Apoptosis signaling in lymphocytes.

Lymphocyte apoptosis is essential for proper function of the immune system. Among other functions, it is responsible for the homeostasis of immune cells and plays a key role in the elimination of autoreactive lymphocytes. Recently, progress has been made in the identification of genes that regulate apoptosis. Studies characterizing the basic apoptosis signaling machinery have begun to reveal the molecular control of processes that modulate lymphocyte apoptosis.     

TLR signaling pathways

Toll-like receptors (TLRs) have been established to play an essential role in the activation of innate immunity by recognizing specific patterns of microbial components. TLR signaling pathways arise from intracytoplasmic TIR domains, which are conserved among all TLRs. Recent accumulating evidence has demonstrated that TIR domain-containing adaptors, such as MyD88, TIRAP, and TRIF, modulate TLR signaling pathways. MyD88 is essential for the induction of inflammatory cytokines triggered by all TLRs. TIRAP is specifically involved in the MyD88-dependent pathway via TLR2 and TLR4, whereas TRIF is implicated in the TLR3- and TLR4-mediated MyD88-independent pathway. Thus, TIR domain-containing adaptors provide specificity of TLR signaling.     

Apoptosis signaling in influenza virus propagation, innate host defense, and lung injury

Programmed cell death is a crucial cellular response frequently observed in IV-infected tissue. This article reviews the current knowledge on the molecular virus-host interactions that induce apoptosis pathways in an IV-infected cell and the functional implications of these cellular signaling events on viral propagation at distinct steps during the viral replication cycle. Furthermore, it summarizes the role of IV-induced apoptosis pathways in equilibrating the host's antiviral immune response between effective viral clearance and development of severe apoptotic lung injury.     

周细胞概念及在血管形成信号转导通路研究中的进展

背景：周细胞广泛分布于除淋巴管外的所有微脉管中,它不仅是微血管的构成成分,还在微血管的发生、发展、稳定、成熟以及再塑形过程中起着重要作用,其信号转导是目前研究的热点。目的：对近年来周细胞与血管生成相关的信号通路研究进展作以综述。方法：以“pricytes; endothelial cells;microvessels; signal transduction”为英文关键词;以“周细胞;内皮细胞;微血管;信号转导”为中文关键词,计算机检索PubMed、万方、知网、中国生物医学文献数据库(CBM),1994至2014年与周细胞、血管生成研究相关的文献,就周细胞及其与内皮细胞相互作用的相关信号通路作一阐述。结果与结论：毛细血管形成早期,周细胞的募集可促使新生毛细血管的发生和发展;血管形成后期,周细胞则抑制内皮细胞增生,促进内皮细胞分化,从而促进血管成熟,维持正常节构和调节其通透性。血小板衍生生长因子B/血小板衍生生长因子受体β、转化生长因子β、血管生成素1/Tie-2、人肝素结合性表皮生长因子/ ErbBs、基质细胞衍生因子1α/CXCR4等信号通路对周细胞及血管生成发挥着重要的调节作用。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Cytokine receptor signaling pathways

Cytokines represent a diverse group of molecules that transmit intercellular signals. These signals may either be autocrine (where the same cell both produces the cytokine and responds to it) or paracrine (where the cytokine is made by one cell and acts on another). Both these situations can occur simultaneously. Cytokines use multiple signaling pathways. This review will focus on signaling by type I cytokines and in particular on signaling by the IL-2 family of cytokines, as an illustrative example. The major signaling pathway that will be discussed is the Jak-STAT pathway, although other pathways will also be reviewed. The Jak-STAT pathway is a very rapid cytosol-to-nuclear signaling pathway that underscores how quickly extracellular signals can be transmitted to the nucleus. Aspects related to cytokine redundancy, pleiotropy, and specificity will be discussed.     

细胞凋亡与自身免疫病

细胞凋亡在维持淋巴细胞稳态及自身耐受中起重要作用.细胞凋亡受多种基因控制与调节,主要可通过外源性和内源性两条通路来触发.而凋亡功能的失常可诱发自身免疫病,如自身免疫淋巴增生综合症、Hashimoto甲状腺炎、Graves病、胰岛素依赖性糖尿病、多发性硬化等.另外凋亡细胞清除缺陷也会诱发自身免疫病.     

Non-canonical Wnt signaling pathways in hematopoiesis

Hematopoietic stem cells (HSCs) are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between the opposing cell fates of self-renewal and initiation of hematopoietic differentiation. Multiple signaling pathways have been implicated in the regulation of HSC cell fate. One such set of pathways are those activated by the Wnt family of ligands. The function of the canonical Wnt signaling pathway, which utilizes β-catenin to regulate gene expression, has been extensively studied in hematopoiesis. However, there is a growing body of evidence that the other Wnt signaling pathways, termed non-canonical, also play an important role. In this review, we will discuss the regulation of hematopoiesis by the Wnt signaling pathways, focusing on the potential functions of non-canonical Wnt signaling pathways.     

Tyrosine kinase signaling pathways in neutrophils

Neutrophils play a critical role in antimicrobial host defense, but their improper activation also contributes to inflammation-induced tissue damage. Therefore, understanding neutrophil biology is important for the understanding, diagnosis, and therapy of both infectious and inflammatory diseases. Neutrophils express a large number of cell-surface receptors that sense extracellular cues and trigger various functional responses through complex intracellular signaling pathways. During the last several years, we and others have shown that tyrosine kinases play a critical role in those processes. In particular, Src-family and Syk tyrosine kinases couple Fc-receptors and adhesion receptors (integrins and selectins) to various neutrophil effector functions. This pathway shows surprising similarity to lymphocyte antigen receptor signaling and involves various other enzymes (e.g. PLCγ2), exchange factors (e.g. Vav-family members) and adapter proteins (such as ITAM-containing adapters, SLP-76, and CARD9). Those mediators trigger various antimicrobial functions and play a critical role in coordinating the inflammatory response through the release of inflammatory mediators, such as chemokines and LTB₄. Interestingly, however, tyrosine kinases have a limited direct role in the migration of neutrophils to the site of inflammation. Here, we review the role of tyrosine kinase signaling pathways in neutrophils and how those pathways contribute to neutrophil activation in health and disease.     

MAP-kinase signaling pathways in T cells.

The family of MAP-kinases include ERKs, p38 MAP-kinases and JNKs. Recently, the role of MAP-kinases in T lymphocytes has attracted particular interest. Genetically modified mouse models have brought insight into the specific function of each MAP-kinase pathway in T lymphocyte biology. Studies clearly show that these pathways are not redundant and that the role of each pathway depends on the T cell type and differentiation stage.     

血管生成中周细胞相关信号通路的研究进展

周细胞(pericytes)作为一种血管外周细胞包绕在微血管壁外侧,支持血管结构的稳定.周细胞向新生血管周围募集成为新生血管成熟的标志性事件.周细胞由于参与肿瘤血管新生、糖尿病性血管病变、缺氧/缺血性血管增生等诸多病理过程而成为研究的重点.研究生理性及病理性状态下血管生成过程中周细胞相关信号转导通路,对深入理解周细胞的生物学功能及其在相关疾病中的作用有重要意义.     

凋亡及其相关蛋白在肿瘤治疗中的研究进展

凋亡,最初也称生理性或程序性细胞死亡,是与细胞和组织动力学广泛联系的一种基本的生物学现象[1].凋亡可发生于正常细胞生理过程,如细胞生长、分化与老化,亦可作为重要的生物体防御机制,参与损伤修复及恶性细胞的清除,而后者在治疗诱导的肿瘤消退以及肿瘤的发生和演进中发挥重要作用[2-6].诸多生理及病理因素皆可激发凋亡.目前普遍认为,细胞群体的稳定,包括增生、分化和死亡均与凋亡机制的调节密切相关,这些过程中的任何一个功能失调都会导致失控性细胞生长或分化异常.而对抗和逃避凋亡也是肿瘤发生发展的重要机制之一,近年来对凋亡相关蛋白靶向性治疗肿瘤的研究较多,它代表了目前肿瘤研究和治疗的一个重要方向[7-10].本文就此作一简单综述.     

Mitogenic signaling pathways in airway smooth muscle

Increased airway smooth muscle mass has been demonstrated in patients with asthma, bronchopulmonary dysplasia and most recently, cystic fibrosis. These observations emphasize the need for further knowledge of the events involved in airway smooth muscle mitogenesis and hypertrophy. Workers in the field have developed cell culture systems involving tracheal and bronchial myocytes from different species. An emergent body of literature indicates that mutual signal transduction pathways control airway smooth muscle cell cycle entry across species lines. This article reviews what is known about mitogen-activated signal transduction in airway myocytes. The extracellular signal regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI 3-kinase) pathways appear to be key positive regulators of airway smooth muscle mitogenesis; recent studies have also demonstrated specific roles for reactive oxygen and the JAK/STAT pathway. It is also possible that growth factor stimulation of airway smooth muscle concurrently elicits signaling through negative regulatory intermediates such as p38 mitogen-activated protein (MAP) kinase and protein kinase C (PKC) delta, conceivably as a defense against extreme growth.     

应激相关的热休克信号转导通路的研究进展

随着社会的发展和医疗技术的不断进步与完善,人们的健康水平有了大幅度的提高。但急性梗塞(如脑梗、心梗)、感染性疾病(如败血症)等仍有较高的发病率和死亡率。特别是随着我国社会和经济的发展,老年人群的结构比例明显增高,心脑血管疾病和感染引起的疾病将进一步增加。而且随着     

凋亡及其相关蛋白在肿瘤治疗中的研究进展

凋亡,最初也称生理性或程序性细胞死亡,是与细胞和组织动力学广泛联系的一种基本的生物学现象[1].凋亡可发生于正常细胞生理过程,如细胞生长、分化与老化,亦可作为重要的生物体防御机制,参与损伤修复及恶性细胞的清除,而后者在治疗诱导的肿瘤消退以及肿瘤的发生和演进中发挥重要作用[2-6].诸多生理及病理因素皆可激发凋亡.目前普遍认为,细胞群体的稳定,包括增生、分化和死亡均与凋亡机制的调节密切相关,这些过程中的任何一个功能失调都会导致失控性细胞生长或分化异常.而对抗和逃避凋亡也是肿瘤发生发展的重要机制之一,近年来对凋亡相关蛋白靶向性治疗肿瘤的研究较多,它代表了目前肿瘤研究和治疗的一个重要方向[7-10].本文就此作一简单综述.     

Toll-like receptor signaling in the lysosomal pathways

Summary:  The lysosomal pathway digests material received by two main routes, phagocytosis and autophagy. Cells use phagocytosis to ingest extracellular particles by invaginations of the plasma membrane. In autophagy, a double membrane structure isolates portions of the cytoplasm to target it for degradation. During infection, phagocytes use both of these cellular functions to restrict microbial replication and at the same time to orchestrate an appropriate response against the invader. Toll-like receptor recognition of a pathogen initiates an innate immune response against the pathogen that includes production of inflammatory cytokines, upregulation of costimulatory molecules to prime an adaptive immune response, and activation of phagocytosis and autophagy. Signaling through this family of receptors also produces a hybrid response in which proteins that participate in autophagy are recruited to phagosomes, resulting in expedited microbial elimination. In this review, we discuss recent views on how Toll-like receptors direct microbes to final destruction by regulating the different pathways that lead to the lysosome.     

小胶质细胞及其相关炎性信号通路

小胶质细胞作为中枢系统重要的免疫效应细胞,在中枢神经系统损伤及疾病处理中发挥着不可忽视的作用。本文从小胶质细胞的生物学特性及其相关的炎性信号通路（Notch信号通路、Toll样信号通路、AMPK信号通路、NF-κB信号通路）两大方面探讨,以期为临床抗炎药物的开发提供新思路。