Progress in the research of epigenetic regulation of airway smooth muscle cells in asthma / 基础医学与临床

Hyperplasia of smooth muscle cells is a major aspect of airway remodeling in asthma .In recent years.It is found that the epigenetic regulation plays an important role on the proliferation of airway smooth muscle cells and the secretion of inflammatory cytokines , including DNA methyltransferase inhibitors to inhibit the phenotype trans-formation;histone acetylation related with hypertrophy .In addition , the microRNA is potentially related with the regulation of a variety of physiological functions of airway smooth muscle cells of asthma model , including inhibition of proliferation and release of inflammatory factors .Hope that epigenetics can become a new target for the treatment of asthma .

Expressions and clinical significance of Nanog and CD44 protein in lung cancer / 实用医学杂志

Objective To detect the expressions and clinical significance of Nanog and CD44 protein in lung cancer. Methods The expressions of Nanog and CD44 were detected by immunohistochemistry in 50 cases of lung cancer, 32 cases of benign lesion lung tissue and 18 cases of paraneoplastic normal lung tissue. Then their relationships with clinicopathological factors were analyzed. Results The expression of Nanog in lung cancer was significantly higher than those in benign lesion lung tissue and paraneoplastic normal lung tissue (P 0.05). The expressions of Nanog and CD44 in squamous cell carcinomas were higher than those in adenocarcinomas and small cell lung carcinomas (P 0.05). The positive correlation was also noted between the expressions of Nanog and CD44 in lung cancer (r = 0.564, P < 0.05). Conclusion Nanog and CD44 proteins may participate in the genesis and progression of lung cancer. Nanog protein is a potential diagnostic marker and therapeutic target for lung cancer.

The Diagnostic Value of Sox2 mRNA Transcription Level in Bronchoscopy Biopsy Specimens in Lung Cancer / 天津医药

Objective To study the diagnostic value of Sox2 mRNA transcription level in bronchoscopic biopsy specimens from lung cancer patients. Methods The expression of Sox2 mRNA was detected using RT-PCR from 100 hu-man lung cancer biopsy and 18 non-cancer lung biopsy through bronchoscopy. The expression of Sox2 protein was examined by immunohistochemistry from 50 cases of lung cancer biopsy, 32 cases of benign lung lesions and 18 cases of pericarcino-matous normal lung tissues. Then the relationships between Sox2 mRNA transcription level and lung cancer clinical patho-logical parameters were analyzed to test the diagnostic value of Sox2 transcription level. Results The transcription of Sox2 mRNA and its protein expression level were significantly higher in lung cancer than that in benign pulmonary disease tissues (P＜0.05). The transcription of Sox2 mRNA was not correlated with age, gender, histology, lymph node metastasis, TNM stage and differentiation of lung cancer patients (P>0.05). The Sox2 mRNA yielded an area of 0.748 under the ROC curve with the sensitivity of 85.0%and the specificity of 61.1%, taking the cut-off value of 0.513. Conclusion The Sox2 mRNA might be a useful diagnostic marker for lung cancer.

Effect of TLR4/PI3K-related signaling molecules on the migration of asthmatic airway smooth musde cells induced by airway epithelial cells / 中华微生物学和免疫学杂志

ObjectiveTo explore the effect of TLR4,PI3K and NF-κB on the migration of asthmatic airway smooth muscle cell(ASMCs) induced by airway epithelial cells.MethodsPrimary ASMCs were cultured by the method of cell digestion.Cell culture supernatant of RTE cells were collected by TNF-α stimulation of epithelial cells.Detected the IL-8 and RANTES levels in the supernatant.The effect of TLR4/PI3K-related signaling molecules on the migration of asthmatic ASMCs induced by epithelial cells were detected by Modified Boyden chemotaxis chamber with anti-TLR4 antibody,Wortmannin and PDTC drugs as a tool.ResultsThe levels of IL-8 and RANTES in the supernatant of TNF-αgroups were significantly increased,and that in the 20 ng/ml group was significantly higher than other groups ( P＜0.01 ).Compared with control group,the transmembrane migration of asthmatic ASMCs from other groups was significantly increased (P＜0.01 ).The transmembrane migration of asthmatic ASMCs from treated groups was significantly increased than asthma group (P＜0.01).The migration of asthmatic ASMCs from TNF-α+anti-TLR4 antibody group,TNF-α+Wortmannin group and TNF-α+Wortmannin+PDTC were significantly decreased than that of TNF-αgroup( P＜0.01 ).The migration of asthmatic ASMCs from TNF-α+Wortmannin+PDTC were significantly decreased than that of TNF-α+Wortmannin group (P＜0.05).ConclusionTLR4/PI3K-related signaling molecules involved in the transmembrane migration of asthmatic ASMCs induced by airway epithelial cells and may be one of the mechanisms of airway remodeling of asthma.

Expression of heme oxygenase-1 in the peripheral blood mononuclear cells from asthmatic patients / 华中科技大学学报（医学）（英德文版）

To explore the expression of heme oxygenase-1 (HO-1) in the peripheral blood mononuclear cells (PBMCs) and its relationship with pulmonary ventilation function in asthmatic patients, 18 asthmatic patients and 18 healthy subjects were selected. HO-1 protein and mRNA levels in PBMCs were measured by immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Blood carbon monoxide Hb (COHb), serum total IgE and pulmonary ventilatory function were observed. Our results showed that the percentage of cells positive for immunohistochemical staining of HO-1 were significantly higher in asthmatic patients (41.72 +/- 7.44) % than that in with healthy subjects (10.45 +/- 4.36) % (P < 0.001) and the optical density of PBMC HO-1 mRNA was higher in asthmatic patients (26.05 +/- 4.14) than that in healthy subjects (10. 82 +/- 4.26) (P < 0.001). The relation analysis showed that PBMC HO-1 protein and mRNA levels had significantly negative relation with FEV1%, PEFR, MEFR50%, respectively (r = -0.51-0.89, P < 0.05-0.001, respectively) and a positive relation with COHb and serum total IgE (r = 0.48-0. 85, 0.05-0.001, respectively). It is concluded that the expression of PBMC HO-1 protein and mRNA increased significantly in asthmatic patients, and HO-1 may play a significant role in the pathogenesis of asthma. The expression of HO-1 may bear a relation with severity of asthma.

Expression of Heme Oxygenase-1 in the Peripheral Blood Mononuclear Cells from Asthmatic Patients / 华中科技大学学报（医学）（英德文版）

To explore the expression of heme oxygenase-1 (HO-1) in the peripheral blood mononuclear cells (PBMCs) and its relationship with pulmonary ventilation function in asthmatic patients, 18 asthmatic patients and 18 healthy subjects were selected. HO-1 protein and mRNA levels in PBMCs were measured by immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Blood carbon monoxide Hb (COHb), serum total IgE and pulmonary ventilatory function were observed. Our results showed that the percentage of cells positive for immunohistochemical staining of HO-1 were significantly higher in asthmatic patients (41.72±7.44) % than that in with healthy subjects (10.45±4.36) % (P<0.001) and the optical density of PBMC HO-1 mRNA was higher in asthmatic patients (26.05±4.14) than that in healthy subjects (10.82±4.26) (P<0.001). The relation analysis showed that PBMC HO-1 protein and mRNA levels had significantly negative relation with FEV1 %, PEFR, MEFR50 %, respectively (r=-0.51-0.89, P<0.05-0.001, respectively) and a positive relation with COHb and serum total IgE (r=0.48-0.85, 0.05-0.001, respectively). It is concluded that the expression of PBMC HO-1 protein and mRNA increased significantly in asthmatic patients, and HO-1 may play a significant role in the pathogenesis of asthma. The expression of HO-1 may bear a relation with severity of asthma.

Effect of levcromakalim on ET-1 induced proliferation and expression of protein kinase C in vascular smooth muscle cells / 中国临床药理学与治疗学

AIM:To observe the effect of levcromakalim(Lev) on endthelin-1(ET-1) induced proliferation and the expression of protein kinase C(PKC) in cultured rat vascular smooth muscle cells(VSMCs).METHODS: VSMCs were isolated from rat aorta and were cultured with different concentrations of Lev in vitro after stimulated to proliferation by ET-1(10~(-8)(mol?L~(-1))).Vitality of VSMCs was detected by MTT;DNA replication was evaluated by 3H-TdR method.Flow cytometry was used to analyze cell cycle and apoptosis.The expression of PKC? protein and mRNA were determined by Western blot and reverse transcription-polymerase chain reaction(RT-PCR).RESULTS:Vitality of VSMCs and 3H-TdR intermingle rate were decreased(P

Effects of chloride channel blocker on hypoxia induced rat pulmonary hypertension / 中国临床药理学与治疗学

AIM: To investigate the therapeutic effect of chloride channel blocker tamoxifen on hypoxia pulmonary hypertension in rats.METHODS: Sixty male Wistar rats were randomly divided into therapeutic group(H/Q group),hypoxia group(H group),normal control group(C group).Mean pulmonary artery pressure(mPAP),the ratio of the weight of right ventricle to that of left ventricle plus septum[RV(LV+S)],and the ratio of the pulmonary arteriole wall area to that of vascular total area(WA/TA),were measured at 4,7,14,21 days.RESULTS:The mPAP began to increase from 7 days,and reached peak at 21 days in hypoxia group,however it is obviously lower in therapeutic group at same time.The ratio of RV(LV+S) began to increase from 14 days,and reached peak at 21 days in hypoxia group,however it is obviously lower in therapeutic group at same time.The ratio of WA/TA at 21 days in hypoxia group was significantly higher than therapeutic group,respectively(P

Nuclear factor-kappa B in signal conduction of protein kinase C in T lymphocytes from an asthmatic guinea pig model / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To explore the role of nuclear factor-kappa B (NF-kappa B) in the signal conduction of protein kinase C (PKC) regulated proliferation, apoptosis and expression of Th2 cytokines -- interleukin-4 (IL-4) and interleukin-5 (IL-5) of T lymphocytes in the bronchial alveolus lavage fluid (BALF).</p><p><b>METHODS</b>T lymphocytes were isolated and purified from BALF of asthmatic guinea pigs in normal and asthmatic groups, and were stimulated with PKC agitator phorbol 12-myristate 13-acetate (PMA) and NF-kappa B inhibitor pyrrolidine dithiocarbamate (PDTC), respectively. The expressions of NF-kappa B, IL-4 and IL-5 mRNA and protein, the proliferation and apoptosis of T lymphocytes were observed by immunohistochemistry, in situ hybridization, ELISA, MTT and TUNEL, respectively.</p><p><b>RESULTS</b>The activation of NF-kappa B, proliferation response, and expression of IL-4 and IL-5 mRNA and protein in T lymphocytes stimulated by PMA were significantly higher than those of their blank control (P < 0.01), while those indexes of T lymphocytes stimulated by PMA and PDTC simultaneously were significantly lower than those stimulated by PMA alone (P < 0.01). The apoptotic index of T lymphocytes stimulated with PMA were significantly lower than that of their blank control (P < 0.01), and the apoptotic index of asthmatic guinea pig T lymphocytes stimulated with PMA and PDTC simultaneously were significantly higher than that stimulated by PMA alone (P < 0.01). The significant positive correlations were found between the activation of NF-kappa B and the proliferation (r = 0.64, P < 0.001), and the expression of IL-4 and IL-5 mRNA and protein of T lymphocytes, respectively (r = 0.55 - 0.68, P < 0.001). There was also significant negative correlation between the activation of NF-kappa B and apoptosis of T lymphocytes (r = 0.62, P < 0.001).</p><p><b>CONCLUSIONS</b>NF-kappa B may participate in the signal conduction of PKC regulated proliferation, apoptosis and expression of IL-4 and IL-5 of T lymphocytes in asthma. The activation of NF-kappa B in PKC signal conduction pathway of T lymphocytes may play an important role in the pathogenesis of asthma.</p>

Effect of nuclear factor kappa B on TNF-? induced proliferation,apoptosis and the expression of TGF-?_1 in airway smooth muscle cells / 中国病理生理杂志

AIM:To investigate the effect of nuclear factor kappa B(NF-?B)on proliferation,apoptosis and the expression of TGF-?1 in airway smooth muscle cells(ASMCs).METHODS:Cultured ASMCs were divided into three groups and stimulated with or without TNF-? and pyrrolidine dithiocarbamate(PDTC)in vitro.Reverse transcriptase-polymerase chain reaction(RT-PCR)was used to detect the expression of TGF-?1 mRNA.The location and protein expression of PCNA and Bcl-2 were observed by immunocytochemical staining.The protein expression of TGF-?1 and NF-?B was detected by Western blotting.The proliferation and apoptosis of ASMCs were also observed.RESULTS:The activity of NF-?B in TNF-? group was significantly higher than that in control group and TNF-? plus PDTC group,respectively(P

Inhibitory effect of breviscapine on primary cultural calf pulmonary artery smooth muscle cell proliferotion / 中国药理学通报

AIM To explore the effect of breviscapine on primary cultural calf pulmonary artery smooth muscle cell (PASMC) proliferation. METHODS By primary cuture of calf PASMC, the effect of PASMC proliferation was analysed using MTT colorimetry, flow cytomerty, Giemsa staining. RESULTS Compared with control group, PASMC proliferations in breviscapine group was significantly inhibited from G 0/G 1 to S phases in the cell cycle. CONCLUSION Breviscapine could significantly inhibit PASMC profiferation. The mechanism for this may due to inhibition of protein kinase C.

Expression of nuclear factor-?B in asthmatic guinea pigs and the effect of erigeron breviscapus on it / 中国病理生理杂志

AIM: To explore the expression of nuclear factor-?B(NF-?B) in asthmatic guinea pigs, and the effect of erigeron breviscapus, a protein kinase C(PKC) inhibitor, on the expression of nuclear factor-?B(NF-?B). METHODS: 48 guinea pigs were randomly divided into 6 groups ( n= 8). Airway resistance and eosinophilic inflammation of airway wall were examined, the expression of NF-?B in the lung tissue was detected by immunohistochemical staining. RESULTS: The expression of NF-?B was mainly found in airway epithelium, all the asthmatic animals showed significantly higher optical densities than that of the normal control group( P