疏通化纤丸对小鼠免疫功能的调节作用

目的观察疏通化纤丸对小鼠免疫功能的影响。方法以地塞米松引起小鼠免疫功能低下 ,以左旋咪唑作阳性对照 ,测定疏通化纤丸对免疫功能正常和低下小鼠巨噬细胞吞噬功能、血清溶血素含量以及ConA诱导T淋巴细胞增殖的作用。结果疏通化纤丸能明显提高免疫功能正常和低下小鼠的廓清指数、吞噬指数 ,能促进ConA诱导的正常小鼠脾淋巴细胞的增殖 ,而左旋咪唑仅对免疫低下的小鼠才有提高以上指标的功能。结论疏通化纤丸对机体免疫功能具有显著的提高作用。     

辅助性T淋巴细胞17在肝细胞癌发生发展中的作用

肝细胞癌是世界上最常见的恶性肿瘤之一,对于如何提高肝细胞癌治愈率和降低其复发及转移一直是人们研究的重点。辅助性T淋巴细胞(Th)17是一种重要的CD4+Th亚型,在感染、自身免疫反应及肿瘤微环境中具有重要作用。介绍了Th17及其相关细胞因子的发现,归纳了其在肝细胞癌发生及进展过程中的作用机制及相关临床意义,为Th17在肝细胞癌治疗新靶点及判断预后方面提供一些见解。     

Clinical significance of variations in levels of Epstein-Barr Virus (EBV) antigen and adaptive immune response during chronic active EBV infection in children

Abstract

Pediatric patients were recruited to analyze differences in Epstein-Barr virus (EBV) copy numbers and adaptive immune reactions in children with chronic active vs acute EBV infection (CAEBVI vs AEBVI), as well as to examine the relationship between these parameters and the pathogenesis of CAEBVI. Fluorescent qPCR was used to assess EBV-DNA levels, while ELISA, antibody affinity, flow cytometry, and heterophil agglutination (HA) assays were used to evaluate patient EBV-adaptive humoral and cellular immunity. Lastly, ELISPOT was employed to assess interferon (IFN)-γ secretory functions of EBV-specific cytotoxic T-lymphocytes (CTL) as a marker of subject EBV-specific adaptive cellular immunity. The results indicated that, compared with AEBVI patients or normal children, there was a dramatic elevation in viral copy levels, viral capsid antigen (VCA)-IgA, early antigen (EA)-IgA, and EA-IgG, but a lack of EBV nuclear antigen (EBNA)-IgG and a negative HA in CAEBVI patients (p?<?0.01). These subjects also had decreased CD4⁺, CD8⁺ (naïve), CD8⁺CD38⁺, and effective memory T-lymphocyte levels compared with AEBVI patients (p?<?0.01), and decreased EBV-specific CTL function compared with normal children (p?<?0.01). These results suggest that there is a disturbance in EBV antigen availability and in both the adaptive humoral and cellular immune responses in patients with CAEBVI, and that these outcomes may be associated with the chronic active re-infection process itself associated with CAEBVI.     

Group sequential enrichment design incorporating subgroup selection

An important component of clinical trials in drug development is the analysis of treatment efficacy in patient subgroups (subpopulations). Because of concerns of multiplicity and of the small sample sizes often involved, such analyses can present substantial statistical challenges and may lead to misleading conclusions. As a confirmatory seamless phase II/III design, we propose an adaptive enrichment group sequential procedure whereby resources can be concentrated on subgroups most likely to respond to treatment. Stopping boundaries are defined through upper and lower spending functions. The procedure is presented in terms of the efficient score, enabling the analysis of normal, binary, or time‐to‐event data. It addresses the dilution effect by eliminating populations at the first stage that appear likely to derive no therapeutic benefit. It subsequently proceeds with the definitive assessment of treatment efficacy among the remaining pooled populations using a group sequential design. The procedure provides strong protection of familywise type I error rate, and we employ a bootstrap algorithm to obtain point and interval estimates that are adjusted for the selection bias. We give examples to demonstrate how the design is used. We make comparisons with adaptive two‐stage combination test procedures and with a group sequential test that does not account for the presence of subgroups. Numerical results show that the procedure has high power to detect subgroup‐specific effects and the use of multiple interim analysis points can lead to substantial sample size savings. Copyright © 2013 John Wiley & Sons, Ltd.     

Herpesvirus entry mediator (HVEM) attenuates signals mediated by the lymphotoxin β receptor (LTβR) in human cells stimulated by the shared ligand LIGHT

Signals mediated by members of the tumor necrosis factor receptor superfamily modulate a network of diverse processes including initiation of inflammatory responses and altering cell fate between pathways favoring survival and death. Although such pathways have been well-described for the TNF-α receptor, less is known about signaling induced by the TNF superfamily member LIGHT and how it is differentially altered by expression of its two receptors LTβR and HVEM in the same cell. We used cell lines with different relative expression of HVEM and LTβR to show that LIGHT-induced signals mediated by these receptors were associated with altered TRAF2 stability and RelA nuclear translocation. Production of the inflammatory chemokine CXCL10 was primarily mediated by LTβR. Higher expression of HVEM was associated with cell survival, while unopposed LTβR signaling favored pathways leading to apoptosis. Importantly, restoring HVEM expression in cells with low endogenous expression recapitulated the phenotype of cells with higher endogenous expression. Together, our data provide evidence that relative expression of HVEM and LTβR modulates canonical NF-κB and pro-apoptotic signals stimulated by LIGHT.     

复发性口腔溃疡免疫细胞的效应

复发性口腔溃疡是口腔科常见多发性疾病,与多种因素导致的自体免疫失衡有关。表现为免疫细胞活性和数量上的改变,特别是高表达或不正常表达CD4+、 CD8+细胞以及 CD4+/ CD8+的改变,并伴有多种细胞因子的变化,包括 IL-2 、IL-6、IL-8﹑IL-10、INF-γ 和TNF-α等多种细胞因子的异常表达以及相关细胞因子的基因突变导致的基因多态性。T淋巴细胞介导的细胞免疫在复发性口腔溃疡疾病的发生、发展过程中起重要作用。     

Synthetic immunostimulatory oligonucleotides in experimental and clinical practice

BackgroundOligonucleotides belong to a class of macromolecules with great potential for research and various therapeutic applications. Their mechanisms of action are extremely diverse, although they are rather homogeneous in composition. Single-stranded oligodeoxynucleotides are not only inhibitors of gene expression, but their CpG sequence motifs may activate the innate immune response. Recent progress made in preclinical and clinical testing, as well as the case of the most recently discovered RNA interference technology, will help to overcome efficacy problems of the previous approaches of the ‘standard therapy’ of such diseases as tumors and various infections.MethodsThe aim of this article is to present various therapeutic aspects of oligonucleotides, and to review the most significant therapeutic applications of synthetic oligonucleotides. This paper presents a comprehensive review of current literature on various therapeutic properties of synthetic oligonucleotides.ConclusionsThe available results gathered from preclinical and clinical studies suggest that TLR9-targeted therapy of oligonucleotides can stimulate both innate and adaptive immunity. It also appears that CpG ODNs are generally safe, although moderate adverse effects, based on a backbone-related mechanism have been reported. The presented studies demonstrate that adjuvant CpG ODN can unify an immune response that leads to enhanced antigen-specific Ab formation. CpG ODN may therefore provide a unique approach to enhancing the efficacy of immunization, including the strengthening of antitumor immunity.     

Statins can induce myasthenia gravis

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are commonly prescribed for prevention of cardiovascular morbidity. A rare side effect of statin medication is the induction of autoimmune illnesses, including myasthenia gravis (myasthenia). Here we present two patients with seropositive myasthenia that developed 4 weeks after initiation of atorvastatin, increasing the total reported patients to seven. Reviewing recent literature we highlight the connections between statins, auto-immunity and myasthenia. Statins may favour T-cell phenotypes that reduce cell-mediated immunity but could increase antibody-mediated humoral immunity.