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Catharina I. Delebinski Monika Twardziok Susann Kleinsimon Florian Hoff Katharina Mulsow Jana Rolff Sebastian J?ger Angelika Eggert Georg Seifert 《PloS one》2015,10(8)
Aqueous Viscum album L. extracts are widely used in complementary cancer medicine. Hydrophobic triterpene acids also possess anti-cancer properties, but due to their low solubility they do not occur in significant amounts in aqueous extracts. Using cyclodextrins we solubilised mistletoe triterpenes (mainly oleanolic acid) and investigated the effect of a mistletoe whole plant extract on human acute myeloid leukaemia cells in vitro, ex vivo and in vivo. Single Viscum album L. extracts containing only solubilised triterpene acids (TT) or lectins (viscum) inhibited cell proliferation and induced apoptosis in a dose-dependent manner in vitro and ex vivo. The combination of viscum and TT extracts (viscumTT) enhanced the induction of apoptosis synergistically. The experiments demonstrated that all three extracts are able to induce apoptosis via caspase-8 and -9 dependent pathways with down-regulation of members of the inhibitor of apoptosis and Bcl-2 families of proteins. Finally, the acute myeloid leukaemia mouse model experiment confirmed the therapeutic effectiveness of viscumTT-treatment resulting in significant tumour weight reduction, comparable to the effect in cytarabine-treated mice. These results suggest that the combination viscumTT may have a potential therapeutic value for the treatment AML. 相似文献
23.
Prey animals must balance antipredatory behaviour with foraging behaviour. According to the risk allocation hypothesis, prey increase antipredatory behaviour and reduce foraging activity during pulses of high risk, but with continuous risk, other activities must continue and antipredatory behaviour decreases despite the risk. We studied the impact of lynx presence on the vigilance behaviour of wild roe deer under conditions of (i) a pulsed elevated risk by experimentally spreading lynx urine as an olfactory cue, and (ii) continuous risk by comparing an area where lynx was eradicated 160 years ago to an area where lynx has been re‐introduced 30 years ago. Roe deer were extremely vigilant in response to the predator olfactory cue; however, roe deer vigilance did not differ measurably among areas with or without potential lynx presence. Deer were more vigilant before sunset than during the night at both study areas, probably due to long‐term adaptation of roe deer to human hunting during daytime. Vigilance decreased from August to September even though activity of lynx increases in autumn, which may be a result either of increased foraging due to decrease in food quality in autumn, or of changes in social organization of the deer. Our results suggested that the degree of vigilance depends on environmental cues. We found that roe deer respond to lynx urine despite a long absence of lynx in the ecosystem. Our results support the risk allocation hypothesis for responses to pulses of high risk but not for responses to continuous elevated levels of risk. 相似文献
24.
Andreas Becker Jana F. Liewald Gerhard Wegener 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1998,168(3):159-167
Hypertrehalosaemic hormones stimulate trehalogenesis while inhibiting glycolysis in cockroach fat body. Signal transduction
of the hypertrehalosaemic peptide Bld HrTH was examined in isolated fat body of the Argentine cockroach Blaptica dubia with respect to its effects on the increase in trehalose production and decrease in the content of the glycolytic activator
fructose 2,6-bisphosphate in the tissue. Cyclic AMP does not seem to be involved in these processes as the cAMP analogue cpt-cAMP
and the phosphodiesterase inhibitor IBMX, which both permeate cell membranes, had no effect on either parameter. Octopamine
at physiological concentrations (10−7 mol · l−1) was also ineffective, but at 10−5 mol · l−1 or above, octopamine stimulated trehalose production although the content of fructose 2,6-bisphosphate in fat body was not
affected. Both calcium entry and the release of Ca2+ from intracellular stores seem to be involved in the action of the hormone. If Ca2+ was omitted from the incubation medium, the hormone stimulated trehalose production less, though still significantly, whereas
the hormone effect on fructose 2,6-bisphosphate was completely abolished in the absence of extracellular Ca2+. With Ca2+ present in the medium, the effect of the hormone on fructose 2,6-bisphosphate could be fully mimicked by the calcium ionophore
A23187, suggesting that calcium entry is a␣decisive step in this signalling pathway. Trehalose production, on the other hand,
was increased by thimerosal and thapsigargin which increase cytosolic Ca2+ from intracellular stores, whereas thimerosal in the absence of extracellular Ca2+ increased rather than decreased the content of fructose 2,6-bisphosphate, thus dissociating the two effects, which are normally
coordinated by the hormone. Trehalose production and the content of fructose 2,6-bisphosphate were not significantly affected
by mepacrine and mellitin, which are known to inhibit, respectively stimulate, phospholipase A2. Our data suggest that the effects of Bld HrTH on the stimulation of trehalose production and reduction of fructose 2,6-bisphosphate
content in fat body are mediated by Ca2+, but that different signalling pathways are involved, suggesting that the two processes, although they are functionally linked,
could be regulated separately.
Accepted: 10 November 1997 相似文献
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The objective of this study was to assess the LIF (leukemia inhibitory factor) concentration in uterine flushing and serum (ELISA) of women with proven fertility, infertile women and women with recurrent miscarriage. In addition, progesterone level was determined in serum. A decreased production of LIF in the uterine microenvironment was found in states of impaired fertility. With a cut-off point of 8.23 pg/ml for LIF level in uterine flushings we have achieved 86.7% sensitivity and 100% specificity in detection of women with idiopathic infertility compared to fertile controls. No correlation between LIF in serum and uterine flushing was demonstrated, rendering LIF measurements in serum useless for diagnosis of impaired infertility. We conclude that LIF measurement in uterine flushing could be a useful diagnostic tool to predict unsuccessful implantation. 相似文献
27.
Sebastian Damerow Anne-Christin Lamerz Thomas Haselhorst Jana Führing Patricia Zarnovican Mark von Itzstein Fran?oise H. Routier 《The Journal of biological chemistry》2010,285(2):878-887
The Leishmania parasite glycocalyx is rich in galactose-containing glycoconjugates that are synthesized by specific glycosyltransferases that use UDP-galactose as a glycosyl donor. UDP-galactose biosynthesis is thought to be predominantly a de novo process involving epimerization of the abundant nucleotide sugar UDP-glucose by the UDP-glucose 4-epimerase, although galactose salvage from the environment has been demonstrated for Leishmania major. Here, we present the characterization of an L. major UDP-sugar pyrophosphorylase able to reversibly activate galactose 1-phosphate into UDP-galactose thus proving the existence of the Isselbacher salvage pathway in this parasite. The ordered bisubstrate mechanism and high affinity of the enzyme for UTP seem to favor the synthesis of nucleotide sugar rather than their pyrophosphorolysis. Although L. major UDP-sugar pyrophosphorylase preferentially activates galactose 1-phosphate and glucose 1-phosphate, the enzyme is able to act on a variety of hexose 1-phosphates as well as pentose 1-phosphates but not hexosamine 1-phosphates and hence presents a broad in vitro specificity. The newly identified enzyme exhibits a low but significant homology with UDP-glucose pyrophosphorylases and conserved in particular is the pyrophosphorylase consensus sequence and residues involved in nucleotide and phosphate binding. Saturation transfer difference NMR spectroscopy experiments confirm the importance of these moieties for substrate binding. The described leishmanial enzyme is closely related to plant UDP-sugar pyrophosphorylases and presents a similar substrate specificity suggesting their common origin. 相似文献
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29.
Lisette Van Hove Kim Lecomte Jana Roels Niels Vandamme HannaKaisa Vikkula Isabelle Hoorens Katia Ongenae Tino Hochepied Giacomo Donati Yvan Saeys Sven R Quist Fiona M Watt Geert van Loo Esther Hoste 《EMBO reports》2021,22(5)
Fibroblasts are a major component of the microenvironment of most solid tumours. Recent research elucidated a large heterogeneity and plasticity of activated fibroblasts, indicating that their role in cancer initiation, growth and metastasis is complex and context‐dependent. Here, we performed genome‐wide expression analysis comparing fibroblasts in normal, inflammatory and tumour‐associated skin. Cancer‐associated fibroblasts (CAFs) exhibit a fibrotic gene signature in wound‐induced tumours, demonstrating persistent extracellular matrix (ECM) remodelling within these tumours. A top upregulated gene in mouse CAFs encodes for PRSS35, a protease capable of collagen remodelling. In human skin, we observed PRSS35 expression uniquely in the stroma of high‐grade squamous cell carcinomas. Ablation of PRSS35 in mouse models of wound‐ or chemically‐induced tumorigenesis resulted in aberrant collagen composition in the ECM and increased tumour incidence. Our results indicate that fibrotic enzymes expressed by CAFs can regulate squamous tumour initiation by remodelling the ECM. 相似文献
30.
This paper is a study of the effect of exogenous DNA of different genetic origins on the repair of meristematic cells of primary roots ofVicia faba, damaged by 24 hour treatment with 0·01mm solution of Ypenyl. Both kinds of DNA,i.e. isologous and heterologous, stimulated cell proliferation which was decreased by the action of the radiomimetic and influenced both dynamics of production of chromosome aberrations and the interchromosomal distribution of induced damage. While heterologous DNA increased the frequency of aberrations after all recovery periods studied, isologous DNA significantly decreased the number of chromosomal aberrations. Heterologous DNA increased at the same time the relative number of breaks in the group of small chromosomes, while by the action of isologous DNA the number of aberrations related to this group of chromosomes was relatively decreased. 相似文献