缺氧诱导因子1α蛋白质水平及活性调节

缺氧诱导因子 1α不仅对于机体在缺氧条件下维持正常的生理功能具有特别重要的意义 ,还在肿瘤的生长以及神经细胞凋亡等病理过程中起关键作用。缺氧诱导因子 1α能调节许多下游基因的表达水平 ,但人们对其自身的蛋白质水平和转录活性调节机制尚知之不多。最新的研究发现缺氧诱导因子 1α的蛋白质水平和转录活性调节机制涉及多个信号通路 ;在缺氧诱导因子 1α的蛋白质水平和转录活性调节机制中 ,羟基化调节和蛋白磷酸化调节起主导作用     

缺氧诱导因子在骨肉瘤中的相关研究进展

缺氧是包括骨肉瘤在内的实体肿瘤的普遍特征。缺氧诱导因子是肿瘤细胞在缺氧条件下的重要调节因子。研究缺氧诱导因子在骨肉瘤的相关机制能为骨肉瘤的治疗提供新思路,本文就缺氧诱导因子的结构功能、缺氧诱导因子与骨肉瘤干细胞、缺氧诱导因子与骨肉瘤放疗抵抗、缺氧诱导因子与骨肉瘤多药耐药、缺氧诱导因子的抑制剂等相关研究进行综述。     

缺氧诱导因子1在肿瘤细胞免疫逃避中的作用（英文）

缺氧是肿瘤的重要特征。在肿瘤发生过程中,缺氧诱导因子1是协调缺氧变化的重要的调节因子。缺氧和缺氧诱导因子1可以调节肿瘤内的免疫应答,缺氧通过激活缺氧诱导因子1及其下游信号通路诱导肿瘤细胞产生多种机制以逃避免疫系统的识别和攻击。作者主要综述了缺氧诱导因子1介导的肿瘤免疫逃避,以及针对缺氧诱导因子1靶向药物的开发。     

缺氧诱导因子1在肿瘤细胞免疫逃避中的作用

缺氧是肿瘤的重要特征。在肿瘤发生过程中,缺氧诱导因子1是协调缺氧变化的重要的调节因子。缺氧和缺氧诱导因子1可以调节肿瘤内的免疫应答,缺氧通过激活缺氧诱导因子1 及其下游信号通路诱导肿瘤细胞产生多种机制以逃避免疫系统的识别和攻击。作者主要综述了缺氧诱导因子1介导的肿瘤免疫逃避,以及针对缺氧诱导因子1靶向药物的开发。     

TRIM蛋白家族调节NF-κB信号通路的研究进展

正核因子-κB(Nuclear factor-kappa B,NF-κB)作为重要的核转录因子参与调节机体的免疫应答,一旦其调节发生异常将会导致免疫疾病、神经退行性病变、新陈代谢疾病、肿瘤等。磷酸化、泛素化等转录后修饰可调节NF-κB信号通路。E3泛素连接酶在泛素化的过程中起重要作用~([1])。TRIM(Tripartite motif)蛋白是E3泛素连接酶中RING家族成员,由     

缺氧诱导因子与骨稳态失衡类疾病的相关性

背景:缺氧诱导因子是骨缺氧微环境中关键的基因表达调节因子,了解缺氧诱导因子在骨形成、骨重塑中的作用机制及其对骨稳态失衡类疾病的影响,对探索骨稳态失衡类疾病的防治新途径具有重要意义.目的:查阅国内外相关医学文献,对缺氧诱导因子在骨形成、骨重塑过程中的作用机制,以及对缺氧诱导因子与骨稳态失衡类疾病相关性的研究进展进行综述分...     

泛素缀合酶样蛋白的研究概况

在泛素缀合途径中,泛素缀合酶起关键作用,各种不同的泛素缀合酶决定了泛素缀合途径功能的多样性。泛素缀合酶样蛋白存序列和二、三级结构上类似于泛素缀合酶,但不具备泛素缀合酶的泛素缀合活性。泛素缀合酶样蛋白可能是蛋白泛素化的新的调节因子。     

缺氧诱导因子新进展

目的缺氧诱导因子是细胞对于缺氧主要的应答因子,缺氧诱导因子由α和β两个亚基组成。缺氧、重金属、细胞因子等能抑制α亚基的降解,α亚基与β亚基结合成有活性的异二聚体,转移到细胞核内,调节多种靶基因的转录。缺氧诱导因子除参与缺氧时细胞稳态的维持,还在胚胎发育,细胞分化,肿瘤生长中发挥作用。     

DUT通过靶向RIG-I正调控RLR介导的抗病毒信号通路

目的探究DUT(deoxyuridine triphosphate nucleotidohydrolase, dUTPase)对RIG-I(retinoic acid-inducible gene I)介导的RLR(RIG-I-like receptors)抗病毒先天免疫的研究。方法采用免疫共沉淀的方法检测DUT与RIG-I之间的相互作用以及DUT对RIG-I介导的泛素化修饰的影响;应用非变性聚丙烯酰胺凝胶电泳实验验证DUT对RIG-I或仙台病毒(Sendai virus,SeV)诱导的IRF3二聚化的作用;利用双荧光素酶报告基因实验检测RIG-I或SeV介导的DUT对干扰素启动子IFN-β的激活效果;通过实时荧光定量PCR实验检测DUT对SeV诱导的IFN-β转录的影响。结果 DUT与RIG-I相互作用,过表达DUT促进RIG-I或SeV诱导的IRF3的二聚化水平以及IFN-β启动子的活性。此外,过表达DUT也加强了SeV诱导的IFN-β启动子的转录水平,研究结果还表明DUT促进RIG-I泛素化修饰及RIG-I K63泛素化修饰,并且通过与RIG-I之间的相互作用增强RNF135、MEX3C、TRIM4介导的RIG-I K63泛素化修饰。结论 DUT是RIG-I介导的针对RNA病毒天然免疫应答的正调节因子。     

头帕肿瘤综合征蛋白与肿瘤坏死因子受体介导的坏死样凋亡

头帕肿瘤综合征蛋白(cylindromatosis,CYLD)是一种去泛素化酶,其C-末端USP结构域具有催化功能,可移除受体相互作用蛋白激酶1(receptor interacting protein kinase 1,RIPK1)的K63连接泛素链,调节RIPK1的泛素化水平,从而参与调节肿瘤坏死因子受体1(tumor necrosis factor receptor 1, TNFR1)介导的RIPK依赖的细胞坏死样凋亡等病理生理过程。阐明CYLD对RIPK1去泛素化调节的详细机制,寻找针对CYLD的特异性抑制剂,可为与坏死样凋亡相关的损伤与疾病提供治疗的新策略。     

Psychological sense of community in Australia and the challenges of change

Social change is a phenomenon experienced in all societies, whether from gradual passages and time and interaction with other groups, or through the more immediate impacts such as war, invasion, or physical catastrophe. How societies manage change indicates much about their abilities to survive and the type of social cohesion that will be evidenced. In this article, the authors investigate the use of common symbols and shared history as ways of either maintaining social identity and moving with change, or using them in negative ways to resist change. The case study of immigration to Australia is used to demonstrate that members of the community are able to identify a series of salient identity markers—whether they wish to accept all of them or not—as the types of knowledge that all members share. Many of the markers reflect decades of passed history, but are seen as foundational to Australia today. Although they are core to identity, they are the types of symbols that are grasped as a lifestyle under threat by those who are newcomers. Often the markers are there as more unconscious constructions, to be evoked at times of high emotion to indicate what must be “saved” for current ideas to survive. The authors discuss the meanings of these markers as ways in which the identity of members of the community has been established. But these are seen as reminders, or glorifications, of the past, and how such markers are able to be captured and (mis)used by narrow populist and extremist interest groups. The challenge of managing change is how to build forward, maintaining those markers of real social value, and incorporating the new ones that are brought by newcomers, and those that are developed together. © 2002 Wiley Periodicals, Inc.     

Perils of mercury

The historical items pertaining to mercury are outlined, and its toxicity and former medicinal uses are discussed. The diversity of the toxic effects by the different forms of mercury as well as the routes of administration are illustrated in three case reports. The importance of diaphoresis in the treatment of mercury poisoning as well as the status of the use of chelating agents are reviewed. The need for the surveillance of mercury and the prevention of exposure to mercury from environmental and dietary sources are emphasized. The importance of excluding mercury toxicity in patients with psychiatric and neurological disorders is stressed.     

Health problems associated with consumption of fish and the role of aquatic environments in the transmission of human diseases

The majority of the numerous fish parasites are harmless to man and many domestic animals because when eaten with their fish hosts, they are digested. However, some of the fish parasites with larval stages in freshwater or marine teleosts have zoonotic potential if eaten raw or partially cooked. These are usually parasites, which have a piscivorous mammalian carnivore as their normal final host and are able to infect man because of the low host specificity of the adult stage. The major groups of fish parasite that are known as potentially dangerous pathogens of man belong to the helminth groups cestoda, trematoda, nematoda and rarely acanthocephala. However, bacterial and viral disease of man transmitted through fish are not uncommon. Toxic substances, metals and insecticides used to control human diseases in aquatic environments may accumulate in fish in po1lluted waters at such levels as to constitute a health risk to the consumer. Other health problems associated with fish arise from its perishable nature for example, in adequate handling, processing and storage, which may lead to the accumulation of microbes enhancing the risk of food poisoning. The aquatic environment in Africa constitutes a breeding habitat to several vectors of human diseases such as mosquitoes, snails and black flies. This paper reviews the role played by fish in transmitting diseases to humans as well as the importance of the aquatic environments in the transmission of human diseases such as Malaria, Schistosomiasis and onchocerciasis.     

The 'consciousness primitive': a competence model of mind and will

Questions about mind and will are usually raised as though mind and will are either present or absent. Here, a view is presented to suggest that they are only a particular instantiation of a 'consciousness primitive', present in lower animals as well as in primitive portions of the human brain. Physiological variables, drugs and transmitters alter it in order to produce discontinuous products, such as learning, motivation, emotions etc., which are usually studied by performance models as though they are distinctive functions of the brain.     

Formation and germination of fungal arthroconidia

A large variety of fungi are known to produce asexual spores known as arthroconidia. These propagules are formed by segmentation of existing hyphae and may form by several mechanisms. The specific processes of formation may lead to acropetal, basipetal, or random formation of endoarthroconidia or exoarthroconidia. The development of arthroconidia is a survival response to the depletion of nutrients or other environmental stresses and, in at least one case, is accompanied by the excretion of high levels of antibiotics. Arthroconidia are generally not as resistant to physical factors as are other fungal reproductive structures and are also susceptible to a variety of antibiotics and disinfectants. Arthroconidia are produced by some medically important fungi and in some cases, such as coccidioidomycosis, they are the principal means of dissemination. Germination of arthroconidia in complex media generally does not require specific "activation" events.     

Hepatic manifestations of lymphomas

The various hepatic manifestations of malignant lymphomas are discussed as well as the methods employed to detect hepatic involvement in those diseases. Hepatomegaly is infrequent in early Hodgkin's disease and, when present, may represent a nonspecific reactive phenomenon. Hepatomegaly is more common in non-Hodgkin's lymphomas and various leukemias and usually represents neoplastic involvement of that organ. Radiographic procedures and liver function studies are unreliable in detecting liver involvement although correlation of the various data increases diagnostic accuracy. Morphological manifestations of these diseases are discussed as well as those methods which are best suited for diagnosis.     

Problems with ultrasonic measurements of shear modules of structured media

The elastic constants of linearly elastic, isotropic or anisotropic bone material are required for many numerical simulations. These constants are often measured ultrasonically, but this can lead to mistakes, especially if shear modules of spongiosa are considered. The reason is that spongiosa is a structure composed of trabeculae, each of which acts as a kind of beam which allows longitudinal, shear and also bending waves to propagate; the bending waves are as fast as the longitudinal waves and are indistinguishable from the shear waves. Furthermore, mistakes in measuring Young's modulus cannot be avoided in every case. Several numerical simulations of wave propagations in homogeneous media, and especially in periodically and irregularly structured media, were carried out via the application of explicit finite element codes. Results showing the above-mentioned effects are presented and discussed. These can help to explain in detail why mistakes may occur during ultrasonic measurements.     

Lipoxins and aspirin-triggered 15-epi-lipoxins are endogenous components of antiinflammation: emergence of the counterregulatory side

Eicosanoids are known to play important roles in cell-cell communications and as intracellular signals that are critical components of multi-cellular responses such as acute inflammation and reperfusion injury. Recent findings have given rise to several new concepts that are reviewed here regarding the generation of eicosanoids and their impact in inflammation. Lipoxins (LX) are trihydroxytetraene-containing eicosanoids that can be generated within the vascular lumen during platelet-leukocyte interactions and at mucosal surfaces via leukocyte-epithelial cell interactions. During these cell-cell interactions, transcellular biosynthetic pathways are used as major LX biosynthetic routes, and thus, in humans, LX are formed in vivo during multi-cellular responses such as inflammation, atherosclerosis, and in asthma. This branch of the eicosanoid cascade generates specific tetraene-containing products that serve as stop signals, in that they regulate key steps in leukocyte trafficking and prevent leukocyte-mediated acute tissue injury. Of interest here are recent results indicating that aspirin's mechanism of action also involves the triggering of novel carbon 15 epimers of LX or 15-epi-LX that mimic the bioactions of native LX. Here, an overview of these recent developments is presented, with a focus on the cellular and molecular interactions of these novel antiinflammatory lipid mediators.     

Interaction of dendritic cells with biomaterials

The interconnections between innate and adaptive immunity, with a focus on dendritic cells (DCs), in the context of combination products, are discussed. Biomaterials are shown to act as an adjuvant in the enhancement of the adaptive immune response to co-delivered antigen. Biomaterials are considered as agonists for DC maturation and several hypotheses as to the mechanism by which DCs recognize and respond to biomaterials are presented. There is the conceptualization of biomaterials with the idea of 'danger signals'. The goal is to design biomaterials to control DC phenotype and in this way control immune responses to combination products.