Inflammation and cell signaling最新文献_第2页

Potential Contribution of Microbiome In Neurodegenerative Diseases: Alzheimer's Disease 微生物组在神经退行性疾病中的潜在贡献:阿尔茨海默病

Inflammation and cell signaling

Pub Date : 2017-10-17 DOI: 10.14800/ICS.1595

R. Kumari, Nirmal Verma, J. Paul

Alzheimer’s Disease (AD) is characterized by a slowly progressive decline of cognition and memory and is the most frequent cause of dementia. HM contribute to the regulation of multiple neuro-chemical and neuro-metabolic pathways. The pathological features of AD include amyloid beta peptide (Aβ) deposition, neuronal tangle formation and granulovacuolar degeneration. Aβ protein is a normal part of the innate immune system, the body's first-line defense against infection. However recent report shows that Ab expression protects against fungal and bacterial infections in mouse, nematode, and cell culture models of AD. However, recent research has shown that these proteins are also expressed on bacterial and fungal cell surfaces and might contribute to immune response. In addition to commensal microbes there are other pathogens like Chlamydophila pneumoniae, Toxoplasma gondii, HIV- associated neurocognitive disorders (HAND, Viroids, Hepatitis, Cytomegalovirus have been suspected to be involved in AD. Microbes are proposed to be involved in pathophysiology of neurodegenerative disease through their ability to produce relevant neurotransmitter level, immune modulation due to excess inflammation and translocation to brain from the site of infection trough blood or lymphatic system. Here we elaborated on the emerging ideas showing the contribution of the gut microbiome to human neurological diseases with special emphasis on AD. The evidences outlined in this review may prove useful in designing further studies for taxonomic and functional profiling of microbiota in patients with AD leading to new advanced therapeutic inventions.

阿尔茨海默病(AD)的特点是认知和记忆的缓慢进行性下降，是痴呆症的最常见原因。HM参与多种神经化学和神经代谢途径的调节。阿尔茨海默病的病理特征包括淀粉样肽(Aβ)沉积、神经元缠结形成和颗粒空泡变性。a β蛋白是先天免疫系统的正常组成部分，是人体抵御感染的第一道防线。然而，最近的报告显示，在AD的小鼠、线虫和细胞培养模型中，Ab表达对真菌和细菌感染有保护作用。然而，最近的研究表明，这些蛋白质也在细菌和真菌细胞表面表达，并可能有助于免疫反应。除了共生微生物外，其他病原体如肺炎衣原体、刚地弓形虫、HIV相关神经认知障碍(HAND)、类病毒、肝炎、巨细胞病毒等也被怀疑与AD有关。微生物通过产生相关的神经递质水平、过度炎症引起的免疫调节以及从感染部位通过血液或淋巴系统转运到大脑的能力，被认为参与了神经退行性疾病的病理生理。在这里，我们详细阐述了新兴的观点，显示肠道微生物群对人类神经系统疾病的贡献，特别强调AD。本文概述的证据可能有助于设计进一步的研究，以进行AD患者微生物群的分类和功能分析，从而导致新的先进治疗发明。

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引用次数: 3

RNA N6-adenosine methylation (m6A) steers epitranscriptomic control of herpesvirus replication RNA n6 -腺苷甲基化(m6A)引导疱疹病毒复制的表转录组控制

Inflammation and cell signaling

Pub Date : 2017-10-17 DOI: 10.14800/ICS.1604

Fengchun Ye

Latency is a hallmark of all herpesviruses, during which the viral genomes are silenced through DNA methylation and suppressive histone modifications. When latent herpesviruses reactivate to undergo productive lytic replication, the suppressive epigenetic marks are replaced with active ones to allow for transcription of viral genes. Interestingly, by using Kaposi’s sarcoma-associated herpesvirus (KSHV) as a model, we recently demonstrated that the newly transcribed viral RNAs are also subjected to post-transcriptional N6-adenosine methylation (m6A). Blockade of this post-transcriptional event abolishes viral protein expression and halts virion production. We found that m6A modification controls RNA splicing, stability, and protein translation to regulate viral lytic gene expression and replication. Thus, our finding for the first time reveals a critical role of this epitranscriptomic mechanism in the control of herpesviral replication, which shall shed lights on development of novel strategies for the control of herpesviral infection.

潜伏期是所有疱疹病毒的一个特征，在此期间，病毒基因组通过DNA甲基化和抑制性组蛋白修饰而沉默。当潜伏的疱疹病毒重新激活进行多产的裂解复制时，抑制的表观遗传标记被活性标记所取代，从而允许病毒基因的转录。有趣的是，通过使用卡波西肉瘤相关疱疹病毒(KSHV)作为模型，我们最近证明了新转录的病毒rna也受到转录后n6 -腺苷甲基化(m6A)的影响。阻断这一转录后事件可消除病毒蛋白表达并停止病毒粒子的产生。我们发现m6A修饰控制RNA剪接、稳定性和蛋白质翻译，从而调节病毒裂解基因的表达和复制。因此，我们的发现首次揭示了这种表转录组学机制在控制疱疹病毒复制中的关键作用，这将为开发控制疱疹病毒感染的新策略提供启示。

引用次数: 15

Studies on the mechanisms of bile acid initiated hepatic inflammation in cholestatic liver injury 胆汁淤积性肝损伤中胆汁酸引发肝脏炎症机制的研究

Inflammation and cell signaling

Pub Date : 2017-06-19 DOI: 10.14800/ICS.1561

Shi-Ying Cai, J. Boyer

The mechanism of bile acid induced cholestatic liver injury remains controversial, thus hindering the development of new therapies for these diseases. In this research highlight, we briefly review the evolution of our understanding of the pathogenesis of bile acid induced liver injury, and summarize our recent findings on this topic. Our data suggests that under pathophysiological conditions bile acid induced liver injury is mediated by inflammatory responses that are initiated from stressed hepatocytes. We conclude by mentioning potential new therapeutic approaches for treating cholestatic liver injury based on these pathophysiologic concepts.

胆汁酸诱导胆汁淤积性肝损伤的机制仍然存在争议，从而阻碍了这些疾病的新疗法的发展。在本研究重点中，我们简要回顾了我们对胆汁酸诱导肝损伤发病机制的认识演变，并总结了我们在这一主题上的最新发现。我们的数据表明，在病理生理条件下，胆汁酸诱导的肝损伤是由应激肝细胞引发的炎症反应介导的。最后，我们提出了基于这些病理生理学概念的治疗胆汁淤积性肝损伤的潜在新治疗方法。

引用次数: 11

Development of a novel cytoplasmic hydroxyl radical-targeting antioxidant (TA293) that suppresses cellular senescence, inflammation, and apoptosis 一种新的胞质羟基自由基靶向抗氧化剂(TA293)的发展，抑制细胞衰老，炎症和凋亡

Inflammation and cell signaling

Pub Date : 2017-05-24 DOI: 10.14800/ICS.1539

T. Sakai, J. Imai, Tomohiro Ito, H. Takagaki, M. Ui, S. Hatta

Hydroxyl radicals ( • OH) exhibit the strongest oxidation potential of any reactive oxygen species (ROS) and react non-specifically with cellular components, such as nucleic acids, lipids and proteins. While mitochondrial • OH incites oxidative damage resulting in mitochondrial dysfunction, the actions of cytoplasmic • OH remain unknown as no cytoplasmic • OH-specific scavenger has been identified to date. To solve this problem, we developed the cytoplasm- and mitochondrion-specific • OH-targeted scavengers TA293 and mitoTA293, respectively. As expected, TA293 and mitoTA293 scavenged • OH, but not O 2 – or H 2 O 2 . Notably, TA293 scavenged pyocyanin-induced cytoplasmic • OH, but not mitochondrial radicals induced by antimycin A. Conversely, mitoTA293 scavenged • OH only in the mitochondria in vivo and in vitro . Interestingly, we found that cytoplasmic • OH plays a central role in cytoplasm ROS-induced oxidative stress, which potentiates cellular senescence, inflammation, and apoptosis in the kidney and lung. Based on these findings, we believe that TA293 could be a novel tool to study the effects of • OH damage within the cytoplasm.

羟基自由基(•OH)在所有活性氧(ROS)中表现出最强的氧化电位，并与细胞成分(如核酸、脂质和蛋白质)发生非特异性反应。虽然线粒体•OH刺激氧化损伤导致线粒体功能障碍，但细胞质•OH的作用仍然未知，因为迄今为止还没有发现细胞质•OH特异性清除剂。为了解决这个问题，我们分别开发了细胞质特异性和线粒体特异性•oh靶向清除剂TA293和mitoTA293。正如预期的那样，TA293和mitoTA293清除•OH，但不清除o2 -或h2o2。值得注意的是，TA293清除了pyocyanin诱导的细胞质•OH，但不清除抗霉素a诱导的线粒体自由基。相反，mitoTA293仅在体内和体外清除线粒体中的•OH。有趣的是，我们发现细胞质•OH在细胞质ros诱导的氧化应激中起着核心作用，而氧化应激会增强肾和肺的细胞衰老、炎症和凋亡。基于这些发现，我们认为TA293可能成为研究细胞质中•OH损伤影响的新工具。

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引用次数: 0

Aberrant function of neutrophils in asthma 中性粒细胞在哮喘中的异常功能

Inflammation and cell signaling

Pub Date : 2017-04-17 DOI: 10.14800/ICS.1535

Meijia Wang, Jianping Zhao, Jungang Xie

Asthma is a chronic inflammatory airway disease, with an array of cells involved in the pathogenesis of the disease. The role of neutrophils in asthma pathogenesis is controversial. This review highlights the mechanisms of neutrophils about their aberrant functionality involved in asthma and factors contributed to impaired response to corticosteroids, which may contribute to a better understanding of asthma pathogenesis and consequently, facilitate the development of novel strategies for managing and treating neutrophilia in asthma.

哮喘是一种慢性炎症性气道疾病，有一系列的细胞参与疾病的发病机制。中性粒细胞在哮喘发病中的作用尚存争议。本文综述了中性粒细胞在哮喘中的异常功能机制，以及导致对皮质类固醇反应受损的因素，这可能有助于更好地了解哮喘的发病机制，从而促进哮喘中性粒细胞管理和治疗的新策略的发展。

引用次数: 0

S100A8/A9, a potent biomarker and clinical candidate for the treatment of uveitis S100A8/A9，一种治疗葡萄膜炎的有效生物标志物和临床候选物

Inflammation and cell signaling

Pub Date : 2017-03-06 DOI: 10.14800/ICS.1512

Zai-Long Chi, Xiaodan Dai

Uveitis, the pathological condition of inflammation of the uvea, commonly causes severe visual impairment and blindness. Possible causes of uveitis include infection, injury, or an autoimmune or inflammatory disease. However, the pathogenesis of uveitis is not fully understood. Glucocorticoids are widely used for the treatment of uveitis, but long-term steroid use carries a risk of potential complications. Early diagnosis and proper treatment are important to prevent the complications of uveitis. Thus far, researchers have not identified an effective biological marker for auxiliary diagnosis or an appropriate method for monitoring the inflammatory activity of uveitis. S100A8/A9, also known as calprotectin, belongs to the Ca 2+ -binding S100 protein family; is mainly expressed in myeloid leukocytes; and plays a prominent role in a variety of pathological process, such as inflammation, infection and autoimmune diseases. Extracellular S100A8/A9 released from granulocytes and monocytes has recently gained a great deal of attention as a critical alarmin for the modulation of the inflammatory response. This review will summarize recent insights into the biological function of S100A8/A9 in uveitis and provide an outlook on diagnostic, inflammation monitoring and therapeutic applications targeting S100A8/A9 for the treatment of uveitis.

葡萄膜炎是葡萄膜炎症的病理状态，通常会导致严重的视力障碍和失明。葡萄膜炎的可能原因包括感染、损伤、自身免疫性疾病或炎症性疾病。然而，葡萄膜炎的发病机制尚不完全清楚。糖皮质激素被广泛用于治疗葡萄膜炎，但长期使用类固醇有潜在并发症的风险。早期诊断和适当治疗对预防葡萄膜炎并发症至关重要。到目前为止，研究人员还没有找到一种有效的生物标志物来辅助诊断葡萄膜炎，也没有一种合适的方法来监测葡萄膜炎的炎症活性。S100A8/A9，又称钙保护蛋白，属于ca2 +结合蛋白S100家族;主要表达于髓系白细胞;并在多种病理过程中发挥突出作用，如炎症、感染和自身免疫性疾病。最近，粒细胞和单核细胞释放的胞外S100A8/A9作为炎症反应调节的关键警报因子受到了广泛关注。本文将对S100A8/A9在葡萄膜炎中的生物学功能的最新研究进展进行综述，并对S100A8/A9在葡萄膜炎诊断、炎症监测和治疗中的应用进行展望。

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引用次数: 1

Emerging role of zinc homeostasis by zinc transporter ZIP7 in intestinal homeostatic self-renewal 锌转运蛋白ZIP7在肠道内稳态自我更新中的新作用

Inflammation and cell signaling

Pub Date : 2017-02-20 DOI: 10.14800/ics.1509

W. Ohashi, K. Hase, T. Fukada

There has been a growing interest in the biological significance of zinc and its regulatory mechanism in the development of tissue and in the maintenance of tissue homeostasis. The intestinal epithelium undergoes a continuous self-renewing process to maintain the intestinal homeostasis. Moreover, dysregulation of this process often causes various intestinal disorders including inflammatory bowel disease, ulcer, and cancer. However, the molecular basis of zinc-dependent regulation of intestinal epithelial cell turnover is not fully understood. In this research highlight, we describe that the zinc transporter ZIP7 (highly expressed in undifferentiated epithelial cells) plays a critical role in the intestinal epithelial self-renewal process by alleviating the ER stress during vigorous proliferative response. Our findings also provide evidence showing that the fine-tuning of intracellular zinc homeostasis by ZIP7 is essential to maintain epithelial homeostasis in the intestine.

人们对锌的生物学意义及其在组织发育和维持组织稳态中的调节机制越来越感兴趣。肠上皮经历了一个持续的自我更新过程，以维持肠道内稳态。此外，这一过程的失调经常导致各种肠道疾病，包括炎症性肠病、溃疡和癌症。然而，锌依赖调节肠上皮细胞更新的分子基础尚不完全清楚。在本研究重点中，我们描述了锌转运蛋白ZIP7(在未分化上皮细胞中高度表达)在肠上皮自我更新过程中发挥关键作用，在剧烈增殖反应中减轻内质网应激。我们的研究结果也提供了证据，表明ZIP7对细胞内锌稳态的微调对于维持肠道上皮稳态至关重要。

引用次数: 0

Vitellogenin in inflammation and immunity in social insects 群居昆虫炎症和免疫中的卵黄原蛋白

Inflammation and cell signaling

Pub Date : 2017-02-14 DOI: 10.14800/ICS.1506

Heli Salmela, L. Sundström

Social insects, such as the honey bee and ants, form vast colonies that are only rivalled by human settlements. Living in dense, often stationary groups is prone to increase disease transmission. Yet, social insect queens and certain worker types can lead lengthy lives compared to the life span of most solitary insects. Social insects appear to have modified insulin/insulin like signaling pathway that regulates insect life history. This modification results in extremely elevated levels of the multifunctional lipoprotein vitellogenin in the individuals with longer life span. Vitellogenin is an egg-yolk precursor, but it also regulates caste-related behaviors in social insects, has shielding effects in inflammation and infection, and it is a mediator of transgenerational immunity. Here, we compile what is known about the life span and immune actions of vitellogenin and the evolution of this protein in the honey bee and ants. Recently we identified proteins homologous to vitellogenin in several Hymenopteran species, and showed that at least one of these vitellogenin-like proteins can have a protective role similar to vitellogenin in the honey bee. The newly identified vitellogenin homologs hint that the regulation of social insect life span can be more complex than thought before.

群居昆虫，如蜜蜂和蚂蚁，形成了只有人类才能与之匹敌的庞大群体。生活在人口密集、往往静止不动的群体中，容易增加疾病传播。然而，与大多数独居昆虫的寿命相比，群居昆虫女王和某些工蜂类型的寿命更长。群居昆虫似乎改变了调节昆虫生活史的胰岛素/胰岛素样信号通路。这种修饰导致长寿个体的多功能脂蛋白卵黄原蛋白水平极高。卵黄原蛋白是一种卵黄前体，但它也调节社会性昆虫的种姓相关行为，在炎症和感染中具有屏蔽作用，并且是跨代免疫的中介。在这里，我们汇编了关于卵黄蛋白原的寿命和免疫作用以及该蛋白在蜜蜂和蚂蚁中的进化的已知信息。最近，我们在几种膜翅目昆虫中发现了与卵黄蛋白原同源的蛋白，并表明至少有一种卵黄蛋白原样蛋白在蜜蜂中具有类似于卵黄蛋白原的保护作用。新发现的卵黄蛋白同源物暗示，群居昆虫寿命的调节可能比以前认为的要复杂得多。

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引用次数: 27

RNA N⁶-adenosine methylation (m⁶A) steers epitranscriptomic control of herpesvirus replication. RNA n6 -腺苷甲基化(m6A)引导疱疹病毒复制的表转录组控制。

Inflammation and cell signaling

Pub Date : 2017-01-01 Epub Date: 2017-10-17

Fengchun Ye

Latency is a hallmark of all herpesviruses, during which the viral genomes are silenced through DNA methylation and suppressive histone modifications. When latent herpesviruses reactivate to undergo productive lytic replication, the suppressive epigenetic marks are replaced with active ones to allow for transcription of viral genes. Interestingly, by using Kaposi's sarcoma-associated herpesvirus (KSHV) as a model, we recently demonstrated that the newly transcribed viral RNAs are also subjected to post-transcriptional N⁶-adenosine methylation (m⁶A). Blockade of this post-transcriptional event abolishes viral protein expression and halts virion production. We found that m⁶A modification controls RNA splicing, stability, and protein translation to regulate viral lytic gene expression and replication. Thus, our finding for the first time reveals a critical role of this epitranscriptomic mechanism in the control of herpesviral replication, which shall shed lights on development of novel strategies for the control of herpesviral infection.

潜伏期是所有疱疹病毒的一个特征，在此期间，病毒基因组通过DNA甲基化和抑制性组蛋白修饰而沉默。当潜伏的疱疹病毒重新激活进行多产的裂解复制时，抑制的表观遗传标记被活性标记所取代，从而允许病毒基因的转录。有趣的是，通过使用卡波西肉瘤相关疱疹病毒(KSHV)作为模型，我们最近证明了新转录的病毒rna也受到转录后n6 -腺苷甲基化(m6A)的影响。阻断这一转录后事件可消除病毒蛋白表达并停止病毒粒子的产生。我们发现m6A修饰控制RNA剪接、稳定性和蛋白质翻译，从而调节病毒裂解基因的表达和复制。因此，我们的发现首次揭示了这种表转录组学机制在控制疱疹病毒复制中的关键作用，这将为开发控制疱疹病毒感染的新策略提供启示。

引用次数: 0

Studies on the mechanisms of bile acid initiated hepatic inflammation in cholestatic liver injury. 胆汁淤积性肝损伤中胆汁酸引发肝脏炎症机制的研究。

Inflammation and cell signaling

Pub Date : 2017-01-01 Epub Date: 2017-06-19

Shi-Ying Cai, James L Boyer

The mechanism of bile acid induced cholestatic liver injury remains controversial, thus hindering the development of new therapies for these diseases. In this research highlight, we briefly review the evolution of our understanding of the pathogenesis of bile acid induced liver injury, and summarize our recent findings on this topic. Our data suggests that under pathophysiological conditions bile acid induced liver injury is mediated by inflammatory responses that are initiated from stressed hepatocytes. We conclude by mentioning potential new therapeutic approaches for treating cholestatic liver injury based on these pathophysiologic concepts.

胆汁酸诱导胆汁淤积性肝损伤的机制仍然存在争议，从而阻碍了这些疾病的新疗法的发展。在本研究重点中，我们简要回顾了我们对胆汁酸诱导肝损伤发病机制的认识演变，并总结了我们在这一主题上的最新发现。我们的数据表明，在病理生理条件下，胆汁酸诱导的肝损伤是由应激肝细胞引发的炎症反应介导的。最后，我们提出了基于这些病理生理学概念的治疗胆汁淤积性肝损伤的潜在新治疗方法。

引用次数: 0