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ABSTRACT: Background and Objectives The role of CCR2-V64I polymorphism in various cancers has been reported in many studies. However, results from published studies on the association between CCR2-V64I polymorphism and cancer risk are conflicting. Therefore, we performed a meta-analysis to estimate the overall cancer risk associated with the polymorphism. METHODS: Electronic searches of Pubmed and EMBASE were conducted for all publications on the association between this variant and cancer. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association. RESULTS: Sixteen studies with 2661 cancer patients and 5801 healthy controls were included. Overall, significant association was found between the CCR2-V64I polymorphism and cancer risk (OR=1.84, 95% CI=1.35-2.51, AA vs GA/GG, p=0.37). In the subgroup analysis stratified by cancer types, there was a significant association between this polymorphism and bladder cancer (OR=2.06, 95% CI=1.02-4.15, AA vs GA/GG, p=0.11), cervical cancer (OR=3.34, 95% CI=1.48-7.50, AA vs GG, p=0.56), and oral cancer (OR=2.04, 95% CI=1.46-2.84, GA vs GG, p=0.70). In the subgroup analysis stratified by ethnicities, an increased cancer risk was also found in Europeans (OR=2.31, 95% CI=1.45-3.68, AA vs GA/GG, p=0.16) and Asians (OR=1.88, 95% CI=1.12-3.16, AA vs GA/GG, p=0.92). CONCLUSION: This meta-analysis suggested that CCR2-V64I polymorphism may contribute to an increased risk of cancer.
Gene 04/2013; · 2.34 Impact Factor
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ABSTRACT: BACKGROUND: A variety of studies have evaluated the associations between polymorphisms in the promoter regions of the hMLH1 and cancer risk. However, the results remain inconclusive. To better understand the roles of the hMLH1 polymorphisms and cancer risk, we conducted a comprehensive meta-analysis to investigate the association between the hMLH1 -93 G/A and 1151 T/A (Val384Asp) polymorphisms and cancer risk in Asian population. METHODS: we performed a meta-analysis by conducting searches of the published studies in Pub Med, CNKI, CBM, ISI web of knowledge and Google scholar search databases. Finally, 12 studies were included into our meta-analysis. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the associations between hMLH1 polymorphisms and cancer risk. Statistical analysis was performed with Review Manager 5.0. RESULTS: Twelve studies addressing two hMLH1 polymorphisms were analyzed among a total of 4128 cancer cases and 4678 controls. For hMLH1 -93G/A, there was no evidence that the hMLH1-93 G/A polymorphism was significantly associated with an increased cancer risk (P > 0.05) in Asian populations (heterozygote comparison: OR=0.89 [95% CI (0.75, 1.060)] P=0.20; dominant model comparison: OR=0.98 [95% CI (0.83, 1.15)] P=0.79). In subgroup analysis based on cancer types and the sources of control, no associations were found in Colorectal, Gastric cancer and "other cancers" under the any gene model except for lung cancer (recessive model comparison: OR=1.69 [95% CI (1.30, 2.19)] P<0.0001). For hMLH1 1151 T/A, the polymorphism significantly associated with an increased cancer risk in Asians: OR = 1.88 [95% CI (1.49, 2.25)], P<0.0001, OR = 1.87 [95% CI (1.49, 2.25)], P<0.0001. CONCLUSIONS: Our investigations demonstrated that the hMLH1-93 G/A polymorphism is not a candidate for susceptibility to overall cancers, and that the hMLH1 1151 T/A polymorphism is significantly associated with higher cancer risk in Asian populations. Further studies with large sample size for hMLH1 should be conducted.
Gene 04/2013; · 2.34 Impact Factor
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ABSTRACT: Background: It has been of great interest whether mometasone furoate (MF) is better than other inhaled corticosteroids (ICSs) as the controller therapy in patients with moderate or severe asthma who had previously been taking ICSs. Objective: The aim of this meta-analysis is to thoroughly compare the efficacy and safety of MF versus other ICSs with equipotent daily doses in those patients. Methods: Relative databases were searched. Randomised controlled trials of more than or equal to 4 weeks' treatment duration comparing MF with other ICSs were reviewed. Results: Six trials with 1354 randomised patients met the inclusion criteria. Significant differences favouring MF were found in all indices of pulmonary function. MF was superior compared to other ICSs in decreasing the frequency of rescue medication use and morning difficulty breathing score. There was no significant difference between MF and other ICSs therapy in morning wheezing score, cough score and percentage of patients with no nocturnal awakenings due to asthma. For the treatment-related adverse effects (AEs), treatment-related severe AEs, discontinuations due to AEs and some common symptom of AEs, MF was all similar to other ICSs in their incidence. Conclusions: In adult patients with moderate or severe asthma who had previously been taking ICSs, MF was superior to other ICSs with equipotent daily doses as controller monotherapy in improving pulmonary function and decreasing the frequency of rescue medication use, and was similar to other ICSs in the incidence of AEs. These results demonstrated the priority of MF in asthma therapy.
Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 03/2013; 31(1):26-35. · 0.65 Impact Factor
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ABSTRACT: PURPOSE: Matrix metalloproteinase (MMP) 1, MMP2, MMP3 and MMP9 are important members of the MMP family. Recently, many studies have been carried out on the association between polymorphisms of MMP1 -1607 1G/2G, MMP2 -735 C/T, MMP2 -1306 C/T, MMP3 -1171 5A/6A and MMP9 -1562 C/T and lung cancer risk. However the results of these studies remained inconclusive due to conflicting results from different case-control studies. To clarify these associations, we conducted a meta-analysis. METHODS: We conducted a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database (date from Jan 2000 to Aug 2012). Overall and subgroup analysis by the ethnicity of study population was carried out. Odds ratio (OR) with 95% confidence interval (95%CI) were used to assess the strength of the association. RESULTS: There were 17 studies involving five polymorphic sites in four MMP genes. For MMP1 -1607,increased lung cancer risk was found under dominant model (MMP1 -1607 1G/2G: OR=1.14, 95%CI=1.03-1.26 , P=0.01 ), but not in Caucasian population. For MMP2 -1306 C/T, T polymorphism decreased lung cancer risk under dominant and recessive models (dominant, OR=0.63, 95%CI=0.46-0.88, P=0.0006; recessive, OR=0.61, 95%CI=0.38-0.99, P=0.04). For MMP9 -1562 C/T, TT genotype decreased this risk under the recessive model (OR=0.38, 95%CI=0.19-0.75, P=0.005), but not in Asian population. For MMP2 -735 C/T and MMP3 -1171 5A/6A, there was no association between this polymorphism and lung cancer risk under the dominant and recessive models. CONCLUSIONS: MMP1 -1607 1G/2G polymorphism increased lung cancer risk in Asians. It was also found thatMMP2 -1306 C/T polymorphism decreased lung cancer risk in Asians, while MMP9 -1562 C/T polymorphism decreased lung cancer risk in Caucasians. No significant difference was found in any genotype of MMP2 -735 C/T and MMP3 -1171 5A/6A. Further studies with large sample size should be carried out.
Gene 01/2013; · 2.34 Impact Factor
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ABSTRACT: IL-12 plays a very important role in the development and progress of cancer. IL-12B rs3212227 polymorphism has been reported and many studies have focused on the role of this polymorphism in various cancers. However, the association between IL-12B rs3212227 polymorphism and cancer risk remains controversial. Therefore, we performed a systematic meta-analysis to estimate the overall cancer risk associated with this gene polymorphism and to quantify any potential between-study heterogeneity. PubMed and Embase databases were searched for case-control studies published up to April 1, 2012 that investigated IL-12B rs3212227 polymorphism and cancer risk. Odds ratios (OR) with 95 % confidence intervals (95 % CI) were used to access the strength of this association. Heterogeneity among articles and publication bias were also verified. Ten studies with 2,954 cancer patients and 3,276 healthy controls were included. This meta-analysis showed that there was a significant association between IL-12B rs3212227 polymorphism and overall cancer risk (CC/AC vs AA: OR = 1.32, 95 % CI = 1.06-1.63). When stratified by cancer type, we found a significant increased risk in cervical and nasopharyngeal cancer (OR = 1.34, 95 % CI = 1.04-1.73; OR = 2.03, 95 % CI = 1.57-2.63, respectively). In the stratified analysis, we also observed a similar association in population-based studies (OR = 1.34, 95 % CI = 1.00-1.80), Asian populations (OR = 1.33, 95 % CI = 1.06-1.67) and European populations (OR = 1.54, 95 % CI = 1.04-2.28). According to the results of our meta-analysis, IL-12B rs3212227 polymorphism probably is associated with a high risk of cancer.
Molecular Biology Reports 10/2012; · 2.93 Impact Factor
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ABSTRACT: To establish a better method of primary culture for alveolar epithelial type II cells (AEC II) and to study its bionomics,
alveolar epithelial type II cells were isolated by digestion with trypsin and collagenase, which were then purified by plated
into culture flask coated with rat immunoglobulin G. The purified AEC II were identified by alkaline phosphatase staining,
electron microscopy, immunocytochemical staining of pulmonary surfactant protein A (SPA). The SPA expression and transfection
characteristics were compared with those of A549 cell line. The results showed that AEC II could be isolated by digestion
with trysin and collagenase and purified by adhesive purification by using IgG, with a yield of about 2–3 × 107, and a purity of about 75%–84%. Cells could be quickly identified with AKP staining. AEC II were different from A549 cell
line in terms of SPA expression and transfection characteristics. It is concluded that adhesive purification with IgG can
improve the purity of AEC II, and AKP staining is simple in cell identification. AEC II can not be completely replaced by
A549 cells in some studies because the differences between them, such as SPA expression.
Key wordsalveolar epithelial type II cells-primary culture-bionomics
Journal of Huazhong University of Science and Technology 04/2012; 27(6):653-656. · 0.38 Impact Factor
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ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a complex systemic disorder characterized by both local pulmonary and systemic inflammation. Many studies suggested that activation of circulating inflammatory cells and increased circulating levels of inflammatory cytokines occur in COPD. Interleukin (IL)-18 is a unique proinflammatory cytokine that mediates its effects by binding to the IL-18 receptor (IL-18R). In the present study, the expression of IL-18 in serum and IL-18R on peripheral blood T lymphocytes was analyzed. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of IL-18 and interferon (IFN)-γ, and high sensitivity C-reactive protein (hsCRP) were measured by chemiluminiscent immunoassay. Expression of IL-18R was examined using a three-color flow cytometry method. In total, 120 subjects were recruited including 32 nonsmokers, 30 current smokers and 58 stable COPD patients. Serum levels of IL-18 and hsCRP were significantly higher in stable COPD patients than those in nonsmokers and current smokers. A significant negative correlation existed between pulmonary function and serum level of IL-18 rather than hsCRP in stable COPD patients. The proportions of IL-18Rα-expressing T lymphocytes and CD8(+) T lymphocytes were significantly higher in stable COPD patients than in nonsmokers and current smokers. The current study extended prior analyses by examining IL-18R expression in peripheral blood. The results suggested that IL-18/IL-18R system was active in peripheral blood of COPD patients.
COPD Journal of Chronic Obstructive Pulmonary Disease 04/2012; 9(4):375-81. · 1.79 Impact Factor
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ABSTRACT: Introduction: Inhaled corticosteroids (ICS) and oral leukotriene receptor antagonists (LTRA) are effective drugs used in the management of asthma as controller monotherapy in adolescents and adults, although there are debates as to which one is better. Objectives: To thoroughly compare the efficacy and tolerability of ICS vs LTRA in adolescents and adults with mild to moderate asthma. Methods: Relative database were searched for the review. Randomized controlled trials of more than or equal to 4 weeks' treatment duration comparing ICS with LTRA were reviewed. Results and Conclusion: Twenty-four trials with 6197 randomized adolescents and adults with mild to moderate asthma met the inclusion criteria with a minimum duration of 4 weeks' treatment. Significant differences favouring ICS were found in all indices of pulmonary function. Other significant benefits of ICS were shown in symptoms, nocturnal awakenings, rescue-medication use, symptom-free days and quality of life. As to each special symptom of adverse effects, ICS was similar to LTRA in the incidence of headache, nausea and throat discomfort, but significantly higher in the incidence of hoarseness and oral pharyngeal candidiasis. Concerning withdrawal because of adverse events potentially related to treatment, ICS was similar to LTRA but significantly superior to LTRA in decreasing the asthma exacerbations or attacks during the treatment period. These results show that ICS may be the better drug in terms of efficacy and tolerability, except hoarseness and oral pharyngeal candidiasis, and should thus have priority over LTRA in asthma monotherapy in adolescents and adults. Please cite this paper as: Yang D, Luo H, Wang J, Bunjhoo H, Xu Y and Xiong W. Comparison of inhaled corticosteroids and leukotriene receptor antagonists in adolescents and adults with mild to moderate asthma: a meta-analysis. Clin Respir J 2012; DOI:10.1111/j.1752-699X.2012.00287.x.
The Clinical Respiratory Journal 02/2012; · 1.06 Impact Factor
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ABSTRACT: Overexpression of Cyclin D1 and Bcl-xL proteins has often been found in non-small-cell lung cancer (NSCLC). These two genes may play a significant role in tumorigenesis. However, the combined inhibition of the two genes in vitro is unclear in NSCLC. In this study, the effect of a combined intervention on Cyclin D1 and Bcl-xL in NSCLC is assessed and discussed. Three recombinant plasmids that expressed a cytomegalovirus (CMV) promoter-driven micro30 short hairpin RNA (shRNA) targeting the Cyclin D1 gene (Cyclin D1 shRNA), the Bcl-xL gene (Bcl-xL shRNA) and a combination of the two genes (Cyclin D1-Bcl-xL shRNA), based on the plasmid pcDNA6.2-GW/EmGFP-miR, were constructed. The cell lines A549 and NCI-H441 were divided into four groups; blank control (untreated cells), Cyclin D1 shRNA, Bcl-xL shRNA and Cyclin D1-Bcl-xL shRNA (transfected cells), respectively. The expression of mRNA and protein of Cyclin D1 or Bcl-xL was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. The apoptosis and proliferation of the two cell lines were evaluated by dimethylthiazol-diphenyltetrazolium bromide (MTT), cell count and flow cytometry. The recombinant plasmid sufficiently mediated the RNA interference (RNAi) effects in A549 and NCI-H441 cells. The expression levels of mRNA and protein of Cyclin D1 or Bcl-xL in the three intervention groups were significantly reduced compared to the untreated cells (P<0.05). No statistical differences were found among the combined shRNAs and single shRNA regarding Cyclin D1 or Bcl-xL, respectively (P>0.05). In the assessment of proliferation and apoptosis, it was found that in all three intervention groups there was significant inhibition of cell proliferation and promotion of cell apoptosis compared with the untreated cells (P<0.05). Furthermore, the combined interference of the two genes was more effective than either single interference (P<0.05). Our results suggested that the combined targeting of Cyclin D1 and Bcl-xL genes has potential for NSCLC investigation, providing increased efficacy over Cyclin D1 or Bcl-xL inhibition alone.
Experimental and therapeutic medicine 02/2012; 3(2):255-260.
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ABSTRACT: The association between body mass index (BMI) and mortality in patients suffering from chronic obstructive pulmonary disease (COPD) has been a subject of interest for decades. However, the evidence is inadequate to draw robust conclusions because some studies were generally small or with a short follow-up.
We carried out a search in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE database for relevant studies. Relative risks (RRs) with 95% confidence interval (CI) were calculated to assess the association between BMI and mortality in patients with COPD. In addition, a baseline risk-adjusted analysis was performed to investigate the strength of this association.
22 studies comprising 21,150 participants were included in this analysis. Compared with patients having a normal BMI, underweight individuals were associated with higher mortality (RR = 1.34, 95% CI = 1.01-1.78), whereas overweight (RR = 0.47, 95% CI = 0.33-0.68) and obese (RR = 0.59, 95% CI = 0.38-0.91) patients were associated with lower mortality. We further performed a baseline risk-adjusted analysis and obtained statistically similar results.
Our study showed that for patients with COPD being overweight or obese had a protective effect against mortality. However, the relationship between BMI and mortality in different classes of obesity needed further clarification in well-designed clinical studies.
PLoS ONE 01/2012; 7(8):e43892. · 4.09 Impact Factor
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Tao Wang,
Guangwei Luo,
Yi Hu,
Fajiu Li,
Jing Ma,
Jianmiao Wang,
Peng Zuo, Weining Xiong,
Xiansheng Liu,
Jianping Zhao,
Shengdao Xiong,
Zhenxiang Zhang,
Chenghong Li,
Su Zhao,
Jiemin Sun,
Yongjian Xu
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ABSTRACT: This study compared the efficacy and safety of tiotropium bromide inhalation powder (spiriva) and doxofylline oral tablet (doxofylline) in the treatment of chronic obstructive pulmonary disease (COPD). A multi-center, randomized, double-blind, double-dummy, parallel-controlled study involved 127 eligible stable moderate to severe COPD patients treated with inhaled tiotropium dry powder (18 μg/day) or oral doxofylline tablets (0.2 g/time, 2 times a day) for 12 and 24 weeks. Before and after treatment for 12 weeks and 24 weeks, respectively, pulmonary function, 6-min walking distance and dyspnea index were recorded. The results showed that in both tiotropium group and doxofylline groups, after 12-week treatment, FEV(1), FEV(1)/FVC% and 6-min walk distance were significantly higher than those before the medication, while dyspnea index decreased as compared with that before treatment. After 24-week treatment, a slight improvement in the measures was observed as compared with that of 12-weeks treatment, but the difference was not statistically significant. With both 12-week and 24-week treatment, the effect of tiotropium was slightly better than that of doxofylline tablets, with the difference being statistically insignificant. The major adverse events in the tiotropium group and doxofylline group were observed in 9 cases (9.9%) and 12 cases (12.9%), respectively, and no statistically significant difference was found between them. We are led to conclude that both tiotropium at 18 μg a day and doxofylline tablets at 0.2 g/day (two times a day) are effective and safe for the treatment of COPD.
Journal of Huazhong University of Science and Technology 10/2011; 31(5):614-8. · 0.38 Impact Factor
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ABSTRACT: We sought to determine whether the aryl hydrocarbon receptor (AhR) and interleukin (IL)-22 may be involved in the pathogenesis of the peripheral blood mononuclear cells (PBMCs) in allergic asthmatic patients and whether their expression may be related to the severity of the disease.
Blood samples were obtained from each subject with allergic asthma (n =18), controlled asthma (n = 17) and healthy controls (n = 12) respectively. The PBMCs were collected for AhR mRNA detection by real-time quantitative polymerase chain reaction (PCR). The plasma was collected for IL-22 protein detection by enzyme-linked immunosorbent assay (ELISA).
The expression of AhR mRNA in PBMCs and IL-22 protein in plasma of patients with allergic asthma were higher than those in controlled asthma cases and healthy controls. The plasma concentrations of IL-22 had negative correlation with the predicted percentage of forced expiratory volume in the first second (FEV1%) and the percentage of FEV1 and forced vital capacity (FEV1/FVC%) and it was positively correlated with the asthma severity score (ASS) of the asthmatics.
Our results suggested that both AhR and IL-22 might be involved in the pathogenesis of allergic asthma in human and the level of IL-22 might have some relationship with the severity of the disease.
Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 09/2011; 29(3):266-72. · 0.65 Impact Factor
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ABSTRACT: It is not clear whether combination therapy with tiotropium plus formoterol has greater efficacy, without increasing the burden of adverse events, compared with tiotropium alone. This meta-analysis was performed to evaluate the differences in efficacy and adverse events associated with combination therapy compared with tiotropium alone, in patients with stable COPD.
MEDLINE, EMBASE, CINAHL and the Cochrane trials database were searched for this analysis. Randomized controlled trials of 2 or more weeks of treatment with tiotropium plus formoterol or arformoterol, compared with tiotropium alone, were reviewed. Studies were pooled to yield odds ratio (OR) or weighted mean differences (WMD), with 95% confidence interval (CI).
Eight trials, involving 1868 randomized patients, met the inclusion criteria. Treatment with tiotropium plus formoterol significantly improved the average FEV(1) (WMD 105 mL, 95% CI: 69-142), average FVC (WMD 135 mL, 95% CI: 96-174) and trough FEV(1) (WMD 53 mL, 95% CI: 30-76), compared with tiotropium alone, although the difference was not statistically significant for trough FVC. The mean change in transitional dyspnoea index (TDI) was markedly greater with tiotropium plus formoterol (WMD 1.50, 95% CI: 1.01-1.99) than with tiotropium alone, and there was a similar difference in the proportion of patients with a clinically significant change in TDI (OR 2.34, 95% CI: 1.58-3.46). There tended to be fewer adverse events and COPD exacerbations with tiotropium plus formoterol, compared with tiotropium alone, but the differences were not statistically significant.
Tiotropium plus formoterol significantly improved lung function and symptom scores compared with tiotropium alone. There was a trend towards a reduction in adverse events, although the difference was not statistically significant. Long-term trials are necessary to evaluate the effects of tiotropium plus formoterol and to clarify the role of combination therapy, compared with tiotropium alone.
Respirology 02/2011; 16(2):350-8. · 2.42 Impact Factor
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ABSTRACT: Increasing evidence indicates that eosinophils contribute greatly to airway remodeling in asthma. Since interleukin-5 (IL-5) plays a critical role in the regulation of eosinophils in asthma, anti-IL-5 therapy may be a novel approach to inhibit airway remodeling in asthma.
In this study, we applied a recombinant adeno-associated virus vector-mediated antisense IL-5 gene delivery (rAAV-ASIL-5) system to investigate its effect on airway remodeling in ovalbumin (OVA)-sensitized and -challenged rats.
rAAV-ASIL-5 was used to infect OVA-sensitized and -challenged rats. IL-5 protein in bronchoalveolar lavage fluid (BALF) was detected by ELISA. The eosinophils in BALF were counted. Transforming growth factor (TGF)-β1- and TGF-β2-positive cells in the peribronchial space were detected by immunohistochemical staining. Lung tissue was collected for Sirius red staining and histological analysis.
rAAV-ASIL-5 significantly decreased the level of IL-5 protein, the number of eosinophils in BALF and the numbers of TGF-β1- and TGF-β2-positive cells in the peribronchial space. The area of Sirius red staining in airways was also decreased. Moreover, the rAAV-ASIL-5 treatment inhibited the increase in total bronchial wall area and airway smooth muscle area.
These results suggest that rAAV-ASIL-5-based gene therapy could be used to inhibit airway remodeling in allergic rats.
International Archives of Allergy and Immunology 01/2011; 154(3):207-15. · 2.40 Impact Factor
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DI Jin,
Ying Chen,
Zhengyun Wang,
Siwei Wang,
Hansvin Bunjhoo,
Jing Zhu,
Yong Cao, Weining Xiong,
Shengdao Xiong,
Yongjian Xu,
Huijuan Fang
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ABSTRACT: The aim of this study was to investigate the diagnostic value of interleukin 22 (IL-22) and carcinoembryonic antigen (CEA) in tuberculous pleural effusions (TPEs) and malignant pleural effusions (MPEs). Pleural effusion samples from 56 patients were classified on the basis of diagnosis as TPE (n=28) and MPE (n=28). The concentration of IL-22 was determined by ELISA. Lactate dehydrogenase (LDH), adenosine dehydrogenase (ADA) and CEA levels were also determined in all patients. A significant difference was observed in the levels of ADA and CEA (P<0.01), but not in the levels of LDH (P>0.05) between TPE and MPE. The concentration of IL-22 in TPE was significantly higher compared to MPE (P<0.01). With a threshold value of 49 pg/ml, IL-22 had a sensitivity of 82.14% (23/28) and a specificity of 96.43% (27/28) for differential diagnosis. The combined detection of IL-22 and CEA had a sensitivity of 100% (28/28) and a specificity of 96.43% (27/28) to distinguish TPE from MPE. TPEs showed significantly higher levels of IL-22 compared to MPEs. The combined detection of IL-22 and CEA may be more valuable in the differential diagnosis between TPE and MPE.
Experimental and therapeutic medicine 01/2011; 2(6):1205-1209.
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ABSTRACT: Th2-derived cytokines, including interleukin-4 (IL-4), are considered to play an important role in the development of airway remodeling of asthma.
Our previous study has demonstrated that a recombinant adeno-associated virus containing antisense against IL-4 gene (rAAV-asIL4) vector could significantly suppress the expression of IL-4 protein and airway inflammation in the rat models of allergic asthma. In this study, we applied the rAAV-asIL4 vector to allergic rats to investigate the effects of anti-IL4 therapy on airway remodeling in allergic asthma.
rAAV-asIL4 was used to infect the ovalbumin (OVA)-sensitized and challenged rats by tail-vein injection. IL-4 protein in bronchoalveolar lavage fluid (BALF) was detected by enzyme-linked immunosorbent assay. The number of eosinophils in BALF was counted. Transforming growth factor-beta1 (TGF-beta1) and TGF-beta2-positive cells in the peribronchial space were detected by immunohistochemical staining, and collagen deposition beneath the basement membrane was detected by Sirius red stain. The lung tissues were collected for histologic analysis of total bronchial wall area (W(At)) and airway smooth muscle area (W(Am)).
rAAV-asIL4 significantly decreased IL-4 protein in BALF of OVA-sensitized and challenged rats. The number of eosinophils in BALF, the TGF-beta1 and TGF-beta2-positive cells in the peribronchial space were also suppressed. Moreover, the rAAV-asIL4 treatment inhibited the area of Sirius red staining in airways and the increase in W(At) and W(Am).
These results suggest that rAAV-asIL4 may attenuate the airway remodeling process relevant to the inhibition of airway inflammation. This study provides elementary evidence for the potential utility of rAAV-asIL4 as an approach to gene therapy for asthmatic airway remodeling.
Journal of Asthma 11/2010; 47(9):951-8. · 1.52 Impact Factor
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ABSTRACT: Beta-defensin-2 (BD-2) plays an important role in host defense against pathogenic microbe challenge by its direct antimicrobial activity and immunomodulatory functions. The present study aimed to determine whether genetic up-regulation of rat BD-2 (rBD-2) could ameliorate chronic Pseudomonas aeruginosa lung infection in rats.
Plasmid-encoding rBD-2 was delivered to lungs in vivo using linear polyethylenimine at 48 h before challenging with seaweed alginate beads containing P. aeruginosa. Macroscopic and histopathological changes of the lungs, bacterial loads, inflammatory infiltration, and the levels of cytokines/chemokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, kertinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2)] were measured at 3 and 7 days post-infection (p.i.).
The overexpression of rBD-2 resulted in a significant increase in animal survival rate (at 3 days p.i.), a significant decrease in bacterial loads in the lungs (at 3 and 7 days p.i.), and significantly milder lung pathology. In addition, the overexpression of rBD-2 led to increased infiltration of polymorphonuclear neutrophils (PMN), and elevated protein expression of cytokines/chemokines (IL-1beta, TNF-alpha, KC and MIP-2) at the early stage of infection (at 3 days p.i.), at the same time as being dramatically decreased at the later stage of infection (at 7 days p.i.).
Genetic up-regulation of rBD-2 increased animal survival rate, and reduced bacterial loads in lungs after bacterial infection. The overexpression of rBD-2 also modulated the production of several cytokines/chemokines and increased PMN recruitment at the early stage of infection. Our findings indicate that the enhancement of BD-2 may be an efficacious intervention for chronic P. aeruginosa lung infection.
The Journal of Gene Medicine 03/2010; 12(3):276-86. · 2.48 Impact Factor
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ABSTRACT: Background and objective: The accumulation of eosinophils in airways is an important characteristic of asthma. The process is primarily mediated by interleukin-5 (IL-5) secreted by Th2 lymphocytes. This study explored a new approach to asthma therapy in which allergic rats were transfected with the IL-5 antisense gene delivered by the recombinant adeno-associated virus (rAAV-ASIL-5).Methods: The viral vector rAAV-ASIL-5 was constructed and the IL-5 antisense gene transfected into allergic rats. The levels of IL-5, IgE, eotaxin and eosinophilic cationic protein (ECP) in sera and bronchoalveolar lavage fluid (BALF) were measured by ELISA. The inflammatory responses in lung tissues were evaluated by histological study.Results: The levels of IL-5 protein in serum and BALF were significantly decreased in the allergic rats treated with rAAV-ASIL-5 (P < 0.05). Serum ovalbumin-specific IgE was reduced in treated rats compared with untreated rats (P < 0.05). rAAV-ASIL-5 treatment also reduced eosinophils in the peripheral blood and BALF, as well as the ECP and eotaxin levels in serum and BALF (P < 0.05). There was significantly less inflammation in the lungs of rAAV-ASIL-5-treated rats than in those of untreated rats. No obvious pathological damage to the kidneys and livers of the rats treated with rAAV was observed.Conclusions: Treatment with rAAV-ASIL-5 inhibited the accumulation of eosinophils and airway inflammation in the rat model of allergic asthma by suppressing IL-5 production. These results suggest that rAAV-ASIL-5-based gene therapy may be used for the treatment of allergic asthma.
Respirology 12/2009; 15(1):132 - 140. · 2.42 Impact Factor
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ABSTRACT: The accumulation of eosinophils in airways is an important characteristic of asthma. The process is primarily mediated by interleukin-5 (IL-5) secreted by Th2 lymphocytes. This study explored a new approach to asthma therapy in which allergic rats were transfected with the IL-5 antisense gene delivered by the recombinant adeno-associated virus (rAAV-ASIL-5).
The viral vector rAAV-ASIL-5 was constructed and the IL-5 antisense gene transfected into allergic rats. The levels of IL-5, IgE, eotaxin and eosinophilic cationic protein (ECP) in sera and bronchoalveolar lavage fluid (BALF) were measured by ELISA. The inflammatory responses in lung tissues were evaluated by histological study.
The levels of IL-5 protein in serum and BALF were significantly decreased in the allergic rats treated with rAAV-ASIL-5 (P < 0.05). Serum ovalbumin-specific IgE was reduced in treated rats compared with untreated rats (P < 0.05). rAAV-ASIL-5 treatment also reduced eosinophils in the peripheral blood and BALF, as well as the ECP and eotaxin levels in serum and BALF (P < 0.05). There was significantly less inflammation in the lungs of rAAV-ASIL-5-treated rats than in those of untreated rats. No obvious pathological damage to the kidneys and livers of the rats treated with rAAV was observed.
Treatment with rAAV-ASIL-5 inhibited the accumulation of eosinophils and airway inflammation in the rat model of allergic asthma by suppressing IL-5 production. These results suggest that rAAV-ASIL-5-based gene therapy may be used for the treatment of allergic asthma.
Respirology 11/2009; 15(1):132-40. · 2.42 Impact Factor
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ABSTRACT: This study aims to research the expression of spleen tyrosine kinase (Syk) in non-small cell lung cancer (NSCLC) and the relationship
between Syk and clinicopathologic factors and p53. Immunohistochemistry was applied to detect the expression of Syk and p53
protein in 39 cases of NSCLC (23 cases of lung squamous cell cancer, 16 cases of lung adenocarcinoma) and tumor-surrounding
normal lung tissues. The positive rate of Syk was 46.15% (18/39) and 100% (39/39) in NSCLC and tumorsurrounding normal lung
tissues, respectively. The expression level of Syk in NSCLC was significantly lower than that in tumor-surrounding normal
lung tissues (P = 0.000). The Syk expression was positively correlated with the p53 expression in NSCLC specimens (P = 0.025). There was no significant association between Syk expression and lymph node metastasis, differentiation degree,
tumor size and tumor node metastasis (TNM). The present study demonstrated that Syk was aberrantly expressed in the NSCLC
and might have a significant impact on tumor growth and progression.
Frontiers of Medicine in China 02/2009; 3(1):41-44.
