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91.
Caio Cesar de Souza Alves Adam Collison Luke Hatchwell Maximilian Plank Matthew Morten Paul S. Foster Sebastian L. Johnston Cristiane Fran?a da Costa Mauro Vieira de Almeida Henrique Couto Teixeira Ana Paula Ferreira Joerg Mattes 《PloS one》2013,8(11)
Background
Severe asthma is associated with T helper (TH) 2 and 17 cell activation, airway neutrophilia and phosphoinositide-3-kinase (PI3K) activation. Asthma exacerbations are commonly caused by rhinovirus (RV) and also associated with PI3K-driven inflammation. Anthraquinone derivatives have been shown to reduce PI3K-mediated AKT phosphorylation in-vitro.Objective
To determine the anti-inflammatory potential of anthraquinones in-vivo.Methods
BALB/c mice were sensitized and challenged with crude house dust mite extract to induce allergic airways disease and treated with mitoxantrone and a novel non-cytotoxic anthraquinone derivative. Allergic mice were also infected with RV1B to induce an exacerbation.Results
Anthraquinone treatment reduced AKT phosphorylation, hypoxia-inducible factor-1α and vascular endothelial growth factor expression, and ameliorated allergen- and RV-induced airways hyprereactivity, neutrophilic and eosinophilic inflammation, cytokine/chemokine expression, mucus hypersecretion, and expression of TH2 proteins in the airways. Anthraquinones also boosted type 1 interferon responses and limited RV replication in the lung.Conclusion
Non-cytotoxic anthraquinone derivatives may be of therapeutic benefit for the treatment of severe and RV-induced asthma by blocking pro-inflammatory pathways regulated by PI3K/AKT. 相似文献92.
Antonella Antonelli Carla Sfara Serafina Battistelli Barbara Canonico Marcella Arcangeletti Elisabetta Manuali Sonia Salamida Stefano Papa Mauro Magnani 《PloS one》2013,8(10)
Superparamagnetic iron oxide (SPIO) and ultra small superparamagnetic iron oxide (USPIO) nanoparticles have been developed as magnetic resonance imaging (MRI) contrast agents. Iron oxide nanoparticles, that become superparamagnetic if the core particle diameter is ~ 30nm or less, present R1 and R2 relaxivities which are much higher than those of conventional paramagnetic gadolinium chelates. Generally, these magnetic particles are coated with biocompatible polymers that prevent the agglomeration of the colloidal suspension and improve their blood distribution profile. In spite of their potential as MRI blood contrast agents, the biomedical application of iron oxide nanoparticles is still limited because of their intravascular half-life of only few hours; such nanoparticles are rapidly cleared from the bloodstream by macrophages of the reticulo-endothelial system (RES). To increase the life span of these MRI contrast agents in the bloodstream we proposed the encapsulation of SPIO nanoparticles in red blood cells (RBCs) through the transient opening of cell membrane pores. We have recently reported results obtained by applying our loading procedure to several SPIO nanoparticles with different chemical physical characteristics such as size and coating agent. In the current investigation we showed that the life span of iron-based contrast agents in the mice bloodstream was prolonged to 12 days after the intravenous injection of murine SPIO-loaded RBCs. Furthermore, we developed an animal model that implicates the pretreatment of animals with clodronate to induce a transient suppression of tissue macrophages, followed by the injection of human SPIO-loaded RBCs which make it possible to encapsulate nanoparticle concentrations (5.3-16.7mM Fe) higher than murine SPIO-loaded RBCs (1.4-3.55mM Fe). The data showed that, when human RBCs are used as more capable SPIO nanoparticle containers combined with a depletion of tissue macrophages, Fe concentration in animal blood is 2-3 times higher than iron concentration obtained by the use of murine SPIO-loaded RBCs. 相似文献
93.
Claire Cunningham Akshay Srivastava Estelle Collin Sibylle Grad Mauro Alini Abhay Pandit J. Gerard Wall 《PloS one》2013,8(12)
Degeneration of the intervertebral discs (IVD) is a leading cause of neck and low back pain. Degeneration begins in the central nucleus pulposus region, leading to loss of IVD osmotic properties. Regeneration approaches include administration of matrix-mimicking scaffolds, cells and/or therapeutic factors. Cell-targeting strategies are likely to improve delivery due to the low cell numbers in the IVD. Single-chain antibody fragments (scFvs) that bind IVD cells were isolated for potential delivery of therapeutics to degenerated IVD. The most cell-distal domain of neural cell adhesion molecule 1 (NCAM1) was cloned and expressed in Escherichia coli. Phage display technology was used to isolate a human scFv against the recombinant domain by panning a scFv library on the immobilised protein. The isolated scFv bound cultured rat astrocytes, as well as bovine nucleus pulposus and annulus fibrosus cells in immunocytochemical studies. The scFv also labelled cells in bovine spinal cord and six-month and two-year old bovine IVD sections by immunohistochemistry. Antibody fragments can provide cell-binding moieties at improved cost, time, yield and functionalisation potential over whole antibodies. The described scFv has potential application in delivery of therapeutics to NCAM1-expressing cells in degenerated IVD. 相似文献
94.
Luigi Ornano Alessandro Venditti Mauro Ballero Cinzia Sanna Luana Quassinti Massimo Bramucci Giulio Lupidi Fabrizio Papa Sauro Vittori Filippo Maggi Armanodoriano Bianco 《化学与生物多样性》2013,10(8):1464-1474
The essential oils of Artemisia arborescens growing in Sardinia (Italy), collected during three plant growth stages, i.e., from the vegetative stage to post‐blooming time, were characterized. Moreover, the in vitro antiproliferative and antioxidant activities of the oil isolated from aerial parts collected in February were evaluated. The essential oils belonged to the β‐thujone/chamazulene chemotype, notably with the highest amount of chamazulene (ca. 52%) ever detected up to now in the genus Artemisia and, in general, in essential oils. Quantitative variations in the oil composition were observed as the plant passes from the vegetative to the blooming stage. The oil was tested for its potential tumor cell growth‐inhibitory effect on T98G, MDA‐MB 435S, A375, and HCT116 human cell lines, using the MTT (=3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) assay. The highest activity was observed on A375 and HCT116 cell lines, with IC50 values of 14 μg/ml. Moreover, the in vitro antioxidant and free radical‐scavenging assays revealed the oil to be an effective scavenger of the ABTS radical cation, with an activity comparable to that of Trolox®. These results support the use of A. arborescens oil for the treatment of inflamed skin conditions. Finally, the composition of the polar fraction of the A. arborescens aerial parts was also examined, and the main component detected was 5‐O‐caffeoylquinic acid, which was identified for the first time in this plant. 相似文献
95.
Vivienne C.M. Neeve Angela Pyle Veronika Boczonadi Aurora Gomez-Duran Helen Griffin Mauro Santibanez-Koref Ulrike Gaiser Peter Bauer Andreas Tzschach Patrick F. Chinnery Rita Horvath 《Mitochondrion》2013,13(6):743-748
Exome sequencing identified compound heterozygous mutations in the recently discovered mitochondrial methionyl-tRNA formyltransferase (MTFMT) gene in two sisters with mild Leigh syndrome and combined respiratory chain deficiency. The mutations lead to undetectable levels of the MTFMT protein. Blue native polyacrylamide gel electrophoresis showed decreased complexes I and IV, and additional products stained with complex V antibodies, however the overall steady state level of mt-tRNAMet was normal. Our data illustrate that exome sequencing is an excellent diagnostic tool, and its value in clinical medicine is enormous, however it can only be optimally exploited if combined with detailed phenotyping and functional studies. 相似文献
96.
Manuela Polimeni Elena Valente Daniela Ulliers Ghislain Opdenakker Philippe E. Van den Steen Giuliana Giribaldi Mauro Prato 《PloS one》2013,8(8)
Recently matrix metalloproteinase-9 (MMP-9) and its endogenous inhibitor (tissue inhibitor of metalloproteinase-1, TIMP-1) have been implicated in complicated malaria. In vivo, mice with cerebral malaria (CM) display high levels of both MMP-9 and TIMP-1, and in human patients TIMP-1 serum levels directly correlate with disease severity. In vitro, natural haemozoin (nHZ, malarial pigment) enhances monocyte MMP-9 expression and release. The present study analyses the effects of nHZ on TIMP-1 regulation in human adherent monocytes. nHZ induced TIMP-1 mRNA expression and protein release, and promoted TNF-α, IL-1β, and MIP-1α/CCL3 production. Blocking antibodies or recombinant cytokines abrogated or mimicked nHZ effects on TIMP-1, respectively. p38 MAPK and NF-κB inhibitors blocked all nHZ effects on TIMP-1 and pro-inflammatory molecules. Still, total gelatinolytic activity was enhanced by nHZ despite TIMP-1 induction. Collectively, these data indicate that nHZ induces inflammation-mediated expression and release of human monocyte TIMP-1 through p38 MAPK- and NF-κB-dependent mechanisms. However, TIMP-1 induction is not sufficient to counterbalance nHZ-dependent MMP-9 enhancement. Future investigation on proteinase-independent functions of TIMP-1 (i.e. cell survival promotion and growth/differentiation inhibition) is needed to clarify the role of TIMP-1 in malaria pathogenesis. 相似文献
97.
Tanya L. Medley Milena Furtado Nicholas T. Lam Rejhan Idrizi David Williams Paul J. Verma Mauro Costa David M. Kaye 《PloS one》2013,8(11)
Background
Disturbances in oxygen levels have been found to impair cardiac organogenesis. It is known that stem cells and differentiating cells may respond variably to hypoxic conditions, whereby hypoxia may enhance stem cell pluripotency, while differentiation of multiple cell types can be restricted or enhanced under hypoxia. Here we examined whether HIF-1alpha modulated Wnt signaling affected differentiation of iPS cells into beating cardiomyocytes.Objective
We investigated whether transient and sustained hypoxia affects differentiation of cardiomyocytes derived from murine induced pluripotent stem (iPS) cells, assessed the involvement of HIF-1alpha (hypoxia-inducible factor-1alpha) and the canonical Wnt pathway in this process.Methods
Embryoid bodies (EBs) derived from iPS cells were differentiated into cardiomyocytes and were exposed either to 24 h normoxia or transient hypoxia followed by a further 13 days of normoxic culture.Results
At 14 days of differentiation, 59±2% of normoxic EBs were beating, whilst transient hypoxia abolished beating at 14 days and EBs appeared immature. Hypoxia induced a significant increase in Brachyury and islet-1 mRNA expression, together with reduced troponin C expression. Collectively, these data suggest that transient and sustained hypoxia inhibits maturation of differentiating cardiomyocytes. Compared to normoxia, hypoxia increased HIF-1alpha, Wnt target and ligand genes in EBs, as well as accumulation of HIF-1alpha and beta-catenin in nuclear protein extracts, suggesting involvement of the Wnt/beta-catenin pathway.Conclusion
Hypoxia impairs cardiomyocyte differentiation and activates Wnt signaling in undifferentiated iPS cells. Taken together the study suggests that oxygenation levels play a critical role in cardiomyocyte differentiation and suggest that hypoxia may play a role in early cardiogenesis. 相似文献98.
Mohsen Koohestani Richard Perdriau Yves Le Dréan Mauro Ettorre Maxim Zhadobov 《Bioelectromagnetics》2020,41(5):369-381
This paper presents the design of a resonant system for in vitro studies to emulate the exposure of a monolayer of cells to a wireless power transfer system operating at 13.56 MHz. The design procedure targets a system, which maximizes the specific absorption rate (SAR) uniformity on the plane where the layer is cultured, as well as SAR efficiency (defined as SAR over the input power), within the size constraints of a standard incubator. Three resonant wireless power transfer systems with different commonly used loop/coil geometries (cylindrical with circular and square cross-sections and annular) were compared with assess the configuration maximizing the considered design criteria. The system performance in terms of reflection and transmission coefficients, as well as generated E- and H-fields, was characterized numerically and experimentally inside the incubator. Moreover, SAR was computed at the monolayer level. The system equipped with cylindrical coils with square cross-sections led to a high electromagnetic field uniformity in in vitro biological samples. In particular, the uniformities in E and SAR at the layer level were within 7.9% and 5.5%, respectively. This was achieved with the variation in H below the usually considered ±5% limit. © 2020 Bioelectromagnetics Society 相似文献
99.
Carine Emer Pedro Jordano Marco A. Pizo Milton C. Ribeiro Fernanda R. da Silva Mauro Galetti 《Biotropica》2020,52(1):81-89
Seed dispersal interactions involve key ecological processes in tropical forests that help to maintain ecosystem functioning. Yet this functionality may be threatened by increasing habitat loss, defaunation, and fragmentation. However, generalist species, and their interactions, can benefit from the habitat change caused by human disturbance while more specialized interactions mostly disappear. Therefore, changes in the structure of the local, within fragment, networks can be expected. Here we investigated how the structure of seed dispersal networks changes along a gradient of increasing habitat fragmentation. We analyzed 16 bird seed dispersal assemblages from forest fragments of a biodiversity-rich ecosystem. We found significant species–, interaction–, and network–area relationships, yet the later was determined by the number of species remaining in each community. The number of frugivorous bird and plant species, their interactions, and the number of links per species decreases as area is lost in the fragmented landscape. In contrast, network nestedness has a negative relationship with fragment area, suggesting an increasing generalization of the network structure in the gradient of fragmentation. Network specialization was not significantly affected by area, indicating that some network properties may be invariant to disturbance. Still, the local extinction of partner species, paralleled by a loss of interactions and specialist–specialist bird–plant seed dispersal associations, suggests the functional homogenization of the system as area is lost. Our study provides empirical evidence for network–area relationships driven by the presence/absence of remnant species and the interactions they perform. 相似文献
100.
Paul Faustin Seke Etet Lorella Vecchio Patrice Bogne Kamga Elias Nchiwan Nukenine Mauro Krampera Armel Hervé Nwabo Kamdje 《生物化学与生物物理学报:癌评论》2013
Wnts are a family of evolutionary-conserved secreted signaling molecules critically involved in a variety of developmental processes and in cell fate determination. A growing body of evidence suggests that Wnt signaling plays a crucial role in the influence of bone marrow stromal microenvironment on the balance between hematopoietic stem cell self-renewal and differentiation. Emerging clinical and experimental evidence also indicates Wnt signaling involvement in the disruption of the latter balance in hematologic malignancies, where the stromal microenvironment favors the homing of cancer cells to the bone marrow, as well as leukemia stem cell development and chemoresistance. In the present review, we summarize and discuss the role of the canonical Wnt signaling pathway in normal hematopoiesis and hematologic malignancies, with regard to recent findings on the stromal microenvironment involvement in these process and diseases. 相似文献