The human small-intestinal microbiota is characterised by relatively large and dynamic Streptococcus populations. In this study, genome sequences of small-intestinal streptococci from S. mitis, S. bovis, and S. salivarius species-groups were determined and compared with those from 58 Streptococcus strains in public databases. The Streptococcus pangenome consists of 12,403 orthologous groups of which 574 are shared among all sequenced streptococci and are defined as the Streptococcus core genome. Genome mining of the small-intestinal streptococci focused on functions playing an important role in the interaction of these streptococci in the small-intestinal ecosystem, including natural competence and nutrient-transport and metabolism. Analysis of the small-intestinal Streptococcus genomes predicts a high capacity to synthesize amino acids and various vitamins as well as substantial divergence in their carbohydrate transport and metabolic capacities, which is in agreement with observed physiological differences between these Streptococcus strains. Gene-specific PCR-strategies enabled evaluation of conservation of Streptococcus populations in intestinal samples from different human individuals, revealing that the S. salivarius strains were frequently detected in the small-intestine microbiota, supporting the representative value of the genomes provided in this study. Finally, the Streptococcus genomes allow prediction of the effect of dietary substances on Streptococcus population dynamics in the human small-intestine.
The greater celandine ‘Chelidonium majus’ and its main alkaloid chelidonine have previously been shown to exert high cytotoxicity against cancer cells. Furthermore, chelidonine is proposed to possess pro-apoptotic and anti-metastatic properties. Within the present study, the effects chelidonine on several HNSCC cell lines, as well as primary cells, were analyzed with respect to growth, migration, angiogenesis and apoptosis. Chelidonine suppressed the growth of all tested HNSCC cell lines, including a paclitaxel-resistant and P-glycoprotein (MDR1) overexpressing cell line, but not in a clear dose-dependent manner. Mucosal keratinocytes were also strongly affected by chelidonine, while fibroblasts proved to be much more resistant. Chelidonine failed to trigger apoptosis at physiological concentrations in HNSCC cell lines. Based on a spheroid invasion model chelidonine suppressed invasion of FaDu cells effectively on gelatin, fibronectin, collagen I, laminin and Matrigel®. However, invasion inhibition of the more aggressively invading cell line HLaC78 largely failed. Using the tube formation assay, chelidonine effectively inhibited angiogenesis. Expression analysis revealed an upregulation of the xenobiotic metabolism genes CYP1A1 and MDR1 by chelidonine. In summary, chelidonine appeared to exert only minor impact on head and neck cancer cells. Chelidonine did not produce clear dose-dependent and cell-type specific cytotoxicity nor did it trigger apoptosis strongly.
Using a quantitative reverse transcriptase PCR assay, the mRNA expression of five putative drug resistance-related genes were assessed in normal peripheral (n = 14) and bone marrow (n = 4) mononuclear cells from healthy donors and patients with acute myeloid leukaemia (n = 11). The mRNA levels of MDR1, the multidrug resistance-associated protein and glutathione-S-transferase π were equally expressed in both compartments. Bcl-2 mRNA was slightly higher in the leukaemic marrow samples. However, topoisomerase IIα mRNA levels were found to be much higher in normal and leukaemic marrow cells compared to peripheral blood (p < 0.01), which may, in part, reflect the different proliferation pattern of the mononuclear cells in the two compartments. Such findings could be important for researchers using bulk assays in a mix of samples from peripheral blood or bone marrow to investigate prognostic factors in patients with leukaemia.
C 12 H 40 Cl 6 N 4 O 4 P 4 Zn 3 ,monoclinic, C2/c (no. 15), a =16.8933(5) Å, b =9.1740(4) Å, c =21.5013(7) Å,Source of material 0.78 g(7.17 mmol)(Dimethylphosphoryl)methanamine (dpma) wasdissolved in basicethanol(p.a.,adjustedtopH8-9 by an ammonium hydroxide solution (20%),1,5 ml). To get amolar ratio of 3:4 zinc(II)chloride : dpma,0.73 g(5.38 mmol) zinc(II)chloride was added to the solution. The reaction mixture was heated to 50°C and stirred for 2h.Cooling to room temperature yielded in a viscose liquid. Recrystallization from ethanol -byslow evaporation at 60°C -g ave needle shaped colourless crystals. The Ramanspectrum was measured using aneodymium doted yttrium-aluminum-garnet-laser (Nd:YAG) on aM ultiRam spectrometer from Bruker, 4000-60 cm -1 :3282(w), 3254(m), 3224(w,
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