健脾益气解毒方联合化疗治疗晚期结直肠癌的疗效评价

目的:探讨健脾益气解毒方联合化疗治疗晚期结直肠癌的疗效及其对患者免疫功能、生活质量的影响。方法:选择2010年6月至2015年12月在我院进行治疗的晚期结直肠癌患者80例,随机分为两组,每组40例。对照组患者接受FOLFIRI化疗,观察组患者在对照组基础上服用健脾益气解毒汤。比较两组患者治疗的临床疗效、治疗前后机体免疫功能、生活质量的变化情况及治疗期间不良反应的发生情况。结果:治疗后,观察组患者治疗的疾病控制率、CD4~+以及CD4~+/CD8~+、KPS评分均显著高于对照组(P0.05),中医证侯评分及脾虚证候评分、白细胞减少、Ⅰ-Ⅱ级中性粒细胞减少以及肝损伤等不良事件的发生率均显著低于对照组(P0.05)。结论:健脾益气解毒汤联合化疗治疗晚期结直肠癌可有效提高临床疗效,改善患者免疫功能及生活质量。     

Dynamic expression of immune response genes in the sea bass, Dicentrarchus labrax, experimentally infected with the monogenean Diplectanum aequans

The sea bass, Dicentrarchus labrax, is one of the most extensively farmed marine fishes in the Mediterranean. Under the high-density condition common in aquaculture, the monogenean gill parasite Diplectanum aequans can cause significant economic losses. This study used real-time quantitative PCR to investigate the dynamic expression of immune response genes in sea bass infected with Diplectanum aequans. The target genes, interleukin-1 (IL-1beta, transforming growth factor (TGF-beta and T-cell receptor (TCR-beta), were studied in the gills and spleen of the sea bass from the first day of infection until thirty days post- infection. Our results showed that there was an increase in IL-1beta gene expression in the spleen and gills and in TGF-beta gene expression in the gills of infected fish. These results show that parasitic infection induced a local inflammatory reaction and that reaction was restricted to the site of infection. Finally, the absence of relationship between TCR-beta expression and the parasitic infection suggests that the adaptive immune system is not involved in the response against this parasite.     

BALB/c突变无毛小鼠特异性免疫功能的研究

目的　BALB c突变无毛小鼠的皮肤和被毛结构的突变是否影响机体的免疫功能 ,为此研究其免疫功能。方法　通过流式细胞仪和ELISA方法。对特异性免疫指标CD4+ 、CD3+ 、CD8+ 、CD19+ 、IgG进行检测。结果　各项指标雌雄之间差异不显著 ,无毛小鼠的各项指标均低于其他表型的指标。各组之间方差分析结果 :CD8+ 差异显著 ,其他指标差异不显著。IgG抗体的吸光度的结果 ,三种表型之间差异不显著。结论　该小鼠的皮肤和被毛突变对免疫功能有一定的影响。     

Alteration of Toll-like receptor 4 activation by 4-hydroxy-2-nonenal mediated by the suppression of receptor homodimerization

Toll-like receptors (TLRs) detect invading microbial pathogens and initiate immune responses as part of host defense mechanisms. They also respond to host-derived substances released from injured cells and tissues to ensure wound healing and tissue homeostasis. Dysregulation of TLRs increases the risk of chronic inflammatory diseases and immune disorders. Inflammatory events are often accompanied by oxidative stress, which generates lipid peroxidation products such as 4-hydroxy-2-nonenal (4-HNE). Therefore, we investigated if 4-HNE affects TLR activation. We found that 4-HNE blocked LPS (a TLR4 agonist)-induced activation of NFκB and IRF3 as well as expression of IFNβ, IP-10, RANTES, and TNFα. To investigate the mechanism of inhibition by 4-HNE, we examined its effects on TLR4 dimerization, one of the initial steps in TLR4 activation. 4-HNE suppressed both ligand-induced and ligand-independent receptor dimerization. The thiol donors, DTT and NAC, prevented the inhibitory effects of 4-HNE on TLR4 dimerization, and LC–MS/MS analysis showed that 4-HNE formed adducts with cysteine residues of synthetic peptides derived from TLR4. These observations suggest that the reactivity of 4-HNE with sulfhydryl moieties is implicated in the inhibition of TLR4 activation. Furthermore, inhibition of TLR4 activation by 4-HNE resulted in down-regulation of the phagocytic activity of macrophages. Collectively, these results demonstrate that 4-HNE blocks TLR4-mediated macrophage activation, gene expression, and phagocytic functions, at least partly by suppressing receptor dimerization. They further suggest that 4-HNE influences innate immune responses at sites of infection and inflammation by inhibiting TLR4 activation.     

Expression and function of T cell homing molecules in Hodgkin’s lymphoma

Circulating T lymphocytes enter a tissue if they express appropriate chemokine receptors and adhesion molecules to engage ligands presented at this site. To aid rational development of T cell-based therapies for Hodgkin's lymphoma (HL), we have assessed the expression and function of homing receptors on tumour-infiltrating T cells in HL and compared them with T cells from unaffected lymph nodes and colorectal cancer tissue. Chemokine receptors CXCR3, CXCR4 and CCR7 were expressed on a large proportion of T cells within HL tissue and mediated chemotaxis to purified chemokine. The corresponding ligands (CXCL10, CXCL12, CCL21) were expressed on the malignant cells and/or vascular endothelium. Adhesion molecules including CD62L were widely expressed on HL-derived T cells and their corresponding ligands were detected on vessels within the tumour. This homing phenotype was distinct from T cells isolated from colorectal cancer, but matched closely the phenotype of T cells from unaffected lymph nodes. Thus, T cell recruitment to HL resembles entry of na?ve/central memory T cells into normal lymph nodes. This has important implications for current approaches to treat HL using T cells activated and expanded in vitro that lack CCR7 and CD62L expression.     

红色诺卡氏菌的生物活性

为了考察红色诺卡氏菌菌体(NC)的生物活性, 通过一定浓度的NC对小鼠灌胃给药, 检测其毒性及对免疫器官、巨噬细胞(MΦ)吞噬功能的影响和对肉瘤S180抑制作用。结果表明小鼠口服NC, LD50>10 g/kg; NC明显增加小鼠胸腺脾脏重量、提升白细胞数量和提高小鼠MΦ的吞噬活性; 对小鼠腹腔MΦ具有明显的激活作用, 激活了的MΦ能增强抑杀白色念珠菌作用, 正常的小鼠MΦ也有一定的杀菌作用, 两者差异显著; 对小鼠S180腹水型转实体瘤具有明显的抑制作用。由此得出的结论是, NC毒性低, 能显著增强机体     

Selenium supplementation influences growth performance, antioxidant status and immune response in lambs

To investigate and compare the effect of inorganic and organic Se supplementation, 18 male lambs (24.68 ± 2.89 kg mean body weight, about 8–9 months of age) were divided into three groups of six animals in each, following randomized block design. While animals in the control group (Gr I) were fed a standard TMR containing 195 g/kg crushed maize grain, 175.5 g/kg soybean meal, 260 g/kg wheat bran, 13 g/kg mineral mixture (without Se), 6.5 g/kg common salt and 350 g/kg wheat straw, animals in Gr II and Gr III were additionally supplemented with 0.15 mg Se/kg of diet through sodium selenite (inorganic Se) and Jevsel-101 (organic Se), respectively. Experimental feeding was done for a period of 90 days. To assess the humoral immune response, all the lambs were intramuscularly inoculated with a single dose (2 mL) of Haemorrhagic septicaemia oil adjuvant vaccine on day 0; and blood samples were collected on day 0, 30, 60 and 90. Supplementation of Se had no effect on serum total cholesterol, total protein, albumin, globulin, albumin:globulin ratio, T₃, T₄, T₄:T₃ ratio; serum Ca and P levels and SGOT and SGPT activity. However, there was a significant increase in the serum Se level, RBC GSH-Px activity and humoral immune response in both the Se supplemented groups as compared to control group. Average daily gain (g) was highest (110) in Gr III, followed by Gr II (98.2) and lowest in Gr I (89.1). Thus, supplementation of organic as well as inorganic Se was found to improve the growth rate, humoral immune response and antioxidant status of the lambs; and between two sources, organic Se was more effective than inorganic Se.     

Effect of natural or vaccine-induced porcine circovirus type 2 (PCV2) immunity on fetal infection after artificial insemination with PCV2 spiked semen

The objectives of this study were to determine if vaccination against porcine circovirus type 2 (PCV2) or previous PCV2 infection of the dam are sufficient to prevent fetal infection when dams are artificially inseminated with PCV2-spiked semen. Nine sows (Sus domestica) were allocated into three groups of three dams each: The PCV2 naïve negative control Group 1 was artificially inseminated with extended PCV2 DNA negative semen during estrus, whereas the extended semen used in the vaccinated Group 2 (PCV2 vaccine was given 8 wk before insemination) and PCV2-exposed Group 3 (infected with PCV2 12 wk before insemination) was spiked with 5 mL of PCV2 inoculum with a titer of 10^4.2 tissue culture infectious dose (TCID₅₀) per milliliter at each breeding. The dams in the vaccinated and PCV2-exposed groups were positive for PCV2 antibody but negative for PCV2 DNA in serum at the time of insemination. Three negative control dams, two vaccinated dams, and three dams with previous PCV2 exposure became pregnant and maintained pregnancy to term. After artificial insemination, viremia was detected in one of three vaccinated dams and in two of three dams with previous PCV2 exposure. At farrowing, PCV2 infection was not detected in any piglets or fetuses expelled from the negative control dams or from dams with previous PCV2 exposure. In litters of the vaccinated dams, 15 of 24 live-born piglets were PCV2 viremic at birth, with 6 of 26 fetuses having detectable PCV2 antigen in tissues. In conclusion, vaccine-induced immunity did not prevent fetal infection in this sow model using semen spiked with PCV2.     

Contrasting Evolutionary Patterns in Drosophila Immune Receptors

Vertebrate immune system molecules that bind directly to parasites are commonly subject to strong directional natural selection, probably because they are engaged in an evolutionary arms race with parasites. We have investigated whether similar patterns of evolution are seen in components of the Drosophila immune system that bind parasite-derived molecules. In insects, TEPs (thioester-containing proteins) function as opsonins, binding to parasites and promoting their phagocytosis or encapsulation. The Drosophila melanogaster genome encodes four TEPs, three of which are upregulated after an immune challenge. We report that two of these three Drosophila genes evolve rapidly under positive selection and that, in both TepI and TepII, the “bait-like region” (also known as the variable region) shows the strongest signature of positive selection. This region may be the site of proteolytic cleavage that leads to the activation of the molecule. It is possible that the proteolytic activation of TEPs is a target of host-parasite coevolution, with parasites evolving to prevent proteolysis, which in turn favors mutations in the bait-like region that restore the response. We also sequenced three gram-negative binding proteins (GNBPs) and two immune-induced peptides with strong homology to the GNBPs. In contrast to the Tep genes, the GNBP genes are highly conserved. We discuss the reasons why different components of the immune system have such different patterns of evolution. [Reviewing Editor: Dr. Willie Swanson]