膀胱癌组织中端粒酶活性检测的意义

目的探讨膀胱癌组织端粒酶活性与膀胱癌病理参数的关系及其临床意义。方法应用改良的TRAP法对40例膀胱癌组织、20例膀胱癌癌旁2cm膀胱组织和10例正常膀胱组织进行端粒酶活性的检测,用Yecan酶免分析仪连续测定其450～630nm的OD值。结果40例膀胱癌组织端粒酶活性强度OD值为0.567±0.251。正常膀胱组织无端粒酶活性存在。癌组织端粒酶活性强度OD值高于癌旁组织OD值(P<0.01)。端粒酶活性强度OD值Ⅲ级>Ⅱ级>Ⅰ级(P<0.05),OD 值在膀胱癌中随分级的增加呈上升趋势。浸润性膀胱癌端粒酶活性OD值明显高于浅表性膀胱癌端粒酶活性OD值(P<0.01)。淋巴结转移的膀胱癌端粒酶活性OD值明显高于无淋巴结转移的膀胱癌端粒酶活性OD值(P<0.05)。复发膀胱癌端粒酶活性OD值明显高于原发膀胱癌端粒酶活性OD 值(P<0.05)。结论膀胱癌组织中端粒酶阳性率及端粒酶活性强度OD值显著高于正常膀胱组织。端粒酶阳性率与膀胱癌病理分级、临床分期、淋巴结是否转移以及是否复发无关。但端粒醇活性强度OD值与膀胱癌的分级、分期、淋巴结转移以及复发有关。膀胱癌各病理参数中端粒酶阳性率经统计学比较差异无显著性,用端粒酶活性强度OD值作为比较可能更能显示其真正的临床意义。     

Antimicrobial activity of the biogenically synthesized core-shell Cu@Pt nanoparticles

The interest in the biological synthesis of mono metal nanoparticles has been visible for years. As more attention is also given to the biological methods of synthesizing bimetallic nanoparticles, this work used the Agrimoniae herba extract in order to obtain bimetallic core-shell Cu@Pt nanoparticles. The formed core-shell Cu@Pt nanoparticles were characterized by Ultraviolet–Visible (UV–vis), Fourier Transform-Infrared (FT-IR), Scanning electron microscopy (SEM), Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM) measurements. The obtained core-shell Cu@Pt nanoparticles were analysed in terms of their antibacterial activity. It was discovered that the synthesized nanoparticles exhibited maximum activity against gram-negative bacteria E. coli ATCC 25922, S. aureus ATCC 25923, and P. aeruginosa NCTC 6749. The core-shell Cu@Pt nanoparticles also exhibited activity against the yeast C. albicans ATCC 10231 and dermatophytes T. mentagrophytes ATCC 9533.     

HAZ,a novel peptide with broad-spectrum antibacterial activity

ObjectiveThe growing microbial resistance to antibiotics is a global public concern, which creates serious needs for newer antimicrobial agents. Antimicrobial peptides (AMPs) are increasingly exploited in drug development as therapeutic candidates. Here, we aimed to design and characterize a novel peptide with broad spectrum antimicrobial activity.MethodsHybridization and sequence modification approaches were used to design the novel peptide, named HAZ, aiming at optimizing the physicochemical parameters involved in antimicrobial activity. Peptide activities were assessed alone or combined with different selected antibiotics against various sensitive and drug-resistant bacterial strains. In addition, the hemolysis and the cytotoxic activities of HAZ peptide were evaluated on human red blood cells and epithelial adenocarcinoma cells (A549), respectively.ResultsHAZ peptide was sequentially modified to result in favored physicochemical parameters (helicity 95.24 %, hydrophobic ratio 47 %, and net charge of 8 + ). Functional assessment of HAZ revealed significant antimicrobial activity, with MIC values of 15 – 20 µM against tested bacterial strains. It also exhibited biofilm eradication activity at slightly higher concentrations. HAZ-antibiotics combinations exhibited a synergistic action mode that led to dramatic decrease in the MIC values for both HAZ peptide and the antibiotic. Such efficacy was accompanied with minimal hemolytic toxicity on human erythrocytes. Importantly, HAZ displayed promising anticancer activity against human lung cancer cells.ConclusionRationally-designed antimicrobial peptides offer promising alternatives to the current antibiotics for management of infectious diseases. HAZ peptide is a broad-spectrum AMP, and a promising candidate for antimicrobial and anticancer drug development.     

Antimicrobial activity,phenolic profile and role in the inflammation of propolis

Nowadays a great amount of information regarding chemical and biological aspects of bee products is available in the literature, but few data on its therapeutic uses are found. The aim of this study was to evaluate the phenolic profile, the in vitro antimicrobial activity and effect in the hyaluronidase enzyme (widely related with the inflammation process) of propolis harvested in Portugal. The efficacy of three extracts (hydro-alcoholic, methanolic and aqueous) was also compared. It was chosen the hydro-alcoholic extract, because this was the most effective for extracting phenolic compounds. The antimicrobial activity was accessed in Gram-positive and Gram-negative bacteria and yeasts, isolated from different biological fluids and the results were then compared with the obtained for reference microorganisms. The propolis from Bragança was the one that possessed the highest polyphenols’ content. The sample from Beja showed the less significant inhibition of the hyaluronidase enzyme. Concerning the antimicrobial activity, Candida albicans was the most resistant and Staphylococcus aureus the most sensitive. The reference microorganisms were more sensitive than the ones isolated from biological fluids.     

Antimicrobial Activity of 6-Paradol and Related Compounds

The seeds of Aframomum melegueta K. Schum. (Zingiberaceae) yielded 6-paradol (1) and 6-shogaol (2) as the major antimycobacterium agents, based on a bioactivity-guided fractionation. These isolates were found to be active against Mycobacterium chelonei, M. intracellulare, M. smegmatis and M. xenopi (MIC 10-15 µg/ml). Derivatives were prepared in an attempt to define some of the structural parameters needed for antimicrobial activity. The desmethyl derivative of 1 retained the antimycobacterial activity and was found to be more active against Candida albicans than 1 and 2. Gingerone (9), not previously reported in this source, was found to be inactive. The identity of the compounds were confirmed by spectral analyses (UV, IR, NMR, and EIMS) and by comparison with reported data.     

Antimicrobial activity and chemical composition of some essential oils

In this study the composition and antimicrobial properties of essential oils obtained from Origanum onites, Mentha piperita, Juniperus exalsa, Chrysanthemum indicum, Lavandula hybrida, Rosa damascena, Echinophora tenuifolia, Foeniculum vulgare were examined. To evaluate the in vitro antibacterial activities of these eight aromatic extracts; their in vitro antimicrobial activities were determined by disk diffusion testing, according to the NCCLS criteria. Escherichia coli (ATTC 25922), Staphylococcus aureus (ATCC 25923) and Pseudomonas aeruginosa (ATTC 27853 were used as standard test bacterial strains. Origanum onites recorded antimicrobial activity against all test bacteria, and was strongest against Staphylococcus aureus. For Rosa damascena, Mentha piperita and Lavandula hybrida antimicrobial activity was recorded only to Staphylococcus aureus. Juniperus exalsa, and Chrysanthemum indicum exhibited antibacterial activities against both Staphylococcus aureus and Escherichia coli. We also examined the in vitro antimicrobial activities of some components of the essential oils and found some components with antimicrobial activity.     

7-Aza-des-A-steroids with Antimicrobial and Cytotoxic Activity

This paper describes a convenient approach to the 7-aza-des-A-steroid (6,6a,7,8,9,9a-hexahydro-5H-cyclopenta[h]quinoline) scaffold starting from Grundmann’s ketone using two different pyridine annulation protocols. The biological evaluation of the pyridine and pyridinium products revealed that these compounds unexpectedly do not interfere with ergosterol and cholesterol biosynthesis. The pyridinium compound 6 showed significant antimicrobial and cytotoxic activities which are most likely due to its detergent-like structure.     

Synthesis and antimicrobial activity of some novel 2-(p-substituted-phenyl)-5-substituted-carbonylaminobenzoxazoles

A series of 2-(p-substituted-phenyl)-5-substituted-carbonylamino benzoxazole derivatives (5-22) was synthesized and their antimicrobial activities determined in comparison to several control drugs. The synthesized compounds were tested in vitro against Staphylococcus aureus, Streptococcus faecalis and Bacillus subtilis as Gram-positive, Pseudomonas aeruginosa and Escherichia coli as Gram-negative bacteria and the yeast Candida albicans. Microbiological results showed that the compounds possessed a diffuse spectrum of antibacterial activity against these microorganisms. Compound 9 which bears a phenylacetamido moiety at position 5 and a 4-fluorophenyl group at the 2-position of benzoxazole ring was the most active derivative against S. aureus, S. faecalis and P. aeruginosa with a MIC value of 12.5 microg/ml. Compound 11 provided higher potency than the other tested compounds against B. subtilis at a MIC value of 12.5 microg/ml. Compounds 5-22 showed antifungal activity against C. albicans with MIC values between 50 and 12.5 microg/ml.     

Synthesis and antimicrobial activity of novel tetrahydrobenzothienopyrimidines

Due to the rapidly growing number of resistant strains of bacteria, the search for antibacterial agents with new modes of action will always remain an important and challenging task. Thus, the reaction of 2-substituted or unsubstituted-4-(4-acetylanilino)-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidine derivatives 1-3 with the hydrazine derivatives, semi and/or thiosemicarbazides, provided the corresponding hydrazones 4-6 and semi and/or thiosemicarbazones 7-9. Claisen-Schmidt condensation of compounds 1 or 2 with the appropriate aldehyde yielded the chalcones 10, 11 which, when treated with hydroxylamine hydrochloride gave rise to the isoxazoline-containing compounds 12, 13. Furthermore, reacting the respective chalcones 10, 11 with different hydrazines, urea and/or thiourea, furnished compounds 14, 15, 16, and 17 respectively. Representative compounds were tested for their antimicrobial activity against Candida albicans and certain gram-positive and gram-negative bacteria. Their MICs were then determined. Compound 15e, showed a broad spectrum of activity while most of the other compounds showed varying antimicrobial activity.     

磷霉素对肠球菌体外抗菌活性的实验研究

目的：研究磷霉素对肠球菌的体外抗菌活性,并与8种常用抗菌药进行对比,为临床药物选择提供参考。方法：收集2018年1月~12月患者临床标本中分离的肠球菌187株,用全自动细菌鉴定药敏分析仪测定8种抗菌药对肠球菌的体外抗菌活性,采用纸片扩散（K-B）测定磷霉素的抗菌活性,结果以CLSI 2017版标准判断;应用WHONET 5.6软件分析分离病原菌的分布和耐药情况。结果：在187株肠球菌中有屎肠球菌97株,粪肠球菌86株,其他肠球菌4株。未见万古霉素（天然耐药菌株除外）、替考拉宁耐药的菌株,对磷霉素、利奈唑胺、氨苄西林、利福平、四环素、红霉素、环丙沙星的敏感率分别为85.6%、80.7%、49.7%、17.1%、36.4%、7.5%、0.5%。结论：磷霉素对肠球菌有较强的体外抗菌活性,可作为治疗肠球菌感染的首选用药。     

Antimicrobial and demelanizing activity of Ganoderma lucidum extract,p-hydroxybenzoic and cinnamic acids and their synthetic acetylated glucuronide methyl esters

Mushroom extracts or isolated compounds may be useful in the search of new potent antimicrobial agents. Herein, it is described the synthesis of protected (acetylated) glucuronide derivatives of p-hydroxybenzoic and cinnamic acids, two compounds identified in the medicinal mushroom Ganoderma lucidum. Their antimicrobial and demelanizing activities were evaluated and compared to the parent acids and G. lucidum extract. p-Hydroxybenzoic and cinnamic acids, as also their protected glucuronide derivatives revealed high antimicrobial (antibacterial and antifungal) activity, even better than the one showed by commercial standards. Despite the variation in the order of parent acids and the protected glucuronide derivatives, their antimicrobial activity was always higher than the one revealed by the extract. Nevertheless, the extract was the only one with demelanizing activity against Aspergillus niger. The acetylated glucuronide derivatives could be deprotected to obtain glucuronide metabolites, which circulate in the human organism as products of the metabolism of the parent compounds.     

Antimicrobial and antioxidant effects of phenolic constituents from Klainedoxa gabonensis

Bioassay-guided fractionation of the methanol extract of the stem bark of Klainedoxa gabonensis Pierre ex Engl. (Irvingiaceae) afforded 12 compounds, namely, ellagic acid (1), ellagic acid 3,3′-dimethylether (2), gallic acid (3), methyl gallate (4), lupeol (5), β-amyrin (7), erythrodiol (8), oleanolic acid (9), betulinic acid (6), hederagenin (10), bayogenin acid (11), and stigmasterol-3-O-β-d-glucopyranoside (12). Compounds 1-3 and 7-12 were isolated for the first time from this genus. The structures were established on the basis of 1D/2D NMR experiments and mass spectrometric data. Crude extract, fractions (A, B, C and D) and pure compounds were tested for their antimicrobial activity using paper disk agar diffusion assay. The test delivered a range of low to high activities for phenolic compounds 1-4, low or missing activities for terpenoid compounds 5-11, and impressive very high antibacterial/antifungal values for two fractions C and D probably due to synergistic effects of compounds. The broth microdilution assay revealed MICs of 15.4-115.1?μg/mL for phenolic compounds, MICs higher than 1?mg/mL for terpenoids and MICs of 4.5-30.3?μg/mL for fractions C and D. The determination of the radical scavenging activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay gave high antioxidant values for the methanol extract and fraction D (IC₅₀ 10.45 and 5.50?μg/mL) as well as for the phenolic compounds 1-4 (IC₅₀ 45.50-48.25?mM) compared to the standard 3-t-butyl-4-hydroxyanisole (BHA) (IC₅₀ 44.20?mM).     

Antimicrobial activity of novel 4H-4-oxoquinolizine compounds against extensively drug-resistant Acinetobacter baumannii strains

The aim of this study was to screen lead compounds exhibiting potent in vitro antimicrobial activity against multidrug-resistant (MDR) Acinetobacter baumannii strains from a library of chemical compounds. In a high-throughput screening analysis of 7520 compounds representative of 340,000 small molecules, two 4H-4-oxoquinolizine compounds were the most active against A. baumannii ATCC 17978. Subsequent selection and analysis of 70 4H-4-oxoquinolizine compounds revealed that the top 7 compounds were extremely active against extensively drug-resistant (XDR) A. baumannii isolates. These compounds commonly carried a 1-cyclopropyl-7-fluoro-4-oxo-4H-quinolizine-3-carboxylic acid core structure but had different C-8 and/or C-9 moieties. Minimum inhibitory concentrations (MICs) of the seven compounds against fluoroquinolone-resistant A. baumannii isolates were found to be in the range of 0.02–1.70?µg/mL regardless of the mutation types in the quinolone resistance-determining region (QRDR) of GyrA and ParC. Cytotoxicity of the seven compounds was observed in HeLa and U937 cells at a concentration of 50?µg/mL, which was >32.5- to 119-fold higher than the MIC₉₀ for A. baumannii isolates. In conclusion, novel 4H-4-oxoquinolizine compounds represent a promising scaffold on which to develop antimicrobial agents against drug-resistant A. baumannii strains.     

人工合成抗菌肽生物信息学分析及其抑菌活性研究

目的：对溶血性较高的天然抗菌肽Temporin-1Dra进行氨基酸替换,以期获得低毒性、对白色念珠耐药菌株具有抑菌活性的抗菌肽。方法：采用生物信息学相关软件对改造之后的天然抗菌肽Temporin-1Dra进行分析,主要包括抗菌肽形成概率、理化性质、二级结构的预测;测定合成多肽的最低抑菌浓度,杀菌曲线,部分抑菌浓度指数（FIC index）。结果：对天然抗菌肽进行生物信息学分析改造得到多肽[G4、T5、N8K]Temporin-1Dra,对耐氟康唑（FLC）白色念珠菌的MIC值为128 μg·mL-1;MIC范围内溶血率＜5%;3 h内MIC浓度下杀菌效率显著,且呈现浓度依赖性;与FLC联用的FIC index为0.375,与FLC联合用药有协同作用。结论：改造之后的抗菌肽[G4、T5、N8K]Temporin-1Dra（HFLKKLVKLAKKIL-NH2）对白色念珠菌耐药菌株具有抑制作用,体外溶血性低、杀菌效果显著。     

Antimicrobial effect of phlorotannins from marine brown algae

Marine organisms exhibit a rich chemical content that possess unique structural features as compared to terrestrial metabolites. Among marine resources, marine algae are a rich source of chemically diverse compounds with the possibility of their potential use as a novel class of artificial food ingredients and antimicrobial agents. The objective of this brief review is to identify new candidate drugs for antimicrobial activity against food-borne pathogenic bacteria. Bioactive compounds derived from brown algae are discussed, namely phlorotannins, that have anti-microbial effects and therefore may be useful to explore as potential antimicrobial agents for the food and pharmaceutical industries.     

Synthesis and antimicrobial activity of some pyridinyliminothiazoline derivatives

The synthesis of some pyridinyliminothiazoline derivatives starting from N-pyridine-N'-phenyl thiourea and alpha-halogenoacetophenones is described. The chemical structures of the compounds were elucidated. The prepared compounds were tested for antimicrobial activity.     

家蝇抗菌肽抗菌活性及抗菌机制的初步研究

目的　研究家蝇抗菌肽的抗菌活性及抗菌机制。方法　用损伤感染的方法诱导家蝇幼虫表达抗菌肽 ,通过 Sephadex过滤层析和 HL PC技术纯化提取 ,用平板法和稀释法作抗菌活性试验 ,并用电子扫描技术研究抗菌肽的抗菌机制。结果　家蝇抗菌肽对铜绿假单胞菌、大肠埃希氏菌、耐甲氧西林金黄色葡萄球菌( MRSA)均有明显的抗菌活性。大肠埃希氏菌与 5 0 μg/ml的纯化抗菌肽溶液一起 37℃孵育 6 0 min后 ,大肠埃希氏菌不能存活。经电镜扫描观察发现 ,细菌的细胞膜出现破损和穿孔现象。结论　家蝇抗菌肽具有明显的广谱抗菌活性 ,对阴性杆菌和阳性球菌均有杀伤作用。抗菌肽的抗菌机制是通过破坏细菌的细胞膜而杀伤细菌的     

Screening of Iranian Plants for Antimicrobial Activity

The methanol extracts of 306 plants of 52 families obtained from Northeast of Iran (Khorasan Province), were tested for antimicrobial activity (in vitro) using the cylinder plate assay method. Activity against Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Pseudomonas aeruginosa, Morganella morganii (Gram negative), Bacillus subtilis and Staphylococcus aureus (Gram positive) and Candida albicans is discussed.     

抗菌肽的抗肿瘤研究进展

抗菌肽（AMPs）是具有抗菌活性的一类多肽,广泛存在于生物界。抗菌肽对肿瘤细胞有广谱杀伤作用,却对正常的哺乳动物细胞没有毒性作用。本文概述抗菌肽杀伤肿瘤细胞的多种作用机制,并探讨了将其开发为新型抗肿瘤药物的可行性。