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41.
Cervia D Martini D Garcia-Gil M Di Giuseppe G Guella G Dini F Bagnoli P 《Apoptosis : an international journal on programmed cell death》2006,11(5):829-843
Most antitumour agents with cytotoxic properties induce apoptosis. The lipophilic compound euplotin C, isolated from the ciliate
Euplotes crassus, is toxic to a number of different opportunistic or pathogenic microorganisms, although its mechanism of action is currently
unknown. We report here that euplotin C is a powerful cytotoxic and pro-apoptotic agent in mouse AtT-20 and rat PC12 tumour-derived
cell lines. In addition, we provide evidence that euplotin C treatment results in rapid activation of ryanodine receptors,
depletion of Ca2+ stores in the endoplasmic reticulum (ER), the release of cytochrome c from the mitochondria, activation of caspase-12, and activation of caspase-3, leading to apoptosis. Intracellular Ca2+ overload is an early event which induces apoptosis and is parallelled by ER stress and the release of cytochrome c, whereas caspase-12 may be activated by euplotin C at a later stage in the apoptosis pathway. These events, either independently
or concomitantly, lead to the activation of the caspase-3 and its downstream effectors, triggering the cell to undergo apoptosis.
These results demonstrate that euplotin C may be considered for the design of cytotoxic and pro-apoptotic new drugs. 相似文献
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Atzeni F Sarzi-Puttini P Dell' Acqua D de Portu S Cecchini G Cruini C Carrabba M Meroni PL 《Arthritis research & therapy》2006,8(1):R3
Studies on autoantibody production in patients treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors reported contradictory results. We investigated in a prospective study the efficacy of a treatment with human monoclonal anti-TNF-alpha antibody (adalimumab) in patients with rheumatoid arthritis (RA) and we evaluated the relationship between treatment efficacy and the incidence and titers of disease-associated and non-organ-specific autoantibodies. Fifty-seven patients with RA not responsive to methotrexate and treated with adalimumab were enrolled. Antinuclear, anti-double-stranded(ds)DNA, anti-extractable nuclear antigens, anti-cardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI) autoantibodies, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies were investigated at baseline and after 6 and 12 months of follow-up. Comparable parameters were evaluated in a further 55 patients treated with methotrexate only. Treatment with adalimumab induced a significant decrease in RF and anti-CCP serum levels, and the decrease in antibody titers correlated with the clinical response to the therapy. A significant induction of antinuclear autoantibodies (ANA) and IgG/IgM anti-dsDNA autoantibodies were also found in 28% and 14.6% patients, respectively, whereas aCL and anti-beta2GPI autoantibodies were not detected in significant quantities. No association between ANA, anti-dsDNA, aCL and anti-beta2GPI autoantibodies and clinical manifestations was found. Clinical efficacy of adalimumab is associated with the decrease in RF and anti-CCP serum levels that was detected after 24 weeks and remained stable until the 48th week of treatment. Antinuclear and anti-dsDNA autoantibodies, but not anti-phospholipid autoantibodies, can be induced by adalimumab but to a lower extent than in studies with other anti-TNF blocking agents. 相似文献
45.
Dini C Collette P Drochon N Guillot JC Lemoine G Mauvais P Aszodi J 《Bioorganic & medicinal chemistry letters》2000,10(16):1839-1843
Tunicamycins (TCMs) and liposidomycins (LPMs) are naturally occurring inhibitors of the bacterial translocase (MraY). Based on structure-activity relationship (SAR) studies, a molecular model has been proposed for their inhibitory mechanism. This study points out the importance of the nucleoside moiety of liposidomycins in the inhibition of MraY. A simplified molecule (I) based on the liposidomycin core structure has been synthesised and tested on MraY. The compound displayed a moderate inhibitory activity (IC50 = 50 microM). The validation of the molecular model was then performed by synthesising higher homologues of I, containing an additional stereocentre in the 5' position (XIV and XV). In agreement with the prediction, only the (S) isomer XV showed significant activity against MraY (IC50 = 5 microM). 相似文献
46.
As part of an effort to discover novel antibacterial agents, a new and efficient synthesis was established in order to provide a large amount of UDP-N-acetylmuramic acid (UDP-MurNAc). 相似文献
47.
Dini C Didier-Laurent S Drochon N Feteanu S Guillot JC Monti F Uridat E Zhang J Aszodi J 《Bioorganic & medicinal chemistry letters》2002,12(8):1209-1213
The synthesis and inhibitory activity against MraY of a series of simplified analogues of liposidomycins are described. These compounds were mainly obtained by performing parallel synthesis in the 6'-position of a scaffold that gathers key features found necessary for the binding to MraY. Thus, inhibitory activity was improved from 5300 to 140 nM. This improvement was correlated with the length and lipophilicity of substituents, but was found to be independent of the nature of the chemical bond generated. In addition, some of these inhibitors presented encouraging antibacterial activities. 相似文献
48.
FL Soares IS Melo AC Dias FD Andreote 《World journal of microbiology & biotechnology》2012,28(5):2195-2203
It is believed that the exposure of organisms to harsh climate conditions may select for differential enzymatic activities,
making the surviving organisms a very promising source for bioprospecting. Soil bacteria play an important role in degradation
of organic matter, which is mostly due to their ability to decompose cellulose-based materials. This work focuses on the isolation
and identification of cellulolytic bacteria from soil found in two environments with stressful climate conditions (Antarctica
and the Brazilian semi-arid caatinga). Cellulolytic bacteria were selected using enrichments at high and low temperatures
(4 or 60°C) in liquid media (trypic soy broth—TSB and minimum salt medium—MM) supplemented with cellulose (1%). Many of the
isolates (119 out of 254—46.9%) displayed the ability to degrade carboxymethyl-cellulose, indicating the presence of endoglucolytic
activity, while only a minority of these isolates (23 out of 254—9.1%) showed exoglucolytic activity (degradation of avicel).
The obtained isolates revealed a preferential endoglucolytic activity according to the temperature of enrichments. Also, the
identification of some isolates by partial sequencing of the 16S rRNA gene indicated that the Bacteroidetes (e.g., Pedobacter, Chryseobacterium and Flavobacterium) were the main phylum of cellulolytic bacteria isolated from soil in Antarctica; the Firmicutes (e.g., Bacillus) were more commonly isolated from samples from the caatinga; and Actinobacteria were found in both types of soil (e.g., Microbacterium and Arthrobacter). In conclusion, this work reports the isolation of bacteria able to degrade cellulose-based material from soil at very low
or very high temperatures, a finding that should be further explored in the search for cellulolytic enzymes to be used in
the bioenergy industry. 相似文献
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50.
A number of studies have shown that tumor cells fuse with other tumor and non-tumor cells. In the present study on tumor cell lines derived from glioblastoma, breast cancer, and melanoma, we estimated the frequency of fusion between tumor cells by establishing the fraction of cells with whole tumor-genome duplication in each cell line. Together with this, the capacity of the tumor cell lines to spread through a basement membrane scaffold was assessed, in order to test the hypothesis that pericellular proteolysis by enzymatic release in the spaces of intercellular contact could account for differences in the fusogenicity of tumor cells. The difference in invasiveness between the cell lines accounted for their specific amount of cells with tumor-genome duplication, which, depending on the cell line analyzed, ranged from 2% to 25% of the total cells. These results support the hypothesis that cell-to-cell invasion eliciting membrane fusion causes polyploidization in tumor cells. 相似文献