NF-κB信号通路与炎症性肠病

炎症是多种细胞及细胞因子参与的机体防御性反应,但严重或长期的炎症则会造成机体损伤.炎症性肠病(inflammatory bowel disease,IBD)是一组以慢性、周期性炎症为特征的胃肠道疾病,长期、反复的胃肠道炎症不仅影响患者生活质量,而且增加了肠道纤维化及癌变的风险,而核因子Kappa B(nuclear f...     

Notch和NF-κB信号通路与心肌重塑相关性研究进展

心肌重塑是心血管疾病的共同病理过程,可见于高血压、动脉粥样硬化、心肌缺血、心肌病、心力衰竭等,是心血管疾病发生、发展和维持的病理基础。研究发现有多重因素参与心肌重塑的发生发展,同时这些因素相互促进,共同维持心肌重塑的发展。Notch信号通路由一组在进化上高度保守的细胞膜配体、受体及下游分子组成。细胞间受体配体作用可激活Notch信号转导过程,从而直接调节基因转录,使细胞基因表达受相邻细胞调控。Notch信号在细胞分化、胚胎发育、组织自我更新过程     

核因子-κB信号通路与动脉粥样硬化

目前研究认为动脉粥样硬化是慢性炎症性疾病，NF-κB／IκB信号通路在调控炎症反应起着重要作用，研究发现NF—κB／IκB信号通路的异常激活与动脉粥样硬化疾病的发生、发展有密切关系。抑制NF—κB／IκB信号通路的活化，可望为动脉粥样硬化的防治开辟一条新的途径。本文就近年来NF—κB／IκB信号通路与动脉粥样硬化研究进展做一复习。     

基于NF-κB信号通路的中医药防治心肌纤维化研究进展

以核因子-κB(NF-κB)信号通路为切入点探究中医药防治心肌纤维化的作用机制。心肌纤维化是多数心血管疾病(如心肌梗死、高血压、肥厚型心肌病、心肌炎及主动脉狭窄等)的共同病理机制,其持续性进展将最终导致心力衰竭和死亡等不良临床预后。NF-κB信号作为经典的炎症反应通路,通过诱导炎性因子在心肌组织中聚集导致胶原沉积及成纤维细胞增殖,最终导致心肌纤维化的发生,NF-κB信号通路在心肌纤维化进展过程中发挥重要的作用。而中医药在抗心肌纤维化方面具有多组分、多途径、多靶点作用的优势,针对心肌纤维化的复杂分子机制,可以作用于多种细胞因子及信号分子网络。     

NF-κB信号通路与骨质疏松

核因子Kappa B(NF-κB)最初发现是一种能与免疫球蛋白κ轻链基因增强子κB序列特异结合并调节κ轻链转录的核蛋白因子.随后发现NF-κB参与细胞生长、分化及炎症反应等基因表达调控[1,2],同时研究表明在很多常见的情况下出现NF-κB的异常激活或抑制,如肿瘤、糖尿病、动脉粥样硬化等,这些都表明NF-κB无论是在正常还是疾病状态下都扮演着重要的角色[3].骨质疏松(OP)是以骨量减少、骨的微观结构退化为特征的,致使骨的脆性增加以及易于发生骨折的一种全身性骨骼疾病.OP发生是由于骨形成和骨吸收的失衡,大量研究表明,NF-κB信号通路不仪在骨形成和骨吸收起着重要作用,而且通过与其他信号通路相互联系,彼此作用,影响OP的发生.因此,我们就NF-κB信号通路在成骨细胞和破骨细胞中的作用进行综述.     

IL-33通过调节NF-κB信号通路促进肝癌细胞增殖和迁移

目的 探讨IL-33通过对NF-κB信号通路及炎症因子的调控,对肝癌HepG2细胞增殖和迁移的影响。方法 RT-PCR检测IL-33在不同肝癌细胞系中的表达,Western Blot检测IL-33对HepG2细胞NF-κB信号通路激活相关蛋白(NF-κB、p-NF-κB、IKB、p-IKB)的调控,ELISA检测IL-33对HepG2细胞中IL-1α、IL-1β、IL-6、IL-18等炎症因子释放的调控,EdU增殖实验检测IL-33对HepG2细胞增殖的影响,CCK8实验检测IL-33对HepG2细胞24 h和48 h活力的影响,Transwell小室实验和划痕实验检测IL-33对HepG2细胞迁移的影响。结果 IL-33 mRNA表达分别为LO2(1.01±0.01)、MHCC97H(1.08±0.05)、LM3(1.76±0.21)、HepG2(3.88±0.35)、SMCC7721(2.24±0.43)和Hep3B(2.13±0.30),差异有统计学意义(F=19.621,P=0.001)。IL-33处理24 h组中IL-1α(3185.25±194.67)、IL-1β(2103...     

NF-κB与神经损伤

核因子-κB（NF-κB）是一种广泛存在于真核细胞内,可将信息从胞浆传至胞核并引起相应基因表达的重要转录因子。近年研究表明,NF-κB存在于神经系统几乎所有类型的细胞中,主要包括神经元、星形胶质细胞、小胶质细胞和少突细胞,在神经塑型、神经发育及神经变性等过程中具有独特作用。广泛参与神经系统的病理、生理过程。现就NF-κB与神经损伤的关系及其研究进展综述如下。     

Rel/NF-κB信号传导通路与溃疡性结肠炎生物治疗策略的关系

目前认为溃疡性结肠炎 (UC)是特定免疫功能障碍与遗传因素、环境因素相互作用的结果 ,其主要治疗药物是类固醇激素和抗炎药。但这些药物不能彻底治愈UC ,并有副作用。NF κB是一种与许多基因的转录启动有关的核因子。它是Rel/NF κB信号传导通路的关键成员。通过靶基因的表达产物 ,NF κB参与免疫反应、感染、炎症以及细胞调亡、细胞周期和分化的调控 ,故与人类多种疾病 ,如炎症、肿瘤的发病关系极为密切[1] 。如何通过调控该信号通路来控制相关疾病是当前研究的热点。现将Rel/NF κB信号传导通路与UC的生物治疗策略作一综述。     

Survivin、NF-κB与肝癌的研究进展

原发性肝细胞癌(HCC)是常见的严重危害人类健康的恶性肿瘤之一,全世界每年一半以上的新发HCC病例在我国,其发病率和死亡率居各种恶性肿瘤的前列。近年来的研究表明,肿瘤不仅是一种增殖失控的疾病,而且也是一种细胞凋亡异常的疾病[1]。细胞增殖与凋亡之间的动态平衡是维持机体稳     

核因子-κB信号通路与缺血性心脏病关系的研究进展

<正>缺血性心脏病(IHD)早已被证实有多重炎性反应的有效参与,而核因子(NF)-κB信号通路又是免疫应答、炎症反应、细胞增殖、细胞凋亡和肿瘤发生的核心。因此认识NF-κB与IHD的关系,对预防、诊断和治疗IHD至关重要,而NF-κB在其中的调控作用又十分复杂,随着对NF-κB的深入研究,如何利用调控其信号通路从而达到降低IHD危害的目的是一个亟待解决的问题,同时也成为防治IHD的重要靶点。     

HBV表面抗原preS1激活Wnt信号通路导致肝癌发生的机制研究

目的 探究HBV表面抗原preS1促使正常肝细胞向癌化肝细胞发展的具体机制。方法 分析临床样本和细胞模型中HBV表面抗原preS1与肝癌发生的相关性和内在机制。结果 临床标本分析发现,HBV携带者肝癌组织切片中CD133+肝癌干细胞数量高于对照组。进一步研究发现,HBV的表面膜蛋白preS1可以上调肝细胞癌化相关因子。利用免疫共沉淀技术,我们发现preS1与β-catenin存在相互作用。preS1通过抑制β-catenin的磷酸化激活Wnt信号通路。结论 HBV表面抗原preS1通过抑制β-catenin的磷酸化,激活Wnt信号通路,促进正常肝细胞向癌化肝细胞转化。     

Lower serum viral loads in young patients with hepatitis-B-virus-related hepatocellular carcinoma

Advanced age and high hepatitis B virus (HBV) DNA level are risk factors associated with the development of HBV-related hepatocellular carcinoma (HCC). However, little is known about the role of viral load in the carcinogenesis of HCC in young people. A total of 183 HBV-related HCC patients and 202 HBV carriers were therefore enrolled to compare serum viral loads in young (40 years of age) age groups. Other factors associated with the development of HCC were also analysed. The results showed that serum alanine aminotransferase (38.7 +/- 24.1 vs 58.4 +/- 65.4 IU/L, P = 0.006) and HBV DNA levels (log(10) titre: 4.20 +/- 1.33 vs 4.80 +/- 1.39, P = 0.053) were lower in young HCC patients than in old HCC patients. There was a positive correlation between age and serum HBV DNA level in HCC patients but a negative correlation in HBV carriers. Young HCC patients with HBV genotype B infection had higher viral loads than those with genotype C infection (log(10) titre: 4.79 +/- 1.34 vs 3.27 +/- 0.60, P = 0.001). By multivariate logistic regression analyses, high serum HBV DNA level was associated with the development of HCC in old patients [odds ratio (OR) 1.584, 95% confidence interval (CI) 1.075-2.333] rather than in young patients (OR 0.848, 95% CI 0.645-1.116). In conclusion, viral factors in association with the development of HBV-related HCC in young patients may be different from their old counterparts. The complicated interplay between host and virus could be responsible for the emergence and aggressive outcome of early-onset HCC.     

肝癌患者血清HBV基因型、外膜大蛋白定量检测的临床意义

目的探讨血清乙型肝炎病毒(HBV)基因型及HBV外膜大蛋白(LHBs)水平与肝细胞癌的关系。方法对61例肝癌、65例慢性活动性乙型肝炎患者及10例HBV携带者的血清HBV基因型、HBV LHBs进行检测。结果136例中,B基因型56例(41.0%),C基因型76例(55.9%),B、C混合型1例(0.7%),B、D混合型3例(2.2%);随病情加重,C基因型比例增加;不同基因型HBV感染的肝癌患者间HBV DNA、HBV LHBs水平存在明显差异;慢性活动性肝炎患者二者无统计学差异。结论本地区HBV以B、C基因型为主,不同基因型HBV感染在肝癌的发生中可能存在不同机制。     

Genetic polymorphisms of cytochrome P450 in patients with hepatitis C virus-associated hepatocellular carcinoma

BACKGROUND: The carcinogenic process can be modulated by exposure to endogenous or environmental substance(s) acting as carcinogens or protocarcinogens. Polymorphic enzymes of cytochrome P450 (CYP) that play a role in detoxication/toxication of such substances via metabolization may account for the interpatient variability of clinical course in cancers such as hepatocellular carcinoma (HCC). Many CYP genetic polymorphisms, which may change enzyme activity, are known to exist in Japanese. The aim of the present study was to compare the frequencies of CYP polymorphisms between hepatitis C virus (HCV)-related HCC patients and healthy subjects. METHODS: Seven mutant alleles and related genotypes of CYP in 44 HCV-positive HCC patients were chosen as follows: *1C heterozygous, *1C homozygous and *1F homozygous for CYP1A2, *4A homozygous for CYP2A6, *2A or *3 heterozygous, *2A or *3 homozygous and *2A and *3 heterozygous for CYP2C19, and *10/*5 homozygous for CYP2D6. These mutant alleles have been reported to change the CYP enzyme activity in Japanese. The frequencies of the mutant alleles and genotypes were then compared with those reported in healthy Japanese. RESULTS AND CONCLUSION: There is no statistically significant difference in genetic mutant alleles between the two groups, except for the genotype of CYP2A6*4A homozygous. The frequency of this genotype in the HCC patients (0.144) is significantly higher than that in healthy Japanese (0.034; P < 0.05; odds ratio 3.36). The clinical significance related to HCC is unknown. Further evaluation of CYP2A6*4A (deletion type) in HCV-related HCC patients is required.     

肝癌患者血清中乙型肝炎病毒基因分型及临床意义

目的:探讨血清中乙型肝炎病毒(HBV)基因型及HBV DNA水平与肝细胞癌的关系。方法:应用巢式聚合酶链反应扩增乙型肝炎病毒与基因,用末端标记方法对PCR产物标记并直接测序,测序结果和GenBank中登录的标准基因型序列相比较,应用荧光定量PCR法检测HBV DNA水平。对61例肝癌、65例慢性乙型肝炎、10例乙型肝炎病毒携带者进行了检测。结果:136例中B基因型59例(43.4%)、C基因型77例(56.6%),随着病情加重,C基因型比例逐渐增高;不同基因型HBV感染的肝癌患者间HBV DNA水平差异有显著意义,P<0.05;在慢性乙型肝炎患者中,HBV DNA水平差异无显著性意义。结论:本地区乙型肝炎病毒以B、C基因型为主,乙型肝炎病毒C基因型及高水平的HBV DNA感染与肝癌的发生相关。     

Role of N-acetyltransferase polymorphisms in hepatitis B related hepatocellular carcinoma: impact of smoking on risk

BACKGROUND: Persistent infection with hepatitis B virus (HBV) causes chronic phasic necroinflammation and regenerative proliferation in the liver. The sustained hepatocellular proliferation may render chronic HBV carriers more susceptible to the effects of environmental carcinogens. Aromatic amines are potential hepatocarcinogens in humans. N-acetyltransferase (NAT) is involved in the metabolic activation and detoxification of these compounds. AIMS: To investigate if genetic polymorphisms in N-acetylation are related to hepatocellular carcinoma (HCC) among chronic HBV carriers. METHODS: Genotyping of NAT1 and NAT2 was performed using polymerase chain reaction-restriction fragment length polymorphism on peripheral leucocyte DNA from 151 incident cases of HCC and 211 controls. All subjects were male, and were chronic HBV surface antigen carriers. RESULTS: A significant association between NAT2 genetic polymorphism and HCC was observed among chronic HBV carriers who were smokers but not among those who were non-smokers. For smoking HBV carriers, the odds ratios of developing HCC for those heterozygous and homozygous for the NAT2*4 functional allele compared with those without any copies of the functional allele (reference group) were 2.67 (95% confidence interval 1.15-6.22) and 2.58 (95% confidence interval 1.04-6.43), respectively. The interaction between cigarette smoking and the presence of the NAT2*4 allele just failed to reach statistical significance (p=0.06). No association between NAT1 genotype and HCC was evident overall or within the smoking stratified subgroups. CONCLUSIONS: Our results suggest that NAT2 activity may be particularly critical in smoking related hepatocarcinogenesis among chronic HBV carriers. Our data also indirectly support a role for tobacco smoke derived aromatic amines in the aetiology of HCC.     

Dietary iron overload in the African and hepatocellular carcinoma.

Dietary iron overload occurs commonly in parts of sub-Saharan Africa. It results from the consumption of large volumes of traditional beer that is home-brewed in iron pots or drums and consequently has a high iron content. The liver becomes iron overloaded and may develop portal fibrosis or, less often, cirrhosis. A genetic predisposition to the condition has been suggested, but no putative gene has yet been identified. Although originally believed not to cause hepatocellular carcinoma, recent case-control studies have shown African Blacks with dietary iron overload to be at increased risk for the tumour and a causal association has been confirmed in an animal model. The mechanisms of iron-induced malignant transformation are yet to be fully characterised, but the close association between cirrhosis and hepatocellular carcinoma in patients with hereditary haemochromatosis and the lesser association in those with dietary iron overload, suggests that chronic necroinflammatory hepatic disease contributes to the malignant transformation. Increased hepatic iron may, however, also be directly carcinogenic. Probable mechanisms include the generation of reactive oxygen intermediates and the resultant chronic oxidative stress that damages hepatocytes and proteins, causes lipid peroxidation, and induces strand breaks, DNA unwinding, and mutations in tumour-suppressor genes and critical DNA repair genes.     

茵陈蒿汤抑制JAK2/STAT3信号通路调控肝癌细胞增殖与凋亡

目的 探索茵陈蒿汤的抗肝癌作用及其机制.方法 体外培养HepG2肝癌细胞,分为对照组和茵陈蒿汤低、中、高浓度(12.5、25、50μg/mL)组.通过CCK-8检测细胞活力、EdU染色观察茵陈蒿汤对HepG2肝癌细胞增殖的影响,钙黄绿素/PI细胞染色观察茵陈蒿汤对肝癌细胞存活能力的影响.通过Western blot检测...     

原发性肝癌患者DNA损伤修复酶基因多态性分析

目的探讨DNA损伤修复酶基因多态性与原发性肝癌发生发展的关系。方法 PCR-RFLP法检测150例肝癌患者（肝癌组）和150例健康体检者（对照组）DNA损伤修复酶基因的表型,并进行比较。结果肝癌组XRCC1 Arg399Gln位点野生型的比率明显低于对照组（P〈0.05）;XRCC1（Arg194Trp、Arg280His）、hOGG1Ser326Cys位点多态性型别在两组中出现的频率相近（P〉0.05）;各基因位点不同表型者的尿8-羟基脱氧鸟苷（8-OHdG）水平相比,P均〉0.05。结论 DNA修复酶基因多态性与肝癌的发生发展无明确的相关关系。     

Loss of heterozygosity on chromosome 16 in hepatocellular carcinoma

In order to understand the molecular genetics of human hepatocellular carcinoma (HCC) a common chromosomal abnormality in HCC was examined using restriction fragment length polymorphism (RFLP) analysis. Sixty-eight HCC specimens were examined for loss of heterozygosity at 11 different chromosomal arms including 1p, 5p, 11p, 11q, 13q, 14q, 15q, 16p, 16q, 18q, and 19q. Losses were not detected on chromosome 1, 5, 14, 15 or 19, and the frequencies of losses were low (11-19%) for chromosomes 11, 13 and 18. In contrast, loss of heterozygosity was frequently observed for three different loci on chromosome 16, the HBA locus at 16p13.3 (22%), the MT2 locus at 16q21-22.1 (15%) and the HP locus at 16q22.1-22.2 (39%). There was no remarkable difference in the frequencies of loss of heterozygosity at these loci among HBV related HCC, HCV related HCC and neither virus (NBNC) related HCC. Thus, the results indicate that at least three different genetic abnormalities in chromosome 16 are commonly observed in various HCC, and that this chromosome may have some important role(s) in recessive genetic changes which generate this tumour.