• 【北京和山东省食用动物来源肠球菌的流行和耐药性。】 复制标题 收藏 收藏
    DOI:10.1111/jam.12054 复制DOI
    作者列表:Liu Y,Liu K,Lai J,Wu C,Shen J,Wang Y
    BACKGROUND & AIMS: AIMS:To evaluate the prevalence and antimicrobial resistance of Enterococcus species from chickens and pigs in Beijing and Shandong Province, China. METHODS AND RESULTS:Swab samples were collected from four farms in Beijing and two in Shandong Province in 2009 and tested for Enterococcus. Minimum inhibitory concentrations of antimicrobial agents were determined using broth microdilution or agar screening methods. A total of 453 Enterococcus isolates were recovered, belonging to six different Enterococcus species. All isolates were sensitive to vancomycin. Resistance to tetracycline (92.5%), amikacin (89.4%), erythromycin (72.8%) and rifampin (58.1%), and high-level streptomycin resistance (HLSR, 50.3%) were prevalent, while resistance to penicillins (7.9% to penicillin and 4.2% to ampicillin) was rare. The resistance rates to phenicols (chloramphenicol and florfenicol) and enrofloxacin, and high-level gentamicin resistance (HLGR) were approximately 30%. The vast majority of the Enterococcus isolates were classified as multidrug-resistant organisms. CONCLUSIONS:Resistance of Enterococcus sp. to most antimicrobials was more prevalent in China than in European or other Asian countries. SIGNIFICANCE AND IMPACT OF THE STUDY:Our findings reveal a high level of antimicrobial resistance in Enterococcus isolates from food animals in China and underline the need for prudent use of antibiotics in chicken and pig production to minimize the spread of antibiotic-resistant enterococci.
    背景与目标:
  • 【成人脑脊液转移装置感染: 脑室内抗菌治疗的作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.jinf.2012.11.006 复制DOI
    作者列表:Wilkie MD,Hanson MF,Statham PF,Brennan PM
    BACKGROUND & AIMS: OBJECTIVES:The precise role for intraventricular (IVT) antimicrobials in combination with systemic antibiotics in management of cerebrospinal fluid (CSF) diversion device-associated infections is uncertain. We evaluated our current practice, comparing dual therapy against systemic antimicrobials alone. METHODS:All adult patients with at least two consecutive CSF isolates who were treated for CSF diversion device-related infection over a 5-year period (2005-2010) were identified retrospectively. Clinical and laboratory parameters, microbiology, surgical and antimicrobial management, and treatment outcomes were analysed. RESULTS:Forty-eight patients were identified - 25 received IVT and systemic antibiotics (group A), and 23 systemic antibiotics alone (group B). Clinical features were similar between groups, as were causative organisms. CSF leucocyte counts differed slightly (A > B, p = 0.067) but no laboratory parameters differed significantly. Infected devices were generally revised (A = 92%, B = 91%). Mean times to CSF sterilisation and normalisation of CSF microscopy were significantly shorter for group A (p < 0.05 and p < 0.005 respectively), as was duration of hospital stay (p < 0.002) and required length of systemic antimicrobial therapy (p < 0.001). CONCLUSIONS:Our findings indicate that IVT antibiotics enhance clinical and microbiological recovery and should therefore be considered for patients with CSF infection associated with a CSF diversion device. We recommend further evaluation of this approach in a prospective, randomised, controlled trial.
    背景与目标:
  • 【有机锡和有机铅化合物与模型脂质膜的疏水和亲水相互作用的作用。】 复制标题 收藏 收藏
    DOI:10.1515/znc-1997-3-412 复制DOI
    作者列表:Gabrielska J,Sarapuk J,Przestalski S
    BACKGROUND & AIMS: The present study was conducted to clarify the mechanism of toxicity of organic compounds using lipid model membranes (liposomes and planar lipid membranes). The compounds studied were trialkyltin and trialkyllead chlorides, dialkyltin dichlorides and some inorganic forms of those metals. Two different (anionic and cationic) detergents were also used in the experiments to change the surface properties of liposomes. As a measure of interaction between the compounds studied and model membranes were the release of liposome bound praseodymium and the change in stability of planar membranes under the influence of those compounds. On the basis of the results obtained it was postulated that the mechanism of interaction between tin- and leadorganics and model lipid membranes is a combination of different factors featuring interacting sides. The most important properties determining the behaviour of organic compounds in the interaction were lipophilicity and polarity of different parts of the organics and the steric arrangement they can take in the medium. On the other hand, the surface potential of the lipid bilayer and the environment of the lipid molecules, that play a significant role in the availability of the lipid bilayer to the organics, were important factors in the interaction.

    背景与目标: 本研究旨在阐明使用脂质模型膜 (脂质体和平面脂质膜) 对有机化合物的毒性机理。研究的化合物是三烷基锡和三烷基氯化铅,二烷基锡二氯化物以及这些金属的某些无机形式。实验中还使用了两种不同的 (阴离子和阳离子) 洗涤剂来改变脂质体的表面性质。作为研究化合物与模型膜之间相互作用的量度,脂质体结合镨的释放以及在这些化合物的影响下平面膜的稳定性变化。根据获得的结果,推测锡和铅有机物与模型脂质膜之间的相互作用机理是具有相互作用方面的不同因素的组合。决定有机化合物在相互作用中的行为的最重要特性是有机物不同部分的亲脂性和极性以及它们在介质中可以采用的空间排列。另一方面,脂质双层的表面电势和脂质分子的环境在脂质双层对有机物的可用性中起着重要作用,是相互作用的重要因素。
  • 【第二个大质粒编码O119:H2和一些典型的O111肠致病性大肠杆菌菌株中的结合转移和抗菌素耐药性。】 复制标题 收藏 收藏
    DOI:10.1128/JB.00349-07 复制DOI
    作者列表:Nwaneshiudu AI,Mucci T,Pickard DJ,Okeke IN
    BACKGROUND & AIMS: :A novel and functional conjugative transfer system identified in O119:H2 enteropathogenic Escherichia coli (EPEC) strain MB80 by subtractive hybridization is encoded on a large multidrug resistance plasmid, distinct from the well-described EPEC adherence factor (EAF) plasmid. Variants of the MB80 conjugative resistance plasmid were identified in other EPEC strains, including the prototypical O111:NM strain B171, from which the EAF plasmid has been sequenced. This separate large plasmid and the selective advantage that it confers in the antibiotic era have been overlooked because it comigrates with the virulence plasmid on conventional gels.
    背景与目标: : 通过消减杂交在O119:H2肠致病性大肠杆菌 (EPEC) 菌株MB80中鉴定出的新颖且功能强大的共轭转移系统被编码在大型多药耐药质粒上,与描述明确的EPEC粘附因子 (EAF) 质粒不同。在其他EPEC菌株中鉴定了MB80共轭抗性质粒的变体,包括原型O111:NM菌株B171,从中对EAF质粒进行了测序。这种单独的大质粒及其在抗生素时代赋予的选择性优势被忽略了,因为它与常规凝胶上的毒力质粒共同存在。
  • 【化学遗传学: 用小分子化合物阐明生物系统。】 复制标题 收藏 收藏
    DOI:10.1038/sj.jid.5700853 复制DOI
    作者列表:Kawasumi M,Nghiem P
    BACKGROUND & AIMS: :Chemical genetics employs diverse small-molecule compounds to elucidate biological processes in a manner analogous to the mutagenesis strategies at the core of classical genetics. Screening small-molecule libraries for compounds that induce a phenotype of interest represents the forward chemical genetic approach, whereas the reverse approach involves small molecules targeting a single protein. Here, we review key differences between the goals for small-molecule screening in industry versus academia, recent developments in high-throughput screening, and publicly available resources of compound collections, screening facilities, and databases. A particularly exciting outcome of a chemical genetic screen is the discovery of a previously unknown role for a protein in a pathway together with compounds that affect the function of that protein. In illustrative cases, such discoveries have led to progress toward therapeutic development and more commonly have increased the size of the small molecule "toolbox" available to the research community for the study of biological processes.
    背景与目标: : 化学遗传学采用多种小分子化合物来阐明生物学过程,其方式类似于经典遗传学核心的诱变策略。筛选诱导感兴趣表型的化合物的小分子文库代表了正向化学遗传方法,而反向方法涉及靶向单个蛋白质的小分子。在这里,我们回顾了工业界与学术界小分子筛选的目标,高通量筛选的最新发展以及化合物集合,筛选设施和数据库的公开资源之间的主要差异。化学遗传筛选的一个特别令人兴奋的结果是发现了一种蛋白质在途径中的先前未知的作用以及影响该蛋白质功能的化合物。在说明性的情况下,这样的发现导致了治疗发展的进展,并且更常见的是增加了供研究界用于研究生物过程的小分子 “工具箱” 的大小。
  • 【来自甲虫二分法防御素的抗菌合成肽对小鼠的细胞毒性和抗原性。】 复制标题 收藏 收藏
    DOI:10.1016/j.intimp.2006.06.007 复制DOI
    作者列表:Koyama Y,Motobu M,Hikosaka K,Yamada M,Nakamura K,Saido-Sakanaka H,Asaoka A,Yamakawa M,Isobe T,Shimura K,Kang CB,Hayashidani H,Nakai Y,Hirota Y
    BACKGROUND & AIMS: :Synthetic peptides, peptides A (Arg-Leu-Tyr-Leu-Arg-Ile-Gly-Arg-Arg-NH(2)) and B (Arg-Leu-Arg-Leu-Arg-Ile-Gly-Arg-Arg-NH(2)), derived from the beetle Allomyrina dichotoma defensin, have antimicrobial activities. Immunotoxicological effect of these peptides was evaluated by cytotoxicity of mouse peritoneal macrophages. In addition, antigenicity of these peptides was studied by evaluating antibody responses in mice immunized with these peptides. The toxicity of peptide A toward mouse peritoneal cells was less than that of polymyxin B, when morphologically evaluated in a cytotoxicity test. Almost all of mice injected intraperitoneally (i.p.) with either peptide A or B at 50-150 mg/kg survived, whereas all mice injected i.p. with polymyxin B at the doses of more than 25 mg/kg died within 24 h. Interestingly, almost all of mice injected intravenously with these peptides at the doses of 10 and 25 mg/kg also survived. Furthermore, mice immunized with these peptides conjugated with keyhole limpet hemocyanin (KLH) showed little or negligible anti-peptide A or B antibody production, although anti-KLH antibody was significantly produced. The results indicated that peptides A and B were less cytotoxic than polymyxin B and also had poor antigenicity to produce specific antibody in mice.
    背景与目标: : 合成肽,肽A (Arg-Leu-Tyr-Leu-Arg-Ile-Gly-Arg-NH(2)) 和B (Arg-Leu-Arg-leg-Arg-Ile-Gly-Arg-NH(2)),衍生自甲虫二分蛋白防御素,具有抗菌活性。通过小鼠腹膜巨噬细胞的细胞毒性评估了这些肽的免疫毒理学作用。此外,通过评估用这些肽免疫的小鼠中的抗体反应,研究了这些肽的抗原性。在细胞毒性测试中进行形态学评估时,肽A对小鼠腹膜细胞的毒性小于多粘菌素B。几乎所有以50-150 mg/kg腹膜内 (i.p.) 注射肽A或B的小鼠均存活,而所有注射i.p.的小鼠均存活。多粘菌素b的剂量超过25 mg/kg,在24小时内死亡。有趣的是,几乎所有以10和25 mg/kg剂量静脉注射这些肽的小鼠也都存活了。此外,用这些与锁孔血蓝蛋白 (KLH) 缀合的肽免疫的小鼠显示出很少或可忽略的抗肽A或B抗体产生,尽管显着产生了抗KLH抗体。结果表明,肽A和肽B的细胞毒性低于多粘菌素B,并且在小鼠中产生特异性抗体的抗原性也较差。
  • 【在抗菌素耐药生物的传播研究中定义相关性: 跨研究定义的变异性以及不同方法对研究结论的影响。】 复制标题 收藏 收藏
    DOI:10.1086/668780 复制DOI
    作者列表:Greenblatt RM,Han JH,Nachamkin I,Tolomeo P,Lautenbach E
    BACKGROUND & AIMS: OBJECTIVE:Comparison of studies evaluating patient-to-patient transmission of organisms is difficult, given the lack of standardized criteria. We used fluoroquinolone-resistant Escherichia coli (FQREC) as a model to characterize variability in definitions of relatedness across studies and to evaluate the resultant impact on study conclusions. DESIGN:Narrative review and cohort study. METHODS:The narrative review compared relatedness criteria across studies of FQREC. Additionally, an existing database was used to compare relatedness of isolates on the basis of molecular criteria alone versus molecular plus clinical criteria with different temporal cutoffs (hospitalization overlap of ≥1 day or allowance for nonoverlap of hospitalization dates of ≤7 days or ≤30 days). RESULTS:Forty-six articles met narrative review inclusion criteria. Sixteen studies exclusively utilized molecular criteria to define relatedness. Thirty studies included molecular and clinical criteria. Of these, 6 included temporal data (ie, time period of isolate identification), 10 included patient location, and 14 included proximity and temporal criteria. For the database analysis, 353 patients were colonized with FQREC. There were 2 main clusters containing 48 and 17 related isolates within 49 pulsed-field gel electrophoresis types. Among the clusters, 18.4% of isolates were related by molecular criteria. Incorporating clinical criteria, fewer isolates were considered related: 5.7% of isolates using 30-day criteria, 3.1% using 7-day criteria, and 1.4% using 1-day overlap. CONCLUSIONS:There is considerable variability in definitions of relatedness of FQREC. Utilizing molecular criteria alone to define relatedness overestimates transmission compared with definitions including clinical criteria. Standard definitions of relatedness in studies of antimicrobial-resistant organisms are needed.
    背景与目标:
  • 【虎杖茎和芽的酚类化合物和抗氧化活性。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Samejo MQ,Memon S,Khan KM,Rajput SM,Gul S,Memon GZ,Panhwar QK
    BACKGROUND & AIMS: :In the present study we demonstrate the identification of phenolic compounds and the phenolic contents of the methanol extracts from stem and buds of Calligonum polygonoides with antioxidant activity. Eleven and nine phenolic compounds were identified and quantified from stem and buds, respectively by high-performance liquid chromatography (HPLC). p-Coumaric acid was predominant in stem and gallic acid in buds. In general, the samples with the highest phenolic contents had the highest antioxidant activities. Stem and buds sparked attention due to their high phenolic contents and antioxidant activities. The Results from present study reveal that the C. polygonoides could be considered as a promising source of antioxidant phytochemicals.
    背景与目标: : 在本研究中,我们证明了酚类化合物的鉴定以及具有抗氧化活性的caligonum polygonoides茎和芽中甲醇提取物的酚类含量。通过高效液相色谱 (HPLC) 分别从茎和芽中鉴定出11种和9种酚类化合物并对其进行定量。对香豆酸在茎中占主导地位,在芽中占主导地位。通常,酚类含量最高的样品具有最高的抗氧化活性。茎和芽由于其高酚类含量和抗氧化活性而引起了人们的关注。本研究的结果表明,多角藻可被认为是抗氧化剂植物化学物质的有希望的来源。
  • 【新型三环化合物作为凋亡蛋白 (IAP) 拮抗剂抑制剂的设计,立体选择性合成和生物学评估。】 复制标题 收藏 收藏
    DOI:10.1016/j.bmc.2013.07.020 复制DOI
    作者列表:Asano M,Hashimoto K,Saito B,Shiokawa Z,Sumi H,Yabuki M,Yoshimatsu M,Aoyama K,Hamada T,Morishita N,Dougan DR,Mol CD,Yoshida S,Ishikawa T
    BACKGROUND & AIMS: :We recently reported the discovery of octahydropyrrolo[1,2-a]pyrazine A as a lead compound for an inhibitor of apoptosis proteins (IAP) antagonist. To develop IAP antagonists with favorable PK profiles, we designed novel tri-cyclic compounds, octahydro-1H-cyclopropa[4,5]pyrrolo[1,2-a]pyrazines 1 and 2 based on co-crystal structural analysis of A with cellular IAP-1 (cIAP-1). The additional cyclopropane moiety was used to block the predicted metabolic site of compound A without detriment to the binding affinity for cIAP. Compounds 1 and 2 were stereoselectively synthesized via intermediates 4a and 5b', which were obtained by Simmons-Smith cyclopropanation of ethylester 3a and silyl ether 3b'. Compounds 1 and 2 showed strong growth inhibition in MDA-MB-231 breast cancer cells and improved metabolic stability in comparison to A. Compound 2 exhibited significant in vivo PD effects to increase tumor necrosis factor-alpha mRNA in a dose dependent manner.
    背景与目标: : 我们最近报道了八氢吡咯并 [1,2-a] 吡嗪A作为凋亡蛋白抑制剂 (IAP) 拮抗剂的领先化合物的发现。为了开发具有良好PK谱的IAP拮抗剂,我们设计了新的三环化合物,octahydro-1H-cyclopropa[4,5] 吡咯并 [1,2-a] 吡嗪1和2基于A与细胞IAP-1 (cIAP-1) 的共晶体结构分析。额外的环丙烷部分用于阻断化合物A的预测代谢位点,而不损害对cIAP的结合亲和力。化合物1和2通过中间体4a和5b' 立体选择性合成,它们是通过乙酸酯3a和甲硅烷基醚3b' 的Simmons-Smith环丙烷化获得的。与A相比,化合物1和2在MDA-MB-231乳腺癌细胞中显示出强烈的生长抑制作用,并改善了代谢稳定性。化合物2表现出显著的体内PD效应,以剂量依赖性方式增加肿瘤坏死因子-α mRNA。
  • 【从东方火腹蟾蜍 (Bombina orientalis) 的皮肤分泌物中发现了两种具有抗菌和抗癌活性的bombinin肽。】 复制标题 收藏 收藏
    DOI:10.1111/cbdd.13055 复制DOI
    作者列表:Zhou C,Wang Z,Peng X,Liu Y,Lin Y,Zhang Z,Qiu Y,Jin M,Wang R,Kong D
    BACKGROUND & AIMS: :Amphibian skin secretions are known to contain numerous peptides with a large array of biological activities. Bombinins are a group of amphibian-derived peptides with broad spectrum antimicrobial activities that have been only identified from the ancient toad species, Bombina. In this study, we described the identification and characterization of a novel bombinin precursor which encoded a bombinin-like peptide (BLP-7) and a novel bombinin H-type peptide (named as Bombinin H-BO) from the skin secretion of Oriental fire-bellied toad, Bombina orientalis. The primary structures of both mature peptides were determined by combinations of molecular cloning of peptide precursor-encoding cDNAs and mass spectrometry techniques. Secondary structure prediction revealed that both peptides had cationic amphipathic α-helical structural features. The synthetic replicate of BLP-7 displayed more potent antimicrobial activity than Bombinin H-BO against Gram-positive and Gram-negative bacteria and yeast. Also, in vitro antitumour assay showed that both peptides possessed obvious antiproliferative activity on three human hepatoma cells (Hep G2/SK-HEP-1/Huh7) at the non-toxic doses. These results indicate the peptide family of bombinins could be a potential source of drug candidates for anti-infection and anticancer therapy.
    背景与目标: 已知两栖动物皮肤分泌物含有大量具有大量生物活性的肽。Bombinins是一组具有广谱抗菌活性的两栖动物衍生肽,仅从古代蟾蜍物种Bombina中鉴定出。在这项研究中,我们描述了一种新的bombinin前体的鉴定和表征,该前体编码了一种bombinin样肽 (BLP-7) 和一种新的bombinin H型肽 (称为Bombinin H-BO),来自东方火腹蟾蜍的皮肤分泌物,东方Bombina。通过编码肽前体的cdna的分子克隆和质谱技术的组合确定了两种成熟肽的一级结构。二级结构预测表明,两种肽均具有阳离子两亲性 α-螺旋结构特征。BLP-7的合成复制比Bombinin H-BO对革兰氏阳性和革兰氏阴性细菌和酵母表现出更有效的抗菌活性。此外,体外抗肿瘤测定表明,两种肽在无毒剂量下对三种人肝癌细胞 (Hep G2/SK-HEP-1/Huh7) 具有明显的抗增殖活性。这些结果表明,bombinins的肽家族可能是抗感染和抗癌治疗的候选药物的潜在来源。
  • 【金 (I) 化合物的新靶标: 金诺芬抑制谷胱甘肽-S-转移酶。】 复制标题 收藏 收藏
    DOI:10.1016/j.jinorgbio.2012.08.006 复制DOI
    作者列表:De Luca A,Hartinger CG,Dyson PJ,Lo Bello M,Casini A
    BACKGROUND & AIMS: :Nowadays, gold compounds occupy a relevant position constituting a promising class of experimental anticancer metallodrugs. Several research efforts have been devoted to the investigations of the pharmacological properties of gold(I) complexes bearing phosphine ligands, such as the antiarthritic drug auranofin, that has also been shown to produce anticancer effects in vitro. In spite of the numerous studies that appeared in the literature the biological mechanisms of action of auranofin and analogues are still controversial. Here, we report on the inhibition effects of glutathione S-transferase P1-1 (GST P1-1) exerted by auranofin. The compound was able to inhibit GST P1-1 with a calculated IC(50) of 32.9±0.5μM. Interestingly, the inhibition of GST P1-1 and its cysteine mutants by the gold(I) compound is essentially the same, suggesting that probably the cysteine residues are not so essential for enzyme inactivation in contrast to other reported inhibitors. High-resolution electrospray ionisation Fourier transform ion cyclotron mass spectrometry (ESI FT-ICR MS) studies allowed characterising the binding of the compound with GST enzymes at a molecular level, confirming that similar gold binding sites may be present in the wild-type protein and its Cys mutants.
    背景与目标: : 如今,金化合物占据了重要地位,构成了一类有前途的实验性抗癌金属药物。已经进行了一些研究工作,致力于研究带有膦配体的金 (I) 配合物的药理特性,例如抗关节炎药物金诺芬,该药物在体外也具有抗癌作用。尽管文献中出现了许多研究,但金诺芬和类似物的生物学作用机制仍然存在争议。在这里,我们报告了金诺芬对谷胱甘肽S-转移酶P1-1 (GST P1-1) 的抑制作用。该化合物能够抑制GST P1-1,计算出的IC(50) 为32.9 ± 0.5微米。有趣的是,金 (I) 化合物对GST P1-1及其半胱氨酸突变体的抑制基本相同,这表明与其他报道的抑制剂相比,半胱氨酸残基可能对酶失活不是那么重要。高分辨率电喷雾电离傅里叶变换离子回旋加速器质谱 (ESI ft-icr MS) 研究可以在分子水平上表征该化合物与GST酶的结合,从而证实野生型蛋白及其Cys突变体中可能存在相似的金结合位点。
  • 【掺银磷酸盐基玻璃的抗菌效果。】 复制标题 收藏 收藏
    DOI:10.1002/jbm.a.30808 复制DOI
    作者列表:Ahmed I,Ready D,Wilson M,Knowles JC
    BACKGROUND & AIMS: :In this study a range of phosphate-based glasses (PBG) doped with silver have been investigated for their antimicrobial activities. In disk diffusion assays, these compositions demonstrated microbistatic effects against a range of organisms including Staphylococcus aureus, Escherichia coli, Bacillus cereus, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and Candida albicans. The data obtained from the above studies allowed for an additional range of PBG containing lower amounts of silver to be studied for their effects on the growth and viability of S. aureus, E. coli, and C. albicans. PBG containing 3 and 5 mol % Ag were bactericidal for S. aureus and E. coli and significantly decreased the growth rate of C. albicans. A decrease in the dissolution rates of the glasses was seen with increasing Ag content over the range of concentrations investigated. Overall, 3 mol % Ag incorporated into the PBG investigated was sufficient to mount a potent antibacterial effect against the test organisms, and these compositions also gave excellent long-term release of Ag ions into the medium.
    背景与目标: : 在这项研究中,已经研究了一系列掺有银的磷酸盐基玻璃 (PBG) 的抗菌活性。在圆盘扩散测定中,这些组合物显示出对多种生物的微双基地作用,包括金黄色葡萄球菌,大肠杆菌,蜡样芽孢杆菌,铜绿假单胞菌,耐甲氧西林金黄色葡萄球菌和白色念珠菌。从上述研究中获得的数据允许研究另外范围的含少量银的PBG对金黄色葡萄球菌,大肠杆菌和白色念珠菌的生长和生存能力的影响。含有3和5 mol % Ag的PBG对金黄色葡萄球菌和大肠杆菌具有杀菌作用,并显着降低了白色念珠菌的生长速度。在所研究的浓度范围内,随着Ag含量的增加,玻璃的溶解速率降低。总体而言,将3 mol % 的Ag掺入所研究的PBG中足以对测试生物产生有效的抗菌作用,并且这些组合物还可以将Ag离子长期释放到培养基中。
  • 【基于PCR的新型抗菌肽brevinin-2R在大肠杆菌中的基因合成,分子克隆,高水平表达,纯化和鉴定。】 复制标题 收藏 收藏
    DOI:10.1007/s12010-007-8024-z 复制DOI
    作者列表:Mehrnejad F,Naderi-Manesh H,Ranjbar B,Maroufi B,Asoodeh A,Doustdar F
    BACKGROUND & AIMS: :Brevinin-2R, a member of a new family of antimicrobial peptides isolated from the skin of Rana ridibunda, displays antimicrobial activity against bacteria and fungi. In this study, we have used an assembly PCR method for the fast and extremely accurate synthesis of the brevinin-2R gene. A total of six primers were assembled in a single step PCR, and the assembly was then amplified by PCR to produce the final gene. The synthetic gene was cloned into the pET32a (+) vector to allow the expression of brevinin-2R as a Trx fusion protein in Escherichia coli. The results indicated that the expression level of the fusion protein could reach up to 25% of the total cell proteins. The expression products could be easily purified by Ni-NTA chromatography and released from the fusion protein by factor Xa protease. The peptide displayed antimicrobial activity similar to that of the purified brevinin that was reported earlier. This method allows the fast synthesis of a gene that optimized the overexpression in the E. coli system and production of sufficiently large amounts of peptide for functional and structural characterizations.
    背景与目标: : Brevinin-2R是从Rana ridibunda皮肤中分离出的抗菌肽新家族的成员,对细菌和真菌具有抗菌活性。在这项研究中,我们使用了组装PCR方法来快速,极其准确地合成brevinin-2R基因。在单步PCR中总共组装了六个引物,然后通过PCR扩增组装以产生最终基因。将合成基因克隆到pET32a (+) 载体中,以使brevinin-2R作为Trx融合蛋白在大肠杆菌中表达。结果表明,融合蛋白的表达水平最高可达细胞总蛋白的25%。表达产物可以很容易地通过Ni-NTA色谱法纯化,并通过因子Xa蛋白酶从融合蛋白中释放出来。该肽具有与先前报道的纯化的brevinin相似的抗菌活性。这种方法可以快速合成优化大肠杆菌系统中过表达的基因,并产生足够大量的肽以进行功能和结构表征。
  • 【烯丙基硫醇和各种葱属化合物对Hep-G2细胞胆固醇合成和分泌的影响。】 复制标题 收藏 收藏
    DOI:10.1016/s0742-8413(00)00106-7 复制DOI
    作者列表:Cho BH,Xu S
    BACKGROUND & AIMS: :The present study was undertaken to compare the effects of allyl mercaptan (AM), a major metabolite of garlic, with several garlic constituents and extracts on cytotoxicity, cholesterol synthesis and its secretion in Hep-G2 cells. The cells were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), and treated with 5, 25, 50, 125, 250 and 500 microg/ml of AM, diallyl disulfide (DD), diallyl trisulfide (DT), steam-distilled garlic oil (SD) or vinyl-dithiin oil of garlic (VD) for 4 h. At concentrations up to 50 microg/ml, no significant cytotoxic effect was found in any group, but at concentrations above 250 microg/ml, the cell viability decreased drastically in all groups compared to the control. The treatment of cells with 25 microg/ml (non-cytotoxic concentration) of AM, DD, DT, SD for 4 h significantly inhibited [3H]acetate incorporation into cholesterol compared to that of the control (P < 0.05). The secretion of cholesterol into the medium was also significantly decreased in all groups except for VD. The treatment of cells with those allium constituents had no effect on either [3H]acetate incorporation into fatty acids or [3H]glycerol incorporation into triglyceride or phospholipid.
    背景与目标: : 本研究旨在比较大蒜的主要代谢产物烯丙基硫醇 (AM) 与几种大蒜成分和提取物对细胞毒性,胆固醇合成及其在Hep-G2细胞中的分泌的影响。细胞在补充有10% 胎牛血清 (FBS) 的Dulbecco改良Eagle培养基 (DMEM) 中生长,并用5、25、50、125、250和500微克/毫升的AM,二烯丙基二硫化物 (DD),二烯丙基三硫化物 (DT) 处理,蒸汽蒸馏大蒜油 (SD) 或大蒜的乙烯基二硫肽油 (VD) 4小时。在高达50微克/毫升的浓度下,在任何组中没有发现显著的细胞毒性作用,但是在高于250微克/毫升的浓度下,与对照组相比,所有组中的细胞活力急剧下降。用25微克/毫升 (非细胞毒性浓度) 的AM,DD,DT,与对照组相比,SD 4 h显着抑制 [3H] 乙酸盐掺入胆固醇 (P <0.05)。除VD外,所有组的胆固醇分泌也显着降低。用那些葱属成分处理细胞对 [3H] 乙酸掺入脂肪酸或 [3H] 甘油掺入甘油三酸酯或磷脂。
  • 【耐甲氧西林金黄色葡萄球菌克隆的抗菌药敏模式的多样性。】 复制标题 收藏 收藏
    DOI:10.1007/s10096-012-1698-3 复制DOI
    作者列表:Ghaznavi-Rad E,Neela V,Nor Shamsudin M,Ghasemzadeh Moghaddam H,Tavakol M,van Belkum A,Etemadi MR,Andar-Ali AF
    BACKGROUND & AIMS: :Methicillin-resistant Staphylococcus aureus (MRSA) is well known for its epidemicity, with the emergence of new clones on a daily basis. Diversity in the clonal types of MRSA challenges the success of treatment, as different clones respond to different sets of antibiotics. However, the antibiotic susceptibility among the isolates within the same clones is largely unexplored. In a previous study on MRSA epidemiology in Malaysia, we identified six major clonal complexes (ST-239-CC8, ST-1-CC1, ST-188-CC1, ST-22-CC22, ST-7-CC7 and ST-1283-CC8). In the present study, we investigated the antibiotic susceptibility patterns of isolates of different clones. Three hundred and eighty-nine MRSA isolates were subjected to the disc diffusion test, oxacillin minimum inhibitory concentration (MIC) determination and assessment of the distribution of macrolide, lincosamide and streptogramin B (MLS(B)) resistance genes. Thirty-six different antibiotic profiles were observed: 30 (83.3 %) among ST-239, 2 (5.6 %) among ST-1283 and 1 (2.8 %) each for ST-1, ST-7, ST-22 and ST-188. All ST-239 (362, 9 %) isolates were multiple drug-resistant (MDR; resistant to more than three classes of antibiotics) and had oxacillin MICs >256 mg/l. Among the 385 clindamycin-resistant isolates, 375 (96.4 %) illustrated inducible resistance (D-zone-positive), while 10 (2.6 %) showed constitutive resistance. The vast majority of the macrolide-resistant isolates carried the ermA gene (95.1 %), followed by ermC (12.9 %). Diversity in the antibiotic susceptibilities of isolates within the clones emphasises the need for continuous surveillance of MDR strains to prescribe the correct antibiotic rather than empirical treatment. This will likely reduce the emergence of new endemic or epidemic resistant MRSA clones.
    背景与目标: : 耐甲氧西林金黄色葡萄球菌 (MRSA) 以其流行而闻名,每天都有新的克隆出现。MRSA克隆类型的多样性对治疗的成功提出了挑战,因为不同的克隆对不同的抗生素有反应。然而,同一克隆中分离株之间的抗生素敏感性在很大程度上尚未得到探索。在先前的马来西亚MRSA流行病学研究中,我们确定了六个主要的克隆复合物 (ST-239-CC8,ST-1-CC1,ST-188-CC1,ST-22-CC22,ST-7-CC7和ST-1283-CC8)。在本研究中,我们调查了不同克隆分离株的抗生素敏感性模式。对389株MRSA分离株进行了圆盘扩散测试,苯唑西林最低抑制浓度 (MIC) 测定以及评估大环内酯类,林可酰胺和链霉菌素B (MLS(B)) 抗性基因的分布。观察到36种不同的抗生素谱: ST-239中有30种 (83.3%),ST-1283中有2种 (5.6%),ST-1,ST-7,ST-22和ST-188各1种 (2.8%)。所有ST-239 (362、9%) 分离株均具有多重耐药性 (MDR; 对三类以上抗生素耐药),并且苯唑西林mic> 256 mg/l。在385的克林霉素抗性分离株中,375 (96.4%) 表示诱导型抗性 (D区阳性),而10 (2.6%) 表示组成型抗性。绝大多数大环内酯类抗性分离株携带ermA基因 (95.1%),其次是ermC (12.9%)。克隆中分离株的抗生素敏感性多样性强调需要持续监测MDR菌株以开出正确的抗生素而不是经验治疗。这可能会减少新的地方性或抗流行病的MRSA克隆的出现。

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