The Nutritional Therapy Council, an independent body established by a group of professional associations representing nutritional therapists, with funding from the UK Department of Heath, launched a voluntary national registration scheme in 2006 for practitioners of nutritional therapy, a bioscience-based branch of CAM. Registration of practitioners of complementary and alternative medicine (CAM) has been proposed as an important measure towards assuring the safety of individuals choosing to use therapies that are outside the practice of mainstream medicine. The study provides an overview of H isotope distribution in the major molecular constituents of intact bacterial cells, offering insight into the mechanisms underlying the metabolic control on the H isotopic composition of biomarker precursors. Non-aliphatic H positions as a whole exhibited similar net fractionation factors to the lipids. Besides, enzyme malfunctioning caused by 2H substitution is likely to promote proteolysis, which could also contribute to the 2H depletion in proteins. This depletion is likely related to the dynamic regulation of central metabolic pathways that gradually builds up 2H in tricarboxylic acid (TCA) cycle intermediates though continuous interaction with water, leading to the rapid synthesis of isotopically light amino acids early in the cell cycle and the production of isotopically enriched FAs late in the cell cycle. Aliphatic H in proteins was significantly depleted in 2H relative to FAs by 290–640‰. The net fractionation of fatty acids (FAs) relative to water and glucose was consistent with that in studies employing natural 2H abundance, suggesting the 10% deuterated environment does not alter isotope fractionation during FA biosynthesis. In the 10% 2H glucose experiment, the corresponding 2H uptake was 2.0%, 1.4% and 2.5%, respectively, and 1.9% for the bulk cell. In the 10% 2H water experiment, the 2H abundance of the bulk cell was 4.5% the 2H uptake by membrane lipids, aliphatic H in proteins, and all the non-aliphatic H positions (including nucleic acids and sugars) was 6.2%, 2.3% and 6.2%, respectively. Using multi-nuclear ( 1H, 2H and 13C) solid state nuclear magnetic resonance (NMR) spectroscopy and gas chromatography–mass spectrometry (GC–MS), we were able to track the incorporation of 1H and 2H metabolic fluxes into different cellular components of Escherichia coli during growth on two sets of media: (i) 10% deuterated water and non-deuterated glucose, and (ii) non-deuterated water and 10% deuterated glucose. Recent studies reveal substantial variability in biosynthetic 2H/ 1H fractionation between lipids and water, which highlights the effect of central metabolic pathways on the H isotopic composition of the end products. These results implicated that SAD could be developed as a leading compound to target cancer stem cells and would be a promising agent to treat lung cancer patients. Although SAD did not affect the expression of ABCG2 mRNA, it shortened the half-life of ABCG2 protein by activating calpain 1. The MTT assay showed the sorted SP cells were sensitive to SAD and we also found SAD could inhibit the sphere-forming ability of SP cells. Furthermore, SAD could down-regulate the expression of ABCG2 and decrease the percentage of SP cells in lung cancer cells. In this study, we found secalonic acid D (SAD), a metabolite of marine-derived mangrove endophytic fungus, showed potent anticancer effect on ABCB1-, ABCC1- and ABCG2- overexpressing multidrug resistance cells by MTT assay. ABCG2 is found to confer the side population (SP) phenotype, multidrug resistance (MDR) and tumor recurrence. The side population cells characterized by the ability to transport Hoechst 33342 out of cells have been identified as cancer stem-like cells.
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