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HDAC inhibitors improve CRISPR-mediated HDR editing efficiency in iPSCs

Science China(Life Sciences) 2021年第9期64卷 1449-1462页

作者： Jian-Ping Zhang Zhi-Xue ya.g Feng Zhang ya-Wen Fu Xin-Yue Dai Wei Wen Beldon Zhang Hannah choi Wanqiu Chen Meredith Brown David Baylink Lei Zhang Hongyu Qiu Charles Wang Tao Cheng Xiao-Bing Zhang State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China School of Medicine Loma Linda UniversityLoma LindaCA 92354USA Center for genomics School of MedicineLoma Linda UniversityLoma LindaCA 92350USA CAMS Key Laboratory of gene Therapy for Blood Diseases Tianjin 300020China Center for Stem Cell Medicine Chinese Academy of Medical SciencesTianjin 300020China Department of Stem Cell&Regenerative Medicine Peking Union Medical CollegeTianjin 300020China Tianjin Key Laboratory of gene Therapy for Blood Diseases Tianjin 300020China Center of Molecular and Translational Medicine Institution of Biomedical ScienceGeorgia State UniversityAtlantaGA 30303USA

genome-edited human induced pluripotent stem cells(iPSCs)hold great promise for therapeutic ***,low editing efficiency has hampered the applications of CRISPR-Cas9 technology in creating knockout and homology-directed repair(HDR)-edited iPSC lines,particularly for silent *** is partially due to chromatin compaction,inevitably limiting Cas9 access to the target *** the six HDAC inhibitors we examined,vorinostat,or suberoylanilide hydroxamic acid(SAHA),led to the highest HDR efficiency at both open and closed loci,with acceptable *** inhibitors equally increased non-homologous end joining(NHEJ)editing efficiencies(~50%)at both open and closed loci,due to the considerable HDAC inhibitor-mediated increase in Cas9 and sgRNA ***,we observed more substantial HDR efficiency improvement at closed loci relative to open chromatin(2.8 vs.1.7-fold change).These studies provide a new strategy for HDRediting of silent genes in iPSCs.

关键词： HDAC inhibitors CRISPR-Cas9 genome editing iPSC

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glucose-responsive artificial promoter-mediated insulin gene transfer improves glucose control in diabetic mice

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World Journal of gastroenterology 2012年第44期18卷 6420-6426页

作者： Jaeseok Han Eung-Hwi Kim Woohyuk choi Hee-Sook Jun Department of Microbiology and Infectious Diseases University of Calgary3330 Hospital Drive N.W.CalgaryAlberta T2N 4N1Canada Del E.Webb Neuroscience Aging and Stem Cell Research CenterSanford Burnham Medical Research InstituteLa JollaCA 92037United States Lee gil ya Cancer and Diabetes Institute Gachon University7-45 SondodongYeonsu-kuIncheon 406-840South Korea College of Pharmacy Gachon University7-45 Sondo-dongYeonsu-kuIncheon 406-840South Korea

AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese ***:We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level *** intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter(rAd-SP-rINSfur) into diabetic Lepr db/db mice.A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control(rAd-CMV-βgal).Blood glucose levels and body weights were monitored for 50 *** and insulin tolerance tests were *** staining was performed to investigate islet morphology and insulin ***:Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d,whereas the rAd-CMV-βgal control virus-injected mice remained *** tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve(AUC):21 508.80 ± 2248.18 vs 62 640.00 ± 5014.28,P gnificantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice(AUC:9150.17 ± 1007.78 vs 11 994.20 ± 474.40,P gher concentration of insulin than those from rAd-CMV-βgal-injected ***:Based on these results,we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.

关键词： Insulin gene therapy Synthetic promoter glucose-responsive element Liver-specific promoter Type 2 diabetes

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Supplemental blue light increases growth and quality of greenhouse pak choi depending on cultivar and supplemental light intensity

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Journal of Integrative Agriculture 2018年第10期17卷 2245-2256页

作者： ZHENg Yin-jian ZHANg Yi-ting LIU Hou-cheng LI ya-min LIU Ying-liang HAO yan-wei LEI Bing-fu College of Horticulture South China Agricultural University College of Materials and Energy South China Agricultural University

To evaluate the supplementary blue light intensity on growth and health-promoting compounds in pak choi（Brassica campestris *** ***）,four blue light intensity treatments（T0,T50,T100 and T150 indicate 0,50,100,and 150μmol m^（-2） s^（-1）,respectively）were applied 10 days before harvest under greenhouse *** of cultivars（greenand red-leaf pak choi）under T50 had the highest yield,content of chlorophyll and *** light intensity increasing,antioxidant compounds（vitamin C and carotenoids）significantly increased,while nitrate content showed an opposite *** health-promoting compounds（phenolics,flavonoids,anthocyanins,and glucosinolates）were significantly higher under supplementary light treatment than T0,so as the antioxidant capacity（2,2-diphenyl-1-picrylhydrazyl and ferric-reducing antioxidant power）.The species-specific differences in photosynthetic pigment and health-promoting compounds was found in green-and red-leaf pak choi.T50 treatment could be used for yield improvement,whereas T100 treatment could be applied for quality *** showed that blue light intensity can regulate the accumulation of biomass,morphology and health-promoting compounds in pak choi under greenhouse conditions.

关键词： blue light antioxidant compounds health-promoting compounds species-specific pak choi

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8-Hydroxydeoxyguanosine:Not mere biomarker for oxidative stress,but remedy for oxidative stress-implicated gastrointestinal diseases

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World Journal of gastroenterology 2012年第4期18卷 302-308页

作者： Chan-Young Ock Eun-Hee Kim Duck Joo choi Ho Jae Lee Ki-Baik Hahm Myung Hee Chung Lab of Translational Medicine Gachon University of Medicine and ScienceLee Gil Ya Cancer and Diabetes Institute Department of gastroenterology Gachon Graduate School of MedicineGil Hospital Sungkyunkwan University Samsung Advanced Institute for Biomedical Research

Reactive oxygen species （ROS） attack guanine bases in DNA easily and form 8-hydroxydeoxyguanosine （8-OHdg）, which can bind to thymidine rather than cytosine, based on which, the level of 8-OHdg is gen- erally regarded as a biomarker of mutagenesis conse- quent to oxidative stress. For example, higher levels of 8-OHdg are noted in Helicobacter pylori-associated chronic atrophic gastritis as well as gastric cancer. However, we have found that exogenous 8-OHdg can paradoxically reduce ROS production, attenuate the nuclear factor-KB signaling pathway, and ameliorate the expression of proinflammatory mediators such as interleukin （IL）-I, IL-6, cyclo-oxygenase-2, and induc- ible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase （NOX）-I, NOX organizer-1 and NOX activator-1 in vari- ous conditions of inflammation-based gastrointestinal （gI） diseases including gastritis, inflammatory bowel disease, pancreatitis, and even colitis-associated carci- nogenesis. Our recent finding that exogenous 8-OHdg was very effective in either inflammation-based or oxidative-stress-associated diseases of stress-related mucosal damage has inspired the hope that synthetic 8-OHdg can be a potential candidate for the treatment of inflammation-based gI diseases, as well as the pre- vention of inflammation-associated gI cancer. In this editorial review, the novel fact that exogenous 8-OHdg can be a functional molecule regulating oxidative- stress-induced gastritis through either antagonizing Rac-guanosine triphosphate binding or blocking the signals responsible for gastric inflammatory cascade is introduced.

关键词： 8-hydroxydeoxyguanosine Oxidative stress Inflammation Carcinogenesis Prevention

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白菜的EST标记及其对油菜的通用性

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遗传 2005年第3期27卷 410-416页

作者：忻雅崔海瑞张明龙林容杓崔水莲浙江大学农业与生物技术学院原子核农业科学研究所杭州310029 忠南大学园艺系

根据白菜的表达序列标签,设计了28对引物。在对引物、dNTP、MgCl2的浓度及退火温度等参数进行测试后,建立了合适的PCR反应体系。在此反应体系下,以构建EST的白菜自交系A的DNA为模板,对设计的引物进行了筛选,发现有18对引物能对白菜DNA... 详细信息

根据白菜的表达序列标签,设计了28对引物。在对引物、dNTP、MgCl2的浓度及退火温度等参数进行测试后,建立了合适的PCR反应体系。在此反应体系下,以构建EST的白菜自交系A的DNA为模板,对设计的引物进行了筛选,发现有18对引物能对白菜DNA扩增出产物。用筛选出来的引物分别对17个白菜类品种进行PCR扩增,用琼脂糖凝胶电泳分析其产物的多态性,发现10对引物有多态性,占筛选引物的55.6%。为检测白菜EST标记的通用性,进一步利用设计的引物对不同油菜品种的DNA进行PCR扩增。在检测的28对引物中,共有24对引物能扩增出产物,占引物总数的85.7%,显示多态性的引物为18对,占引物总数的64.3%.。在对白菜DNA能扩增出产物的18对引物中,对油菜完全可用,且有13对引物产生多态性。而在那些对白菜未扩增出产物的10对引物中,也有6对能扩增出产物,其中5对显示多态性。结果证明,通过EST建立分子标记是可行的,而且这种标记对近缘物种是可通用的。

关键词：白菜表达序列标签(EST) 分子标记通用性

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Different risk factors for advanced colorectal neoplasm in young adults

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World Journal of gastroenterology 2016年第13期22卷 3611-3620页

作者： Ji Yeon Kim Yoon Suk Jung Jung Ho Park Hong Joo Kim Yong Kyun Cho Chong Il Sohn Woo Kyu Jeon Byung Ik Kim Kyu Yong choi dong Il Park Comprehensive Health Care Center Korea Cancer Center Hospital Korea Institute of Radiological and Medical Sciences Department of Internal Medicine Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine

AIM: To compare the risk of developing advanced colorectal neoplasm(ACRN) according to age in ***: A total of 70428 Koreans from an occupational cohort who underwent a colonoscopy between 2003 and 2012 at Kangbuk Samsung Hospital were retrospectively selected. We evaluated and compared odds ratios(OR) for ACRN between the young-adults(ya gy, high-grade dysplasia, or invasive ***: In the ya.group, age(OR = 1.08, 95%CI: 1.06-1.09), male sex(OR = 1.26, 95%CI: 1.02-1.55), current smoking(OR = 1.37, 95%CI: 1.15-1.63), family history of colorectal cancer(OR = 1.46, 95%CI: 1.01-2.10), diabetes mellitus related factors(OR = 1.27, 95%CI: 1.06-1.54), obesity(OR = 1.23, 95%CI: 1.03-1.47), CEA(OR = 1.04, 95%CI: 1.01-1.09) and low-density lipoprotein-cholesterol(OR = 1.01, 95%CI: 1.01-1.02) were related with an increased risk of ACRN. However, age(OR = 1.08, 95%CI: 1.06-1.09), male sex(OR = 2.12, 95%CI: 1.68-2.68), current smoking(OR = 1.38, 95%CI: 1.12-1.71), obesity(OR = 1.34, 95%CI: 1.09-1.65) and CEA(OR = 1.05, 95%CI: 1.01-1.09) also increased the risk of ACRN in the OA ***: The risks of ACRN differed based on age group. Different colonoscopic screening strategies are appropriate for particular subjects with risk factors for ACRN, even in subjects younger than 50 years.

关键词： Young-adult Advanced colorectal neoplasm Risk factors Age Metabolic abnormality

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Effect of probiotics on growth performance, development of small intestinal tract and microbial populations in broilers

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Journal of Agricultural Science and Technology 2009年第4期3卷 24-31,39页

作者： LEI yan ZHANg Ke-ying DINg Xue-mei BAI Shi-ping JUNg Sik choi Animal Nutrition Institute Sichuan Agricultural University Ya ＇an 625014 China Engineering Research Center of Animal Disease-Resistance Nutrition of China Ministry of Education Sichuan Agricultural University Ya ＇an 625014 China JSC Bio-teek Company Korea 4490205 Korea

The experiment was conducted using a total of 1392 one-day-old, Cobb commercial male broilers to investigate the effects of a commercial probiotic addition in diet on growth, the development of the small intestine and microbial populations of broilers. Broilers were randomly allotted by BW to 1 of 6 replicate cages （29 chicks per cage） for each of 8 treatments in a randomized block design involving one factorial arrangement of treatments. Dietary treatments included the basal diet （including corn, soybean, rapeseed, cottonseed meal） added with 100 mg/kg antibiotic, 0%, 0.05%, 0.1%, 0.15%, 0.2%, 0.25% or 0.3%. The experiment last 42 d and divided into the starter period （1-21 d） and the finisher period （22-42 d）. The results showed that there were significant differences in broiler body weight （BW）（P〈0.001）, average daily feed intake （ADFI）（P=0.033）, relative length of the duodenum （P〈0.001）, jejunum （P=0.008）, ileum （P〈0.001） and the populations of lactobacillus （P〈0.001） and coliform （P〈0.001） in the rectum between the probiotics treatments and the control treatment only in the starter period of the trails. No significant differences were observed in intestinal morphology parameters in two periods of the experiment. Our results indicated that the probiotic was able to improve the performance of broiler chickens, and it was better in the starter period to be used than in the finisher period.

关键词： probiotic broiler chickens performance intestine development microbial population

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白菜EST-SSR信息分析与标记的建立

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园艺学报 2006年第3期33卷 549-554页

作者：忻雅崔海瑞卢美贞姚艳玲金基强林容杓崔水莲浙江大学农业与生物技术学院原子核农业科学研究所忠南大学园艺系

数量迅速增加的EST为开发新的SSR标记提供了宝贵的资源。本研究对4584条白菜EST进行了搜索,共检索出474个SSR,检出率为10·3%,包括40种重复基元。其中二核苷酸和三核苷酸重复单元的EST-SSR占主导地位,二者出现的频率基本相近,占总SSR的... 详细信息

数量迅速增加的EST为开发新的SSR标记提供了宝贵的资源。本研究对4584条白菜EST进行了搜索,共检索出474个SSR,检出率为10·3%,包括40种重复基元。其中二核苷酸和三核苷酸重复单元的EST-SSR占主导地位,二者出现的频率基本相近,占总SSR的近83%;其它重复类型所占比例均不足5%。gA和gAA是二、三核苷酸中的优势重复类型,分别占二、三核苷酸重复类型的71·5%和37·5%。设计了15对EST-SSR引物,在合适的PCR反应体系下,以构建EST的白菜自交系A的DNA为模板,对设计的EST-SSR引物进行筛选,发现15对EST-SSR引物都能扩增出产物。进一步用这些可扩增的引物对28个白菜品种进行PCR扩增,发现7对引物显示多态性,占引物总数的46·7%。此结果表明,根据EST建立EST-SSR标记是一条简便而又有效的途径。

关键词：白菜 EST SSR信息标记

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白菜EST-SSR标记的通用性

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细胞生物学杂志 2006年第2期28卷 248-252页

作者：忻雅崔海瑞张明龙姚艳玲卢美贞金基强林容杓崔水莲浙江大学原子核农业科学研究所杭州市农业科学研究院生物所杭州310024 忠南大学园艺系

EST-SSR是从表达序列标签(expressedsequencetag,EST)中开发的新型简单序列重复(simplesequencerepeat,SSR)标记。根据白菜EST设计了15对SSR引物,对白菜、油菜、玉米、高粱、水稻和茶树等进行了PCR,研究了白菜的EST-SSR标记在不同物种... 详细信息

EST-SSR是从表达序列标签(expressedsequencetag,EST)中开发的新型简单序列重复(simplesequencerepeat,SSR)标记。根据白菜EST设计了15对SSR引物,对白菜、油菜、玉米、高粱、水稻和茶树等进行了PCR,研究了白菜的EST-SSR标记在不同物种间的通用性。所设计的引物对不同白菜品种、近缘种油菜和远缘种玉米、高粱、水稻和茶树的扩增成功率分别为100%、93.3%、80%、93.3%、93.3%和86.7%。在15对引物中,有11对在远缘种中都有扩增产物,而且一些引物可显示多态性,多态性引物分别占了可扩增引物的33.3%、28.6%、28.6%和61.5%。这些结果表明,白菜EST-SSR引物具有较高的通用性,这对于比较基因组学研究有重要意义。

关键词： SSR标记通用性白菜 SSR引物表达序列标签简单序列重复比较基因组学扩增产物多态性 EST

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美国退伍军人事务部/国防部成人脑卒中康复治疗管理临床实践指南(执行简写版)

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中国康复理论与实践 2006年第1期12卷 2-4页

作者： Barbara Bates John Y. choi Pamela W. Duncan Jonathan J. glasberg glenn D. graham Richard C. Katz Kerri Lamberty Dean Reker Richard Zorowitz 杨雅琴（译）王拥军（译）不详首都医科大学附属北京天坛医院神经内科北京市100050

背景专家委员会制定的卒中康复指南应用于退伍军人健康管理部门及国防部卫生保健系统。方法根据以前发表的指南,委员会利用美国预防服务特别工作组制定的标准,评价了截至到2002年发表的文献。指南根据临床随机化实验、非对照性研究等证... 详细信息

背景专家委员会制定的卒中康复指南应用于退伍军人健康管理部门及国防部卫生保健系统。方法根据以前发表的指南,委员会利用美国预防服务特别工作组制定的标准,评价了截至到2002年发表的文献。指南根据临床随机化实验、非对照性研究等证据提出建议(如缺乏确定的数据则根据专家组的建议)。结果Ⅰ级水平的建议包括:在多学科康复环境中或卒中单元中传递卒中治疗,通过NI HSS对卒中患者进行评价,早期启动康复治疗,对吞咽困难患者进行吞咽功能筛查,积极进行二级预防,预防深静脉血栓等。推荐应用标准化的评价工具制定适合每个患者的全面的治疗计划。强烈建议进行抗抑郁及情感波动方面的治疗。语言治疗师应评价患者的交流及认知障碍,并在需要时提供治疗。患者、家属及护理者是康复小组的重要成员,应当介入康复的全部疗程。这些建议在以下网站可查询:http://***/cgi/content/full/36/9/e100。并附有每项建议的全文证据表。结论这些建议应平等地应用于所有临床环境中的所有卒中康复患者,而不是仅针对联邦医疗系统的临床问题或资源。

关键词： AHA/ASA发表的实践指南卒中康复生活质量

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