肺癌CT征象与核因子-kappaβ表达

目的：观察肺癌的核因子-kappaβ（NF-κB）表达水平与CT影像的特点,探讨二者之间的相关性。方法：收集未经任何治疗的80例周围型肺癌及19例炎症占位组织学标本,采用免疫组织化学streptavidin peroxide（S-P）法检测NF-κB的核内表达水平。同时收集所有病变的CT图像资料,观察肿瘤的影像学特点并进行记录。首先分析NF-κB表达在良恶性占位中有无差异,再分析在不同病理类型的肺癌中有无差异。然后以肿块大小（直径≤5cm组和〉5cm组）、有无毛刺、分叶、坏死、转移这五个特点各分为两组,并就各组对应的NF-κB表达进行分析。结果：NF-κB在肺癌中表达明显高于在炎症病变中的表达,而在不同病理类型的肺癌中的表达无差异。CT表现有毛刺、已有转移者标本中NF-κB表达较没有毛刺及未发生转移组高;瘤体有坏死者表达较没有坏死者低。肿瘤大小组间及有无分叶之间其NF-κB表达未见明显差异。结论：NF-κB在肺癌中表达明显高于在炎症病变中的表达,对应的CT征像有其特点,可能与肺癌的浸润及转移相关。     

TNP-470 Inhibits Oxidative Stress,Nitric Oxide Production and Nuclear Factor Kappa B Activation in a Rat Model of Hepatocellular Carcinoma

The objective of this study is to determine if treatment with the angiogenesis inhibitor TNP-470 results in impairment of oxidative stress, inhibition of nuclear factor kappa B (NF-κB) activation and decrease of nitric oxide production in an experimental model of rat hepatocarcinogenesis. Tumour was induced by diethylnitrosamine and promoted by two-thirds hepatectomy plus acetaminofluorene administration. Experiments were carried out at 28 weeks after initiating the treatment. TNP-470 was administered at 30 mg/kg, three times per week from 20 to 28 weeks. Carcinomatous tissue growing outside dysplastic nodules and a marked expression of placental glutathione S-transferase were detected in rats with induced carcinogenesis. Liver concentrations of thiobarbituric acid reactive substances, reduced glutathione (GSH) and glutathione disulfide (GSSG) were significantly higher than those of controls and there was a significant increase in the GSSG/GSH ratio. Tumour growth was accompanied by augmented expression of inducible nitric oxide synthase, activation of (NF-κB) and proteolysis of IkappaB. All these effects were absent in animals receiving TNP-470. Our results indicate that TNP-470 inhibits oxidative stress, nitric oxide production and NF-κB activation induced by experimental hepatocarcinogenesis. These changes would contribute to the beneficial effects of TNP-470 in cancer treatment.     

RANKL在成釉细胞瘤骨吸收机制中的作用

目的:检测RANKL在成釉细胞瘤(ameloblastoma,AM)组织中的表达情况及探讨RANKL在AM骨吸收机制中的作用.方法:通过免疫组化方法检测RANKL在AM组织中的表达情况;通过建立AM细胞/新生大鼠骨细胞共培养体系,观察AM细胞诱导破骨细胞形成的活性,再以OPG(RANKL的抑制剂)进行干预,观察OPG对AM细胞诱导破骨细胞形成活性的影响.结果:RANKL在AM组织中有恒定的表达;AM细胞能够诱导新生大鼠骨细胞分化为成熟的破骨细胞,但此活性可被OPG明显抑制.结论:AM细胞诱导破骨细胞形成可能是AM骨吸收过程中局部破骨细胞形成的重要来源和机制,而RANKL在此过程中发挥重要作用.     

Activation of Nuclear Factor Kappa B in the Hepatic Stellate Cells of Mice with Schistosomiasis Japonica

Schistosomiasis japonica is a serious tropical parasitic disease in humans, which causes inflammation and fibrosis of the liver. Hepatic stellate cells (HSCs) are known to play an important role in schistosome-induced fibrosis, but their role in schistosome-induced inflammation is still largely unknown. Here, we use a murine model of schistosomiasis japonica to investigate the role that nuclear factor kappa B (NF-κB), a critical mediator of inflammatory responses, plays in schistosome-induced inflammation. We revealed that NF-κB was significantly activated in HSCs at the early stage of infection, but not at later stages. We also show that the expression levels of several chemokines regulated by NF-κB signaling (Ccl2, Ccl3 and Ccl5) were similarly elevated at early infection. TLR4 signaling, one of the strongest known inducers of NF-κB activation, seemed not activated in HSCs post-infection. Importantly, we found that levels of miR-146 (a known negative regulator of NF-κB signaling) in HSCs opposed those of NF-κB signaling, elevating at later stage of infection. These results indicate that HSCs might play an important role in the progression of hepatic schistosomiasis japonica by linking liver inflammation to fibrosis via NF-κB signaling. Moreover, our work suggests that miR-146 appeared to regulate this process. These findings are significant and imply that manipulating the function of HSCs by targeting either NF-κB signaling or miR-146 expression may provide a novel method of treating hepatic schistosomiasis japonica.     

A Computational Model of Lipopolysaccharide-Induced Nuclear Factor Kappa B Activation: A Key Signalling Pathway in Infection-Induced Preterm Labour

Preterm birth is the single biggest cause of significant neonatal morbidity and mortality, and the incidence is rising. Development of new therapies to treat and prevent preterm labour is seriously hampered by incomplete understanding of the molecular mechanisms that initiate labour at term and preterm. Computational modelling provides a new opportunity to improve this understanding. It is a useful tool in (i) identifying gaps in knowledge and informing future research, and (ii) providing the basis for an in silico model of parturition in which novel drugs to prevent or treat preterm labour can be “tested”. Despite their merits, computational models are rarely used to study the molecular events initiating labour. Here, we present the first attempt to generate a dynamic kinetic model that has relevance to the molecular mechanisms of preterm labour. Using published data, we model an important candidate signalling pathway in infection-induced preterm labour: that of lipopolysaccharide (LPS) -induced activation of Nuclear Factor kappa B. This is the first model of this pathway to explicitly include molecular interactions upstream of Nuclear Factor kappa B activation. We produced a formalised graphical depiction of the pathway and built a kinetic model based on ordinary differential equations. The kinetic model accurately reproduced published in vitro time course plots of Lipopolysaccharide-induced Nuclear Factor kappa B activation in mouse embryo fibroblasts. In this preliminary work we have provided proof of concept that it is possible to build computational models of signalling pathways that are relevant to the regulation of labour, and suggest that models that are validated with wet-lab experiments have the potential to greatly benefit the field.     

核因子-KB在腹部火器伤肠管穿透后肺组织细胞凋亡中的作用

目的：探讨腹部火器伤肠管穿透后核因子-κB在肺组织细胞凋亡中的作用,了解腹部火器伤肠管穿透后继发性肺损伤机制。方法：健康长白仔猪42头随机等分为对照组和伤后1h、2h、4h、8h、12h和24h组,实验组建立腹部火器伤肠管穿透模型后,用免疫组化图像分析法测定各组肺组织内NF-κB活性,同时用TUNEL测定肺组织细胞凋亡变化情况。结果：伤后各组肺组织内NF-κB活性明显高于对照组,并于伤后8h出现高峰。肺组织细胞凋亡指数伤后显著增高（P〈0.05）,并与NF-κB活性变化基本一致。结论：腹部火器伤肠管穿透后肺组织内NF-κB活性增强,肺细胞凋亡增多,从而继发导致肺损伤     

核因子-κB 在腹部火器伤肠管穿透后肺组织细胞凋亡中的作用*

目的:探讨腹部火器伤肠管穿透后核因子-κB在肺组织细胞凋亡中的作用,了解腹部火器伤肠管穿透后继发性肺损伤机制。方法:健康长白仔猪42头随机等分为对照组和伤后1h、2h、4h、8h、12h和24h组,实验组建立腹部火器伤肠管穿透模型后,用免疫组化图像分析法测定各组肺组织内NF-κB活性,同时用TUNEL测定肺组织细胞凋亡变化情况。结果:伤后各组肺组织内NF-κB活性明显高于对照组,并于伤后8h出现高峰。肺组织细胞凋亡指数伤后显著增高(P<0.05),并与NF-κB活性变化基本一致。结论:腹部火器伤肠管穿透后肺组织内NF-κB活性增强,肺细胞凋亡增多,从而继发导致肺损伤。