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World J Gastroenterol ; 25(33): 4835-4849, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31543677


Liver fibrosis is the common pathological basis of all chronic liver diseases, and is the necessary stage for the progression of chronic liver disease to cirrhosis. As one of pathogenic factors, inflammation plays a predominant role in liver fibrosis via communication and interaction between inflammatory cells, cytokines, and the related signaling pathways. Damaged hepatocytes induce an increase in pro-inflammatory factors, thereby inducing the development of inflammation. In addition, it has been reported that inflammatory response related signaling pathway is the main signal transduction pathway for the development of liver fibrosis. The crosstalk regulatory network leads to hepatic stellate cell activation and proinflammatory cytokine production, which in turn initiate the fibrotic response. Compared with the past, the research on the pathogenesis of liver fibrosis has been greatly developed. However, the liver fibrosis mechanism is complex and many pathways involved need to be further studied. This review mainly focuses on the crosstalk regulatory network among inflammatory cells, cytokines, and the related signaling pathways in the pathogenesis of chronic inflammatory liver diseases. Moreover, we also summarize the recent studies on the mechanisms underlying liver fibrosis and clinical efforts on the targeted therapies against the fibrotic response.

Dig Liver Dis ; 51(12): 1665-1670, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31420229


BACKGROUND: Helicobacter pylori (H. pylori) infection in gastric mucosa is the main risk factor for gastric cancer. The purpose of this study was to assess the value of the linked-color imaging (LCI) score for the identification of H. pylori-associated gastritis. METHODS: A total of 358 patients were enrolled in the study. H. pylori was positive in 127 cases and negative in 231 cases. Redness of fundus glands, granular erosion, purple mucus (+) and mucus lake turbidity were investigated by the LCI mode of endoscopy. Logistic regression was used to screen the observation indexes and their relative partial regression coefficients, which were helpful for the differential diagnosis of H. pylori infection. Then, each observation index was scored according to the partial regression coefficient. RESULTS: Using a total scores of 3.5 as the cut-off value, the sensitivity and specificity were 83.8% and 99.5%, respectively, for the differential diagnosis of H. pylori gastritis. The area under the curve was 95.3%. CONCLUSIONS: The LCI score showed high sensitivity and specificity for the differential diagnosis of H. pylori-associated gastritis and is an effective method for identifying H. pylori infection in gastric mucosa.

PLoS Biol ; 16(4): e2002909, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29652889


The rostromedial tegmental nucleus (RMTg), also called the GABAergic tail of the ventral tegmental area, projects to the midbrain dopaminergic system, dorsal raphe nucleus, locus coeruleus, and other regions. Whether the RMTg is involved in sleep-wake regulation is unknown. In the present study, pharmacogenetic activation of rat RMTg neurons promoted non-rapid eye movement (NREM) sleep with increased slow-wave activity (SWA). Conversely, rats after neurotoxic lesions of 8 or 16 days showed decreased NREM sleep with reduced SWA at lights on. The reduced SWA persisted at least 25 days after lesions. Similarly, pharmacological and pharmacogenetic inactivation of rat RMTg neurons decreased NREM sleep. Electrophysiological experiments combined with optogenetics showed a direct inhibitory connection between the terminals of RMTg neurons and midbrain dopaminergic neurons. The bidirectional effects of the RMTg on the sleep-wake cycle were mimicked by the modulation of ventral tegmental area (VTA)/substantia nigra compacta (SNc) dopaminergic neuronal activity using a pharmacogenetic approach. Furthermore, during the 2-hour recovery period following 6-hour sleep deprivation, the amount of NREM sleep in both the lesion and control rats was significantly increased compared with baseline levels; however, only the control rats showed a significant increase in SWA compared with baseline levels. Collectively, our findings reveal an essential role of the RMTg in the promotion of NREM sleep and homeostatic regulation.

Movimentos Oculares/fisiologia , Vias Neurais/fisiologia , Receptores Muscarínicos/genética , Sono/fisiologia , Área Tegmentar Ventral/fisiologia , Animais , Channelrhodopsins/genética , Channelrhodopsins/metabolismo , Clozapina/análogos & derivados , Clozapina/farmacologia , Dopamina/metabolismo , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/fisiologia , Núcleo Dorsal da Rafe/anatomia & histologia , Núcleo Dorsal da Rafe/efeitos dos fármacos , Núcleo Dorsal da Rafe/fisiologia , Eletrodos Implantados , Eletroencefalografia , Genes Reporter , Ácido Ibotênico/toxicidade , Locus Cerúleo/anatomia & histologia , Locus Cerúleo/efeitos dos fármacos , Locus Cerúleo/fisiologia , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Mesencéfalo/anatomia & histologia , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/fisiologia , Vias Neurais/anatomia & histologia , Vias Neurais/efeitos dos fármacos , Optogenética , Parte Compacta da Substância Negra/anatomia & histologia , Parte Compacta da Substância Negra/efeitos dos fármacos , Parte Compacta da Substância Negra/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores Muscarínicos/metabolismo , Privação do Sono/fisiopatologia , Técnicas Estereotáxicas , Área Tegmentar Ventral/anatomia & histologia , Área Tegmentar Ventral/efeitos dos fármacos , Vigília/fisiologia , Ácido gama-Aminobutírico/metabolismo
Sheng Wu Gong Cheng Xue Bao ; 22(2): 220-5, 2006 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-16607947


The cDNA encoding human Vascular Endothelial Growth Factor 165 (VEGF165) was amplified using RT-PCR from human tonsil tissue and cloned into eukaryotic expression vector pcDNA3.1 (+). The recombinant plasmid pcDNA/V was transferred into 293 cells mediated by liposome and the cells stably expressing VEGF were selected under the pressure of G418. ELISA and Western blotting demonstrated that the eukaryotic expression vector pcDNA/V was successfully constructed and its corresponding protein could be expressed efficiently in vitro. Chick Charioallantoic Membrane (CAM) bioassay showed that recombinant protein has biological activity of hVEGF. Model rats with acute myocardial ischemia were used to further study the expression of VEGFin vivo. The model rats were divided randomly into three groups: control group, pcDNA3.1 (+) group and pcDNA/V group. 50microL naked plasmid DNA or saline was intramyocardially injected at three sites into the border zone of infarction. The hearts of rats were excised and fixed histologically, then the infarction sizes were studied by immunohistochemical staining and electron microscope after four weeks. Immunohistochemical staining for VEGF appeared to be negative in control and pcDNA3.1 (+) groups. In pcDNA/V group, myocardial cells in infarction border zone showed positive staining for VEGF in cytoplasm. Ultrastructural anaylsis showed that there were visible hyperplasia of vascular endothilium in pcDNA/V group. The control and pcDNA3.1 (+) groups showed less capillary hyperplasia. In this study, VEGF165 gene was successfully cloned and its protein expressed in vitro and in vivo was of bioactivity, which provides a basis for the further study of biological functions of human VEGF.

Terapia Genética , Infarto do Miocárdio/terapia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Linhagem Celular , Galinhas , Membrana Corioalantoide/irrigação sanguínea , Modelos Animais de Doenças , Humanos , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/genética , Transfecção , Fator A de Crescimento do Endotélio Vascular/biossíntese