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1.
Recent studies indicated that interleukin(IL)-17, growth-related oncogene(GRO)-α and IL-8 play an important role in the pathogenesis of nasal polyps. However, the effects of the increased amount of IL-17 and the production of GRO-α and IL-8 in human nasal polyp fibroblasts are not completely understood. This study aimed to determine the effects of the increased IL-17 on the changes of GRO-α and IL-8 expression in human nasal polyp fibroblasts and further investigate the mechanism of neutrophil infiltration in nasal polyps. Nasal polyp fibroblasts were isolated from six cases of human nasal polyps, and the cells were stimulated with five different concentrations of IL-17. Real-time fluorescence quantitative polymerase chain reaction(RT-PCR) was used to detect the mRNA expression of GRO-α and IL-8. The mRNA of GRO-α and IL-8 was expressed in unstimulated controls and remarkably increased by stimulation with IL-17. Moreover, the levels of GRO-α and IL-8 produced by fibroblasts were increased gradually with the increases in IL-17 concentrations. The present study showed that nasal fibroblasts can produce GRO-α and IL-8, and their production is remarkably enhanced by IL-17 stimulation, thereby clarifying the mechanism of the IL-17 mediated neutrophil infiltration in nasal polyps. These findings might provide a rationale for using IL-17 inhibitors as a treatment for nasal inflammatory diseases such as nasal polyps.  相似文献   

2.
胃溃疡炎症机制及中医药防治进展   总被引:6,自引:0,他引:6  
幽门螺杆菌(Hp)感染可导致慢性胃炎、消化性溃疡、淋巴瘤,也是胃癌的高危因子。大量的基础与临床研究结果表明,炎症反应是Hp致病的重要机制之一,炎症细胞浸润胃黏膜后释放的炎性细胞因子作为第二信使始终参与这一过程。  相似文献   

3.
Background Studies have shown that the drug resistance of gastric cancer cells can be modulated by abnormal expression of microRNAs (miRNAs).We investigated the role of miR-503 in the development of cisplatin resistance in human gastric cancer cell lines.Methods MiR-503 expression was measured by quantitative real-time PCR.MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and clonogenic assays were used to examine changes in cell viability and the drug resistance phenotype of cancer cells associated with upregulation or downregulation of the miRNA.A dual-luciferase activity assay was used to verify target genes of miR-503.Immunohistochemistry,Western blotting analysis,and a flow cytometric apoptosis assay were used to elucidate the mechanism by which miR-503 modulates drug resistance in cancer cells.Results MiR-503 was significantly downregulated in gastric cancer tissues and several gastric cancer cell lines.Additionally,downregulation of miR-503 in the cisplatin (DDP)-resistant gastric cancer cell line SGC7901/DDP was concurrent with the upregulation of insulin-like growth factor-1 receptor (IGF1R) and B-cell lymphoma 2 (BCL2) expression compared with the parental SGC7901 cell line.An in vitro drug sensitivity assay showed that overexpression of miR-503 sensitized SGC7901/DDP cells to cisplatin.The luciferase activity of reporters driven by IGF1R and BCL2 3'-untranslated regions in SGC7901/DDP cells suggested that IGF1R and BCL2 were both direct target genes of miR-503.Enforced miR-503 expression in SGC7901/DDP cells reduced expression of the target proteins,inhibited proliferation,and sensitized the cells to DDP-induced apoptosis.Conclusion Our findings suggest that hsa-miR-503 modulates cisplatin resistance of human gastric cancer cells at least in part by targeting IGF1R and BCL2.  相似文献   

4.
Objective Diabetic nephropathy (DN) is the major cause of end-stage renal disease worldwide and its prevalence continues to increase.Currently,therapies for DN provide only partial renoprotection; hence new targets for therapeutic intervention need to be identified.In this review,we summarized the new target,sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway,explored its potential therapeutic role in the prevention and treatment of DN.Data sources Most relevant articles were mainly identified by searching PubMed in English.Study selection Mainly original articles and critical review articles by major pioneer investigators in this field were selected to be reviewed.Results SphK1/S1P pathway can be activated by hyperglycemia,advanced glycation end products,and many proinflammatory cytokines,which leads to fibronectin,transforming growth factor-31 up-regulation and AP-1 activation.And then it could promote glomerular mesangial cells proliferation and extracellular matrix accumulation,mediating the initiation and progression of diabetic renal fibrosis.Conclusions SphK1/S1P pathway is closely correlated with the pathogenesis of DN.The results suggest that SphK1/ S1P pathway as a new target for clinically improving DN in future is of great prospect.  相似文献   

5.
The relationship between T cell immunoglobulin domain and mucin domain protein 3(Tim-3)/Galectin(Gal)-9 pathway and recurrent spontaneous abortion(RSA) was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin(IL)-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas(P〈0.05) and healthy fertile non-pregnant controls(P〈0.05), but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas(P〈0.05) and healthy fertile non-pregnant controls(P〈0.05). It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.  相似文献   

6.
Inflammation and lung function decline are the main pathophysiological features of chronic obstructive pulmonary disease (COPD). Acupuncture can improve lung function in patients with COPD, but the underlying mechanisms are not well understood. Orexins (OXs), which are found in peripheral plasma, are neuropeptides that regulate respiration and their levels are related to COPD. Therefore, we hypothesized that acupuncture might alter OXs, reduce lung inflammation and improve lung function in COPD. METHODS: COPD was induced in rats by exposure to cigarette smoke for 8 weeks and injecting with lipopolysaccharide twice. Electroacupuncture (EA) was performed at Feishu (BL13) and Zusanli (ST36) for 30 min/d for 2 weeks. Rat lung function and morphology were assessed after EA. The levels of tumor necrosis factor-α (TNF-a) and intedeukin-1β (IL-16) in bronchoalveolar lavage fluid (BALF) and orexin A and B levels in the lung tissue were detected by enzyme-linked immunosorbent assay. OX receptor mRNA levels and immunopositive cells were assessed with real-time polymerase chain reaction and immunohistochemical methods, respectively. The relationships among lung function, cell factors, and OX levels were analyzed by Pearson correlation analyses. RESULTS: Compared with the control group, lung function was significantly decreased in the rats with COPD (P〈0.05). There were obvious increases in TNF-α and IL-1β levels in BALF (P〈0.05 and P〈0.01, respectively), orexin A level in lung tissue (P〈0.01; but not orexin B) and mRNA expressions of OX 1 type receptor (OXR1) and OX 2 type receptor (OXR2) in lung tissue (P〈0.05 and P〈0.01, respectively); the integrative optical densities (IODs) of both receptors were greater in the COPD group (P〈0.05). For rats with COPD subjected to EA, lung function was improved (P〈0.05). There were notable decreases in TNF-a and IL-1β levels (P〈0.05 and 〈0.01, respectively) in BALF. Orexin A, but not orexi  相似文献   

7.
To research the erythrocytes of condition of innate immunity in the children patients with RA and SLE, comparing with changes of activity of CD35 (CR1) on the erythrocyte between these two kinds of diseases, and further discuss the pathogenesis of these two kinds of diseases in children. The reaction of innate immunity of erythrocytes, lymphocytes and neutrophils which isolated from fresh blood of patients with RA and SLE to tumor cells was measured, and then the levels of expression of CD35 by using flow cytometry (FCM) were measured. The rosette rate of erythrocyte, lymphocytes and granulocytes adhering to cancer cell in the children patients with RA were higher than counterparts of normal controls (P〈0.001) respectively; the rosette rate of erythrocyte, lymphocytes and granulocytes adhering to tumor cells in the children patients with SLE were lower than counterparts of normal controls (P〈0.001) respectively. The rosette rate of these to tumor cells of children patients with RA, showed the highest figure change during different phases, including progression phase〉stationary phase 〉 extinction phase. And the rosette rates in these three groups were significantly higher than ones of that in normal controls. The expression of CD35 on the erythrocyte of children patients with RA was significantly higher than that of normal controls (P〈0.001), while that of patients with SLE was significantly lower than that of normal controls (P〈0.001). The CD35 on the red cells showed significantly positive correlation (γ=0.804, P〈0.01) with adhering erythrocytes and positively correlation with the rate of lymphocytes (P〈0.05). The native immune function of children patients with SLE or RA was out of balance, and perhaps its changes have a relation with activity of diseases. It was suggested that the erythrocyte immunity function may be a new indicator to the condition of children patients with RA or SLE to judge the development and prognosis.  相似文献   

8.
Objective To clarify the pathogenesis of Kaposi's Sarcoma (KS) in Xinjiang. Methods Study the high occurrence of KS in Xinjiang through case-control study. Collecting both the KS patients' and controls' blood samples, Then some cytokines' serum level and immune state were tested such as IL-6, TNF-α, IFN-γ, VEGF, Neopterin, β2-MG in serum of KS patients and control group by ELISA. The infection rate of Human herpesvirus 8 (HHV-8) was tested by nested PCR. Results We found KS didn't show relationship to geography and environment. The level of VEGF, TNF-α, IL-6, neopterin and β2-miroglobin in serum of KS were higher than those of the controls'. The p was respectively 0.003, 0.008, 0.005, 0.036, 0.006. The positive infection rate of HHV-8 in KS patient was 88.2%. Compared with the positive infection rate of control (20.5%), p〈0.001. Conclusion We consider the disorder of the level of cytokines, the infection of HHV-8 are related with the pathogenesis of KS in Xinjiang.  相似文献   

9.
Objective To study the effect of Shenfu on the expression of bax and bcl-2 in small intestinal mucosal epithelial cells after ischemic reperfusion injury and explore the effect of Shenfu on small intestinal mucosal epithelial cells apoptosis. Methods 36 SD rats were randomized into three groups, each consisting of 12 rats: Sham group (S group), Ischemic reperfusion group (IR group), Shenfu group (SF group), Ischemic reperfusion models were made by ligated the superior menseneric artery for 1 hour followed by 2 hrs reperfusion. Histological mucosal damage in each group was graded according to Chiu's score. Immunohistochemistry detected the expression of bax and bcl-2, and obtained the optical density (OD) value using a color image pattern analysis system, and then calculated the ratio of bcl-2/bax. TUNEL method measured apoptotic intestinal mucosal epithelial cells, and calculated the apoptotic index. Results There were edema and epithelial impairment in part of villus and the integral was higher in SF group than S group (P〈0.05), but lower than IR group (P〈0.01). Compared IR group with S group and SF group, the average OD value of bcl-2 and bax had significant statistic difference (P〈0.01), and the average OD value of bcl-2 in SF group was higher than in S group (P〈0.05), meanwhile bcl-2/bax was significantly lower in IR group than in S group and SF group (P〈0.01), but that was higher in SF group than in S group (P〈0.05). Apoptotic index in IR group was significantly higher than that in other two groups (P〈0.01), and that in SF group was higher than in S group (P〈0.05). Conclusion Shenfu can enhance the expression of bcl-2, decrease the expression of bax, meanwhile increase the ratio of bcl-2/bax, inhibit small intestinal mucosal epithetlial cells apoptosis, and protect small intestine mucosal epithetlial after ischemic reperfusion.  相似文献   

10.
目的观察益智健脑颗粒联合针灸对阿尔茨海默病(Alzheimers disease,AD)大鼠学习记忆的影响。方法将大鼠随机分为假手术组(A组)、模型组(B组)、针灸组(C组)、益智+针灸组(D组)各10只,B、C、D 3组分别以海马CA1区注射β淀粉样蛋白25-35(Aβ25-35)造模,A组注射等量的双蒸水,各组分别治疗20 d后行Morris水迷宫试验,观察大鼠学习记忆能力变化。结果B组较A组的平均潜伏期明显延长,差异具有统计学意义(P〈0.05);与B组比较,C组、D组的平均潜伏期明显缩短,过台次数增多,差异具有统计学意义(P〈0.05,P〈0.01);与C组比较,D组的潜伏期缩短,过台次数增多,差异具有统计学意义(P〈0.05)。结论益智健脑颗粒联合针灸能够提高Aβ25-35介导的AD模型大鼠的学习记忆能力。  相似文献   

11.
Background The mutation frequencies of three common deafness genes (MT-RNR1 m.1555A〉G,GJB2,and SLC26A4) among patients with nonsyndromic sensorineural hearing loss (NSHL) were different in previous studies.Inconsistent selection criteria for recruiting patients could have led to differences in estimating the frequencies of genetic mutations thus resulting in different mutation frequencies among these studies.The aim of this study was to reveal the differences in the mutation spectrums of the three common genes between familial and sporadic Chinese Han patients.Methods Totally,301 familial probands and 703 sporadic patients with NSHL were enrolled in this study.Three genes,MT-RNR1 m.1555A〉G,GJB2,and SLC26A4,were screened for mutation in our study cohort.A X2 test was performed to compare the mutation frequencies between the two groups.Results The study showed that the disease-causing mutation frequencies of MT-RNR1 m.1555A〉G,GJB2,and SLC26A4 were 12.29%,14.62%,and 18.27% in familial probands and 3.56%,18.63%,and 18.92% in sporadic patients,respectively.The mutation frequency of MT-RNR1 m.1555A〉G in familial probands was significantly higher than in sporadic patients (X2 test,P=0.000),while there were no significant differences in the mutation frequencies of GJB2 and SLC26A4 between the familial and sporadic groups (X2 test,P 〉0.05).Conclusions It is necessary to reveal the differences in gene mutation frequencies between patients of different sources or characteristics by comparative studies in order to avoid selection bias.The mutations of GJB2,SLC26A4,and MTRNR1 m.1555A〉G are the most important etiological factors in Chinese Han patients,among which SLC26A4 might be the most frequent.  相似文献   

12.
13.
Objective: We have continued previous work in which we demonstrated that #117 and #372 amino acids contributed to the high activities of human CYP2A13 in catalyzing 4-methylnitrosamino-1-(3-pyridyl)-1-butanone(NNK) and aflatoxin BI(AFB1) carcinogenic activation. The present study was designed to identify other potential amino acid residues that contribute to the different catalytic characteristics of two CYP2A enzymes, CYP2A6 and CYP2A13, in nicotine metabolism and provide insights of the substrate and related amino acid residues interactions. Methods: A series of reciprocally substituted mutants of CYP2A6lle^300→ Phe, CYP2A6Gly^301aAla, CYP2A6Ser^369 → Gly, CYP2A13Phe^300→ Ile, CYP2A13Ala^301 → Gly and CYP2A13Gly^369 → Set were generated by site-directed mutagenesis/baculovirus-Sf9 insect cells expression. Comparative kinetic analysis of nicotine 5'hydroxylatin by wild type and mutant CYP2A proteins was performed. Results:All amino acid residue substitutions at 300, 301 and 369 caused significant kinetic property changes in nicotine metabolism. While CYP2A6Ile^300→ Phe and CYP2A6Gly^301→Ala mutations had notable catalytic efficiency increases compared to that for the wild type CYP2A6, CYP2A13Phe^300→Ile and CYP2A13Ala^301→Gly replacement introduced remarkable catalytic efficiency decreases. In addition, all these catalytic efficiency alterations were caused by Vmax variations rather than Km changes. Substitution of #369 residue significantly affected both Km and Vmax values. CYP2A6Ser^369 → Gly increase the catalytic efficiency via a significant Km decrease versus Vmax enhancement, while the opposite effects were seen with CYP2A13Gly^369 → Ser. Conclusion:#300, #301 and #369 residues in human CYP2A6/13 play important roles in nicotine 5' -oxidation. Switching #300 or #301 residues did not affect the CYP2A protein affinities toward nicotine, although these amino acids are located in the active center. Set369 to Gly substitution indirectly affected nicotine binding by  相似文献   

14.
Cardiotrophin-1 (CT-1) activates a distinct form of cardiac muscle cell hypertrophy in which the sarcomeric units are assembled in series. The aim of the study was to determine the expres- sion pattern of sarcomeric contractile protein α-actin, specialized eytoskeletal protein α-actinin and mitochondrial uncoupling protein-2 (UCP2) in myocardial remodeling induced by chronic exposure to CT-1. Kunming mice were intraperitoneally injected with carboxy-terminal polypeptide (CP) of CT-1 (CT-1-CP, 500 μg·kg-1·day^-1) for 1, 2, 3 and 4 week (s), respectively (4 groups obtained according to the injection time, n=10 each, with 5 males and 5 females in each group), Those injected with physiological saline for 4 weeks served as controls (n=10, with 5 males and 5 females). The heart tissues of mice were harvested at 1, 2, 3 or 4 week (s). Immunohistochemistry (IHC) and Western blotting (WB) were used to detect the distribution and expression of sarcomeric α-actin, α-aetinin and mitoehondrial UCP2 in myocardial tissues. IHC showed that α-actin was mainly distributed around the nuclei of cardiomyo- cytes, α-actinin concentrated around the striae and UCP2 scattered rather evenly in the plasma. The ex- pression of α-actin was slightly greater than that of α-actinin and UCP2 in the control group (IHC: χ^2=6.125; WB: F=0.249, P〉0.05) and it gradually decreased after exposure to CT-1-CP. There was no significant difference in the expression of α-actin between the control group and the CT-1-CP-treated groups (χ^2=7.386, P〉0.05). But Western blotting revealed significant difference in the expression of α-actin between the control group and the 4-week CT-1-CP-treated group (F=2.912; q=4.203, P〈0.05). Moreover, it was found that the expression of α-actinin increased stepwise with the exposure time in CT-1-CP-treated groups and differed significantly between CT-1-CP-treated groups and the control group (ICH: χ^2=21.977; WB: F=50.388; P〈0.01). The e  相似文献   

15.
Background Bacterial inflammation is a common complication in patients with leukemia,and sulfur dioxide (SO2) is a bioactive molecule in modulating Gram-negative bacilli infection.This study aimed to examine the changes in SO2,nuclear factor-κB (NF-κB),and interleukin-8 (IL-8) levels in pediatric acute lymphoblastic leukemia (ALL) with Gram-negative bacterial inflammation.Methods Fifty-five ALL children were enrolled in this study,including 30 males and 25 females,aged 3-13 years,and the median age was 7.8 years.All these children who accepted chemotherapy for ALL were divided into the control group (before chemotherapy),the infection group (after chemotherapy with infection),and the recovery group (the infection was controlled after 1 week).The serum level of SO2 was detected using high performance liquid chromatography with fluorescence assay,and NF-κB and IL-8 levels were measured by enzyme-linked immunosorbent assay (ELISA).Human THP-1 cells were cultured,induced,and differentiated into macrophages,which were divided into five groups and each group was cultured with different stimulators:lipopolysaccharide (LPS) group,LPS+L-aspartate-β-hydroxamate (HDX) group,LPS+SO2 group,SO2,and control groups.NF-κB level and IL-8 protein contents by ELISA were examined in each group.Results In comparison with those of the control group,levels of serum SO2,NF-κB,and IL-8 of the infection group were significantly increased (P <0.05),while those of the recovery group were significantly decreased (P <0.05).A positive correlation was found between levels of serum SO2 and intracellular NF-κB/IL-8,and the correlation coefficients were 0.671 and 0.798 (P <0.05),respectively.According to the results found in human THP-1 cells,levels of NF-κB and IL-8 in LPS group were significantly increased compared with those of the control group (P <0.05); when compared with those in LPS group,levels of NF-κB in LPS+HDX group further increased significantly (P <  相似文献   

16.
Background Previous studies have shown that prostaglandins (PGs) dramatically stimulate healing processes in bone.However,the effect of prostaglandin l2 (PGI2) on fracture healing remains unclear.To investigate the effect of PGI2,a study on fracture healing process in closed tibia fractures was designed.Methods Thirty-six Sprague-Dawley male rats were randomized into two groups.On the first day,their right tibias were fractured by three-point bending technique.The study group (n=18) received a single injection of 10 μg/kg iloprost for 5 days,while the control group (n=18) received saline solution in the same way.On the 7th,14th and 28th days following the fracture,six rats were sacrificed and their right legs were harvested in each group.The progression of fracture healing was assessed for each specimen by the scores of radiography (by Lane-Sandhu) and histology (by Huo et al).Results On the 7th day,the radiographic and histologic scores were equal.On the 14th day radiographic total score was 6 and histologic total score was 23 in the iloprost group,whereas radiographic total score was 11 and histologic total score was 33 in the control group.On the 14th day radiographic and histologic scores were significantly decreased in the iloprost group compared to the control group (P 〈0.05).On the 28th day radiographic total score was 12 and histologic total score was 37 in the iloprost group,whereas radiographic total score was 15 and histologic total score was 40 in the control group.On the 28th day although there was a decrease in radiographic and histologic scores of the iloprost group acording to control group,it was not statistically significant (P 〉0.05).Conclusion Iloprost delays fracture healing in early stage in rats.  相似文献   

17.
The primary objective of the present study is to investigate the therapeutic effect of bone marrow-derived mesenchymal stem cells (MSCs) on bleomycin (BLM)-induced lung injury of rats and the effect on transforming growth factor-β (TGF-β) and monocyte chemoattractant protein-1 (MCP-1). MSCs were isolated from SD rats. The recipients rats were divided randomly into four groups: lung injury group, MSC treatment group, MSC control group and normal control group. Rats of lung injury group and MSC treatment group were perfused with BLM of 5mg/kg (0.2-0.3ml) intratracheally, others were perfused with normal saline. After twelve hours, rats of MSC treatment group and MSC control group were injected MSCs of 0.5×10^6per rat into tail vein. Haematoxylin-eosin staining was used to observe the morphology in lung tissue. ELISA was used to detect the contents of TGF-β and MCP-1 in serum and bronchoalveolar lavage fluid (BALF). Collagen content of the lung tissue was assessed by hydroxyproline (HYP) concentration. It was found that the thickness of alveolar wall and lung interstitium were significantly reduced in the rats of MSC treatment group compared with the lung injury group. HYP content in lung interstitium, TGF-β and MCP-1 in serum and BALF were increased significantly in rats of lung injury group two weeks after BLM perfusion, but they were reduced significantly in the rats of MSC treatment group compared with the injured rats. These observations provide evidence that MSCs engraftment could alleviate bleomycin-induced lung injury and fibrosis in rats and the therapeutic effects might relate with the decrease of TGF-β and MCP-1.  相似文献   

18.
A study was performed to make different activities ^131Ⅰ radioactive seeds for tumor bearing mice of U87. The ^131Ⅰ radioactive seeds of 89, 115, 185, 340MBq were sealed in soft plastic tube. Absorbed dose were measured by film and were calculated by S value which was made by Monte Carlo. When the tumor of U89 appeared in the nude mice, these seeds were implanted near the tumor. Then the size of'tumor was measured and the curves of tumor growth were made. After all of these, the continuous low dose rate radiation of long time by ^131Ⅰwas discussed.  相似文献   

19.
Aarsenic trioxide (AT) has a long history of use in both traditional Chinese medicine and in modem medicine in asthma therapy. Recently, Yin et al' found that AT even at small doses reduced the airway inflammation of sensitized guinea pigs. However the mechanism underlying this is still largely unknown. Interleukin 13 (IL-13), as one of the important TH2 cytokines, plays an important role in asthma pathogenesis through promoting eosinophilic inflammation,  相似文献   

20.
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