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Cerebral Dopamine Neurotrophic Factor:A Potential Therapeutic Agent for Parkinson's Disease

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Neuroscience Bulletin 2017年第5期33卷 568-575页

作者： Tingting Tang Yong Li Qian Jiao Xixun Du Hong Jiang Department of Physiology Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders State Key Disciplines: Physiology Medical College of Qingdao University Qingdao 266071 China

The application of neurotrophic factors （NTFs） is a promising therapeutic strategy for neurodegenerative disorders such as Parkinson＇s disease （PD）. Many NTFs have been reported to enhance the survival, regeneration, and differentiation of neurons and to induce synaptic plasticity. However, because of their potential side-effects and low efficacy after clinical administration, more potent treatments for neurodegenerative disorders are being sought. Cerebral dopamine neurotrophic factor （CDNF）, a newly-identified NTF homologous to mesencephalic astrocyte-derived NTF, is structurally and functionally different from other NTFs, providing new hope especially for PD patients. In various animal models of PD, CDNF is efficient in protecting and repairing dopaminergic neurons, and it inhibits endoplasmic reticulum stress, neuroinflam- mation, and apoptosis. Recent progress in all facets of CDNF research has enabled researchers to better under- stand its beneficial effects in the treatment of PD.

关键词： Cerebral dopamine neurotrophic factorParkinson＇s disease - Neuroprotection - Anti-inflammatory · Anti-apoptotic

The effects of ghrelin on midbrain neural stem cells differentiation to dopaminergic neurons by mediating Wnt/β-catenin signaling pathway

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The effects of ghrelin on midbrain neural stem cells differe...

Expression and function of DMT1 without IRE in C6 cells mediated by recombinant adenovirus

中国生理学会张锡钧基金会第十三届全国青年优秀生理学学术论文交流及评奖会议、中国生理学会第十一届全国青年生理学工作者学术会议

作者：焦倩 Bing Gong Xixun Du Junxia Xie Hong Jiang 青岛大学医学院 Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines:Physiology Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders Medical College of Qingdao University

Objective:Ghrelin,a 28 amino acid hormone mainly produced in the stomach,could enhance neural stem cells(NSCs) proliferation and differentiation in adult animals.In the present study,we investigated t

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Frontiers of Medicine 2009年第1期3卷 67-71页

作者： Xixun Du Huamin XU Hong JIANG Jun WANG Lei WANG Junxia XIE State Key Disciplines:Physiology(in incubation) Department of PhysiologyMedical College of Qingdao UniversityQingdao 266071China

Divalent metal transporter 1(DMT1)is a ferrous iron import protein.The improper expression of DMT1 is involved in neurodegenerative diseases.In the present study,we constructed a recombinant adenovirus containing the gene of DMT1 without the iron response element(DMT1-IRE)and investigated its expression and function in the C6 glioma cell line.The DMT1-IRE gene,obtained by RT-PCR,was cloned into the shuttle plasmid-ing pAdTrack-CMV containing greenﬂuorescent protein(GFP)reporter gene.Linearized plasmid pAdTrack-CMV-DMT1-IRE was subsequently co-transformed into Escher-ichia coli(E.coli)BJ5183 cells along with an adenoviral backbone plasmid pAdEasy-1 after digestion with Pme I.Pac I-digested pAdEasy1-DMT1-IRE was then transfected into E1-transformed human embryonic kidney cells(HEK293 cells),in which recombinant adenoviruses were generated within 7 to 10 days.The results demon-strated that we obtained the DMT1-IRE gene.pAdEasy1-DMT1-IRE yielded a large fragment,plus a smaller fragment of 4.5 kb after digestion with Pac I.PCR conﬁrmed pAdEasy1-DMT1-IRE contained gene DMT1-IRE,indicating the successful construction of recombi-nant adenovirus plasmid containing DMT1-IRE.GFPﬂuorescence further conﬁrmed the generation of recombi-nant AdDMT1-IRE adenovirus.AdDMT1-IRE could efﬁciently infect C6 glioma cells.And cell viability decreased in AdDMT1-IRE infected cells after iron overload compared to the control.These results suggest that the over expressed DMT1-IRE can aggravate the iron induced cell death due to its iron inﬂux function.

关键词： divalent metal transporter 1 recombinant adenovirus homologous recombination iron

A dural substitute based on oxidized quaternized guar gum/porcine peritoneal acellular matrix with improved stability, antibacterial and anti-adhesive properties

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Chinese Chemical Letters 2023年第3期34卷 424-429页

作者： Xiaoshuang Yu Pengfei Yue Xu Peng Hongmei Ding Ningning Lei xixun Yu College of Polymer Science and Engineering Sichuan UniversityChengdu 610065China West China Hospital of Sichuan University Department of BiotherapyCancer CenterState Key Laboratory of BiotherapyChengdu 610041China Experimental and Research Animal Institute Sichuan UniversityChengdu 610065China

Trauma and neurosurgery often result in dural defects and are followed by serious complications or even death, finding suitable dural replacement materials to repair the defective dura has important clinical significance. Porcine peritoneal acellular matrix(PPAM) is a promising alternative material, but its poor stability makes it difficult to meet the various needs of dural reconstruction. In this work, we developed a novel antibacterial cross-linking agent oxidized quaternized guar gum(OQGG) and used it for the first time to stabilize PPAM to construct a dural mater substitute(OQGG-PPAM). The results showed that 1.5%OQGG-PPAM presented suitable mechanical property as well as good thermal stability and resistance to enzymatic degradation. It also exhibited good antibacterial activity and good anti-leakage ability. Furthermore, 1.5% OQGG-PPAM not only exhibited excellent cell compatibility but also significantly stimulated the secretion of b FGF and VEGF from seeded cells which was convenient for dural remodeling. In vivo experiment, it also exhibited the excellent histocompatibility and good anti-adhesion property. This study showed that OQGG can be used as a novel antibacterial cross-linking reagent for crosslinking natural tissues and 1.5% OQGG-PPAM was a potential candidate material for dura mater substitute.

关键词： Oxidized quaternized guar gum dural substitute Porcine peritoneal acellular matrix Antibacterial

Decomposition of Fast and Slow Cloud Responses to Quadrupled CO_(2)Forcing in BCC–AGCM2.0 over East Asia

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Advances in Atmospheric Sciences 2022年第12期39卷 2188-2202页

作者： xixun ZHOU Bing XIE Hua ZHANG Jingyi HE Qi CHEN State Key Laboratory of Severe Weather Chinese Academy of Meteorological SciencesBeijing 100081China University of Chinese Academy of Sciences Beijing 100049China Laboratory for Climate Studies of China Meteorological Administration National Climate CenterBeijing 100081China

In this study,the decomposed fast and slow responses of clouds to an abruptly quadrupled CO_(2)concentration(approximately 1139 ppmv)in East Asia(EA)are obtained quantitatively by using a general circulation model,BCC–AGCM2.0.Our results show that in the total response,the total cloud cover(TCC),low cloud cover(LCC),and high cloud cover(HCC)all increased north of 40°N and decreased south of 40°N except in the Tibetan Plateau(TP).The mean changes of the TCC,LCC,and HCC in EA were–0.74%,0.38%,and–0.38%in the total response,respectively;1.05%,–0.03%,and 1.63%in the fast response,respectively;and–1.79%,0.41%,and–2.01%in the slow response,respectively.By comparison,we found that changes in cloud cover were dominated by the slow response in most areas in EA due to the changes in atmospheric temperature,circulation,and water vapor supply together.Overall,the changes in the cloud forcing over EA related to the fast and slow responses were opposite to each other,and the final cloud forcing was dominated by the slow response.The mean net cloud forcing(NCF)in the total response over EA was–1.80 W m^(–2),indicating a cooling effect which partially offset the warming effect caused by the quadrupled CO_(2).The total responses of NCF in the TP,south China(SC),and northeast China(NE)were–6.74 W m^(–2),6.11 W m^(–2),and–7.49 W m^(–2),respectively.Thus,the local effects of offsetting or amplifying warming were particularly obvious.

关键词： cloud cover cloud forcing quadrupled CO_(2) fast and slow responses

大鼠帕金森病模型中α-突触核蛋白对干扰素调节因子1的调控及其机制

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南方医科大学学报 2021年第11期41卷 1641-1648页

作者：牟斐斐陈曦杜希恂焦倩毕明霞姜宏青岛大学国家生理学重点(培育)学科山东青岛266071

目的研究α-突触核蛋白(α-Syn)对干扰素调节因子1(IRF-1)表达的影响及其分子机制。方法选用α-Syn过表达的SHSY5Y细胞以及3月龄、6月龄A53Tα-Syn转基因小鼠,应用Real-time PCR和Western blot技术检测IRF-1表达的变化,免疫荧光染色和... 详细信息

目的研究α-突触核蛋白(α-Syn)对干扰素调节因子1(IRF-1)表达的影响及其分子机制。方法选用α-Syn过表达的SHSY5Y细胞以及3月龄、6月龄A53Tα-Syn转基因小鼠,应用Real-time PCR和Western blot技术检测IRF-1表达的变化,免疫荧光染色和核浆蛋白分离技术观察IRF-1亚细胞定位情况。不同浓度的蛋白酶体抑制剂MG132(0、0.01、0.05、0.1、0.2、0.5、1、2μmol/L)以及溶酶体抑制剂氯喹(0、5、10、30、50、100、150、200μmol/L)处理SH-SY5Y细胞24 h,检测细胞存活率。选用不引起细胞损伤的最大浓度0.2μmol/LMG132和30μmol/L氯喹处理SH-SY5Y细胞24 h,检测IRF-1蛋白水平的变化。观察α-Syn对MDM2蛋白水平的影响,并进一步通过泛素化实验检测IRF-1泛素化水平的变化。结果α-Syn过表达不影响IRF-1 mRNA水平,却可显著上调其蛋白水平(P<0.01),并且IRF-1在胞核表达的比例升高,发生核移位现象(P<0.001)。不同浓度的MG132和氯喹处理后细胞存活率随浓度升高而逐渐降低,不引起细胞损伤的最大浓度分别为0.2μmol/L和30μmol/L。0.2μmol/L MG132处理后可加剧α-Syn引起的IRF-1蛋白水平的升高(P<0.01),而30μmol/L氯喹处理后IRF-1蛋白表达无明显变化。α-Syn过表达导致MDM2蛋白水平降低(P<0.01),进而抑制IRF-1的泛素化修饰。结论α-Syn通过泛素-蛋白酶体途径,抑制MDM2介导的IRF-1泛素化修饰,进而上调IRF-1蛋白表达。

关键词：帕金森病 α-突触核蛋白干扰素调节因子1 神经免疫

Improving the efficiency of the CRISPR-Cas12a system with tRNA-crRNA arrays

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The Crop Journal 2020年第3期8卷 403-407页

作者： xixun Hu Xiangbing Meng Jiayang Li Kejian Wang Hong Yu State Key Laboratory of Rice Biology China National Rice Research InstituteChinese Academy of Agricultural SciencesHangzhou 310006ZhejiangChina State Key Laboratory of Plant Genomics and National Center for Plant Gene Research(Beijing) Institute of Genetics and Developmental BiologyThe Innovative Academy of Seed DesignChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

CRISPR-Cas12a offers a convenient tool for multiplex genome editing in rice. However, the CRISPR-Cas12a system displays variable editing efficiency across genomic loci, with marked influence by CRISPR RNAs(crRNAs). To improve the efficiency of the CRISPR-Cas12a system for multiplex genome editing, we identified various architectures and expression strategies for crRNAs. Transformation of binary vectors loaded with engineered CRISPR-Cas12a systems into rice calli and subsequent sequencing revealed that a modified tRNA-crRNA array not only efficiently achieved rice multiplex genome editing, but also successfully edited target sites that were not edited by the crRNA array. This improvement contributes to the application of the CRISPR-Cas12a system in plant genome editing, especially for genomic loci that have hitherto been difficult to edit.

关键词： crRNA CRISPR-Cas12a tRNA-crRNA array Genome editing Editing efficiency

Development and Application of CRISPR/Cas System in Rice

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Rice science 2019年第2期26卷 69-76,I0004-I0006页

作者： REN Jun HU xixun WANG Kejian WANG Chun State Key Laboratory of Rice Biology China National Rice Research Institute Chinese Academy of Agricultural Sciences

In the past several years, the CRISPR(clustered regularly interspaced short palindromic repeats)/Cas(CRISPR-associated protein) system has been harnessed as an efficient and powerful tool for targeted genome editing in different prokaryotic and eukaryotic species. Here, we review the development and application of CRISPR/Cas system in rice, emphasizing different varieties of CRISPR/Cas systems have been applied, strategies for multiplex editing, methods for precise gene insertion and replacement, and efficient systems for base editing and site-specific transcriptional regulation. In addition, the biosecurity of CRISPR/Cas system is also discussed, including transgene-free methods and off-target effects of CRISPR/Cas system. Thus, the development and application of CRISPR/Cas system will have significant impact on functional genomic research and variety improvement in rice.

关键词： rice CRISPR Cas genome editing protospacer adjacent motif

Targeted mutagenesis in rice using CRISPR-Cpf1 system

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Journal of Genetics and Genomics 2017年第1期44卷 71-73页

作者： xixun Hu Chun Wang Qing Liu Yaping Fu Kejian Wang State Key Laboratory of Rice Biology China National Rice Research InstituteChinese Academy of Agricultural Sciences Hangzhou 310006 China

Cpf1 is a class 2/type V CRISPR effector that has been recently harnessed for genome editing （Zetsche et al., 2015; Hut et al., 2016; Kim et al., 2016）. Cpff recognizes thymidine-rich sequence as the protospacer-adjacent motif （PAM） at the 5＇ end of target sequences. In addition, Cpfl requires only a single shorter crRNA and cleaves DNA in a staggered fashion with 5＇ overhangs （Zetsche et al., 2015）.

关键词： Targeted mutagenesis in rice using CRISPR-Cpf1 system tRNA