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[No] Need for Speed: Late-onset Diseases as Evolution's Power Brakes [否]需要速度:迟发性疾病作为进化的动力刹车
Pub Date : 2018-04-02 DOI: 10.4172/2168-9296.1000194
R. Petkova, S. Chakarov
Degenerative disease and cancer are the top causes of death in middle and advanced age and it seems that this trend will continue, at least in the near future. Modern medicine has an impressive arsenal of methods and tools to detect monitor and control a wide variety of diseases and conditions, including diseases with onset in middle and advanced age. Nevertheless, they are very rarely completely cured. Why, despite all the efforts of research and healthcare, we still keep failing in our efforts to cure late-onset diseases? It might be that we are trying to fight against laws of Nature that were purposely put in place so that evolution may go on but could not advance before its time. Relatively recently, we proposed the hypothesis that 'death of old age' and cancer may be viewed as Nature-made mechanisms or larger-scale checkpoints that keep the rate of evolution in check and preserve the population and the species at the expense of individuals. At this point in our development, we cannot change the rules of Nature. It is within our power, however, to anticipate, prevent and modify the outcomes of late-onset disease. Thus, we ought to keep on with research and development aimed at management of late-onset disease and improving the quality of life for the patients.
退行性疾病和癌症是导致中老年死亡的主要原因,而且这一趋势似乎还将继续,至少在不久的将来是这样。现代医学拥有令人印象深刻的方法和工具库,可以检测、监测和控制各种各样的疾病和状况,包括中老年发病的疾病。然而,他们很少被完全治愈。为什么,尽管所有的研究和医疗努力,我们仍然无法治愈晚发性疾病?这可能是因为我们正在试图与自然法则作斗争,这些自然法则是故意设置的,以便进化可以继续进行,但不能提前进行。最近,我们提出了一个假设,即“老年死亡”和癌症可能被视为自然创造的机制或更大规模的检查点,它们控制着进化的速度,以牺牲个体为代价保护种群和物种。在我们发展的这个阶段,我们不能改变自然规律。然而,我们有能力预测、预防和改变迟发性疾病的后果。因此,我们应该继续研究和开发,旨在管理晚发性疾病,提高患者的生活质量。
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引用次数: 0
Cardiac Repair and Regeneration 心脏修复与再生
Pub Date : 2018-01-22 DOI: 10.4172/2168-9296.1000193
D. Lunn, Vanessa Wazny, S. Cutie, Guo N. Huang
The regenerative capacity of the heart varies drastically across the animal kingdom. Certain species, such as zebrafish and newts, display a remarkable innate ability for heart regeneration. In contrast, heart regeneration in adult mammals is limited. Heart regenerative potential also varies during organismal development. For example, while neonatal mice can regenerate their hearts, this is lost during the first week after birth. Understanding cardiac regenerative pathways will play a critical role in discovering therapeutic approaches to stimulate human cardiac regeneration. In this review, we explore the known strategies to stimulate intrinsic heart regeneration and highlight current cell replacement therapies.
在动物王国中,心脏的再生能力差别很大。某些物种,如斑马鱼和蝾螈,表现出非凡的天生心脏再生能力。相比之下,成年哺乳动物的心脏再生是有限的。心脏再生潜能在机体发育过程中也会发生变化。例如,虽然新生小鼠可以再生心脏,但这在出生后的第一周就会丧失。了解心脏再生途径将在发现刺激人类心脏再生的治疗方法中发挥关键作用。在这篇综述中,我们探讨了刺激心脏再生的已知策略,并强调了当前的细胞替代疗法。
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引用次数: 8
Mystery of the Genetic Code 遗传密码之谜
Pub Date : 2018-01-15 DOI: 10.4172/2168-9296.1000192
M. Inouye
There are a total of 64 genetic codons assigned to the 20 amino acids and termination codons. The fact that all living organisms share the same codon assignment for individual amino acids indicates that all living organisms on the earth originated from the same organism. Mysteriously, however, the number of codons for individual amino acids does not necessarily correlate to amino acid usages in currently living organisms. In this article, I will discuss this mystery of the genetic code.
共有64个遗传密码子分配到20个氨基酸和终止密码子。所有的生物体都有相同的氨基酸密码子,这一事实表明地球上所有的生物体都起源于同一个生物体。然而,神秘的是,单个氨基酸的密码子数量并不一定与当前生物体中氨基酸的使用相关。在这篇文章中,我将讨论遗传密码的奥秘。
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引用次数: 0
Neurocristopathies: How New Discoveries in Neural Crest Research Changed our Understanding 神经嵴病变:神经嵴研究的新发现如何改变了我们的认识
Pub Date : 2018-01-01 DOI: 10.4172/2168-9296.1000195
Guillermo A Vega-López, Manuel J. Aybar
Guillermo A Vega-Lopez1* and Manuel J Aybar1,2 1Institute of Biology "Dr. Francisco D. Barbieri", National University of Tucumán, Tucumán, Argentina 2Higher Institute of Biological Research (INSIBIO, CONICET-UNT), Tucumán, Argentina *Corresponding author: Guillermo A Vega-Lopez, Faculty of Biochemistry, Chemistry and Pharmacy, Institute of Biology "Dr. Francisco D. Barbieri", National University of Tucumán, Tucumán, Argentina, Tel: 03814107214; E-mail: gvegalopez@fbqf.unt.edu.ar
Guillermo A Vega-Lopez1*和Manuel J Aybar1,2阿根廷国立大学Tucumán, Tucumán生物研究所“Francisco D. Barbieri博士”2阿根廷高等生物研究所(INSIBIO, CONICET-UNT), Tucumán *通讯作者:阿根廷国立大学Tucumán, Tucumán生物研究所“Francisco D. Barbieri博士”Guillermo A Vega-Lopez,生物化学、化学和药学院,电话:03814107214;电子邮件:gvegalopez@fbqf.unt.edu.ar
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引用次数: 0
Identification with SILAC Proteomics of Novel Short Linear Motifs in Demethylase Enzymes Regulated During Myoblast Differentiation 用SILAC蛋白质组学鉴定成肌细胞分化过程中调节的去甲基酶的新型短线性基序
Pub Date : 2018-01-01 DOI: 10.4172/2168-9296.1000198
Dimitra Tsakona, Panagiota A. Galliou, N. Papanikolaou
Methylation and demethylation of Lysine and Arginine on proteins is quantitatively an extensive and functionally a significant post-translational modification yet there is a dearth of information at a functional systems level. Using SILAC proteomics and high resolution mass spectrometry we have identified eight demethylase and two methylase proteins whose levels are regulated during myogenic differentiation in a mouse myoblast-to-myocyte model. Using the general methylation inhibitor adenosine dialdehyde (AdOX) we established that methylation is required for differentiation. Whole proteome analysis revealed that 1134 out of 4600 proteins identified were differentially expressed, of which 488 were up-regulated and 646 down-regulated. Of these, two were methylases and eight were demethylases. Notably, five of the eight enzymes demethylate Lysine 9 on histone 3 (H3K9) whereas two also demethylate H3K4. Lastly, we have identified short linear motifs (SliMs) in the demethylase enzymes that are enriched in differentiation. We briefly discuss the significance of our findings within a developmental/epigenomics framework.
赖氨酸和精氨酸在蛋白质上的甲基化和去甲基化在数量上是广泛的,在功能上是重要的翻译后修饰,但在功能系统水平上缺乏信息。利用SILAC蛋白质组学和高分辨率质谱法,我们鉴定了8种去甲基化酶和2种甲基化酶蛋白,它们的水平在小鼠成肌细胞到肌细胞模型的成肌分化过程中受到调节。使用一般甲基化抑制剂腺苷二醛(AdOX),我们确定甲基化是分化所必需的。全蛋白质组分析显示,在鉴定的4600个蛋白中,有1134个蛋白存在差异表达,其中上调488个,下调646个。其中两种是甲基化酶,八种是去甲基化酶。值得注意的是,八种酶中有五种能使组蛋白3 (H3K9)上的赖氨酸9去甲基化,而两种酶也能使H3K4去甲基化。最后,我们在分化过程中富集的去甲基酶中发现了短线性基序(SliMs)。我们简要地讨论了在发育/表观基因组学框架内我们的发现的意义。
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引用次数: 2
Lipid Raft Major Protein, Flotillin-2 in Gastric Cancer 胃癌中的脂筏主要蛋白flotilin -2
Pub Date : 2018-01-01 DOI: 10.4172/2168-9296.1000196
Ze-ying Ouyang, Fulgencio Nsue Eyene Nfumu, Jiayi Zhang, A-Kao Zhu, Ru-In Jian, Qian Li, Ting Liu
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引用次数: 0
Cilia Function as a Target for Respiratory Diseases and TCM 纤毛功能作为呼吸系统疾病的靶点与中医
Pub Date : 2018-01-01 DOI: 10.4172/2168-9296.1000191
Shuai Li, Qingqing Wang
Cilia in the lungs have a primary role in many respiratory diseases. Disruption of ciliated epithelial cell functions results in excess mucus in the airways, termed watery phlegm according to the Traditional Chinese Medicine Theory. Traditional Chinese Medicine prescription to treat respiratory diseases caused by watery phlegm attenuate cilia shortening, aid the clearance of ciliated epithelial cells and reduce excess mucus in the airways. Further studies are required to determine the role and mechanism of Traditional Chinese Medicine decoction and its analogous formulae and this might help develop new drugs for the treatment of respiratory diseases.
肺部纤毛在许多呼吸道疾病中起主要作用。纤毛上皮细胞功能的破坏导致气道粘液过多,根据中医理论称为水样痰。中药方剂用于治疗水样痰引起的呼吸道疾病,使纤毛缩短,帮助纤毛上皮细胞的清除,减少气道内多余的粘液。中药汤剂及其类似方剂的作用和作用机制有待进一步研究,这可能有助于开发治疗呼吸系统疾病的新药。
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引用次数: 0
Microbiological Quality Assessment at Different Stages of Frozen Amniotic Allograft Processing for Safe Tissue Banking Activities 同种异体羊膜冷冻移植处理不同阶段微生物质量评价
Pub Date : 2018-01-01 DOI: 10.4172/2168-9296.1000197
Arifuzzaman, Naznin Akhtar, S. M. Asaduzzaman
Human Amniotic Membrane (HAM) is widely used as biological dressing material in reconstructive skin surgery, abdominal and vaginal reconstruction, plastic and cosmetic surgery and in ophthalmologic surgery. The objective of this study was to assess microbial quality of HAM during different stages of frozen HAM allograft processing and determination of antimicrobial susceptibility of isolated microorganisms. For this purpose, twelve amniotic sacs were collected from normal vaginal delivery of seronegative mother from Azimpur maternity, Dhaka, Bangladesh. Initial bioburden was determined by using Nutrient Agar (NA), McConkey Agar, EMB Agar, Potato Dextrose Agar (PDA). Total Viable Bacterial Count (TVBC) was calculated and Initial bacterial load was ranged from 39 to 5.25×103. No fungus was found. A total 28 bacterial isolates were selected. These bacterial isolates were identified on the basis of cultural (e.g. colony size, shape, opacity), morphological (e.g. gram reaction, cell shape and arrangement) and biochemical characterization (e.g. catalase, oxidase, carbohydrate fermentation, MR test and VP test). Of them, eight bacterial isolates were identified as Staphylococcus aureus, two were Staphylococcus epidermidis, nine were Escherichia coli, three were Salmonella typhimurium, one was Enterobacter aerogenes, one was Pseudomonas aeruginosa, four were Acinetobacter baumanii. Then, antimicrobial susceptibility pattern of isolated microorganisms were determined against ten antibiotics which includes Amphicillin, Streptomycin, Gentamycin, Neomycin, Imipenem, Vancomycin, Cloxacillin, Polymixin-B, Penicillin-G and Ciprofoxacin. It was found that, all bacterial isolates were sensitive to streptomycin and Penicillin-G. Thus, Streptomycin-Penicillin-G (Strep-P) cocktail was formulated and was used for the preparation of frozen AM. Then, bioburden was again determined by spread plate technique using the same media. Bacterial load in the processed HAM were ranged from 33 to 3.94 2. After then, HAM was preserved by using Dulbeco’s Modified Eagles Media (DMEM) and glycerol (1:1 ratio) and was stored at -80°C. Microbial quality of the preserved samples were checked at 07, 14, 21 & 30 days and no bioburden was found. Thus, it can be said that the antibiotic cocktail was suitable to remove the culturable microorganisms associated with HAM.
人羊膜(HAM)作为生物敷料广泛应用于皮肤再造术、腹部和阴道再造术、整形美容手术和眼科手术。本研究的目的是评估火腿在冷冻异体火腿加工的不同阶段的微生物质量,并测定分离的微生物的抗菌敏感性。为此,从孟加拉国达卡Azimpur产妇血清阴性的正常阴道分娩中收集了12个羊膜囊。采用营养琼脂(NA)、McConkey琼脂、EMB琼脂、马铃薯葡萄糖琼脂(PDA)测定初始生物负荷。计算总活菌数(TVBC),初始细菌负荷范围为39 ~ 5.25×103。没有发现真菌。共分离出28株细菌。根据培养(如菌落大小、形状、不透明度)、形态学(如革兰氏反应、细胞形状和排列)和生化表征(如过氧化氢酶、氧化酶、碳水化合物发酵、MR试验和VP试验)对这些分离的细菌进行鉴定。其中,金黄色葡萄球菌8株,表皮葡萄球菌2株,大肠杆菌9株,鼠伤寒沙门菌3株,产气肠杆菌1株,铜绿假单胞菌1株,鲍曼不动杆菌4株。然后,测定分离微生物对氨苄青霉素、链霉素、庆大霉素、新霉素、亚胺培南、万古霉素、氯西林、Polymixin-B、青霉素- g、环丙沙星等10种抗生素的药敏模式。结果发现,所有分离菌株均对链霉素和青霉素- g敏感。因此,我们配制了链霉素-青霉素- g (Streptomycin-Penicillin-G, Strep-P)鸡尾酒,并将其用于制备冷冻AM。然后,使用相同的培养基,用铺板技术再次测定生物负荷。处理后的火腿细菌负荷范围为33 ~ 3.94 2。然后用Dulbeco 's Modified Eagles培养基(DMEM)和甘油(1:1比例)保存,-80°C保存。保存样品于第7、14、21和30天进行微生物质量检查,未发现生物负担。因此,可以认为鸡尾酒抗生素适合去除与HAM相关的可培养微生物。
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引用次数: 0
Protein Profile Involved in Mammalian Oocyte Maturation, Fertilization and Early Embryogenesis (Pre-Implantation) 参与哺乳动物卵母细胞成熟、受精和早期胚胎发生(着床前)的蛋白谱
Pub Date : 2017-12-14 DOI: 10.4172/2168-9296.1000189
Bongkoch Turathum, Morakot Sroyraya
Proteomic analysis of oocytes can help identify proteins that are involved in female meiotic maturation and early embryonic development. Many proteins with well-defined functions have been identified during oocyte maturation. High levels of MPF, MAPK, Mos and low levels of cAMP play an essential role in the resumption of meiosis I. Following germinal vesicle breakdown, chromosome condensation and spindle formation occurred at metaphase I by assembly of the meiotic apparatus, which includes the proteins NuMA, γ-tubulin and Polo-like kinase 1. The metaphase II arrest is a result of high levels of MPF and MAPK. Proteins involved in the stress response and redox regulation, including peroxiredoxin, GST and HSF1, are also necessary for protection against oxidative stress. During fertilization, the sperm-egg interaction requires egg surface proteins, oocyte zona pellucida, molecular chaperones, GPI-anchored proteins and CD9 to recognize sperm proteins and prevent polyspermy. Following gamete fusion, resumption and complete of meiosis II is induced by GTP and CaM kinase II activation, which inactivates MPF and activation of the anaphase promoting complex/cyclosome results in sister chromatid separation. Decondensation of the sperm head begins after zona penetration and GSH and NPM2 are necessary for male pronuclear formation. MAPK inactivation is required for pronuclear formation. At the cleavage stage, the maternal effect proteins PADI6, FLOPED and FILIA are essential for embryonic progression past the two-cell stage. After cell adhesion, cell junctions and the cytoskeleton play an important role in compaction of the morula. Par6, Par3 and protein kinase C are components of the apical polarity complex and are important for formation of the blastocoel cavity. During the blastocyst stage, TEAD4 and CDX2 are required for trophoectoderm formation. This proteomic analysis of oocytes has improved our understanding of the molecular processes that regulate oocyte maturation, fertilization and pre-implantation in mammals.
卵母细胞的蛋白质组学分析可以帮助鉴定参与雌性减数分裂成熟和早期胚胎发育的蛋白质。在卵母细胞成熟过程中发现了许多功能明确的蛋白。高水平的MPF、MAPK、Mos和低水平的cAMP在减数分裂I的恢复中起着至关重要的作用。随着生发囊泡的破裂,染色体凝集和纺锤体的形成发生在中期I,其中包括蛋白质NuMA、γ-微管蛋白和polo样激酶1。中期II骤停是强积金和MAPK水平高的结果。参与应激反应和氧化还原调节的蛋白质,包括过氧化物还氧蛋白、GST和HSF1,也是防止氧化应激所必需的。在受精过程中,精卵相互作用需要卵子表面蛋白、卵母细胞透明带、分子伴侣蛋白、gpi锚定蛋白和CD9来识别精子蛋白,防止多精现象的发生。配子融合后,GTP和CaM激酶II的激活诱导减数分裂II的恢复和完成,MPF失活,后期促进复合体/环体的激活导致姐妹染色单体分离。精子头部的去浓缩在精子带穿透后开始,GSH和NPM2是形成雄性原核所必需的。MAPK失活是原核形成所必需的。在卵裂阶段,母体效应蛋白PADI6、FLOPED和FILIA对胚胎发育过二细胞期至关重要。细胞粘附后,细胞连接和细胞骨架对桑葚胚的压实起重要作用。Par6、Par3和蛋白激酶C是顶极性复合物的组成部分,对囊胚腔的形成起重要作用。在囊胚阶段,TEAD4和CDX2是滋养外胚层形成所必需的。卵母细胞的蛋白质组学分析提高了我们对哺乳动物调节卵母细胞成熟、受精和着床前的分子过程的理解。
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引用次数: 3
Unraveling the Myth of Foxa2 in Endocrine Formation of the Pancreatic Lineages 揭开Foxa2在胰腺谱系内分泌形成中的神话
Pub Date : 2017-07-19 DOI: 10.4172/2168-9296.1000186
S. Willmann
Diabetes mellitus is a severe disease caused by the autoimmune destruction and/or secreting defects of the β-cells with a global prognosis of 844 million patients in the next 20 years (The World Health Organization). The differences are stated either as T1D (Type1 Diabetes) or T2D (Type 2 Diabetes), focusing on the occurrence of the disease itself and the inheritance either early in life, at the beginning of the adulthood or in adults. Further studies are progressively made in the process of pregnancy, where a specific subset of diabetes appears for the expectant mother. Thus, making the disease itself a complex challenge in the world health population and on focus in the field of Research and Development. The focus is driven by elucidating the different factors in the maturation steps of the pancreatic insulin-secreting β-cell, impairment in this β-cells lead either to T1D or T2D. The main factor which accelerates the progression of the developing pancreas suggests being the fork head box (Fox) gene Foxa2, targeted deletions of Foxa2 in mice led to increased adiposity on a high-fat diet and decreased adipocyte glucose uptake and glycolysis. Interestingly, the null allele of Foxa2 leads to severe defects in embryogenesis and death at the embryonic stage (E) 10-11, suggesting an important role in the process of organogenesis. Thereby, Foxa2 and its target genes may shed light in specifically elucidating the transcriptional and signaling network which drives the lineage formation within the pancreas and suggests to be a promising target for creating the β-cell in vivo. Insights into the unique expression of Foxa2 in pancreatic organogenesis will accelerate our understanding of pancreatic development and highlight current findings in the field of diabetes.
糖尿病是一种由自身免疫破坏和/或β细胞分泌缺陷引起的严重疾病,未来20年全球预后为8.44亿患者(世界卫生组织)。这种差异被称为T1D(1型糖尿病)或T2D(2型糖尿病),重点是疾病本身的发生和遗传,无论是在生命早期,在成年期开始还是在成年期。在怀孕过程中逐步进行进一步的研究,其中孕妇出现了糖尿病的特定子集。因此,使该病本身成为世界卫生人口和研究与发展领域的一个复杂挑战。重点是通过阐明胰腺胰岛素分泌β细胞成熟步骤中的不同因素,β细胞损伤导致T1D或T2D。加速胰腺发育进程的主要因素是叉头盒(Fox)基因Foxa2, Foxa2在小鼠中的靶向缺失导致高脂肪饮食中肥胖增加,脂肪细胞葡萄糖摄取和糖酵解减少。有趣的是,Foxa2的零等位基因会导致胚胎发生中的严重缺陷和胚胎期死亡(E) 10-11,这表明Foxa2在器官发生过程中起重要作用。因此,Foxa2及其靶基因可能有助于特异性阐明驱动胰腺内谱系形成的转录和信号网络,并表明Foxa2是在体内产生β细胞的有希望的靶标。深入了解Foxa2在胰腺器官发生中的独特表达将加速我们对胰腺发育的理解,并突出当前在糖尿病领域的发现。
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引用次数: 0
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Cell & developmental biology
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