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981.
Fernanda de Oliveira Demitto Renata Claro Ribeiro do Amaral Flaviane Granero Maltempe Vera Lúcia Dias Siqueira Regiane Bertin de Lima Scodro Mariana Aparecida Lopes Katiany R. Caleffi-Ferracioli Pedro Henrique Canezin Rosilene Fressatti Cardoso 《PloS one》2015,10(2)
The aim of the present study was to evaluate the effect of the combination of rifampicin (RIF) and verapamil (VP) against the Mycobacterium tuberculosis H37Rv reference strain and six multidrug-resistant (MDR) M. tuberculosis clinical isolates by determining Time-Kill Curves and the ability to efflux drug by fluorometry. The RIF+VP combination showed synergism in one MDR clinical isolate. For the other five MDR clinical isolates, the drug combination showed no interaction. The MDR clinical isolate had lower ethidium bromide (EtBr) accumulation when exposed to the RIF+VP combination, compared with RIF and VP exposure alone. The other MDR clinical isolates showed no significant difference in EtBr accumulation. These results suggest greater efflux action in one of the MDR clinical isolates compared with the M. tuberculosis H37Rv reference strain. The other five MDR isolates may have additional mechanisms of drug resistance to RIF. The use of the RIF+VP combination made one MDR bacillus more susceptible to RIF probably by inhibiting efflux pumps, and this combination therapy, in some cases, may contribute to a reduction of resistance to RIF in M. tuberculosis. 相似文献
982.
John H. Moore Caio C. D. Pinheiro Edna I. Zaenker David T. Bolick Glynis L. Kolling Edward van Opstal Francisco J. D. Noronha Pedro H. Q. S. De Medeiros Raphael S. Rodriguez Aldo A. Lima Richard L. Guerrant Cirle A. Warren 《PloS one》2015,10(7)
BackgroundClostridium difficile is a major identifiable and treatable cause of antibiotic-associated diarrhea. Poor nutritional status contributes to mortality through weakened host defenses against various pathogens. The primary goal of this study was to assess the contribution of a reduced protein diet to the outcomes of C. difficile infection in a murine model.MethodsC57BL/6 mice were fed a traditional house chow or a defined diet with either 20% protein or 2% protein and infected with C. difficile strain VPI10463. Animals were monitored for disease severity, clostridial shedding and fecal toxin levels. Select intestinal microbiota were measured in stool and C. difficile growth and toxin production were quantified ex vivo in intestinal contents from untreated or antibiotic-treated mice fed with the different diets.ResultsC. difficile infected mice fed with defined diets, particularly (and unexpectedly) with protein deficient diet, had increased survival, decreased weight loss, and decreased overall disease severity. C. difficile shedding and toxin in the stool of the traditional diet group was increased compared with either defined diet 1 day post infection. Mice fed with traditional diet had an increased intestinal Firmicutes to Bacteroidetes ratio following antibiotic exposure compared with either a 2% or 20% protein defined nutrient diet. Ex vivo inoculation of cecal contents from antibiotic-treated mice showed decreased toxin production and C. difficile growth in both defined diets compared with a traditional diet.ConclusionsLow protein diets, and defined nutrient diets in general, were found to be protective against CDI in mice. Associated diet-induced alterations in intestinal microbiota may influence colonization resistance and clostridial toxin production in a defined nutrient diet compared to a traditional diet, leading to increased survival. However, mechanisms which led to survival differences between 2% and 20% protein defined nutrient diets need to be further elucidated. 相似文献
983.
Raoni Pais Siqueira éverton de Almeida Alves Barbosa Marcelo Depólo Polêto Germanna Lima Righetto Thiago Vargas Seraphim Rafael Locatelli Salgado Joana Gasperazzo Ferreira Marcus Vinícius de Andrade Barros Leandro Licursi de Oliveira Angelo Brunelli Albertoni Laranjeira Márcia Rogéria Almeida Abelardo Silva Júnior Juliana Lopes Rangel Fietto J?rg Kobarg Eduardo Basílio de Oliveira Robson Ricardo Teixeira Júlio César Borges Jose Andrés Yunes Gustavo Costa Bressan 《PloS one》2015,10(8)
Dysregulation of pre-mRNA splicing machinery activity has been related to the biogenesis of several diseases. The serine/arginine-rich protein kinase family (SRPKs) plays a critical role in regulating pre-mRNA splicing events through the extensive phosphorylation of splicing factors from the family of serine/arginine-rich proteins (SR proteins). Previous investigations have described the overexpression of SRPK1 and SRPK2 in leukemia and other cancer types, suggesting that they would be useful targets for developing novel antitumor strategies. Herein, we evaluated the effect of selective pharmacological SRPK inhibition by N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340) on the viability of lymphoid and myeloid leukemia cell lines. Along with significant cytotoxic activity, the effect of treatments in regulating the phosphorylation of the SR protein family and in altering the expression of MAP2K1, MAP2K2, VEGF and FAS genes were also assessed. Furthermore, we found that pharmacological inhibition of SRPKs can trigger early and late events of apoptosis. Finally, intrinsic tryptophan fluorescence emission, molecular docking and molecular dynamics were analyzed to gain structural information on the SRPK/SRPIN340 complex. These data suggest that SRPK pharmacological inhibition should be considered as an alternative therapeutic strategy for fighting leukemias. Moreover, the obtained SRPK-ligand interaction data provide useful structural information to guide further medicinal chemistry efforts towards the development of novel drug candidates. 相似文献
984.
Compositional and immunobiological analyses of extracellular vesicles released by Candida albicans 下载免费PDF全文
Gabriele Vargas Juliana D. B. Rocha Debora Leite Oliveira Priscila Costa Albuquerque Susana Frases Suelen S. Santos Joshua Daniel Nosanchuk Andre Marco Oliveira Gomes Lia C. A. S. Medeiros Kildare Miranda Tiago J. P. Sobreira Ernesto S. Nakayasu Emma A. Arigi Arturo Casadevall Allan J. Guimaraes Marcio L. Rodrigues Celio Geraldo Freire‐de‐Lima Igor C. Almeida Leonardo Nimrichter 《Cellular microbiology》2015,17(3):389-407
The release of extracellular vesicles (EV) by fungal organisms is considered an alternative transport mechanism to trans‐cell wall passage of macromolecules. Previous studies have revealed the presence of EV in culture supernatants from fungal pathogens, such as Cryptococcus neoformans, Histoplasma capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii, Malassezia sympodialis and Candida albicans. Here we investigated the size, composition, kinetics of internalization by bone marrow‐derived murine macrophages (MO) and dendritic cells (DC), and the immunomodulatory activity of C. albicans EV. We also evaluated the impact of EV on fungal virulence using the Galleria mellonella larvae model. By transmission electron microscopy and dynamic light scattering, we identified two populations ranging from 50 to 100 nm and 350 to 850 nm. Two predominant seroreactive proteins (27 kDa and 37 kDa) and a group of polydispersed mannoproteins were observed in EV by immunoblotting analysis. Proteomic analysis of C. albicans EV revealed proteins related to pathogenesis, cell organization, carbohydrate and lipid metabolism, response to stress, and several other functions. The major lipids detected by thin‐layer chromatography were ergosterol, lanosterol and glucosylceramide. Short exposure of MO to EV resulted in internalization of these vesicles and production of nitric oxide, interleukin (IL)‐12, transforming growth factor‐beta (TGF‐β) and IL‐10. Similarly, EV‐treated DC produced IL‐12p40, IL‐10 and tumour necrosis factor‐alpha. In addition, EV treatment induced the up‐regulation of CD86 and major histocompatibility complex class‐II (MHC‐II). Inoculation of G. mellonella larvae with EV followed by challenge with C. albicans reduced the number of recovered viable yeasts in comparison with infected larvae control. Taken together, our results demonstrate that C. albicans EV were immunologically active and could potentially interfere with the host responses in the setting of invasive candidiasis. 相似文献
985.
Monica F. Lima Vaz João Vitor F. de Oliveira Ricardo J. Cassella Wagner F. Pacheco 《Luminescence》2015,30(3):337-342
This work reports the development and optimization of a flow injection analysis system with fluorescence detection (FIA–FLUO) for gatifloxacin (GFX) determination in organized medium. The analytical system was based on the enhanced fluorescence of gatifloxacin in micellar medium containing sodium dodecyl sulfate (SDS) at pH 6.0. The influence of physical (carrier flow rate, sample volume and volume of reaction coil) and chemical (pH, concentration of buffer and concentration of SDS) parameters that could affect the performance of the FIA system was evaluated in order to reach optimum conditions in terms of sensitivity and analytical throughput. Under optimized conditions, the FIA–FLUO system allowed the injection of 40 samples per hour with a limit of quantification of 72 µg/L and a RSD of 3.5% at 0.20 mg/L. Real samples of commercial pharmaceutical formulations containing GFX were analyzed, and no statistical difference was observed between the results obtained using the developed system and those obtained using the reference method based on high‐performance liquid chromatography with UV detection. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
986.
Length–weight relationship of 37 fish species from the Taquari River (Paranapanema Basin,Brazil) 下载免费PDF全文
A. B. Nobile E. M. Brambilla F. P. de Lima D. Freitas‐Souza I. L. Bayona‐Perez E. D. Carvalho 《Zeitschrift fur angewandte Ichthyologie》2015,31(3):580-582
This work describes the length–weight relationship (LWR) of 37 fish species from the Taquari River, one of the tributaries of the Jurumirim Reservoir in the high Paranapanema Basin, São Paulo, Brazil. Information was not yet available in FishBase on LWRs of 22 of the fish species and maximum weights (Wt) of 24 of the fish species. New maximum standard lengths are presented for nine species as well as weights for two fish species. 相似文献
987.
Fabiana Greyce Oliveira Almeida Priscila Ferreira de Aquino Afonso Duarte Le?o de Souza Antonia Queiroz Lima de Souza Sonia do Carmo Vinhote Thaís Messias Mac-Cormick Marcelo Soares da Mota Silva Sidney Raimundo Silva Chalub Juliana de Saldanha da Gama Fischer Paulo Costa Carvalho Maria da Gloria da Costa Carvalho 《Biological research》2015,48(1)
Background
DNA methylation is commonly linked with the silencing of the gene expression for many tumor suppressor genes. As such, determining DNA methylation patterns should aid, in times to come, in the diagnosis and personal treatment for various types of cancers. Here, we analyzed the methylation pattern from five colorectal cancer patients from the Amazon state in Brazil for four tumor suppressor genes, viz.: DAPK, CDH1, CDKN2A, and TIMP2 by employing a polymerase chain reaction (PCR) specific to methylation. Efforts in the study of colorectal cancer are fundamental as it is the third most of highest incidence in the world.Results
Tumor biopsies were methylated in 1/5 (20 %), 2/5 (40 %), 4/5 (80 %), and 4/5 (80 %) for CDH1, CDKN2A, DAPK, and TIMP2 genes, respectively. The margin biopsies were methylated in 3/7 (43 %), 2/7 (28 %), 7/7 (100 %), and 6/7 (86 %) for CDH1, CDKN2A, DAPK, and TIMP2, respectively.Conclusions
Our findings showed DAPK and TIMP2 to be methylated in most samples from both tumor tissues and adjacent non-neoplastic margins; thus presenting distinct methylation patterns. This emphasizes the importance of better understanding of the relation of these patterns with cancer in the context of different populations. 相似文献988.
Ana Flávia Mar?al-Pessoa Carmen Lucia Bassi-Branco Cristiana dos Santos Barbosa Salvatierra Luiz Fabrizio Stoppiglia Letícia Martins Ignacio-Souza Sílvia Regina de Lima Reis Roberto Vilela Veloso Marise Auxiliadora de Barros Reis Everardo Magalh?es Carneiro Antonio Carlos Boschero Vanessa Cristina Arantes Márcia Queiroz Latorraca 《Biological research》2015,48(1)
Background
Gap junctions between β-cells participate in the precise regulation of insulin secretion. Adherens junctions and their associated proteins are required for the formation, function and structural maintenance of gap junctions. Increases in the number of the gap junctions between β-cells and enhanced glucose-stimulated insulin secretion are observed during pregnancy. In contrast, protein restriction produces structural and functional alterations that result in poor insulin secretion in response to glucose. We investigated whether protein restriction during pregnancy affects the expression of mRNA and proteins involved in gap and adherens junctions in pancreatic islets. An isoenergetic low-protein diet (6% protein) was fed to non-pregnant or pregnant rats from day 1–15 of pregnancy, and rats fed an isocaloric normal-protein diet (17% protein) were used as controls.Results
The low-protein diet reduced the levels of connexin 36 and β-catenin protein in pancreatic islets. In rats fed the control diet, pregnancy increased the levels of phospho-[Ser279/282]-connexin 43, and it decreased the levels of connexin 36, β-catenin and beta-actin mRNA as well as the levels of connexin 36 and β-catenin protein in islets. The low-protein diet during pregnancy did not alter these mRNA and protein levels, but avoided the increase of levels of phospho-[Ser279/282]-connexin 43 in islets. Insulin secretion in response to 8.3 mmol/L glucose was higher in pregnant rats than in non-pregnant rats, independently of the nutritional status.Conclusion
Short-term protein restriction during pregnancy prevented the Cx43 phosphorylation, but this event did not interfer in the insulin secretion. 相似文献989.
990.
The anaphase-promoting complex/cyclosome (APC/C) is a multi-subunit E3 ubiquitin ligase that plays a major role in the progression of the eukaryotic cell cycle. This unusual protein complex targets key cell cycle regulators, such as mitotic cyclins and securins, for degradation via the 26S proteasome by ubiquitination, triggering the metaphase-to-anaphase transition and exit from mitosis. Because of its essential role in cell cycle regulation, the APC/C has been extensively studied in mammals and yeasts, but relatively less in plants. Evidence shows that, besides its well-known role in cell cycle regulation, the APC/C also has functions beyond the cell cycle. In metazoans, the APC/C has been implicated in cell differentiation, disease control, basic metabolism and neuronal survival. Recent studies also have shed light on specific functions of the APC/C during plant development. Plant APC/C subunits and activators have been reported to play a role in cellular differentiation, vascular development, shoot branching, female and male gametophyte development and embryogenesis. Here, we discuss our current understanding of the APC/C controlling plant growth. 相似文献