Influence of Danshen Injection on airway inflammation and CD4^+ CD25^+ regulatory T cells of asthmatic rats

Objective： To investigate the influence of Danshen Injection on airway inflammation and CD4^＋CD25^＋ regulatory T cells（CD4^＋CD25^＋ Tr） of asthmatic rats, and elucidate the possible mechanism of Danshen Injection in treatment of asthma. Methods： 30 Wister rats were randomly divided into control group, asthma group and Danshen Injection treated group. Bronchoalveolar lavage fluids （BALF） were collected, and cytology studies were conducted. Lung tissues were obtained and pathologic analyses were done with hematoxylin and eosin stain （HE）. Flow cytometry was used to detect the CD4^＋CD25^＋ Tr ratio in peripheral blood mononuclear cells （PBMCs）. Results： Total cell, the percentage of lymphocytes, neutrophils and eosinophils （Eos） in BALF of Danshen Injection-treated group were lower than that in asthma group （P〈0.05, P〈0.01）. Compared with asthma group, less infiltration of inflammatory cells in lung tissues was observed in Danshen Injection-treated group. CD4^＋CD25^＋ Tr of asthma group was lower than that of control and Danshen Injection treated group （P〈0.05）. Conclusion： Danshen Injection can suppress airway inflammation of asthmatic rats, probably by increasing the number of CD4^＋CD25^＋ Tr.

The expression of CD40 and CD40L on the surface of peripheral blood mononuclear cells in asthmatic rats and the effect of anti-CD40L McAb on Th1 and Th2 cytokines

Objective： To investigate the expression of CD40 and CD40 ligand （CD4OL） on the surface of peripheral blood mononuclear cells（PBMCs） in asthmatic rats and the effect of anti-CD40L McAb on cytokines of PBMCs. Methods： Flow cytometry and RT-PCR were used to detect the expression of CD40 and CD40L of PBMCs in asthmatic rats. After the PBMCs was treated with anti-CD40L McAb, ELISA was used to detect the IL-4 and IFN-γ levels of culture supernatants. Results： Compared with the normal control group, the expression of CD40 and CD40L of PBMCs in asthmatic rats increased （P 〈 0.05）. Compared with the untreated group, the level of IL-γ and the ratio of IL-4/IFN-γ decreased after the PBMCs was treated with anti-CD40L McAb（P 〈 0.05）. Conclusion： The expression of CD40 and CD40L on the surface of PBMCs in asthmatic rats was up-regulated. Anti-CD40L McAb can rectify the imbalance of Th1 and Th2 cytokines.

Local administration of liposomal-based Plekhf1 gene therapy attenuates pulmonary fibrosis by modulating macrophage polarization

Idiopathic pulmonary fibrosis(IPF)is a fatal interstitial lung disease with limited therapeutic options.Macrophages,particularly alternatively activated macrophages(M2),have been recognized to contribute to the pathogenesis of pulmonary fibrosis.Therefore,targeting macrophages might be a viable therapeutic strategy for IPF.Herein,we report a potential nanomedicinebased gene therapy for IPF by modulating macrophage M2 activation.In this study,we illustrated that the levels of pleckstrin homology and FYVE domain containing 1(Plekhf1)were increased in the lungs originating from IPF patients and PF mice.Further functionality studies identified the pivotal role of Plekhf1 in macrophage M2 activation.Mechanistically,Plekhf1 was upregulated by IL-4/IL-13 stimulation,after which Plekhf1 enhanced PI3K/Akt signaling to promote the macrophage M2 program and exacerbate pulmonary fibrosis.Therefore,intratracheal administration of Plekhf1 siRNA-loaded liposomes could effectively suppress the expression of Plekhf1 in the lungs and notably protect mice against BLM-induced lung injury and fibrosis,concomitant with a significant reduction in M2 macrophage accumulation in the lungs.In conclusion,Plekhf1 may play a crucial role in the pathogenesis of pulmonary fibrosis,and Plekhf1 siRNA-loaded liposomes might be a promising therapeutic approach against pulmonary fibrosis.

Expression of Syk in non-small cell lung cancer and its relationship with clinicopathological parameters

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 clinico-pathologic 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 can-cer,16 cases of lung adenocarcinoma)and tumor-sur-rounding normal lung tissues.The positive rate of Syk was 46.15%(18/39)and 100%(39/39)in NSCLC and tumor-surrounding normal lung tissues,respectively.The expres-sion 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.