Alveolar echinococcosis (AE) is a zoonotic parasitic disease caused by the infection of Echinococcus multilocularis (E. multilocularis) larvae. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) produces inhibitory signals and induces T cell exhaustion, thereby inhibiting the parasiticidal efficacy of the liver immune system. Therefore, the purpose of this study is to explore how T-cell exhaustion contributes to AE and whether blocking CTLA-4 could reverse T cell exhaustion. Here we discovered that the expression of CTLA-4 was increased in the infiltrating margin around the lesion of the liver from AE patients by using western blot and immunohistochemistry assay. Multiple fluorescence immunohistochemistry identified that CTLA-4 and CD4/CD8 molecules were co-localized. For in vitro experiments, it was found that the sustained stimulation of E. multilocularis antigen could induce T cell exhaustion, blocking CTLA-4-reversed T cell exhaustion. For in vivo experiments, the expression of CTLA-4 was increased in the liver of E. multilocularis-infected mice, and the CTLA-4 and CD4/CD8 molecules were co-localized. Flow cytometry analysis demonstrated that the percentages of both CD4+ T cells and CD8+ T cells in the liver and peripheral blood were significantly increased and induced T exhaustion. When the mice were treated with anti-CTLA-4 antibodies, the number and weight of the lesions decreased significantly. Meanwhile, the flow cytometry results suggested that blocking CTLA-4 could effectively reverse T cell exhaustion and reactivate immune function. Our work reveals that blocking CTLA-4 could effectively reverse the T cell exhaustion caused by E. multilocularis and could be used as a novel target for the treatment of AE.

Objective: To investigate and analyze the effects of LncRNA CASC2 targeting NF-kB p65 on the proliferation, apoptosis and invasion of glioma cells. Methods: We detected the expression of CASC2 in gliomas and healthy brain tissue. The U87 cells were cultivated and transfected with CASC2 mimics and CASC2-NC mimics, while the control group was not transfected. The mRNA expression levels of CASC2, NF-kB P65, as well as cell proliferation, apoptosis, and invasion in each group were detected, and the targeting relationship between CASC2 and NF-kB P65 was verified by dual luciferase assay. Results: The relative expression degree of CASC2 in malignant glioma tissue was significantly lower than that in normal brain tissue (P<0.05). The relative expression of CASC2 in the group of CASC2 mimics was apparently increased (P<0.05), while the relative mRNA expression of NF-kB p65 was significantly decreased (P<0.05). According to CCK-8 experimental data, the absorbance value of the CASC2 mimics group at 450 nm wavelength at 24 h, 48 h and 72 h respectively, were significantly lower than that in the CASC2-NC mimics group and the control group (P<0.05). The test results of flow cytometry showed that the apoptosis rate in the CASC2 mimics group was significantly increased compared to the CASC2-NC mimics group and the control group (P<0.05). In addition, the Transwell detection experiment showed that the amount of cell invasion and migration in the CASC2 mimics group decreased significantly compared to that in the CASC2-NC mimics group and the control group (P<0.05). Conclusion: CASC2 expression was abnormally decreased in glioma tissues, which can inhibit the proliferation and invasion of glioma cell line U87 by targeting the expression of NF-kB p65.

目的:检测高原环境(海拔4 500m)大鼠脑损伤周围局部组织内不同时间点TNF-α和IL-1β蛋白的表达及动态变化;同期与西宁地区(海拔2 200m)大鼠脑损伤周围局部组织各对应时间点相同因子蛋白表达比较,探讨高原环境对大鼠脑损伤局部炎性反应的影响.方法:将健康SD雄性大鼠60只平均、随机分为高原环境组和西宁地区组.每组随机抽取25只建立大鼠创伤性颅脑损伤模型(造模组),各组剩余5只单纯暴露硬膜不打击(对照组).颅脑损伤后第1天、3天、5天、7天、14天应用酶联免疫吸附法检测各组脑损伤大鼠周围组织内TNF-α和IL-1β蛋白含量及变化.结果:高原环境造模组TNF-α、IL-1β第1天、3天、5天、7天、14天表达均比西宁地区造模组同时间点增加,差异有统计学意义(P＜0.05),第14天高原环境造模组TNF-α、IL-1β含量未完全恢复至对照组水平,差异有统计学意义(P＜0.05).结论:高原环境加重了大鼠脑损伤周围局部组织的炎性反应且消退缓慢.

颅脑创伤是临床常见的多发病,高原地区具有高海拔、低氧、低气压、低温等特点,为了适应高原环境的低氧特点,长时间在高原地区生活,大脑在发育过程中需要在功能与结构上都进行改变,因此颅脑损伤后患者的病理生理也较之前发生改变.高原颅脑损伤模型的建立作为颅脑损伤研究的基础,是研究颅脑损伤的关键.文章旨在对高原环境下颅脑损伤模拟方法和各种颅脑损伤模型的建立方法及特点进行综述,以期为临床提供参考价值.