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1.
Prensa méd. argent ; 105(4): 157-164, jun 2019. tab
Artigo em Inglês | LILACS, BINACIS | ID: biblio-1026675

RESUMO

Aim of the study: clinical, immunological and morphological substantiation of the use of a dental stick with biopharmaceuticals in the complex therapy of inflammatory periodontal diseases. Research methods: leukocyte migration test, cytograms, the study of quantitative and qualitative content of spontaneously released mixed saliva, measurement of the total content of protein, the content of secretory immunoglobulin A (sIgA) and lysozyme in it. Clinical improvement of the periodontal tissues condition after treatment by 77% was registered. OHI-S (hygienic index), PI (periodontal disease index), PMA (papillary-marginal-alveolar index) were 7.5, 3.4, and 8.7 times lower, respectively, compared to the pre-treatment group. The depth of periodontal pockets decreased 2.6-3.4 times, the number of sessions per treatment course was reduced to 3-8 visits to the doctor. The amount of mixed saliva (in comparison with the initial data) increased 2.7 times, normal levels were restored and were 1.2 ml higher than control indicators. Protein levels, lysozyme and sIgA concentrations increased and exceeded the pre-treatment level 1.8 times and by 44.5%, respectively. Cytograms data revealed that the number of red blood cells (in one field of view) in the gingiva specimens in inflammatory periodontal diseases (IPD) patients was 2.3 times lower, count of leukocytes with signs of destruction was 13.4 lower and intact leukocyte count was 3.8 times lower. Lymphocyte count was 2 times lower, indicating that the inflammatory process in periodontal tissues was reduced as a re sult of the reduction of the microbial burden: staphylococci and actinomycetes were detected 3 times less often, diplococci ­ 3.5 times less often, filamentous bacteria and streptococci ­ 4 times less often, protists ­ 5 times less often, respectively. The number of cocci microcolonies was 2.7 times higher. The number of fibroblasts (in one field of view) increased threefold, the content of collagen filaments of the normally oriented structure increased 1.4 times, compared to the original data, which indicated the formation of favorable conditions for healing and reparative regeneration processes. The results of the study showed that the use of a dental stick during local IPD therapy is an effective way of correcting changes in clinical and laboratory indicators of local immunity and that dental stick is a promising new dosage form in practical periodontology.


Assuntos
Humanos , Doenças Periodontais/terapia , Contenções Periodontais , Saliva/imunologia , Produtos Biológicos/uso terapêutico , Implantes Dentários , Movimento Celular , Índice Periodontal , Indicadores (Estatística)
2.
Bol. latinoam. Caribe plantas med. aromát ; 17(6): 575-582, nov. 2018. ilus
Artigo em Inglês | LILACS | ID: biblio-1007341

RESUMO

The skin is the largest organ of the human body and its main function is to protect it from the external environment. It is exposed to injuries that require a rapid healing process to recover its functionality. Microorganisms inhabit the skin, which makes up the normal microbial flora, but in situations of injury they can cause infections that slow down the regeneration process. Therefore, there is a great interest in the development of alternative methods to accelerate the regeneration process and prevent infections. In this work, the efficacy of flavonoid 3-O-methylgalangine and the terpenic derivative Filifolinone and its mixtures, isolated from plants of the genus Heliotropium, on the stimulation of cell proliferation was evaluated. The results showed that the mixtures stimulated proliferation and migration in MA104 cells mainly due to the presence of Filifolinone, that together with the known antibacterial activity of 3-O-methylgalangine, opens new alternatives for the use of natural compounds in healing processes.


La piel es el órgano más grande del cuerpo humano y su función principal es protegerla del entorno externo. Está expuesta a lesiones que requieren un proceso de curación rápido para recuperar su funcionalidad. Los microorganismos que habitan en la piel, constituyen la flora microbiana normal, pero en situaciones de lesión pueden causar infecciones que retardan el proceso de regeneración. Por lo tanto, existe un gran interés en el desarrollo de métodos alternativos para acelerar el proceso de regeneración y prevenir infecciones. En este trabajo, se evaluó la eficacia del flavonoide 3-O-metilgalangina y el derivado terpénico Filifolinona y sus mezclas, aisladas de plantas del género Heliotropium, en la estimulación de la proliferación celular. Los resultados mostraron que las mezclas estimularon la proliferación y la migración en las células MA104 debido principalmente a la presencia de Filifolinona, que junto con la actividad antibacteriana conocida de la 3-O-metilgalangina, abre nuevas alternativas para el uso de compuestos naturales en los procesos de curación.


Assuntos
Terpenos/farmacologia , Flavonoides/farmacologia , Heliotropium , Proliferação de Células/efeitos dos fármacos , Terpenos/química , Cicatrização , Flavonoides/química , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/efeitos dos fármacos
3.
Braz. j. med. biol. res ; 51(4): e6867, 2018. graf
Artigo em Inglês | LILACS | ID: biblio-889068

RESUMO

Polydatin, a small molecule from Polygonum cuspidatum, has many biological functions, particularly anti-cancer effects. However, the anti-cancer effects of polydatin in hepatocellular carcinoma (HCC) have not been examined yet. In the present study, MTT assay, BrdU assay, transwell invasion assay, and wound healing assay were performed to determine cell proliferation, invasion and migration. Flow cytometry and TUNEL assay were used to measure cell apoptosis. Quantitative real-time PCR and western blotting assays were used to determine mRNA and protein expression levels. Xenograft experiment was performed to determine the in vivo anti-tumor effect of polydatin. Immunostaining was performed to analyze the expression of caspase-3 and Ki-67. Our results showed that polydatin inhibited cell proliferation in a concentration-dependent and time-dependent manner in the HCC cell lines. Polydatin also induced cell apoptosis in a concentration-dependent manner possibly via increasing the caspase-3 activity, and up-regulating the protein expression of caspase-3, caspase-9, Bax, and down-regulating the protein expression of Bcl-2. In addition, polydatin treatment had an inhibitory effect on cell proliferation, invasion and migration in HCC cell lines. Polydatin treatment also suppressed the Wnt/beta-catenin signaling activities in HCC cells. Polydatin treatment significantly reduced tumor growth in nude mice inoculated with HepG2 cells, suppressed the expression of Ki-67, and increased caspase-3 expression and TUNEL activity. Our data indicated the important role of polydatin for the suppression of HCC progression.


Assuntos
Animais , Masculino , Camundongos , Estilbenos/farmacologia , Movimento Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Glucosídeos/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Medicamentos de Ervas Chinesas , Western Blotting , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Reação em Cadeia da Polimerase em Tempo Real , Citometria de Fluxo , Neoplasias Hepáticas Experimentais/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica
4.
Bauru; s.n; 2018. 98 p. ilus, graf, tab.
Tese em Português | LILACS, BBO - Odontologia | ID: biblio-885097

RESUMO

O osteossarcoma (OS) é o tumor maligno primário mais comum do tecido ósseo, caracterizado pela formação de osteócitos anormais. Apesar do avanço nas terapias convencionais (quimioterapia e retirada do tumor), essas não conseguem eliminar totalmente as células tumorais e impedir a progressão da doença. Recentemente, agentes derivados de fontes naturais ganharam considerável atenção por causa de sua segurança, eficácia e disponibilidade imediata. Nesse sentido, a apocinina, inibidor do complexo NADPH-oxidase, vem sendo estudada como agente antitumoral em alguns tipos de câncer como: pâncreas, próstata, pulmão e mama. Apocinina é um pró-fármaco e sua ação parece estar relacionada à sua conversão produzindo a diapocinina, a qual se mostrou mais efetiva do que a apocinina. Portanto, o objetivo desse estudo é avaliar, in vitro, o potencial antitumoral da apocinina e diapocinina em células de osteossarcoma humano. Para isso, foram utilizados osteoblastos humanos normais (HOb) e osteossarcoma humano imortalizadas (SaOS-2) tratados ou não com apocinina e diapocinina em diversas concentrações. Foram realizados os ensaios de viabilidade celular, alterações morfológicas, apoptose celular, produção de espécies reativas de oxigênio (EROs), formação de colônias, migração, invasão e expressão do fator indutor de hipóxia-1alfa (HIF-1). Também foram conduzidos ensaios para verificar a atividade de metaloproteinase de matriz (MMP) 2 e 9. Os resultados em SaOS-2 mostraram que o tratamento com apocinina nas concentrações de 1,5 e 3 mM; e diapocinina nas concentrações de 0,75 e 1,5 mM reduziram a viabilidade; aumentaram o número de células em apoptose e diminuíram a produção de EROs; sem causar danos às células HOb. Além disso, essas mesmas concentrações inibiram a migração e invasão celular; diminuíram a expressão de HIF-1; e reduziram a atividade de MMP-2 em SaOS-2. Considerando os resultados obtidos, concluímos que a apocinina e diapocinina podem atuar como possíveis moduladores de células tumorais, sendo que a diapocinina mostrou ser mais efetiva nos parâmetros testados.(AU)


Osteosarcoma (OS) is the most common primary malignant tumor of bone tissue, characterized by the formation of abnormal osteocytes. Despite advances in conventional therapies (chemotherapy and surgery) they cannot completely eliminate tumor cells and prevent the progression of the disease. Recently, agents derived from natural sources have achieved considerable attention because of their safety, efficacy and immediate availability of therapies. In this way, apocynin, an inhibitor of the NADPH-oxidase complex, has been studied as an antitumor agent in some types of cancer, such as pancreas, prostate, lung and breast. Apocynin is a prodrug and its action indicate to be related to its conversion to diapocynin, which has been shown to be more efficient than apocynin itself. Thus, the aim of this study is to evaluate, in vitro, the antitumor potential of apocynin and diapocynin in human osteosarcoma cells. For this, normal human osteoblasts (HOb) and immortalized human osteosarcoma cells (SaOS-2) were treated or no-treated with apocynin and diapocynin in various concentrations. Cell viability assay, morphological alterations, cellular apoptosis, reactive oxygen species (ROS) production, colony formation, migration, invasion and expression of hypoxia-inducible factor-1 alpha (HIF-1) were performed. We also performed assays to verify the activity of matrix metalloproteinase (MMP) 2 and 9. The results in SaOS-2 showed that treatment with apocynin at concentrations of 1,5 e 3 mM; and diapocynin at concentrations of 0,75 e 1,5 mM reduced cell viability; increased the number of cells in apoptosis and decreased the production of ROS; without damaging HOb cells. Moreover, these same concentrations inhibited cell migration and invasion; decreased HIF-1 expression; and reduced MMP 2 activity in SaOS-2. Considering the results, we suggest that apocynin and diapocynin may act as possible modulators of tumor cells, and diapocynin has been shown to be more effective.(AU)


Assuntos
Humanos , Acetofenonas/farmacologia , Antineoplásicos/farmacologia , Compostos de Bifenilo/farmacologia , Osteossarcoma/tratamento farmacológico , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Espécies Reativas de Oxigênio/análise , Reprodutibilidade dos Testes , Células Tumorais Cultivadas
5.
Braz. j. med. biol. res ; 51(4): e6803, 2018. graf
Artigo em Inglês | LILACS | ID: biblio-889059

RESUMO

Propofol is an intravenous sedative hypnotic agent of which the growth-inhibitory effect has been reported on various cancers. However, the roles of propofol in endometrial cancer (EC) remain unclear. This study aimed to explore the effects of propofol on EC in vitro and in vivo. Different concentrations of propofol were used to treat Ishikawa cells. Colony number, cell viability, cell cycle, apoptosis, migration, and invasion were analyzed by colony formation, MTT, flow cytometry, and Transwell assays. In addition, the pcDNA3.1-Sox4 and Sox4 siRNA plasmids were transfected into Ishikawa cells to explore the relationship between propofol and Sox4 in EC cell proliferation. Tumor weight in vivo was measured by xenograft tumor model assay. Protein levels of cell cycle-related factors, apoptosis-related factors, matrix metalloproteinases 9 (MMP9), matrix metalloproteinases 2 (MMP2) and Wnt/β-catenin pathway were examined by western blot. Results showed that propofol significantly decreased colony numbers, inhibited cell viability, migration, and invasion but promoted apoptosis in a dose-dependent manner in Ishikawa cells. Moreover, propofol reduced the expression of Sox4 in a dose-dependent manner. Additionally, propofol significantly suppressed the proportions of Ki67+ cells, but Sox4 overexpression reversed the results. Furthermore, in vivo assay results showed that propofol inhibited tumor growth; however, the inhibitory effect was abolished by Sox4 overexpression. Moreover, propofol inhibited Sox4 expression via inactivation of Wnt/β-catenin signal pathway. Our study demonstrated that propofol inhibited cell proliferation, migration, and invasion but promoted apoptosis by regulation of Sox4 in EC cells. These findings might indicate a novel treatment strategy for EC.


Assuntos
Animais , Feminino , Apoptose/efeitos dos fármacos , Neoplasias do Endométrio/tratamento farmacológico , Hipnóticos e Sedativos/farmacologia , Propofol/farmacologia , Fatores de Transcrição SOXC/metabolismo , beta Catenina/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Endométrio/patologia , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Propofol/administração & dosagem , Ensaio Tumoral de Célula-Tronco , Proteínas Wnt/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Braz. j. med. biol. res ; 51(6): e7046, 2018. graf
Artigo em Inglês | LILACS | ID: biblio-889094

RESUMO

Thyroid cancer is a common malignant tumor. Long non-coding RNA colon cancer-associated transcript 1 (lncRNA CCAT1) is highly expressed in many cancers; however, the molecular mechanism of CCAT1 in thyroid cancer remains unclear. Hence, this study aimed to investigate the effect of CCAT1 on human thyroid cancer cell line FTC-133. FTC-133 cells were transfected with CCAT1 expressing vector, CCAT1 shRNA, miR-143 mimic, and miR-143 inhibitor, respectively. After different treatments, cell viability, proliferation, migration, invasion, and apoptosis were measured. Moreover, the regulatory relationship of CCAT1 and miR-143, as well as miR-143 and VEGF were tested using dual-luciferase reporter assay. The relative expressions of CCAT1, miR-143, and VEGF were tested by qRT-PCR. The expressions of apoptosis-related factors and corresponding proteins in PI3K/AKT and MAPK pathways were analyzed using western blot analysis. The results suggested that CCAT1 was up-regulated in the FTC-133 cells. CCAT1 suppression decreased FTC-133 cell viability, proliferation, migration, invasion, and miR-143 expression, while it increased apoptosis and VEGF expression. CCAT1 might act as a competing endogenous RNA (ceRNA) for miR-143. Moreover, CCAT1 activated PI3K/AKT and MAPK signaling pathways through inhibition of miR-143. This study demonstrated that CCAT1 exhibited pro-proliferative and pro-metastasis functions on FTC-133 cells and activated PI3K/AKT and MAPK signaling pathways via down-regulation of miR-143. These findings will provide a possible target for clinical treatment of thyroid cancer.


Assuntos
Humanos , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias da Glândula Tireoide/patologia , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Invasividade Neoplásica/patologia , RNA Longo não Codificante/genética , Transfecção
7.
Univ. med ; 59(3)2018. ilus
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-995004

RESUMO

El desarrollo neurológico humano requiere una serie de pasos que permitan orientar, regular y diferenciar los diversos componentes cerebrales, para así garantizar, de una manera bastante precisa, la correcta organización y funcionamiento de las estructuras neuronales. La neurogénesis está clásicamente dividida en cuatro etapas consecutivas: proliferación, migración, diferenciación y maduración. En los humanos, estas ocurren desde la tercera semana de gestación hasta la vida adulta y precisan de un complejo grupo de paquetes genéticos, así como de algunos factores asociados, que se han ido descubriendo gracias a los avances en la biología molecular. El artículo es una revisión acerca del desarrollo neuroembriológico humano y los componentes genéticos más relevantes encontrados en la literatura.


The human neuronal development requires a number of concrete steps which lead to orientation, regulation and differentiation of several brain components. They must be done to guarantee, in a very precise way, the correct organization and functioning of the neuronal structures. Neurogenesis is commonly divided into four consecutive stages: proliferation, migration, differentiation and maturation. In humans, those stages take place since the third week of prenatal Iife until the adult Iife. They also require a complex group of genetic packs and associated molecular factors, most of which have been recen tly discovered by the molecular biology technology. A review was made about the human neuronal and embryological development and the most relevant genetic components described by the literature so far.


Assuntos
Movimento Celular/genética , Neurogênese/genética , Desenvolvimento Embrionário e Fetal , Diferenciação Celular/genética
8.
São Paulo; s.n; s.n; 2018. 105 p. ilus, tab, graf.
Tese em Inglês | LILACS | ID: biblio-909445

RESUMO

Chromatin remodeler proteins exert an important function in promoting dynamic modifications in the chromatin architecture, rendering the transcriptional machinery available to the condensed genomic DNA. Due to this central role in regulating gene transcription, deregulation of these molecular machines may lead to severe perturbations in the normal cell functions. Loss-of-function mutations in the CHD7 gene, a member of the chromodomain helicase DNA-binding (CHD) family, are the major cause of the CHARGE syndrome in humans. The disease is characterized by a variety of congenital anomalies, including malformations of the craniofacial structures, peripheral nervous system, ears, eyes and heart. In this context, several studies have already shown the importance of CHD7 for proper function of the neural stem cells (NSCs). Interestingly, we found that CHD7 mRNA levels are upregulated in gliomas, when compared to normal brain tissue, therefore, we hypothesized that CHD7 might have a role in the pathogenesis of these tumors. To investigate the possible oncogenic role of CHD7 in glioblastoma (GBM), we adopted gain- and loss-of-function approaches in adherent GBM cell lines. Using CRISPR_Cas9 genome editing, we found that CHD7 deletion suppresses anchorage-independent growth and reduces spheroid invasion in human LN-229 cells. Moreover, deletion of CHD7 delayed tumor growth and improved overall survival in an orthotopic xenograft glioma mouse model. Conversely, ectopic overexpression of CHD7 in LN-428 and A172 cells was found to increase cell motility and invasiveness in vitro and LN-428 tumor growth in vivo. RNAseq analysis showed that alterations of CHD7 expression levels promote changes in several molecular pathways and modulate critical genes associated with cell adhesion and locomotion. However, the mechanisms underlying the effects of CHD7 overexpression in glioma tissue are still not understood. Here, we also generated recombinant plasmid with functional CHD7 promoter activity reported by luciferase assay. This powerful tool should enable future studies to determine the direct targeting relationship between different signal transduction pathways and CHD7 geneexpression. In summary, our findings indicate that GBM cells expressing a high level of CHD7 may exist and contribute to tumor infiltration and recurrence. Further studies should warrant important clinical-translational implications of our findings for GBM treatment


As proteínas remodeladoras de cromatina exercem importante papel, promovendo modificações dinâmicas na arquitetura da cromatina e dando acesso à maquinaria transcricional ao DNA genômico condensado. Devido à esta função central na regulação da transcrição gênica, a desregulação dessas máquinas moleculares pode levar a perturbações graves na função normal das células. Assim, por exemplo, mutações do tipo perda de função no gene CHD7, um membro da família "chromodomain helicase DNA-binding" (CHD), são a principal causa da síndrome de CHARGE em humanos. A doença é caracterizada por uma variedade de anomalias congênitas, incluindo malformações das estruturas craniofaciais, sistema nervoso periférico, orelhas, olhos e coração. Neste contexto, vários estudos já mostraram a importância da proteína CHD7 para o funcionamento normal de células-tronco neurais (NSCs). Curiosamente, descobrimos que os níveis de mRNA de CHD7 estão mais fortemente expressos em gliomas, quando comparados ao tecido cerebral normal, portanto, nós hipotetizamos que CHD7 poderia ter um papel na patogênese desses tumores. Para investigar o possível papel oncogênico de CHD7 em glioblastoma (GBM), utilizamos enfoques de ganho e perda de função em linhagens celulares aderentes de GBM. Utilizando a técnica de CRISPR_Cas9 para edição do genoma, demonstramos que a deleção do gene CHD7 suprime o crescimento independente de ancoragem e reduz a invasão de esferóides em células LN-229 humanas de GBM. Além disso, a deleção de CHD7 reduziu o crescimento do tumor e melhorou a sobrevida em modelo de injeção ortotópica xenográfica em camundongo. Por outro lado, verificou-se que a super-expressão ectópica de CHD7 nas células LN-428 e A172 aumenta não só a motilidade celular e a capacidade de invasão in vitro, mas, também, o crescimento do tumor de LN-428 in vivo. A análise de RNA-seq mostrou que o nocauteamento da sequência codificadora de CHD7 e sua super-expressão promovem alterações em diversas vias moleculares, modulando genes críticosassociados à adesão e locomoção celular. No entanto, os mecanismos subjacentes aos efeitos da super-expressão de CHD7 em tecidos de glioma ainda não são compreendidos. Neste trabalho, geramos um plasmídeo recombinante contendo um fragmento da região promotora de CHD7, o qual se mostrou funcional em ensaios de luciferase. Esta ferramenta permitirá que estudos futuros possam identificar a relação direta entre as diferentes vias de transdução de sinal e a expressão do gene CHD7. Em resumo, nossos achados indicam que células de GBM expressando um alto nível de CHD7 podem existir e contribuir para a infiltração e recorrência do tumor. Estudos posteriores deverão avaliar as possíveis implicações dos resultados apresentados neste trabalho para a translação clínica no tratamento de pacientes com GBM


Assuntos
Montagem e Desmontagem da Cromatina , Glioblastoma/complicações , Movimento Celular/fisiologia , Invasividade Neoplásica
9.
Electron. j. biotechnol ; 29: 13-21, sept. 2017. ilus, tab, graf
Artigo em Inglês | LILACS | ID: biblio-1017057

RESUMO

Background: The past years have witnessed a growing number of researches in biofilm forming communities due to their environmental and maritime industrial implications. To gain a better understanding of the early bacterial biofilm community, microfiber nets were used as artificial substrates and incubated for a period of 24 h in Mauritian coastal waters. Next-generation sequencing technologies were employed as a tool for identification of early bacterial communities. Different genes associated with quorum sensing and cell motility were further investigated. Results: Proteobacteria were identified as the predominant bacterial microorganisms in the biofilm within the 24 h incubation, of which members affiliated to Gammaproteobacteria, Alphaproteobacteria and Betaproteobacteria were among the most abundant classes. The biofilm community patterns were also driven by phyla such as Firmicutes, Bacteroidetes, Chloroflexi, Actinobacteria and Verrucomicrobia. The functional analysis based on KEGG classification indicated high activities in carbohydrate, lipid and amino acids metabolism. Different genes encoding for luxI, lasI, agrC, flhA, cheA and cheB showed the involvement of microbial members in quorum sensing and cell motility. Conclusion: This study provides both an insight on the early bacterial biofilm forming community and the genes involved in quorum sensing and bacterial cell motility.


Assuntos
Água do Mar/microbiologia , Bactérias/crescimento & desenvolvimento , Bactérias/genética , Fenômenos Fisiológicos Bacterianos , Bactérias/isolamento & purificação , Bactérias/classificação , Aderência Bacteriana , Movimento Celular , Biofilmes , Biodiversidade , Percepção de Quorum , Incrustação Biológica , Metagenômica , Sequenciamento de Nucleotídeos em Larga Escala , Maurício
10.
Mem. Inst. Oswaldo Cruz ; 112(8): 551-560, Aug. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-894864

RESUMO

BACKGROUND Chagas disease is a public health problem caused by infection with the protozoan Trypanosoma cruzi. There is currently no effective therapy for Chagas disease. Although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. Reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare. OBJECTIVES The aim of this study was to investigate the migration of bone marrow cells to the heart after T. cruzi infection in a model of chagasic disease in chimeric mice. METHODS To obtain chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft effectiveness was confirmed by flow cytometry. Experimental mice were divided into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT) mice, both of which received 3 × 104 trypomastigotes of the Brazil strain; (iii) non-infected chimeric (Chim) mice; and (iv) non-infected WT mice. FINDINGS At one-month post-infection, iChim and iWT mice showed first degree atrioventricular block with decreased heart rate and treadmill exercise parameters compared to those in the non-infected groups. MAIN CONCLUSIONS iChim mice showed an increase in parasitaemia, myocarditis, and the presence of amastigote nests in the heart tissue compared to iWT mice. Flow cytometry analysis did not detect haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+ cardiomyocytes were not detected in the tissues of chimeric mice.


Assuntos
Animais , Feminino , Camundongos , Trypanosoma cruzi/fisiologia , Células da Medula Óssea/fisiologia , Cardiomiopatia Chagásica/parasitologia , Transplante de Medula Óssea/métodos , Doença de Chagas/parasitologia , Movimento Celular , Doenças dos Animais
11.
Braz. j. med. biol. res ; 50(3): e5396, 2017. graf
Artigo em Inglês | LILACS | ID: biblio-839263

RESUMO

Diabetic retinopathy (DR) is one of the common and specific microvascular complications of diabetes. This study aimed to investigate the anti-angiogenic effect of kaempferol and explore its underlying molecular mechanisms. The mRNA expression level of vascular endothelial growth factor (VEGF) and placenta growth factor (PGF) and the concentrations of secreted VEGF and PGF were measured by qTR-PCR and ELISA assay, respectively. Human retinal endothelial cells (HRECs) proliferation, migration, and sprouting were measured by CCK-8 and transwell, scratching wound, and tube formation assays, respectively. Protein levels were determined by western blot. High glucose (25 mM) increased the mRNA expression levels of VEGF and PGF as well as the concentrations of secreted VEGF and PGF in HRECs, which can be antagonized by kaempferol (25 µM). Kaempferol (5-25 µM) significantly suppressed cell proliferation, migration, migration distance and sprouting of HRECs under high glucose condition. The anti-angiogenic effect of kaempferol was mediated via downregulating the expression of PI3K and inhibiting the activation of Erk1/2, Src, and Akt1. This study indicates that kaempferol suppressed angiogenesis of HRECs via targeting VEGF and PGF to inhibit the activation of Src-Akt1-Erk1/2 signaling pathway. The results suggest that kaempferol may be a potential drug for better management of DR.


Assuntos
Humanos , Retinopatia Diabética/metabolismo , Células Endoteliais/efeitos dos fármacos , Quempferóis/farmacologia , Fator de Crescimento Placentário/antagonistas & inibidores , Retina/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Movimento Celular , Proliferação de Células , Retinopatia Diabética/patologia , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica
12.
Braz. j. med. biol. res ; 50(12): e6138, 2017. graf
Artigo em Inglês | LILACS | ID: biblio-888969

RESUMO

The aim of this study was to investigate the mechanism of propranolol on the regression of hemangiomas. Propranolol-treated hemangioma tissues were collected and the expression of hypoxia inducible factor-1α (HIF-1α) was examined. We also established HIF-1α overexpression and knockdown hemangioma cells, and determined the effects of HIF-1α on the hemangioma cells proliferation, apoptosis, migration and tube formation. Significantly increased HIF-1α level was found in the hemangioma tissues compared to that in normal vascular tissues, whereas propranolol treatment decreased the HIF-1α level in hemangioma tissues in a time- and dose-dependent manner. Moreover, propranolol treatment significantly decreased cell proliferation, migration and tube formation as well as promoted cell apoptosis in HIF-1α overexpression and knockdown hemangioma cells. Propranolol suppressed the cells proliferation, migration and tube formation of hemangioma cells through HIF-1α dependent mechanisms. HIF-1α could serve as a novel target in the treatment of hemangiomas.


Assuntos
Humanos , Propranolol/uso terapêutico , Vasodilatadores/uso terapêutico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hemangioma/tratamento farmacológico , Apoptose/efeitos dos fármacos , Hemangioma/metabolismo
13.
Braz. j. med. biol. res ; 50(8): e6207, 2017. graf
Artigo em Inglês | LILACS | ID: biblio-888978

RESUMO

Both sorafenib and interleukin-27 (IL-27) are antineoplastic drugs. This study aimed to investigate the synergistic effect of these two drugs on bladder cancer cells. HTB-9 and T24 cells were stimulated with IL-27 (50 ng/mL), sorafenib (2 μM) or the synergistic action of these two drugs. The cells without treatment acted as control. Cell proliferation, apoptosis and invasion were measured by bromodeoxyuridine assay, flow cytometry and modified Boyden chamber, respectively. Simultaneously, both modified Boyden chamber and scratch assay were used to assess cell migration. Finally, the phosphorylation levels of key kinases in the Akt/mechanistic target of rapamycin (mTOR)/mitogen-activated protein kinase (MAPK) pathway, and expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were detected by western blot analysis. Stimulation with IL-27 or sorafenib repressed proliferation, migration and invasion but promoted apoptosis, and the effects were all enhanced by the combination of these two drugs in HTB-9 cells. The effect of the combined treatment on bladder cancer cells was verified in T24 cells. Additionally, the phosphorylation levels of AKT, mTOR and MAPK as well as the expression levels of MMP-2 and MMP-9 were all decreased by a single treatment of IL-27 or sorafenib, and further decreased by the combined treatment of these two drugs. The combination of IL-27 and sorafenib inhibited proliferation, migration and invasion and promoted apoptosis of bladder cancer cells compared with mono-drug treatment. Additionally, the AKT/mTOR/MAPK pathway might be implicated in the functional effects by down-regulations of MMP-2 and MMP-9.


Assuntos
Humanos , Antineoplásicos/farmacologia , Interleucina-27/farmacologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Neoplasias da Bexiga Urinária/patologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Niacinamida/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico
14.
São Paulo; s.n; s.n; 2016. 111 p. tab, graf, ilus.
Tese em Português | LILACS | ID: biblio-847481

RESUMO

O câncer colorretal (CCR) é o terceiro tipo de câncer mais comum no mundo. Apesar dos avanços nos tratamentos convencionais, aproximadamente dois terços dos pacientes com CCR são submetidos à cirurgia potencialmente curativa. Entretanto, grande parte desses pacientes evolui mal, apresentando recidivas e/ou metástases. A busca de novos alvos moleculares para a terapia do CCR revelou a proteína celular Prion (PrPC) como um possível candidato. Trabalhos recentes sugerem participação direta ou indireta de PrPC no crescimento de tumores, na formação de metástases, na composição de complexos multiproteicos e na indução de vias de sinalização envolvidas em diversos processos biológicos, como proliferação. Além disso, PrPC foi descrito como um importante modulador do crescimento de tumor colorretal. Resultados prévios mostraram que a interação da proteína PrPC com a proteína HSP70/HSP90 Organizing Protein (HOP) induz proliferação em glioblastomas. HOP é uma proteína predominantemente citoplasmática, podendo também ser secretada associada às vesículas extracelulares. Assim, o presente estudo objetivou avaliar o papel do complexo PrPC-HOP e das vesículas extracelulares no desenvolvimento e progressão dos tumores colorretais. Os nossos resultados mostram que HOP induziu migração e invasão em linhagens de CCR de maneira dependente de PrPC, uma vez que o uso do peptídeo sem atividade que compete pelo sítio ligação de HOP a PrPC inibiu estes processos. Além disso, nossos dados apontaram que o aumento de migração e invasão das células de CCR induzida pela interação PrPC-HOP é mediada pela ativação da via ERK1/2. Os achados in vitro estimularam a avaliação do perfil de expressão de PrPC e HOP por imuno-histoquímica em tecidos de pacientes com diferentes tipos de tumores colorretais. Nossos resultados sugeriram que essas proteínas são importantes no início do desenvolvimento tumoral e na transição de adenomas para adenocarcinomas, não havendo correlação entre a presença de HOP e/ou PrPC com metástase, linfonodos acometidos, estadiamento, sobrevida ou região tumoral versus tecido normal. Em relação ao papel das vesículas extracelulares na progressão dos tumores colorretais, nossos resultados mostraram que linhagens celulares que apresentam padrões parecidos de agressividade tumoral podem ter perfis de secreção de proteínas e vesículas extracelulares bastante diferentes, induzindo, portanto, processos biológicos com intensidades distintas. O meio condicionado e as vesículas extracelulares da linhagem WiDr apresentaram maior potencial de indução de migração quando comparado com a linhagem HCT8. Além disso, a modulação negativa da proteína VPS4, uma das responsáveis pela formação dos corpos multivesiculares, mostrou-se uma abordagem interessante no estudo da secreção de vesículas por células de CCR, uma vez que o dominante negativo de VPS4 promoveu diminuição do cargo proteico e da secreção de vesículas extracelulares, redução da proliferação celular e do efeito indutor do processo de migração na linhagem WiDr. Assim, em conjunto, o presente trabalho indicou que o complexo PrPC-HOP pode ser um bom alvo terapêutico nos processos de migração e invasão em CCR. Ainda, essas proteínas se mostraram importantes nos estágios iniciais da formação dos tumores. A modulação da secreção de vesículas extracelulares pode contribuir para retardar a progressão dos tumores colorretais


Colorectal cancer (CRC) is the third most common type of cancer in the world. Despite improvements in conventional treatments, approximately two-thirds of CRC patients undergo potentially curative surgery. However, most of these patients evolve poorly, showing recurrence and/or metastasis. Search of new molecular targets for CRC therapy revealed the cellular protein Prion (PrPC) as a putative candidate. Recent studies have shown that PrPC exhibit direct or indirect participation in tumor growth, formation of metastasis, composition of multiprotein complexes and induction of signaling pathways involved in many biological processes such as proliferation. Moreover, PrPC has been described as an important modulator of colorectal tumor growth. Previous findings showed that the interaction between PrPC and its ligand HSP70/90 heat shock organizing protein (HOP) induces gliobastoma proliferation. It is well known that HOP localizes mainly in the cytoplasm but HOP is also secreted associated with extracellular vesicles. In this way, the present study sought to evaluate the role of PrPC-HOP complex and extracellular vesicles in the development and progression of CRC. We demonstrate that HOP induces the migration and invasion of CRC cell lines in a PrPC-dependent manner because the use of HOP peptide, which is able to bind to PrPC, blocking PrPC-HOP complex formation, inhibited the migration and invasion processes. In addition, our data showed that the enhancement of migration and invasion induced by PrPC-HOP interaction is mediated by ERK1/2 pathway activation. These in vitro results lead us to evaluate the PrPC and HOP expression by immunohistochemistry in tissues from patients with different tumor types. Our data showed that these proteins could be important for the initial steps of tumor development, represented by the transition from adenoma to adenocarcinoma. No correlation was found among HOP and/or PrPC expression and metastasis, lymph node involvement, staging, survival or tumor area versus normal tissue. Regarding the role of extracellular vesicles in the progression of colorectal tumors, our results showed that cell lines exhibiting similar aggressive tumor behavior can have a different protein secretion pattern and a distinct profile of extracellular vesicles release, which could induce biological process with different intensities. The conditioned medium and the extracellular vesicles derived from WiDr cell line showed a higher potential to induce migration than HCT8 cell line. Moreover, the negative modulation of VPS4, one of the proteins responsible for multivesicular body formation, showed to be an interesting approach in the study of extracellular vesicles secretion secreted by CRC cells; the negative dominant of VPS4 promoted in the WiDr cell line a reduction in the protein cargo and secretion of the extracellular vesicles, a decrease of cell proliferation and induction of migration process. Therefore, taken together, our data highlights that PrPC-HOP complex can be considered a new therapeutic target in migration and invasion processes of CRC. Moreover, these proteins appeared to be important at onset of tumor formation. The modulation of extracellular vesicles secretion may contribute for delaying the progression of colorectal tumors


Assuntos
Neoplasias Colorretais/patologia , Vesículas Extracelulares , Proteínas Priônicas/genética , Movimento Celular , Citometria de Fluxo/métodos
15.
Biol. Res ; 49: 1-10, 2016. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-774432

RESUMO

BACKGROUND: Reprimo (RPRM), a highly glycosylated protein, is a new downstream effector of p53-induced cell cycle arrest at the G2/M checkpoint, and a putative tumor suppressor gene frequently silenced via methylation of its promoter region in several malignances. The aim of this study was to characterize the epigenetic inactivation and its biological function in BC cell lines. METHODS: The correlation between RPRM methylation and loss of mRNA expression was assessed in six breast cancer cell lines by methylation specific PCR (MSP), 5'-Aza-2'-deoxycytidine treatment and RT-PCR assays. MDA-MB-231 cells were chosen to investigate the phenotypic effect of RPRM in cell proliferation, cell cycle, cell death, cell migration and invasion. RESULTS: In the cancer methylome system (CMS) (web-based system for visualizing and analyzing genome-wide methylation data of human cancers), the CpG island region of RPRM (1.1 kb) was hypermethylated in breast cancer compared to normal breast tissue; more interesting still was that ERa(+) tumors showed higher methylation intensity than ERa(-). Downregulation of RPRM mRNA by methylation was confirmed in MDA-MB-231 and BT-20 cell lines. In addition, overexpression of RPRM in MDA-MB-231 cells resulted in decreased rates of cell migration, wound healing and invasion in vitro. However, RPRM overexpression did not alter cell viability, phosphatidylserine (PS) translocation or G2/M cell cycle transition. CONCLUSION: Taken together, these data suggest that RPRM is involved in decreased cell migration and invasion in vitro, acting as a potential tumor suppressor gene in the MDA-MB-231 cell line.


Assuntos
Feminino , Humanos , Neoplasias da Mama/patologia , Proteínas de Ciclo Celular/fisiologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Glicoproteínas/fisiologia , Análise de Variância , Western Blotting , Neoplasias da Mama/genética , Ciclo Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Proteínas de Ciclo Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , Metilação de DNA , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/genética , Invasividade Neoplásica , Reação em Cadeia da Polimerase em Tempo Real , Estatísticas não Paramétricas
16.
Mem. Inst. Oswaldo Cruz ; 110(8): 1010-1016, Dec. 2015. graf
Artigo em Inglês | LILACS | ID: lil-769838

RESUMO

T-cell based vaccines against human immunodeficiency virus (HIV) generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF) co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA)-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity.


Assuntos
Animais , Feminino , Humanos , Vacinas contra a AIDS/imunologia , Antígenos Virais/imunologia , /imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , HIV-1 , Imunidade Celular/imunologia , Vacinas de DNA/imunologia , Adjuvantes Imunológicos/administração & dosagem , /efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Sequência Conservada/imunologia , ELISPOT , Citometria de Fluxo , Vetores Genéticos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Infecções por HIV/prevenção & controle , Antígenos HLA-DR/imunologia , Interferon gama/efeitos dos fármacos , Interferon gama/metabolismo , /metabolismo , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Camundongos Endogâmicos BALB C , Plasmídeos , Ligação Proteica/imunologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
17.
MedicalExpress (São Paulo, Online) ; 2(5)Sept.-Oct. 2015. graf
Artigo em Inglês | LILACS | ID: lil-776669

RESUMO

INTRODUCTION: Astrocytomas are common brain tumors. Increased expression levels of Interleukin-13 Receptor α2 (IL-13RA2) have been reported in astrocytomas. The Interleukin-13 signaling pathway may be associated with cell migration when binding to Interleukin-13 Receptor α1. OBJECTIVE: To investigate Interleukin-13 Receptor α1 (IL-13RA1) and IL13RA2 expression levels in human diffusely infiltrative astrocytomas and test the involvement of Interleukin-13 levels in cell migration in two glioblastoma cell lines. METHODS: IL13RA expression levels were accessed by quantitative real time PCR in 128 samples of astrocytomas and 18 samples of non-neoplastic brain tissues from temporal lobe epilepsy surgery. The impact of IL-13 levels (10 and 20 ng/mL) on cell migration was analyzed by the wound assay in U87MG and A172 cells. RESULTS: Glioblastoma presented higher IL13RA1 and IL13RA2 expression levels compared to lower grades astrocytomas and to non-neoplastic cases. U87MG and A172 cells presented higher expression levels of IL-13RA1 vs. IL-13RA2. A significant difference in migration rate was observed in A172 cells treated with 10 ng/mL of IL-13 vs. control: treated cells presented slower migration than non-treated cells. U87MG cells treated with IL-13 20ng/mL presented slower migration than non-treated cells. This indicates that the IL13Rα1 signaling pathway was not activated, indeed inhibited by the decoy IL-13Rα2, slowing cell migration. This impact occurred with a lesser concentration of IL-13 on the A172 than on the U87MG cell line, because A172 cells have a higher IL-13RA2/A1 ratio. CONCLUSION: The present results suggest IL-13 receptors as possible targets to decrease tumor cell migration.


INTRODUÇÃO Astrocitomas são os tumores cerebrais mais frequentes. Nestes tumores foi observada maior expressão do receptor de Interleucina-13 α2 (IL13RA2). A cascata de sinalização da Interleucina-13 pode estar associada com a migração celular, após sua ligação com o receptor de Interleucina-13 α1 (IL13Rα1). OBJETIVO: Investigar os níveis de expressão dos receptores de Interleucina-13 (IL13RA1 e IL13RA2) em astrocitomas difusamente infiltrativos e avaliar o envolvimento da Interleucina-13 na migração celular de duas linhagens de glioblastoma. MÉTODOS: A expressão dos receptores IL13RA foi analisada por PCR em tempo real, em 128 amostras de astrocitomas e 18 amostras de tecido cerebral não neoplásico, provenientes de cirurgia de epilepsia do lobo temporal. E o impacto da quantidade de IL-13 (10ng/ml e 20ng/ml) em ensaio de migração celular. RESULTADOS: As amostras de Glioblastoma apresentaram maior expressão de IL13RA1 and IL13RA2 comparados com astrocitomas de baixo grau e os casos não-neoplásicos. Nas células U87MG e A172 foi observado maior nível de expressão de IL-13RA1 do que IL-13RA2. Uma diferença significativa na taxa de migração foi obtida em células A172 tratadas com 10 ng/mL comparadas com o controle: as células tratadas apresentaram menor migração que as células não tratadas. As células U87MG tratadas com 20ng/mL de IL-13 apresentaram menor migração celular que as células não tratadas. A diferença na migração celular indica que o caminho de sinalização de IL13Rα1 não foi ativado e foi inibido pelo IL-13Rα2, diminuindo a migração celular. Esse impacto ocorreu com uma concentração menor de IL-13 nas células A172 ao contrário da U87MG, porque as células A172 possuem uma razão IL-13RA2/A1 maior. CONCLUSÃO: os resultados sugerem que os receptores de IL-13 podem ser utilizados como possíveis alvos para a diminuição da migração celular tumoral.


Assuntos
Humanos , Astrocitoma , Neoplasias Encefálicas , Movimento Celular/efeitos dos fármacos , Interleucina-13/administração & dosagem , Receptores de Interleucina-13/administração & dosagem
18.
Bol. latinoam. Caribe plantas med. aromát ; 14(3): 251-262, mayo 2015. tab, ilus, graf
Artigo em Inglês | LILACS | ID: biblio-907487

RESUMO

This search is focused on the study of diet compounds that may have any potential chemopreventive effect against cancer. Some compounds that fulfill this requirement are phytoestrogens. Among them we find genistein (1), the most studied, daidzein (2) and equol (3) (figure 1). To compare the sensitivities of different prostate cancer cells to phytoestrogen treatment, sulphorhodamine B dye assay was performed to determine cell viability. DU-145 and PC-3 prostate cancer cell lines treated with various doses of phytoestrogen (0-12.5-25-50 and 100 μM) for different times (24, 48 and 72h). For cell invasion or migration assay cells were seeded in a Transwell chamber with or without coating Matrigel respectively. DU-145 and PC-3 cells were treated previously with phytoestrogen (50 μM) for 24h. The study showed that equol, daidzein and genistein inhibited migration and invasion in prostate cancer cell lines. Moreover, we analyzed the effects of phytoestrogens in MMP-2 and MMP-9 mRNA expression by RT-PCR. The results indicated that equol, daidzein and genistein diminished the expression of MMP-2 and MMP-9 in a cell-dependent manner. Our data suggested that equol, daidzein and genistein inhibited migration and invasion in prostate cancer cell lines. Moreover, the results also suggest that down-regulation of MMP-2 and MMP- 9 might be involved in the inhibition of invasion of PC-3 and DU-145 cells after genistein, daidzein and equol treatment.


Este trabajo se centra en el estudio de los compuestos de dieta que pueden tener potencial efecto quimiopreventivo contra el cáncer. Algunos de estos compuestos son los fitoestrógenos. Entre ellos encontramos la genisteína (1), el más estudiado, la daidzeína (2) y el equol (3) (figura 1). Para comparar el efecto de estos fitoestrogenos sobre las líneas celulares de cáncer de próstata, DU-145 y PC-3, se utilizó el ensayo de sulforodamina B para determinar la viabilidad celular tras los tratamientos con diferentes concentraciones de fitoestrógenos (0-12.5-25-50-100 μM) durante diferentes tiempos (24, 48, 72 h). Para analizar el efecto sobre la migración celular, las células DU-145 y PC-3 fueron tratadas previamente con una concentración de fitoestrógrno (50 μM) durante 24 horas y sembradas en una cámara Transwell sin recubrir. El estudio mostró que el equol, daidzeína y genisteína inhibió en MMP-2 y MMP-9 expresiones de genes en líneas celulares de cáncer de próstata, la PC-3 y DU-145. Los resultados indicaron que la daidzeína disminuyó la expresión de MMP- 2 y MMP-9 en DU-145 células. Nuestros datos sugieren que equol, daidzeína y genisteína inhiben la migración y la invasión de líneas celulares de cáncer de próstata.


Assuntos
Equol/farmacologia , Genisteína/farmacologia , Isoflavonas/farmacologia , Neoplasias da Próstata , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Dieta , Inibidores de Metaloproteinases de Matriz , Invasividade Neoplásica/prevenção & controle , Fitoestrógenos/farmacologia
19.
J. pediatr. (Rio J.) ; 91(2): 111-121, Mar-Apr/2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-745940

RESUMO

OBJECTIVE: To describe the challenges faced by families caring for children with autism spectrum disorder (ASD) in Brazil and the coping strategies employed. SOURCES: Systematic review of articles published until September of 2013, without language restrictions, using quality appraisal (AMSTAR and CASP/Oxford instruments). SUMMARY OF THE FINDINGS: The literature shows parental emotional overload as one of the main challenges faced by families, especially mothers. The main stressors were diagnostic postponement, difficulty dealing with the diagnosis and associated symptoms, and poor access to health services and social support. The predominant coping strategies found included information exchange between affected families and integrated healthcare network for patient and family support. CONCLUSION: ASD exerts strong influence on family dynamics, resulting in caregiver overload, especially in mothers. The Brazilian Unified Health System needs to provide comprehensive, continuous, and coordinated care to strengthen the patient-family dyad and promote the full development and societal inclusion of children with ASD. .


OBJETIVO: Descrever os desafios encontrados pelas famílias na convivência com crianças portadoras de transtorno do espectro autista (TEA) no Brasil e as estratégias de superação empregadas. FONTE DOS DADOS: Revisão sistemática da literatura com inclusão de artigos publicados até setembro de 2013, sem restrições de idioma. Os artigos incluídos foram submetidos à avaliação de qualidade metodológica por meio do Amstar e Casp/Oxford. SÍNTESE DOS DADOS: Incluem-se estudos provenientes de São Paulo e Rio Grande do Sul com alta e moderada qualidade metodológica. A literatura mostra sobrecarga emocional dos pais como um dos principais desafios encontrados pelas famílias, inclusive com grande tensão sobre as mães. Dentre os fatores relacionados ao estresse estão: postergação diagnóstica, dificuldade de lidar com o diagnóstico e com os sintomas associados, acesso precário ao serviço de saúde e apoio social. Dentre as estratégias de superação destacaram-se: troca de informações entre as famílias afetadas e assistência integralizada da rede de saúde no atendimento do paciente e suporte à família. CONCLUSÃO: Observou-se que o TEA exerce forte influência na dinâmica familiar com sobrecarga dos cuidadores, geralmente da mãe. O Sistema Único de Saúde necessita prover cuidado integral, longitudinal e coordenado com vistas ao fortalecimento do binômio paciente-família e o pleno desenvolvimento e a plena inserção dessas crianças na sociedade. .


Assuntos
Humanos , Biomarcadores/metabolismo , Movimento Celular/fisiologia , Células Gigantes/metabolismo , Macrófagos/metabolismo , Neoplasias/diagnóstico , Biópsia/métodos , Tamanho Celular , Filtração/métodos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Microscopia , Células Neoplásicas Circulantes , Neoplasias/metabolismo
20.
Cad. saúde pública ; 31(4): 722-732, 04/2015.
Artigo em Inglês | LILACS | ID: lil-744848

RESUMO

We aimed to verify doctor's perception of the qualitative research method, via a qualitative study of interviews with questions on the academic profile of doctors and on the methodology. We interviewed 42 professionals, of which 18 had experience with the qualitative method and 24 with the quantitative method. The results showed that knowledge on the qualitative method was virtually nil among "quantitative researchers", who did not value qualitative research, although some of those realized that it would be important to be more accepting in clinical practice. Others only considered the method as subsidiary to quantitative. The majority considered qualitative methods as lacking academic structure, taking too long to conduct empirical studies, and being difficult to publish. All of them criticized the misuse of the method, and the "quantitatives" pointed out the problem of being unable to reproduce. We concluded that widening the use of the qualitative method by doctors requires investment from the beginning of the academic career and participation in qualitative research projects.


El objetivo es verificar la percepción de médicos sobre el método de investigación cualitativa. Se trata de un estudio cualitativo por medio de entrevistas con preguntas sobre el perfil de los médicos y sobre el método. Entrevistamos a 42 profesionales, 18 con experiencia en el método cualitativo y 24 con el cuantitativo. Los resultados mostraron que el conocimiento sobre lo cualitativo es casi nulo entre los "cuantitativistas", que no valoran la investigación cualitativa, aunque algunos se dan cuenta de que sería importante tener un enfoque más amplio en la práctica clínica. Otros la ven como subsidiaria a lo cuantitativo. Sus dificultades para utilizar ese abordaje son: falta de formación, cantidad de tiempo que exigen y problemas de publicación. Todos han criticado el mal uso del método. Los "cuantitativistas" han destacado como fragilidad, la no reproductibilidad. Llegamos a la conclusión de que para ampliar el uso de los abordajes cualitativos entre los médicos es importante invertir en su formación desde el inicio del curso y la participación en proyectos de investigación cualitativa.


Objetivamos verificar a percepção de médicos sobre o método qualitativo de pesquisa. Estudo qualitativo por meio de entrevistas com questões sobre o perfil acadêmico do médico e perguntas abertas a respeito do método. Entrevistamos 42 profissionais, sendo 18 com experiência no método qualitativo e 24 com o quantitativo. Os resultados evidenciaram que o conhecimento sobre o qualitativo é quase nulo entre os pesquisadores "quantitativistas", os quais não valorizam a pesquisa qualitativa, embora alguns percebam que seria importante ter uma postura mais compreensiva na prática clínica. Outros só a veem como subsidiária ao quantitativo. As principais dificuldades da maioria são: falta de formação, tempo longo despendido nos estudos empíricos e dificuldade de publicação. Todos os entrevistados criticaram o mau uso do método, e os "quantitativistas" ressaltaram, como problema, sua não reprodutibilidade. Concluímos que ampliar o uso do método qualitativo por médicos exige investimento na formação desde o início da graduação e participação em projetos de pesquisa qualitativa.


Assuntos
Animais , Humanos , Camundongos , Anilidas/farmacologia , Benzodiazepinonas/farmacologia , /farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Pirimidinas/farmacologia , Proteínas Repressoras/antagonistas & inibidores , Células Cultivadas , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática/efeitos dos fármacos , Neoplasias/patologia , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas Repressoras/agonistas , Proteínas Repressoras/genética , Especificidade por Substrato , Proteínas Supressoras de Tumor/fisiologia
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