Anti-benzopyrene-7,8-diol-9,10-epoxide induces apoptosis via mitochondrial pathway in human bronchiolar epithelium cells independent of the mitochondria permeability transition pore

Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) is a ubiquitous environmental pollutant contained in tobacco smoke, automobile exhausts and barbecued foods. The carcinogenicity of BPDE on animals has been well characterized, whereas its apoptotic effect is not well defined. A recent study has shown that BPDE-mediated apoptotic pathway has varying specificity across different cell lines. Squamous cell carcinoma (SCC) arises from bronchiolar epithelium cells, therefore, we set out to investigate the pulmonary toxicity and apoptotic effect of BPDE in human bronchiolar epithelium cells (16HBE). Our results show BPDE induces mitochondrial-mediated apoptosis in a dose-dependent manner in 16HBE cells. The cleavage of caspase-3,-9 and release of Cytochrome c (cyt c) was regulated during apoptotic stimulation. However, the opening of mitochondria permeability transition pore (mPTP) has not been detected. Furthermore, our data also indicate that the formation of reactive oxygen species (ROS), decline of mitochondrial membrane potential (ΔΨ_m), increasing p53 and decreasing c-Myc levels play important roles in response to BPDE toxicity. In conclusion, these results suggest that BPDE-mediated apoptosis occurs via caspase-9 dependent mitochondria pathway associated with ROS formation, loss of ΔΨ_m, up-regulation of p53 and down-regulation of c-Myc, but independent of the opening of mPTP in 16HBE cells.     

Evaluation of bisphenol A glucuronidation according to UGT1A1*28 polymorphism by a new LC-MS/MS assay

The endocrine disruptor bisphenol A (BPA) is a frequently used chemical in the manufacture of consumer products. In humans, BPA is extensively metabolized to BPA glucuronide (BPAG) by different UDP-glucuronosyltransferase (UGT) isoforms. The study has been performed with the intention to improve the accuracy of published physiologically based pharmacokinetic models and to improve regulatory risk assessments of BPA. In order to gain insight into intestine, kidney, liver, and lung glucuronidation of BPA, human microsomes of all tested organs were used. BPAG formation followed Michaelis-Menten kinetics in the intestine and kidney, but followed substrate inhibition kinetics in the liver. Human lung microsomes did not show glucuronidation activity towards BPA. While the liver intrinsic clearance was very high (857 mL min(-1)kg body weight(-1)), the tissue intrinsic clearances for the kidney and intestine were less than 1% of liver intrinsic clearance. Since BPA is a UGT1A1 substrate, we postulated that the common UGT1A1*28 polymorphism influences BPA glucuronidation, and consequently, BPA detoxification. Hepatic tissue intrinsic clearances for UGT1A1*1/*1, UGT1A1*1/*28, and UGT1A1*28/*28 microsomes were 1113, 1075, and 284 mL min(-1)kg body weight(-1), respectively. Prior to microsomal experiments, the bioproduction of BPAG and stable isotope-labeled BPAG (BPAG(d16)) was performed for the purpose of the reliable and accurate quantification of BPAG. In addition, a sensitive LC-MS/MS analytical method for the simultaneous determination of BPA and BPAG based on two stable isotope-labeled internal standards was developed and validated. In conclusion, our in vitro results show that the liver is the main site of BPA glucuronidation (K(m) 8.9 μM, V(max) 8.5 nmol min(-1) mg(-1)) and BPA metabolism may be significantly influenced by a person's genotype (K(m) 10.0-13.1 μM, V(max) 3.4-16.2 nmol min(-1) mg(-1)). This discovery may be an important fact for the currently on-going worldwide BPA risk assessments and for the improvement of physiologically based pharmacokinetic models.     

耐亚胺培南鲍曼不动杆菌同源性及耐药机制研究

目的调查耐亚胺培南鲍曼不动杆菌在各科室的流行特点,研究其耐药机制。方法收集不同科室分离的耐药菌54株,采用Vitek-2Compact进行药敏实验;采用PFGE分析同源性;PCR及DNA测序检测耐药基因型。结果PFGEA型占77．8％,B型占18．9％。54株菌都携带OXA-66基因,53株菌携带OXA-23基因,41株菌携带16SrRNA甲基化酶annA基因。结论临床科室存在A型耐药菌的克隆播散。产OXA-23型碳青霉烯酶基因及其上游插入序列ISAbaI是其最主要的耐药机制。     

直肠癌组织中PgP蛋白和p16蛋白的表达及临床意义

目的探讨PgP和p16蛋白在直肠癌组织中的表达情况及临床意义。方法应用MaxVisionTM免疫组化的方法对71例直肠癌及癌旁组织进行PgP和p16蛋白检测。结果 PgP的总阳性率为84.51%(60/71)。PgP的阳性表达与直肠癌的淋巴结有无转移有关,与癌组织的分化程度、浸润深度与伴不伴有神经浸润无关。其中低分化腺癌(93.33%,28/30)高于高分化腺癌(82.61%,19/23)、中分化腺癌(72.22%,13/18,P>0.05)。淋巴结无转移组93.48%(43/46)明显高于淋巴结转移组68%(17/25,P<0.05)。伴有神经浸润组85.71%(24/28)与不伴有神经浸润组(83.72%,36/43,P>0.05)两者之间差异无统计学意义。癌组织浸润到浆膜外脂肪组织(87.5%,21/24)高于浸润到肠壁全层(84.21%,32/38),高于浸润到肠壁肌层(77.78%,7/9,P>0.05)。p16蛋白的总阳性率为(64.79%,46/71)。p16蛋白的阳性表达与淋巴结有无转移及组织的分化程度无关,与伴不伴有神经浸润及癌组织的浸润深度有关。其中其低分化腺癌(73.33%,22/30)高于高分化腺癌(60.87%,14/23)和中分化腺癌(55.56%,10/18,P>0.05)。淋巴结转移组(17/25,68%)与淋巴结无转移组(29/46,63.04%)两者之间差异无统计学意义(P>0.05)。不伴有神经浸润组(79.07%,34/43)明显高于伴有神经浸润组(42.86%,12/28,P<0.05)。癌组织浸润到肌层(88.89%8/9)高于浸润到全层(71.05%,27/38),明显高于癌组织浸润到浆膜外脂肪组织(45.83%,11/24,P<0.05)。结论 PgP和p16蛋白的阳性表达与直肠癌的某些临床病理指标相关,可作为对判断直肠癌的恶性程度,预测肿瘤侵袭转移,评估预后的良好指标。     

多层螺旋CT对小肝癌的诊断分析

目的研究小肝癌（SHCC）在l6层螺旋CT（SCT）多期（动脉期、门脉期和延迟期）增强扫描的表现特征。方法对本院经病理证实的56例小肝癌患者的影像学资料进行回顾性分析。结果患者动脉期的病灶数要明显高于门静脉期和延迟期,差异有统计学意义（P〈0.01）,动脉期的敏感性高于门脉期和延迟期。小肝癌总的病灶栓出率为94.6%（53/56）,动脉期、门静脉期和延迟期的病灶检出率分别为87.5%（49/56）、69.6%（39/56）和60.7%（34/56）。结论多层螺旋CT多期增强扫描能够充分反映出小肝癌的血供特点和表现,能够实现早期诊断。     

钡餐与CT检查在食管癌术前诊断中的应用分析

目的探讨食管癌医学影像检查术前诊断价值。方法对本院2009年6月～2011年6月36例经病理证实的食管癌患者术前钡餐和CT表现与手术后病理结果进行比较。结果36例患者中按照Moss分期标准Ⅰ期1例,Ⅱ期5例,Ⅲ期21例,Ⅳ期9例。结论应用钡餐与CT检查可提高食管癌患者的检出率,有助于手术方式的选择及术前分期的确定。     

p53基因第72位密码子基因多态性与HPV16相关宫颈癌

目的探讨湖北地区汉族女性人群中p53基因第72位密码子基因多态性与HPV16相关宫颈癌发生的关系。方法随机选取经PCR检测证实HPV16阳性的宫颈病变病例228例。其中病理证实为宫颈浸润癌的156例作为宫颈癌组,宫颈上皮内瘤变或宫颈炎72例为对照组。用直接PCR法检测新鲜组织标本中p53基因第72位密码子的基因型在宫颈癌组与对照组的分布情况,分析p53codon72基因多态性与HPV16阳性宫颈癌之间的相关性。结果所有样本均成功检测出p53codon72基因型。Pro／Pro、Arg／Pro、Arg／Arg在HPV阳性宫颈癌样本中所占比例分别为22．2％、47．2％、30．6％;在对照组中的比例分别为32．7％、53．2％、14．1％。两组总构成比差异有统计学意义（P=0．010）。与其他两种基因型相比,p53codon72Arg／Arg基因型在HPV16阳性宫颈癌样本检出率明显高于在HPV16阳性宫颈上皮内瘤变及宫颈炎组中的检出率（P=0．004,OR=2．680）。结论p53codon72Arg／Arg基因型是湖北地区汉族女性发生HPV16相关宫颈癌的遗传易感因素。     

手足口病病原学检测及流行病学分析

目的分析信阳市手足口病实验室检测结果,掌握手足口病流行趋势,为本地区手足口病的综合防治提供参考资料。方法采集临床880份诊断为手足口病病例的咽拭子、粪便和肛拭子、疱疹液,应用real time RT-PCR技术检测肠道病毒71型(EV71)、柯萨奇病毒A组16型(CA16)、通用型肠道病毒(EV)。结果 880份检测标本中,肠道病毒总体检出率为74.32%,其中肠道病毒EV71型、CA16型和其它肠道病毒阳性检出率分别为34.66%、17.27%和20.11%。不同病毒阳性检出率差异有统计学意义(χ2=307.45,P<0.01)。880份检测标本中,从发病至采样0～3d病毒核酸检测率最高(83.54%),其次是4～7d(76.87%)。咽拭子、粪便、肛拭和疱疹液阳性率分别为8.33%、78.01%、66.15%和75%。粪便与其它样本的阳性检出率差异有统计学意义(χ2=27.05,P<0.01)。病例发病集中在4～7月份,以EV71感染为主,病毒感染率以<1岁组最高,男女病毒感染率差异无统计学意义(χ2=0.12,P=0.73)。结论信阳市手足口病的病原体主要是EV71,其流行具有明显的年龄、季节界限。     

Avicholic Acid: A Lead Compound from Birds on the Route to Potent TGR5 Modulators

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Endophytic bacterial diversity in roots of Typha angustifolia L. in the constructed Beijing Cuihu Wetland (China)

We investigated the community structure of endophytic bacteria in narrowleaf cattail (Typha angustifolia L.) roots growing in the Beijing Cuihu Wetland, China, using the 16S rDNA library technique. In total, 184 individual sequences were used to assess the diversity of endophytic bacteria. Phylogenetic analysis revealed that 161 clones (87.5%) were affiliated with Proteobacteria, other clones grouped into Cytophaga/Flexibacter/Bacteroids (3.3%), Fusobacteria (3.8%), and nearly 5% were uncultured bacteria. In Proteobacteria, the beta and gamma subgroups were the most abundant, accounting for approximately 46% and 36.6% of all Proteobacteria, respectively. The dominant genera included Rhodoferax, Pelomonas, Uliginosibacterium, Pseudomonas, Aeromonas, Rhizobium, Sulfurospirillum, Ilyobacter and Bacteroides. While some of these endophytic bacteria are capable of fixing nitrogen and can therefore improve plant growth, other endophytes may play important biological roles by removing nitrogen, phosphorus and/or organic matter from the water body and thus have the potential to enhance the phytoremediation of eutrophic water bodies. These bacteria have the potential to degrade xenobiota such as methane, methanol, methylated amines, catechol, oxochlorate, urea, cyanide, and 2,4-dichlorophenol. Hence, the use of certain endophytic bacteria in the process of phytoremediation could be a powerful approach for the restoration of eutrophic systems.