Li H.-X.,Guilin Medical University |
Liu H.,Chongqing Iron and Steel Group |
Wang C.-M.,Guilin Medical University |
Wang H.-J.,Guilin Medical University |
Chen J.,Guilin Medical University
European Review for Medical and Pharmacological Sciences | Year: 2014
OBJECTIVE: This study aims to discuss the function and molecular mechanism of artesunate in resisting pulmonary fibrosis. METHODS: Artesunate was used to stimulate the HFL-I cell line, which restrains the expression of Smad7 protein. Under different conditions, all treatment factors were checked, including Smad7, p-P38, ERK, and p-JNK protein expressions. Flow cytometry was used to detect the cell cycle. For the silent expression of the p-Smad7 protein, Western blot analysis revealed that Smad7, p-P38, and p-JNK proteins decreased compared with those of the non-treatment group. RESULTS: No significant changes were observed in Smad7, p-P38, and p-JNK proteins after the cells with silent p-Smad7 protein expression were stimulated by artesunate (p > 0.5). No significant changes were observed in the expression of Smad7, p-P38, and p-JNK proteins after using TGF-β1 recombination factor to cells whose p-Smad7 protein expression is silent (p > 0.5). CONCLUSIONS: Artesunate blocks the MAPK cell conduction pathway through Smad7 to restrain idiopathic pulmonary fibrosis. Artesunate restraining MAPK passage by smad7 to resist pulmonary fibrosis Table I. Cell cycle of HFL-I cell treated by artesunate. Group G1 G2 S p Art 24h 81.97 10.12 7.92 < 0.05 TGF-β1 24h 54.20 9.08 36.72 < 0.05 Sh Art 24h 76.55 11.02 12.43 > 0.05 Sh TGF-β1 24h 54.88 8.34 36.78 < 0.05 Control 76.89 11.73 11.37 Note: p represent compared with the control group. been recently found closely related to cell proliferation and death and may be the target spot of disease treatment3,9,10. MAPK is a series of serine/threonine kinases and is an important signal system that mediates cell response. MAPK includes three passageway proteins: ERK, c-Jun amino terminal kinase (JNK), and p38 pathways. These pathways activate some transcription factors and regulate gene expression10,11. Research shows that artesunate can resist fibrosis2. Artesunate can inhibit the MAPK level chain in the cytoplasm and restrain the phosphorylation of Smad 2/3 by inhibiting JNK and p38 to resist fibrosis10. Our previous research revealed that TGF/Smad pathway plays an important role in resisting pulmonary fibrosis. In recent years, many studies have studied the effect of TGF/Smad pathway on the MAPK pathway7. In mouse muscle fibroblasts, the p38 inhibitory factor can inhibit the phosphoryla-tion of the Smad connection area12,13. In the human mesangial cell, ERK's inhibitory factor can inhibit the phosphorylation of the Smad connection area and promote the composition of I-type collagen14. Artesunate was used to disturb the HELF cells. Research shows that artesunate resists fibrosis through MAPK. Further research verifies that arte-sunate plays a main role by mediating the Smad protein during the process of resisting fibrosis. Furthermore, artesunate's inhibition of the MAPK pathway through the Smad7 protein has a slight effect on ERK. By contrast, some studies reported that among the three main pathways of MAPK, Smad7 has a limited effect on p38 and mainly goes through JNK and ERK pathways3,15,16. Aside from the adjustment of TGF-β/Smad to the expression of Smad7, many inflammation factors have induction functions to Smad7. These signals or chemicals can regulate the MAPK signaling pathway through Smad79,17. Meanwhile, Smad7 can regulate other signaling pathways7. TGF-β can activate the MAPK signal, and increasing evidence supports the major role of Smad7 in the whole process. The study shows that Smad7 may act as skelemin that mediates the activation of JNK or p38 and has the function of inducing cell death11. As an adaptor, Smad7 can promote the interaction between TRAF6/TAK1 and ALK5, and mediate the process of TGF-β activating p3810,18. Moreover, Smad7 plays a regulative role in the process of BMP2 activating TAK1/p3819. This experiment proves that arte-sunate can resist fibrosis through Smad7's function to p38 in the signal conduction pathway. Conclusions Our previous study has proven that TGF-β plays an important role in resisting pulmonary fi-brosis. In the present study, Smad7 as the main functioning protein of TGF-β mediates TGF-β during cell cycle retardation and cell death, whereas other processes play roles in resisting fi-brosis. This function mechanism has been mentioned by some scholars6,20. However, the present study is the first to report on the function mechanism of artesunate in resisting fibrosis through Smad7. This study provides the molecular mechanism and serves as a basis for the clinical treatment of fibrosis. Acknowledgements This study was supported by Projects of Natural Science Foundation of Guangxi (Grant no: 2011GXNSFA018220) and Scientific Research and Technology Development project (Grant no: 101240084). Conflict of Interest The Authors declare that they have no conflict of interests. 3203.
Zhu B.,Chongqing University |
Liu Q.,Chongqing University |
Zhao D.,Chongqing University |
Ren S.,Chongqing University |
And 3 more authors.
Steel Research International | Year: 2016
Based on the double-flow model, a three-dimensional mathematical model of multiphase flow in RH system has been developed to predict the flow field and gas holdup distribution. Also, the circulation flow rate was measured with the water model. The results show that the nozzle blockage layers have small influence on circulation flow rate, while the effect of the blockage modalities and numbers is significant. Under the interaction of blockage modalities and numbers, the gas holdup distribution is the key factor to determine the circulation flow rate. Symmetrical blockage is an acceptable modality under the condition of a small amount of blockage, but the effect of non-symmetrical blockage on circulation flow rate is more obvious. If the blockage number is more than 3, the up-snorkel must be promptly treated or replaced. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Yin X.,Chongqing Iron and Steel Group |
Zhao Y.,Chongqing Iron and Steel Group |
Yang B.,Chongqing Iron and Steel Group |
Fang H.E.,Chongqing Iron and Steel Group |
And 2 more authors.
Chinese Journal of Clinical Oncology | Year: 2010
Objective: To establish the murine Lewis Lung Carcinoma cell tumor vaccine, LLC/IL-12, which can stably express the IL-12 (interleukin-12) gene, and to assess the antitumor effect of 131I-1E2 (anti-lung cancer monoclonal antibody 1E2 labeled with iodine-131) through tail intravenous injection and the synergistic effect of IL-12 vaccine on 131I-E2 targeted therapy. Methods: LLC/IL-12 tumor vaccine was prepared. Na131I was used to label 1E2 Mab. The model of C57BL/6 mice-transplanted tumor was established and the distribution of 131I-IE2 in mice in different groups was observed by tail intravenous injection of 131I-1E2 or combined with intratumoral injection LLC/ mlL-12. When the tumors were large enough, 40 mice were divided into 4 groups: (1) GT group (Gene therapy, i.e. LLC/mlL-12), (2) RIT group (Radio immunotherapy), (3) PBS group, and (4) GT+RIT group. Tumor volume and weight were measured and tumor-inhibitory ratio was calculated after treatment. Analysis of CTL and NK activity was performed. Results: 131I-1E2 could effectively target tumor tissue, especially when combined with IL-12 vaccine. RIT+GT can up-regulate the expression of IL-12 gene and inhibit the tumor growth compared with GT or RIT alone. There was abundant CD4+ and CD8+ T lymphocyte infiltration in the GT and combined group, and NK and CTL cell activity was improved. There was more 131I-IE2 accumulated in tumor tissue in the combination group. Conclusion: 131I-IE2 can obviously inhibit tumor growth and has potential clinical application value. 131I-IE2 may possibly become a new tumor targeting agent.