RESUMO
In this paper, we aimed to explore the potential mechanism underlying atopic dermatitis (AD) and its association with asthma. The BALB/c mice were randomly assigned to three groups, including the vehicle control (VD) group, the AD group, and the treatment (TR) group. The AD mice model was successfully constructed in the AD and TR group. The dermatitis severity scores and skin lesions were significantly increased in AD mice after DNCB application. Airway responsiveness in the AD group was significantly higher than in the TR group. The number of inflammatory cells was increased in skin lesions and bronchoalveolar lavage fluid (BALF) of AD mice. The levels of IL-4, IL-5, IFN-γ, and OVA-IgE in BALF supernatants of mice in the AD group were higher than those in the VC group. All the changes in AD mice were decreased by tacrolimus. These results indicate that AD may be a significant risk factor for atopic asthma development.
Assuntos
Asma/etiologia , Dermatite Atópica/complicações , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Dinitroclorobenzeno/farmacologia , Eczema , Camundongos , Camundongos Endogâmicos BALB C , Tacrolimo/farmacologiaRESUMO
Nonsmallcell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases, with a 5year survival rate of <15%. 1Oacetylbritannilactone (ABL), a natural chemical component obtained from inula britannica, a Chinese traditional medicine, has been demonstrated to have anticancer activity. In the present study, the antiproliferative and proapoptotic abilities of ABL alone or in combination with gemcitabine in a human NSCLC cell line were investigated. A549 cells were treated in vitro with ABL, gemcitabine, and a combination of ABL and gemcitabine for 72 h. The results demonstrated that ABL and gemcitabine inhibited cell growth and induced apoptosis of A549 cells. These effects were more potent following the combination of ABL and gemcitabine treatment than either agent alone. Furthermore, the signal transduction analysis revealed nuclear factor (NF)κB expression was significantly decreased by ABL and the combination treatment. The inhibitor nuclear factor κBα (IκBα) and Bax levels were upregulated whereas Bcl2 was substantially downregulated following treatment. The present findings suggest that ABL combined with gemcitabine elicits potent apoptosis of lung cancer cells and therefore, ABL has the potential to be developed as a chemotherapeutic agent.
Assuntos
Antineoplásicos/farmacologia , Desoxicitidina/análogos & derivados , Células Epiteliais/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Lactonas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/farmacologia , Combinação de Medicamentos , Sinergismo Farmacológico , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Proteínas I-kappa B/agonistas , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Inibidor de NF-kappaB alfa , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Transdução de Sinais , Proteína X Associada a bcl-2/agonistas , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , GencitabinaRESUMO
This study investigated the effect of Panax notoginseng saponins (PNS) on acute lung injury (ALI) induced by oleic acid (OA) and lipopolysaccharide (LPS). A total of 28 Wistar rats were divided into four groups: sham; sham + PNS; OALPSinduced ALI and ALI + PNS. Lung tissue histology, lung wettodry (W/D) weight ratio, extravascular lung water (EVLW) and epithelial sodium channel α (αENaC) mRNA and protein expression were examined. In addition, levels of inï¬ammatory cytokines, including tumor necrosis factor α (TNFα), interleukin (IL)6 and IL10, as well as total leukocyte and neutrophil counts, were analyzed in rat bronchoalveolar lavage fluid (BALF) and serum. ALI + PNS rats were observed to exhibit significantly lower pulmonary parenchymal damage and EVLW compared with ALI rats. Furthermore, total leukocyte and neutrophil counts, and levels of inï¬ammatory cytokines were significantly decreased following PNS administration in ALI rats. In addition, the decrease in αENaC mRNA and protein expression observed in the lung tissue of ALI rats was partially restored following PNS treatment. PNS treatment was demonstrated to ameliorate OALPSinduced ALI, potentially through restoration of αENaC mRNA and protein expression and through PNSinduced antiinï¬ammatory effects.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/efeitos adversos , Ácido Oleico/efeitos adversos , Panax notoginseng/química , Saponinas/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Canais Epiteliais de Sódio/genética , Canais Epiteliais de Sódio/metabolismo , Interleucina-10/sangue , Interleucina-6/sangue , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Lipopolissacarídeos/administração & dosagem , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND AND OBJECTIVE: Epidemiological evidence indicates a close link between exposure to fungi and deterioration of asthma. However, the role of fungi as an exogenous precipitant for initiation and progression of asthma has been incompletely explored. In this study, the effects of Aspergillus fumigatus exposure on airway inflammation and remodelling in a rat model of chronic asthma were investigated. METHODS: The rat model of chronic asthma was established by systemic sensitization and repeated challenge with ovalbumin (OVA). The asthmatic rats were exposed to chronic intranasal inhalation of A. fumigatus spores. Changes in airway inflammation, remodelling and BHR were measured after exposure to the fungus. RESULTS: Chronic inhalation of A. fumigatus spores elevated the production of T helper 2 (Th2) cytokines, increased the concentration of total serum IgE, and resulted in the recruitment of eosinophils and lymphocyte infiltration into the airways of asthmatic rats. Goblet cell hyperplasia, mucus hyperproduction and subepithelial collagen deposition were also induced by inhalation of the fungus. The remodelling changes induced by inhalation of the fungus paralleled the changes in BHR in this rat model of asthma. CONCLUSIONS: Chronic exposure to A. fumigatus aggravated Th2 airway inflammation, promoted airway remodelling and increased BHR in OVA-sensitized and -challenged rats.
Assuntos
Aspergillus fumigatus , Asma/microbiologia , Asma/patologia , Pneumonia/microbiologia , Pneumonia/patologia , Administração Intranasal , Animais , Aspergillus fumigatus/patogenicidade , Asma/induzido quimicamente , Movimento Celular , Doença Crônica , Colágeno/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Eosinófilos/patologia , Imunoglobulina E/sangue , Masculino , Ovalbumina , Pneumonia/metabolismo , Ratos , Ratos Wistar , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/microbiologia , Hipersensibilidade Respiratória/patologia , Esporos Fúngicos , Células Th2/metabolismo , Células Th2/patologiaRESUMO
OBJECTIVE: A case of primary pigmented nodular adrenal disease (PPNAD) was first diagnosed in Ruijin Hospital, Shanghai, China and molecular genetic research was then carried on the proband and his family members. METHODS: History and laboratory tests were routinely taken. Liddle's test, adrenal CT and pituitary magnetic resonance imaging were also carried out. Complete family history was obtained and eight of the family members donated their blood for DNA extraction. Polymerase chain reaction was done on all the exons of PRKAR1A gene and the product of the reaction was sequenced with ABI 3700. The right adrenal of the patient was then resected, part of the tissue was preserved in liquid nitrogen for DNA/RNA extraction and the remaining sent to Department of Pathology. RESULTS: The patient presented an atypical appearance of Cushing's syndrome. His father had a typical history of cardiac myoma. Cortisone level could not be refrained in Liddle's test for the patient. Imaging examination presented a nodular adrenal and a full pituitary. A novel mutation of PRKAR1A-S147N was found in both the patient's and his father's gene. CONCLUSIONS: This is the first patient diagnosed as PPNAD based on his clinical manifestations, laboratory tests and imaging and pathological examinations. According to the history of his father and the results of molecular genetic analysis, the diagnosis of Carney complex can be established on this patient and his father. It is also the first time that this kind of point mutation was found in Chinese people.