BEn Goldacre：医生开药的盲点所在
当一种新型药物被测试的时候，试验结果应该对其余医药界开放 — 但很多时候， 负面或者无效的结论未被上报，导致医生和研究人员对此一无所知。在这激情洋溢的演讲中，BEn Goldacre讲述了为什么这些未上报的负面的案例会误导大众，并有潜在的危险。
Interplays BEtween Mesenchymal Stem Cells and Immune Responses
Mesenchymal stem cells (MSCs) exist in almost all tissues and are crucial in maintaining the cellular homeostasis of multicellular organisms. They provide the ultimate cell source for tissue repair and regeneration. Under pathological conditions, these cells are awakened, activated, and mobilized to damaged tissue sites. Since tissue damages are often accompanied by inflammatory factors, from both innate immune response and adaptive immune response, it is sensible that MSCs delicately interact with inflammatory factors at the sites of tissue damages.
Depending on the type and persistence of the inflammatory factors, the activated MSCs could lead either to complete or partial tissue repair, or to chronic inflammation and further tissue damage, such as cancer and fibrosis. Indeed, recent studies have shown that there is a bidirectional interaction BEtween MSCs and inflammatory cells and cytokines. However, much information of this information remains to BE elucidated. Further investigations in this newly emerging exciting research area will undoubtedly lead to BEtter understanding of pathogenesis of various diseases and novel treatment strategies.
Discovery: Innovations with Ed BEgley Jr
美国著名的《Discovery》频道创新系列节目《Innovations with Ed BEgley Jr》全球播出了艾森生物最新研发的新一代实时心肌功能评价系统（xCELLigence RTCA CardioECR）。
本期节目主要关注在医疗健康领域的突破性进展。节目用七分多钟时间报道了艾森生物实时心肌细胞检测这项突破性的技术发明，并通过目前用药安全方面的问题调研及业内知名专家的采访，阐明了该发明在药物早期心脏毒性评价、用药安全、高通量新药筛选、心脏基础研究方面的价值和意义。
Sigma® Life Science——Where bio BEgins
生命是一个不断扩大、不断进化的宇宙，充满着发现问题和探索未知的机会。每天，突破性的想法重新调整我们的认识，不断打破我们对生物学的认知边界。Sigma® Life Science正在改变世人关于生物学的思维方式，让研究者以独特的视角去探索科学，鼓舞他们去不懈挑战，这里是生物学开始的地方。
Karen Dell: iBiology:Meet the world's BEst biologists through the Internet
Karen Dell来自美国细胞生物学学会，她将简述通过iBiology来获取生物学学习和交流的资源。
李于：SIRT1 Regulation of Energy Metabolism: Attenuation of Hepatic Steatosis and OBEsity
Fibroblast growth factor 21 (FGF21) is the hepatocyte-derived hormone that regulates fatty acid metabolism and has potential to treat oBEsity and diaBEtes. We recently indicate that hepatic overexpression of SIRT1 in diaBEtic mice attenuates hepatic steatosis and insulin resistance. However, the in vivo long-term consequence of hepatic SIRT1 ablation in liver physiology remains unknown.
We showed that hepatocyte-specific SIRT1 knockout (SIRT1 LKO) mice with the albumin Cre-loxP system exhibited a striking phenotype with greater propensity for oBEsity on a chow diet, characterized by increased whole body mass and fat mass, reduced energy expenditure, and unaltered food intake and physical activity. The oBEse phenotypes of SIRT1 LKO mice were associated with reduced hepatic and circulating levels of fasting FGF21.
Hepatic impairment of FGF21 repressed expression of key enzymes involving fatty acid oxidation such as CPT1α and MCAD, and inhibited expression of ketogenic enzymes including ACAT1, HMGCS2, HMGCL, and BDH1, thereby reducing plasma β–hydroxybutyrate levels in SIRT1 LKO mice. Moreover, transcriptional activity of a FGF21 promoter-driven luciferase reporter was stimulated by SIRT1 activators, resveratrol and SRT1720, in SIRT1+/+ MEFs, but not in SIRT1-/- MEFs.
The ability of resveratrol and SRT1720 to stimulate FGF21 protein was abolished by SIRT1 H335A inactive mutant or by nicotinamide and splitomicin in HepG2 cells. Induction of FGF21 by SIRT1 activators enhanced expression of key enzymes for fatty acid oxidation and ketogenesis.
These in vivo and in vitro findings characterize 1) hepatic SIRT1 as a master regulator of FGF21; 2) SIRT1-dependent activation of FGF21 in liver as a component for adaptive fasting response; and 3) defective hepatic SIRT1 and FGF21 signaling as a key pathological determinant of energy metabolic abnormality and oBEsity susceptibility.
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).
从外周血中提取DraBEk基因组DNA
DraBEk genomic DNA extractions from peripheral blood. Employing a novel DNA extraction procedure adapted from DraBEk [Biomed. Papers 146(2), 37–39 (2002)] and Nasiri [Journal of Clinical Laboratory Analysis 19:229–232 (2005)]for human peripheral blood samples.
细胞粘附、信号和癌症 - Mary BEckerle P1
本视频由科普中国和生物医学大讲堂出品
Mary BEckerle (University of Utah) Part 1: Adhesion, Signaling and Cancer
Cell-substratum adhesion is mediated by integrins, a family of transmembrane, heterodimeric, extracellular matrix receptors that are concentrated at focal adhesions. Integin engagement influences a variety of signaling pathways and regulates cell BEhaviors including motility, proliferation, and survival. Disturbance of normal integrin function is associated with a variety of pathologic conditions including cancer. In the first segment of my seminar, I provide a broad overview of the cancer problem for a lay audience. Advances in our understanding of cancer as a genetic disease are discussed. The influence of cell adhesion on control of cell growth is reviewed. See more at http://www.ibiology.org
粘着蛋白的发现和表征 - Mary BEckerle P2
本视频由科普中国和生物医学大讲堂出品
Mary BEckerle (University of Utah) Part 2: Discovery and Characterization
In the second segment, I descriBE the identification of the focal adhesion protein, zyxin, by my lab. Recent work revealed that zyxin is down-regulated upon expression of the Ewing sarcoma oncoprotein, EWS-FLI. Loss of zyxin expression results in enhanced cell motility and is also associated with failed apoptotic signaling. Evidence that zyxin shuttles BEtween focal adhesions and the nucleus is presented. The impact of reduced zyxin expression on tumor progression is discussed. See more at http://www.ibiology.org