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PURPOSE: Accumulating evidence has shown that dysregulation of microRNA-191 (miR-191) is closely associated with tumorigenesis and progression in a wide range of cancers. This study aimed to explore the potential role of miR-191 in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: miR-191 expression was assessed in 93 ESCC tissue specimens by real-time polymerase chain reaction, and survival analysis was performed via Kaplan-Meier and Cox regression analyses. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, plate colony-forming, BrdU, and Transwell assays were conducted to observe the effect of miR-191 on ESCC proliferation and invasion. Luciferase reporter and western blot assays were taken to identify target genes of miR-191. RESULTS: miR-191 was overexpressed in 93 cases of ESCC, compared with adjacent normal tissues, and miR-191 expression was significantly related to differentiation, depth of invasion, TNM stage, lymph node metastasis, and distant metastasis of tumor. Kaplan-Meier and Cox regression analyses demonstrated that overexpression of miR-191 was an independent and significant predictor of ESCC prognosis. Both gain-of-function and loss-of-function experiments showed that miR-191 promoted ESCC cell proliferation and invasion activities in vitro. Early growth response 1 (EGR1), a tumor suppressor, was predicted as a direct target of miR-191. Luciferase reporter and western blot assays proved that miR-191 reduced EGR1 expression by directly binding its 3' untranslated region. Moreover, EGR1 knockdown by siRNA enhanced ESCC cell growth and invasion. CONCLUSION: Our findings provide specific biological roles of miR-191 in ESCC survival and progression. Targeting the novel miR-191/EGR1 axis represents a potential new therapeutic way to block ESCC development.
Subject(s)
3' Untranslated Regions , Blotting, Western , Bromodeoxyuridine , Carcinogenesis , Carcinoma, Squamous Cell , Cell Proliferation , Epithelial Cells , In Vitro Techniques , Luciferases , Lymph Nodes , Neoplasm Metastasis , Prognosis , Real-Time Polymerase Chain Reaction , RNA, Small InterferingABSTRACT
BACKGROUND:Pulmonary aspergilosis is a disease caused by pulmonary fungal infection. Its diagnosis and treatment is usualy delayed because of nonspecific clinical symptoms, physicial sign and imaging changes as wel as uncertainties of histological and bacterial findings. Therefore, it is necessary to establish mouse models of invasive pulmonary aspergilosis to investigate the underlying pathological mechanism and novel therapeutic methods. OBJECTIVE: To establish mouse models of invasive pulmonary aspergilosis, detect the expression ofγ-interferon, Tol-like receptor 2 and Tol-like receptor 4, and discuss the mechanism of action underlying invasive pulmonary aspergilosis. METHODS:Seventy-five female BALB/c mice of clean grade, aged 6-8 weeks, were randomly and evenly divided into five groups: blank control group (group A), immunosuppressive model group treated with high concentrations of Aspergilus fumigatus spore suspension (group B), normal infection group treated with high concentration of Aspergilus fumigatus spore suspension (group C), immunosuppressive model group treated with low concentration of Aspergilus fumigatus spore suspension (group D), normal infection group treated with low concentration of Aspergilus fumigatus spore suspension (group E). First, mice in the groups B and D were intraperitonealy injected with cyclophosphamide to establish immunosuppressive models. The mice in the groups D, E (108 cfu/mL) and groups B, C (109 cfu/mL) were treated with 12 mL Aspergilus fumigatus spore suspension through the use of nebulizer. Mice in the group A were treated identicaly with sterile PBS. At 1, 3, 5 days of infection, the pathological change of lung tissue was observed, the mass concentration of γ-interferon in bronchoalveolar lavage fluid and the expression levels of γ-interferon mRNA and Tol-like receptor 2 and Tol-like receptor 4 mRNA and protein in the lung tissue were determined. RESULTS AND CONCLUSION:Abscess, spores and very severe bleeding and congestion, widenened alveolar septum and tracheal epithelial cel shedding and necrosis were observed in the mouse lung tissue in the group B. At 5 days of infection, the mass concentration of γ-interferon in bronchoalveolar lavage fluid and the expression ofγ-interferon mRNA in the lung tissue in the group B were significantly decreased compared with the group A (P < 0.05). Tol-like receptor 2 expression was strongly positive in the group B. Tol-like receptor 2 expression in the group C was significantly lower than that in the group B (P< 0.05). Tol-like receptor 4 expression was positive in the groups B and C, and its expression in the group C was significantly greater than in the group B (P < 0.05). The expression of Tol-like receptor 2, 4 mRNA in the mouse lung tissue of group B was significantly increased at 1, 3, 5 days of infection (P < 0.05). These results suggest that atomizing high concentration of aspergilus fumigatus spore suspension to immunosuppressive mice can establish stable invasive pulmonary aspergilosis models with typical pathological features. The infection of aspergilus fumigatus can activate tol-like receptor 2, 4 at the same time, and the pathological mechanism is closely related to organism’s immune defense function.
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Objective:To explore the effects the of Astragalus Polysaccharide on specific immune therapy in a mouse model of asthma.Methods:Ninety SPF(Specific pathogen Free) BALB/c mice were randomly divided into six groups.The experimental groups were sensitized with OVA,treated with SIT or APS or their joint application.Then the mice were excited with 1% OVA.24 hours after the last excition,the numbers of the total inflammation cells and esoinophils(EOS) in BALF were counted.The left lung tissues were used to perform histological analysis.IFN-γ and IL-4 in peripheral blood were analysed by ELISA.Results:After the therapy,asthma-associated lung inflammation was inhibited,and the numbers of total cells and EOS decreased.IFN-γ level was raised and IL-4 level was lowered.Conclusion:APS can enhance SIT.It may result from affecting production of both the IFN-γ and IL-4.
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OBJECTIVE To investigate pathogenetic condition and fungal detection on evaluating acute exacerbation of COPD(AECOPD),and the relation of the severity and risk of death during hospital stay.METHODS Samples of sputum,blood and pleural effusion from patients with bronchopulmonary candidiasis in our respiratory department were collected since from Jul 2007 to Jun 2007.All of patients carried out APACHEⅡ integrating,according to the results of APACHEⅡsubset to Knaus equations to calculate the risk of death during hospital stay.RESULTS Twenty-two strains of fungi were isolated from 119 patients(18.4%).Blood gas analysis of severe COPD patients indicated a respiratory failure tendency,the fungal detection rate was higher than that of mild or median COPD patients.The higher of APACHEⅡ accumulated points,the higher of fungal detection rate,and the higher of risk of death.CONCLUSIONS The most organisms in respiratory tract infection are bacterium.With number of admission times in hospital and severity of pathogenetic condition increased are,the opportunity of fungal infection is raised.Furthermore,the fungal infection associatively with exacerbation.Fungi become the ascendant causative organisms inducing the decrese in pulmonary function and severity of patients,we should think about of it when the therapeutic efficacy is worse.
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Objective To investigate correlation between Ile50Val polymorphism of IL-4 receptor gene and asthma and the impact on plasm total IgE,sIL-4R level.Methods the DNA is isolated from 2ml venous blood from 100 nomal subject and 100 asthma subject.The genetic polymorphism was identified by Allele-specific PCR techniquers,plasm total IgE,sIL-4R level was determined by ELISA.Results The frequency of genetype is significantly different be- tween control group and asthma group x~2=18.94,P
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Objective To investigate the effects of hypoxia on thyroid function in patients suffering from chronic pulmonary heart disease(CPHD).Methods Serum TT 3,TT 4 and TSH in 83 patients with different hypoxia chronic pulmonary heart disease were measured.Observe the changes and relations between TT 3,TT 4,TSH and Pa(O 2).Results The values of TT 3,TT 4 and TSH were (0 71?0 16)?g/L,(62 6?12 3)?g/L and(4 4?0 8)mU/L in patients with mild hypoxia CPHD.(0 49?0 13)?g/L,(33 2?8 5)?g/L and (5 3?0 7)mU/L in patients with moderate hypoxia CPHD.In the patients with severe hypoxia CPHD,they were (0 24?0 07)?g/L,(18 4?4 5)?g/L and (13 1?1 2)mU/L.In control group,they were (0 91?0 36)?g/L,(84 1?15 6)?g/L and (3 7?0 6)mU/L respectively.Pa(O 2) in patients with pulmonary heart disease had a positive relation with TT 3 and TT 4(P