药物类新污染物的微生物降解机制研究进展

环境微生物作为自然界中主要的分解者蕴含着丰富的遗传和代谢多样性,在有机污染物降解中发挥着重要作用。药物被持续不断地释放到环境中,其环境暴露、环境风险和对人体健康的潜在影响已得到广泛关注。研究药物在环境中的微生物降解过程对于药物的环境命运、药物的环境风险评估和药物污染去除技术的开发等具有重要价值。本文重点综述了目前环境中常检出药物的微生物降解途径及其分子机理,总结了目前药物微生物降解研究领域的进展,最后探讨了药物的微生物降解领域未来的研究趋势。     

植物-微生物联合对环境有机污染物降解的研究进展

环境中有机污染物的过量积累对生态系统及人类健康造成严重威胁。近年来,许多学者研究发现植物-微生物联合作用对环境中有机污染物的去除及生态系统的修复具有非常显著的效果。本文主要从植物-内生菌、植物-菌根菌以及植物-根际微生物这三个层面详细阐述植物-微生物联合降解有机污染物的研究现状,分析植物-微生物在联合降解中的作用,揭示植物-微生物联合降解的机理。但就目前而言,植物-微生物联合降解有机污染物仍存在许多问题,植物-微生物联合降解有机污染物的机理及生态学效应仍不清楚。因此,还需要进一步探讨其潜在作用机制并加强应用实践,这将有助于污染生态系统的治理,促进环境可持续发展。     

人工碳纳米材料在环境中的降解与转化研究进展

随着人工碳纳米材料的大量生产和使用,其潜在的生态风险已引起学术界的广泛关注.碳纳米材料在环境中的转化和降解直接影响它们在环境中的归趋及生态毒性,对该过程的研究是确定其环境可容纳量及进行生命周期评价的重要环节.本文概述了主要人工碳纳米材料(碳纳米管、富勒烯)在环境中的化学转化、微生物降解及光降解过程,总结了影响人工碳纳米材料降解的环境与结构因素及降解的机理,指出了现有研究的不足和未来研究的方向.     

有机磷农药微生物降解研究进展

微生物降解是有机磷农药在环境中去毒降解的主要方式,是治理环境污染的一项有效手段。该文综述了有机磷农药降解菌的分离鉴定、降解机理与代谢途径、降解基因的克隆及表达、降解菌制剂和酶制剂的应用、以及有机磷农药微生物降解研究趋势五个方面的研究现状。     

微生物降解农药的研究新进展*

农药中,尤其化学农药中高毒、高残留、难降解的农药是重要的环境污染物,而微生物治理农药污染是一项有效手段,几十年来,在这方面已进行了大量研究。从农药降解菌的种类、工程菌的构建、微生物降解农药的机理、降解特性、影响因素及应用效果等几方面综述了近年这些方面的研究进展,并提出农药微生物降解研究领域的发展趋势和有待进一步解决的问题。     

微生物降解农药研究的新进展

农药尤其是化学农药中高毒、高残留、难降解的农药是重要的环境污染物,而利用微生物治理农药所造成的环境污染是一项有效的手段。从降解农药的微生物的种类、工程菌的构建、微生物降解农药的机理、降解特性、影响因素及应用效果等多方面综述了近年来的研究进展,并提出了微生物降解农药研究领域的发展趋势和有待进一步解决的一些突出问题。     

低温微生物修复石油烃类污染土壤研究进展

耐冷菌、嗜冷菌等低温微生物广泛存在于极地、高山以及高纬度等土壤环境中,是石油烃类污染物在低温条件下降解与转化的重要微生物资源.利用低温微生物的独特优势,石油污染土壤的低温生物修复技术的研究成为当前热点领域.本文系统综述了低温石油烃降解菌的分类及冷适机制,低温微生物对不同类型石油烃组分的降解特征和降解机理,低温环境中接种降解菌、添加营养物质和表面活性剂等强化技术在石油污染土壤中生物修复的应用.以及微生物分子生物学技术在低温微生物降解石油烃的研究现状,为拓展我国石油污染土壤生物修复技术提供参考.     

环境中污染物降解基因的水平转移(HGT)及其在生物修复中的作用

水平基因转移是不同于垂直基因转移的遗传物质的交流方式.在污染环境这一特异生态环境中,降解基因的水平转移有着独特的功能与作用.研究环境中污染物降解基因在微生物间的水平转移,更深入地了解微生物种群适应污染环境的机理,对于评价污染物的环境毒理、生物可降解性以及污染环境的可修复潜力具有重要参考价值.在污染物生物修复实践中,可以通过调控降解基因的水平转移,增强污染环境中微生物的降解能力,更有效地发挥生物修复作用.文章将对环境中细菌间基因交流的机制,污染物降解基因的水平转移对微生物适应污染环境的机理、水平基因转移对代谢途径的进化及其对污染物生物修复作用的影响等方面的研究进展做一综述.     

土壤中高分子量PAHs微生物降解机理及影响因素研究进展

高分子量多环芳烃( HMW PAHs)分子结构复杂,疏水性强,是环境中广泛存在的难降解的有机污染物.微生物降解是去除HMW PAHs的主要途径.本文介绍了PAHs降解菌株的种类和降解机理,以及不同环境因子(营养元素、pH值、土壤结构、通气状况和复合污染)对HMW PAHs降解的影响,提出HMW PAHs污染土壤的进一步研究的方向与重点,旨在为HMW PAHs污染修复研究和微生物降解机理研究提供参考.     

微生物降解硝基芳烃及其卤代衍生物的研究进展

硝基芳烃化合物作为一种重要的化工原料,广泛应用于医药、染料、农药等化工产品的合成。在给人类社会带来空前的物质繁荣的同时,其造成的环境污染问题也成为人类社会面临的重要挑战之一。微生物在这些环境污染物的降解中起着重要的作用。近几十年,环境微生物工作者对微生物降解硝基芳香污染物的各个步骤,包括趋化感应、分解代谢及生物修复进行了大量的研究工作,获得了丰富的知识。本文综述了硝基芳烃及其卤代衍生物的微生物代谢途径、代谢机理、趋化及修复研究进展,并对本领域的研究进行了展望,有助于全面认知硝基芳烃污染物的微生物降解过程,为污染环境修复提供理论基础。     

Quantitative proteomic analysis of ibuprofen-degrading Patulibacter sp. strain I11

Ibuprofen is the third most consumed pharmaceutical drug in the world. Several isolates have been shown to degrade ibuprofen, but very little is known about the biochemistry of this process. This study investigates the degradation of ibuprofen by Patulibacter sp. strain I11 by quantitative proteomics using a metabolic labelling strategy. The whole-genome of Patulibacter sp. strain I11 was sequenced to provide a species-specific protein platform for optimal protein identification. The bacterial proteomes of actively ibuprofen-degrading cells and cells grown in the absence of ibuprofen was identified and quantified by gel based shotgun-proteomics. In total 251 unique proteins were quantitated using this approach. Biological process and pathway analysis indicated a number of proteins that were up-regulated in response to active degradation of ibuprofen, some of them are known to be involved in the degradation of aromatic compounds. Data analysis revealed that several of these proteins are likely involved in ibuprofen degradation by Patulibacter sp. strain I11.     

Formation of catechols via removal of acid side chains from ibuprofen and related aromatic acids

Although ibuprofen [2-(4-isobutylphenyl)-propionic acid] is one of the most widely consumed drugs in the world, little is known regarding its degradation by environmental bacteria. Sphingomonas sp. strain Ibu-2 was isolated from a wastewater treatment plant based on its ability to use ibuprofen as a sole carbon and energy source. A slight preference toward the R enantiomer was observed, though both ibuprofen enantiomers were metabolized. A yellow color, indicative of meta-cleavage, accumulated transiently in the culture supernatant when Ibu-2 was grown on ibuprofen. When and only when 3-flurocatechol was used to poison the meta-cleavage system, isobutylcatechol was identified in the culture supernatant via gas chromatography-mass spectrometry analysis. Ibuprofen-induced washed-cell suspensions also metabolized phenylacetic acid and 2-phenylpropionic acid to catechol, while 3- and 4-tolylacetic acids and 2-(4-tolyl)-propionic acid were metabolized to the corresponding methyl catechols before ring cleavage. These data suggest that, in contrast to the widely distributed coenzyme A ligase, homogentisate, or homoprotocatechuate pathway for metabolism of phenylacetic acid and similar compounds, Ibu-2 removes the acidic side chain of ibuprofen and related compounds prior to ring cleavage.     

Formation of Catechols via Removal of Acid Side Chains from Ibuprofen and Related Aromatic Acids

Although ibuprofen [2-(4-isobutylphenyl)-propionic acid] is one of the most widely consumed drugs in the world, little is known regarding its degradation by environmental bacteria. Sphingomonas sp. strain Ibu-2 was isolated from a wastewater treatment plant based on its ability to use ibuprofen as a sole carbon and energy source. A slight preference toward the R enantiomer was observed, though both ibuprofen enantiomers were metabolized. A yellow color, indicative of meta-cleavage, accumulated transiently in the culture supernatant when Ibu-2 was grown on ibuprofen. When and only when 3-flurocatechol was used to poison the meta-cleavage system, isobutylcatechol was identified in the culture supernatant via gas chromatography-mass spectrometry analysis. Ibuprofen-induced washed-cell suspensions also metabolized phenylacetic acid and 2-phenylpropionic acid to catechol, while 3- and 4-tolylacetic acids and 2-(4-tolyl)-propionic acid were metabolized to the corresponding methyl catechols before ring cleavage. These data suggest that, in contrast to the widely distributed coenzyme A ligase, homogentisate, or homoprotocatechuate pathway for metabolism of phenylacetic acid and similar compounds, Ibu-2 removes the acidic side chain of ibuprofen and related compounds prior to ring cleavage.     

Efficient synthesis and chiral separation of 11C-labeled ibuprofen assisted by DMSO for imaging of in vivo behavior of the individual isomers by positron emission tomography

The pharmacological mechanisms focusing on chiral isomer of ibuprofen are not fully understood. Only the (S)-isomer of ibuprofen inhibits cyclooxygenases, which mediates the generation of prostanoids and thromboxanes. Consequently, (S)-isomers represent a major promoter of the anti-inflammatory effect, and the effects of the (R)-isomers have not been widely discussed. However, more recently, the cyclooxygenase-independent pharmacological effects of ibuprofen have been elucidated. Pharmacokinetic studies with individual isomers of ibuprofen by positron emission tomography should aid our understanding of the pharmacological mechanisms of ibuprofen. The efficient (11)C-labeling of ibuprofen for chiral separation via the TBAF-promoted α-[(11)C]methylation was achieved by using DMSO rather than THF as the reaction solvent. The robust production of the radiochemically labile (11)C-labeled ibuprofen ester was realized by the protective effect of DMSO on radiolysis. After intravenous injection of each enantiomer of [(11)C]ibuprofen, significantly high radioactivity was observed in the joints of arthritis mice when compared to the levels observed in normal mice. However, the high accumulation was equivalent between the enantiomers, indicating that ibuprofen is accumulated in the arthritic joints regardless of the expression of cyclooxygenases.     

Drug release from and hydrolytic degradation of a poly(ethylene glycol) grafted poly(3-hydroxyoctanoate)

Monoacrylate-poly(ethylene glycol)-grafted poly(3-hydroxyoctanoate) (PEGMA-g-PHO) copolymers were synthesized to develop a swelling-controlled release delivery system for ibuprofen as a model drug. The in vitro hydrolytic degradation of and the drug release from a film made of the PEGMA-g-PHO copolymer were carried out in a phosphate buffer saline (pH 7.4) medium. The hydrolytic degradation of the copolymer was strongly dependent on the degree of grafting (DG) of the PEGMA group. The degradation rate of the copolymer films in vitro increased with increasing DG of the PEGMA group on the PHO chain. The copolymer films showed a controlled delivery of ibuprofen to the medium in periods of time that depend on the composition, hydrophilic/hydrophobic characteristics, initial drug loading amount and film thickness of the graft copolymer support. The drug release rate from the grafted copolymer films was faster than the rate of weight loss of the films themselves. In particular, a combination of the low DG of the PEGMA group in the PHO chains with the low ibuprofen solubility in water led to long-term constant release from these matrices in vitro.     

Nitrooxyethylation reverses the healing-suppressant effect of Ibuprofen

Nonsteroidal antiinflammatory drugs like ibuprofen impede tissue repair by virtue of retarding inflammation. The present study was undertaken to explore if linking of nitrooxyethyl ester to ibuprofen reverses its healing-depressant propensity. Nitrooxyethyl ester of ibuprofen (NOE-Ibu) was synthesized in our laboratory through a well-established synthetic pathway. NOE-Ibu was screened for its influence on collagenation, wound contraction and epithelialization phases of healing, and scar size of healed wound in three wound models, namely, incision, dead space, and excision wounds. Besides, its influence on the oxidative stress (levels of GSH and TBARS) was also determined in 10-day-old granulation tissue. NOE-Ibu was further screened for its antiinflammatory activity in rat paw edema model. NOE-Ibu promoted collagenation (increase in breaking strength, granulation weight, and collagen content), wound contraction and epithelialization phases of healing. NOE-Ibu also showed a significant antioxidant effect in 10-day-old granulation tissue as compared to ibuprofen. Results vindicate that the esterification of ibuprofen with nitrooxyethyl group reverses the healing-suppressant effect of ibuprofen. The compound also showed equipotent antiinflammatory activity as ibuprofen.     

The influence of cholesterol on interactions and dynamics of ibuprofen in a lipid bilayer

In this work, molecular dynamics (MD) simulations with atomistic details were performed to examine the influence of the cholesterol on the interactions and the partitioning of the hydrophobic drug ibuprofen in a fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayer. Analysis of MD simulations indicated that ibuprofen molecules prefer to be located in the hydrophobic acyl chain region of DMPC/cholesterol bilayers. This distribution decreases the lateral motion of lipid molecules. The presence of ibuprofen molecules in the bilayers with 0 and 25 mol% cholesterol increases the ordering of hydrocarbon tails of lipids whereas for the bilayers with 50 mol% cholesterol, ibuprofen molecules perturb the flexible chains of DMPC lipids which leads to the reduction of the acyl chain order parameter. The potential of the mean force (PMF) method was used to calculate the free energy profile for the transferring of an ibuprofen molecule from the bulk water into the DMPC/cholesterol membranes. The PMF studies indicated that the presence of 50 mol% cholesterol in the bilayers increases the free energy barrier and slows down the permeation of the ibuprofen drug across the DMPC bilayer. This can be due to the condensing and ordering effects of the cholesterol on the bilayer.     

Differential regulation of anti-inflammatory proteins in human rheumatoid synoviocyte MH7A cell by celecoxib and ibuprofen

Non-steroidal anti-inflammatory drugs are known to be the most widely used drugs to exert their anti-inflammatory activities. It was examined protein expression profiles of human rheumatoid fibroblast-like synoviocyte MH7A cells treated with celecoxib, a selective cyclooxygenase-2 inhibitor, or ibuprofen, a non-selective cyclooxygenase inhibitor, using two-dimensional gel electrophoresis for comparison the mechanism of the drugs. Altered expression pattern in response to celecoxib is significantly different from that of ibuprofen treated cells. When MH7A cells were treated with celecoxib, 28 proteins were affected at their expression levels. Among them, heat shock proteins (Hsp60 and 70), glucose regulated proteins (Hsp75 and 78) were observed to be up-regulated by 1 to 30 microM concentrations of celecoxib but those proteins were not affected in ibuprofen treated cells. On the other hand, the expression of 19 proteins was changed by ibuprofen and the expression of apolipoprotein E, RNA binding motif 4, CTP-phosphocholine cytidylyltransferase, and phospholipase A2 inhibitory protein was only altered by ibuprofen. The expressions of 15 proteins were affected by both celecoxib and ibuprofen. Our results showed that celecoxib and ibuprofen, though they are known to act as cyclooxygenase inhibitors, could exert a different mode of acting mechanisms in anti-inflammatory processes. The chemical proteomic approach will be useful for figuring out the mode of actions of drugs.