镇肝熄风汤对帕金森病大鼠易激惹程度和结膜充血及NQO-1,TH的影响

目的:观察镇肝熄风汤对帕金森病肝大鼠易激惹程度和结膜充血的影响及可能机制。方法:将105只Wistar大鼠随机分为正常组,假手术组,模型组,司来吉兰组(0.9 mg·kg~(-1)·d~(-1)),镇肝熄风汤低、中、高剂量组(8,16,32 g·kg~(-1)·d~(-1)),每组15只。采用附子汤ig联合6-羟基多巴胺单侧损毁黑质法复制帕金森病肝阳上亢型病证结合大鼠模型,灌胃4周。蛋白质免疫印迹(Western blot)及实时荧光定量聚合酶链式反应(Real-time PCR)检测酪氨酸羟化酶(TH)和醌氧化还原酶-1(NQO-1)蛋白和mRNA表达。结果:与假手术组比较,帕金森病肝阳上亢证模型大鼠易激惹程度和结膜充血显著升高,中脑组织NQO-1蛋白和mRNA表达增加,而TH蛋白表达明显降低(P0.05)。与帕金森病肝阳上亢证模型组比较,镇肝熄风汤组大鼠易激惹程度和结膜充血显著降低,TH蛋白表达显著增加,NQO-1蛋白和mRNA表达均明显增加(P0.05),而司来吉兰组大鼠易激惹程度、结膜充血和中脑组织NQO-1蛋白表达无显著性差异。结论:镇肝熄风汤能显著改善帕金森病肝阳上亢证模型大鼠易激惹程度和结膜充血,其机制可能与上调大鼠中脑组织TH和NQO-1分子表达有关。     

Role of pharmacogenomics and pharmacodynamics in the treatment of acute lymphoblastic leukaemia

Pharmacodynamic studies have been used to establish the relationships between the administered dosage and the concentration of drugs and metabolites in the blood or tissues and that between these concentrations and pharmacological effects. Polymorphisms in the genes that encode drug-metabolizing enzymes, drug transporters and drug targets can affect a person's response to therapy and may affect the development of de novo or therapy-related leukaemias. The burgeoning field of pharmacogenomics elucidates inherited differences in drug metabolism and treatment response. Increasingly, pharmacodynamic and pharmacogenomic studies are being used to individualize therapy to enhance efficacy and reduce toxicity.     

NQO1基因C6O9T多态性和环境因素与乳腺癌遗传易感性的关系

目的 探讨醌氧化还原酶1 (quinone oxido-reductase 1,NQO1)基因C609T多态性和环境因素与乳腺癌遗传易感性的关系.方法 采用以医院为基础的病例对照研究收集桂林医学院附属医院2012-10-15-2014-02-15共248例女性乳腺癌患者和该院2013-03-01-2013-12-30共284名女性健康体检者的人口学和环境暴露资料等,并采用TaqManMGB荧光定量聚合酶链反应技术和多因素非条件Logistic回归模型分析NQO1基因C609T在两组中分布频率的差异,以及与环境因素的交互作用.结果 病例组NQO1基因位点CC、CT和TT各基因型频率分别为27.42％、49.60％和22.98％,对照组中基因型频率分别为34.51％、50.35％和15.14％,差异有统计学意义,x2 =6.48,P=0.039.多因素Logistic回归分析表明,与CC基因型相比,CT或TT基因型的个体罹患乳腺癌的风险OR值分别为1.33和2.92.病例组等位基因T频率(47.78％)较对照组(40.32％)增高(x2=6.00,P=0.014),携带T等位基因者患乳腺癌的危险性是C等位基因携带者的1.36倍.交互作用分析表明,NQO1基因C609T多态性与经常熬夜、被动吸烟、精神创伤、睡觉佩戴胸罩、性格和体育锻炼等之间均存在交互作用(P＜0.05),其OR值分别为2.45、3.96、2.40、1.98、0.33和0.52.结论 NQO1基因C609T多态性可能为乳腺癌发病的遗传易感因素,且与环境因素具有协同致癌作用.     

Chemoprevention of liver cancer by plant polyphenols

Primary liver cancer or hepatocellular carcinoma (HCC) is one of the most frequent tumors representing the fifth commonest malignancy worldwide and the third cause of mortality from cancer. Currently, the treatments for HCC are not so effective and new strategies are needed for its fight. Chemoprevention, the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenesis is considered an important way for confronting HCC. Many of the chemopreventive agents are phytochemicals, namely non-nutritive plant chemicals with protective or disease preventive properties. In this review, we focus on plant polyphenols, one of the most important classes of phytochemicals, their chemopreventive properties against HCC and discuss the molecular mechanisms accounting for this activity.     

Significant association of PKM2 and NQO1 proteins with poor prognosis in breast cancer

Pyruvate kinase M2 (PKM2) and NAD(P)H:quinone oxidoreductase-1 (NQO1) have been known to play significant functions in tumorigenesis and development. The association between PKM2 and NQO1 in breast cancer continues, however, to be unclear. In the present study, according to UALCAN and GEPIA database, the mRNA levels of PKM2 and NQO1 in breast primary tumor were significantly higher compared to normal breast tissue. Consonant with these findings, increased expression of both PKM2 and NQO1 were detected in clinical samples and BC cell lines. More importantly, consolidated high expression of NQO1 and PKM2 were obtained to be related with worse clinical stage, relapse, shorter relapse free survival (RFS), and poorer overall survival (OS) in human breast cancer. We subsequently found that knockdown of NQO1 reduced the protein level of PKM2 significantly. Moreover, deletion of PKM2 significantly reduced colony formation, migration and invasion of BC cells. A positive correlation between PKM2 and NQO1 expression was identified by immunohistochemical analyses of 108 specimens of breast cancer patients (rs = 0.60, P = 0.00). Finally, endogenous Co-IP demonstrated that PKM2 and NQO1 interact in breast cancer cells. The results of this study suggest that the correlation between NQO1 and PKM2 might play a critical role during breast tumourigenesis and serve as novel diagnostic biomarkers for breast cancer.     

The melatonin analog 5-MCA-NAT increases endogenous dopamine levels by binding NRH:quinone reductase enzyme in the developing chick retina

NRH:quinone reductase (QR2) is present in the retinas of embryonic and post-hatched (PH) chicks. 5-Methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) is a QR2 ligand that increases cAMP levels in developing retinas, but it does not affect cAMP levels in CHO-QR2 cells. The dopamine quinone reductase activity of QR2 retrieves dopamine, which increases cAMP levels in developing retinas. The objective of the present study was to investigate whether 5-MCA-NAT increases endogenous dopamine levels in retinas from chick embryos and post-hatched chicks. Endogenous dopamine was measured by enzyme-linked immunosorbent assay (ELISA). 5-MCA-NAT increased retinal endogenous dopamine levels at all developmental stages studied and in PH chicks (−log EC50 = 11.62 ± 0.34 M). This effect was inhibited by non-selective antagonists of receptors and melatonin binding sites N-acetyl-2-benzyltryptamine (luzindole, 5 μM), but it was not inhibited by the Mel1b melatonin receptor antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT, 10 nM). The QR2 cosubstrate, N-methyl-dihydronicotinamide (NMH) (−log EC50 = 6.74 ± 0.26 M), increased endogenous dopamine levels in controls and in retinas stimulated with 5-MCA-NAT (3 nM). The QR2 inhibitor benzo[e]pyrene inhibited endogenous dopamine levels in both control (−log IC50 = 7.4 ± 0.28 M) and NMH-stimulated (at 100 nM and 1 μM benzo[e]pyrene concentrations) retinas. Theoretical studies using Molegro Virtual Docking software corroborated these experimental results. We conclude that 5-MCA-NAT increases the level of endogenous dopamine via QR2. We suggest that this enzyme triggers double reduction of the dopamine quinone, recovering dopamine in retinal development.     

Chlorogenic acid protects against liver fibrosis in vivo and in vitro through inhibition of oxidative stress

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