RESUMO
Palmatine (Pal), a plant-based isoquinoline alkaloid, was initially isolated from Coptidis Rhizoma (CR, Huanglian in Chinese) and considered to be a potential non-antibiotic therapeutic agent that can safely and effectively improve Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). However, underlying mechanisms are unclear. In this study, we explored the protective effect of Pal on H. pylori induced CAG in vivo and in vitro. As a result, Pal alleviated the histological damage of gastric mucosa and the morphological changes of gastric epithelial cell (GES-1) caused by H. pylori. Furthermore, Pal significantly inhibited the expression of EGFR-activated ligand genes, including a disintegrin and metalloproteinase 17 (ADAM17) and heparin-binding epidermal growth factor-like growth factor (HB-EGF), and the proinflammatory factors, such as chemokine 16 (CXCL-16) and interleukin 8 (IL-8), were suppressed. In addition, Pal attenuated inflammatory infiltration of CD8+ T cells while promoted Reg3a expression to enhance host defense. Taken together, we concluded that Pal attenuated the MMP-10 dependent inflammatory response in the gastric mucosa by blocking ADAM17/EGFR signaling, which contributed to its gastrointestinal protective effect.
Assuntos
Anti-Inflamatórios/uso terapêutico , Alcaloides de Berberina/uso terapêutico , Gastrite Atrófica/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Inibidores de Metaloproteinases de Matriz/uso terapêutico , Proteína ADAM17/genética , Proteína ADAM17/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Alcaloides de Berberina/farmacologia , Linhagem Celular , Doença Crônica , Receptores ErbB/genética , Receptores ErbB/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Gastrite Atrófica/etiologia , Gastrite Atrófica/genética , Gastrite Atrófica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologia , Helicobacter pylori , Humanos , Masculino , Metaloproteinase 10 da Matriz/genética , Metaloproteinase 10 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Ratos Sprague-DawleyRESUMO
AIMS: In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated. MATERIALS AND METHODS: H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured. KEY FINDINGS: Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.
Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Gastrite Atrófica/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Fatores Reguladores de Interferon/genética , Interferon gama/genética , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL1/antagonistas & inibidores , Quimiocina CXCL1/genética , Quimiocina CXCL1/imunologia , Quimiocina CXCL9/antagonistas & inibidores , Quimiocina CXCL9/genética , Quimiocina CXCL9/imunologia , Doença Crônica , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Gastrite Atrófica/genética , Gastrite Atrófica/imunologia , Gastrite Atrófica/microbiologia , Regulação da Expressão Gênica , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/patogenicidade , Humanos , Fatores Reguladores de Interferon/antagonistas & inibidores , Fatores Reguladores de Interferon/imunologia , Interferon gama/antagonistas & inibidores , Interferon gama/imunologia , Interleucina-17/agonistas , Interleucina-17/genética , Interleucina-17/imunologia , Masculino , Proteínas NLR/antagonistas & inibidores , Proteínas NLR/genética , Proteínas NLR/imunologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Uridina Fosforilase/antagonistas & inibidores , Uridina Fosforilase/genética , Uridina Fosforilase/imunologiaRESUMO
In order to reveal the accumulation trend of polysaccharides in Dendrobium catenatum and determine the effect of sampling time on polysaccharides, D. Catenatum D21 clone was harvested from January to December after culturing for 2 to 5 months in the growth chamber with constant temperature. Polysaccharides were determined by phenol-sulfuric acid method and the monosaccharide compositions were analyzed by pre-column derivative-UPLC. The results showed that the content of polysaccharide and its key component mannose was positively correlated with the culture time, but the contents of polysaccharides in all kinds of culture peaked from 5 to 6 months, which were consistent with the trend of field planting. The results suggested that the trend of polysaccharide accumulation in the plant could be related to the life rhythm of the sensory seasons of D. catenatum, which was significantly affected by the harvesting season, even under the constant condition of the culture chamber.
Assuntos
Dendrobium/química , Polissacarídeos/química , Estações do Ano , Compostos Fitoquímicos/química , TemperaturaRESUMO
BACKGROUND: Carbapenem-resistant Acinetobacter baumannii poses a significant threat to hospitalized patients, as few therapeutic options remain. Thus, we investigated the molecular epidemiology and mechanism of resistance of carbapenem-resistant A.baumannii isolates in Beijing, China. METHODS: Carbapenem-resistant A.baumannii isolates (n = 101) obtained between June 2009 and November 2014 were used. Multilocus sequence typing (MLST) and PCR assays for class C and D ß-lactamase were performed on all isolates. S1 nuclease pulsed-field gel electrophoresis (PFGE) and Southern blot hybridization were performed to identify the resistance gene location. RESULTS: All 101 A.baumannii isolates were highly resistant to frequently used antimicrobials, and were considered multidrug resistant. A total of 12 sequence types (STs) were identified, including 10 reported STs and 2 novel STs. Eighty-seven isolates were classified to clonal complex 92 (CC92), among which ST191 and ST195 were the most common STs. The bla OXA-23 gene was positive in most (n = 95) of the A.baumannii isolates. Using S1-nuclease digestion PFGE and Southern blot hybridization, 3 patterns of plasmids carrying bla OXA-23 were confirmed. ST191 and ST195 (both harboring bla OXA-23 ) caused outbreaks during the study period, and this is the first report of outbreaks caused by ST191 and ST195 in north China. CONCLUSION: bla OXA-23 -producing A.baumannii ST191 and ST 195 isolates can disseminate in a hospital and are potential nosocomial outbreak strains. Surveillance of imipenem-resistant A.baumannii and antimicrobial stewardship should be strengthened.
Assuntos
Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/genética , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , beta-Lactamases/genética , Acinetobacter baumannii/classificação , Acinetobacter baumannii/isolamento & purificação , Técnicas de Tipagem Bacteriana , China/epidemiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Seguimentos , Humanos , Imipenem/uso terapêutico , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Tipagem de Sequências MultilocusRESUMO
In this paper, surface-enhanced Raman scattering (SERS) spectra of maleic hydrazide (MH, 6-hydroxy-3(2H)-pyridazinone) were studied by using citrate-reduced gold colloidal nanoparticles. Comparisons between the prominent SERS bands and the precise mode descriptions predicted through density functional theory (DFT) simulations at the B3LYP/6-311++g(d,p) level allowed an in-depth orientation analysis of the adsorbed species on gold surfaces. And main forms of hydrogen bonds in the solid state of MH were also determined to be O-Hâ¯O. Furthermore, the effects of concentration and pH on the SERS spectra of the molecule were discussed. It is found that with the different adsorbate concentration, the SERS spectra of MH show significant changes in their features, indicating different orientations and adsorption sites of the molecule on the gold colloidal surface. The SERS and absorption spectra under different pH conditions show that a basic environment leads to the deprotonation of N2 and the nearly parallel orientation of the MH molecule on the gold surface. Moreover, the enhanced characteristic bands were observed at MH concentrations down to about 1 ppm with the gold colloids, demonstrating a potential of the technique in the analysis of MH residues.