Urinary tract infections (UTIs) are one of the most common pathological conditions in both community and hospital settings. It has been estimated that about 150 million people worldwide develop UTI each year, with high social costs in terms of hospitalizations and medical expenses. Among the common uropathogens associated to UTIs development, UroPathogenic Escherichia coli (UPEC) is the primary cause. UPEC strains possess a plethora of both structural (as fimbriae, pili, curli, flagella) and secreted (toxins, iron-acquisition systems) virulence factors that contribute to their capacity to cause disease, although the ability to adhere to host epithelial cells in the urinary tract represents the most important determinant of pathogenicity. On the opposite side, the bladder epithelium shows a multifaceted array of host defenses including the urine flow and the secretion of antimicrobial substances, which represent useful tools to counteract bacterial infections. The fascinating and intricate dynamics between these players determine a complex interaction system that needs to be revealed. This review will focus on the most relevant components of UPEC arsenal of pathogenicity together with the major host responses to infection, the current approved treatment and the emergence of resistant UPEC strains, the vaccine strategies, the natural antimicrobial compounds along with innovative anti-adhesive and prophylactic approaches to prevent UTIs.

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Predicting which species will occur together in the future, and where, remains one of the greatest challenges in ecology, and requires a sound understanding of how the abiotic and biotic environments interact with dispersal processes and history across scales. Biotic interactions and their dynamics influence species' relationships to climate, and this also has important implications for predicting future distributions of species. It is already well accepted that biotic interactions shape species' spatial distributions at local spatial extents, but the role of these interactions beyond local extents (e.g. 10 km(2) to global extents) are usually dismissed as unimportant. In this review we consolidate evidence for how biotic interactions shape species distributions beyond local extents and review methods for integrating biotic interactions into species distribution modelling tools. Drawing upon evidence from contemporary and palaeoecological studies of individual species ranges, functional groups, and species richness patterns, we show that biotic interactions have clearly left their mark on species distributions and realised assemblages of species across all spatial extents. We demonstrate this with examples from within and across trophic groups. A range of species distribution modelling tools is available to quantify species environmental relationships and predict species occurrence, such as: (i) integrating pairwise dependencies, (ii) using integrative predictors, and (iii) hybridising species distribution models (SDMs) with dynamic models. These methods have typically only been applied to interacting pairs of species at a single time, require a priori ecological knowledge about which species interact, and due to data paucity must assume that biotic interactions are constant in space and time. To better inform the future development of these models across spatial scales, we call for accelerated collection of spatially and temporally explicit species data. Ideally, these data should be sampled to reflect variation in the underlying environment across large spatial extents, and at fine spatial resolution. Simplified ecosystems where there are relatively few interacting species and sometimes a wealth of existing ecosystem monitoring data (e.g. arctic, alpine or island habitats) offer settings where the development of modelling tools that account for biotic interactions may be less difficult than elsewhere.

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Because nuclear factor-κB (NF-κB) is a ubiquitously expressed proinflammatory transcription factor that regulates the expression of over 500 genes involved in cellular transformation, survival, proliferation, invasion, angiogenesis, metastasis, and inflammation, the NF-κB signaling pathway has become a potential target for pharmacological intervention. A wide variety of agents can activate NF-κB through canonical and noncanonical pathways. Canonical pathway involves various steps including the phosphorylation, ubiquitination, and degradation of the inhibitor of NF-κB (IκBα), which leads to the nuclear translocation of the p50-p65 subunits of NF-κB followed by p65 phosphorylation, acetylation and methylation, DNA binding, and gene transcription. Thus, agents that can inhibit protein kinases, protein phosphatases, proteasomes, ubiquitination, acetylation, methylation, and DNA binding steps have been identified as NF-κB inhibitors. Because of the critical role of NF-κB in cancer and various chronic diseases, numerous inhibitors of NF-κB have been identified. In this review, however, we describe only small molecules that suppress NF-κB activation, and the mechanism by which they block this pathway.

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The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and "leads" which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations.

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Objective To investigate if extracts of Hypericum perforatum (St John's wort) are more effective than placebo in the treatment of depression, are as effective as standard antidepressive treatment, and have fewer side effects than standard antidepressant drugs. Design Systematic review and meta-analysis of trials revealed by searches. Trials 23 randomised trials including a total of 1757 outpatients with mainly mild or moderately severe depressive disorders: 15 (14 testing single preparations and one a combination with other plant extracts) were placebo controlled, and eight (six testing single preparations and two combinations) compared hypericum with another drug treatment. Main outcome measures A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group), and numbers of patients reporting and dropping out for side effects. Results Hypericum extracts were significantly superior to placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01) and similarly effective as standard antidepressants (single preparations 1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94). There were two (0.8%) drop outs for side effects with hypericum and seven (3.0%) with standard antidepressant drugs. Side effects occurred in 50 (19.8%) patients on hypericum and 84 (52.8%) patients on standard antidepressants. Conclusion There is evidence that extracts of hypericum are more effective than placebo for the treatment of mild to moderately severe depressive disorders. Further studies comparing extracts with standard antidepressants in well defined groups of patients and comparing different extracts and doses are needed.

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