Neurodegenerative changes and apoptosis induced by intrauterine and extrauterine exposure of radiofrequency radiation

Adverse health effects of radiofrequency radiation (RFR) on the ongoing developmental stages of children from conception to childhood are scientifically anticipated subject. This study was performed to identify the effects of global system for mobile communications (GSM) modulated mobile phone like RFR in 1800 MHz frequency on oxidative DNA damage and lipid peroxidation beside the apoptotic cell formation, using histopathological and immunohistochemical methods in the brain tissue of 1-month-old male and female New Zealand White rabbits that were exposed to these fields at their mother's womb and after the birth. Oxidative DNA damage and lipid peroxidation levels were investigated by measuring the 8-hydroxy-2′-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels, respectively. Histopathological changes were observed using by hematoxylin and eosin (HE) staining. Apoptotic cells were detected in the examined organs by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining.For both male and female infants; 8-OHdG levels increased in the group exposed to RFR in both intrauterine and extrauterine periods compared to the infants that were never exposed to RFR and the ones were exposed when they reached one month of age (p < 0.05). MDA results were different for male and female rabbits. There was no difference between all female infant groups (p > 0.05), while only intrauterine exposure significantly causes MDA level increase for the male infants. HE staining revealed mild lessions in neuronal necrobiosis in brain tissues of female rabbits that had only intaruterine exposure and male rabbits had only extrauterine exposure. Gliosis were mildly positive in brain tissues of rabbits that are exposed only intrauterine period, also the group exposed both intrauterine and extrauterine periods. However, there was no apoptotic change detected by TUNEL staining in the brain tissues of all groups.     

卵巢浆液性腺癌肿瘤微环境中CD8~+TILs密度及PD-L1的表达与临床意义

目的:研究卵巢浆液性腺癌肿瘤微环境中CD8~+肿瘤浸润淋巴细胞(TILs)密度及癌细胞程序性死亡配体-1(PD-L1)的表达情况与临床意义。方法:收集2004年7月至2010年12月于上海交通大学医学院附属仁济医院行肿瘤细胞减灭术的116例卵巢浆液性腺癌患者组织标本,免疫组化检测肿瘤组织CD8~+TILs密度及癌细胞PD-L1表达情况;Spearman相关性分析癌细胞PD-L1表达水平与癌巢及间质CD8~+TILs数目的关系;采用乘积极限法进行基于癌巢CD8~+TILs密度及肿瘤细胞PD-L1表达的单因素生存分析。结果:卵巢浆液性腺癌PD-L1高表达的比例为70.69%(82/116)。癌细胞PD-L1表达强度与癌巢内的CD8~+TILs数目呈显著负相关(P=0.024),而与间质内的CD8~+TILs数目无相关性(P=0.117)。癌巢CD8~+TILs高密度组患者的中位生存时间(64月)显著高于低密度组(43月),差异有统计学意义(P0.05);乘积极限法的亚组分析显示肿瘤微环境中癌细胞PD-L1低表达癌巢CD8~+TILs高密度组患者的预后较好。结论:卵巢浆液性腺癌肿瘤微环境中癌巢CD8~+TILs密度及癌细胞PD-L1表达水平与患者预后密切相关,重视肿瘤微环境的免疫分型有助于评估患者预后及筛选合适患者实施抗PD-1/PD-L1免疫治疗。     

Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds. Brominated diphenyl ether (BDE)-47 is one of the most prevalent PBDE congeners found in human breast milk, serum and placenta. Despite the presence of PBDEs in human placenta, effects of PBDEs on placental cell function are poorly understood. The present study investigated BDE-47-induced reactive oxygen species (ROS) formation and its role in BDE-47-stimulated proinflammatory cytokine release in a first trimester human extravillous trophoblast cell line, HTR-8/SVneo. Exposure of HTR-8/SVneo cells for 4 h to 20 μM BDE-47 increased ROS generation 1.7 fold as measured by the dichlorofluorescein (DCF) assay. Likewise, superoxide anion production increased approximately 5 fold at 10 and 15 μM and 9 fold at 20 μM BDE-47 with a 1-h exposure, as measured by cytochrome c reduction. BDE-47 (10, 15 and 20 μM) decreased the mitochondrial membrane potential by 47–64.5% at 4, 8 and 24 h as assessed with the fluorescent probe Rh123. Treatment with 15 and 20 μM BDE-47 stimulated cellular release and mRNA expression of IL-6 and IL-8 after 12 and 24-h exposures: the greatest increases were a 35-fold increased mRNA expression at 12 h and a 12-fold increased protein concentration at 24 h for IL-6. Antioxidant treatments (deferoxamine mesylate, (±)α-tocopherol, or tempol) suppressed BDE-47-stimulated IL-6 release by 54.1%, 56.3% and 37.7%, respectively, implicating a role for ROS in the regulation of inflammatory pathways in HTR-8/SVneo cells. Solvent (DMSO) controls exhibited statistically significantly decreased responses compared with non-treated controls for IL-6 release and IL-8 mRNA expression, but these responses were not consistent across experiments and times. Nonetheless, it is possible that DMSO (used to dissolve BDE-47) may have attenuated the stimulatory actions of BDE-47 on cytokine responses. Because abnormal activation of proinflammatory responses can disrupt trophoblast functions necessary for placental development and successful pregnancy, further investigation is warranted of the impact of ROS and BDE-47 on trophoblast cytokine responses.     

Biological Activity of Desulfovibrio desulfuricans Lipopolysaccharides Evaluated via Interleukin-8 Secretion by Caco-2 Cells

Background: Although Desulfovibrio desulfuricans species, besides existing in the natural environment, is also found in the human digestive tract, no information is currently available on its role in the intestinal ecosystem and its activity in regard to the intestinal mucosa. Bacterial products (lipopolysaccharides, LPSs) are generally known for their ability to trigger inflammatory response by stimulating cytokine expression, such as interleukin-8 (IL-8). Methods: Colonic Caco-2 cells were exposed to LPSs isolated from the soil type and intestinal wild strains of D. desulfuricans bacteria. The amount of IL-8 secreted was measured by ELISA. The effects of sodium butyrate and cell preincubation with sodium butyrate on the IL-8 secretion in response to LPSs were also analysed. Results: LPSs from D. desulfuricans down-regulated IL-8 secretion by the cells. Incubation of these cells with butyrate alone resulted in a dose-dependent stimulation of IL-8 release. Butyrate also modulated IL-8 secretion by cells stimulated with LPSs. Conclusions: Our findings suggest the lack of inflammatory response of intestinal mucosa in the presence of LPSs of D. desulfuricans. This response can be conditioned by the natural bacterial product, butyrate, which exerts a stimulatory effect on the IL-8 secretion and modulates its release in response to LPSs.     

Adjuvanting an inactivated influenza vaccine with conjugated R848 improves the level of antibody present at 6 months in a nonhuman primate neonate model

Generation of a potent antibody response that can be sustained over time is highly challenging in young infants. Our previous studies using a nursery-reared nonhuman primate model identified R848 conjugated to inactivated influenza virus as a highly immunogenic vaccine for neonates. Here we determined the effectiveness of this vaccine in mother-reared infants as well as its ability to promote improved responses at 6 months compared to vaccination in the absence of R848. In agreement with our nursery study, R848 conjugated to influenza virus induced a higher antibody response in neonates compared to the non-adjuvanted vaccine. Further, the increase in the response relative to that induced by the non-adjuvanted vaccine was maintained at 6 months suggesting the increased antibody secreting cells that resulted from inclusion of conjugated R848 production were capable of surviving long term. There was no significant difference in quality of antibody (i.e. neutralization or affinity), suggesting the beneficial effect of conjugated R848 during vaccination of neonates with inactivated influenza virus is likely manifest during the early generation of antibody secreting cells.     

Polo样激酶3在前列腺癌中的表达及临床意义

目的探讨Polo样激酶3(Polo-like kinase 3,Plk3)在前列腺癌组织中的表达情况及其临床意义。方法采用免疫组化技术检测68例前列腺癌组织及10例正常前列腺组织中Plk3的表达情况,分析Plk3表达与临床病理特征之间的关系,并通过对TCGA数据库中498例前列腺癌患者的Plk3表达值进行GSEA分析。结果 Plk3在前列腺癌组织中比癌旁组织中表达阳性率高,且差异有统计学意义(P=0.034);Plk3表达与前列腺癌的病理分级、临床分期、T分期、淋巴结转移和远处转移有关(P0.05),与年龄和Gleason score无关(P0.05);GSEA分析结果显示Plk3与前列腺癌的增殖和转移相关(FDR q0.05)。结论 Plk3在前列腺癌中表达增高,并促进前列腺癌的进展,其可能通过促进增殖和转移发挥作用。     

Serum cortisol level and disc displacement disorders of the temporomandibular joint

Temporomandibular disorders (TMD) are a significant public health problem, affecting approximately 5–12% of the population. Objectives: This retrospective cross‐sectional study investigated the relationship between 8 AM serum cortisol levels (8ASC) and disc displacement disorders (DDD) of TMD. One hundred and forty patients with DDD were recruited. Among them, 60 patients comprised the case group of disc displacement without reduction with limited opening (DDWORWLO, age 37·7 ± 17·22), and 80 were ‘other DDD’ for the control group (age 36·4 ± 13·08). The independent variables included domains of demography, history, malocclusion, comorbid symptoms, comorbid TMD and 8ASC. Data were analysed with the chi‐square test, logistic regression and receiver operating characteristic (ROC) curve. Results of multiple logistic regression showed that 8ASC was the only factor significantly related to DDWORWLO (P = 0·006). Receiver operating characteristic analysis of DDWORWLO and 8ASC indicated an area under the curve of 0·669, standard error of 0·049 and P value of 0·001. The adequate cut‐off point of 8ASC was 12·45 (μg dL^?1), with sensitivity of 0·636, and specificity of 0·729. 8 AM serum cortisol level can be used as a clinical clue to differentiate DDWORWLO from other DDD.