银屑病是一种由环境诱因刺激、多基因遗传控制和免疫因素调节等多因素共同作用导致的慢性、炎症性、复发性、系统性疾病,炎症因素在该疾病的发生和发展中具有重要作用。全外显子组测序(whole-exome sequencing,WES)鉴定出黑色素瘤缺乏因...银屑病是一种由环境诱因刺激、多基因遗传控制和免疫因素调节等多因素共同作用导致的慢性、炎症性、复发性、系统性疾病,炎症因素在该疾病的发生和发展中具有重要作用。全外显子组测序(whole-exome sequencing,WES)鉴定出黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)基因为银屑病的易感基因。AIM2基因编码的AIM2蛋白可识别双链DNA,诱导凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a CARD,ASC)的胱天蛋白酶募集结构域(caspase activation and recruitment domain,CARD)招募半胱氨酸天冬氨酸蛋白水解酶-1(cysteine-requiring aspartate protease-1,caspase-1),组成高分子量蛋白复合体——AIM2炎症小体。国内外研究者聚焦于AIM2基因及AIM2炎症小体在银屑病中的作用开展了大量研究,并取得一定的研究进展。本文对近五年来有关AIM2基因及AIM2炎症小体在银屑病中的研究进展进行一综述。展开更多
纤维化发生于机体多种器官组织,持续进展的纤维化改变可导致组织结构被破坏并影响正常功能,甚至引起器官衰竭而死亡,如肺纤维化、心力衰竭、慢性肾病、肺动脉瓣关闭不全等。但目前尚无有效防治策略。慢性持续性炎性反应是纤维化进展的...纤维化发生于机体多种器官组织,持续进展的纤维化改变可导致组织结构被破坏并影响正常功能,甚至引起器官衰竭而死亡,如肺纤维化、心力衰竭、慢性肾病、肺动脉瓣关闭不全等。但目前尚无有效防治策略。慢性持续性炎性反应是纤维化进展的重要机制,近年来发现的黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)炎症小体是一种胞质内多蛋白复合物,通过识别双链DNA(dsDNA)激活并介导炎症因子的成熟释放,所引起的炎性反应可以调控多种通路进而诱导纤维化。本文针对AIM2在纤维化疾病中的最新研究进展作一综述,以期为纤维化的治疗和干预提供新的靶点。展开更多
Background: Up to 5% of patientswith melanoma have a family history of a first-degree relative also being affected. Objectives: To study such families for germline mutations, to help clarify the gene-environment inter...Background: Up to 5% of patientswith melanoma have a family history of a first-degree relative also being affected. Objectives: To study such families for germline mutations, to help clarify the gene-environment interaction in melanoma aetiology. Methods: Thirty-two families in Scotland with melanoma in two or more first-degree relatives are reported for the first time. Peripheral blood DNA was extracted, and denaturing high-performance liquid chromatography analysis performed on exons 1 α and 2 of the CDKN2A gene and their splice junctions. The coding sequences and splice junctions of these exons were sequenced in all samples as confirmation of the chromatographic pattern observed. Results: Seven of the 32 melanoma families (22% ) have CDKN2A mutations. One mutation, H83N, which has not previously been described in melanoma families, was found in one family. In addition, two families have R112G mutations, one family has a G67R mutation, one has an exon 1 α 24-bp duplication where bases 9- 32 are duplicated between bases 32 and 33, and two families have M53I mutations, bringing the total of known Scottish families with the M53I mutation to six. Conclusions: This study brings the total of Scottish families investigated for germlinemutations to 48, and strongly suggests that the M53I mutation originated in Scotland.展开更多
文摘银屑病是一种由环境诱因刺激、多基因遗传控制和免疫因素调节等多因素共同作用导致的慢性、炎症性、复发性、系统性疾病,炎症因素在该疾病的发生和发展中具有重要作用。全外显子组测序(whole-exome sequencing,WES)鉴定出黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)基因为银屑病的易感基因。AIM2基因编码的AIM2蛋白可识别双链DNA,诱导凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a CARD,ASC)的胱天蛋白酶募集结构域(caspase activation and recruitment domain,CARD)招募半胱氨酸天冬氨酸蛋白水解酶-1(cysteine-requiring aspartate protease-1,caspase-1),组成高分子量蛋白复合体——AIM2炎症小体。国内外研究者聚焦于AIM2基因及AIM2炎症小体在银屑病中的作用开展了大量研究,并取得一定的研究进展。本文对近五年来有关AIM2基因及AIM2炎症小体在银屑病中的研究进展进行一综述。
文摘纤维化发生于机体多种器官组织,持续进展的纤维化改变可导致组织结构被破坏并影响正常功能,甚至引起器官衰竭而死亡,如肺纤维化、心力衰竭、慢性肾病、肺动脉瓣关闭不全等。但目前尚无有效防治策略。慢性持续性炎性反应是纤维化进展的重要机制,近年来发现的黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)炎症小体是一种胞质内多蛋白复合物,通过识别双链DNA(dsDNA)激活并介导炎症因子的成熟释放,所引起的炎性反应可以调控多种通路进而诱导纤维化。本文针对AIM2在纤维化疾病中的最新研究进展作一综述,以期为纤维化的治疗和干预提供新的靶点。
文摘Background: Up to 5% of patientswith melanoma have a family history of a first-degree relative also being affected. Objectives: To study such families for germline mutations, to help clarify the gene-environment interaction in melanoma aetiology. Methods: Thirty-two families in Scotland with melanoma in two or more first-degree relatives are reported for the first time. Peripheral blood DNA was extracted, and denaturing high-performance liquid chromatography analysis performed on exons 1 α and 2 of the CDKN2A gene and their splice junctions. The coding sequences and splice junctions of these exons were sequenced in all samples as confirmation of the chromatographic pattern observed. Results: Seven of the 32 melanoma families (22% ) have CDKN2A mutations. One mutation, H83N, which has not previously been described in melanoma families, was found in one family. In addition, two families have R112G mutations, one family has a G67R mutation, one has an exon 1 α 24-bp duplication where bases 9- 32 are duplicated between bases 32 and 33, and two families have M53I mutations, bringing the total of known Scottish families with the M53I mutation to six. Conclusions: This study brings the total of Scottish families investigated for germlinemutations to 48, and strongly suggests that the M53I mutation originated in Scotland.
