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
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
Objective： Lung cancer has emerged as a leading cause of cancer death in the world. Eyes Absent （EYA） is an important and conserved transcriptional regulator of development. The aim of the present study was to iden...Objective： Lung cancer has emerged as a leading cause of cancer death in the world. Eyes Absent （EYA） is an important and conserved transcriptional regulator of development. The aim of the present study was to identify the expression of Drosophila Eyes Absent Hemologue 2 （EYA2） in non-small cell lung cancer （NSCLC） and to investigate their correlation with clinical parameters. Methods： Fresh, paired lung samples （n = 59） of NSCLC were obtained by surgical resection at the Department of Thoracic Surgery of the People＇s Liberation Army General Hospital. Expression of EYA2 were examined by Western blot and immunohistochemical analysis in specimens of NSCLC and paired normal lung tissue. Clinical data, pathologic result and Ki67 expression were collected and subsequent correlation with EYA2 expression was analyzed. Results： EYA2 expression was found located in cytoplasm and nucleus, but mostly in cytoplasm. The expression of EYA2 increased in NSCLC by Western blot and immunohistochemistry, which was correlated with histology type, but not correlated with gender, age, pTNM stage, histological differentiation and lymph node metastasis. Compared with normal lung tissue, the expression of EYA2 significantly was up-regulated in lung adenocarcinoma, while no significant difference in lung squamous cell carcinoma. Expression of EYA2 was uncorrelated with expression of Ki67 in NSCLC. Conclusion： Expression of EYA2 was augmented in lung adenocarcinoma. EYA2 is likely participating in tumorigenesis and development of lung adenocarcinoma as transcriptional activator.展开更多
目的探讨果蝇双翅边缘缺刻同源基因(Notch)信号通路在慢性阻塞性肺疾病(COPD)辅助性T细胞1(Helper T cells 1,Th1)和辅助性T细胞2(Helper T cells 2,Th2)失衡中的作用及芪蛭皱肺颗粒的干预机制。方法70只Wistar大鼠随机挑选10只作为空...目的探讨果蝇双翅边缘缺刻同源基因(Notch)信号通路在慢性阻塞性肺疾病(COPD)辅助性T细胞1(Helper T cells 1,Th1)和辅助性T细胞2(Helper T cells 2,Th2)失衡中的作用及芪蛭皱肺颗粒的干预机制。方法70只Wistar大鼠随机挑选10只作为空白对照组,其余大鼠均采用香烟烟雾(CS)联合气管滴注脂多糖(Lipopolysaccharide,LPS)法建立COPD模型,空白对照组及造模组各随机挑选3只大鼠验证造模是否成功。造模结束进行灌胃给药干预,造模组大鼠随机分为模型对照组、阳性对照组(67.5μg·kg^(-1))及芪蛭皱肺颗粒高中低剂量组(3.24、1.62、0.81 g·kg^(-1)),分别给予生理盐水、醋酸地塞米松混悬液、芪蛭皱肺高、中、低剂量混悬液进行灌胃干预,空白对照组同模型对照组,灌胃等体积生理盐水。经28天造模及28天治疗后,采用动物肺功能测试系统检测吸气峰流速(Peak Inspiratory Flow,PIF)和呼气峰流速(Peak Expiratory Flow,PEF),处死大鼠提取肺脏、脾脏、血清及支气管肺泡灌洗液(BALF),苏木素-伊红(HE)染色评价肺组织病理变化,酶联免疫吸附实验法(ELISA)测定血清及BALF中肿瘤坏死因子-α(TNF-α)含量,流式细胞仪检测脾脏Th1/Th2细胞水平,免疫组织化学法(Immunohistochemistry,IHC)及蛋白免疫印迹法(Western blot)检测肺组织Notch1、Hes家族发状分裂相关增强子1(Hes1)、Hey家族发状分裂相关增强子1(Hey1)蛋白水平,实时荧光定量聚合酶链式反应(Real-time PCR,RT-PCR)检测肺组织Notch1、Hes1、Hey1基因表达水平。结果与空白对照组比较,模型对照组大鼠肺功能显著降低(P<0.05),肺组织出现炎性细胞浸润、支气管结构破坏等病变,血清及BALF中TNF-α含量显著升高(P<0.05),脾Th1细胞百分比显著降低(P<0.05),Th2细胞百分比显著升高(P<0.05),肺组织Notch1、Hes1、Hey1蛋白及mRNA表达显著升高(P<0.05),差异均具有统计学意义;与模型对照组比较,各给药组大鼠肺功能显著升高(P<0.05),肺组织病理损伤均有所减轻,血清及BALF中TNF-α含量显著降低(P<0.05),脾Th1细胞百分比显著升高(P<0.05),Th2细胞百分比显著降低(P<0.05),肺组织Notch1、Hes1、Hey1蛋白及mRNA表达显著降低(P<0.05),差异均具有统计学意义。结论芪蛭皱肺颗粒通过抑制Notch信号通路调节Th1/Th2平衡,从而改善COPD大鼠肺功能及病理损伤,影响其免疫功能。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
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Objective： Lung cancer has emerged as a leading cause of cancer death in the world. Eyes Absent （EYA） is an important and conserved transcriptional regulator of development. The aim of the present study was to identify the expression of Drosophila Eyes Absent Hemologue 2 （EYA2） in non-small cell lung cancer （NSCLC） and to investigate their correlation with clinical parameters. Methods： Fresh, paired lung samples （n = 59） of NSCLC were obtained by surgical resection at the Department of Thoracic Surgery of the People＇s Liberation Army General Hospital. Expression of EYA2 were examined by Western blot and immunohistochemical analysis in specimens of NSCLC and paired normal lung tissue. Clinical data, pathologic result and Ki67 expression were collected and subsequent correlation with EYA2 expression was analyzed. Results： EYA2 expression was found located in cytoplasm and nucleus, but mostly in cytoplasm. The expression of EYA2 increased in NSCLC by Western blot and immunohistochemistry, which was correlated with histology type, but not correlated with gender, age, pTNM stage, histological differentiation and lymph node metastasis. Compared with normal lung tissue, the expression of EYA2 significantly was up-regulated in lung adenocarcinoma, while no significant difference in lung squamous cell carcinoma. Expression of EYA2 was uncorrelated with expression of Ki67 in NSCLC. Conclusion： Expression of EYA2 was augmented in lung adenocarcinoma. EYA2 is likely participating in tumorigenesis and development of lung adenocarcinoma as transcriptional activator.
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。
