P. aeruginosais an opportunistic pathogenic bacterium responsible for both acute and chronic infections. Beyond its natural resistance to many drugs, its ability to form biofilm, a complex biological system, renders ineffective the clearance by immune defense systems and antibiotherapy. The objective of this report is to provide an overview (i) onP. aeruginosabiofilm lifestyle cycle, (ii) on the main key actors relevant in the regulation of biofilm formation byP. aeruginosaincluding QS systems,GacS/GacAandRetS/LadStwo-component systems and C-di-GMP-dependent polysaccharides biosynthesis, and (iii) finally on reported natural and synthetic products that interfere with control mechanisms of biofilm formation byP. aeruginosawithout affecting directly bacterial viability. Concluding remarks focus on perspectives to consider biofilm lifestyle as a target for eradication of resistant infections caused byP. aeruginosa.

The measurement of oxidative damage to cellular DNA is a challenging analytical problem requiring highly sensitive and specific methods. In addition, artefactual DNA oxidation during its extraction and subsequent work-up may give rise to overestimated levels of oxidized DNA bases. In the present study, we have used ¹⁸ O-labelled 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) as an internal standard to evaluate the extent of artefactual DNA oxidation during the critical steps preceding the measurement. The labelled oxidized purine nucleoside was specifically generated in cellular DNA using the recently available generator of ¹⁸ O-labelled singlet oxygen. Artefactual DNA oxidation that could take place during the work-up increases the level of 8-oxodGuo but not of the ¹⁸ O-oxidized nucleoside. Therefore, the ratio between the two compounds, as measured by high performance liquid chromatography coupled to tandem mass spectrometry, allows an unambiguous comparison of different methodologies. The comparison of different DNA extraction protocols led to the conclusion that artefactual DNA oxidation during the extraction step could be minimized if: (i) nuclei are isolated after cell lysis; (ii) desferrioxamine, a transition metal chelator is added to the different extraction buffers; and (iii) sodium iodide (or alternatively guanidine thiocyanate) is used for DNA precipitation. It was also demonstrated that sodium iodide does not decompose the targeted oxidized purine nucleoside. In addition, three different DNA digestion protocols were evaluated and they were found to give rise to similar results. Using the best-studied protocol, the steady-state cellular background level of 8-oxodGuo, in a lymphocyte cell line, was determined to be ∼0.5 lesions/10 ⁶ DNA nucleosides.

Preliminary screening of the Malagasy plantCombretum albiflorumfor compounds attenuating the production of quorum sensing (QS)-controlled virulence factors in bacteria led to the identification of active fractions containing flavonoids. In the present study, several flavonoids belonging to the flavone, flavanone, flavonol and chalcone structural groups were screened for their capacity to reduce the production of QS-controlled factors in the opportunistic pathogenPseudomonas aeruginosa(strain PAO1). Flavanones (i.e. naringenin, eriodictyol and taxifolin) significantly reduced the production of pyocyanin and elastase inP. aeruginosawithout affecting bacterial growth. Consistently, naringenin and taxifolin reduced the expression of several QS-controlled genes (i.e.lasI,lasR,rhlI,rhlR,lasA,lasB,phzA1andrhlA) inP. aeruginosaPAO1. Naringenin also dramatically reduced the production of the acylhomoserine lactonesN-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL) andN-butanoyl-l-homoserine lactone (C4-HSL), which is driven by thelasIandrhlIgene products, respectively. In addition, using mutant strains deficient for autoinduction (ΔlasIand ΔrhlI) and LasR- and RhlR-based biosensors, it was shown that QS inhibition by naringenin not only is the consequence of a reduced production of autoinduction compounds but also results from a defect in the proper functioning of the RlhR–C4-HSL complex. Widely distributed in the plant kingdom, flavonoids are known for their numerous and determinant roles in plant physiology, plant development and in the success of plant–rhizobia interactions, but, as shown here, some of them also have a role as inhibitors of the virulence of pathogenic bacteria by interfering with QS mechanisms.

Pharmacovigilance is essential for developing reliable information on the safety of herbal medicines as used in Europe and the US. The existing systems were developed for synthetic medicines and require some modification to address the specific differences of medicinal herbs. Traditional medicine from many different cultures is used in Europe and the US which adds to the complexities and difficulties of even basic questions such as herb naming systems and chemical variability. Allied to this also is the perception that a 'natural' or herbal product must be safe simply because it is not synthetic which means that the safety element of monitoring for such medicines can be overlooked because of the tag associated with such products. Cooperation between orthodox physicians and traditional practitioners is needed to bring together the full case details. Independent scientific assistance on toxicological investigation, botanical verification can be invaluable for full evaluation of any case report. Systematic pharmacovigilance is essential to build up reliable information on the safety of herbal medicines for the development of appropriate guidelines for safe effective use.

Traditional Chinese medicine (TCM) is an integral part of mainstream medicine in China. Due to its worldwide use, potential impact on healthcare and opportunities for new drug development, TCM is also of great international interest. Recently, a new era for modernisation of TCM was launched with the successful completion of the Good Practice in Traditional Chinese Medicine Research in the Post-genomic Era (GP-TCM) project, the European Union’s Seventh Framework Programme (FP7) coordination action on TCM research. This 3.5-year project that involved inputs from over 200 scientists resulted in the production of 20 editorials and in-depth reviews on different aspects of TCM that were published in a special issue of Journal of Ethnopharmacology (2012; volume 140, issue 3). In this narrative review, we aim to summarise the findings of the FP7 GP-TCM project and highlight the relevance of TCM to modern medicine within a historical and international context. Advances in TCM research since the 1950s can be characterised into three phases: Phase I (1950s-1970s) was fundamental for developing TCM higher education, research and hospital networks in China; Phase II (1980s-2000s) was critical for developing legal, economic and scientific foundations and international networks for TCM; and Phase III (2011 onwards) is concentrating on consolidating the scientific basis and clinical practice of TCM through interdisciplinary, interregional and intersectoral collaborations. Taking into account the quality and safety requirements newly imposed by a globalised market, we especially highlight the scientific evidence behind TCM, update the most important milestones and pitfalls, and propose integrity, integration and innovation as key principles for further modernisation of TCM. These principles will serve as foundations for further research and development of TCM, and for its future integration into tomorrow’s medicine.

Traditional Chinese Medicine (TCM), including Traditional Chinese Medicine drugs (TCM drugs), has been playing a very important role in health protection and disease control for thousands of years in China. Relying on natural products, mainly of herbal origin, used either as raw materials for decoction, as prepared herbal medicines or as formulated traditional medicines, TCM is still widely accepted by Chinese people, especially for chronic diseases treatment. This extensive use warrants safety measures and so TCM drug safety monitoring and risk management are becoming increasingly important tasks for the Chinese State Food and Drug Administration (SFDA). The Adverse Drug Reaction (ADR) monitoring system in China was established both for western and TCM drugs in 1989 as a voluntary reporting system with a National Center collecting and compiling reports. Serious or multi-case reports on individual TCM drug or formulated products are detailed in the Chinese ADR Information Bulletin to inform the public and Drug Administrative authorities for risk management. About 10-15% of the ADR reports received by the National Center are related to TCM drugs and mainly pertaining to the formulated products. In certain cases, the suspension of a particular TCM preparation is decided by SFDA China. The model of safety monitoring and risk management of TCM drugs is still under exploration. Indeed, the characteristics and risk factors associated with these drugs require both proper understanding and control of the risk by strengthening standardization of clinical applications, basic science research, quality control in manufacturing, exploration of the actives monitoring methodology and enhancement of international communication and cooperation.