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81.
Chenyang Han Yi Yang Qiaobing Guan Xiaoling Zhang Heping Shen Yongjia Sheng Jin Wang Xiaohong Zhou Wenyan Li Li Guo Qingcai Jiao 《Journal of cellular and molecular medicine》2020,24(14):8078-8090
The present study was designed to investigate the role of β‐amyloid (Aβ1‐42) in inducing neuronal pyroptosis and its mechanism. Mice cortical neurons (MCNs) were used in this study, LPS + Nigericin was used to induce pyroptosis in MCNs (positive control group), and Aβ1‐42 was used to interfere with MCNs. In addition, propidium iodide (PI) staining was used to examine cell permeability, lactate dehydrogenase (LDH) release assay was employed to detect cytotoxicity, immunofluorescence (IF) staining was used to investigate the expression level of the key protein GSDMD, Western blot was performed to detect the expression levels of key proteins, and enzyme‐linked immunosorbent assay (ELISA) was utilized to determine the expression levels of inflammatory factors in culture medium, including IL‐1β, IL‐18 and TNF‐α. Small interfering RNA (siRNA) was used to silence the mRNA expression of caspase‐1 and GSDMD, and Aβ1‐42 was used to induce pyroptosis, followed by investigation of the role of caspase‐1‐mediated GSDMD cleavage in pyroptosis. In addition, necrosulfonamide (NSA), an inhibitor of GSDMD oligomerization, was used for pre‐treatment, and Aβ1‐42 was subsequently used to observe the pyroptosis in MCNs. Finally, AAV9‐siRNA‐caspase‐1 was injected into the tail vein of APP/PS1 double transgenic mice (Alzheimer's disease mice) for caspase‐1 mRNA inhibition, followed by observation of behavioural changes in mice and measurement of the expression of inflammatory factors and pyroptosis‐related protein. As results, Aβ1‐42 could induce pyroptosis in MCNs, increase cell permeability and enhance LDH release, which were similar to the LPS + Nigericin‐induced pyroptosis. Meanwhile, the expression levels of cellular GSDMD and p30‐GSDMD were up‐regulated, the levels of NLRP3 inflammasome and GSDMD‐cleaved protein caspase‐1 were up‐regulated, and the levels of inflammatory factors in the medium were also up‐regulated. siRNA intervention in caspase‐1 or GSDMD inhibited Aβ1‐42‐induced pyroptosis, and NSA pre‐treatment also caused the similar inhibitory effects. The behavioural ability of Alzheimer's disease (AD) mice was relieved after the injection of AAV9‐siRNA‐caspase‐1, and the expression of pyroptosis‐related protein in the cortex and hippocampus was down‐regulated. In conclusion, Aβ1‐42 could induce pyroptosis by GSDMD protein, and NLRP3‐caspase‐1 signalling was an important signal to mediate GSDMD cleavage, which plays an important role in Aβ1‐42‐induced pyroptosis in neurons. Therefore, GSDMD is expected to be a novel therapeutic target for AD. 相似文献
82.
电针对帕金森病模型小鼠黑质铁染色细胞和铁蛋白表达的影响 总被引:1,自引:0,他引:1
目的探讨电针防治帕金森病的作用机制。方法采用1-甲基-4-苯基1,2,3,6四氢吡啶腹腔注射建立帕金森病小鼠模型,利用组织化学技术以及免疫组织化学技术观察电针对帕金森病小鼠脑黑质铁染色细胞和铁蛋白表达的影响。结果模型组1周、2周、4周小鼠黑质铁染色阳性细胞的数量较正常组明显增多,染色强度也明显增强(P〈0.001;P〈0.01;P〈0.001),电针在3个存活期内均可明显减少帕金森病小鼠黑质铁阳性细胞的数量和染色强度(P〈0.001;P〈0.05;P〈0.001);模型组1周、2周黑质部位铁蛋白的表达与正常组相比都有不同程度下降(P〈0.01;P〈0.001),而电针组2周帕金森病小鼠黑质铁蛋白的表达与模型组相比显著增加(P〈0.01)。结论电针可以通过降低脑内铁的含量,同时增加铁蛋白的表达,从而提高帕金森病模型小鼠脑抗氧化能力,达到保护黑质多巴胺能神经元的目的。 相似文献
83.
The Ugi four-component reaction (U-4CR) was utilized to prepare divalent and trivalent cluster mannosides with different scaffolds. The glycoclusters obtained were tested for their relative inhibitory potency against the binding of yeast mannan to concanavalin A by solid-phase enzyme-linked lectin assays (ELLA) using methyl alpha-D-mannopyranoside as a standard. Among them, a divalent mannoside containing aromatic groups showed the strongest binding affinity to concanavalin A. 相似文献
84.
目的为了为揭示肌萎缩脊髓侧索硬化症(amyotrophic lateral sclerosis,ALS)认知功能障碍的机制提供依据,观察不同年龄ALS转基因小鼠海马中突触囊泡蛋白(synaptophysin,Syp)的表达情况。方法取95d、108d和122dALS转基因鼠海马,应用免疫荧光、Westernblot、RT-PCR技术检测Syp在海马中的表达变化。结果与同窝野生型鼠比较,Syp蛋白和mRNA表达水平在95d龄ALS转基因鼠海马中无明显变化,在108d与122d龄ALS转基因鼠海马中明显降低。结论Syp在ALS转基因鼠海马中表达减少表明,突触可塑性降低是ALS学习记忆能力下降的重要病理学基础。 相似文献
85.
反义寡核苷酸体外抗流感病毒活性 总被引:2,自引:0,他引:2
为了获得具有抗流感病毒活性的反义寡核苷酸,针对A型流感病毒基因组3′和5′端保守序列,设计并合成了多条硫代寡核苷酸(ODN):3′端反义ODN(IV3#)与3′端正义ODN(IV3S);5′端反义ODN(IV4#)与5′端正义ODN(IV4S)以及由5′和3′端正义/反义保守序列组成的复合序列ODN(IV6#和IV7#)。测定了PSODN的体外细胞毒性和在MDCK细胞中对流感病毒复制的影响。结果表明:(1)PSODN浓度高达50μmol/L时对MDCK细胞末表现有毒性作用;(2)与流感病毒基因组5′端互补的ODN IV4#以及由5′和3′端保守序列构成的IV6#ODN和IV7#ODN均具有较高的抗病毒活性;如IV4#ODN浓度为1μmol/L时对流感病毒A/京防/861(H1N1)抑制率近50%,浓度为10μmol/L或更高时抑制率超过70%,且IV4#抑制病毒活性呈现明显的序列和剂量依赖性;(3)IV4#ODN不仅对A型流感病毒H1N1亚型有抑制作用,对H3N2亚型也表现较高的抑制活性;(4)病毒感染复数(MOI)对IV4#ODN抗病毒活性有一定影响,当MOI较低时,IV4#ODN表现的剂量效应关系更加明显。抗流感病毒反义寡核苷核IV4#ODN的发现为进一步研究流感新型药物奠定了实验基础。〖HTH〗关键词〖HTSS〗:流感病毒, 反义寡核苷酸, 体外细胞毒性, 抗病毒活性, 感染复数 相似文献
86.
有关能源消费的代谢机理及生态效率研究是当前生态经济研究领域中的重点和难点,也是政府决策部门、相关行业及人群关注的热点。基于能源代谢分析理念,构建了基于相对变量的城市能源消费碳排放综合生态效率度量模型,对2000—2013年南昌市能源消费结构、碳排放量及其生态效率进行了测算与分析。结果表明:(1)南昌市在2000—2013年,能源消费量和碳排放量整体上呈"N"型曲线上升的一致性变化特征,主要经历了快速增长、短暂下降、恢复平稳增长3个阶段,且煤炭是南昌市能源消费和碳排放的主要来源,短时期内难以改变;(2)南昌市的能源消费效率和碳排放效率整体上在不断优化;(3)南昌市能源消费碳排放综合生态效率经历了较大的波动变化,整体上的生态效率分值并不高;仍需要加大节能减排力度,全面优化南昌市能源消费结构。 相似文献
87.
Diversity and dynamics of the bacterial community involved in pig manure biodegradation in a microbial fermentation bed system 总被引:8,自引:0,他引:8
Qianqian Chen Bo Liu Jieping Wang Jianmei Che Guohong Liu Xiong Guan 《Annals of microbiology》2017,67(7):491-500
Overproduction of livestock manures with unpleasant odors causes significant environmental problems. The microbial fermentation bed (MFB) system is considered an effective approach to recycling utilization of agricultural byproducts and pig manure (PM). To gain a better understanding of bacterial communities present during the degradation of PM in MFB, the PM bacterial community was evaluated at different fermentation stages using 16S rRNA high throughput sequencing technology. The heatmap plot clustered five samples into short-term fermentation stage of 0–10 days and long-term fermentation stage of 15–20 days. The most abundant OTUs at the phylum level were Firmicutes, Actinobacteria and Proteobacteria in the long-term fermentation stage of PM, whereas Firmicutes, Bacteroidetes, and Proteobacteria predominated in the short-term fermentation stage of PM. At the genus level, organic degradation strains, such as Corynebacterium, Bacillus, Virgibacillus, Pseudomonas, Actinobacteria, Lactobacillus, Pediococcus were the predominate genera at the long-term fermentation stage, but were found only rarely in the short-term fermentation stage. C/N ratios increased and the concentration of the unpleasant odor substance 3-hydroxy-5-methylisoxazole (3-MI) decreased with prolonged period of fermentation. Redundancy analysis (RDA) demonstrated that the relative abundance of Firmicutes, Actinobacteria, Acidobacteria and Proteobacteria had a close relationship with degradation of 3-MI and increasing C/N ratio. These results provide valuable additional information about bacterial community composition during PM biodegradation in animal husbandry. 相似文献
88.
Biochemical characterization of the mitochondrial tRNASer(UCN) T7511C mutation associated with nonsyndromic deafness 总被引:6,自引:0,他引:6
Li X Fischel-Ghodsian N Schwartz F Yan Q Friedman RA Guan MX 《Nucleic acids research》2004,32(3):867-877
We report here the biochemical characterization of the deafness-associated mitochondrial tRNASer(UCN) T7511C mutation, in conjunction with homoplasmic ND1 T3308C and tRNAAla T5655C mutations using cybrids constructed by transferring mitochondria from lymphoblastoid cell lines derived from an African family into human mtDNA-less (ρ°) cells. Three cybrids derived from an affected matrilineal relative carrying the homoplasmic T7511C mutation, exhibited ~75% decrease in the tRNASer(UCN) level, compared with three control cybrids. This amount of reduction in the tRNASer(UCN) level is below a proposed threshold to support a normal rate of mitochondrial protein synthesis in lymphoblastoid cell lines. This defect is likely a primary contributor to ~52% reduction in the rate of mitochondrial protein synthesis and marked defects in respiration and growth properties in galactose-containing medium. Interestingly, the T5655C mutation produces ~50% reduction in the tRNAAla level in mutant cells. Strikingly, the T3308C mutation causes a significant decrease both in the amount of ND1 mRNA and co-transcribed tRNALeu(UUR) in mutant cells. Thus, mitochondrial dysfunctions caused by the T5655C and T3308C mutations may modulate the phenotypic manifestation of the T7511C mutation. These observations imply that a combination of the T7511C mutation with two mtDNA mutations accounts for the high penetrance of deafness in this family. 相似文献
89.
Mitochondrial tRNA mutations are one of the important causes of both syndromic and non-syndromic deafness. Of those, syndromic deafness-associated tRNA mutations such as tRNA(Leu(UUR)) 3243A>G are often present in heteroplasmy, while non-syndromic deafness-associated tRNA mutations including tRNA(Ser(UCN)) 7445A>G often occur in homplasmy or in high levels of heteroplasmy. These tRNA mutations are the primary mutations leading to hearing loss. However, other tRNA mutations such as tRNA(Thr) 15927G>A and tRNA(Ser(UCN)) 7444G>A may act in synergy with the primary mitochondrial DNA mutations, modulating the phenotypic manifestation of the primary mitochondrial DNA mutations. Theses tRNA mutations cause structural and functional alteration. A failure in tRNA metabolism caused by these tRNA mutations impaired mitochondrial translation and respiration, thereby causing mitochondrial dysfunctions responsible for deafness. These data offer valuable information for the early diagnosis, management and treatment of maternally inherited deafness. 相似文献
90.