Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation     

Jain M  Nilsson R  Sharma S  Madhusudhan N  Kitami T  Souza AL  Kafri R  Kirschner MW  Clish CB  Mootha VK 《Science (New York, N.Y.)》2012,336(6084):1040-1044

Metabolic reprogramming has been proposed to be a hallmark of cancer, yet a systematic characterization of the metabolic pathways active in transformed cells is currently lacking. Using mass spectrometry, we measured the consumption and release (CORE) profiles of 219 metabolites from media across the NCI-60 cancer cell lines, and integrated these data with a preexisting atlas of gene expression. This analysis identified glycine consumption and expression of the mitochondrial glycine biosynthetic pathway as strongly correlated with rates of proliferation across cancer cells. Antagonizing glycine uptake and its mitochondrial biosynthesis preferentially impaired rapidly proliferating cells. Moreover, higher expression of this pathway was associated with greater mortality in breast cancer patients. Increased reliance on glycine may represent a metabolic vulnerability for selectively targeting rapid cancer cell proliferation.  相似文献   

Adenosine deaminase activity in serum, erythrocytes and lymphocytes of rats infected with Leptospira icterohaemorrhagiae     

Tonin AA  Pimentel VC  da Silva AS  de Azevedo MI  Souza VC  Wolkmer P  Rezer JF  Badke MR  Leal DB  Schetinger MR  Monteiro SG  Lopes ST 《Research in veterinary science》2012,92(2):197-201

Leptospirosis is a systemic disease of humans and domestic animals, mainly dogs, cattle and swine. The course of human leptospirosis varies from mild to severe fatal forms and the most severe form of human leptospirosis is principally caused by Leptospira interrogans serovar icterohaemorrhagiae (L. icterohaemorrhagiae). The enzyme adenosine deaminase (ADA) plays an important role in the production and differentiation of blood cells. The aim of this study was to evaluate the activity of ADA in serum, erythrocytes and lymphocytes of rats infected with L. icterohaemorrhagiae, as compared with non-infected rats. Twenty-four adult rats, divided into two uniform groups (A and B) were used for the enzymatic assays. The animals in Group B were inoculated intraperitoneally with 2×10(8) leptospires/rat, and the rodents in Group A (control) were not-inoculated. Blood collection was performed on days 5 and 15 post-infection (PI) and the blood used to assess the ADA activity. The infection by L.icterohaemorrhagiae altered erythrocyte count, hemoglobin concentration and hematocrit, causing a decrease in all these parameters on day 15 PI. Lymphocytes decreased significantly on day 15 PI, and ADA activity in serum was inhibited in infected rats on days 5 and 15 PI and its activity in erythrocytes were increased on day 5 PI. On day 5 PI, we found an increase in ADA activity in erythrocytes of infected rats. No correlation was observed between hematocrit and erythrocyte ADA activity on days 5 and 15 PI. The ADA activity was inhibited in rats infected on day 15 PI. A positive correlation (r(2)=60) was also observed between the number of lymphocytes and ADA activity in lymphocytes on day 15 PI (P<0.05). In conclusion, our results showed that the ADA activity is altered in serum, lymphocytes and erythrocytes in experimental infection by L.icterohaemorrhagiae in rats, concomitantly with hematological parameters.  相似文献   

Iridoid, phenylethanoid and flavonoid glycosides from Sideritis trojana     

Kirmizibekmez H  Ariburnu E  Masullo M  Festa M  Capasso A  Yesilada E  Piacente S 《Fitoterapia》2012,83(1):130-136

From the MeOH extract of Sideritis trojana, a new iridoid glycoside, 10-O-(E)-feruloylmelittoside (1) was obtained in addition to four known iridoid glycosides [melittoside (2), 10-O-(E)-p-coumaroylmelittoside (3), stachysosides E (4) and G (5)]. Moreover, five phenylethanoid glycosides [verbascoside (6), isoacteoside (7), lamalboside (8), leonoside A (9), isolavandulifolioside (10), three flavone glycosides (isoscutellarein 7-O-[6'-O-acetyl-β-allopyranosyl-(1→2)]-β-glucopyranoside (11), 4'-O-methyisoscutellarein 7-O-[6'-O-acetyl-β-allopyranosyl-(1→2)]-β-glucopyranoside (12), 3'-hydroxy-4'-O-methyisoscutellarein 7-O-[6'-O-acetyl-β-allopyranosyl-(1→2)]-β-glucopyranoside (13) and a benzylalcohol derivative (di-O-methylcrenatin) were obtained and identified. The structures were elucidated on the basis of NMR and HRMS data. All compounds were tested for their antioxidant activity by in vitro TEAC assay and some of them exhibited moderate activity (0.97-1.44 mM) when compared with the reference compound (quercetin 1.86 mM). Glycosides 6-13, the most active compounds in the TEAC assay, were also tested by flow cytometry to evaluate their ability to affect the levels of reactive oxygen species (ROS) in human prostate cancer cells (PC3).  相似文献   

Does canopy mean nitrogen concentration explain variation in canopy light use efficiency across 14 contrasting forest sites?     

Peltoniemi M  Pulkkinen M  Kolari P  Duursma RA  Montagnani L  Wharton S  Lagergren F  Takagi K  Verbeeck H  Christensen T  Vesala T  Falk M  Loustau D  Mäkelä A 《Tree physiology》2012,32(2):200-218

The maximum light use efficiency (LUE?=?gross primary production (GPP)/absorbed photosynthetic photon flux density (aPPFD)) of plant canopies has been reported to vary spatially and some of this variation has previously been attributed to plant species differences. The canopy nitrogen concentration [N] can potentially explain some of this spatial variation. However, the current paradigm of the N-effect on photosynthesis is largely based on the relationship between photosynthetic capacity (A(max)) and [N], i.e., the effects of [N] on photosynthesis rates appear under high PPFD. A maximum LUE-[N] relationship, if it existed, would influence photosynthesis in the whole range of PPFD. We estimated maximum LUE for 14 eddy-covariance forest sites, examined its [N] dependency and investigated how the [N]-maximum LUE dependency could be incorporated into a GPP model. In the model, maximum LUE corresponds to LUE under optimal environmental conditions before light saturation takes place (the slope of GPP vs. PPFD under low PPFD). Maximum LUE was higher in deciduous/mixed than in coniferous sites, and correlated significantly with canopy mean [N]. Correlations between maximum LUE and canopy [N] existed regardless of daily PPFD, although we expected the correlation to disappear under low PPFD when LUE was also highest. Despite these correlations, including [N] in the model of GPP only marginally decreased the root mean squared error. Our results suggest that maximum LUE correlates linearly with canopy [N], but that a larger body of data is required before we can include this relationship into a GPP model. Gross primary production will therefore positively correlate with [N] already at low PPFD, and not only at high PPFD as is suggested by the prevailing paradigm of leaf-level A(max)-[N] relationships. This finding has consequences for modelling GPP driven by temporal changes or spatial variation in canopy [N].  相似文献   

Comparing the intra-annual wood formation of three European species (Fagus sylvatica, Quercus petraea and Pinus sylvestris) as related to leaf phenology and non-structural carbohydrate dynamics     

Michelot A  Simard S  Rathgeber C  Dufrêne E  Damesin C 《Tree physiology》2012,32(8):1033-1045

Monitoring cambial phenology and intra-annual growth dynamics is a useful approach for characterizing the tree growth response to climate change. However, there have been few reports concerning intra-annual wood formation in lowland temperate forests with high time resolution, especially for the comparison between deciduous and coniferous species. The main objective of this study was to determine how the timing, duration and rate of radial growth change between species as related to leaf phenology and the dynamics of non-structural carbohydrates (NSC) under the same climatic conditions. We studied two deciduous species, Fagus sylvatica L. and Quercus petraea (Matt.) Liebl., and an evergreen conifer, Pinus sylvestris L. During the 2009 growing season, we weekly monitored (i) the stem radial increment using dendrometers, (ii) the xylem growth using microcoring and (iii) the leaf phenology from direct observations of the tree crowns. The NSC content was also measured in the eight last rings of the stem cores in April, June and August 2009. The leaf phenology, NSC storage and intra-annual growth were clearly different between species, highlighting their contrasting carbon allocation. Beech growth began just after budburst, with a maximal growth rate when the leaves were mature and variations in the NSC content were low. Thus, beech radial growth seemed highly dependent on leaf photosynthesis. For oak, earlywood quickly developed before budburst, which probably led to the starch decrease quantified in the stem from April to June. For pine, growth began before the needles unfolding and the lack of NSC decrease during the growing season suggested that the substrates for radial growth were new assimilates of the needles from the previous year. Only for oak, the pattern determined from the intra-annual growth measured using microcoring differed from the pattern determined from dendrometer data. For all species, the ring width was significantly influenced by growth duration and not by growth rate, which differs from previous studies. The observed between-species difference at the intra-annual scale is key information for anticipating suitability of future species in temperate forests.  相似文献   

Antiproliferative steroidal glycosides from Digitalis ciliata     

Perrone A  Capasso A  Festa M  Kemertelidze E  Pizza C  Skhirtladze A  Piacente S 《Fitoterapia》2012,83(3):554-562

Two new compounds, a furostanol glycoside (1) and a pregnane glycoside (4), along with eight known compounds, belonging to the classes of spirostane (2,3), pregnane (5–7) and cardenolide (8–10) glycosides, were isolated from the seeds of Digitalis ciliata. Their structures were elucidated by 1D and 2D-NMR experiments as well as ESI-MS analysis. For the first time pregnane glycosides of the diginigenin series have been isolated from D. ciliata. The cytotoxic effects of compounds 1–10 on cell viability of several cancer cell lines, namely human breast cancer (MCF-7), human glioblastoma (T98G), human lung adenocarcinoma (A549), human colon carcinoma (HT-29), and human prostate cancer (PC-3) cell lines were evaluated. Compounds 1, 4, 7 and 8 showed antiproliferative effects against MCF-7, HT-29 and A549 cancer cells with IC₅₀ values ranging from 8.3 to 20 μM. The effects of compounds 1–10 on cell proliferation were evaluated on these three cancer cell lines by cell cycle analysis of DNA content using flow cytometry. Compounds 7, 8 and 10 induced significant changes in G₂/M cell cycle phase of all analyzed cells. The obtained results indicate that compounds 7, 8 and 10 are cytostatic compounds effective in reducing cell proliferation by inducing accumulation of the cells in the G₂/M phase of the cell cycle.  相似文献   

Existence of two O-serotypes in the fish pathogen Pseudomonas anguilliseptica   总被引：1，自引：0，他引：1  

López-Romalde S  Magariños B  Ravelo C  Toranzo AE  Romalde JL 《Veterinary microbiology》2003,94(4):325-333

The serological characteristics of a group of 32 Pseudomonas anguilliseptica strains isolated in Spain from seabream (Sparus aurata) and turbot (Scophthalmus maximus) were compared with a total of 18 collection strains of this bacterial species with different geographical and host origin. The employment of different techniques, including slide agglutination, microagglutination and dot blot, allowed us to establish two serological groups, one comprising practically all the eel isolates, and the other including the majority of isolates from other fish species. The study of the lipopolysaccharides (LPS) and outer membrane proteins (OMP) corroborated these results, indicating that the serological differences among strains are due to the somatic antigen and not to antigenic determinants of protein nature. Therefore, a serological scheme of two "O" serotypes is proposed for P. anguilliseptica. The results obtained will be of importance for epidemiological studies as well as for the design of adequate vaccine formulations.  相似文献   

Solvent transport phenomenon of cellulose microfiber (CMF) reinforced poly (ethylene-co-vinyl acetate) (EVA) composites     

A. Sonia  K. Priya Dasan 《Fibers and Polymers》2013,14(11):1886-1893

Composite films based on EVA with CMF were prepared and characterized for their solvent transport nature. CMF were derived from Hibiscus sabdariffa by steam explosion technique and incorporated in the EVA matrix by extrusion. Solvent transport by the composites was analyzed using hexane, heptane and octane as penetrant molecules. The solvent uptake behavior of EVA/CMF composites is explained on the basis of the penetrant size, temperature and the filler loading. The composite had improved barrier property compared with unfilled EVA. This in turn is an indication of good fiber-matrix interaction in the composite system. Diffusion parameters such as diffusion coefficient, permeation coefficient and Arrhenius activation parameters and thermodynamic parameters such as enthalpy and entropy were evaluated in detail. The mode of transport was found to be Fickian.  相似文献   

Citrantifidiene and citrantifidiol: bioactive metabolites produced by Trichoderma citrinoviride with potential antifeedant activity toward aphids     

Evidente A  Ricciardiello G  Andolfi A  Sabatini MA  Ganassi S  Altomare C  Favilla M  Melck D 《Journal of agricultural and food chemistry》2008,56(10):3569-3573

Two novel metabolites with potential antifeedant activity were isolated from cultures of the fungus Trichoderma citrinoviride strain ITEM 4484 grown in solid-state fermentation on sterile rice kernels. The producing strain was identified at species level by sequence analysis of the internal transcribed spacer regions ITS-1 and ITS-2 of the nuclear rDNA and a fragment of the translation elongation factor gene TEF-1alpha. Fractionation by column chromatography and TLC of the culture organic extract, followed by feeding preference tests on the aphid pest Schizaphis graminum (Rondani), allowed the purification of 5.8 and 8.9 mg/kg of culture of two bioactive metabolites, which were named citrantifidiene and citrantifidiol ( 1 and 2). Citrantifidiene and citrantifidiol, whose structures were determined by spectroscopic methods (NMR and MS) are a symmetrical disubstituted hexa-1,3-dienyl ester of acetic acid and a tetrasubstituted cyclohexane-1,3-diol, respectively. The pure metabolites influenced the feeding preference of S. graminum restraining individuals from feeding on wheat leaves dipped in 5% aqueous methanol solution containing 0.57 mg/mL of citrantifidiene or 0.91 mg/mL of citrantifidiol.  相似文献   

Hypolipidemic effect in cholesterol-fed rats of a soluble fiber-rich product obtained from cocoa husks     

Ramos S  Moulay L  Granado-Serrano AB  Vilanova O  Muguerza B  Goya L  Bravo L 《Journal of agricultural and food chemistry》2008,56(16):6985-6993

A new soluble cocoa fiber product (SCFP), obtained after enzymatic treatment of cocoa husks, was characterized and its potential health effects studied in an animal model of dietary-induced hypercholesterolemia. The SCFP was rich in soluble dietary fiber (DF) and antioxidant polyphenols. Consumption of a cholesterol-rich diet containing the SCFP as a source of DF resulted in lower food intake and body weight gain in comparison with control groups consuming cholesterol-free or cholesterol-rich diets with cellulose as DF. The cholesterol-rich diet caused remarkable hypercholesterolemia. However, the SCFP diminished the negative impact of the cholesterol-rich diet, buffering the decrease of high density lipoprotein-cholesterol, and the increase of total and low density lipoprotein-cholesterol levels, and lipid peroxidation (malondialdehyde levels) induced by the fatty diet. The SCFP also decreased triglyceride levels to values lower than those in the group fed the cholesterol-free diet. These results put forward the potential application of the SCFP as a dietary supplement or functional food ingredient.  相似文献