目的:通过生物信息学分析Nod样受体pyrin结构域蛋白6(Nod-like receptor pyrin domain-containing protein 6,NLRP6)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达模式、生物学功能和免疫细胞浸润关系。方法:利用癌症和肿瘤基因图...目的:通过生物信息学分析Nod样受体pyrin结构域蛋白6(Nod-like receptor pyrin domain-containing protein 6,NLRP6)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达模式、生物学功能和免疫细胞浸润关系。方法:利用癌症和肿瘤基因图谱(the cancer genome atlas,TCGA)、国际肿瘤基因组协作组(International Cancer Genome Consortium,ICGC)、基因表达综合(gene expression omnibus,GEO)数据库及TIMER 2.0数据库、HCCDB数据库、人类蛋白质图谱(The Human Protein Atlas,HPA)数据库、基因表达谱交互分析(Gene Expression Profiling Interactive Analysis,GEPIA)数据库分析NLRP6在HCC中的表达模式、临床预后价值。通过Enrichr数据库分析NLRP6的生物学功能。分析NLRP6表达与HCC免疫细胞浸润关系。此外,基于NLRP6表达构建Nomogram模型预测HCC患者预后。结果:NLRP6表达在多种类型肿瘤(包括HCC)中下调(P<0.05),其低表达与HCC不良预后相关(P<0.05)。京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,EGGK)信号通路和基因本体论(gene ontology,GO)分析结果揭示,NLRP6参与炎症-免疫调节反应,包括原发性免疫缺陷、自然杀伤细胞介导的细胞毒性、Th1和Th2细胞分化等信号通路。NLRP6表达与B细胞(r=-0.202)、CD4^(+)T细胞(r=-0.207)、CD8^(+)T细胞(r=0.153)、中性粒细胞(r=0.201)、巨噬细胞(r=-0.133)和髓树突状细胞(r=-0.245)浸润丰度显著相关;高中性粒细胞浸润丰度与HCC患者更差生存预后相关(P<0.05)。基于NLRP6表达、年龄和TNM分期的Nomogram模型能有效预测HCC患者1年、3年及5年总生存率,提供显著临床净收益。结论:NLRP6可能参与HCC发病机制,与炎症-免疫调节及免疫细胞浸润相关。基于NLRP6表达的Nomogram模型能有效预测HCC患者预后,为临床医师治疗HCC提供新的思路。展开更多
NOD样受体家族含pyrin结构域蛋白3(NOD-like receptor family pyrin domain-containing protein 3,NLRP3)炎症小体是一种蛋白质复合体,可促进Caspase的活化和IL-1β的成熟,在多种炎症的发生、发展过程中起促进作用。牙周炎(periodontiti...NOD样受体家族含pyrin结构域蛋白3(NOD-like receptor family pyrin domain-containing protein 3,NLRP3)炎症小体是一种蛋白质复合体,可促进Caspase的活化和IL-1β的成熟,在多种炎症的发生、发展过程中起促进作用。牙周炎(periodontitis,PD)的发生与牙周组织的菌群失调有关,NLRP3炎症小体参与中性粒细胞、巨噬细胞、破骨细胞(osteoclast,OC)和人牙周膜成纤维细胞(human periodontal liqament fibroblast,HPLF)的活化过程。该文归纳了相关免疫细胞及基质细胞的NLRP3炎症小体对PD的影响,并简述了与NLRP3炎症小体相关的PD治疗新思路。展开更多
Background： Cryopyrin-associated periodic syndrome （CAPS） is a group of rare, heterogeneous autoinflammatory disease characterized by interleukin （IL）-1β-mediated systemic inflammation and clinical symptoms invo...Background： Cryopyrin-associated periodic syndrome （CAPS） is a group of rare, heterogeneous autoinflammatory disease characterized by interleukin （IL）-1β-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervous system, and eyes. It encompasses a spectrum of three clinically overlapping autoinflammatory syndromes including familial cold autoinflammatory syndrome, Muckle-Wells syndrome （MWS）, and neonatal-onset multisystem inflammatory disease. CAPS is associated with gain-of-function missense mutations in NOD-like receptor family pyrin domain-containing protein 3 （NLRP3）, the gene encoding NLRP3. Moreover, most mutations leading to MWS occurred in exon 3 ofNLRP3 gene. Here, we reported a novel mutation occurred in exon 1 ofNLRP3 gene in an MWS patient and attempted to explore the pathogenic mechanism. Methods： Genetic sequence analysis of NLRP3 was performed in an MWS patient who presented with periodic lever, arthralgia, and multiform skin lesions. NLRP3 was also analyzed in this patient＇s parents and 50 healthy individuals. Clinical examinations including X-ray examination, skin biopsy, bone marrow aspiration smear, and blood test of C-reactive protein （CRP）, erythrocyte sedimentation rate （ESR）, serum levels oflL-1β, immunoglobulin E （lgE）, antineutrophil cytoplasmic antibodies, antinuclear antibodies, and extractable nuclear antigen were also analyzed. The protein structure of mutant NLRP3 inflammasome was calculated by SWISS-MODEL software. Proteins of wild type and mutant components ofNLRP3 inflammasome were expressed and purified, and the interaction abilities between these proteins were tested by surface plasmon resonance （SPR） assay. Results： X-ray examination showed no abnormality in the patient＇s knees. Laboratory tests indicated an elevation of CRP （233.24 nag/L） and ESR （67 mm/h） when the patient had fever. Serum IL-1β increased to 24.37 pg/ml, and serum lgE was higher than 2500.00 IU/ml. Other blood tests were no展开更多
慢性肾脏病发病率逐年上升,现已成为威胁全世界公共健康的主要疾病之一。导致慢性肾脏病的基本病因众多,主要包括原发性与继发性肾小球肾炎、糖尿病肾脏疾病、高血压肾损害、肾小管间质病变、遗传性疾病等。而糖尿病肾脏疾病作为慢性肾...慢性肾脏病发病率逐年上升,现已成为威胁全世界公共健康的主要疾病之一。导致慢性肾脏病的基本病因众多,主要包括原发性与继发性肾小球肾炎、糖尿病肾脏疾病、高血压肾损害、肾小管间质病变、遗传性疾病等。而糖尿病肾脏疾病作为慢性肾脏病的病因之一,是糖尿病引起的肾脏微血管病变的并发症,不加以控制可进展为终末期肾病。糖尿病肾脏疾病的具体发病机制尚不完全清晰,主要以高糖等代谢因素导致的免疫介导性炎症对肾脏破坏为主,而近年来发现免疫介导性炎症因素是糖尿病肾脏疾病发生的重要原因之一。在糖尿病肾脏疾病中,机体处在高糖状态下募集如白介素、肿瘤坏死因子等炎症反应细胞在肾脏浸润,从而刺激肾脏微血管病变的发生,这一过程涉及多种信号通路的发生。在天然免疫应答系统中,Toll样受体4(toll like receptor 4,TLR4)以及Nod样受体蛋白3(nod-like receptor family pyrin domain-containing protein 3,NLRP3)炎性小体在肾脏相关免疫炎症疾病中扮演着重要角色。近来研究发现,TLR4以及NLRP3炎性小体与糖尿病肾脏疾病的发病机制密切相关。在高糖条件下可检测到TLR4水平的增高,而TLR4通过识别特异性配体激活核因子κB(nuclear factor-κB,NF-κB)从而激活下游炎症因子的成熟与释放,进一步促进肾脏病变。NLRP3炎性小体在糖尿病患者肾脏的足细胞、系膜细胞等少量存在,NF-κB的活化激活炎性小体的组装与成熟,从而促进炎症因子的释放。因此,TLR4、NLRP3在糖尿病肾脏疾病的发生、发展中发挥着重要作用,本文就这一研究展开相关的阐述。展开更多
文摘目的:通过生物信息学分析Nod样受体pyrin结构域蛋白6(Nod-like receptor pyrin domain-containing protein 6,NLRP6)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达模式、生物学功能和免疫细胞浸润关系。方法:利用癌症和肿瘤基因图谱(the cancer genome atlas,TCGA)、国际肿瘤基因组协作组(International Cancer Genome Consortium,ICGC)、基因表达综合(gene expression omnibus,GEO)数据库及TIMER 2.0数据库、HCCDB数据库、人类蛋白质图谱(The Human Protein Atlas,HPA)数据库、基因表达谱交互分析(Gene Expression Profiling Interactive Analysis,GEPIA)数据库分析NLRP6在HCC中的表达模式、临床预后价值。通过Enrichr数据库分析NLRP6的生物学功能。分析NLRP6表达与HCC免疫细胞浸润关系。此外,基于NLRP6表达构建Nomogram模型预测HCC患者预后。结果:NLRP6表达在多种类型肿瘤(包括HCC)中下调(P<0.05),其低表达与HCC不良预后相关(P<0.05)。京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,EGGK)信号通路和基因本体论(gene ontology,GO)分析结果揭示,NLRP6参与炎症-免疫调节反应,包括原发性免疫缺陷、自然杀伤细胞介导的细胞毒性、Th1和Th2细胞分化等信号通路。NLRP6表达与B细胞(r=-0.202)、CD4^(+)T细胞(r=-0.207)、CD8^(+)T细胞(r=0.153)、中性粒细胞(r=0.201)、巨噬细胞(r=-0.133)和髓树突状细胞(r=-0.245)浸润丰度显著相关;高中性粒细胞浸润丰度与HCC患者更差生存预后相关(P<0.05)。基于NLRP6表达、年龄和TNM分期的Nomogram模型能有效预测HCC患者1年、3年及5年总生存率,提供显著临床净收益。结论:NLRP6可能参与HCC发病机制,与炎症-免疫调节及免疫细胞浸润相关。基于NLRP6表达的Nomogram模型能有效预测HCC患者预后,为临床医师治疗HCC提供新的思路。
文摘NOD样受体家族含pyrin结构域蛋白3(NOD-like receptor family pyrin domain-containing protein 3,NLRP3)炎症小体是一种蛋白质复合体,可促进Caspase的活化和IL-1β的成熟,在多种炎症的发生、发展过程中起促进作用。牙周炎(periodontitis,PD)的发生与牙周组织的菌群失调有关,NLRP3炎症小体参与中性粒细胞、巨噬细胞、破骨细胞(osteoclast,OC)和人牙周膜成纤维细胞(human periodontal liqament fibroblast,HPLF)的活化过程。该文归纳了相关免疫细胞及基质细胞的NLRP3炎症小体对PD的影响,并简述了与NLRP3炎症小体相关的PD治疗新思路。
基金This work was supported by the grant from the National Natural Science Foundation of China （No. 81201267）.
文摘Background： Cryopyrin-associated periodic syndrome （CAPS） is a group of rare, heterogeneous autoinflammatory disease characterized by interleukin （IL）-1β-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervous system, and eyes. It encompasses a spectrum of three clinically overlapping autoinflammatory syndromes including familial cold autoinflammatory syndrome, Muckle-Wells syndrome （MWS）, and neonatal-onset multisystem inflammatory disease. CAPS is associated with gain-of-function missense mutations in NOD-like receptor family pyrin domain-containing protein 3 （NLRP3）, the gene encoding NLRP3. Moreover, most mutations leading to MWS occurred in exon 3 ofNLRP3 gene. Here, we reported a novel mutation occurred in exon 1 ofNLRP3 gene in an MWS patient and attempted to explore the pathogenic mechanism. Methods： Genetic sequence analysis of NLRP3 was performed in an MWS patient who presented with periodic lever, arthralgia, and multiform skin lesions. NLRP3 was also analyzed in this patient＇s parents and 50 healthy individuals. Clinical examinations including X-ray examination, skin biopsy, bone marrow aspiration smear, and blood test of C-reactive protein （CRP）, erythrocyte sedimentation rate （ESR）, serum levels oflL-1β, immunoglobulin E （lgE）, antineutrophil cytoplasmic antibodies, antinuclear antibodies, and extractable nuclear antigen were also analyzed. The protein structure of mutant NLRP3 inflammasome was calculated by SWISS-MODEL software. Proteins of wild type and mutant components ofNLRP3 inflammasome were expressed and purified, and the interaction abilities between these proteins were tested by surface plasmon resonance （SPR） assay. Results： X-ray examination showed no abnormality in the patient＇s knees. Laboratory tests indicated an elevation of CRP （233.24 nag/L） and ESR （67 mm/h） when the patient had fever. Serum IL-1β increased to 24.37 pg/ml, and serum lgE was higher than 2500.00 IU/ml. Other blood tests were no
文摘慢性肾脏病发病率逐年上升,现已成为威胁全世界公共健康的主要疾病之一。导致慢性肾脏病的基本病因众多,主要包括原发性与继发性肾小球肾炎、糖尿病肾脏疾病、高血压肾损害、肾小管间质病变、遗传性疾病等。而糖尿病肾脏疾病作为慢性肾脏病的病因之一,是糖尿病引起的肾脏微血管病变的并发症,不加以控制可进展为终末期肾病。糖尿病肾脏疾病的具体发病机制尚不完全清晰,主要以高糖等代谢因素导致的免疫介导性炎症对肾脏破坏为主,而近年来发现免疫介导性炎症因素是糖尿病肾脏疾病发生的重要原因之一。在糖尿病肾脏疾病中,机体处在高糖状态下募集如白介素、肿瘤坏死因子等炎症反应细胞在肾脏浸润,从而刺激肾脏微血管病变的发生,这一过程涉及多种信号通路的发生。在天然免疫应答系统中,Toll样受体4(toll like receptor 4,TLR4)以及Nod样受体蛋白3(nod-like receptor family pyrin domain-containing protein 3,NLRP3)炎性小体在肾脏相关免疫炎症疾病中扮演着重要角色。近来研究发现,TLR4以及NLRP3炎性小体与糖尿病肾脏疾病的发病机制密切相关。在高糖条件下可检测到TLR4水平的增高,而TLR4通过识别特异性配体激活核因子κB(nuclear factor-κB,NF-κB)从而激活下游炎症因子的成熟与释放,进一步促进肾脏病变。NLRP3炎性小体在糖尿病患者肾脏的足细胞、系膜细胞等少量存在,NF-κB的活化激活炎性小体的组装与成熟,从而促进炎症因子的释放。因此,TLR4、NLRP3在糖尿病肾脏疾病的发生、发展中发挥着重要作用,本文就这一研究展开相关的阐述。
