Regioselective synthesis of plant (iso)flavone glycosides in Escherichia coli

The flavonoids genistein, biochanin A, luteolin, quercetin, and kaempferol are plant natural products with potentially useful pharmacological and nutraceutical activities. These natural products usually exist in plants as glycosides, and their glycosylation has a remarkable influence on their pharmacokinetic properties. The glycosyltransferases UGT71G1 and UGT73C8 from Medicago truncatula are excellent reagents for the regioselective glycosylation of (iso)flavonoids in Escherichia coli grown in Terrific broth. Ten to 20 mg/L of either genistein or biochanin A 7-O-glucoside was produced after feeding genistein or biochanin A to E. coli expressing UGT71G1, and similar levels of luteolin 4’-O- and 7-O-glucosides were produced after feeding luteolin to cultures expressing UGT73C8. For the production of kaempferol 3-O-glucoside or quercetin 3-O-glucoside, the Phe148Val or Tyr202Ala mutants of UGT71G1 were employed. Ten to 16 mg/L of either kaempferol 3-O- or quercetin 3-O-glucosides were produced on feeding kaempferol or quercetin to E. coli expressing these enzymes. More than 90% of the glucoside products were released to the medium, facilitating their isolation

The mechanisms by which polyamines accelerate tumor spread

Increased polyamine concentrations in the blood and urine of cancer patients reflect the enhanced levels of polyamine synthesis in cancer tissues arising from increased activity of enzymes responsible for polyamine synthesis. In addition to their de novo polyamine synthesis, cells can take up polyamines from extracellular sources, such as cancer tissues, food, and intestinal microbiota. Because polyamines are indispensable for cell growth, increased polyamine availability enhances cell growth. However, the malignant potential of cancer is determined by its capability to invade to surrounding tissues and metastasize to distant organs. The mechanisms by which increased polyamine levels enhance the malignant potential of cancer cells and decrease anti-tumor immunity are reviewed. Cancer cells with a greater capability to synthesize polyamines are associated with increased production of proteinases, such as serine proteinase, matrix metalloproteinases, cathepsins, and plasminogen activator, which can degrade surrounding tissues. Although cancer tissues produce vascular growth factors, their deregulated growth induces hypoxia, which in turn enhances polyamine uptake by cancer cells to further augment cell migration and suppress CD44 expression. Increased polyamine uptake by immune cells also results in reduced cytokine production needed for anti-tumor activities and decreases expression of adhesion molecules involved in anti-tumor immunity, such as CD11a and CD56. Immune cells in an environment with increased polyamine levels lose anti-tumor immune functions, such as lymphokine activated killer activities. Recent investigations revealed that increased polyamine availability enhances the capability of cancer cells to invade and metastasize to new tissues while diminishing immune cells' anti-tumor immune functions

Polyamines and cancer: old molecules, new understanding

The amino-acid-derived polyamines have long been associated with cell growth and cancer, and specific oncogenes and tumour-suppressor genes regulate polyamine metabolism. Inhibition of polyamine synthesis has proven to be generally ineffective as an anticancer strategy in clinical trials, but it is a potent cancer chemoprevention strategy in preclinical studies. Clinical trials, with well-defined goals, are now underway to evaluate the chemopreventive efficacy of inhibitors of polyamine synthesis in a range of tissues

Performance enhancement with supplements: incongruence between rationale and practice.

<p>Abstract</p> <p>Background</p> <p>Athletes are expected to consider multiple factors when making informed decision about nutritional supplement use. Besides rules, regulations and potential health hazards, the efficacy of different nutritional supplements in performance enhancement is a key issue. The aim of this paper was to find evidence for informed decision making by investigating the relationship between specific performance-related reasons for supplement use and the reported use of nutritional supplements.</p> <p>Methods</p> <p>The 'UK Sport 2005 Drug Free Survey' data (n = 874) were re-analysed using association [χ²] and 'strength of association' tests [ϕ] to show the proportion of informed choices and to unveil incongruencies between self-reported supplement use and the underlying motives.</p> <p>Results</p> <p>Participants (n = 520) reported supplement use in the pattern of: vitamin C (70.4%), creatine (36.1%), whey protein (30.6%), iron (29.8%), caffeine (23.8%), and ginseng (8.3%) for the following reasons: strength maintenance (38.1%), doctors' advice (24.2%), enhancing endurance (20.0%), ability to train longer (13.3%), and provided by the governing body (3.8%). Of thirty possible associations between the above supplements and reasons, 11 were predictable from literature precedents and only 8 were evidenced and these were not strong (ϕ < .7). The best associations were for the ability to train longer with creatine (reported by 73.9%, χ²= 49.14, p < .001; ϕ = .307, p < .001), and maintaining strength with creatine (reported by 62.6%, χ²= 97.08, p < .001; ϕ = .432, p < .001) and whey protein (reported by 56.1%, χ²= 97.82, p < .001; ϕ = .434, p < .001).</p> <p>Conclusion</p> <p>This study provided a platform for assessing congruence between athletes' reasons for supplement use and their actual use. These results suggest that a lack of understanding exists in supplement use. There is an urgent need to provide accurate information which will help athletes make informed choices about the use of supplements.</p