RESUMO
Increasing evidence suggests that the cerebrospinal ï¬uid-contacting nucleus (CSF-contacting nucleus) mediates the transduction and regulation of pain signals. However, the precise molecular mechanisms remain unclear. Studies show that release of fractalkine (FKN) from neurons plays a critical role in nerve injury-related pain. We tested the hypothesis that release of FKN from the CSF-contacting nucleus regulates neuropathic pain, in a chronic constriction injury rat model. The results show that FKN is expressed by neurons, via expression of its only receptor CX3CR1 in the microglia. The levels of soluble FKN (sFKN) were markedly upregulated along with the increase in FKN mRNA level in rats subjected to chronic constriction injury. In addition, injection of FKN-neutralizing antibody into the lateral ventricle alleviated neuropathic pain-related behavior followed by reduction in microglial activation in the CSF-contacting nucleus. The results indicate that inhibition of FKN release by the CSF-contacting nucleus may ameliorate neuropathic pain clinically.
Assuntos
Núcleo Celular/metabolismo , Líquido Cefalorraquidiano/metabolismo , Quimiocina CX3CL1/metabolismo , Dor Crônica/metabolismo , Neuralgia/metabolismo , Limiar da Dor/fisiologia , Animais , Modelos Animais de Doenças , Injeções Intraventriculares , Masculino , Ratos , Ratos Sprague-Dawley , Regulação para CimaRESUMO
The main aim of this study was to explore the underlying molecular mechanisms and potential target molecules of pancreatic adenocarcinoma. The miRNA (GSE32678) and mRNA (GSE32676) expression profiles of patients with pancreatic ductal adenocarcinoma and healthy controls were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNA and differentially expressed genes were identified by analyzing the microarray algorithm after data preprocessing. Functional analysis was conducted by the Database for Annotation, Visualization and Integrated Analysis. miRNA-mRNA regulation pairs were obtained in TarMir database. The node degree of hsa-miR-200c, hsa-miR-429, and hsa-miR-200b (miRNA), and EFNB2, MYRIP, and PHF17 (mRNA) were extremely high in the miRNA-mRNA network, indicating that these miRNA and mRNA may play a key role in the development of pancreatic cancer. Our study screened out some target miRNAs and mRNAs for pancreatic ductal adenocarcinoma, which may be helpful in its diagnosis and treatment.
Assuntos
Carcinoma Ductal Pancreático/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Padrões de Referência , Neoplasias PancreáticasRESUMO
The aim of this study was to investigate the repair effect of human acellular amniotic membrane (HAAM) loading bone marrow mesenchymal stem cells (BMSCs) on articular cartilage defect in rabbits. Rabbit BMSCs were isolated and cultured, and they were then inoculated on HAAM to prepare the complex of HAAM and BMSCs. Twenty-four rabbits were randomly divided into groups A and B, with 12 animals in each group. The left and right sides were used as the experimental and control sides, respectively. The models of bilateral articular cartilage defect were established. The defect areas on the experimental side in groups A and B were implanted with the complex of HAAM and BMSCs and HAAM alone, respectively. The control sides of the two groups were not implanted with any material. In the 8th and 12th week after surgery, gross observation, histological examination and cartilage defect scoring were performed. In the 8th and 12th postoperative week, gross observation and histological observation showed that dense cartilage-like cells appeared in group A but not in group B, indicating preferable cartilage repair. The cartilage defect score on the experimental side in group A was 5.31 ± 0.68 in the 8th week and 3.23 ± 0.52 in the 12th week, and that in group A was significantly lower than in group B (P < 0.05). HAAM loading BMSCs has a good repair effect on articular cartilage defect under an in vitro environment.