RESUMO
Morpholine is a common chemical used as emulsifier in the preparation of wax coatings for some fruit to help them remain fresh and protect against insects and fungal contamination. It has been reported that morpholine has acute toxic effects on rodents. In the present study, morpholine concentrations were analysed in fruits (citrus fruits, apples, strawberries and grapes) and juices (apple juice and orange juice) in order to determine dietary exposure among the Chinese population. A total of 732 fruit and juice samples were collected during 2015-2016, which covered major foods in China. Fruit and juice consumption data were taken from China National Nutrient and Health Survey (2002) and include data from 16,407 fruit or juice consumers. It was found that mean dietary exposure to morpholine residues from fruits and/or juices for general Chinese consumers and children 2-6 years old were 0.42 and 1.24 µg/kg bw/day, respectively. The 97.5% intake in general Chinese consumers and children 2-6 years old were 2.25 and 6.90 µg/kg bw/day, respectively. The primary food sources of the morpholine dietary intake of general Chinese consumers were citrus fruits (57.4%) and apples (40.8%). These findings suggested that dietary exposure to morpholine in the Chinese population was lower than the acceptable daily intake of morpholine, and there are no health concerns.
Assuntos
Dieta/estatística & dados numéricos , Exposição Dietética , Contaminação de Alimentos/análise , Sucos de Frutas e Vegetais/análise , Frutas/química , Morfolinas/análise , ChinaRESUMO
AIMS: Previous study suggests that mTOR signaling pathway may play an important role in epileptogenesis. The present work was designed to explore the contribution of raptor protein to the development of epilepsy and comorbidities. METHODS: Mice with conditional knockout of raptor protein were generated by cross-bred Rptorflox/flox mice with nestin-CRE mice. The expression of raptor protein was analyzed by Western blotting in brain tissue samples. Neuronal death and mossy fiber sprouting were detected by FJB staining and Timm staining, respectively. Spontaneous seizures were recorded by EEG-video system. Morris water maze, open field test, and excitability test were used to study the behaviors of Rptor CKO mice. RESULTS: As the consequence of deleting Rptor, downstream proteins of raptor in mTORC1 signaling were partly blocked. Rptor CKO mice exhibited decrease in body and brain weight under 7 weeks old and accordingly, cortical layer thickness. After kainic acid (KA)-induced status epilepticus, overactivation of mTORC1 signaling was markedly reversed in Rptor CKO mice. Although low frequency of spontaneous seizure and seldom neuronal cell death were observed in both Rptor CKO and control littermates, KA seizure-induced mossy fiber spouting were attenuated in Rptor CKO mice. Additionally, cognitive-deficit and anxiety-like behavior after KA-induced seizures were partly reversed in Rptor CKO mice. CONCLUSION: Loss of the Rptor gene in mice neural progenitor cells affects normal development in young age and may contribute to alleviate KA seizure-induced behavioral abnormalities, suggesting that raptor protein plays an important role in seizure comorbidities.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/deficiência , Regulação da Expressão Gênica/genética , Transtornos Mentais/etiologia , Transtornos Mentais/genética , Convulsões/complicações , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Ansiedade/etiologia , Ansiedade/genética , Encéfalo/patologia , Modelos Animais de Doenças , Agonistas de Aminoácidos Excitatórios/toxicidade , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Homeodomínio/metabolismo , Ácido Caínico/toxicidade , Aprendizagem em Labirinto/fisiologia , Alvo Mecanístico do Complexo 1 de Rapamicina , Transtornos Mentais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Complexos Multiproteicos/metabolismo , Nestina/genética , Nestina/metabolismo , Proteínas Nucleares/metabolismo , Proteína Regulatória Associada a mTOR , Proteínas Repressoras/metabolismo , Convulsões/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismoAssuntos
Condrócitos/metabolismo , Animais , Conservadores da Densidade Óssea/farmacologia , Diferenciação Celular/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Colágeno Tipo X/genética , Colágeno Tipo X/metabolismo , Genes Reporter , Camundongos , Camundongos Transgênicos , Osteogênese/efeitos dos fármacos , Regiões Promotoras Genéticas , Tamoxifeno/farmacologiaRESUMO
BACKGROUND: Epithelial-mesenchymal transition (EMT) is the major pathophysiological process in lung fibrosis observed in chronic obstructive pulmonary disease (COPD) and lung cancer. Smoking is a risk factor for developing EMT, yet the mechanism remains largely unknown. In this study, we investigated the role of Rac1 in cigarette smoke (CS) induced EMT. METHODS: EMT was induced in mice and pulmonary epithelial cells by exposure of CS and cigarette smoke extract (CSE) respectively. RESULTS: Treatment of pulmonary epithelial cells with CSE elevated Rac1 expression associated with increased TGF-ß1 release. Blocking TGF-ß pathway restrained CSE-induced changes in EMT-related markers. Pharmacological inhibition or knockdown of Rac1 decreased the CSE exposure induced TGF-ß1 release and ameliorated CSE-induced EMT. In CS-exposed mice, pharmacological inhibition of Rac1 reduced TGF-ß1 release and prevented aberrations in expression of EMT markers, suggesting that Rac1 is a critical signaling molecule for induction of CS-stimulated EMT. Furthermore, Rac1 inhibition or knockdown abrogated CSE-induced Smad2 and Akt (PKB, protein kinase B) activation in pulmonary epithelial cells. Inhibition of Smad2, PI3K (phosphatidylinositol 3-kinase) or Akt suppressed CSE-induced changes in epithelial and mesenchymal marker expression. CONCLUSIONS AND GENERAL SIGNIFICANCE: Altogether, these data suggest that CS initiates EMT through Rac1/Smad2 and Rac1/PI3K/Akt signaling pathway. Our data provide new insights into the fundamental basis of EMT and suggest a possible new course of therapy for COPD and lung cancer.
Assuntos
Transição Epitelial-Mesenquimal , Neuropeptídeos/fisiologia , Nicotiana/efeitos adversos , Alvéolos Pulmonares/patologia , Fumaça/efeitos adversos , Proteínas rac1 de Ligação ao GTP/fisiologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Proteína Smad2/fisiologia , Fator de Crescimento Transformador beta1/análise , Fator de Crescimento Transformador beta1/biossínteseRESUMO
Cigarette smoke (CS), the major cause of chronic obstructive pulmonary disease, contains a variety of oxidative components that were implicated in the regulation of Src homology domain 2-containing protein tyrosine phosphatase 2 (Shp2) activity. However, the contribution of Shp2 enzyme to chronic obstructive pulmonary disease pathogenesis remains unclear. We investigated the role of Shp2 enzyme in blockading CS-induced pulmonary inflammation. Shp2 levels were assessed in vivo and in vitro. Mice (C57BL/6) or pulmonary epithelial cells (NCI-H292) were exposed to CS or cigarette smoke extract (CSE) to induce acute injury and inflammation. Lungs of smoking mice showed increased levels of Shp2, compared with those of controls. Treatment of lung epithelial cells with CSE showed elevated levels of Shp2 associated with the increased release of IL-8. Selective inhibition or knockdown of Shp2 resulted in decreased IL-8 release in response to CSE treatment in pulmonary epithelial cells. In comparison with CS-exposed wild-type mice, selective inhibition or conditional knockout of Shp2 in lung epithelia reduced IL-8 release and pulmonary inflammation in CS-exposed mice. In vitro biochemical data correlate CSE-mediated IL-8 release with Shp2-regulated epidermal growth factor receptor/Grb-2-associated binders/MAPK signaling. Our data suggest an important role for Shp2 in the pathological alteration associated with CS-mediated inflammation. Shp2 may be a potential target for therapeutic intervention for inflammation in CS-induced pulmonary diseases.
Assuntos
Pneumonia/imunologia , Pneumonia/patologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/fisiologia , Fumar/efeitos adversos , Fumar/patologia , Produtos do Tabaco/toxicidade , Doença Aguda , Animais , Linhagem Celular , Modelos Animais de Doenças , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/prevenção & controle , Interleucina-8/metabolismo , Interleucina-8/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Pneumonia/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 11/deficiência , Alvéolos Pulmonares/imunologia , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/patologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Fumar/metabolismoRESUMO
Airway inflammation plays important roles in the pathogenesis of acute respiratory distress syndrome (ARDS), asthma and chronic obstructive pulmonary disease (COPD), and anti-inflammatory treatment effectively improves the symptoms of these diseases. To develop the potentially therapeutic compounds for the treatment of pulmonary inflammation, we investigated the effects of licorice flavonoids (LF) extracted from the roots of Glycyrrhiza uralensis (licorice) on lipopolysaccharide (LPS)-induced acute pulmonary inflammation in mice. Acute pulmonary inflammation was induced by intracheal instillation with LPS, treatment with LF at dosages of 3, 10 and 30 mg/kg significantly reduced the LPS-induced inflammatory cells, including neutrophils, macrophages and lymphocytes accumulation in bronchoalveolar lavage fluids (BALF), among these inflammatory cells, LF predominately inhibited neutrophil infiltration, and the maximal effect (30 mg/kg) was as comparable as dexamethasone treatment at 1 mg/kg. Consistent with its effects on neutrophil infiltration, LF treatment significantly increased LPS-induced BALF superoxide dismutase activity, and significantly decreased lung myeloperoxidase activity as well. Furthermore, treatment with LF at 30 mg/kg significantly reduced LPS-induced lung TNFalpha and IL-1beta mRNA expression at 6 h and 24 h after LPS instillation, respectively. Finally, LF at different dosages not only significantly decreased the elevation of lung water content, but also markedly attenuated LPS-induced histological alteration. Therefore, we suggest that LF effectively attenuates LPS-induced pulmonary inflammation through inhibition of inflammatory cells infiltration and inflammatory mediator release which subsequently reduces neutrophil recruitment into lung and neutrophil-mediated oxidative injury, and this study provides with the potential rationale for development of anti-inflammatory compounds from flavonoid extracts of licorice.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Flavonoides/uso terapêutico , Glycyrrhiza/química , Infiltração de Neutrófilos/imunologia , Neutrófilos/imunologia , Pneumonia/tratamento farmacológico , Doença Aguda , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Feminino , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Peroxidase/antagonistas & inibidores , Peroxidase/metabolismo , Pneumonia/imunologia , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To evaluate the pharmacological effects of Liangyuan Pipagao on cough reflex and ciliary action. Liangyuan Pipagao is a compound preparation of traditional Chinese medicine. METHODS: Cough was induced by aerosol citric acid in guinea pigs and aerosol capsacin in mice. Excretion function of the airway in mice was determined by phenol red method. Ciliary movement function of frog esophagus was examined by a migration method of charcoal granules. RESULTS: Liangyuan Pipagao inhibited both the citric acid-induced cough in guinea pigs and capsacin-induced cough in mice. ID(50)value 2.64 g/kg (95%Cl1.12 approximately 6.19) and 11.40 g/kg (95%Cl5.76 approximately 22.58) respectively. Further, Liangyuan Pipagao increased phenol red excretion in mice airways and stimulated ciliary action of frog esophagusin a dose-dependent fashion. ED(50) value 7.70 g/kg (95%Cl 4.62 approximately 12.83) and EC(25) value 1.07 X 10(-4) (95% Cl 0.394 approximately 2.92x10(-4)) respectively. CONCLUSION: Liangyuan Pipagao a traditional Chinese medicine may have anti-tussive as well as expectorant actions.