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1.
DNA Cell Biol ; 37(9): 798-804, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30059260

ABSTRACT

Duchenne muscular dystrophy is the most common and severe form of progressive muscular dystrophy. Previous results showed an increased survival in double knockout mice (dko) when treated with adipose-derived CD146+ cells. In this study, we analyzed the effect of CD146+ cells compared to mesenchymal stem/stromal cells (MSCs) derived from the same human adipose sample when injected in the dko mouse model without immunosuppression. Both CD146+ cells and MSCs increased the survival of treated mice when compared to vehicle-injected mice, with a more prominent effect of CD146+ cells than MSCs. Both CD146+ cells and MSCs suppressed peripheral blood mononuclear cell proliferation, indicating immunomodulatory properties. Co-culture experiments showed that MSCs have a more inflammatory profile expression, and angiogenesis assay showed that CD146+ cells can improve blood vessel formation. CD146+ cells can extend survival of muscular dystrophy mice more efficiently than MSCs, possibly due to immunomodulatory and angiogenic properties. Further investigations focusing on exogenous CD146+ cell role in vivo will improve cell therapy understanding and effectiveness.


Subject(s)
Adipocytes/cytology , CD146 Antigen/metabolism , Disease Models, Animal , Mesenchymal Stem Cells/cytology , Muscular Dystrophy, Animal/therapy , Neovascularization, Physiologic , Adipocytes/metabolism , Animals , Cell Differentiation , Cell Proliferation , Cells, Cultured , Coculture Techniques , Human Umbilical Vein Endothelial Cells/cytology , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/metabolism , Mesenchymal Stem Cells/metabolism , Mice , Mice, SCID , Muscular Dystrophy, Animal/metabolism , Muscular Dystrophy, Animal/pathology
2.
Anticancer Res ; 37(9): 4747-4758, 2017 09.
Article in English | MEDLINE | ID: mdl-28870893

ABSTRACT

In cancer, mesenchymal stem/stromal cells (MSCs) have been considered as vehicles for targeted delivery of drugs due to their inherent tropism toward primary and metastatic tumors. However, it is still unclear whether MSCs could be therapeutically explored without significant harm, since a great amound of evidence indicates that MSCs are able to exert both tumor-suppressive and pro-oncogenic effects. Here, we discuss how MSCs might adopt a pro- or anti-inflammatory profile in response to changes within the tumor microenvironment and how these features may lead to opposite outcomes in tumor development. Additionally, we address how differences in experimental design might impact interpretation and consistency of the current literature in this specific field. Finally, we point-out critical issues to be addressed at a pre-clinical stage, regarding safety and therapeutic effectiveness of MSCs application in cancer treatment.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Neoplasms/therapy , Animals , Antineoplastic Agents , Disease Models, Animal , Humans , Neoplasms/immunology , Tumor Microenvironment
3.
Cell ; 163(5): 1204-1213, 2015 Nov 19.
Article in English | MEDLINE | ID: mdl-26582133

ABSTRACT

Duchenne muscular dystrophy (DMD), caused by mutations at the dystrophin gene, is the most common form of muscular dystrophy. There is no cure for DMD and current therapeutic approaches to restore dystrophin expression are only partially effective. The absence of dystrophin in muscle results in dysregulation of signaling pathways, which could be targets for disease therapy and drug discovery. Previously, we identified two exceptional Golden Retriever muscular dystrophy (GRMD) dogs that are mildly affected, have functional muscle, and normal lifespan despite the complete absence of dystrophin. Now, our data on linkage, whole-genome sequencing, and transcriptome analyses of these dogs compared to severely affected GRMD and control animals reveals that increased expression of Jagged1 gene, a known regulator of the Notch signaling pathway, is a hallmark of the mild phenotype. Functional analyses demonstrate that Jagged1 overexpression ameliorates the dystrophic phenotype, suggesting that Jagged1 may represent a target for DMD therapy in a dystrophin-independent manner. PAPERCLIP.


Subject(s)
Calcium-Binding Proteins/genetics , Disease Models, Animal , Intercellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Muscular Dystrophy, Duchenne/genetics , Animals , Cell Proliferation , Dog Diseases/genetics , Dogs , Dystrophin/deficiency , Dystrophin/genetics , Female , Genome-Wide Association Study , Jagged-1 Protein , Male , Mice , Muscular Dystrophy, Animal/genetics , Pedigree , Penetrance , Serrate-Jagged Proteins , Transcriptome , Zebrafish , Zebrafish Proteins
4.
Rev. bras. farmacogn ; 21(6): 963-971, Nov.-Dec. 2011. graf, tab
Article in English | LILACS | ID: lil-602302

ABSTRACT

Cancer constitutes the second main mortality cause in the world, after cardiovascular diseases. In spite of the progresses in the chemotherapeutics treatments, many patients fail chemotherapy, mainly because of side effects or multi-drugs resistance, proving the need and importance of the research for new molecules with anticancer activity, more effective and with smaller adverse effects. Various compounds derived from plant secondary metabolites are commonly used in the chemotherapy against cancer and the natural products play an important role in the research for new molecules. Among several molecules of natural origin evaluated by MTT assay in murine tumor cell lines [breast (LM3) and lung (LP07)] the quinona-methide triterpenes tingenone and pristimerin showed marked cytotoxic activity presenting IC50 around 2 and 5 µM respectively. The structure-activity relationship suggests that rings A and B containing an α, ß-unsaturated carbonyl group are essential for the observed cytotoxic activity. The interaction between these positions and acetylcisteyne residues suggests a probable mechanism of action. The in vitro mutagenic activity was also evaluated by the Salmonella microsome assay (Ames test) for pristimerin and tingenone with and without metabolic activation (S9) in the strains TA98, TA97a, TA100 and TA102, none of which showed mutagenic potential in any strains. Estrogenic and anti-estrogenic activities were also studied by the e-screen assay in MCF-7 cells with negative results. The present data point to the importance of pristimerin and tingenone as representative of an emerging class of potential anticancer chemicals.

5.
PLoS One ; 5(11): e14136, 2010 Nov 30.
Article in English | MEDLINE | ID: mdl-21152435

ABSTRACT

Marfan syndrome is an autosomal dominant disease of connective tissue caused by mutations in the fibrillin-1 encoding gene FBN1. Patients present cardiovascular, ocular and skeletal manifestations, and although being fully penetrant, MFS is characterized by a wide clinical variability both within and between families. Here we describe a new mouse model of MFS that recapitulates the clinical heterogeneity of the syndrome in humans. Heterozygotes for the mutant Fbn1 allele mgΔloxPneo, carrying the same internal deletion of exons 19-24 as the mgΔ mouse model, present defective microfibrillar deposition, emphysema, deterioration of aortic wall and kyphosis. However, the onset of a clinical phenotypes is earlier in the 129/Sv than in C57BL/6 background, indicating the existence of genetic modifiers of MFS between these two mouse strains. In addition, we characterized a wide clinical variability within the 129/Sv congenic heterozygotes, suggesting involvement of epigenetic factors in disease severity. Finally, we show a strong negative correlation between overall levels of Fbn1 expression and the severity of the phenotypes, corroborating the suggested protective role of normal fibrillin-1 in MFS pathogenesis, and supporting the development of therapies based on increasing Fbn1 expression.


Subject(s)
Disease Models, Animal , Gene Expression , Marfan Syndrome/genetics , Microfilament Proteins/genetics , Animals , Base Sequence , Cells, Cultured , Embryo, Mammalian/cytology , Embryo, Mammalian/metabolism , Fibrillin-1 , Fibrillins , Fibroblasts/cytology , Fibroblasts/metabolism , Fluorescent Antibody Technique , Genotype , Humans , Marfan Syndrome/metabolism , Marfan Syndrome/pathology , Mice , Mice, 129 Strain , Mice, Inbred C57BL , Mice, Knockout , Microfilament Proteins/metabolism , Phenotype , Reverse Transcriptase Polymerase Chain Reaction
6.
Neotrop. entomol ; 39(6): 898-905, nov.-dic. 2010. ilus, tab
Article in Portuguese | LILACS | ID: lil-572468

ABSTRACT

The objective of this study was to determine the effects of forest fragmentation on ant richness in a landscape of Atlantic Forest in Northeast Brazil. More specifically, the ant richness was related to the attributes of fragments (area and distance from the fragment central point to the edge), landscape (forest cover surrounding the fragments), and tree community (plant density, richness, and percentage of shade tolerant species). The surveys were carried out in 19 fragments located in Alagoas State from October 2007 to March 2008. Samples were collected through a 300 m transect established in the center of each fragment, where 30 1-m² leaf litter samples were collected at 10 m intervals. A total of 146 ant species was collected, which belonged to 42 genera, 24 tribes and nine subfamilies. The attributes of fragments and landscape did not influence ant richness. On the other hand, tree density explained ca. 23 percent of ant richness. In relation to functional groups, both density and richness of trees explained the richness of general myrmicines (the whole model explained ca. 42 percent of the variation in this group) and percentage of shade tolerant trees explained the richness of specialist predator ants (30 percent for the whole model). These results indicate that ant fauna is more influenced by vegetation integrity than by fragment size, distance to edge or forest cover surrounding fragments.


Subject(s)
Animals , Ecosystem , Trees , Ants , Brazil , Population Dynamics
7.
Neotrop Entomol ; 39(6): 898-905, 2010.
Article in Portuguese | MEDLINE | ID: mdl-21271055

ABSTRACT

The objective of this study was to determine the effects of forest fragmentation on ant richness in a landscape of Atlantic Forest in Northeast Brazil. More specifically, the ant richness was related to the attributes of fragments (area and distance from the fragment central point to the edge), landscape (forest cover surrounding the fragments), and tree community (plant density, richness, and percentage of shade tolerant species). The surveys were carried out in 19 fragments located in Alagoas State from October 2007 to March 2008. Samples were collected through a 300 m transect established in the center of each fragment, where 30 1-m² leaf litter samples were collected at 10 m intervals. A total of 146 ant species was collected, which belonged to 42 genera, 24 tribes and nine subfamilies. The attributes of fragments and landscape did not influence ant richness. On the other hand, tree density explained ca. 23% of ant richness. In relation to functional groups, both density and richness of trees explained the richness of general myrmicines (the whole model explained ca. 42% of the variation in this group) and percentage of shade tolerant trees explained the richness of specialist predator ants (30% for the whole model). These results indicate that ant fauna is more influenced by vegetation integrity than by fragment size, distance to edge or forest cover surrounding fragments.


Subject(s)
Ecosystem , Trees , Animals , Ants , Brazil , Population Dynamics
8.
RFO UPF ; 8(2): 7-10, jul.-dez. 2003. ilus
Article in Portuguese | LILACS, BBO - Dentistry | ID: lil-391776

ABSTRACT

A síndrome Melkersson-Rosenthal é idiopática caracterizada por uma ou mais das seguintes manifestações: edema orofacial recorrente, causando aumento gradual dos tecidos envolvidos, paralisia facial recorrente e língua plicata. O inicío da manifestação ocorre, geralmente, na infância e recidivas são comuns. Os tratamentos sugeridos são empíricos e incluem uso de antibióticos e antiflamatórios corticosteróides e cirurgia para excisão de tecidocicatricial e decompressão nervosa. Este trabalho apresenta características clínicas, meios de diagnóstico e tratamento dessa patologia através da apresentação de um caso clínico acompanhado no Serviço de Cirurgia e Traumatologia Bucomaxilofacial do Complexo Hospitalar da Santa Casa desde 2000. O paciente do relato é do genero masculino, apresentava a tríade de sintomatologia da doença completa e acreditava ser portador de alguma neoplasia. O paciente apresentou melhora ao ser tratado com clofazamina


Subject(s)
Humans , Male , Adult , Crohn Disease
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