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1.
Biol. Res ; 52: 59, 2019. graf
Article in English | LILACS | ID: biblio-1100911

ABSTRACT

OBJECTIVES: In varicose veins, vascular smooth muscle cells (VSMCs) often shows phenotypic transition and abnormal proliferation and migration. Evidence suggests the FOXC2-Notch pathway may be involved in the pathogenesis of varicose veins. Here, this study aimed to explore the role of long non-coding RNA FOXC2-AS1 (FOXC2 antisense RNA 1) in phenotypic transition, proliferation, and migration of varicose vein-derived VSMCs and to explore whether the FOXC2-Notch pathway was involved in this process. METHODS: The effect of FOXC2-AS1 on the proliferation and migration of human great saphenous vein smooth muscle cells (SV-SMCs) was analyzed using MTT assay and Transwell migration assay, respectively. The levels of contractile marker SM22α and synthetic marker osteopontin were measured by immunohistochemistry and Western blot to assess the phenotypic transition. RESULTS: The human varicose veins showed thickened intima, media and adventitia layers, increased synthetic VSMCs, as well as upregulated FOXC2-AS1 and FOXC2 expression. In vitro assays showed that FOXC2-AS1 overexpression promoted phenotypic transition, proliferation, and migration of SV-SMCs. However, the effect of FOXC2-AS1 overexpression could be abrogated by both FOXC2 silencing and the Notch signaling inhibitor FLI-06. Furthermore, FOXC2-AS1 overexpression activated the Notch pathway by upregulating FOXC2. CONCLUSION: FOXC2-AS1 overexpression promotes phenotypic transition, proliferation, and migration of SV-SMCs, at least partially, by activating the FOXC2-Notch pathway.


Subject(s)
Humans , Saphenous Vein/metabolism , Cell Movement/physiology , Myocytes, Smooth Muscle/metabolism , Cell Proliferation/physiology , Forkhead Transcription Factors/metabolism , Phenotype , Saphenous Vein/pathology , Signal Transduction , Up-Regulation , Cells, Cultured , Myocytes, Smooth Muscle/pathology
2.
Braz. j. med. biol. res ; 52(4): e7728, 2019. graf
Article in English | LILACS | ID: biblio-1001506

ABSTRACT

Pituitary adenoma is one of the most common tumors in the neuroendocrine system. This study investigated the effects of long non-coding RNAs (lncRNAs) highly up-regulated in liver cancer (HULC) on rat secreting pituitary adenoma GH3 cell viability, migration, invasion, apoptosis, and hormone secretion, as well as the underlying potential mechanisms. Cell transfection and qRT-PCR were used to change and measure the expression levels of HULC, miR-130b, and FOXM1. Cell viability, migration, invasion, and apoptosis were assessed using trypan blue staining assay, MTT assay, two-chamber transwell assay, Guava Nexin assay, and western blotting. The concentrations of prolactin (PRL) and growth hormone (GH) in culture supernatant of GH3 cells were assessed using ELISA. The targeting relationship between miR-130b and FOXM1 was verified using dual luciferase activity. Finally, the expression levels of key factors involved in PI3K/AKT/mTOR and JAK1/STAT3 pathways were evaluated using western blotting. We found that HULC was highly expressed in GH3 cells. Overexpression of HULC promoted GH3 cell viability, migration, invasion, PRL and GH secretion, as well as activated PI3K/AKT/mTOR and JAK1/STAT3 pathways. Knockdown of HULC had opposite effects and induced cell apoptosis. HULC negatively regulated the expression of miR-130b, and miR-130b participated in the effects of HULC on GH3 cells. FOXM1 was a target gene of miR-130b, which was involved in the regulation of GH3 cell viability, migration, invasion, and apoptosis, as well as PI3K/AKT/mTOR and JAK1/STAT3 pathways. In conclusion, HULC tumor-promoting roles in secreting pituitary adenoma might be via down-regulating miR-130b, up-regulating FOXM1, and activating PI3K/AKT/mTOR and JAK1/STAT3 pathways.


Subject(s)
Humans , Animals , Rats , Pituitary Neoplasms/pathology , Adenoma/pathology , RNA, Long Noncoding/physiology , Enzyme-Linked Immunosorbent Assay , Transfection , Adenoma/genetics , Adenoma/metabolism , Cell Movement/physiology , Cell Survival/physiology , Blotting, Western , Apoptosis/physiology , MicroRNAs/analysis , Cell Line, Tumor , STAT3 Transcription Factor/analysis , Janus Kinase 1/analysis , Janus Kinase 1/metabolism , Cell Migration Assays , Forkhead Box Protein M1/analysis , Forkhead Box Protein M1/metabolism , Luciferases
3.
São Paulo; s.n; s.n; 2018. 105 p. ilus, tab, graf.
Thesis in English | LILACS | ID: biblio-909445

ABSTRACT

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


Subject(s)
Glioblastoma/complications , Chromatin Assembly and Disassembly , Cell Movement/physiology , Neoplasm Invasiveness
4.
J. appl. oral sci ; 26: e20180077, 2018. graf
Article in English | LILACS, BBO | ID: biblio-954491

ABSTRACT

Abstract Objective This study evaluated the influence of platelet-rich plasma (PRP) on the behaviour of human gingival fibroblasts (hGFs), including fibroblast proliferation, migration and colony formation. Methods PRP was obtained from the human peripheral blood of a healthy volunteer and then was diluted into platelet concentrations of 1%, 2% and 5%. The proliferation of hGFs was determined by two methods: (1) Cell-number counting with a haemocytometer method at days 1, 3, 5 and 7; (2) Colony-forming unit-fibroblast (CFU-F) assay at 2 weeks. The migration of hGFs was evaluated with scratch assay, then recorded digital images were analysed by Image-Analysis J 1.51j8 software to compare the remaining artificial wound areas between PRP groups at 0, 24 and 48 hours. Results All hGFs that were cultivated in media with 1%, 2% and 5% PRP showed their ability to proliferate and migrate. Cell numbers incubated with 1% PRP increased significantly during the first three days and peaked at day 5, tending to be similar to their proliferation in complete medium. With concentrations of 2% and 5% PRP, hGFs outgrew and peaked at day 3, which was faster than with those in medium with 1% PRP. Especially, hGFs in the group 5% PRP proliferated with higher cell numbers than those in the other remaining groups at day 3. The hGF colony number that was formed in the group 5% PRP was significantly higher than those in the groups 1% and 2% PRP. Scratch assay showed hGFs in the groups 2% and 5% PRP almost filled the artificial wound and migrated more effectively than in the group 1% PRP at 24 hours, which was significant. Conclusion In this study, perhaps the medium with 5% PRP is the dominant option, promoting the abilities of hGFs to heal wounds, because of its fast and effective impact on cell proliferation, colony formation and migration.


Subject(s)
Humans , Cell Movement/physiology , Reproducibility of Results , Cell Proliferation/physiology , Fibroblasts/drug effects , Fibroblasts/physiology , Time Factors , Cell Count , Cell Movement/drug effects , Cells, Cultured , Culture Media , Cell Proliferation/drug effects , Platelet-Rich Plasma , Gingiva/cytology
5.
Braz. j. med. biol. res ; 51(12): e7574, 2018. graf
Article in English | LILACS | ID: biblio-974257

ABSTRACT

Bone fracture is a common medical condition, which may occur due to traumatic injury or disease-related conditions. Evidence suggests that microRNAs (miRNAs) can regulate osteoblast differentiation and function. In this study, we explored the effects and mechanism of miR-221 on the growth and migration of osteoblasts using MC3T3-E1 cells. The expression levels of miR-221 in the different groups were measured by qRT-PCR. Then, miR-221 mimic and inhibitor were transfected into MC3T3-E1 cells, and cell viability and migration were measured using the CCK-8 assay and the Transwell migration assay. Additionally, the expression levels of differentiation-related factors (Runx2 and Ocn) and ZFPM2 were measured by qRT-PCR. Western blot was used to measure the expression of cell cycle-related proteins, epithelial-mesenchymal transition (EMT)-related proteins, ZFPM2, and Wnt/Notch, and Smad signaling pathway proteins. miR-221 was significantly up-regulated in the patients with lumbar compression fracture (LCM) and trochanteric fracture (TF). miR-221 promoted ALP, Runx2, and OPN expressions in MC3T3-E1 cells. miR-221 overexpression significantly increased cell proliferation, migration, differentiation, and matrix mineralization, whereas suppression of miR-221 reversed these effects. Additionally, the results displayed that ZFPM2 was a direct target gene of miR-221, and overexpression of ZFPM2 reversed the promoting effects of miR-221 overexpression on osteoblasts. Mechanistic study revealed that overexpression of miR-221 inactivated the Wnt/Notch and Smad signaling pathways by regulating ZFPM2 expression. We drew the conclusions that miR-221 overexpression promoted osteoblast proliferation, migration, and differentiation by regulation of ZFPM2 expression and deactivating the Wnt/Notch and Smad signaling pathways.


Subject(s)
Humans , Animals , Rabbits , Cell Differentiation/physiology , Cell Movement/physiology , MicroRNAs/physiology , Cell Proliferation/physiology , DNA-Binding Proteins/physiology , Fractures, Bone/blood , Osteoblasts/physiology , Reference Values , Transcription Factors/blood , Cell Survival/physiology , Blotting, Western , Analysis of Variance , 3T3 Cells , MicroRNAs/blood , DNA-Binding Proteins/blood
6.
Braz. j. med. biol. res ; 51(10): e7423, 2018. tab, graf
Article in English | LILACS | ID: biblio-951708

ABSTRACT

Epithelial cell migration is an essential response to enteric pathogens such as enteropathogenic Escherichia coli (EPEC). This study aimed to investigate the effects of EPEC infection on intestinal epithelial cell migration in vitro, as well as the involvement of type III secretion system (T3SS) and Rho GTPases. Crypt intestinal epithelial cells (IEC-6) were infected with EPEC strains (E2348/69, ΔescF, and the LDI001 strain isolated from a malnourished Brazilian child) and commensal E. coli HS. Wound migration and cell death assays were performed at different time-points. Transcription and expression of Rho GTPases were evaluated using real-time PCR and western blotting. Overall, EPEC E2348/69 reduced migration and increased apoptosis and necrosis levels compared to EPEC LDI001 and E. coli HS strains. Moreover, EPEC LDI001 impaired cell migration at a higher level than E. coli HS and increased necrosis after 24 hours compared to the control group. The different profiles of virulence genes between the two wild-type EPEC strains, characterized by the absence of espL and nleE genes in the LDI001, might explain the phenotypic results, playing significant roles on cell migration impairment and cell death-related events. Moreover, the type III secretion system is determinant for the inhibition of intestinal epithelial cell migration by EPEC 2348/69, as its deletion prevented the effect. Active Rac1 concentrations were increased in E2348/69 and LDI001-infected cells, while the T3SS-deficient strain did not demonstrate this activation. This study contributes with valuable insight to characterize the mechanisms involved in the impairment of intestinal cell migration induced by EPEC.


Subject(s)
Humans , Cell Movement/physiology , rho GTP-Binding Proteins/physiology , Virulence Factors/genetics , Epithelial Cells/microbiology , Enteropathogenic Escherichia coli/pathogenicity , Type III Secretion Systems/physiology , Blotting, Western , Apoptosis , Virulence Factors/physiology , Real-Time Polymerase Chain Reaction , Flow Cytometry
7.
Yonsei Medical Journal ; : 234-240, 2017.
Article in English | WPRIM | ID: wpr-126252

ABSTRACT

PURPOSE: MicroRNAs are small non-coding RNAs that play important roles in vascular smooth muscle cell (VSMC) function. This study investigated the role of miR-379 on proliferation, invasion, and migration of VSMCs and explored underlying mechanisms thereof. MATERIALS AND METHODS: MicroRNA, mRNA, and protein levels were determined by quantitative real-time PCR and western blot. The proliferative, invasive, and migratory abilities of VSMCs were measured by CCK-8, invasion, and wound healing assay, respectively. Luciferase reporter assay was used to confirm the target of miR-379. RESULTS: Platelet-derived growth factor-bb was found to promote cell proliferation and suppress miR-379 expression in VSMCs. Functional assays demonstrated that miR-379 inhibited cell proliferation, cell invasion, and migration. Flow cytometry results further showed that miR-379 induced apoptosis in VSMCs. TargetScan analysis and luciferase report assay confirmed that insulin-like growth factor-1 (IGF-1) 3'UTR is a direct target of miR-379, and mRNA and protein levels of miR-379 and IGF-1 were inversely correlated. Rescue experiments showed that enforced expression of IGF-1 sufficiently overcomes the inhibitory effect of miR-379 on cell proliferation, invasion, and migration in VSMCs. CONCLUSION: Our results suggest that miR-379 plays an important role in regulating VSMCs proliferation, invasion, and migration by targeting IGF-1.


Subject(s)
Apoptosis , Cell Movement/physiology , Cell Proliferation/physiology , Humans , Insulin , Insulin-Like Growth Factor I/physiology , MicroRNAs/physiology , Muscle, Smooth, Vascular/cytology , Proto-Oncogene Proteins c-sis/physiology , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Sincalide/physiology , Wound Healing/physiology
8.
Biol. Res ; 49: 1-10, 2016. ilus, graf, tab
Article in English | LILACS | ID: lil-774432

ABSTRACT

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.


Subject(s)
Female , Humans , Breast Neoplasms/pathology , Cell Cycle Proteins/physiology , Cell Movement/physiology , Cell Proliferation/physiology , Glycoproteins/physiology , Analysis of Variance , Blotting, Western , Breast Neoplasms/genetics , Cell Cycle , Cell Line, Tumor , Cell Survival , Cell Cycle Proteins/genetics , Cell Movement/genetics , Cell Proliferation/genetics , DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Glycoproteins/genetics , Neoplasm Invasiveness , Real-Time Polymerase Chain Reaction , Statistics, Nonparametric
9.
Biol. Res ; 49: 1-10, 2016. ilus, graf
Article in English | LILACS | ID: biblio-950860

ABSTRACT

BACKGROUND: Glioblastoma is one of the most aggressive cancers of the brain. Malignant traits of glioblastoma cells include elevated migration, proliferation and survival capabilities. Galectins are unconventionally secreted glycan-binding proteins that modulate processes of cell adhesion, migration, proliferation and apoptosis by interacting with beta-galactosides of cell surface glycoproteins and the extracellular matrix. Galectin-8 is one of the galectins highly expressed in glioblastoma cells. It has a unique selectivity for terminally sialylated glycans recently found enhanced in these highly malignant cells. A previous study in glioblastoma cell lines reported that Gal-8 coating a plastic surface stimulates two-dimensional motility. Because in other cells Gal-8 arrests proliferation and induces apoptosis, here we extend its study by analyzing all of these processes in a U87 glioblastoma cell mode.l METHODS: We used immunoblot and RT-PCR for Gal-8 expression analysis, recombinant Gal-8 produced in a bacteria system for Gal-8 treatment of the cells, and shRNA in lentivirus transduction for Gal-8 silencing. Cell migration as assessed in transwell filters. Cell proliferation, cell cycle and apoptosis were analyzed by FACS. RESULTS: Gal-8 as a soluble stimulus triggered chemotactic migration of U87 cells across the polycarbonate filter of transwell chambers, almost as intensively as fetal bovine serum. Unexpectedly, Gal-8 also enhanced U87 cell growth. Co-incubation of Gal-8 with lactose, which blocks galectin-glycan interactions, abrogated both effects. Immunoblot showed Gal-8 in conditioned media reflecting its secretion. U87 cells transduced with silencing shRNA in a lentiviral vector expressed and secreted 30-40 % of their normal Gal-8 levels. These cells maintained their migratory capabilities, but decreased their proliferation rate and underwent higher levels of apoptosis, as revealed by flow cytometry analysis of cell cycle, CFSE and activated caspase-3 staining. Proliferation seemed to be more sensitive than migration to Gal-8 expression levels. CONCLUSIONS: Gal-8, either secreted or exogenously enriched in the media, and acting through extracellular glycan interactions, constitutes a strong stimulus of directional migration in glioblastoma U87 cells and for the first time emerges as a factor that promotes proliferation and prevents apoptosis in cancerous cells. These properties could potentially contribute to the exaggerated malignancy of glioblastoma cells.


Subject(s)
Humans , Animals , Cattle , Brain Neoplasms/pathology , Glioblastoma/pathology , Galectins/physiology , Time Factors , Brain Neoplasms/genetics , Tumor Cells, Cultured , Cell Movement/physiology , Apoptosis/physiology , Glioblastoma/genetics , Reverse Transcriptase Polymerase Chain Reaction , Galectins/analysis , Galectins/pharmacology , Galectin 1/analysis , Galectin 1/physiology , Galectin 3/analysis , Galectin 3/physiology , Cell Line, Tumor , Cell Proliferation/physiology , Flow Cytometry/methods
10.
J. pediatr. (Rio J.) ; 91(2): 111-121, Mar-Apr/2015. tab, graf
Article in English | LILACS | ID: lil-745940

ABSTRACT

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. .


Subject(s)
Humans , Biomarkers/metabolism , Cell Movement/physiology , Giant Cells/metabolism , Macrophages/metabolism , Neoplasms/diagnosis , Biopsy/methods , Cell Size , Filtration/methods , In Situ Hybridization, Fluorescence , Kaplan-Meier Estimate , Microscopy , Neoplastic Cells, Circulating , Neoplasms/metabolism
11.
Salud colect ; 11(1): 67-86, ene.-mar. 2015. ilus
Article in Spanish | LILACS | ID: lil-746685

ABSTRACT

Este artículo explica las dificultades que tienen las farmacéuticas innovadoras para retribuir a sus accionistas con dividendos atractivos. El problema es el resultado de la caducidad de las patentes de los medicamentos estrella (blockbusters) y las dificultades que tienen en desarrollar nuevos medicamentos estrella. Una solución que las empresas han encontrado es acelerar la ejecución de los ensayos clínicos para obtener, en el menor tiempo posible, el permiso de comercialización y así incrementar el tiempo monopólico de ventas de los nuevos medicamentos. En este contexto, los autores describen la forma en que las farmacéuticas innovadoras acortan el tiempo de ejecución de los ensayos en América Latina y las consecuencias en la calidad de los datos que se obtienen, en la protección de los derechos humanos de los sujetos de experimentación, y en el cumplimiento de los principios éticos aprobados en las declaraciones universales.


This article explains the difficulties innovative pharmaceutical firms have in repaying shareholders with attractive dividends. The problem is the result of the expiration of the patents of blockbuster drugs and the difficulties that the firms have in bringing new blockbuster drugs to the market. One of the solutions companies have found has been to accelerate the implementation of clinical trials in order to expedite the commercialization of new drugs. Doing so increases the period in which they can sell drugs at monopoly prices. We therefore discuss how innovative pharmaceutical firms shorten the implementation time of clinical trials in Latin America and the consequences such actions have on the quality of the collected data, the protection of human rights of the subjects of experimentation, and compliance with the ethical principles approved in international declarations.


Subject(s)
Animals , Mice , Algorithms , Cell Movement/physiology , Decision Support Techniques , Extracellular Matrix Proteins/metabolism , Gene Expression Regulation/physiology , Models, Biological , Signal Transduction/physiology , Computer Simulation , Logistic Models
12.
Mem. Inst. Oswaldo Cruz ; 110(1): 151-153, 03/02/2015. tab, graf
Article in English | LILACS | ID: lil-741612

ABSTRACT

The Brazilian Amazon Region is a highly endemic area for hepatitis B virus (HBV). However, little is known regarding the genetic variability of the strains circulating in this geographical region. Here, we describe the first full-length genomes of HBV isolated in the Brazilian Amazon Region; these genomes are also the first complete HBV subgenotype D3 genomes reported for Brazil. The genomes of the five Brazilian isolates were all 3,182 base pairs in length and the isolates were classified as belonging to subgenotype D3, subtypes ayw2 (n = 3) and ayw3 (n = 2). Phylogenetic analysis suggested that the Brazilian sequences are not likely to be closely related to European D3 sequences. Such results will contribute to further epidemiological and evolutionary studies of HBV.


Subject(s)
Humans , Carcinoma, Hepatocellular , Cell Movement/physiology , Liver Neoplasms , Matrix Metalloproteinase 9/genetics , Signal Transduction/physiology , Tissue Inhibitor of Metalloproteinase-1/genetics , Cell Line, Tumor/cytology , Cell Line, Tumor/physiology , Collagenases/genetics , Dipeptides/pharmacology , Matrix Metalloproteinase Inhibitors , Matrix Metalloproteinase 1/genetics , /genetics , /genetics , /genetics , Protease Inhibitors/pharmacology , Signal Transduction/drug effects , Transfection
13.
Biol. Res ; 48: 1-15, 2015. ilus, graf, tab
Article in English | LILACS | ID: biblio-950812

ABSTRACT

BACKGROUND: The collective cell migration of stratified epithelial cells is considered to be an important phenomenon in wound healing, development, and cancer invasion; however, little is known about the mechanisms involved. Furthermore, whereas Rho family proteins, including RhoA, play important roles in cell migration, the exact role of Rho-associated coiled coil-containing protein kinases (ROCKs) in cell migration is controversial and might be cell-type dependent. Here, we report the development of a novel modified scratch assay that was used to observe the collective cell migration of stratified TE-10 cells derived from a human esophageal cancer specimen. RESULTS: Desmosomes were found between the TE-10 cells and microvilli of the surface of the cell sheet. The leading edge of cells in the cell sheet formed a simple layer and moved forward regularly; these rows were followed by the stratified epithelium. ROCK inhibitors and ROCK small interfering RNAs (siRNAs) disturbed not only the collective migration of the leading edge of this cell sheet, but also the stratified layer in the rear. In contrast, RhoA siRNA treatment resulted in more rapid migration of the leading rows and disturbed movement of the stratified portion. CONCLUSIONS: The data presented in this study suggest that ROCKs play an important role in mediating the collective migration of TE-10 cell sheets. In addition, differences between the effects of siRNAs targeting either RhoA or ROCKs suggested that distinct mechanisms regulate the collective cell migration in the simple epithelium of the wound edge versus the stratified layer of the epithelium.


Subject(s)
Humans , Cell Movement/physiology , RNA, Small Interfering/pharmacology , rho-Associated Kinases/physiology , Esophageal Neoplasms , MicroRNAs/physiology , Cell Line, Tumor , rho-Associated Kinases/antagonists & inhibitors
14.
Braz. j. med. biol. res ; 47(6): 470-477, 06/2014. tab, graf
Article in English | LILACS | ID: lil-709452

ABSTRACT

The purpose of this investigation was to analyze the proliferative behavior of rabbit corneal epithelium and establish if any particular region was preferentially involved in epithelial maintenance. [3H]-thymidine was injected intravitreally into both normal eyes and eyes with partially scraped corneal epithelium. Semithin sections of the anterior segment were evaluated by quantitative autoradiography. Segments with active replication (on) and those with no cell division (off) were intermingled in all regions of the tissue, suggesting that the renewal of the epithelial surface of the cornea followed an on/off alternating pattern. In the limbus, heavy labeling of the outermost layers was observed, coupled with a few or no labeled nuclei in the basal stratum. This suggests that this region is a site of rapid cell differentiation and does not contain many slow-cycling cells. The conspicuous and protracted labeling of the basal layer of the corneal epithelium suggests that its cells undergo repeated cycles of replication before being sent to the suprabasal strata. This replication model is prone to generate label-retaining cells. Thus, if these are adult stem cells, one must conclude that they reside in the corneal basal layer and not the limbal basal layer. One may also infer that the basal cells of the cornea and not of the limbus are the ones with the main burden of renewing the corneal epithelium. No particular role in this process could be assigned to the cells of the basal layer of the limbal epithelium.


Subject(s)
Animals , Male , Rabbits , Epithelium, Corneal/anatomy & histology , Epithelium, Corneal/physiology , Limbus Corneae/cytology , Stem Cells/physiology , Autoradiography , Cell Proliferation , Cell Movement/physiology , Cornea/anatomy & histology , Eye/anatomy & histology , Intravitreal Injections , Thymidine , Tritium
15.
Biol. Res ; 47: 1-9, 2014. ilus, tab
Article in English | LILACS | ID: biblio-950754

ABSTRACT

Diabetic retinopathy is one of the most important causes of blindness. The underlying mechanisms of this disease include inflammatory changes and remodeling processes of the extracellular-matrix (ECM) leading to pericyte and vascular endothelial cell damage that affects the retinal circulation. In turn, this causes hypoxia leading to release of vascular endothelial growth factor (VEGF) to induce the angiogenesis process. Alpha-1 antitrypsin (AAT) is the most important circulating inhibitor of serine proteases (SERPIN). Its targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, proteinase 3 (PR-3) and plasminogen activator (PAI). AAT modulates the effect of protease-activated receptors (PARs) during inflammatory responses. Plasma levels of AAT can increase 4-fold during acute inflammation then is so-called acute phase protein (APPs). Individuals with low serum levels of AAT could develop disease in lung, liver and pancreas. AAT is involved in extracellular matrix remodeling and inflammation, particularly migration and chemotaxis of neutrophils. It can also suppress nitric oxide (NO) by nitric oxide sintase (NOS) inhibition. AAT binds their targets in an irreversible way resulting in product degradation. The aim of this review is to focus on the points of contact between multiple factors involved in diabetic retinopathy and AAT resembling pleiotropic effects that might be beneficial.


Subject(s)
Humans , Animals , Serine Proteinase Inhibitors/therapeutic use , alpha 1-Antitrypsin/therapeutic use , Diabetic Retinopathy/drug therapy , Cell Hypoxia , Serine Proteinase Inhibitors/metabolism , Cell Movement/physiology , Chemotaxis/physiology , alpha 1-Antitrypsin/metabolism , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism , Inflammation Mediators/antagonists & inhibitors , Nitric Oxide Synthase/antagonists & inhibitors , Protective Agents/metabolism , Receptors, Proteinase-Activated/metabolism , Diabetic Retinopathy/physiopathology , Free Radicals , Inflammation/metabolism , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/therapeutic use , Neutrophils/physiology
16.
Mem. Inst. Oswaldo Cruz ; 108(7): 825-831, 1jan. 2013.
Article in English | LILACS | ID: lil-696015

ABSTRACT

Developing thymocytes interact with thymic epithelial cells (TECs) through cell-cell interactions, TEC-derived secretory moieties and extracellular matrix (ECM)-mediated interactions. These physiological interactions are crucial for normal thymocyte differentiation, but can be disrupted in pathological situations. Indeed, there is severe thymic atrophy in animals acutely infected with Trypanosoma cruzi due to CD4+CD8+ thymocyte depletion secondary to caspase-mediated apoptosis, together with changes in ECM deposition and thymocyte migration. We studied an in vitro model of TEC infection by T. cruzi and found that infected TEC cultures show a reduced number of cells, which was likely associated with decreased proliferative capacity, but not with increased cell death, as demonstrated by bromodeoxyuridine and annexin-V labelling. The infected TEC cultures exhibited increased expression of fibronectin (FN), laminin (LM) and type IV collagen. Importantly, treatment with FN increased the relative number of infected cells, whereas treatment with anti-FN or anti-LM antibodies resulted in lower infection rates. Consistent with these data, we observed increased thymocyte adhesion to infected TEC cultures. Overall, these results suggest that ECM molecules, particularly FN, facilitate infection of the thymic epithelium and that the consequent enhancement of ECM expression might be associated with changes in TEC-thymocyte interactions.


Subject(s)
Animals , Male , Chagas Disease/metabolism , Epithelial Cells/metabolism , Extracellular Matrix/metabolism , Fibronectins/metabolism , Thymocytes/metabolism , Thymus Gland/metabolism , Cell Adhesion/physiology , Cell Communication/physiology , Cell Movement/physiology , Disease Models, Animal , Epithelial Cells/parasitology , Mice, Inbred BALB C , Thymocytes/parasitology , Thymus Gland/cytology
17.
Arq. bras. cardiol ; 101(2): 141-148, ago. 2013. ilus, tab
Article in Portuguese | LILACS | ID: lil-685389

ABSTRACT

FUNDAMENTO: O fator de crescimento endotelial vascular (VEGF - vascular endothelial growth factor) induz a mobilização de células progenitoras endoteliais (CPEs) com capacidade de proliferação e diferenciação em células endoteliais, contribuindo, dessa forma, para o processo angiogênico. OBJETIVO: Buscamos avaliar o comportamento de CPEs em pacientes com doença cardíaca isquêmica e angina refratária que receberam injeções intramiocardicas de 2000 µg de VEGF165 como terapia única. MÉTODOS: O estudo foi uma subanálise de um ensaio clínico. Pacientes com doença cardíaca isquêmica avançada e angina refratária foram avaliados para inclusão no estudo. Os critérios de inclusão foram: sinais e sintomas de angina e/ou insuficiência cardíaca apesar de tratamento medicamentoso máximo e área de isquemia miocárdica de, no mínimo, 5% conforme avaliado por uma tomografia computadorizada por emissão de fóton único (TCEFU). Os critérios de exclusão foram: idade > 65 anos, fração de ejeção do ventrículo esquerdo < 25% e cancer diagnosticado. Os pacientes cujos níveis de CPE foram avaliados foram incluídos. A intervenção consistiu na administração de 2000 µg de VEGF 165 de plasmídeo injetado no miocárdio isquêmico. A frequência de células CD34+/KDR+ foi analisada por citometria de fluxo antes e 3, 9, e 27 dias após a intervenção. RESULTADOS: Um total de 9 pacientes foram incluídos, 8 homens, média de idade de 59,4 anos, fração de ejeção ventricular esquerda de 59,3%, e classe de angina predominante III. Observou-se um aumento significativo dos níveis de CPEs no terceiro dia após a intervenção. Todavia, 9 e 27 dias após a intervenção, os níveis de CPEs foram similares aos basais. CONCLUSÃO: Identificamos uma mobilização transitória de CPE, com pico no terceiro dia após a intervenção com VEGF 165 em pacientes com angina refratária. Todavia, os níveis de CPEs apresentaram-se semelhantes aos basais 9 e 27 dias após a intervenção.


BACKGROUND: Vascular endothelial growth factor (VEGF) induces mobilization of endothelial progenitor cells (EPCs) with the capacity for proliferation and differentiation into mature endothelial cells, thus contributing to the angiogenic process. OBJECTIVE: We sought to assess the behavior of EPCs in patients with ischemic heart disease and refractory angina who received an intramyocardial injections of 2000 µg of VEGF 165 as the sole therapy. METHODS: The study was a subanalysis of a clinical trial. Patients with advanced ischemic heart disease and refractory angina were assessed for eligibility. Inclusion criteria were as follows: signs and symptoms of angina and/or heart failure despite maximum medical treatment and a myocardial ischemic area of at least 5% as assessed by single-photon emission computed tomography (SPECT). Exclusion criteria were as follows: age > 65 years, left ventricular ejection fraction < 25%, and a diagnosis of cancer. Patients whose EPC levels were assessed were included. The intervention was 2000 µg of VEGF 165 plasmid injected into the ischemic myocardium. The frequency of CD34+/KDR+ cells was analyzed by flow cytometry before and 3, 9, and 27 days after the intervention. RESULTS: A total of 9 patients were included, 8 males, mean age 59.4 years, mean left ventricular ejection fraction of 59.3% and predominant class III angina. The number of EPCs on day 3 was significantly higher than that at baseline (p = 0.03); however, that on days 9 and 27 was comparable to that at baseline. CONCLUSION: We identified a transient mobilization of EPCs, which peaked on the 3th day after VEGF 165 gene therapy in patients with refractory angina and returned to near baseline levels on days 9 and 27.


Subject(s)
Female , Humans , Male , Middle Aged , Angina Pectoris/therapy , Cell Movement/genetics , Endothelial Cells/physiology , Genetic Therapy/methods , Multipotent Stem Cells/physiology , Vascular Endothelial Growth Factor A/genetics , Cell Movement/physiology , Multipotent Stem Cells/cytology , Myocardial Ischemia/therapy , Neovascularization, Physiologic/genetics , Plasmids/genetics , Time Factors , Treatment Outcome
18.
Braz. dent. j ; 24(2): 128-135, Mar-Apr/2013. tab, graf
Article in English | LILACS | ID: lil-675657

ABSTRACT

As dogs are good models for in vivo studies, it is interesting to evaluate the behavior of canine gingival fibroblasts (CGF) in vitro, so that these cells could be seeded on a matrix and later studied in vivo. The aim of this study was to perform a morphological, functional and biochemical analysis of CGF, comparing it with human gingival fibroblasts (HGF), as well as to evaluate the change of their characteristics over several passages. Using gingival fibroblasts from 3 dogs and 3 humans in the subculture (Sub), first (P1), third (P3), fifth (P5) and seventh (P7) passages, the following parameters were assessed: cell morphology, spreading, adhesion, viability and total protein content. The results showed no major differences between the passages in terms of morphology and spreading, and a tendency of greater adhesion and viability for HGF when compared with CGF. The total protein content was significantly higher for HGF. HGF exhibited greater functional and biochemical activity in vitro compared to CGF. Higher numbers at Sub were observed for both CGF and HGF in all evaluated parameters. The differences do not prevent the use of CGF for tissue engineering, but its use seems to be more appropriate in the subculture or first passage.


Resumo Como os cães são um bom modelo para estudos in vivo, é interessante avaliar o comportamento de fibroblastos gengivais de cão (CGF) in vitro, para que essas células possam ser cultivadas em uma matriz e estudadas in vivo posteriormente. O objetivo do presente estudo foi realizar uma análise morfológica, funcional e bioquímica de CGF, comparando-os a fibroblastos gengivais humanos (HGF), bem como avaliar as alterações dessas características ao longo de várias passagens. Usando fibroblastos gengivais de 3 cães e 3 indivíduos na subcultura (Sub), primeira (P1), terceira (P3), quinta (P5) e sétima (P7) passagens, os seguintes parâmetros foram avaliados: morfologia, espraiamento, adesão, viabilidade e conteúdo de proteína total. Os resultados mostraram não haver diferenças significativas quanto à morfologia e espraiamento, e uma tendência a maior adesão e viabilidade para HGF, quando comparados a CGF. O conteúdo de proteína total foi significativamente maior para HGF. HGF exibiram maior atividade funcional e bioquímica in vitro quando comparados a CGF. Maiores valores na Sub foram observados para ambos, CGF e HGF, em todos os parâmetros avaliados. As diferenças não impedem o uso de CGF na engenharia tecidual, contudo, seu uso é mais apropriado na subcultura ou primeira passagem. .


Subject(s)
Animals , Dogs , Humans , Fibroblasts/cytology , Gingiva/cytology , Cell Count , Cell Culture Techniques , Cell Shape , Cells, Cultured , Cell Adhesion/physiology , Cell Movement/physiology , Cell Survival/physiology , Fibroblasts/metabolism , Fibroblasts/physiology , Models, Animal , Primary Cell Culture , Proteins/analysis , Time Factors , Tissue Engineering/methods
19.
Bauru; s.n; 2013. 197 p. ilus, tab, graf.
Thesis in Portuguese | LILACS, BBO | ID: lil-707699

ABSTRACT

Apesar dos avanços sobre a efetiva participação das células T reguladoras (Treg) na resposta imune antitumoral, ainda existem vários pontos que precisam ser esclarecidos. Visto que, os fatores que controlam a migração destas células para o microambiente tumoral ainda não estão totalmente definidos, o esclarecimento dos mecanismos de migração de células Treg no contexto do câncer poderia fornecer novos alvos para o desenvolvimento de terapias mais específicas. Diversos modelos de estudo demonstraram que o recrutamento preferencial de células Treg ao invés de outros tipos de células T pode ser explicado pela expressão diferencial de receptores de quimiocinas como o CCR5. Assim, é de extrema importância estabelecer qual é o papel de CCR5 na migração de células Treg em tumores induzidos quimicamente e seu envolvimento no desenvolvimento tumoral. Baseado no exposto, o presente estudo analisou o envolvimento de CCR5 na migração de células Treg e a sua correlação com o desenvolvimento de carcinoma espinocelular (CEC) induzido quimicamente. Os resultados obtidos demonstraram que camundongos geneticamente deficentes de CCR5 (CCR5KO) apresentaram baixo número de células Treg nas lesões e foram menos suscetíveis ao desenvolvimento de carcinoma espinocelular. Na fase de progressão tumoral verificou-se o desenvolvimento de CEC in situ por animais CCR5KO em combinação com a maior infiltração leucocitária, enquanto camundongos do grupo controle (WTCEC) apresentaram lesões de CEC bem diferenciado associado à elevada frequência de células Treg no microambiente tumoral e menor infiltração leucocitária. Interessantemente, a transferência adotiva de células Treg CCR5+ para animais CCR5KO (CCR5CEC Treg) resultou no acúmulo destas células no microambiente tumoral, elevado nível de CCL4, CCL17 e CCL22, e aumento da suscetibilidade desses animais à carcinogênese química. Verificou-se o desenvolvimento de CEC indiferenciado por animais CCR5CEC Treg e este foi...


Considering the advances on the effective participation of regulatory T cells (Treg) in the antitumor immune response, there are still several points that need to be clarified. The mechanisms that control the Treg cells migration to the tumor microenvironment are not completely defined, for these reason, establish these mechanisms could provide new targets for the development of more specific therapies. Several study models have demonstrated that preferential recruitment of Treg cells rather than other types of T cells can be explained by the differential expression of chemokine receptors such as CCR5. Thus, the present study examined the involvement of CCR5 in the migration of Treg cells and their correlation with the development of squamous cell carcinoma (SCC) chemically induced. The results showed that CCR5 knockout mice (CCR5KO) showed a low number of Treg cells in the lesions and these animals were less susceptible to the development of squamous cell carcinoma. SCC in situ was developed in CCR5KO mice and associated with high leukocytes infiltration, whereas the development SCC well differentiated in the control group (WTSCC) was associated with a high number of Treg cells and lower leukocyte infiltration in the tumor microenvironment. Interestingly, adoptive transfer of CCR5+Treg cells to CCR5KO mice (CCR5SCC Treg) resulted in the accumulation of these cells, high levels of CCL4, CCL17 and CCL22 in the tumor microenvironment and increased susceptibility to chemical carcinogenesis. CCR5SCCTreg mice developed SCC undifferentiated associated with a higher incidence of macrophages, myeloid and dendritic cells, CD19+, CD4+ T, CD8+ T lymphocytes, and Treg cells in the stage of tumor progression. Another relevant aspect of our study was the observation that adoptive transfer of CD4+CD25-CCR5+ T cells to CCR5KO animals (CCR5SCC CD4+) induced the development of SCC moderately differentiated with intermediate features observed in the WTSCC and CCR5SCC Treg...


Subject(s)
Animals , Male , Mice , Carcinoma, Squamous Cell/pathology , T-Lymphocytes, Regulatory/pathology , /physiology , Carcinoma, Squamous Cell/chemically induced , Biomarkers, Tumor/analysis , Cell Movement/physiology , Time Factors
20.
Arq. bras. cardiol ; 98(2): 182-191, fev. 2012. ilus, tab
Article in Portuguese | LILACS | ID: lil-614517

ABSTRACT

O exercício físico mobiliza Células Progenitoras Endoteliais (CPE) para o sangue periférico. Entretanto, esse efeito parece depender de características do exercício, como duração e intensidade. O objetivo do presente trabalho foi verificar, por meio de revisão sistemática, o impacto de uma única sessão de exercício aeróbico sobre a mobilização de CPE em indivíduos sadios e os potenciais mecanismos envolvidos. A busca bibliográfica foi realizada nas bases de dados eletrônicas SciELO, LILACS, Cochrane, ClinicalTrials.gov, SPORTDiscus e Medline, em maio de 2011. Dos 178 estudos inicialmente identificados, 12 atenderam aos critérios de inclusão e foram classificados quanto à qualidade mediante critérios da escala PEDro. A magnitude e a duração da resposta de mobilização das CPE foram maiores após a realização de exercícios de longa/ultralonga duração e estão correlacionadas com níveis plasmáticos de fator de crescimento endotélio vascular (VEGF). O pico de mobilização dessas células em resposta a uma sessão de exercício máximo ou submáximo, com duração de até uma hora, ocorre no período imediatamente após o esforço até uma hora após sua interrupção. Um possível mecanismo é a biodisponibilidade do Óxido Nítrico (NO). A idade dos indivíduos e a intensidade do exercício parecem interferir na resposta de mobilização das CPE. Exercícios de longa/ultralonga duração promovem mobilização mais acentuada das CPE quando comparados a exercícios máximos ou submáximos. Os mecanismos envolvem a liberação do VEGF em exercícios de longa/ultralonga duração e a biodisponibilidade de NO em exercícios máximo e submáximo com até uma hora de duração.


Physical exercise mobilizes endothelial progenitor cells (EPCs) to peripheral blood. However, this effect seems to depend on exercise characteristics, such as duration and intensity. The aim of this systematic review was to verify the impact of a single bout of aerobic exercise on the mobilization of EPCs in healthy individuals, and the potential mechanisms involved. The bibliographic search was conducted on the following electronic databases in May 2011: SciELO, LILACS, Cochrane, ClinicalTrials.gov, SPORTDiscus and Medline. Of the 178 articles initially identified, 12 met the inclusion criteria and were classified regarding quality according to the PEDro scale. The magnitude and duration of the EPC mobilization response were higher after long/ultralong duration exercises, and they are correlated with vascular endothelial growth factor (VEGF) plasma levels. The EPC mobilization peak in response to a maximal or submaximal single bout of exercise lasting up to one hour occurs immediately after the exercise or within the first hour after it. One possible mechanism is nitric oxide (NO) bioavailability. The individuals' age and exercise intensity seem to interfere with the EPC mobilization response. Long/ultralong duration exercises promote more pronounced EPC mobilization as compared with maximal or submaximal exercises. The mechanisms involve VEGF release in long/ultralong duration exercises and NO bioavailability in maximal or submaximal exercises lasting less than one hour.


El ejercicio físico moviliza Células Progenitoras Endoteliales (CPE) hacia la sangre periférica. Entre tanto, ese efecto parece depender de características del ejercicio, como duración e intensidad. El objetivo de este estudio fue verificar, por medio de revisión sistemática, el impacto de una única sesión de ejercicio aeróbico sobre la Movilización de CPE en individuos sanos y los potenciales mecanismos envueltos. La búsqueda bibliográfica fue realizada en las bases de datos electrónicas SciELO, LILACS, Cochrane, ClinicalTrials.gov, SPORTDiscus y Medline, en mayo de 2011. De los 178 estudios inicialmente identificados, 12 respondieron a los criterios de inclusión y fueron clasificados en cuanto a la calidad mediante criterios de la escala PEDro. La magnitud y la duración de la respuesta de Movilización de las CPE fueron mayores después de la realización de ejercicios de larga/ultra larga duración y están correlacionadas con niveles plasmáticos de factor de crecimiento endotelio vascular (VEGF). El pico de Movilización de esas células en respuesta a una sesión de ejercicio máximo o submáximo, con duración de hasta una hora, ocurre en el período inmediatamente después del esfuerzo y hasta una hora después de su interrupción. Un posible mecanismo es la biodisponibilidad del Óxido Nítrico (NO). La edad de los individuos y la intensidad del ejercicio parecen interferir en la respuesta de Movilización de las CPE. Ejercicios de larga/ultra larga duración promueven Movilización más acentuada de las CPE cuando son comparados a ejercicios máximos o submáximos. Los mecanismos envuelven la liberación del VEGF en ejercicios de larga/ultra larga duración y la biodisponibilidad de NO en ejercicios máximo y submáximo con hasta una hora de duración.


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Young Adult , Cell Movement/physiology , Endothelial Cells/physiology , Exercise/physiology , Nitric Oxide/metabolism , Vascular Endothelial Growth Factor A/blood , Endothelial Cells/cytology , Time Factors
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