Bmp4在白色脂肪向棕色脂肪转化中的作用与机制研究
白色脂肪组织内棕色脂肪功能的激活有利于减轻体重和改善代谢。骨形成蛋白4 （Bone Morphologenetic protein 4， Bmp4）可以促使多潜能干细胞向前脂肪细胞定向。在本研究中，我们发现人体白色脂肪组织内Bmp4的mRNA水平与体重指数（BMI）呈负相关，提示脂肪组织内高表达水平的Bmp4有利于控制体重。我们利用转基因小鼠模型在脂肪组织内特异性过表达Bmp4后发现，Bmp4促使小鼠白色脂肪细胞脂滴和细胞大小显著减小。进一步实验证实白色脂肪细胞内线粒体生成增加，脂肪酸氧化基因表达增加，从而导致小鼠整体基础氧耗增加，血脂降低和胰岛素敏感性增加等一系列代谢变化。另外，体外前脂肪细胞3T3-L1分化过程中加入Bmp4处理也可使细胞获得类棕色的表型。干扰Bmp4转基因小鼠白色脂肪内PGC1α的表达可以逆转Bmp4所引起的白色脂肪棕色化的表型，说明Bmp4所引起的脂肪组织发育的变化时通过PGC1α这一关键基因起作用，Bmp4激活的P38/MAPK/ATF2/PGC1α信号通路发挥主要功能。与此一致的是，脂肪组织特异性敲除Bmp4的小鼠出现脂肪组织体积增加，血脂水平增高，胰岛素敏感性降低等一系列变化，从反方面证实了Bmp4对于诱导白色脂肪棕色化和改变代谢的作用。Bmp4这种新功能的阐明Bmp4可能为临床干预肥胖和改善胰岛素敏感性提供新思路。
Bmp4在白色脂肪向棕色脂肪转化中的作用与机制研究
白色脂肪组织内棕色脂肪功能的激活有利于减轻体重和改善代谢。骨形成蛋白4 （Bone Morphologenetic protein 4， Bmp4）可以促使多潜能干细胞向前脂肪细胞定向。在本研究中，我们发现人体白色脂肪组织内Bmp4的mRNA水平与体重指数（BMI）呈负相关，提示脂肪组织内高表达水平的Bmp4有利于控制体重。我们利用转基因小鼠模型在脂肪组织内特异性过表达Bmp4后发现，Bmp4促使小鼠白色脂肪细胞脂滴和细胞大小显著减小。进一步实验证实白色脂肪细胞内线粒体生成增加，脂肪酸氧化基因表达增加，从而导致小鼠整体基础氧耗增加，血脂降低和胰岛素敏感性增加等一系列代谢变化。另外，体外前脂肪细胞3T3-L1分化过程中加入Bmp4处理也可使细胞获得类棕色的表型。干扰Bmp4转基因小鼠白色脂肪内PGC1α的表达可以逆转Bmp4所引起的白色脂肪棕色化的表型，说明Bmp4所引起的脂肪组织发育的变化时通过PGC1α这一关键基因起作用，Bmp4激活的P38/MAPK/ATF2/PGC1α信号通路发挥主要功能。与此一致的是，脂肪组织特异性敲除Bmp4的小鼠出现脂肪组织体积增加，血脂水平增高，胰岛素敏感性降低等一系列变化，从反方面证实了Bmp4对于诱导白色脂肪棕色化和改变代谢的作用。Bmp4这种新功能的阐明Bmp4可能为临床干预肥胖和改善胰岛素敏感性提供新思路。
Novel signaling by the IKK complex
Signal transduction plays a pivot role in regulating cell functions, from proliferation, differentiation, programmed cell death, and transformation. Deregulation of signal transduction could lead to various human diseases even cancer. Extracellular signals are transmitted into cells via an intracellular signaling network that is composed of multiple signaling pathways, dictating cellular functions, such as growth, differentiation, programmed death (apoptosis) and transformation.
Although we have learnt a great deal about the architecture of the intracellular signaling network, our understanding of its biology is limited. The work in my laboratory focuses on elucidating molecular mechanisms underlying plasticity and specificity of intracellular signaling network using c- Jun N-terminal protein kinase (JNK) and IkB kinase (IKK)/NF-kappaB as molecular probes and understanding the impact of deregulating the intracellular signaling network on human diseases
Simultaneous quantification of 47 gene expression in FFPE samples by a novel PCR-free approach
基因表达(gene expression)是指细胞在生命过程中，把储存在DNA顺序中遗传信息经过转录和翻译，转变成具有生物活性的蛋白质分子。生物体内的各种功能蛋白质和酶都是同相应的结构基因编码的。差别基因表达(differential gene expression)指细胞分化过程中，奢侈基因按一定顺序表达，表达的基因数约占基因总数的5%～10%。
Erich Gnaiger：Life Style and Mitochondrial Competence – Modern Drugs for T2 Diabetes in Aging and Degenerative Diseases.
D. Swarovski Research Laboratory (Mitochondrial Physiology), Dept. General, Visceral and Transplant Surgery, Innsbruck Medical University; and OROBOROS INSTRUMENTS, Innsbruck, Austria. - Email: erich.gnaiger@oroboros.at
The contribution of mitochondrial dysfunction to the etiology of T2 diabetes and a range of preventable metabolic diseases is the subject of intensive current research with world-wide health implications.
Recently these investigations gained depth and scope by technological advances for diagnosis of mitochondrial function by comprehensive OXPHOS analysis using high-resolution respirometry [1,2]. Fundamental questions of a causal relationship, however, between compromised mitochondrial function and development of T2 diabetes remain to be resolved [3,4] to optimize prevention and treatment of insulin resistance.
For preventable diseases such as T2 diabetes, the evolutionary background of mitochondrial competence provides a solid basis for improved and broad application of a well established modern drug, mtLSD.
Post-industrial societies are characterized by a high-energy input lifestyle with diminished physical activity and high incidence of non-transmittable diseases, in comparison to human populations where physical work is essentially important for sustaining life and in which degenerative diseases (T2 diabetes, various cancers, Alzheimer's) are essentially absent [5]. The capacity of oxidative phosphorylation (OXPHOS) is increased or maintained high by a life style involving endurance exercise and strength training [6].
Life style changes from the age of 20-30 years to the elderly, but is subject to change and intervention. Depending on group selection in cross-sectional studies, OXPHOS capacity declines from the age of 20-30 years [7,8], or is independent of age up to 80 years [9,10].
Independent of age, there is a strong decline of OXPHOS capacity in human vastus lateralis from BMI of 20 to 30 [1]. At a BMI >30, a threshold OXPHOS capacity is reached in human v. lateralis that may be characteristic of a low-grade inflammatory state (‘mitochondrial fever’).
Onset of degenerative diseases (T2 diabetes, neuromuscular degeneration, various cancers) and mitochondrial dysfunction interact in an amplification loop progressing slowly with age, such that cause and effect of mitochondrial dysfunction cannot be distinguished. Diminished antioxidant capacity at low mitochondrial density is an important mechanistic candidate in the state of mitochondrial fever.
For implementing a life style supporting mitochondrial competence and preventing degenerative diseases in modern societies, we need (1) extended research programmes focused on the causative link between mitochondrial competence and effective prevention of degenerative diseases, (2) educational programmes on mitochondrial physiology targeted at general practitioners, teachers and the society at large, (3) cooperation of health care and insurance organizations to support preventive life style activities, and (4) do not miss any opportunity in taking the lead in living the mtLife Style Drug (mtLSD).
Generating B-lymphoblastoid cell lines using Epstein Barr virus transformation.
Generating immortalized B-lymphoblastoid cell lines via Epstein Barr virus transformation using the B95-8 EBV-infected and producing marmoset cell line.
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基因型快速微生物鉴定系统MicroSEQ-Gmp生产的好伙伴
1. 微生物鉴定发展趋势 2. 快速微生物鉴定系统MicroSEQ产品介绍和应用 3. 快速微生物鉴定系统MicroSEQ工作流程和结果分析
“抗体药物研发进展与临床应用研究” 空中讲坛 .mp4
抗体药是药物发展历史上的里程碑，颠覆了传统药物发展的格局，FDA批准第一个治疗性抗体药物也已有三十余年。随着抗体药物研发进程的不断推动，抗体药物的适应症也逐渐扩大，从癌症、自身免疫病快速拓展到眼科疾病、高血脂、骨质疏松、哮喘、多发性硬化症等多个疾病领域，同时在抗病毒和细菌感染，心脑血管，糖尿病以及罕见病治疗等领域也发挥越来越重要的作用。 抗体药物的广泛应用正推动着抗体药物企业迅猛发展，药物研发也面临着表达量和稳定性的挑战。针对这些挑战，越来越多的企业在早期研究与验证中选择使用噬菌体/酵母展示文库筛选多样性抗体，KingFisher Apex高通量自动磁珠纯化系统在这个过程中具有重要作用。未来抗体药物在抗肿瘤领域和自身免疫类领域的治疗中将发挥巨大作用，抗体药物的无限潜力也将逐步被发掘。 MedSci梅斯&生物谷携手ThermoFisher 赛默飞世尔科技（中国）有限公司，邀请相关行业专家为大家分享抗体药物研发与应用进展和相关最新科研成果！