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
Background:L-dopa(Levodopa)is well known for managing PD(Parkinson’s disease);however,its prolonged use caused dyskinesia(LID).Due to the varied presentation of LID,effective treatment options are scarce.Flavonoids r...Background:L-dopa(Levodopa)is well known for managing PD(Parkinson’s disease);however,its prolonged use caused dyskinesia(LID).Due to the varied presentation of LID,effective treatment options are scarce.Flavonoids reported their neuroprotective activity by ameliorating acetylcholinesterase,monoamine oxidase,and neuroinflammation.Kaempferol is anotherflavonoid bearing these potentials.Aim:To evaluate neuroprotective activity of kaempferol in dyskinetic rats.Methods:PD was developed in Sprague-Dawley rats by injecting combination of L-ascorbic acid(10µL)+6-OHDA(12µg)in medial forebrain bundle to induce neuronal damage in substantial nigra(SNr).LID was induced by administrating combination of L-dopa(20 mg/kg)+benserazide HCl(5 mg/kg)for 42 days.Rats were concomitantly treated with amantadine(40 mg/kg)or kaempferol(25,50,and 100 mg/kg,p.o.).Results:Kaempferol(50 and 100 mg/kg)markedly(p<0.05)inhibited LID-induced abnormal involuntary movements(AIMs)and alternation in motor function.Kaempferol administration considerably(p<0.05)inhibited reduced mitochondrial complex activities,serotonin and dopamine levels,Bcl-2,and Tyrosine hydroxylase protein expressions in SNr.Additionally,kaempferol considerably(p<0.05)attenuated increased cFOS,FosB,Parkin,and Pdyn mRNAs expressions,Bax,cleaved caspase-3,caspase-3,and pJNK proteins levels;DOPAC and 5-HIAA levels in SNr.A positive correlation was reported between cFOS,FosB,Parkin,Pdyn,apoptosis,and TH with AIMs.Conclusion:Kaempferol effectively attenuated L-dopa-induced AIMs and dyskinesia via amelioration of alterations in cFOS,FosB,Parkin,Pdyn,Tyrosine hydroxylase,and apoptosis in the brain SNr.展开更多
背景心脏衰老是老年人心血管疾病患病率升高的主要原因之一,了解心肌衰老的发病机制以及发现老年心血管疾病的新治疗靶点至关重要。目的探讨黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)在小鼠心肌衰老模型中的作用。方法通过生物信...背景心脏衰老是老年人心血管疾病患病率升高的主要原因之一,了解心肌衰老的发病机制以及发现老年心血管疾病的新治疗靶点至关重要。目的探讨黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)在小鼠心肌衰老模型中的作用。方法通过生物信息学分析AIM2在年轻小鼠与老龄小鼠心室中具体的表达差异。在动物水平上,将雄性BALB/C小鼠按照年龄分为年轻组(2月龄)和老龄组(14月龄),分别检测两组小鼠心肌中AIM2、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a CARD,ASC)、半胱天冬酶-1(cysteinyl aspartate specific proteinase-1,Caspase-1)在蛋白和mRNA水平上的变化。在细胞水平上,首先应用不同浓度的D-gal(0 g/L、10 g/L、20 g/L、50 g/L)处理H9C2心肌细胞制备细胞衰老模型,采用CCK-8法检测细胞活力,以确定复制心肌细胞衰老的D-gal浓度;应用选定浓度的D-gal处理H9C2细胞,将细胞分为对照组和衰老组,采用β-半乳糖苷酶染色检测细胞衰老程度,利用Western blot、免疫荧光和RT-qPCR等方法检测心肌细胞中AIM2、ASC、Caspase-1在蛋白和mRNA水平的变化。结果生物信息学结果显示老龄小鼠心室肌中AIM2表达水平较年轻组升高。动物实验中,老龄组小鼠心室中AIM2、ASC、Caspase-1的蛋白和mRNA水平均较年轻组升高(P<0.05)。细胞研究中,使用CCK-8法测定细胞活力,结合细胞状态采用20 g/L的D-gal处理H9C2建立细胞衰老模型,衰老组AIM2、ASC、Caspase-1在蛋白和mRNA水平均较对照组升高(P<0.05)。结论生物信息学、在体与离体实验结果显示,在心肌衰老过程中AIM2在蛋白和mRNA水平均升高,AIM2在心肌衰老的发生和发展中可能发挥了一定作用,为心肌衰老发生机制研究提供了新思路。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Background:L-dopa(Levodopa)is well known for managing PD(Parkinson’s disease);however,its prolonged use caused dyskinesia(LID).Due to the varied presentation of LID,effective treatment options are scarce.Flavonoids reported their neuroprotective activity by ameliorating acetylcholinesterase,monoamine oxidase,and neuroinflammation.Kaempferol is anotherflavonoid bearing these potentials.Aim:To evaluate neuroprotective activity of kaempferol in dyskinetic rats.Methods:PD was developed in Sprague-Dawley rats by injecting combination of L-ascorbic acid(10µL)+6-OHDA(12µg)in medial forebrain bundle to induce neuronal damage in substantial nigra(SNr).LID was induced by administrating combination of L-dopa(20 mg/kg)+benserazide HCl(5 mg/kg)for 42 days.Rats were concomitantly treated with amantadine(40 mg/kg)or kaempferol(25,50,and 100 mg/kg,p.o.).Results:Kaempferol(50 and 100 mg/kg)markedly(p<0.05)inhibited LID-induced abnormal involuntary movements(AIMs)and alternation in motor function.Kaempferol administration considerably(p<0.05)inhibited reduced mitochondrial complex activities,serotonin and dopamine levels,Bcl-2,and Tyrosine hydroxylase protein expressions in SNr.Additionally,kaempferol considerably(p<0.05)attenuated increased cFOS,FosB,Parkin,and Pdyn mRNAs expressions,Bax,cleaved caspase-3,caspase-3,and pJNK proteins levels;DOPAC and 5-HIAA levels in SNr.A positive correlation was reported between cFOS,FosB,Parkin,Pdyn,apoptosis,and TH with AIMs.Conclusion:Kaempferol effectively attenuated L-dopa-induced AIMs and dyskinesia via amelioration of alterations in cFOS,FosB,Parkin,Pdyn,Tyrosine hydroxylase,and apoptosis in the brain SNr.
文摘背景心脏衰老是老年人心血管疾病患病率升高的主要原因之一,了解心肌衰老的发病机制以及发现老年心血管疾病的新治疗靶点至关重要。目的探讨黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)在小鼠心肌衰老模型中的作用。方法通过生物信息学分析AIM2在年轻小鼠与老龄小鼠心室中具体的表达差异。在动物水平上,将雄性BALB/C小鼠按照年龄分为年轻组(2月龄)和老龄组(14月龄),分别检测两组小鼠心肌中AIM2、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a CARD,ASC)、半胱天冬酶-1(cysteinyl aspartate specific proteinase-1,Caspase-1)在蛋白和mRNA水平上的变化。在细胞水平上,首先应用不同浓度的D-gal(0 g/L、10 g/L、20 g/L、50 g/L)处理H9C2心肌细胞制备细胞衰老模型,采用CCK-8法检测细胞活力,以确定复制心肌细胞衰老的D-gal浓度;应用选定浓度的D-gal处理H9C2细胞,将细胞分为对照组和衰老组,采用β-半乳糖苷酶染色检测细胞衰老程度,利用Western blot、免疫荧光和RT-qPCR等方法检测心肌细胞中AIM2、ASC、Caspase-1在蛋白和mRNA水平的变化。结果生物信息学结果显示老龄小鼠心室肌中AIM2表达水平较年轻组升高。动物实验中,老龄组小鼠心室中AIM2、ASC、Caspase-1的蛋白和mRNA水平均较年轻组升高(P<0.05)。细胞研究中,使用CCK-8法测定细胞活力,结合细胞状态采用20 g/L的D-gal处理H9C2建立细胞衰老模型,衰老组AIM2、ASC、Caspase-1在蛋白和mRNA水平均较对照组升高(P<0.05)。结论生物信息学、在体与离体实验结果显示,在心肌衰老过程中AIM2在蛋白和mRNA水平均升高,AIM2在心肌衰老的发生和发展中可能发挥了一定作用,为心肌衰老发生机制研究提供了新思路。