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1.
Chronic hepatitis is a major cause of liver cancer, so earlier treatment of hepatitis might be reducing liver cancer incidence. Hepatitis can be induced in mice by treatment with Concanavalin A (Con A); the resulting liver injury causes significant CD4+ T cell activation and infiltration. In these T cells, Roquin, a ring-type E3 ubiquitin ligase, is activated. To investigate the role of Roquin, we examined Con A-induced liver injury and T cell infiltration in transgenic (Tg) mice overexpressing Roquin specifically in T cells. In Roquin Tg mice, Con A treatment caused greater increases in both the levels of liver injury enzymes and liver tissue apoptosis, as revealed by TUNEL and H&E staining, than wild type (WT) mice. Further, Roquin Tg mice respond to Con A treatment with greater increases in the T cell population, particularly Th17 cells, though Treg cell counts are lower. Roquin overexpression also enhances increases in pro-inflammatory cytokines, including IFN-γ, TNF-α and IL-6, upon liver injury. Furthermore, Roquin regulates the immune response and apoptosis in Con A induced hepatitis via STATs, Bax and Bcl2. These findings suggest that over-expression of Roquin exacerbates T-cell mediated hepatitis.  相似文献   
2.
Chemokines are important mediators of cell migration, and thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) are well-known typical inflammatory chemokines involved in atopic dermatitis (AD). (+)-Nootkatone is the major component of Cyperus rotundus. (+)-Nootkatone has antiallergic, anti-inflammatory, and antiplatelet activities. The purpose of this study was to investigate the effect of (+)-nootkatone on tumor necrosis factor α (TNF-α)/interferon γ (IFN-γ)-induced expression of Th2 chemokines in HaCaT cells. We found that (+)-nootkatone inhibited the TNF-α/IFN-γ-induced expression of TARC/CCL17 and MDC/CCL22 mRNA in HaCaT cells. It also significantly inhibited TNF-α/IFN-γ-induced activation of nuclear factor kappa B (NF-κB), p38 mitogen-activated protein kinase (MAPK), and protein kinase Cζ (PKCζ). Furthermore, we showed that PKCζ and p38 MAPK contributed to the inhibition of TNF-α/IFN-γ-induced TARC/CCL17 and MDC/CCL22 expression by blocking IκBα degradation in HaCaT cells. Taken together, these results suggest that (+)-nootkatone may suppress TNF-α/IFN-γ-induced TARC/CCL17 and MDC/CCL22 expression in HaCaT cells by inhibiting of PKCζ and p38 MAPK signaling pathways that lead to activation of NF-κB. We propose that (+)-nootkatone may be a useful therapeutic candidate for inflammatory skin diseases such as AD.  相似文献   
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目的:探讨和比较不同手术术式治疗涉及桡骨远端的骨肉瘤的手术适应症选择,临床疗效和安全性。方法:将2005 年-2014 年我院收治的涉及到桡骨远端并进行外科手术治疗的骨巨细胞瘤患者共88 例进行回顾性分析。根据影像学Campanacci分级,主 要手术方法分为以下三种,分别为:A组:微波天线高温原位灭活,自体髂骨,异体骨粒符合骨水泥重建修复术;B:瘤骨切除并腓 骨移植术;C:瘤骨刮除灭活并原位植骨术。结合详实的随访资料对两组患者在术后的复发率,腕关节功能(Enneking)等情况给予 分析和评价。结果:A 组复发率为10.87 %,腕关节功能MSTS93 功能评分为26.32± 2.92分。B 组复发率为0,腕关节术后的 MSTS93 功能评分为22.85± 4.16 分。C 组复发率为30.24 %。腕关节术后的MSTS93 功能评分为26.97± 2.84 分。三组相比,A、 B 与C 组在复发率中有明显统计学差异(P<0.05),A 组、C组的术后功能评分明显优于B 组(P<0.05),但两组之间无统计学差异 (P>0.05)。A 组中有1 例切口表层感染,B 组中有2 例皮肤感染,均经加强换药后治愈。结论:瘤段切除手术能够有效的降低复发 率,但局部功能恢复较差,容易出现切口感染等并发症。微波灭活手术可以有效的杀灭肿瘤组织并保证良好的功能性,但复发率 相对较高。在临床工作中应根据患者具体病情和需要给予针对性的手术方案。  相似文献   
5.
Three-dimensional (3D) tumor spheroids are utilized in cancer research as a more accurate model of the in vivo tumor microenvironment, compared to traditional two-dimensional (2D) cell culture. The spheroid model is able to mimic the effects of cell-cell interaction, hypoxia and nutrient deprivation, and drug penetration. One characteristic of this model is the development of a necrotic core, surrounded by a ring of G1 arrested cells, with proliferating cells on the outer layers of the spheroid. Of interest in the cancer field is how different regions of the spheroid respond to drug therapies as well as genetic or environmental manipulation. We describe here the use of the fluorescence ubiquitination cell cycle indicator (FUCCI) system along with cytometry and image analysis using commercial software to characterize the cell cycle status of cells with respect to their position inside melanoma spheroids. These methods may be used to track changes in cell cycle status, gene/protein expression or cell viability in different sub-regions of tumor spheroids over time and under different conditions.  相似文献   
6.
We propose a novel parallel computing framework for a nonlinear finite element method (FEM)-based cell model and apply it to simulate avascular tumor growth. We derive computation formulas to simplify the simulation and design the basic algorithms. With the increment of the proliferation generations of tumor cells, the FEM elements may become larger and more distorted. Then, we describe a remesh and refinement processing of the distorted or over large finite elements and the parallel implementation based on Message Passing Interface to improve the accuracy and efficiency of the simulation. We demonstrate the feasibility and effectiveness of the FEM model and the parallelization methods in simulations of early tumor growth.  相似文献   
7.
Epidemiological studies showed that isoflurane, a general anesthetic widely used in surgery including those for the children, is associated with impairment of neurodevelopment and neurodegenerative diseases, such as Alzheimer’s disease (AD) and age-related macular degeneration (AMD), which are related to the accumulation of reactive oxygen species (ROS). Astragaloside (AS) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge. In this study, we used retinal pigment epithelial cells, which share plenty of features with neurodegenerative diseases such as AD and AMD to investigate the effect of AS. Cell cycle re-entry and proapoptosis were seen in retinal pigment epithelium (RPE) cells treated with isoflurane, which was alleviated by pretreatment of AS. Further, tumor necrosis factor receptor-associated factor 5 (TRAF5) and downstream nuclear factor-κB (NF-κB) were investigated to elucidate the molecular mechanism underlying protective effect of AS. RPE cells exposed to isoflurane expressed higher TRAF5 and NF-κB than those pretreated with AS, suggesting a critical role of TRAF5 therein. In Morris water maze (MWM) assay, Sprague-Dawley rats pretreated with AS and then exposed to isoflurane spent less time in swimming to the platform, and their TRAF5 expression was significantly lower than those received anesthesia alone. Further studies on the consequence of forced downregulation or upregulation are warranted that may employ cutting-edge technologies such as optogenetics to overcome the difficulties in manipulating expression of TRAF5. Although the link between TRAF5 and neurodegeneration requires more in-depth investigations, our study provide a novel hint on the pathological mechanism of isoflurane and suggest a potential target for eliminating persistent side effect of anesthesia.  相似文献   
8.
沉默信息调节因子1(SIRT1)是Sirtuin 家族中的一员,属于烟酰胺(NAD+)依赖的Ⅲ类组蛋白去乙酰化酶,能通过对多种非组蛋白及组蛋白赖氨酸残基进行去乙酰化修饰调节基因表达。近来的研究发现,SIRT1不仅能使肿瘤抑制因子去乙酰化,促进肿瘤发生,还能使肿瘤促进因子去乙酰化,抑制肿瘤发生。SIRT1与肿瘤的生物学特性密切相关,影响肿瘤分期及患者预后。在消化系统肿瘤中,SIRT1具有双面性,既可作为抑癌因子,也可发挥癌因子的作用。近年来,许多研究对SIRT1在肿瘤中的作用靶点及相关信号通路做了深入研究,关于SIRT1在肿瘤中作用机制的新研究不断出现。SIRT1已成为人们攻克肿瘤的一个研究热点。本文通过对SIRT1在肿瘤中的双重作用,尤其是在消化系统肿瘤中的不同作用靶点和参与的信号通路作一综述,希望为临床上治疗消化系统肿瘤提供更有说服力的证据。  相似文献   
9.
目的:探讨能谱CT优化胃肿瘤扫描辐射剂量对肾上腺嗜铬细胞瘤的诊断价值。方法:采用回顾性、抽样、随机研究方法选择2012年9月到2017年2月在我院诊治的肾上腺嗜铬细胞瘤患者59例作为研究对象,所有患者都给予常规CT扫描与能谱CT优化胃肿瘤扫描,记录和比较辐射剂量与图像质量。结果:所有病例包膜均完整,边缘清楚,肿瘤内见单发或多发低密度区,肿瘤实质区呈不均匀显著强化。常规CT与能谱CT的图像质量主观评分分别为3.89±0.45分和4.54±0.34分;常规CT与能谱CT图像的胃肿瘤CT值分别为31.94±6.39HU和35.29±5.19HU,对比都有显著差异(P0.05)。能谱CT图像的膀胱和皮下脂肪图像噪声值都显著低于常规CT图像,对比差异都有统计学意义(P0.05);能谱CT扫描的CTDIvol和DLP分别为12.39±3.48mGy和624.10±39.19mGy.cm,都显著低于常规CT扫描的14.09±4.13mGy和653.92±56.29mGy.cm(P0.05)。结论:能谱CT优化胃肿瘤扫描在肾上腺嗜铬细胞瘤诊断中的应用能有效减少辐射剂量与图像噪声,提高图像CT值与主观质量,临床应用价值更高。  相似文献   
10.
Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes in latently infected cells. LANA mediates KSHV DNA replication and segregates episomes to progeny nuclei. The structure of the LANA DNA binding domain was recently solved, revealing a positive electrostatic patch opposite the DNA binding surface, which is the site of BET protein binding. Here we investigate the functional role of the positive patch in LANA-mediated episome persistence. As expected, LANA mutants with alanine or glutamate substitutions in the central, peripheral, or lateral portions of the positive patch maintained the ability to bind DNA by EMSA. However, all of the substitution mutants were deficient for LANA DNA replication and episome maintenance. Mutation of the peripheral region generated the largest deficiencies. Despite these deficiencies, all positive patch mutants concentrated to dots along mitotic chromosomes in cells containing episomes, similar to LANA. The central and peripheral mutants, but not the lateral mutants, were reduced for BET protein interaction as assessed by co-immunoprecipitation. However, defects in BET protein binding were independent of episome maintenance function. Overall, the reductions in episome maintenance closely correlated with DNA replication deficiencies, suggesting that the replication defects account for the reduced episome persistence. Therefore, the electrostatic patch exerts a key role in LANA-mediated DNA replication and episome persistence and may act through a host cell partner(s) other than a BET protein or by inducing specific structures or complexes.  相似文献   
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