基于GEO数据库筛选不明原因复发性流产的枢纽基因及信号通路

目的 利用生物信息学方法筛选不明原因复发性流产(URSA)相关差异表达基因(DEGs)及信号通路,以期为URSA的诊断和治疗提供新思路。方法 从GEO数据库中筛选数据集,利用R软件DESeq 2包筛选DEGs,应用DAVID数据库对DEGs进行GO和KEGG分析,通过STRING数据库构建DEGs的蛋白质-蛋白质相互作用(PPI)网络,再通过Cytoscape软件筛选出URSA的最显著模块及枢纽(Hub)基因,并对其进行可视化处理。采用GSE26787数据集验证Hub基因的差异表达。结果 经筛选共得到432个DEGs,其中121个DEGs上调,311个DEGs下调。GO富集分析显示,DEGs参与细胞分裂、有丝分裂核分裂、姐妹染色单体的凝聚力和信号转导等生物过程(BP);细胞成分(CC)位于纺锤体、染色体着丝粒点、纺锤体两极、中体;分子功能(MF)与蛋白结合、微管结合、受体活性等相关;KEGG富集分析表明,DEGs富集于自然杀伤(NK)细胞介导的细胞毒性、细胞周期、p53信号通路、抗原加工和呈递、精氨酸和脯氨酸代谢通路。通过PPI网络筛选得到与URSA密切相关的5个Hub基因,分别为CC...     

通过生物信息学分析鉴定干燥综合征的关键基因

目的：使用生物信息学方法鉴定干燥综合征（SS）的关键差异表达基因（DEGs）。方法：从基因数据库中下载GSE23117和GSE127952的基因表达谱,用GEO2R在线工具和Venn软件筛选出其中的DEGs。通过DAVID网站进行GO和KEGG分析。使用STRING工具建立蛋白质-蛋白质相互作用（PPI）网络,用Cytoscape软件进行模块分析。结果：在SS标本中总共检测到31个DEGs重叠区域。其中28个上调基因和3个下调基因主要在免疫炎症中起作用。KEGG分析显示DEGs与细胞因子-细胞因子受体相互作用、趋化因子信号通路、阿米巴病和白细胞跨内皮迁移有关。PPI和模块分析显示CXCL9、CXCL11、CXCL13、CCR1、CD69、PTPRC、GPR183、MMP9和IL-10基因显著富集。结论：CXCL9、CXCL11、CXCL13、CCR1、CD69、PTPRC、GPR183、MMP9和IL-10可能与SS的发生和进展有关。     

特应性皮炎的遗传学及免疫学研究进展

特应性皮炎(AD)为遗传过敏性疾病,患者及其家族的基因筛选结果显示,AD与其他炎症性皮肤病、自身免疫疾病存在染色体区域的交迭。候选基因的研究为探讨AD的发病机理提供了新的视野。由皮肤浸润的T细胞、树突状细胞、肥大细胞和血管内皮细胞所产生的多种趋化细胞因子配体(CCL)和受体(CCR)在AD的发病机制中起到了重要作用。细胞因子的不同表达状态和基因识别的高效方法将有助于进一步仔细研究AD的综合特点,也有助于定义AD的诊断标准和治疗。     

CXCR3及其配体与皮肤病

趋化因子作为具有多种生物活性的多肽受到重视，本文回顾了CXC趋化因子受体3及其配体γ干扰素诱导性肽－10，γ干扰素诱导性单核细胞因子和γ干扰素诱导性T细胞α化学趋化因子的结构，它们之间相互作用，生物学功能，受体活化后细胞内信号传导途径以及它们及变态反应性皮肤病，银屑病，部分皮肤肿瘤及结缔组织病的关系。     

CXCR3及其配体与皮肤病

趋化因子作为具有多种生物活性的多肽受到重视。本文回顾了CXC趋化因子受体 3及其配体γ干扰素诱导性肽 10、γ干扰素诱导性单核细胞因子和γ干扰素诱导性T细胞α化学趋化因子的结构、它们之间相互作用、生物学功能、受体活化后细胞内信号传导途径以及它们与变态反应性皮肤病、银屑病、部分皮肤肿瘤及结缔组织病的关系     

HIV感染的分子免疫发病机理

从细胞因子分布型失衡、活化诱导的T细胞凋亡、HIV基因产物的作用、抗原呈递细胞缺陷、粘附受体与趋化因子受体的作用等方面综述了HIV感染的分子免疫发病机理。     

Wnt信号转导通路及其在皮肤肿瘤中的作用

Wnt信号转导通路与胚胎发育及肿瘤发生密切相关。目前认为Wnt通路的组成主要包括：细胞外因子Wnt、跨膜受体卷曲蛋白、散乱蛋白、结肠腺瘤样息肉病基因产物、β-连环蛋白及T细胞因子／淋巴样增强因子等一系列蛋白。细胞外因子Wnt激活的信号与受体结合后，通过胞质蛋白的一系列相互作用，能够使胞浆内β-连环蛋白保持稳定并累积，进而入核与转录因子T细胞因子／淋巴样增强因子联合作用激活靶基因的转录，而且在Wnt信号通路的不同阶段有各种蛋白因子进行调控。Wnt信号通路的异常激活与人类某些肿瘤的发生、发展有关。     

STAT／SOCS在银屑病发病机制中的作用

银屑病的发病可能与异常活化的Th1细胞分泌IFN-γ等细胞因子有关，这些细胞因子主要通过Jak／sTAT信号传导通路实现胞内信息传递，诱导一系列炎症相关基因的过度表达，促使银屑病发生发展。STATl、STAT3、SOCS1、SOCS3在银屑病皮损角质形成细胞内的表达升高，STATl、STAT3的异常活化可以促进细胞过度的分化增殖并抑制细胞凋亡，而SOCSl、SOCS3能抑制Jak／sTAT信号传导通路的信息传递。银屑病角质形成细胞内STAT1、STAT3和SOCS1、SOCS3的表达水平可能是治疗银屑病的潜在药物作用靶点。     

HIV感染的分子免疫发病机理

从细胞因子分布型失衡，活化诱地的Ｔ细胞凋亡，ＨＩＶ基因产物的作用，抗原呈递细胞缺陷，粘附受体与趋化因子肥体的作用等方面综述了ＨＩＶ感染的分子免疫发病机理。     

Dectin-1受体信号通路研究进展

β-葡聚糖是真菌细胞壁的主要成分,近年研究发现,树突状细胞相关性C型植物凝集素-1(dectin-1)受体可作为真菌的主要模式识别受体,通过对β-葡聚糖的识别及信号转导,诱导机体产生一系列的细胞因子和趋化因子,启动免疫功能。Dectin-1受体广泛分布于单核巨噬细胞系统、树突状细胞及中性粒细胞等。本文主要对Dectin-1受体的结构、作用机制和信号通路进行综述。     

采用生物信息学方法筛选和分析白癜风差异表达基因

目的:通过生物信息学方法探索与白癜风进展相关的信号通路和基因。方法:从GEO数据库中下载白癜风芯片检测数据集GSE75819,利用R语言软件中limma包的LMFit和eBayes函数筛选15例印度白癜风患者皮损与非皮损组织间的差异表达基因（DEG）。通过京都基因与基因组数据库（KEGG）、基因本体论（GO）分析和基因...     

Screening of differentially expressed genes and predominant expression of β variable region of T cell receptor in peripheral T cells of psoriatic patients

Psoriasis is a skin disease featuring epithelial cell hyper-proliferation and T cell infiltration. Abnormal T cell immune responses play an important role in psoriatic pathogenesis. To screen differentially expressed genes in T cells of patients with plaque psoriasis, analyze the predominant expression of the β variable region of T cell receptors and discuss the role of T cells in the pathogenesis of psoriasis. High throughput RNA sequencing and Real-time PCR were used. Results: A total of 907 genes were differentially expressed in peripheral T cells of patients with psoriasis. Among them, 695 genes were mapped to the Gene Ontology database, 14 gene terms were significantly enriched, and 418 genes were involved in signaling pathways such as apoptosis, B cell receptor signaling and T cell receptor signaling. TRBV2, TRBV5-7, TRBV6-6/6-9, TRBV12, TRBV24 and TRBV29 were significantly up-regulated in psoriatic patients compared to healthy subjects, among which, TRBV6-6/6-9, TRBV12 and TRBV29 are predominantly expressed in psoriatic patients. Many genes were differentially expressed in T cells of psoriatic patients, especially the TRBV gene family, which were predominantly expressed in T cells and might play an important role in abnormal immune responses of T cells in psoriatic patients.     

Gene Expression Patterns of Cutaneous Squamous Cell Carcinoma and Actinic Keratosis: Biomarkers Screening for Skin Disease Diagnosis

BackgroundActinic keratosis (AK) was an intraepidermal tumor which caused by ultraviolet irradiation-induced skin damage.ObjectiveThe aim was to screen biomarkers for development of skin disease by comparing the gene expression profiles between cutaneous squamous cell carcinoma (CSCC) and AK.Methods{"type":"entrez-geo","attrs":{"text":"GSE45216","term_id":"45216"}}GSE45216 with 30 cutaneous squamous cell carcinoma patients and 10 actinic keratosis patients were downloaded and significance analysis of microarrays was processed to screen differently expressed genes (DEGs). Fisher''s exact test was processed for DEGs enrichment. Pathway relationship network systematically reflected the signal conduction and synergism between enriched pathways based on Kyoto Encyclopedia of Genes and Genomes database. Gene co-expression network was constructed according to gene expression data. Quantitative real-time-PCR was used to verify screened biomarkers.ResultsTotal 410 DEGs were screened and enriched into various functions, such as signal transduction and negative regulation of apoptotic process. They also participated into cytokine-cytokine receptor interaction and focal adhesion. The pathway relationship network was constructed with 27 nodes. Hub nodes with higher degree of this network were mitogen-activated protein kinase signaling pathway and apoptosis. The gene co-expression network was constructed with 39 nodes. Thereinto, hub node was ELOVL fatty acid elongase. The expression levels of ELOVL4 and HPGD were significantly higher in CSCC samples than that in AK samples, while the expression levels of INHBA and LAMC2 in CSCC samples were significantly lower than that in AK samples.ConclusionThese screened genes, including ELOVL4, HPGD, INHBA and LAMC2, played important roles in transformation from AK to CSCC.     

Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling

IL-13 has been implicated in the pathogenesis of allergic diseases, including atopic dermatitis (AD). However, a direct role of IL-13 in AD has not been established. We aimed to develop an inducible transgenic model in which IL-13 can be expressed in the skin and to define the resulting dermal phenotype and mechanisms involved. The keratin 5 promoter was used with a tetracycline-inducible system to target IL-13 to the skin. The clinical manifestations, dermal histology, cytokine gene regulation, and systemic immune responses in the transgenic mice were assessed. IL-13 was produced exclusively in the skin and caused a chronic inflammatory phenotype characterized by xerosis and pruritic eczematous lesions; dermal infiltration of CD4+ T cells, mast cells, eosinophils, macrophages, and Langerhans cells; upregulation of chemokine and cytokine genes, including thymic stromal lymphopoietin; and skin remodeling with fibrosis and increased vasculature. The dermal phenotype was accompanied by elevated serum total IgE and IgG1 and increased production of IL-4 and IL-13 by CD4+ cells from lymphoid tissues and peripheral blood mononuclear cells. IL-13 is a potent stimulator of dermal inflammation and remodeling and this transgenic model of AD is a good tool for investigating the underlying mechanisms in the pathogenesis of AD.     

皮肤黑素瘤中囊泡胺转运蛋白1的免疫浸润景观和预后价值的鉴定

 目的 评估囊泡胺转运蛋白1(VAT1)在皮肤黑素瘤（SKCM）中的免疫浸润景观和预后价值。方法采用基因表达谱交互分析(GEPIA)方法分析VAT1在SKCM中的mRNA表达,利用人类蛋白图谱(HPA)进行蛋白质水平的验证。通过GEPIA的生存模块评估VAT1对SKCM患者生存的影响,并利用GSE98394数据集进行验证。从TCGA下载SKCM的数据集,采用单因素Cox分析评估VAT1与生存率的关系,利用GSE98394数据集进行验证。利用肿瘤免疫评估资源(TIMER)检测SKCM中免疫浸润水平与VAT1表达以及SKCM累积存活率的相关性。使用CIBERSORT的相关模块进一步探讨VAT1与肿瘤免疫浸润的相关性。结果在SKCM中,VAT1的mRNA和蛋白质表达水平较正常人高。生存曲线和单因素Cox分析显示VAT1表达上调是预后不良的因素。VAT1的表达水平与SKCM中CD8+T细胞、巨噬细胞、中性粒细胞和树突状细胞的浸润水平呈负相关（P均<0.01）。此外,VAT1高表达组与低表达组相比,驻留记忆CD4+T细胞、活化的记忆CD4+T细胞、M1巨噬细胞、驻留肥大细胞、调节性T细胞、活化的NK细胞、浆细胞等免疫细胞组成比例上差异均有统计学意义（P均<0.05）。结论VAT1是SKCM潜在的预后生物标志物,且与免疫浸润有关。     

Histamine-containing mast cells and their relationship to NGFr-immunoreactive nerves in prurigo nodularis: a reappraisal

The mast cell, which is a histamine-containing cell, has been found to have far more functions in skin inflammation than hitherto understood. To investigate the appearance of mast cells in prurigo nodularis, histamine immunohistochemistry in combination with nerve growth factor receptor (NGFr) double-staining as well as electron microscopic studies were performed. The results revealed that the histamine-containing cell number was increased in the lesional dermis. The mast cell size was also increased and the shape had become more dendritic. They tended to contact the epidermis and even infiltrated into it. In the histamine and NGFr double-staining, both an increased histamine-containing mast cell number and an increased number of NGFr-immuno-reactive nerve fiber profiles were revealed in the upper dermis of the prurigo nodularis lesional skin. Mast cells were seen in close vicinity to NGFr-positive nerves and sometimes even seemingly to contact single nerve fibers. At the ultrastructural level, it is obvious that the mast cell bodies become larger, having more abundant cytoplasm and organelles (e.g. mitochondria), but comparatively fewer characteristic granules. Mast cells were often observed to sprout long dendrites, with or without granules. The cells were also frequently seen to contact other cell types, and a mast cell infiltration into the epidermis was also found. The statistical results of mast cell numbers showed a significant increase in prurigo nodularis lesional skin compared to the normal controls. The present results further indicate that mast cells, together with cutaneous nerve fibers, are actively involved in the pathogenesis of the disease.     

Differential expression and function of Toll-like receptors in Langerhans cells: comparison with splenic dendritic cells

Toll-like receptors are key elements in pathogen recognition by the host immune system. Although the expression pattern and functions of Toll-like receptors have been studied in a variety of cytokine-induced dendritic cells, it remains unknown whether Toll-like receptor stimulation influences maturation and cytokine production of authentic Langerhans cells. We purified murine epidermal Langerhans cells along with splenic dendritic cell using a panning method. Langerhans cells expressed Toll-like receptor 2, 4, and 9 but not 7, the pattern of which suggests Langerhans cells are the closest to one of the murine dendritic cell lineage, CD11c+11b+8 alpha-4-. Then we stimulated Toll-like receptor 2, 4, and 9 with the corresponding ligand, Staphylococcus aureus Cowan 1, lipopolysaccharide, and CpG, and found that all of these stimuli upregulated expression of B7-1 and B7-2 in splenic dendritic cells but not in Langerhans cells. As in human Langerhans cells, stimulation of murine Langerhans cells with Staphylococcus aureus Cowan 1, lipopolysaccharide, and CpG overall resulted in T helper 1-polarizing cytokine production (namely, induction of IL-12p40 and inhibition of TARC (thymus and activation-regulated chemokine)/CCL17). Exceptionally, lipopolysaccharide exhibited no effect on IL-12p40 production by Langerhans cells and inhibited IL-12p40 production by splenic dendritic cells. These results may represent the functional heterogeneity between Langerhans cells and splenic dendritic cells, and are important for better understanding of innate immunity to bacterial infections differentially regulated in the skin and spleen. MeSH terms: Toll-like receptors, Langerhans cells, dendritic cells.     

IL-22在银屑病发病机制中的作用

研究显示,白介素22能促进上皮细胞产生异常炎症介质.白介素22是一种重要的细胞因子,主要由Th17细胞产生,参与炎性细胞浸润,细胞增殖,细胞迁移及防御作用等.在银屑病皮损中,白介素22水平升高,其通过与角质形成细胞表面白介素22受体结合,导致细胞因子和炎症介质改变,起到趋化炎性细胞,促角质形成细胞增殖,抑制角质形成细胞分化的作用,是银屑病发病中重要的细胞因子.介绍银屑病皮疹中白介素22促进炎症细胞浸润和角质化细胞增殖的作用,以及银屑病中角质形成细胞活化产物的变化并通过白介素22治疗银屑病的疗效应证实其作用.

Abstract：

Studies have shown that IL-22 could promote epithelial cells to produce abnormal inflammatory mediators.IL-22 is an important cytokine mainly produced by Th17 cells and participates in inflammatory cell infiltration, cell proliferation, migration, defense, and so on.In psoriatic lesions, the expression level of IL-22 is elevated.By binding to its receptor on the surface of keratinocytes, IL-22 can alter the expressions of cytokines and inflammatory mediators, induce the chemotaxis of inflammatory cells, promote the proliferation and inhibit the differentiation of keratinocytes.Therefore, IL-22 is an important cytokine in the pathogenesis of pasoriasis.This paper describes the upregulatory effect of IL-22 on inflammatory cell infiltration and keratinocyte proliferation, alterations in products of activated keratinocytes in psoriasis, as well as the role of IL-22 in the pathogenesis of psoriasis which has been evidenced by the therapeutic effect of IL-22 on psoriasis.