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141.
Emmanuelle Braud Muriel Duflos Guillaume Le Baut Pierre Renard Bruno Pfeiffer Gordon Tucker 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):253-257
The synthesis and pharmacological evaluation of new 3-(imidazol-4(5)-ylmethylene)-2,3-dihydrobenzo[b]furan-2-ones 8-10 and 3-(3,5-dimethylpyrrol-2-ylmethylene)-2,3-dihydrobenzo[b]furan-2-one 11, analogues of SU-5416, as potential inhibitors of angiogenesis, are reported. Compounds 8 and 11 were prepared by a Knoevenagel reaction starting from 2-hydroxyphenylacetic acid 2 and 4-formylimidazole 5 or 2-formyl-3,5-dimethylpyrrole 7, followed by acid-catalysed cyclodehydration. For compounds 9 and 10, an alternative method was used; it consisted in carrying out the Knoevenagel reaction with the 2,3-dihydrobenzo[b]furan-2-ones 3 and 4. The antiangiogenic activity of these compounds was evaluated in the three-dimensional in vitro rat aortic rings test at 1 μM. At this concentration, compound 11 induced a decrease of angiogenesis comparable to that observed with SU-5416; the vascular density index at 1 μM of 11 and SU-5416 were 30±10 and 22±4% of control, respectively. 相似文献
142.
Julien Giron-Michel Sandy Azzi Silvano Ferrini Salem Chouaib Giovanni Camussi Pierre Eid Bruno Azzarone 《Cytokine & growth factor reviews》2013,24(1):13-22
Experiments in IL-15?/? and IL-15Rα?/? mice show that intra-renal IL-15, through IL-15Rα behaves as an epithelial survival factor. Recent data highlight new functions of IL-15 in renal homeostasis mediated by IL-15Rγ (CD132). Indeed, in CD132+ renal epithelial tubular cells IL-15 preserves E-cadherin expression inhibiting epithelial-mesenchymal transition (EMT). By contrast, during allograft rejection, the increased intra-graft IL-15 expression favors tubular destruction facilitating the intraepithelial recruitment of CD8 T cells expressing the E-cadherin ligand CD103. In renal cancer, loss of CD132 by epithelial cells defines a tumoral microenvironment where IL-15 triggers E-cadherin down-regulation and EMT. Finally, in CD132+ renal cancer stem cells IL-15 induces the generation of non-tumorigenic epithelial cells sensitive to cytotoxic drugs. These findings are discussed in the light of IL-15-based immunotherapy for renal cancer. 相似文献
143.
Yohan Mourgaud Éric Martinez Alain Geffard Bruno Andral Jean-Yves Stanisiere Jean-Claude Amiard 《Biomarkers》2013,18(6):479-490
Mussels were translocated from a shell-fish breeding area (Sète, on the French Mediterranean coast) to sites exposed to trace element inputs in April 2000. They were recovered 3 months later. Whole soft tissues from all of the sites (n = 97) were analysed for arsenic, cadmium, chromium, copper, mercury, nickel, lead and zinc. Metallothioneins (MTs) were also measured in the digestive gland and in the remaining tissues (allowing calculation of whole soft tissue concentrations) at 22 of the 97 sites. MT concentrations in the digestive gland and the whole soft tissues were strongly correlated. The condition index varied with food availability at different sites. This did not influenced MT concentrations in the whole soft tissues, whereas the condition index was negatively correlated to trace element concentrations. A model is proposed to minimize this influence of condition. Metal concentrations adjusted using this model showed significant correlations with MT levels for those metals (cadmium, copper, nickel and zinc) that are known to bind to this protein, with the exception of mercury. Even in moderately contaminated sites, measurement of the MT level in the soft tissues of mussels was generally able to discriminate between different levels of contamination, allowing the use of a simplified procedure compared with dissection of the digestive gland. It is recommended to avoid translocation and sampling during the reproductive period, which is well documented for commercial species such as Mytilus sp. 相似文献
144.
The Cannabinoid Receptor Type 2 as Mediator of Mesenchymal Stromal Cell Immunosuppressive Properties
Francesca Rossi Maria Ester Bernardo Giulia Bellini Livio Luongo Antonella Conforti Iolanda Manzo Francesca Guida Luigia Cristino Roberta Imperatore Stefania Petrosino Bruno Nobili Vincenzo Di Marzo Franco Locatelli Sabatino Maione 《PloS one》2013,8(11)
Mesenchymal stromal cells are non-hematopoietic, multipotent progenitor cells producing cytokines, chemokines, and extracellular matrix proteins that support hematopoietic stem cell survival and engraftment, influence immune effector cell development, maturation, and function, and inhibit alloreactive T-cell responses. The immunosuppressive properties of human mesenchymal stromal cells have attracted much attention from immunologists, stem cell biologists and clinicians.Recently, the presence of the endocannabinoid system in hematopoietic and neural stem cells has been demonstrated. Endocannabinoids, mainly acting through the cannabinoid receptor subtype 2, are able to modulate cytokine release and to act as immunosuppressant when added to activated T lymphocytes.In the present study, we have investigated, through a multidisciplinary approach, the involvement of the endocannabinoids in migration, viability and cytokine release of human mesenchymal stromal cells.We show, for the first time, that cultures of human mesenchymal stromal cells express all of the components of the endocannabinoid system, suggesting a potential role for the cannabinoid CB2 receptor as a mediator of anti-inflammatory properties of human mesenchymal stromal cells, as well as of their survival pathways and their capability to home and migrate towards endocannabinoid sources. 相似文献
145.
Rafaela T. P. Sant'Anna Emily V. Monteiro Juliano R. T. Pereira Roberto B. Faria 《PloS one》2013,8(12)
This work presents a new clock reaction based on ozone, iodine, and chlorate that differs from the known chlorate-iodine clock reaction because it does not require UV light. The induction period for this new clock reaction depends inversely on the initial concentrations of ozone, chlorate, and perchloric acid but is independent of the initial iodine concentration. The proposed mechanism considers the reaction of ozone and iodide to form HOI, which is a key species for producing non-linear autocatalytic behavior. The novelty of this system lies in the presence of ozone, whose participation has never been observed in complex systems such as clock or oscillating reactions. Thus, the autocatalysis demonstrated in this new clock reaction should open the possibility for a new family of oscillating reactions. 相似文献
146.
Vincent Fraisier Amal Kasri Stéphanie Miserey-Lenkei Jean-Baptiste Sibarita Deepak Nair Adeline Mayeux Sabine Bardin Yusuke Toyoda Ina Poser Andrei Poznyakovskiy Bruno Goud Anthony A. Hyman Ariane Dimitrov 《PloS one》2013,8(12)
The Golgi apparatus is an intracellular compartment necessary for post-translational modification, sorting and transport of proteins. It plays a key role in mitotic entry through the Golgi mitotic checkpoint. In order to identify new proteins involved in the Golgi mitotic checkpoint, we combine the results of a knockdown screen for mitotic phenotypes and a localization screen. Using this approach, we identify a new Golgi protein C11ORF24 (NP_071733.1). We show that C11ORF24 has a signal peptide at the N-terminus and a transmembrane domain in the C-terminal region. C11ORF24 is localized on the Golgi apparatus and on the trans-Golgi network. A large part of the protein is present in the lumen of the Golgi apparatus whereas only a short tail extends into the cytosol. This cytosolic tail is well conserved in evolution. By FRAP experiments we show that the dynamics of C11ORF24 in the Golgi membrane are coherent with the presence of a transmembrane domain in the protein. C11ORF24 is not only present on the Golgi apparatus but also cycles to the plasma membrane via endosomes in a pH sensitive manner. Moreover, via video-microscopy studies we show that C11ORF24 is found on transport intermediates and is colocalized with the small GTPase RAB6, a GTPase involved in anterograde transport from the Golgi to the plasma membrane. Knocking down C11ORF24 does not lead to a mitotic phenotype or an intracellular transport defect in our hands. All together, these data suggest that C11ORF24 is present on the Golgi apparatus, transported to the plasma membrane and cycles back through the endosomes by way of RAB6 positive carriers. 相似文献
147.
David Cros Albert Flori Léifi Nodichao Alphonse Omoré Bruno Nouy 《Tropical plant biology》2013,6(1):26-36
Oil palm (Elaeis guineensis Jacq.) produces bunches throughout the year, following annual cycles marked by a peak season, with genetic diversity regarding the regularity of the annual profile of bunch production. The aim of this study was to understand this diversity among a set of oil palm crosses. We hypothesized that this diversity originated from differential responses to water balance and bunch load. Seven crosses with different production cycles were studied during 6 years in Benin, where dry seasons are marked. Phenological stages of phytomer development were recorded from leaf appearance to bunch harvest. Inequality in the distribution over the months of the year of phytomers at each stage was quantified using the Gini coefficient. We found that annual variations in the rate of early abortions, sex ratio, time between leaf opening and appearance of female inflorescence (AFI) and time between AFI and flowering strongly contributed to the diversity in production profile among crosses. To a lesser extent, annual variations in the time of bunch maturation also generated diversity in the production profile. Sex ratio was positively correlated with water balance and negatively with bunch load when leaves were around axil number -25 (approximately 29 months before harvest). Early abortions were positively correlated with bunch load when leaves were at axil number 10 (approximately 9 months before harvest). Correlations varied among crosses, indicating differential responses of crosses to variations in water balance and bunch load, which eventually created significant diversity among crosses regarding the regularity of bunch production profiles. 相似文献
148.
Fabien Dépis Eric Hatterer Romain Ballet Bruno Daubeuf Laura Cons Sophie Glatt Walter Reith Marie Kosco-Vilbois Yann Dean 《MABS-AUSTIN》2013,5(4):555-564
Fc-modified anti-human CD3ε monoclonal antibodies (mAbs) are in clinical development for the treatment of autoimmune diseases. These next generation mAbs have completed clinical trials in patients with type-1 diabetes and inflammatory bowel disease demonstrating a narrow therapeutic window. Lowered doses are ineffective, yet higher pharmacologically-active doses cause an undesirable level of adverse events. Thus, there is a critical need for a return to bench research to explore ways of improving clinical outcomes. Indeed, we recently reported that a short course of treatment affords synergy, providing long-term disease amelioration when combining anti-mouse CD3 and anti-mouse tumor necrosis factor mAbs in experimental arthritis. Such strategies may widen the window between risk and benefit; however, to more accurately assess experimentally the biology and pharmacology, reagents that mimic the current development candidates were required. Consequently, we engineered an Fc-modified anti-mouse CD3ε mAb, 2C11-Novi. Here, we report the functional characterization of 2C11-Novi demonstrating that it does not bind FcγR in vitro and elicits little cytokine release in vivo, while maintaining classical pharmacodynamic effects (CD3-TCR downregulation and T cell killing). Furthermore, we observed that oral administration of 2C11-Novi ameliorated progression of remitting-relapsing experimental autoimmune encephalitis in mice, significantly reducing the primary acute and subsequent relapse phase of the disease. With innovative approaches validated in two experimental models of human disease, 2C11-Novi represents a meaningful tool to conduct further mechanistic studies aiming at exploiting the immunoregulatory properties of Fc-modified anti-CD3 therapies via combination therapy using parenteral or oral routes of administration. 相似文献
149.
Background
Nulliparity is a major risk factor of preeclampsia investigated in numerous trials of its prevention.Objective
We aimed to assess whether these trials considered nulliparity in subject selection or analysis of results.Search Strategy
01 April 2013 search of MEDLINE via PubMed, EMBASE and the Cochrane Library. 01 April 2013 search of trials registered in Clinicaltrials.gov.Selection Criteria
Randomised controlled trials and metaanalyses of preeclampsia prevention with no restriction to period of publication or language. Metaanalyses were selected to fully identify relevant trials.Data Collection and Analysis
One reader appraised each selected article/registered protocol using a pretested, standardized data abstraction form developed in a pilot test. For each article, he recorded whether both nulliparous and multiparous were included and, in case of mixed populations, whether randomisation was stratified, and whether subgroup analyses had been reported. For registered protocols, he only assessed whether it was planned to include mixed populations.Main Results
88 randomised controlled trials were identified, representing 83,396 included women. In 58 of the 88 articles identified (65.9%), preeclampsia was the primary outcome. In 31 of these (53.4%), the investigation combined nulliparous and multiparous women; only two reports in 31 (6.5%) stated that randomisation was stratified on parity and only four (12.9%) described a subgroup analysis by parity. Of the 30 registered trials, 20 (66.6%) planned to include both nulliparous and multiparous women.Conclusion
Parity is largely ignored in randomised controlled trials of preeclampsia prevention, which raises difficulties in interpreting the results. 相似文献150.
Alessandra Nicoletti Elisa Bruno Martina Nania Edoardo Cicero Silvia Messina Clara Chisari Josita Torrisi Davide Maimone Roberto Marziolo Salvatore Lo Fermo Francesco Patti Salvatore Giammanco Mario Zappia 《PloS one》2013,8(12)