RESUMO
Many central nervous system (CNS) diseases were thought to be untreatable due to the presence of the blood-brain barrier (BBB). The chemokine gradients secreted from CNS parenchyma can induce macrophage migration to the brain, induce firm adherence to the endothelium of BBB, and eventually to enter the brain parenchyma. Macrophages migrating into CNS can promote neuron regeneration, induce inflammation and angiogenesis. These properties can potentially allow macrophages to act as carriers for drug/nano formulations across the BBB, and reach the potential target sites. Many nanomaterials cannot be used for the management of CNS diseases because of their low carrying efficiency. Macrophage which transports nanomaterials to pathological sites is rendered as an attractive tool for the transportation of drugs to previously inaccessible regions within the brain parenchyma. Nanomaterials engulfed by macrophages can be released at target sites, and be used for therapeutic or diagnostic purposes. In this review, we focus on macrophages as the cell-carrier to deliver nano-drugs into CNS, describe the biological behavior of macrophages during pathological conditions and discuss the application of cell drug delivery system in recent years.
Assuntos
Doenças do Sistema Nervoso Central , Sistemas de Liberação de Medicamentos , Macrófagos , Preparações Farmacêuticas , Barreira Hematoencefálica , Doenças do Sistema Nervoso Central/tratamento farmacológico , HumanosRESUMO
High expression of connexins was found in a variety of cancers, but their role is still controversial. We investigated whether connexin43 (Cx43) contributed to bladder carcinogenesis through MAPK activation. In this study, we found that Cx43 expression was significantly increased in bladder cancer tissues and cell line. Overexpression of Cx43 in bladder cancer 5637 cells increased cell proliferation, promoted cell cycle progression, and inhibited apoptosis. Western blot showed that JNK and ERK pathways were dramatically activated in Cx43-overexpressed cells. Conversely, knockdown of Cx43 inhibited cell proliferation by increasing apoptosis and causing cell cycle arrest, concomitant with inhibition of JNK and ERK signaling. In addition, JNK and ERK pathways were also activated in bladder cancer tissues. In conclusion, abnormal high expression and cytoplasmic localization of Cx43 contributed to bladder cancer. Inhibition of Cx43 activity could be a potential therapeutic strategy for preventing the progression of bladder cancer.
Assuntos
Conexina 43/genética , Conexina 43/metabolismo , Citoplasma/metabolismo , Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Regulação para Cima , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismoRESUMO
OBJECTIVES: To study the rat brain trauma injury model and investigate the rules of transformation of expression of synaptophysin and its relationship between histology and radiology alternation after brain trauma injury. METHODS: 24 SD male rats aged three months were randomly divided into 4 groups,including a control group of 6 rats.The experimental group rats were received operation to build free falling brain trauma injury model.The rat were analyzed at 2,4,8 weeks after injury.The experimental group rat were killed after CT scan and functional evaluation,histological changes were measured through HE staining.Synaptophysin were observed by using immunofluorescence method and Western blot. RESULTS: After brain injury the functional evaluation of rat showed dysneuria.Edema and necrosis in neurons and local congestion at 24 h after injury,necrosis and solubility liquefaction at 2 weeks after injury,and histological defects at 4 weeks and 8 weeks after injury,were observed in HE staining in experimental group.The significant cerebral low density shadows at 24 h after injury,lightened in 2 weeks after injury,and disappeared at 4 weeks and 8 weeks after injury,left only the bone defects in CT images.Expression of synaptophysin in brain tissue was decreased from 2 weeks after injury and it was mild increased at 8 weeks after injury evaluated by immunofluorescence method and Western blot. CONCLUSIONS: The functional evaluation,histological and CT scan result indicate that we have built the rat brain trauma injury model successfully.The damage of synapse was correlated with histological and radiological result.The expression of synaptophysin was decreased form acute stage and gradually increased until 8 weeks after injury.This study can be applied as control in research of nerve regeneration after brain trauma injury.