An overview of nanofiber-based antibacterial drug design

Introduction: Conventional administration of antibacterial drugs to the human body can cause vital problems such as dose dependent systemic toxicity and bacterial resistance which prevent the healing process. In this regard, recent studies have been devoted to producing nanofiber based antibacterial drug delivery approaches which surpass bacterial resistance and toxicological issues.

Areas covered: This review summarizes latest developments in the production of antibacterial nanofibers, nanofiber based antibacterial action mechanisms and release profiles of nanofibers. In the first section, key challenges of antibacterial nanofibers and release and non-release antibacterial action mechanisms of nanofibers are highlighted. In the second section, routes of antibacterial nanofiber design have been given. Factors affecting drug release mechanisms have been discussed elaborately in the final section. Literature was surveyed from research articles, standard sources (WOS and Scopus) and clinical trials.

Expert opinion: New generation nanofibers provide high drug loading capacity and efficiency with their high surface area and tunable pore size. They also enable sustained and controlled release of antibacterial drugs with basic (direct incorporation, physically adsorption or chemically surface modification of antibacterial drugs), advanced (core–shell structure, nanoparticle decorated and multidrug loaded) and smart (stimuli responsive) antibacterial nanofiber design strategies.     

Chemical composition and medicinal properties of Nigella sativa Linn.

The black cumin or Nigella sativa L. seeds have many acclaimed medicinal properties such as bronchodilatory, hypotensive, antibacterial, antifungal, analgesic, anti-inflammatory and immunopotentiating and are universally accepted as a panacea. This review article has surveyed the relevant literature on Nigella sativa from 1960-1998 and examines the scientific evidence for these medicinal claims and highlights areas in need of research.     

抗菌药物对氟康唑动态抗真菌作用及透过生物膜的影响

目的：测定试验用抗菌药物与氟康唑联合的动态抗真菌作用,并评价试验用抗菌药物对氟康唑透过生物膜的影响。方法：采用活菌计数法描绘联合用药对白色念珠菌的动态杀菌曲线,以“三明治”透膜实验法评价试验用抗菌药物对氟康唑透过生物膜的影响。结果：试验抗菌药物对氟康唑有不同程度的增效作用,其中米诺环素和利福平对氟康唑透过耐药白色念珠菌生物膜的作用及其对氟康唑动态抗真菌的增效作用最强,氧氟沙星、阿奇霉素等次之。结论：试验用抗菌药物能促进氟康唑透过白色念珠菌生物膜,增强氟康唑的动态抗真菌作用。     

中药对细菌生物被膜作用机制的研究进展

如今越来越多耐药细菌的出现,对于细菌耐药的研究显得更为迫切,而现今的研究已经发现细菌的生物被膜是其耐药作用的一个独特机制。许多中药被发现对于细菌的生物被膜具有抑制作用,是细菌耐药性研究中一个独特的研究领域。通过查阅分析国内外有关中药对细菌生物被膜抗菌作用的文献,从细菌生物被膜形成过程、细菌生物被膜的耐药机制以及中药对于细菌生物被膜的作用等方面进行综述,为进一步研究中药的抗菌作用提供参考。     

Chemical composition of <Emphasis Type="Italic">Nigella sativa</Emphasis> Linn: Part 2 Recent advances

The black cumin or Nigella sativa L. seeds have many acclaimed medicinal properties such as bronchodilatory, hypotensive, antibacterial, antifungal, analgesic, anti-inflammatory and immunopotentiating. This review article is an update on the previous article published on Nigella sativa L. in this journal in 1999. It covers the medicinal properties and chemical syntheses of the alkaloids isolated from the seeds of the herb.     

Biofilm phosphorus uptake capacity as a tool for the assessment of pollutant effects in river ecosystems

Biofilms are a key component in the nutrient removal from the water column. However, nutrient uptake by biofilms may be hampered by the occurrence of pollutants or other stressors. This study aimed: (i) to investigate the biofilm phosphorus (P) uptake capacity as a relevant process for the maintenance of fluvial water quality and (ii) to explore the sensitivity of this process to different chemical and environmental stressors. We conducted chamber experiments to test for the relevance of biofilm P uptake capacity (PUC) as a tool to detect effects of pollutants on river self-depuration. PUC was calculated by measuring P temporal decay after performing controlled P-spikes in chambers with biofilm-colonized tiles. Four different experiments were conducted to evaluate the response of PUC to: (a) several river waters from increasing polluted sites; (b) the effect of the bactericide triclosan (TCS); (c) the combined effect of TCS and grazers; and (d) the effect of TCS after a drought episode that affected the biofilms. These experiments showed that biofilms decreased their PUC along the pollution gradient. The biofilm PUC was significantly reduced after receiving high TCS concentrations, though lower TCS concentrations also affected the biofilm when this was submitted to grazing pressure. PUC decrease was induced by flow interruption which further enhanced the TCS negative effects. Overall, PUC was sensitive to the effects of pollutants like TCS as well as to the action of biological (grazing) and environmental (drought) factors. The study also showed that multiple stressors enhance the negative effects of pollutants on the PUC of biofilms. Our study values the use of biofilms’ PUC as a sensitive ecological-based tool to assess the effects of chemicals on freshwater communities and their derived functioning in river ecosystems.     

An investigation on the antibacterial, cytotoxic, and antibiofilm efficacy of starch-stabilized silver nanoparticles

The increased emergence of drug resistant microbes creates a major challenge to the scientific community for successful development of effective therapeutics. The antimicrobial activities of silver ions are well known, but limited information is available on the effects of green silver-nanoparticles (AgNPs) on human pathogens. In this article, we evaluated the antibacterial activity of starch-stabilized AgNPs against a panel of human pathogens commonly associated with air, water and food borne infections. The shape and size distribution of AgNPs were characterized by transmission electron microscopy. We showed that AgNPs were more effective against Gram-positive and Gram-negative pathogens as compared with acid-fast bacteria. AgNPs were not cytotoxic to macrophages at the bactericidal concentration and can augment intracellular killing potential of macrophages. Furthermore, we showed that AgNPs disrupt biofilm formation and exhibit better antibacterial activity compared to human cationic antimicrobial peptide LL-37. In summary, our data suggest AgNPs as a promising template for the design of novel antibacterial agents.     

Mutagenesis by environmental pollutants and bio-monitoring of environmental mutagens

There is serious concern about the adverse effects of environmental pollutants on human health. Various mutagens, which pollute air, water, and food, possibly induce mutations in humans, and are suspected of causing cancer. Environmental mutagens, such as polycyclic aromatic hydrocarbons (PAH) and heterocyclic amines are known to bind to nucleotides, resulting in the formation of DNA adducts. Some DNA adducts are fixed as mutations through replication of DNA. Reactive oxygen species generated by pollutants also induce the formation of DNA adducts. DNA adducts have been detected as a marker for the exposure of humans and wild life to mutagens. Because of its high sensitivity the 32P-postlabel-thin layer chromatography (TLC) method is widely used for the analysis of DNA adducts formed by PAH and related bulky compounds. However, new systems are required for detecting mutations induced in genomic DNA in vivo to monitor environmental mutagens. Recently, transgenic animals, in which a target gene for detecting mutations is integrated, have been developed. With these transgenic animals, not only mutant frequency but mutation spectra can be determined. We review here recent advances in the detection of DNA adducts formed by environmental pollutants and their application for biological monitoring of environmental mutagens. We also discuss transgenic animals as important tools for evaluating the total mutagenic potential of environmental chemicals.     

Removal of dichloroacetic acid from drinking water by using adsorptive ozonation

Chloroacetic acids, formed during the disinfection process in potable water production, are considered to pose a potential risk to human health. This article deals with dichloroacetic acid (DCAA) removal from drinking water by using a process of bentonite based adsorptive ozonation. This process is formed by combined addition of ozone, bentonite and Fe³⁺. During the reaction, DCAA is removed by the joint effect of adsorption, ozonation and catalytic oxidation. In addition, under the effect of the adsorption, natural organic matters (NOM) can be adsorbed onto the bentonite surface, resulting in a reduced scavenging effect toward HO· radicals, and hence eliminate the negative effect of NOM on DCAA removal. At the initial stage of the reaction, Fe³⁺ is rapidly hydrolyzed to polycations and adsorbed onto the bentonite surface or into its structural layers. This positively charges the surface of the bentonite and increases its surface area, resulting in a strong adsorption of HA or DCAA. Furthermore, Fe³⁺ catalyzes ozone decomposition to form HO· thus further improving the efficiency. The adsorptive ozonation has been shown to be potentially advantageous in destruction of toxic, dissolved pollutants in drinking water, and appears to have great potential for a wide range of treatment applications.     

Toxicity and Carcinogenicity of Chromium Compounds in Humans

Chromium is a human carcinogen primarily by inhalation exposure in occupational settings. Although lung cancer has been established as a consequence of hexavalent chromium exposure in smokers and nonsmokers, some cancers of other tissues of the gastrointestinal and central nervous systems have also been noted. Except for a few reports from China, little is known about the health risks of environmental exposures to chromium. Likewise, there has been a lack of epidemiological studies of human exposure to hexavalent Cr by drinking water or ingestion, and it has been suggested that humans can perhaps tolerate hexavalent Cr at higher levels than the current drinking water standard of 50 ppb. This review highlights the most recent data on the induction of skin tumors in mice by chronic drinking-water exposure to hexavalent chromium in combination with solar ultraviolet light. This experimental system represents an important new animal model for chromate-induced cancers by ingestion of drinking water, and it suggests by extrapolation that chromate can likely be considered a human carcinogen by ingestion as well. The potential use of this animal model for future risk assessment is discussed.     

The relationship between structural parameters and antibacterial biofilm activity for alkyl rhamnoside as a novel amphiphilic material

In the present study, we aimed to explore the structure-activity relationship for the new amphiphilic material rhamnoside with antibacterial biofilm activity, and provide the basis for selecting rhamnoside with the optimum antibacterial biofilm activity. A series of alkyl rhamnosides with different carbon chain lengths were obtained by a simple and effective synthesis method. The structure was characterized by ¹H NMR spectrum, and their critical micelle concentration (CMC) was measured by fluorescence probe method. The hydrophilic and lipophilic balance (HLB) value was obtained by calculation. The minimal inhibitory concentration (MIC) of Staphylococcus aureus was determined by the broth double dilution method. The effect of biofilm inhibition and biofilm disruption was assayed by crystal violet method. The results showed that with the increase of carbon chain length, the CMC and HLB of alkyl rhamnosides displayed a linear downward trend, indicating that the lipophilicity and surface activityof the alkyl rhamnoside were increased. At the same time, the antibacterial activity in vitro produced the maximum, ie, 12-hydroxydecanoyl rhamnoside had the strongest antibacterial activity in vitro. Similarly, this material also exhibited the strongest antibacterial biofilm activity in vitro. The results of this study demonstrated that the most potent active material was obtained through the structure-activity relationship and it could be applied antibacterial biofilms in clinical practice.     

Numerical descriptors for the characterization of chiral compounds and their applications in modeling biological and toxicological activities

Due to the advancement in chiral synthesis and separation technology and the new regulatory policies for chiral pharmaceuticals several manufacturers are replacing the previously marketed racemate chemicals with single enantiomeric products, the so called chiral switch. Though 25% of agrochemicals are chiral in nature, most of them are sold as racemates or enantiomer enriched products. Chiral pesticides and some of the pharmaceuticals reach the human food chain as pollutants. Stereoisomers (enantiomers and diastereoisomers) not only differ from one another in their medicinal effects, but also in their phramacokinectic (adsorption, distribution, biotransformation and excretion) profiles and toxicological properties. Several recent attempts have been reported in the literature on developing mathematical models to predict the properties of chiral molecules from structure and such methods utilized numerical characterization. A comparison of different mathematical approaches on the numerical characterization of molecules with chiral center(s) and a brief background on the importance of stereochemistry in pharmacology, agrochemistry and environmental toxicology is presented.     

Infections associated with medical devices: pathogenesis, management and prophylaxis

The insertion or implantation of foreign bodies has become an indispensable part in almost all fields of medicine. However, medical devices are associated with a definitive risk of bacterial and fungal infections. Foreign body-related infections (FBRIs), particularly catheter-related infections, significantly contribute to the increasing problem of nosocomial infections. While a variety of micro-organisms may be involved as pathogens, staphylococci account for the majority of FBRIs. Their ability to adhere to materials and to promote formation of a biofilm is the most important feature of their pathogenicity. This biofilm on the surface of colonised foreign bodies is regarded as the biological correlative for the clinical experience with FBRI, that is, that the host defence mechanisms often seem to be unable to handle the infection and, in particular, to eliminate the micro-organisms from the infected device. Since antibacterial chemotherapy is also frequently not able to cure these infections despite the use of antibacterials with proven in vitro activity, removal of implanted devices is often inevitable and has been standard clinical practice. However, in specific circumstances, such as infections of implanted medical devices with coagulase-negative staphylococci, a trial of salvage of the device may be justified. All FBRIs should be treated with antibacterials to which the pathogens have been shown to be susceptible. In addition to systemic antibacterial therapy, an intraluminal application of antibacterial agents, referred to as the 'antibiotic-lock' technique, should be considered to circumvent the need for removal, especially in patients with implanted long-term catheters.To reduce the incidence of intravascular catheter-related bloodstream infections, specific guidelines comprising both technological and nontechnological strategies for prevention have been established. Quality assurance, continuing education, choice of the catheter insertion site, hand hygiene and aseptic techniques are aspects of particular interest. Furthermore, all steps in the pathogenesis of biofilm formation may represent targets against which prevention strategies may be directed. Alteration of the foreign body material surface may lead to a change in specific and nonspecific interactions with micro-organisms and, thus, to a reduced microbial adherence. Medical devices made out of a material that would be antiadhesive or at least colonisation resistant would be the most suitable candidates to avoid colonisation and subsequent infection. Another concept for the prevention of FBRIs involves the impregnation of devices with various substances such as antibacterials, antiseptics and/or metals. Finally, further studies are needed to translate the knowledge on the mechanisms of biofilm formation into applicable therapeutic and preventive strategies.     

壳聚糖/酸活化凹凸棒黏土复合物对双氯芬酸钠的吸附及体外释放

目的研究壳聚糖/酸活化凹凸棒黏土(酸化凹土)复合物对双氯芬酸钠的吸附作用和体外释放性能。方法采用紫外分光度法讨论复合物中壳聚糖的体积、pH值、吸附时间对吸附率和累积释放度的影响。结果在吸附介质pH=7和吸附4 h条件下,复合物对双氯芬酸钠的吸附率和释放度可达到80%以上。结论壳聚糖/酸化凹土复合物对双氯芬酸钠具有较好的吸附和释放性能,体外释放符合Higuchi方程。     

益生菌与抗菌治疗

随着时代的发展,抗生素的发现和滥用造成了严重的抗生素耐药,由此所产生的细菌耐药性也成为了困扰人们的棘手问题。然而,近10多年来,随着与人类健康相关的益生菌问题不断被发现和解答,相关的应用研究也呈现出“前所未有”的态势。本文对益生菌在“帮助”,以及“替代”抗生素的抗菌治疗研究方面的作用机制和治疗效果,做一简要的综述。     

Nigella sativa (black cumin) ameliorates potassium bromate-induced early events of carcinogenesis: diminution of oxidative stress

Potassium bromate (KBrO3) is a potent nephrotoxic agent. In this paper, we report the chemopreventive effect of Nigella sativa (black cumin) on KBrO3-mediated renal oxidative stress, toxicity and tumor promotion response in rats. KBrO3 (125 mg/kg body weight, intraperitoneally) enhances lipid peroxidation, gamma-glutamyl transpeptidase, hydrogen peroxide and xanthine oxidase with reduction in the activities of renal antioxidant enzymes and renal glutathione content. A marked increase in blood urea nitrogen and serum creatinine has also been observed. KBrO3 treatment also enhances ornithine decarboxylase (ODC) activity and [3H] thymidine incorporation into renal DNA. Prophylaxis of rats orally with Nigella sativa extract (50 mg/kg body weight and 100 mg/kg body weight) resulted in a significant decrease in renal microsomal lipid peroxidation (P < 0.001), gamma-glutamyl transpeptidase (P < 0.001), H2O2 (P < 0.001) and xanthine oxidase (P < 0.05). There was significant recovery of renal glutathione content (P < 0.01) and antioxidant enzymes (P < 0.001). There was also reversal in the enhancement of blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Data suggest that Nigella sativa is a potent chemopreventive agent and may suppress KBrO3-mediated renal oxidative stress, toxicity and tumour promotion response in rats.     

细菌药物主动外排系统在生物被膜耐药中的作用

摘要：细菌生物被膜的产生使传统抗菌药物难以对其进行有效的清除,进而导致严重感染的复发和持续性感染, 是人类目 前面临的又一新的挑战。生物被膜细菌中由于营养物质和代谢产物的积累,促使药物主动外排系统相关基因表达明显增加, 使 外排泵转运多种不同类型的化合物能力增强,从而产生多重耐药表型,是引起细菌耐药的主要机制之一;外排泵基因的表达对 生物被膜细菌的生长和耐药性增强方面有着重要作用。本文从生物被膜耐药的影响因素、药物主动外排系统参与生物被膜形成 及其影响、外排泵抑制剂对生物被膜耐药的影响几个方面对细菌药物主动外排系统在生物被膜耐药中的作用进行综述。     

Photocatalysts synthesized via plant mediated extracts for degradation of organic compounds: A review of formation mechanisms and application in wastewater treatment

Photocatalysis is a promising technology to remove several persistent and recalcitrant pollutants in water and wastewater. Most of the conventional chemical and physical synthesis routes of photocatalysts result in the release of toxic pollutants to the environment and hence green synthesis is a better alternative. Green synthesis of photocatalyst using plants, fungi, bacteria, yeast, and other biological sources is widely explored in recent years. The presence of various biomolecules used in green synthesis replaces conventional reducing and stabilizing agents such as hydrazine, sodium borohydride, ascorbic acids, and other polymer substitutes. This review focuses on the synthesis of photocatalysts using plant extracts through different synthesis routes and explores the efficacy of photocatalyst synthesized via plant extract mediated synthesis routes in the photodegradation of organic compounds present in water. The pathway as well as the factors affecting the formation of photocatalysts, the role of plant extract in the photocatalytic properties are explored in detail. The action of plant-mediated photocatalyst on the pollutant and the underlying predominant degradation mechanism are also discussed. Besides, this study gives an insight into the recyclability of the photocatalyst synthesized via plant extract mediated synthesis routes and addresses future perspectives and the challenges of green photocatalysts.     

反义技术在新型抗菌药物研发中的应用

抗生素耐药菌株的出现及迅速蔓延对人类生命安全构成了严重威胁,为解决这一问题,迫切需要研发新型抗菌药物。反义技术在这一领域中发挥着越来越重要的作用。本文重点综述了反义技术在以下几个方面的应用,包括寻找新的抗菌药物作用靶点、利用反义技术构建敏感菌从天然化合物库中筛选新型抗菌药物、采用反义技术抑制耐药基因的表达从而逆转耐药菌对现有抗生素的敏感性。另外,本文还讨论了人工合成的反义核酸的抗菌活性,并分析了其作为抗菌药物存在的问题及今后的发展前景。