarkable transcriptomic variation.Transcriptome analyses of antiretroviral therapy(ART)-free chronically infected HIV-1 patients with different clinical...Human immunodeficiency virus(HIV)-infected individuals exhibit remarkable transcriptomic variation.Transcriptome analyses of antiretroviral therapy(ART)-free chronically infected HIV-1 patients with different clinical outcomes are likely to aid the development of vaccine and immune therapies.Here,we performed microarray analyses on whole-blood derived RNA from 89 ART-free HIV-1-infected individuals from 2 cohorts.The differentially expressed genes were analyzed between long-term non-progressors,viremic non-progressors and typical progressors,and between elite controllers and non-elite controllers among the long-term nonprogressors.Several genes related to T-cell growth,proliferation and differentiation and antiapoptosis were upregulated,whereas interferon-stimulated genes and inflammatory genes were significantly downregulated in long-term non-progressors and viremic non-progressors.The observations above were further confirmed in the set of 261 genes that correlated with disease progression during a 5-year follow-up,which included 51 genes significantly associated with slower disease progression,and 210 genes associated with aggressive disease progression.Overall,our data suggest that it is vital to maintain the homeostasis of the immune system when mounting antiviral immune responses.Immune therapeutics able to reconstruct immune homeostasis are likely to be required for immune reconstitution in the context of ART,such as the administration of interleukin-7,healthy allogenic CD4^(+)T cells(providing CD4^(+)T-cell growth factors),or Tregs.展开更多
基金supported in part by the National Key S&T Special Projects on Major Infectious Diseases (Grant No. 2008ZX10001-002, 2008ZX10001-012)the National Natural Science Foundation of China (No. 30700706)
文摘Neutralizing antibodies are considered to be an important protective parameter used in HIV-1 vaccine evaluation. However, the exact role that neutralizing antibodies plays in controlling the disease progression of HIV-1 infected peoples is still undetermined. In this paper, we compared the protective function of the neutralizing antibody response in the plasma from LTNP and TP against clade B and clade C pseudoviruses. No difference in the neutralizing activities between the plasma from LTNP and TP was found, which was consistent with the most recent reports. In addition, no correlations between the titer or breadth and CD4+ or viral load in HIV-1 infected individuals were found. The protective roles played by neutralizing antibodies in controlling disease progression of HIV-1 infected people need to be considered in a new viewpoint.
文摘目的:了解中国HIV感染长期不进展者(Long-Term Non-Progressor,LTNP)T细胞表面IL-7(Interleukin-7,IL-7)受体的表达,分析其与疾病进展的关系。方法:收集LTNP组、HIV组、AIDS组及健康对照组(每组各20例)的抗凝全血,用流式细胞仪检测IL-7受体的表达,并分析IL-7受体表达与血浆中IL-7水平的相关性。结果:LTNP组CD4+T、CD8+T、中枢记忆T细胞(Central memory T cells,Tcm)、效应记忆性T细胞(Effector memory T cells,Tem)表面IL-7受体表达水平明显高于无症状HIV感染组(HIV组)、AIDS病人组(AIDS组)(P<0.05),LTNP组初始T细胞(Na ve T cells,Na ve)、终末分化效应记忆型T细胞(Terminallydifferentiated effector memory T cells,Tem/td)表面IL-7受体表达水平与HIV组、AIDS组间差异无统计学意义。HIV/AIDS患者IL-7受体在CD4+T和CD8+T细胞上表达的百分率与血浆IL-7水平呈明显负相关(P<0.05),与CD4+T细胞数量呈明显的正相关(P<0.05),与病毒载量呈明显负相关(P<0.05)。结论:外周血T细胞表面IL-7受体表达与HIV疾病进展密切相关,LTNP组T细胞保持较高水平的IL-7受体表达,可能是保护因素之一。
文摘Patients with extensive ulcerative colitis(UC) of more than eight years duration have an increased risk of colorectal cancer. Molecular biomarkers for dysplasia and cancer could have a great clinical value in managing cancer risk in these UC patients. Using a wide range of molecular techniques- including cutting-edge OMICS technologies- recent studies have identified clinically relevant biomarker candidates from a variety of biosamples, including colonic biopsies, blood, stool, and urine. While the challenge remains to validate these candidate biomarkers in multi-center studies and with larger patient cohorts, it is certain that accurate biomarkers of colitis-associated neoplasia would improve clinical management of neoplastic risk in UC patients. This review highlights the ongoing avenues of research in biomarker development for colitis-associated colorectal cancer.
基金This work was supported by the National Grand Program on Key Infectious Disease Control(No.2017ZX10202102)the National Nature Science Foundation of China(No.81561128008).
文摘Human immunodeficiency virus(HIV)-infected individuals exhibit remarkable transcriptomic variation.Transcriptome analyses of antiretroviral therapy(ART)-free chronically infected HIV-1 patients with different clinical outcomes are likely to aid the development of vaccine and immune therapies.Here,we performed microarray analyses on whole-blood derived RNA from 89 ART-free HIV-1-infected individuals from 2 cohorts.The differentially expressed genes were analyzed between long-term non-progressors,viremic non-progressors and typical progressors,and between elite controllers and non-elite controllers among the long-term nonprogressors.Several genes related to T-cell growth,proliferation and differentiation and antiapoptosis were upregulated,whereas interferon-stimulated genes and inflammatory genes were significantly downregulated in long-term non-progressors and viremic non-progressors.The observations above were further confirmed in the set of 261 genes that correlated with disease progression during a 5-year follow-up,which included 51 genes significantly associated with slower disease progression,and 210 genes associated with aggressive disease progression.Overall,our data suggest that it is vital to maintain the homeostasis of the immune system when mounting antiviral immune responses.Immune therapeutics able to reconstruct immune homeostasis are likely to be required for immune reconstitution in the context of ART,such as the administration of interleukin-7,healthy allogenic CD4^(+)T cells(providing CD4^(+)T-cell growth factors),or Tregs.
