Oxidative DNA and RNA damage and their prognostic values during Salmonella enteritidis-induced intestinal infection in rats

Abstract

Emerging evidence suggests that microbial pathogens may induce oxidative stress in infected hosts. The aim of the present study was to investigate the relationship between changes in oxidative stress and intestinal infection with and without antibiotic treatment in animal models. Sprague-Dawley (SD) rats were divided into three groups: rats infected with Salmonella enterica serovar Enteritidis (S. enteritidis), rats infected with S. enteritidis followed by norfloxacin treatment, and the control group. To evaluate oxidative stress changes, levels of 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) and 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dGsn), which represented oxidative damage to RNA and DNA, respectively, were analysed in urine and tissue samples. In urine, the level of 8-oxo-Gsn increased significantly after oral exposure to S. enteritidis (p?≤?0.001) and returned to baseline after recovery. Notably, norfloxacin treatment decreased the level of 8-oxo-Gsn in urine significantly (p?=?0.001). Changes of 8-oxo-Gsn measured in tissues from the small intestine, colon, liver and spleen were consistent with 8-oxo-Gsn measured in urine. Our study suggested that 8-oxo-Gsn in urine may serve as a highly sensitive biomarker for evaluating the severity of S. enteritidis infection and the effectiveness of antibiotic treatment against infection.     

The Prognostic Role of BRAF Mutation in Metastatic Colorectal Cancer Receiving Anti-EGFR Monoclonal Antibodies: A Meta-Analysis

Background

BRAF mutation has been investigated as a prognostic factor in metastatic colorectal cancer (mCRC) undergoing anti-EGFR monoclonal antibodies (moAbs), but current results are still inconclusive. The aim of this meta-analysis was to evaluate the relationship between BRAF mutation status and the prognosis of mCRC patients treated with moAbs.

Methods

Eligible studies were identified by systematically searching Pubmed, the Cochrane Library, Web of Knowledge, and OVID. Risk ratio (RR) for overall response rate (ORR), Hazard ratios (HRs) for Progression free survival (PFS) and Overall survival (OS) were extracted or calculated. Prespecified subgroup analyses were conducted in KRAS wild-type and in different study types. The source of between-trial variation was explored by sensitivity analyses. Quality assessment was conducted by the Hayden’s criteria.

Results

A total of twenty one trials including 5229 patients were identified for the meta-analysis. 343 patients displayed BRAF mutations of 4616 (7.4%) patients with known BRAF status. Patients with BRAF wild-type (WT) showed decreased risks of progression and death with an improved PFS(HR 0.38, 95% confidence intervals 0.29–0.51) and an improved OS (HR 0.35 [0.29–0.42]), compared to BRAF mutant. In KRAS WT population, there were even larger PFS benefit (HR 0.29[0.19,0.43]) and larger OS benefit (HR 0.26 [0.20,0.35]) in BRAF WT. A response benefit for BRAF WT was observed (RR 0.31[0.18,0.53]) in KRAS WT patients, but not observed in unselected patients (RR 0.76 [0.43–1.33]). The results were consistent in the subgroup analysis of different study types. Heterogeneity between trials decreased in the subgroup and explained by sensitivity analysis. No publication bias of ORR, PFS and OS were detected.

Conclusions

The results indicate that BRAF mutant is a predictive biomarker for poor prognosis in mCRC patients undergoing anti-EGFR MoAbs therapy, especially in KRAS WT patients. Additional large prospective trials are required to confirm the predictive role of BRAF status.     

探寻肝再生磷酸酶3在膀胱癌细胞T24中的作用

目的：已经有研究证明肝再生磷酸酶3（PhosphataseofRegeneratingLiver-3,PRL-3）在消化道肿瘤的发生发展过程中起到重要作用,但其在膀胱癌中发挥何种作用尚不清楚,本次研究主要探寻PRL-3在膀胱癌细胞T24中作用,以求为膀胱癌的治疗提供新思路。方法：采用siRNA干涉的方法下调T24中PRL-3蛋白表达水平,通过westernblot方法检测干涉效果,绘制细胞生长曲线、构建裸鼠种植瘤模型,检测PRL-3下调对细胞体外及体内增殖的影响。结果：我们所设计的siRNA能够下调PRL-3在A498细胞中的表达（F=7．26,P〈0．05）,细胞生长曲线显示下调PRL-3能够抑制细胞的增殖,这种作用从干涉后的第60h开始,随时间增加作用愈加明显（F≥8．35,P〈0．05）;动物实验表明,siRNA下调PRL-3能够抑制T24细胞在活体内的增殖,从干涉后第21天开始这种作用开始体现出来（F≥10．46,P〈0．05）,并且干涉组的肿瘤肿瘤明显低于两个对照组（F=13．63,P〈0．05）。结论：我们构建的siRNA能够在T24细胞中实现对PRL．3蛋白的下调,siRNA介导的PRL-3蛋白下调能够明显抑制T24细胞在活体外及活体内的增殖,这初步证明PRL-3在膀胱癌中发挥重要的作用。随着我们对PRL-3分子进一步深入的了解,揭示其发挥作用的具体机制,PRL-3很可能成为膀胱癌基因治疗的新靶点。     

生长调节剂调控龙眼冲梢的研究

为高效、安全地调控龙眼冲梢,在龙眼花芽形态分化开始期(露红点期)和花穗主轴长6～9 cm的花穗展叶期,施用生长调节剂,比较了不同方法调控龙眼冲梢的效果。结果发现龙眼花芽形态分化开始期树冠喷施200 mg/kg乙烯利+150 mg/kg多效唑混合液和土施多效唑每株4 g处理控冲梢效果都显著高于对照,冲梢率分别是10.5%和7.6%,在花穗小叶处于展叶期虹吸输300 mg/kg乙烯利防控龙眼冲梢有效且安全。     

江西省弄蝶四新纪录(鳞翅目:弄蝶总科)(英文)

通过对外形特征和外生殖器特征的检视,发现江西省弄蝶四新纪录:无斑珂弄蝶指名亚种Caltoris bromus bromus(Leech,1894)、襟弄蝶中南亚种Pseudocoladenia dan fabia(Evans,1949)、灰陀弄蝶黎氏亚种Thoressa gupta leechii(Evans,1932)和南岭陀弄蝶Thoressa xiaoqingae Huang&Zhan,2004。标本均采自江西九连山国家级自然保护区。文中提供了成虫标本照片。     

Nucleostemin基因在卵巢上皮性肿瘤的表达及与病理分型的关系

目的：研究核干细胞因子Nucleostemin（NS）基因在卵巢上皮性肿瘤中的表达,探讨其与肿瘤病理分型的关系。方法：采用RT-PCR及Western blot检测36例卵巢癌组织手术标本,32例卵巢良性上皮肿瘤组织手术标本,12例正常卵巢组织标本中Nu-cleostemin基因及相应蛋白的表达,采用分组对照的方法对比3组样本中NS基因及蛋白的表达情况,并进行相对定量研究。采用统计学方法检测NS基因的表达是否与临床病理分级及血清CA125存在关联。结果：①卵巢癌组织中NS的阳性表达率显著高于良性肿瘤组织及正常卵巢组织;②卵巢癌组织中,淋巴结转移组NS的表达水平高于未转移组;③临床分期Ⅲ期组的表达水平高于ⅠB期组;④中、低分化组的表达水平高于高分化组。结论：卵巢癌组织中存在NS基因的高表达,其表达量与组织类型无关,而与临床TNM分期及组织分级正相关。     

沙冬青AmNAC3转录因子基因在抗旱性和抗寒性中的功能鉴定

为了研究强抗逆植物沙冬青Am NAC3转录因子基因在抗旱性和抗寒性中的功能,首先利用半定量RT-PCR方法对该基因进行了表达分析。结果表明,在室内培养的沙冬青幼苗中,Am NAC3有一定量的基础表达,在干旱胁迫下其转录水平明显上调,而在低温胁迫下其表达上调较弱。然后利用5'RACE技术获得该基因的5'端序列及全长cDNA序列,并利用RT-PCR方法克隆到其全长编码区(846bp)。将编码区片段构建到植物表达载体上,利用农杆菌介导法获得转基因拟南芥。进一步分析表明,转基因拟南芥对于干旱和低温胁迫的抗性表型与野生型无明显差异,但其离体叶片的失水率和气孔开度均大于野生型。此外,转基因幼苗中气孔开闭相关基因ABI1和ABI2的表达量降低。这些结果表明,Am NAC3可能主要在响应干旱胁迫和调节气孔开闭及叶片保水性中发挥功能,而在抵抗低温胁迫中无明显作用。     

气质联用结合多变量分析研究蜂蜜的挥发性成分

为探究不同蜜源蜂蜜中的挥发性标记物并籍以对这些蜂蜜进行有效区分,本研究优化了静态顶空气相色谱-质谱联用技术(SHS-GC-MS)检测蜂蜜中挥发性化合物的方法,采用此方法分析了油菜蜜、椴树蜜、荆条蜜和洋槐蜜等4种蜂蜜总计38份样品的挥发性成分,并结合主成分分析(PCA)和聚类分析(CA)等对蜂蜜进行区分。研究结果表明,采用SHS-GC-MS共检测到23种化合物。4种蜂蜜的挥发性成分在物质种类或含量上存在明显差异,其中3-苯丙酸乙酯可作为油菜蜜的典型挥发性代谢物质;1-异丙烯基-3-甲基苯和反式玫瑰醚可作为椴树蜜的典型挥发性代谢物质;在荆条蜜和洋槐蜜中均未发现典型挥发性代谢物质。PCA可以将4种蜂蜜进行很好地区分,PC1、PC2和PC3累计贡献率达到77.3%,表明模型有效;当临界值取10时,CA可以将同种蜂蜜聚为一类。SHS-GC-MS检测的蜂蜜挥发性成分结果结合多变量分析,可用于区分不同蜜源蜂蜜。研究结果为蜂蜜溯源和鉴别提供了理论依据。