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Objective To study the effect of inhibiting the phosphorylation of signal transducer and activator of transcription-3 (STAT3) on Th2 cell-mediated airway inflammation and airway remodeling,and to explore the role of STAT3 in the pathophysiology of bronchial asthma.Methods Forty Balb/c mice were randomly divided into control group(n =10),asthma group(n =10),AG490 by intraperitoneal group (n =10),and AG490 by inhalation group (n =10).The mice were sensitized with ovalbumin to establish the asthmatic model.The histological changes were evaluated by means of HE staining,while total broalchial wall thickness(Wat) and smooth muscle thickness(Wam) were measured by using image analysis system.The percentages of collagen deposition were detected by way of Masson's trichrome staining; the bronchoalveolar lavage fluid (BALF) were collected,the total cell and the cell differentials were counted,the levels of IL-4,IL-5 in BALF were measured by enzyme-linked immunosorbent assay; the lung tissue extracts were analyzed for phosphorylation of STAT3 (p-STAT3) by Western blot.The SPSS 13.0 software was used to analyze the data.Results 1.The histological changes by HE staining showed that less inflammatory cells infiltration in airway and around the pulmonary vascular in AG490 administration groups compared with asthmatic group.Wat,Wam and the percentages of collagen deposition in AG490 administration groups was significantly lower than that in asthmatic group(F =49.5,41.7,58.2,all P ＜ 0.05).2.The level of p-STAT3 in the lung of AG490 administration groups were significantly lower than those in asthmatic group(F =34.17,P ＜ 0.05).3.The total cells and eosinophils amounts in BALF of AG490 administration groups were significantly lower than those in asthmatic group (F =42.5,64.7,all P ＜ 0.05).The levels of IL-4,IL-5 in BALF of AG490 administration groups were significantly lower than those in asthmatic group,respectively (F =39.2,75.1,all P ＜ 0.05).Conclusions STAT3 signaling pathway is pivotal in Th2 cell-mediated airway inflammation and airway remodeling in asthmatic models,and AG490 can ameliorate airway inflammation and airway remodeling efficiently by inhibiting the phosphorylation of STAT3,and targeting this signaling pathway may be a novel therapy for asthma.
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Objective To evaluate the relationship between airway inflammation before treatment and asthma status and response to inhaled corticosteroids treatment in children with mild or moderate asthma. Methods Eighty-seven children diagnosed with mild or moderate asthma were enrolled as study group, 20 healthy children as control group. Sputum induction, cellular differential count, and the assaying of mediators in sputum supernatant were performed before treatment with corticosteroids. Eosinophil cationic protein were measured by enzyme-linked fluorescent assay, interleukin-8 and transforming growth factor-β_1 (TGF-β_1) were measured by enzyme linked immunosorbent assay. Pulmonary function tests were performed for small airway function on the baseline and methacholine bronchial provocation tests were performed to screen airway hyperresponsiveness. SPSS13.0 software was used to analyze the data. Results (1) Among the 87 patients, 64 patients were studied as eosinophil asthma (EA) group, 23 patients as non-eosinophil asthma (NEA) group according to the ratio of eosinophils in sputum. The percentages of inflammatory cells and level of ECP, IL-8 were of significant difference between the two groups (P < 0.05), other indexes as FEV_1% pred, PEF% pred, moderate-severe AHR%. small airway function were also of significant difference between the two groups (P < 0.05). (2) Patients in EA group showed significant improvement in pulmonary function, bronchial hyperresponsiveness and small airway function after treatment with inhaled corticosteroids compared with NEA group. (3) Multiple stepwise regression analysis showed that among the different baseline variants considered only baseline FEVl%pred, sputum eosinophil percentages (EOS%), sputum TGF-β_1 significantly correlated with the response to inhaled cortieosteroids, moreover, sputum eosinophil percentages had the closest correlation (β= 0.583, t = 6.214, P < 0.05). Conclusions There were different patterns of airways inflammation in children with mild or moderate asthma. Sputum eosinophilia was associated with asthma status. Low sputum eosinophils, low FEV_1%pred, high sputum TGF-β_1 before treatment predict poor response to treatment with inhaled corticosteroids. Evaluation of those baseline indexes may be helpful to an individualized therapeutic regime.
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The levels of total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, apolipoprotein (APO) A1 and APO B were lower in Bai Ku Yao than those in Han nationalities (all P<0.01). There was no significant difference in serum triglyceride levels and the ratio of Apo A1 to Apo B between two nationalities. Dyslipidemia was positively correlated with body mass index, waist circumference, total energy and total fat intakes, and inversely correlated with degree of physical activity and total dietary fiber intake in both ethnic groups. In addition, dyslipidemia was also positively correlated with age and alcohol consumption in Han, but not in Bai Ku Yao.
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BACKGROUND: The problem of the high rate of acute restenosis at an early and advanced stage has been a hot spot, while the stent with paclitaxel (poly-L-lactide, PLLA/polyglycolic acid, PGA) degradable material will resolve it. OBJECTIVE: To seek an ideal biologic degradable material used in biologic degradable stent. DESIGN, TIME AND SETTING: The comparative cytological study was performed at the Laboratory of Toxicology, Institute of Public Health, Jilin University (Key Laboratory of Radiobiology of Ministry of Public Health of China, Key Laboratory of Toxicology of Jilin Province) from July 2003 to July 2005. MATERIALS: Paclitaxel degradable material (PLLA/PGA) (PLLA:PGA= 9: l ) were offered by Changchun Applied Chemistry Institute of Chinese Academy of Science). Human umbilical arterial smooth muscle cells (SMCs) were purchased from Boster, Wuhan, China. METHODS: The sixth passage of SMCs were digested by 0.25% Trypsin under ambient temperature for 3 minutes, incubated in 10 mL 10% ox serum BMEM, and made into SMC suspension. The materials kept in hypothermal disinfectant Co60 were heated to 37 ℃ by waterbath after surface treatment, and then placed in a 6-well culture plate. SMC suspension was added into the middle of the materials. The density of cells was about 5×106/cm2. Cell suspension diffused around the materials gradually. At last, 10% ox serum BMEM culture solution was added into it, and cultivated in a 5% CO2 incubator at 37 ℃. The growth of cells in and surrounding the materials was observed by inverted microscope everyday. MAIN OUCOME MEASURES: The materials were obtained after culture for 3, 6, 12, 19, 26, 34 days and vacuum dehydration, and were weighed. The weight loss of materials was compared before and after culture. The average degradable rate of materials was calculated.RESULTS: Degradable material had no influence on the development of SMCs. The average degradation rate ex vivo was 0.45% per day. CONCLUSION: PLLA/PGA with good cellular compatibility could be applied to intravascular stents.
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Objective To detect the serum lipids levels in the subjects aged 40 years and over in the Guangxi Bai Ku Yao population. Methods A total of 485 subjects of Bai Ku Yao and 501 Han people aged 40 years and over were surveyed by cluster sampling methods. Informations on demography, diet and lifestyle were collected by standard questionnaires. Blood pressure, height,weight, waist circumference, serum lipids and apolipoproteins (apo) were measured, and body mass index (BMI) was calculated. Results Education level, height, weight, BMI, waist circumference,blood pressure levels, hypertensive prevalence, and the intakes of total energy, total fat, total protein, dietary cholesterol, and salt were higher in Han than in Bai Ku Yao (P<0.05 or P<0.01),whereas physical activity level, and the intakes of carbohydrate, vegetal protein, and total dietary fiber were higher in Bai Ku Yao than in Han (all P<0.001). The serum levels of total cholesterol,high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apo A1, and apo B were significantly lower in Bai Ku Yao than in Han [(4. 43±0. 90)vs. (4.96±1.04)mmol/L, P<0. 001;(1.73±0. 42) vs. (2.01±0. 49) mmol/L, P<0. 001;(2. 62±0. 75) vs. (2. 72±0. 78)mmol/L, P<0. 05;(1. 36±0. 33) vs. (1. 48±0. 24)g/L, P<0. 001;and (0. 86±0.23) vs. (0. 95±0. 22)g/L,P<0. 001 ;respectively]. There were no significant differences in serum triglyceride level and the ratio of apo Al over apo B between the two ethnic groups (P>0. 05). Conclusions There are significant differences in lipids levels and the risk factors between Bai Ku Yao and Han populations, which might result from different dietary habits, life styles, and physical activities.
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Aim To study the effect of S-methylisothiourea(SMT) on adriamy ci n (ADM) induced myocardial lipid peroxidation in rats.Methods T hirty-two Wistar rats were randomly divided into four groups: control group;SMT treated group ( SMT5.0 mg?kg -1,iv,only 1 time);ADM treated group (ADM 5.0 mg?kg -1, ip, only 1 time ); ADM with SMT treated group (the dos ageand method of ADM and SMT were similar to ADM treated group and SMT treated g roup, respectively).24 hour after of administration of the drugs, rats of all t he groups were killed.TBA method, DTNB method, nitrate reductase method, pyrogal lol autoxidation method and hemoglobin-oxidation method were used to determine the contents of lipid peroxide(LPO)and nitric oxide (NO), the activities of glut athione peroxidase (GPx) and superoxide dismutase (SOD) in myocardium, respectiv ely. The level of nitrotyrosine (NT) was determined by immunohistochemical metho d in myocardium.Results SMT significantly reduced the contents of LPO and NO, the activity of inducible nitric oxide synthase (iNOS), the level of NT in myocardium (P0.05).Conclusion SMT can inhibit myocardial lipid peroxidation induced by ADM. The mechanism may be that SMT can selective ly inhibited the activity of iNOS in myocardium induced by ADM, reduce productio n of NO in myocardium, thereby reduce production of peroxynitrite and protect the activities of SOD and GPx in myocardium.
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AIM: To study the effect of S-methylisothiourea(SMT) on adriamycin(ADM)-induced changes of superoxide dismutase and alutathione peroxidase activities in myocardial tissue of rats.METHODS: Rats were treated with ADM by intraperioneal injection (10.0 mg/kg body weight),and then the ADM-treated rats were intervened by SMT at different dosages by intravenous injection(once a day for three days).The contents of malondialdehyde(MDA) and NO_2~-/ NO_3~-,the activities of manganes superoxied dismutase(MnSOD),copper-zinc superoxide dismutase(Cu-Zn SOD),glutathione peroxidase(GPx) and inducible nitric oxide synthase(iNOS) were determined by spectrophotometry in myocardial tissue.The activity of isoenzymic CK-MB of creatine kinase(CK) was determined by enzymic rate method in serum.The expression of MnSOD mRNA,Cu-ZnSOD mRNA,GPx mRNA and iNOS mRNA were detected by reverse transcription-ploymerase chain reaction.RESULTS: The contents of MDA,NO~-_2/ NO~-_3,and iNOS activity of myocardial tissue,the activity of CK-MB in serum in SMT(5.0,10.0,20.0 mg/kg) intervention groups were significantly lower than those in ADM-treated group(P
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AIM: To study the effect of fructose-1, 6-diphosphate (FDP) on adriamycin(ADM)-induced cardiomyocyte apoptosis in rats. METHODS: Twenty-four Wistar rats were randomly divided into three groups: control group, ADM treated group and FDP intervention group. The contents of malondialdehyde (MDA) and NO - 2/NO - 3, the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were determined by colorimetric method in myocardial tissue, and the cardiomyocyte apoptosis was detected by TUNEL method in myocardial tissue, and the expression of inducible nitric oxide synthase (iNOS) mRNA, Bcl-2 mRNA and Bax mRNA in myocardial tissue were detected by in situ hybridization. RESULTS: The contents of NO - 2/NO - 3 and MDA in myocardial tissue, the expressive levels of iNOS mRNA and Bax mRNA in cardiomyocyes and its apoptotic amounts in FDP intervention group were significantly lower than those in ADM treated group ( P