Prenatal polybrominated diphenyl ethers exposure and anogenital distance in boys from a Shanghai birth cohort

Background

Polybrominated diphenyl ethers (PBDEs) are major brominated flame retardant (BFR) chemicals with endocrine-disrupting properties. One small-scale study on humans has suggested that prenatal exposure to PBDEs is adversely related to anogenital distance (AGD) a sensitive marker for prenatal androgen exposure. The aim of the present study was to examine the associations between prenatal exposure to PBDEs and AGD among boys 0–4 years of age in a cohort study.

Vacuolating cytotoxin purified fromHelicobacter pyloricauses mitochondrial damage in human gastric cells

We investigated the effects of vacuolating cytotoxin (VacA) prepared fromHelicobacter pylorion the metabolism of gastric epithelial cells, AZ-521. VacA caused the ATP levels to decrease in a time-dependent manner; by approximately 20% in 6 h, 35% in 12 h and 50% in 24 h, at a concentration of 120 nM. This decrease was also dependent on the concentration of VacA. To evaluate the impairment of mitochondria by VacA, mitochondrial membrane potential was estimated by flow cytometric analysis using 3, 3′-dihexyloxacarbocyanine iodide as a substrate. VacA decreased membrane potential with the relative fluorescence intensity of AZ-521 cells in 6 h from 52±3 to 24±1. Treatment of the cells with bafilomycin A1, a specific inhibitor of vacuolar ATPase proton pump, showed no apparent effect on these changes in the levels of ATP and the mitochondrial membrane potential. Secondly, we estimated the effect of VacA on oxygen consumption. VacA inhibited oxygen consumption in AZ-521 cells: the levels of PO₂in the medium of control cells decreased by 73% in 3 h and 37% in 6 h, whereas those in VacA-treated cells were 84% in 3 h and 59% in 6 h. Flow cytometric analysis showed the number of cells in the G₀/G₁phase was increased by VacA. Taken together, VacA induced an inactivation of energy metabolism followed by mitochondrial damage, leading to impairment of the cell cycle in gastric epithelial cells.     

Cloning and characterization of three hemolysin genes from Aeromonas salmonicida

Two hemolysin genes (ASH3 and ASH4) of Aeromonas salmonicida strain 17-2 and one (ASH1) of A. salmonicida ATCC14174 were cloned into the cosmid vector charomid 9-36 in Escherichia coli DH1. The overall amino acid sequence of the ASH3 was similar to that of the aerolysins of Aeromonas hydrophila and Aeromonas sobria, and hemolysins AHH3, AHH4, and AHH5 of A. hydrophila, and hemolysin ASA1 of A. sobria. The sequence of ASH4 was similar to that of the AHH1 hemolysin of A. hydrophila. The ASH4 hemolysin contains some homologous sequence regions of the Vibrio vulnificus and Vibrio cholerae cytolysin-hemolysin. Both ASH3 and ASH4 DNA probes reacted with all 104 strains of A. salmonicida, whereas the ASH1 DNA probe did not hybridize with any of the 104 strains studied except strain ATCC14174. ASH1 and ASH3 were broad spectrum hemolysins with most activity against rabbit and horse erythrocytes, respectively, whereas ASH4 hemolysin did not lyse bovine and horse erythrocytes. ASH3 and ASH4, but not ASH1, were activated by trypsin.     

FcRγ promotes T cell apoptosis in Fas-deficient mice

Deficiency of Fas or its ligand leads to lymphocyte accumulation, lymphadenopathy, splenomegaly, and autoimmunity in mice and humans. Although the Fas pathway is important for limiting the number of peripheral T cells, inactivation of other pro-apoptotic molecules can also perturb T cell homeostasis independently of and/or in concert with Fas deficiency. Here, we show that combined deficiency of Fas and the Fc receptor common γ signaling chain (FcRγ) results in worsened T cell accumulation in comparison with mice lacking Fas alone, with a particularly marked increase in the number of TCRαβ⁺CD4⁻CD8⁻ double negative (DN) T cells. LPR FcRγ^−/− mice exhibited reduced survival due to progressive lymphadenopathy. We further investigated the mechanisms whereby FcRγ deficiency promotes lymphoproliferative disease in Fas-mutant mice. Interestingly, there were no significant differences in T cell proliferation between LPR FcRγ^+/+ and LPR FcRγ^−/− mice in vivo and in vitro. However, FcRγ deletion resulted in significantly decreased peripheral T cell apoptosis. Importantly, the observed increase in apoptosis was restricted to a subset of FcRγ⁺ T cells. These T cells, but not those lacking FcRγ expression, exhibited increased activation of caspases 3 and 9, indicating a role for FcRγ in driving their apoptosis. FcRγ⁺ DN T cells also showed enhanced sensitivity to TCR restimulation-induced cell death (RICD) despite lacking Fas, suggesting that TCR stimulation of autoreactive T cells in vivo may serve to eliminate FcRγ⁺ T cells and thus exert partial control over lymphoproliferative disease. Hence, our data reveal a novel role for FcRγ in promoting peripheral T cell apoptosis in Fas-deficient mice, which may be of significant value in understanding autoimmune lymphoproliferative syndromes.     

植物灭螺剂螺威对大鼠的急性吸入毒性观察

目的 目的 观察植物灭螺剂50%螺威对大鼠的急性吸入毒性。方法 方法 20只成年Wistar大鼠, 雌雄各半, 通过动式吸 入染毒装置给予5 000 mg/m3 50%螺威母药, 染毒2 h, 观察14 d内大鼠死亡与恢复情况, 计算该药对大鼠的半数致死剂量 （LC50 ）。结果 结果 染毒过程中大鼠活动减少, 个别大鼠出现搔抓症状; 染毒结束后症状消失。在染毒后14 d观察期内无大 鼠死亡。螺威对雌、 雄大鼠急性吸入LC50均> 5 000 mg/m3 , 属于低毒级。结论 结论 50%螺威母药在5 000 mg/m3 浓度下经呼 吸道急性进入大鼠机体2 h, 不会引起大鼠死亡, 但在生产、 使用该灭螺剂时仍需佩戴防护用品。     

T-cell regeneration: all repertoires are not created equal

The importance of the thymus for T-cell development is a central tenet of modern immunology, but thymic-independent T-cell generation has also been described. Recent human studies have shown that the balance between thymic-dependent and thymic-independent pathways of T-cell regeneration is primarily determined by age, and that thymic-independent pathways are generally inadequate for restoration of host immunocompetence.     

Recombinant rabies virus expressing dog GM-CSF is an efficacious oral rabies vaccine for dogs

Developing efficacious oral rabies vaccines is an important step to increase immunization coverage for stray dogs, which are not accessible for parenteral vaccination. Our previous studies have demonstrated that recombinant rabies virus (RABV) expressing cytokines/chemokines induces robust protective immune responses after oral immunization in mice by recruiting and activating dendritic cells (DCs) and B cells. To develop an effective oral rabies vaccine for dogs, a recombinant attenuated RABV expressing dog GM-CSF, designated as LBNSE-dGM-CSF was constructed and used for oral vaccination in a dog model. Significantly more DCs or B cells were activated in the peripheral blood of dogs vaccinated orally with LBNSE-dGM-CSF than those vaccinated with the parent virus LBNSE, particularly at 3 days post immunization (dpi). As a result, significantly higher levels of virus neutralizing antibodies (VNAs) were detected in dogs immunized with LBNSE-dGM-CSF than with the parent virus. All the immunized dogs were protected against a lethal challenge with 4500 MICLD₅₀ of wild-type RABV SXTYD01. LBNSE-dGM-CSF was found to replicate mainly in the tonsils after oral vaccination as detected by nested RT-PCR and immunohistochemistry. Taken together, our results indicate that LBNSE-dGM-CSF could be a promising oral rabies vaccine candidate for dogs.     

玉竹提取物对心肌缺血再灌注损伤大鼠心肌细胞线粒体损伤及凋亡的保护作用

目的:探究玉竹提取物对心肌缺血再灌注损伤大鼠心肌细胞线粒体损伤及凋亡的保护作用。方法:选取雄性Wistar大鼠60只,随机分为假手术组、模型组、玉竹提取物低、中、高剂量组及银杏内酯B组,采用可逆性左前降支结扎法建立心肌缺血再灌注模型,给予大鼠心肌缺血30 min,再灌注120 min。玉竹提取物低、中、高剂量组及银杏内酯B组在缺血前30 min给予玉竹提取物100,200,300 mg·kg-1及银杏内酯B 60 mg·kg-1腹腔注射,假手术组及模型组给予相同体积0.9%Na Cl溶液腹腔注射;记录大鼠血流动力学指标;采用原位末端转移酶标记法(TUNEL)染色观察各组大鼠心室肌细胞凋亡情况;采用透射电子显微镜观察大鼠心肌线粒体形态及病理变化,采用酶联免疫吸附法(ELISA)检测大鼠心肌组织游离脂肪酸(FFA),三磷酸腺苷(ATP),腺苷酸(AMP),乳酸(LAC)含量;采用蛋白免疫印迹法(Western blot)检测各组大鼠心室肌组织半胱氨酸蛋白酶(Caspase)-3,Caspase-9,Caspase-12蛋白的表达。分离心肌线粒体检测其超氧化物歧化酶(SOD)活性及丙二醛(MDA)及游离钙含量。结果:与假手术组比较,模型组大鼠左室收缩最大压、左心室压力最大上升速率下降,左室舒张末压、左心室压力最大下降速率升高,心肌细胞凋亡明显,心肌组织FFA,LAC含量升高,Caspase-3,Caspase-9,Caspase-12蛋白表达明显增加,ATP/AMP值明显降低,线粒体膜崩解、内嵴明显消失(P0.05);与模型组比较,玉竹提取物低、中、高剂量及银杏内酯B组大鼠血流动力学指标、心肌细胞凋亡程度及心肌线粒体病理变化均有改善,心肌组织FFA,LAC含量明显降低,Caspase-3,Caspase-9,Caspase-12蛋白表达降低,ATP/AMP值明显升高(P0.05)。结论:玉竹提取物可改善大鼠心肌缺血再灌注损伤,减少心肌细胞凋亡,其机制可能与保护线粒体,增强心肌细胞线粒体能量代谢有关。