Global cities and cultural diversity: challenges and opportunities for young people's nutrition.

Childhood obesity is a common concern across global cities and threatens sustainable urban development. Initiatives to improve nutrition and encourage physical exercise are promising but are yet to exert significant influence on prevention. Childhood obesity in London is associated with distinct ethnic and socio-economic patterns. Ethnic inequalities in health-related behaviour endure, underpinned by inequalities in employment, housing, access to welfare services, and discrimination. Addressing these growing concerns requires a clearer understanding of the socio-cultural, environmental and economic contexts of urban living that promote obesity. We explore opportunities for prevention using asset based-approaches to nutritional health and well-being, with a particular focus on adolescents from diverse ethnic backgrounds living in London. We focus on the important role that community engagement and multi-sectoral partnership play in improving the nutritional outcomes of London's children. London's children and adolescents grow up in the rich cultural mix of a global city where local streets are characterised by diversity in ethnicities, languages, religions, foods, and customs, creating complex and fluid identities. Growing up with such everyday diversity we argue can enhance the quality of life for London's children and strengthen their social capital. The Determinants of young Adult Social well-being and Health longitudinal study of about 6500 of London's young people demonstrated the positive impact of cultural diversity. Born to parents from over a hundred countries and exposed to multi-lingual households and religious practices, they demonstrated strong psychological resilience and sense of pride from cultural straddling, despite material disadvantage and discrimination. Supporting the potential contribution of such socio-cultural assets is in keeping with the values of social justice and equitable and sustainable development. Our work signals the importance of community engagement and multisectoral partnerships, involving, for example, schools and faith-based organisations, to improve the nutrition of London's children.

A novel HSP90 modulator with selective activity against thyroid cancers in vitro.

BACKGROUND: Heat shock protein 90 (HSP90) is a chaperone protein regulating several client proteins involved in thyroid cancer development. The purpose of this study was to mechanistically evaluate a novel, natural product drug with anticancer activity in thyroid cancer cell lines in vitro for future translational applications. METHODS: A total of 285 natural plant extracts and compounds were evaluated for anticancer activity by MTS assay. Apoptosis and cell cycle arrest were characterized by annexin V-propidium iodide (PI) flow cytometry. HSP90 and client protein modulation, as well as apoptosis confirmation, as demonstrated by Western blot analysis. RESULTS: Of the 285 compounds and products tested, 45 demonstrated antiproliferative activity in thyroid cancers by MTS assay. BTIMNP_D004 demonstrated the greatest inhibition (IC(50) = 155-2,890 nM in thyroid cancers). Activity was cancer-cell selective compared to fibroblasts, with increased potency over 17-AAG in BCPAP, FTC133, and DRO81-1 cells. D004 modulated cell cycle arrest after 18 hours (G(1)/G(0) --> S and G(2)/M) with 30% FTC133 cells shifted, 22% BCPAP cells shifted, and 15% SW1736 cells shifted versus controls (P < .01, P < .01, and P < .05, respectively). A total of 1 muM D004 induced significant apoptosis, with 76% BCPAP cells gated after 18 hours (annexin V-PI staining vs <3% in controls, P < .01; and 80% FTC133 cells vs 4% controls; P < .01). Western blot analysis demonstrated modulation of HSP90 expression levels, with inhibition of HSF-1, AKT, and caspase-3 expression, and cleavage of PARP in both BCPAP and FTC133 cells. CONCLUSION: BTIMNP_D004 is a novel natural product drug with anticancer activity against thyroid cancers in vitro, and may act through induction of apoptosis, modulation of cell cycle arrest, and modulation of heat shock chaperone proteins including HSP90. These preliminary in vitro data support future preclinical studies for translational applications.

Bioactive pyridine-N-oxide disulfides from Allium stipitatum.

From Allium stipitatum, three pyridine-N-oxide alkaloids (1-3) possessing disulfide functional groups were isolated. The structures of these natural products were elucidated by spectroscopic means as 2-(methyldithio)pyridine-N-oxide (1), 2-[(methylthiomethyl)dithio]pyridine-N-oxide (2), and 2,2'-dithio-bis-pyridine-N-oxide (3). The proposed structure of 1 was confirmed by synthetic S-methylthiolation of commercial 2-thiopyridine-N-oxide. Compounds 1 and 2 are new natural products, and 3 is reported for the first time from an Allium species. All compounds were evaluated for activity against fast-growing species of Mycobacterium, methicillin-resistant Staphylococcus aureus, and a multidrug-resistant (MDR) variants of S. aureus. Compounds 1 and 2 exhibited minimum inhibitory concentrations (MICs) of 0.5-8 microg/mL against these strains. A small series of analogues of 1 were synthesized in an attempt to optimize antibacterial activity, although the natural product had the most potent in vitro activity. In a whole-cell assay at 30 microg/mL, 1 was shown to give complete inhibition of the incorporation of (14)C-labeled acetate into soluble fatty acids, indicating that it is potentially an inhibitor of fatty acid biosynthesis. In a human cancer cell line antiproliferative assay, 1 and 2 displayed IC(50) values ranging from 0.3 to 1.8 microM with a selectivity index of 2.3 when compared to a human somatic cell line. Compound 1 was evaluated in a microarray analysis that indicated a similar mode of action to menadione and 8-quinolinol by interfering with the thioredoxin system and up-regulating the production of various heat shock proteins. This compound was also assessed in a mouse model for in vivo toxicity.

Antibacterial activity of two canthin-6-one alkaloids from Allium neapolitanum.

The emergence of multidrug-resistant strains of many human pathogens has led to an urgent need for the discovery and development of new antimicrobial agents. As part of an ongoing investigation into the antibacterial properties of the Alliaceae, the isolation of 1 (canthin-6-one), 2 (8-hydroxy-canthin-6-one) and 3 (5(zeta)-hydroxy-octadeca-6(E)-8(Z)-dienioc acid)) from A. neapolitanum, a perennial bulbous herb found in open pastures of the Mediterranean is reported. Compounds 1 and 2 were isolated by Sephadex LH-20 from fractions exhibiting a positive reaction with Dragendorff's reagent on TLC, compound 3 was isolated after HPLC purification of Sephadex fractions. Structures were elucidated by extensive 1D and 2D NMR experiments and are in accordance with published data, however, the 13C NMR data for compound 2 and the 1H and 13C NMR data for compound 3 are reported here for the first time. Canthin-6-one alkaloids are well-known constituents of the Simaroubaceae and Rutaceae, and display a wide range of biological activities. These metabolites are reported as constituents of the Alliaceae here for the first time, and displayed minimum inhibitory concentrations (MICs) in the range 8-32 microg/mL against a panel of fast-growing Mycobacterium species and 8-64 microg/mL against multidrug-resistant (MDR) and methicillin-resistant (MRSA) strains of Staphylococcus aureus. Compound 3 displayed antimycobacterial activity in the range of 16-32 microg/mL.

An antibacterial hydroxy fusidic acid analogue from Acremonium crotocinigenum.

A fusidane triterpene, 16-deacetoxy-7-beta-hydroxy-fusidic acid (1), was isolated from a fermentation of the mitosporic fungus Acremonium crotocinigenum. Full unambiguous assignment of all (1)H and (13)C data of 1 was carried out by extensive one- and two-dimensional NMR studies employing HMQC and HMBC spectra. Compound 1 was tested against a panel of multidrug-resistant (MDR) and methicillin-resistant Staphylococcus aureus (MRSA) strains and showed minimum inhibitory concentration values of 16 microg/ml.

Phytochemistry and antimycobacterial activity of Chlorophytum inornatum.

In a project to investigate plant derived natural products from the Liliaceae with activity against fast-growing strains of mycobacteria, we have identified two new metabolites from Chlorophytum inornatum. The active principle, a new homoisoflavanone (1) was identified as 3-(4'-methoxybenzyl)-7,8-methylenedioxy-chroman-4-one. The metabolite assigned as 7-(1'-hydroxyethyl)-2-(2''-hydroxyethyl)-3,4-dihydrobenzopyran (2) was characterised by extensive 1- and 2D NMR spectroscopy. The antimycobacterial activity of this plant was mainly due to the homoisoflavonoid which exhibited minimum inhibitory values ranging from 16-256 microg/ml against four strains of fast-growing mycobacteria.

The antimycobacterial components of hops (Humulus lupulus) and their dereplication.

Bioassay-guided fractionation of a hexane extract of strobile hops (Humulus lupulus) was undertaken to isolate and characterize the antimycobacterial constituents using the fast-growing mycobacterial species Mycobacterium fortuitum. Activity was associated with a low polarity fraction and 1H NMR spectra indicated the presence of a fatty acid mixture with unsaturated components. GC-MS of the derivatives indicated the presence of palmitic, stearic and oleic acids with small quantities of lignoceric, arachidic, behenic and linoleic acids. These compounds were assessed against M. fortuitum and all saturated fatty acids were inactive at concentrations greater than 256 microg/ml, whereas the unsaturated fats oleic and linoleic acids displayed minimum inhibitory concentrations of between 4 and 16 microg/ml against the fast-growing species tested. The widespread occurrence of these components could render screening for antimycobacterials from natural sources highly problematic without adequate dereplication. We propose that GC-MS of derivatised components of lipophilic extracts be a first step before any antimycobacterial bioassay-guided study, as this technique is the method of choice for dereplication of fatty acids.