Moderate protection is induced by a chimeric protein composed of leucine aminopeptidase and cathepsin L1 against Fasciola hepatica challenge in sheep

Leucine aminopeptidase (FhLAP) and cathepsin L1 (FhCL1) of Fasciola hepatica play a critical role in parasite feeding, migration through host tissue, and immune evasion. These antigens have been tested for immune protection as single components with variable degrees of success. The chimeric-protein approach could improve protection levels against fasciolosis. Previously, we reported the design and construction of a chimeric protein composed of antigenic sequences of FhLAP and FhCL1 of F. hepatica. The goal of the present study was to express and evaluate the immune-protective capacity of this chimeric protein (rFhLAP-CL1) in sheep. Animals were randomly allocated into five groups with five animals in each group. Groups 1, 2 and 3 were immunized twice with 100 μg, 200 μg and 400 μg of rFhLAP-CL1 emulsified with Quil A adjuvant, whereas groups 4 and 5 were the adjuvant control and infection control groups, respectively. The animals were then challenged with 200 metacercariae two weeks after the rFhLAP-CL1 booster. The fluke burden was reduced by 25.5%, 30.7% (p < 0.05) and 46.5% (p < 0.01) in sheep immunized with 100 μg, 200 μg and 400 μg of chimeric protein, respectively, in comparison to the infection control group. There was a reduction of 22.7% (p < 0.05) and 24.4% (p < 0.01) in fecal egg count in groups 2 and 3, respectively, compared to the infection control group. Sheep immunized with chimeric protein produced F. hepatica excretion-secretion product-specific total IgG antibody, which were increased after challenge. Moreover, the levels of rFhLAP-CL1-specific IgG1 and IgG2 isotypes in immunized sheep increased rapidly two weeks after the first immunization and were significantly more elevated than those of the control groups, indicating a mixed Th1/Th2 response. This is a preliminary evaluation of the chimeric protein rFhLAP-CL1 as a possible immunogen against F. hepatica infection in sheep.     

嗜肺军团菌致病性与效应蛋白的研究进展

嗜肺军团菌是一种可以引起军团菌肺炎和庞蒂亚克热的兼性胞内病原菌，主要侵染阿米巴原虫和人类巨噬细胞。该菌在宿主胞内能依靠Dot/Icm IVB型分泌系统产生的效应蛋白成功逃避溶酶体的降解。本文主要对嗜肺军团菌的致病物质、胞内存活与增殖机制及其效应蛋白的生物学功能进行综述，详细介绍嗜肺军团菌的毒力因子与致病机制，为军团病防治的研究提供新思路，也为其他胞内病原菌所致感染性疾病的研究提供重要的借鉴意义。     

Cerebrovascular inflammation promotes the formation of brain metastases

Brain metastases are the most prevalent intracranial malignancy. Patient outcome is poor and treatment options are limited. Hence, new avenues must be explored to identify potential therapeutic targets. Inflammation is a known critical component of cancer progression. Intratumoral inflammation drives progression and leads to the release of circulating tumor cells (CTCs). Inflammation at distant sites promotes adhesion of CTCs to the activated endothelium and then initiates the formation of metastases. These interactions mostly involve cell adhesion molecules expressed by activated endothelial cells. For example, the vascular cell adhesion molecule-1 (VCAM-1) is known to promote transendothelial migration of cancer cells in different organs. However, it is unclear whether a similar mechanism occurs within the specialized environment of the brain. Our objective was therefore to use molecular imaging to assess the potential role of VCAM-1 in promoting the entry of CTCs into the brain. First, magnetic resonance imaging (MRI) and histological analyses revealed that cerebrovascular inflammation induced by intracranial injection of lipopolysaccharide significantly increased the expression of VCAM-1 in the Balb/c mouse brain. Next, intracardiac injection of 4T1 mammary carcinoma cancer cells in animals with cerebrovascular inflammation yielded a higher brain metastasis burden than in the control animals. Finally, blocking VCAM-1 prior to 4T1 cells injection prevented this increased metastatic burden. Here, we demonstrated that by contributing to CTCs adhesion to the activated cerebrovascular endothelium, VCAM-1 improves the capacity of CTCs to form metastatic foci in the brain.     

加味香砂六君子汤对胃癌大鼠的实验研究

目的:探究并分析加味香砂六君子汤通过抑制Wnt信号通路对胃癌大鼠桩蛋白(paxillin)、大鼠凋亡相关蛋白(RelA)表达的影响。方法:选取健康成年Wistar大鼠120只,按照随机数字表法分为对照组和观察组,每组60只,对2组大鼠进行胃癌造模处理,对照组大鼠又随机分为未处理组、处理(生理盐水)后8周组、处理(生理盐水)后12周组,每组20只。观察组大鼠又随机分为未处理组、处理(汤药)后8周组、处理(汤药)后12周组,每组20只。观察2组大鼠处理前、处理后8周、处理后12周paxillin、RelA。结果:2组大鼠处理前后体质量差异有统计学意义(P<0.05),2组大鼠处理前体质量比较差异无统计学意义(P>0.05),处理后,2组大鼠体质量有所降低,但观察组大鼠降低程度明显小于对照组(P<0.05);2组大鼠处理前后wnt-1、paxillin、RelA水平差异有统计学意义(P<0.05),2组大鼠处理前wnt-1、paxillin、RelA水平比较差异无统计学意义(P>0.05),处理后,2组大鼠wnt-1、paxillin、RelA水平呈降低趋势,但观察组大鼠wnt-1、paxillin、RelA水平明显小于对照组,差异有统计学意义(P<0.05)。结论:加味香砂六君子汤能有效通过抑制wnt以降低胃癌大鼠paxillin、RelA的表达。     

The impact of current treatment modalities on the outcomes of patients with melanoma brain metastases: A systematic review

Patients with melanoma brain metastases (MBM) still have a very poor prognosis. Several treatment modalities have been investigated in an attempt to improve the management of MBM. This review aimed to evaluate the impact of current treatments for MBM on patient- and tumor-related outcomes, and to provide treatment recommendations for this patient population. A literature search in the databases PubMed, Embase, Web of Science and Cochrane was conducted up to January 8, 2019. Original articles published since 2010 describing patient- and tumor-related outcomes of adult MBM patients treated with clearly defined systemic therapy were included. Information on basic trial demographics, treatment under investigation and outcomes (overall and progression-free survival, local and distant control and toxicity) were extracted. We identified 96 eligible articles, comprising 95 studies. A large variety of treatment options for MBM were investigated, either used alone or as combined modality therapy. Combined modality therapy was investigated in 71% of the studies and resulted in increased survival and better distant/local control than monotherapy, especially with targeted therapy or immunotherapy. However, neurotoxic side-effects also occurred more frequently. Timing appeared to be an important determinant, with the best results when radiotherapy was given before or during systemic therapy. Improved tumor control and prolonged survival can be achieved by combining radiotherapy with immunotherapy or targeted therapy. However, more randomized controlled trials or prospective studies are warranted to generate proper evidence that can be used to change the standard of care for patients with MBM.     

热疗对肿瘤免疫微环境中免疫细胞及免疫相关细胞因子的影响

随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。