The role of Itch-mediated PPARγ ubiquitination in adipocyte differentiation

脂质过氧化物酶体增殖物激活受体γ（PPARγ）属于Ⅱ型核受体超家族成员，在脂肪及小肠组织中高表达。作为重要的核转录因子，PPARγ与视黄醇类X受体α(retinoidXreceptorα)形成异二聚体，随后结合在过氧化物酶体增殖物反应元件(PPRE)上，从而调控与脂肪分化、脂质代谢、炎症应答相关的靶基因表达，其功能的异常与糖尿病、肥胖等代谢疾病密切相关。临床上，PPARγ也被作为重要的药物靶点用于相关疾病的治疗。 PPARγ的翻译后修饰对其生物学功能有重要影响。我们发现C2-WW-HECTE3泛素连接酶家族成员Itch可以和PPARγ相互结合并对其进行非典型泛素化修饰。这种非典型的泛素化修饰...The peroxisome proliferator-activated receptor gamma (PPARγ) belongs to typeⅡnuclear receptor superfamily, which is highly expressed in adipose tissue and intestine. As a crucial transcriptional factor, PPARγ forms a heterodimer with retinoid X receptor α and subsequently binds to PPAR-responsive regulatory elements to regulate its target genes which involved in adipogenesis, lipid metabolism, inf...学位：理学硕士院系专业：生命科学学院_细胞生物学学号：2162013115253

Clone、construction and expression of Synechocystis sp.PCC 6803 Acetyl- CoA carboxylase gene for fat production

在化石燃料日益枯竭、环境污染逐渐威胁人类生存的今天，生物柴油在提供可再生能源的同时还可以减少温室气体，从而受到世界各国的广泛重视。蓝藻为光合自养微生物，是大气碳循环主要贡献者，其生物柴油产量是油料作物的8～24倍。乙酰辅酶A羧化酶(acetyl-coenzymeAcarboxylase，ACCase)是生物体内脂肪生物合成的关键酶，研究发现，过量表达ACCase能够促进生物体脂肪的合成。相对于蓝藻，大肠杆菌具有遗传背景清楚、生长速度快等特点，利用基因工程构建的大肠杆菌表达系统是目前最常用的外源基因表达系统，在转基因生产中占据着主导地位。 本文以集胞藻Synechocystissp.PCC68...With the increasingly severe problems of energy crisis and environmental pollution, biodiesel has been attracting more and more attention worldwide by providing renewable energy and reducing greenhouse emissions. As photoautotrophic microorganisms, Cyanobacteria are major contributors to atmospheric carbon cycle, the biodiesel productivity of which is 8 to 24 times of that observed in oilseeds. Ac...学位：理学博士院系专业：生命科学学院_微生物学学号：2162006015330

Effects of <i>ELOVL4</i> gene overexpress on the synthesis efficiency of n3 and n6 very long chain polyunsaturated fatty acids

AIM:To compare the synthesis efficiency of n3 and n6 very long chain polyunsaturated fatty acid(VLC-PUFA)by overexpressing ELOVL4 protein, providing guidance for treating Stargardt-like macular dystrophy(STGD3).<p>METHODS:To establish recombinant adenovirus with the ELOVL4 protein and green fluorescent protein, transferred into cultured PC12 cells. The cells were divided into 3 groups: PC12, PC12+Ad-<i>GFP</i> and PC12+Ad- <i>ELOVL4</i>, former two groups serve as controls. <i>ELOVL4</i> gene expression was quantified by qRT-PCRs. ELOVL4 protein was analyzed by Western-Blot(WB). The transduced cells were treated with both EPA and AA(1:1). After 48h of incubation, cells were collected, total lipids extracted and fatty acid methyl esters prepared and analyzed by gas chromatography-mass spectrometry(GC-MS). <p>RESULTS: When supplemented together, 20:5n3(EPA)and 20:4n6(AA)were efficiently taken up at almost the same amounts in the PC12 cells regardless of ELOVL4 expression. The ELOVL4-expressing cells elongated both EPA and AA to a series of n3 and n6 VLC-PUFAs. From 20:5n3/EPA, 34:5n3 and 36:5n3 account for 0.71% and 1.6%, respectively. From 20:4n6/DHA, 34:4n6 and 36:4n6 were only 0.46% and 0.61%, respectively. The total relative mol% of n3 VLC-PUFAs synthesized from EPA was almost two times that of n6 VLC-PUFAs synthesized from AA.<p>CONCLUSION: <i>ELOVL4</i> protein preferentially elongates n3 PUFA to VLC-PUFAs over n6 PUFA. Dietary supplementation of appropriate n3/n6 PUFAs may provide STGD3 patients with some therapeutic benefits

3种饲料添加剂对吉富罗非鱼幼鱼生长性能、消化酶活性和肝、肠组织结构的影响

为探讨中草药提取物、胆汁酸、微生态制剂对吉富罗非鱼(Oreochromis niloticus)生长性能、消化酶活性和肝、肠组织结构的影响,以基础饲料为对照,分别在每千克基础饲料中添加中草药提取物(1、2 g)、胆汁酸(0.1、0.2 g)、微生态制剂(1、2 g)配制成6种试验饲料,选取平均体质量为(32.75±5.75)g的吉富罗非鱼幼鱼483尾,随机分为7处理,每处理3平行,每平行23尾,共进行养殖实验45 d。结果显示:与对照组相比,低剂量使用此3种添加剂均有改善实验鱼生长和饲料利用的趋势。饲料中添加胆汁酸显著提高了吉富罗非鱼的增重率和特定增长率;饲料中添加微生态制剂组的吉富罗非鱼的肥满度最大,但各处理组之间差异不显著;中草药组的增重率与特定生长率与对照组之间无差异。饲料中添加微生态制剂和0.1 g/kg胆汁酸的实验鱼肠道脂肪酶活性显著高于中草药提取物2 g/kg的处理组;各组间的肠道淀粉酶、蛋白酶活性差异不显著。与对照组相比,各处理组实验鱼的前肠绒毛个数和肌肉层厚度有增加的趋势;添加1 g/kg微生态制剂的实验鱼中肠绒毛长度显著高于中草药组。结果表明:饲料中添加1 g/kg中草药提取物,0.2 g/kg胆汁酸,1 g/kg微生态制剂可在一定程度上提高吉富罗非鱼幼鱼的生长性能。大北农水产科技集团企业自立项目(DBN-A-E20160001

The nuclear receptor Nur77 could improve the lipid accumulation in Non-Alcoholic Fatty Liver Disease (NAFLD) in cooperation with SREBP-1c

非酒精性脂肪肝是一直困扰我国和全世界人口的慢性疾病，发病率在20%左右，也就是说每5个中国人，就有一个是非酒精性脂肪肝的携带者。而FDA推荐的《非酒精性脂肪肝病诊疗指南》中，并没有明确有效的预防和治疗非酒精性脂肪肝的药物。所以，明确肝脏细胞脂质代谢的调控机制，筛选出可以改善脂质堆积的药物是迫在眉睫的。本课题通过80份病例的分析，试图寻找到能够调控脂质代谢中关键的转录因子SREBP-1c的蛋白。我们使用组织免疫的方法来检测患者肝脏穿刺样品中的Nur77表达量。结果发现，随着病情的加重Nur77表达量逐步降低，而SREBP-1c的含量则有显著地上调。随后，我们又建立了非酒精性脂肪肝的细胞体外和小鼠...Nonalcoholic fatty liver is a chronic disease that has plagued our country and the world's population. The incidence rate is about 20%, which means there is one non-alcoholic fatty liver carrier every five Chinese people. Even though in FDA recommended "non-alcoholic fatty liver disease diagnosis and treatment guidelines", there is no clear and effective prevention and treatment of non-alcoholic f...学位：理学硕士院系专业：药学院_化学生物学学号：3232014115339

Clinical Observation on Zaoshu Yinchen Prescription in the Treatment of Nonalcoholic Steatohepatitis

目的探究皂术茵陈方治疗非酒精性脂肪性肝炎的临床效果。方法选择我院2015年5月—2016年2月非酒精性脂肪性肝炎患者132例,随机分组。西医治疗组采用多烯磷脂酰胆碱治疗;皂术茵陈组在西医治疗组基础上给予皂术茵陈方治疗。比较两组患者非酒精性脂肪性肝炎治疗效果;治疗前后丙氨酸氨基转移酶、门冬氨酸氨基转移酶、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇;不良反应发生率。结果皂术茵陈组患者非酒精性脂肪性肝炎治疗效果比西医治疗组高,P〈0.05;皂术茵陈组治疗前后丙氨酸氨基转移酶、门冬氨酸氨基转移酶、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇比西医治疗组好,P〈0.05;两组患者均未出现严重不良反应。结论皂术茵陈方治疗非酒精性脂肪性肝炎的临床效果确切,可有效改善患者病情和肝功能、血脂指标,无明显不良作用,值得推广。Objective To investigate the clinical effect of Zaoshu Yinchen prescription in the treatment of nonalcoholic steatohepatitis. Methods 132 cases of patients with nonalcoholic steatohep＇atitis in our hospital from May 2015 to February 2016 were randomly divided into two groups. The Western medicine treatment group was treated with polyene phosphatidyl choline. The Zaoshu Yinchen group was treated with Zaoshu Yinchen prescription on the basis of Western medicine treatment group. The therapeutic effect, alanine aminotransferase, aspartate aminotransferase, low density lipoprotein cholesterol, high density lipoprotein cholesterol before and after treatment and the incidence of adverse reaction was compared, respectively. Results The therapeutic effect of Zaoshu Yinchen group was higher than that of Western medicine group P 〈 0.05. After treatment, alanine aminotransferase, aspartate aminotransferase, low density lipoprotein cholesterol, high density lipoprotein cholesterol of Zaoshn Yinchen group better than that of Western medicine group P 〈 0.05. There were no serious adverse reactions between two groups. Conclusion The Zaoshu Yinehen prescription in the treatment of nonalcoholic steatohepatitis has exactly clinical effect, can effectively improve the patient＇ s condition and liver function, blood fat index, has no obvious side effects, and is worthy of promotion