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| 1 | 靶向PDCD5-Caspase-3融合基因过表达对HepG2肝癌细胞增殖与凋亡的影响显示文摘目的探讨靶向PDCD5-Caspase-3融合基因过表达对Hep G2肝癌细胞体外增殖与凋亡的影响。方法利用基因重组技术构建PDCD5-Caspase-3融合基因,克隆到带有EGFP基因的GV358慢病毒表达载体,与辅助质粒共同转染293T细胞,通过同源重组,获得融合基因重组慢病毒PDCD5-Caspase-3。体外转染人肝癌Hep G-2细胞72 h后,Western bolt检测肝癌Hep G-2细胞中PDCD5蛋白和Caspase-3蛋白表达,CCK-8法检测PDCD5-Caspase-3融合基因过表达对Hep G-2肝癌细胞增殖的影响,流式细胞术观察其对细胞凋亡的影响。结果 PDCD5-Caspase-3融合基因过表达可增加Hep G-2肝癌细胞中PDCD5蛋白和Caspase-3蛋白合成(P<0.05);与对照组或空白组相比,转染72 h后实验组细胞增殖能力下降(P<0.05);与对照组或空白组比较,转染72 h后实验组细胞凋亡率增加(P<0.05)。结论促凋亡基因PDCD5和Caspase-3联合表达可抑制Hep G2肝癌细胞增殖,并促进其凋亡,可作为肝癌治疗潜在靶点。 | 胥丹 姜淮芜 蒲羽 | 2018 | 中国现代医学杂志2018，28，24： | 9 |
| 2 | 基于纳米基因载体的动植物遗传转化研究进展显示文摘转基因技术在动植物优良新品种的培育中发挥着重要作用,而随着纳米生物技术的发展,基于纳米材料构建基因载体的动植物转基因技术,对于发展动植物转基因新方法以及加速转基因种质材料的大规模制备、优良新品种的培育进程具有更为重要的意义。综述了纳米基因载体的种类与性质,并结合动植物遗传育种的研究进展,分析了纳米基因载体相比于其他载体的特点及优势,同时,重点阐述了基于纳米基因载体的基因转染技术的基本原理和操作过程,及其在动植物遗传转化中的应用,以期为动植物基因工程改造提供新思路。 | 王安琪 朱华新 赵翔 崔建霞 王琰 崔海信 | 2018 | 生物技术进展2018，8，4： | 5 |
| 3 | 利用CRISPR/Cas9技术在活体青年猕猴脑内进行基因编辑诱导其出现孤独症谱系障碍的行为表型显示文摘尽管CRISPR/Cas9基因编辑技术被广泛应用于人类疾病建模工作,但此前并无人利用该技术在非人灵长类脑内通过对疾病相关基因的编辑诱导出猕猴的行为表型.本研究利用AAV介导的CRISPR/Cas9技术,对活体猕猴海马脑区中与孤独症谱系障碍(ASD)和瑞特综合症(RTT)发病密切相关的MECP2基因进行编辑,基因编辑组猕猴(n=7)与其自身基因编辑前作为对照,同时与注射空载病毒的对照组猕猴(n=4)相比,其在基因编辑后出现了部分与孤独症临床症状十分相似的行为学改变,包括社交障碍、睡眠节律紊乱、对外界刺激的迟钝和手部精细运动受损等.可是另一些典型的孤独症症状,比如刻板运动,又没有在这些基因编辑猴中被观察到.以上现象提示不同的脑区在该疾病中可能扮演不同的角色.本研究利用上述技术能够快速高效地在猕猴上复制出相关疾病的症状,也为今后探索快速成模的转基因工程猕猴疾病模型奠定了基础.此类猕猴模型将为脑疾病的机理研究以及治疗作出重要贡献. | 吴诗昊 李霄 秦冬冬 张琳恒 程田林 陈枝芳 聂彬彬 任晓峰 吴晶 王文超 胡英周 谷依琳 吕龙宝 尹勇 胡新天 仇子龙 | 2021 | Science Bulletin2021，66，9： | 4 |
| 4 | Caspase-3基因过表达抑制LN-18人神经胶质瘤细胞移植瘤生长显示文摘目的观察靶向caspase-3基因过表达对LN-18人神经胶质瘤细胞移植瘤生长的影响并探讨其机制。方法化学合成caspase-3基因序列,通过同源重组,获得caspase-3基因过表达慢病毒。设置转染组、对照组和空白组,其中转染组细胞转染caspase-3基因过表达慢病毒,对照组细胞转染含阴性序列基因重组慢病毒,空白组细胞不加病毒上清液,慢病毒转染LN-18人神经胶质瘤细胞72 h后测定病毒转染效率,蛋白质印迹法评估caspase-3蛋白表达。制备裸鼠神经胶质瘤荷瘤模型,细胞接种后每3天测量肿瘤体积,21 d后处死动物,剥离肿瘤组织,比较各组瘤块大小,TUNEL法观察各组肿瘤组织内细胞凋亡情况。结果 caspase-3基因过表达慢病毒能有效感染LN-18人神经胶质瘤细胞,体外细胞转染率达到83.7%,转染72 h后,转染组caspase-3蛋白表达显著增加;转染组LN-18人神经胶质瘤细胞移植裸鼠皮下,肿瘤生长速度明显小于对照组和空白组,至移植后21 d,转染组、对照组和空白组移植瘤体积分别为(0.52±0.17)cm^3、(2.61±0.22)cm^3和(2.38±0.19)cm^3,F=104.241,P=0.021 89;移植后21 d,与对照组和空白组相比,转染组移植瘤细胞凋亡显著增加(P <0.001)。结论 caspase-3基因过表达慢病毒转染LN-18人神经胶质瘤细胞可明显促进caspase-3蛋白合成,抑制LN-18神经胶质瘤细胞体内移植后生长,显著增加肿瘤细胞凋亡,可作为神经胶质瘤治疗新手段。 | 葛风 蒋云召 王泳 | 2019 | 实用医学杂志2019，35，9： | 4 |
| 5 | Bax-Caspase-3融合基因过表达对MGC-803胃癌细胞增殖、凋亡和迁移的影响显示文摘本研究通过构建Bax-Caspase-3融合基因,慢病毒转染人MGC-8O3胃癌细胞72 h后检测细胞中Bax蛋白和Caspase-3蛋白表达,观察Bax-Caspase-3融合基因过表达对MGC-803胃癌细胞增殖、凋亡及迁移的影响。结果表明,慢病毒转染Bax-Caspase-3融合基因72 h后,MGC-803胃癌细胞中Bax蛋白和Caspase-3蛋白水平显著增加,细胞增殖能力明显降低,细胞凋亡率明显增加,细胞迁移能力明显降低。 | 刘畅 田兴 蒋志强 李剑 张珉 周东民 | 2019 | 中华普通外科杂志2019，34，6： | 3 |
| 6 | A novel missense variant in ACAA1 contributes to early-onset Alzheimer’s disease,impairs lysosomal function,and facilitates amyloid-p pathology and cognitive decline显示文摘Alzheimer’s disease(AD)is characterized by progressive synaptic dysfunction,neuronal death,and brain atrophy,with amyloid-p(Ap)plaque deposits and hyperphosphorylated tau neurofibrillary tangle accumulation in the brain tissue,which all lead to loss of cognitive function.Pathogenic mutations in the well-known AD causal genes including APP,PSEN1,and PSEN2 impair a variety of pathways,including protein processing,axonal transport,and metabolic homeostasis.Here we identified a missense variant rs117916664(c.896T>C,p.Asn299Ser[p.N299S])of the acetyl-CoA acyltransferase 1(ACM1)gene in a Han Chinese AD family by whole-genome sequencing and validated its association with early-onset familial AD in an independent cohort.Further in vitro and in vivo evidence showed that ACAA1 p.N299S contributes to AD by disturbing its enzymatic activity,impairing lysosomal function,and aggravating the Ap pathology and neuronal loss,which finally caused cognitive impairment in a murine model.Our findings reveal a fundamental role of peroxisome-mediated lysosomal dysfunction in AD pathogenesis. | Rongcan Luo Yu Fan Jing Yang Maosen Ye Deng-Feng Zhang Kun Guo Xiao Li Rui Bi Min Xu Lu-Xiu Yang Yu Li Xiaoqian Ran Hong-Yan Jiang Chen Zhang Liwen Tan Nengyin Sheng Yong-Gang Yao | 2021 | Signal Transduction and Targeted Therapy2021，6，9： | 1 |
| 7 | Increased attention to snake images in cynomolgus monkeys: an eye-tracking study显示文摘Previous studies have revealed faster detection of snake images in humans and non-human primates(NHPs),suggesting automatic detection of evolutionary fear-relevant stimuli.Furthermore,human studies have indicated that general fear-relevance rather than evolutionary relevance is more effective at capturing attention.However,the issue remains unclarified in NHPs.Thus,in the present study,we explored the attentional features of laboratory-reared monkeys to evolutionary and general fear-relevant stimuli(e.g.,images of snakes,capturing gloves).Eye-tracking technology was utilized to assess attentional features as it can provide more accurate latency and variables of viewing duration and frequency compared with visual search task(VST)and response latency adopted in previous studies.In addition,those with autism spectrum disorder(ASD)show abnormal attention to threatening stimuli,including snake images.Rett syndrome(RTT)is considered a subcategory of ASD due to the display of autistic features.However,the attentional features of RTT patients or animal models to such stimuli remain unclear.Therefore,we also investigated the issue in MECP2 gene-edited RTT monkeys.The influence of different cognitive loads on attention was further explored by presenting one,two,or four images to increase stimulus complexity.The eye-tracking results revealed no significant differences between RTT and control monkeys,who all presented increased viewing(duration and frequency)of snake images but not of aversive stimuli compared with control images,thus suggesting attentional preference for evolutionary rather than general fear-relevant visual stimuli.Moreover,the preference was only revealed in visual tasks composed of two or four images,suggesting its cognitive-load dependency. | Bo Zhang Zhi-Gang Zhou Yin Zhou Yong-Chang Chen | 2020 | Zoological Research2020，41，1： | 0 |
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