Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interfe...Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome activation.Despite this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive.Consequently,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in CRC.Our findings showed a reduced AIM2 expression in most CRC cell lines.Elevation of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell apoptosis.Further research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and proliferation.Altogether,our achievements distinctly underscored AIM2’s antitumor role in CRC.AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.展开更多
In traumatic brain injury, absent in melanoma 2(AIM2) has been demonstrated to be involved in pyroptotic neuronal cell death. Although the pathophysiological mechanism of spinal cord injury is similar to that of brain...In traumatic brain injury, absent in melanoma 2(AIM2) has been demonstrated to be involved in pyroptotic neuronal cell death. Although the pathophysiological mechanism of spinal cord injury is similar to that of brain injury, the expression and cellular localization of AIM2 after spinal cord injury is still not very clear. In the present study, we used a rat model of T9 spinal cord contusive injury, produced using the weight drop method. The rats were randomly divided into 1-hour, 6-hour, 1-day, 3-day and 6-day(post-injury time points) groups. Sham-operated rats only received laminectomy at T9 without contusive injury. Western blot assay revealed that the expression levels of AIM2 were not significantly different among the 1-hour, 6-hour and 1-day groups. The expression levels of AIM2 were markedly higher in the 1-hour, 6-hour and 1-day groups compared with the sham, 3-day and 7-day groups. Double immunofluorescence staining demonstrated that AIM2 was expressed by NeuN+(neurons), GFAP+(astrocytes), CNPase+(oligodendrocytes) and CD11 b+(microglia) cells in the sham-operated spinal cord. In rats with spinal cord injury, AIM2 was also found in CD45+(leukocytes) and CD68+(activated microglia/macrophages) cells in the spinal cord at all time points. These findings indicate that AIM2 is mainly expressed in neurons, astrocytes, microglia and oligodendrocytes in the normal spinal cord, and that after spinal cord injury, its expression increases because of the infiltration of leukocytes and the activation of astrocytes and microglia/macrophages.展开更多
目的探讨血清黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)和白三烯B4(leukotriene B4,LTB4)水平与急性缺血性脑卒中(acute ischemic stroke,AIS)患者预后的相关性。方法收集2020年2月~2021年2月期间于西安交通大学第一附属医院、西...目的探讨血清黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)和白三烯B4(leukotriene B4,LTB4)水平与急性缺血性脑卒中(acute ischemic stroke,AIS)患者预后的相关性。方法收集2020年2月~2021年2月期间于西安交通大学第一附属医院、西安交通大学附属红会医院、咸阳市第一人民医院和泾阳县医院接受组织型纤溶酶原激活剂(tissue plasminogen activator,tPA)进行静脉溶栓治疗的138例AIS患者的临床资料进行回顾性分析。收集患者治疗三月后的改良Rankin评分量表(modified Rankin rating scale,mRS)评价其神经功能情况。依据mRS评分将AIS患者分为预后良好组(mRS评分≤2分,n=87)和预后不良组(mRS评分>2分,n=51)。采用酶联免疫吸附试验检测血清AIM2和LTB4水平。收集患者入院时的美国国立卫生研究院卒中患者神经功能缺损(neurological deficits in stroke patients at the National Institutes of Health,NIHSS)评分、梗死体积和侧支循环建立状况等信息。分析血清AIM2和LTB4水平、入院NIHSS评分、梗死体积和侧支循环建立状况与AIS患者预后的相关性。建立多因素Logistic回归模型分析rt-PA静脉溶栓后AIS患者预后不良的危险因素。结果与预后良好组比较,预后不良组的血清AIM2(1161.51±338.56pg/ml vs 964.77±171.94pg/ml)和LTB4水平(137.99±35.49pg/ml vs 117.85±21.60pg/ml)明显增高,差异具有统计学意义(t=4.638,4.148,均P<0.01)。Logistic回归分析发现AIS患者血清AIM2和LTB4水平增高、梗死体积增大、入院NIHSS评分增高及侧支循环建立状况较差均为AIS患者预后不良的独立危险因素(均P<0.05)。相关性分析显示AIS患者的血清AIM2和LTB4水平分别与梗死体积和入院NIHSS评分呈正相关性(r=0.374,0.334;0.233,0.304,均P<0.05)。AIM2和LTB4水平增高患者的侧支循环建立状况较差(均P<0.01)。受试者工作特征(receiver operating characteristic,ROC)曲线分析显示AIM2,LTB4及联合检测诊断AIS预后不良的曲线下面积(area under curve,AUC)分别为0.706(95%CI:0.607~0.806,P=0.000),0.745(95%CI:0.655~0.835,P=0.000)和0.740(95%CI:0.648~0.833,P=0.000);约登系数分别为0.424,0.386和0.422;敏感度和特异度分别为60.80%,81.60%;62.70%,75.90%;68.60%,75.80%。AIM2和LTB4诊断AIS预后不良的截断值分别为1065.93pg/ml和130.68pg/ml。结论血清AIM2和LTB4水平增高可能增加AIS患者rt-PA静脉溶栓后预后不良的风险,因此检测患者血清AIM2和LTB4水平可以为AIS患者的预后评估提供依据。展开更多
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
目的人类干扰素诱导基因家族之一的人类干扰素诱导蛋白(absent in melanoma 2,AIM2)被视为抑癌基因,但目前其抑癌机制仍不清楚。文中研究AIM2诱发乳腺癌细胞凋亡的分子机制。方法建立Tet-Off诱导模式系统来诱发AIM2大量表达,MCF-7 t TA-...目的人类干扰素诱导基因家族之一的人类干扰素诱导蛋白(absent in melanoma 2,AIM2)被视为抑癌基因,但目前其抑癌机制仍不清楚。文中研究AIM2诱发乳腺癌细胞凋亡的分子机制。方法建立Tet-Off诱导模式系统来诱发AIM2大量表达,MCF-7 t TA-AIM2细胞为实验组,MCF-7 t TA-Luc细胞为对照组。Western blot检测AIM2在乳腺癌细胞株的表达及亚细胞定位,XTT assay分析AIM2对细胞增殖的影响。应用膜联蛋白V-FITC和碘化丙啶染色行检测细胞凋亡,Western blot检测细胞凋亡的机制。结果文中建立的Tet-Off诱导系统可使t TA结合到TRE,从而促进AIM2基因转录,进而使AIM2蛋白大量表达。在诱导4 d后,可在细胞质及细胞核中检测到AIM2的表达,随诱导天数的增加其表达量增加。AIM2表达于细胞质及细胞核中。由XTT assay可知,MCF-7 t TA-AIM2细胞株在诱导6 d后生长速率减慢。诱导AIM2大量表达后,其FITC荧光凋亡百分比显著增加(2.36%vs 14.45%,P<0.01)。AIM2大量表达后抑制抗凋亡蛋白-Bcl-x L表达,增加促凋亡蛋白-Bad、Bax,并且活化caspases进而造成DNA修复蛋白PARP裂解。结论在乳腺癌Tet-Off诱导系统中,AIM2影响细胞增殖,刺激线粒体促使细胞走向凋亡。展开更多
目的:炎症反应尤其是炎症小体及炎症细胞因子的过度表达,是影响急性脑梗死发生、发展的重要原因之一,包括脑梗死的起始、梗死后损伤的进展和恢复。本研究主要探讨黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)、白细胞介素-1β(interle...目的:炎症反应尤其是炎症小体及炎症细胞因子的过度表达,是影响急性脑梗死发生、发展的重要原因之一,包括脑梗死的起始、梗死后损伤的进展和恢复。本研究主要探讨黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)、白细胞介素-1β(interleukin-1β,IL-1β)和白细胞介素-18(interleukin-18,IL-18)在急性脑梗死患者血浆中的表达及意义。方法:纳入急性脑梗死患者85例为脑梗死组,根据神经功能缺损严重程度、脑梗死面积及发病后第90天的改良Rankin量表(Modified Rankin Scale,mRS)评分分为轻、中及重度组,小、中及大面积组,预后良好组及预后不良组。纳入同期健康体检者85例为对照组。采用酶联免疫吸附(enzyme-linked immunosorbnent assay,ELISA)法检测AIM2、IL-1β和IL-18在这两组人群血浆中的表达水平。结果:脑梗死组血浆AIM2、IL-1β和IL-18水平均明显高于对照组,差异均具有统计学意义(均P<0.001)。脑梗死组亚组比较示:患者血浆AIM2、IL-1β和IL-18水平在重度神经功能缺损严重程度组>中度组>轻度组,在大面积脑梗死组>中面积组>小面积组,在预后不良组>预后良好组,差异均具有统计学意义(均P<0.05);血浆AIM2水平与美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分、脑梗死面积及mRS评分呈正相关(分别r=0.791、r=0.710、r=0.763,均P<0.001),IL-1β水平与NIHSS评分、脑梗死面积及mRS评分呈正相关(分别r=0.716、r=0.690、r=0.688,均P<0.001),IL-18水平与NIHSS评分、脑梗死面积及mRS评分呈正相关(分别r=0.714、r=0.638、r=0.653,均P<0.001);血浆AIM2与IL-1β、IL-18水平呈正相关(分别r=0.828、r=0.751,均P<0.001)。结论:AIM2、IL-1β和IL-18在急性脑梗死患者血浆中表达上调,而且与急性脑梗死患者的神经功能缺损严重程度、脑梗死面积及预后密切相关,提示AIM2、IL-1β和IL-18可能在急性脑梗死的发生、发展中起重要作用。展开更多
基金supported by the Gusu Medical Key Talent Project of Suzhou City of China(GSWS2020005)the New Pharmaceutics and Medical Apparatuses Project of Suzhou City of China(SLJ2021007)+3 种基金the Suzhou City Key Clinical Disease Diagnosis and Treatment Technology Special Project,China(LCZX202129)Wujiang Science and Educational Health Revitalization Fund Project,Suzhou,China(WWK202015)the Scientific Research Project of Suzhou Ninth People’s Hospital,Suzhou,China(YK202008)and Suzhou“Science and Education”Youth Science and Technology Project,Suzhou,China(KJXW2020075).
文摘Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome activation.Despite this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive.Consequently,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in CRC.Our findings showed a reduced AIM2 expression in most CRC cell lines.Elevation of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell apoptosis.Further research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and proliferation.Altogether,our achievements distinctly underscored AIM2’s antitumor role in CRC.AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.
基金supported by the National Natural Science Foundation of China,No.81772321(to HZL),81571194(to HZL),81471277(to JGH)a grant from the Key Program of Anhui Province for Outstanding Talents in Universities in China,No.gxbjZD2016071(to HZL),2014H012(to HZL)
文摘In traumatic brain injury, absent in melanoma 2(AIM2) has been demonstrated to be involved in pyroptotic neuronal cell death. Although the pathophysiological mechanism of spinal cord injury is similar to that of brain injury, the expression and cellular localization of AIM2 after spinal cord injury is still not very clear. In the present study, we used a rat model of T9 spinal cord contusive injury, produced using the weight drop method. The rats were randomly divided into 1-hour, 6-hour, 1-day, 3-day and 6-day(post-injury time points) groups. Sham-operated rats only received laminectomy at T9 without contusive injury. Western blot assay revealed that the expression levels of AIM2 were not significantly different among the 1-hour, 6-hour and 1-day groups. The expression levels of AIM2 were markedly higher in the 1-hour, 6-hour and 1-day groups compared with the sham, 3-day and 7-day groups. Double immunofluorescence staining demonstrated that AIM2 was expressed by NeuN+(neurons), GFAP+(astrocytes), CNPase+(oligodendrocytes) and CD11 b+(microglia) cells in the sham-operated spinal cord. In rats with spinal cord injury, AIM2 was also found in CD45+(leukocytes) and CD68+(activated microglia/macrophages) cells in the spinal cord at all time points. These findings indicate that AIM2 is mainly expressed in neurons, astrocytes, microglia and oligodendrocytes in the normal spinal cord, and that after spinal cord injury, its expression increases because of the infiltration of leukocytes and the activation of astrocytes and microglia/macrophages.
文摘目的探讨血清黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)和白三烯B4(leukotriene B4,LTB4)水平与急性缺血性脑卒中(acute ischemic stroke,AIS)患者预后的相关性。方法收集2020年2月~2021年2月期间于西安交通大学第一附属医院、西安交通大学附属红会医院、咸阳市第一人民医院和泾阳县医院接受组织型纤溶酶原激活剂(tissue plasminogen activator,tPA)进行静脉溶栓治疗的138例AIS患者的临床资料进行回顾性分析。收集患者治疗三月后的改良Rankin评分量表(modified Rankin rating scale,mRS)评价其神经功能情况。依据mRS评分将AIS患者分为预后良好组(mRS评分≤2分,n=87)和预后不良组(mRS评分>2分,n=51)。采用酶联免疫吸附试验检测血清AIM2和LTB4水平。收集患者入院时的美国国立卫生研究院卒中患者神经功能缺损(neurological deficits in stroke patients at the National Institutes of Health,NIHSS)评分、梗死体积和侧支循环建立状况等信息。分析血清AIM2和LTB4水平、入院NIHSS评分、梗死体积和侧支循环建立状况与AIS患者预后的相关性。建立多因素Logistic回归模型分析rt-PA静脉溶栓后AIS患者预后不良的危险因素。结果与预后良好组比较,预后不良组的血清AIM2(1161.51±338.56pg/ml vs 964.77±171.94pg/ml)和LTB4水平(137.99±35.49pg/ml vs 117.85±21.60pg/ml)明显增高,差异具有统计学意义(t=4.638,4.148,均P<0.01)。Logistic回归分析发现AIS患者血清AIM2和LTB4水平增高、梗死体积增大、入院NIHSS评分增高及侧支循环建立状况较差均为AIS患者预后不良的独立危险因素(均P<0.05)。相关性分析显示AIS患者的血清AIM2和LTB4水平分别与梗死体积和入院NIHSS评分呈正相关性(r=0.374,0.334;0.233,0.304,均P<0.05)。AIM2和LTB4水平增高患者的侧支循环建立状况较差(均P<0.01)。受试者工作特征(receiver operating characteristic,ROC)曲线分析显示AIM2,LTB4及联合检测诊断AIS预后不良的曲线下面积(area under curve,AUC)分别为0.706(95%CI:0.607~0.806,P=0.000),0.745(95%CI:0.655~0.835,P=0.000)和0.740(95%CI:0.648~0.833,P=0.000);约登系数分别为0.424,0.386和0.422;敏感度和特异度分别为60.80%,81.60%;62.70%,75.90%;68.60%,75.80%。AIM2和LTB4诊断AIS预后不良的截断值分别为1065.93pg/ml和130.68pg/ml。结论血清AIM2和LTB4水平增高可能增加AIS患者rt-PA静脉溶栓后预后不良的风险,因此检测患者血清AIM2和LTB4水平可以为AIS患者的预后评估提供依据。
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。
文摘目的人类干扰素诱导基因家族之一的人类干扰素诱导蛋白(absent in melanoma 2,AIM2)被视为抑癌基因,但目前其抑癌机制仍不清楚。文中研究AIM2诱发乳腺癌细胞凋亡的分子机制。方法建立Tet-Off诱导模式系统来诱发AIM2大量表达,MCF-7 t TA-AIM2细胞为实验组,MCF-7 t TA-Luc细胞为对照组。Western blot检测AIM2在乳腺癌细胞株的表达及亚细胞定位,XTT assay分析AIM2对细胞增殖的影响。应用膜联蛋白V-FITC和碘化丙啶染色行检测细胞凋亡,Western blot检测细胞凋亡的机制。结果文中建立的Tet-Off诱导系统可使t TA结合到TRE,从而促进AIM2基因转录,进而使AIM2蛋白大量表达。在诱导4 d后,可在细胞质及细胞核中检测到AIM2的表达,随诱导天数的增加其表达量增加。AIM2表达于细胞质及细胞核中。由XTT assay可知,MCF-7 t TA-AIM2细胞株在诱导6 d后生长速率减慢。诱导AIM2大量表达后,其FITC荧光凋亡百分比显著增加(2.36%vs 14.45%,P<0.01)。AIM2大量表达后抑制抗凋亡蛋白-Bcl-x L表达,增加促凋亡蛋白-Bad、Bax,并且活化caspases进而造成DNA修复蛋白PARP裂解。结论在乳腺癌Tet-Off诱导系统中,AIM2影响细胞增殖,刺激线粒体促使细胞走向凋亡。
文摘目的:炎症反应尤其是炎症小体及炎症细胞因子的过度表达,是影响急性脑梗死发生、发展的重要原因之一,包括脑梗死的起始、梗死后损伤的进展和恢复。本研究主要探讨黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)、白细胞介素-1β(interleukin-1β,IL-1β)和白细胞介素-18(interleukin-18,IL-18)在急性脑梗死患者血浆中的表达及意义。方法:纳入急性脑梗死患者85例为脑梗死组,根据神经功能缺损严重程度、脑梗死面积及发病后第90天的改良Rankin量表(Modified Rankin Scale,mRS)评分分为轻、中及重度组,小、中及大面积组,预后良好组及预后不良组。纳入同期健康体检者85例为对照组。采用酶联免疫吸附(enzyme-linked immunosorbnent assay,ELISA)法检测AIM2、IL-1β和IL-18在这两组人群血浆中的表达水平。结果:脑梗死组血浆AIM2、IL-1β和IL-18水平均明显高于对照组,差异均具有统计学意义(均P<0.001)。脑梗死组亚组比较示:患者血浆AIM2、IL-1β和IL-18水平在重度神经功能缺损严重程度组>中度组>轻度组,在大面积脑梗死组>中面积组>小面积组,在预后不良组>预后良好组,差异均具有统计学意义(均P<0.05);血浆AIM2水平与美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分、脑梗死面积及mRS评分呈正相关(分别r=0.791、r=0.710、r=0.763,均P<0.001),IL-1β水平与NIHSS评分、脑梗死面积及mRS评分呈正相关(分别r=0.716、r=0.690、r=0.688,均P<0.001),IL-18水平与NIHSS评分、脑梗死面积及mRS评分呈正相关(分别r=0.714、r=0.638、r=0.653,均P<0.001);血浆AIM2与IL-1β、IL-18水平呈正相关(分别r=0.828、r=0.751,均P<0.001)。结论:AIM2、IL-1β和IL-18在急性脑梗死患者血浆中表达上调,而且与急性脑梗死患者的神经功能缺损严重程度、脑梗死面积及预后密切相关,提示AIM2、IL-1β和IL-18可能在急性脑梗死的发生、发展中起重要作用。
