MicroRNA-708-3p as a potential therapeutic target via the ADAM17-GATA/STAT3 axis in idiopathic pulmonary fibrosis

Bo Liu,Rongrong Li,Jinjin Zhang,Chao Meng,Jie Zhang,Xiaodong Song,Changjun Lv 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

MicroRNAs (miRNAs) are important diagnostic markers and therapeutic targets for many diseases. However, the miRNAs that control the pathogenesis of idiopathic pulmonary fibrosis (IPF) and act as potential therapeutic targets for the disease are rarely studied. In the present study, we analyzed the function and regulatory mechanism of microRNA-708-3p (miR-708-3p) and evaluated this marker’s potential as a therapeutic target in IPF. The clinical and biological relevance of fibrogenesis for miR-708-3p was assessed in vivo and in vitro, specifically in matching plasma and tissue samples from 78 patients with IPF. The data showed that the miR-708-3p levels decreased during fibrosis and inversely correlated with IPF. The experiments showed that the decreased miR-708 promoter activity and primer-miR-708(pri-miR-708) expression were the potential causes. By computational analysis, a dual luciferase reporter system, rescue experiments and a Cignal Finder 45-Pathway system with siADAM17 and a miR-708-3p mimic, we identified that miR-708-3p directly regulates its target gene, a disintegrin and metalloproteinase 17 (ADAM17), through a binding site in the 3′ untranslated region, which depends on the GATA/STAT3 signaling pathway. Finally, an miR-708-3p agomir was designed and used to test the therapeutic effects of the miR-708-3p in an animal model. Small-animal imaging technology and other experiments showed that the dynamic image distribution of the miR-708-3p agomir was mainly concentrated in the lungs and could block fibrogenesis. In conclusion, the miR-708-3p– ADAM17 axis aggravates IPF, and miR-708-3p can serve as a potential therapeutic target for IPF.

Utility of VEGF and sVEGFR-1 in Bronchoalveolar Lavage Fluid for Differential Diagnosis of Primary Lung Cancer

Cao, Chao,Sun, Shi-Fang,Lv, Dan,Chen, Zhong-Bo,Ding, Qun-Li,Deng, Zai-Chun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Published data have shown that the levels of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-1 (sVEGFR-1) in plasma and pleural effusion might be usefulness for lung cancer diagnosis. Here, we performed a prospective study to investigate the utility of VEGF and sVEGFR-1 in bronchoalveolar lavage fluid (BALF) for differential diagnosis of primary lung cancer. A total of 56 patients with solitary pulmonary massed by chest radiograph or CT screening were enrolled in this study. BALF and plasma samples were obtained from all patients and analyzed for VEGF and sVEGFR-1 using a commercially available sandwich ELISA kit. The results showed that the levels of VEGF in BALF were significantly higher in patients with a malignant pulmonary mass compared with patients with a benign mass (P < 0.001). However, no significant difference of sVEGFR-1 in BALF was found between malignant and non-malignant groups (P = 0.43). With a cut-off value of 214 pg/ml, VEGF showed a sensitivity and specificity of 81.8% and 84.2%, respectively, in predicting the malignant nature of a solitary pulmonary mass. Our study suggests that VEGF is significantly increased in BALF among patients with lung cancer than in benign diseases. Measurement of VEGF in BALF might be helpful for differential diagnosis of primary lung cancer.

Construction of a Protein-Protein Interaction Network for Chronic Myelocytic Leukemia and Pathway Prediction of Molecular Complexes

Zhou, Chao,Teng, Wen-Jing,Yang, Jing,Hu, Zhen-Bo,Wang, Cong-Cong,Qin, Bao-Ning,Lv, Qing-Liang,Liu, Ze-Wang,Sun, Chang-Gang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Background: Chronic myelocytic leukemia is a disease that threatens both adults and children. Great progress has been achieved in treatment but protein-protein interaction networks underlining chronic myelocytic leukemia are less known. Objective: To develop a protein-protein interaction network for chronic myelocytic leukemia based on gene expression and to predict biological pathways underlying molecular complexes in the network. Materials and Methods: Genes involved in chronic myelocytic leukemia were selected from OMIM database. Literature mining was performed by Agilent Literature Search plugin and a protein-protein interaction network of chronic myelocytic leukemia was established by Cytoscape. The molecular complexes in the network were detected by Clusterviz plugin and pathway enrichment of molecular complexes were performed by DAVID online. Results and Discussion: There are seventy-nine chronic myelocytic leukemia genes in the Mendelian Inheritance In Man Database. The protein-protein interaction network of chronic myelocytic leukemia contained 638 nodes, 1830 edges and perhaps 5 molecular complexes. Among them, complex 1 is involved in pathways that are related to cytokine secretion, cytokine-receptor binding, cytokine receptor signaling, while complex 3 is related to biological behavior of tumors which can provide the bioinformatic foundation for further understanding the mechanisms of chronic myelocytic leukemia.

Fabrication of Photopolymer Hierarchical Micronanostructures by Coupling Electrospinning and Photolithography for SERS Substrates

Wen-Yi Zhang,Xin-Ze Xiao,Chao Lv,Jia Zhao,Gong Wang,Xuan Gu,Ran Zhang,Bin-Bin Xu,Dan-Dan Zhang,Ai-Wu Li,Yong-Lai Zhang,Hong-Bo Sun 한국고분자학회 2013 Macromolecular Research Vol.21 No.3

Reported here is the fabrication of photopolymer hierarchical micronanostructures through a combinative process of electrospinning and subsequent photolithography. Electrospun SU-8 (epoxy-based negative photoresist)nanofiber films have been patterned into gratings with periods of 100, 200, 300, and 400 μm, respectively. Deposition of a silver nanolayer on these interlaced nanofiber films would lead to the formation of various plasmonic nanostructures,and therefore, giving rise to abundant surface-enhanced Raman scattering (SERS) “hot spots”. In the detection of Rhodamine 6G (R6G), probing molecule, the resultant SERS substrates show both high sensitivity and good reproducibility. The SERS enhancement factor could reach as high as ~108, indicating high efficiency. The fabrication of patterned, highly efficient SERS substrates may hold a great promise for the integration of SERS substrates in various microdevices such as microfluidic chips.

The characteristics of genistin-induced inhibitory effects on intestinal motility

Yong-jian Xiong,Da-peng Chen,Bo-chao Lv,Fang-fei Liu,Li Wang,Yuan Lin 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.3

Genistin belongs to isoflavones. Based on thefacts that genistin exerts inhibitory effects on the contractilityof vascular smooth muscle,the present study wasdesigned to characterize the effects of genistin on intestinalcontractility and evaluate its potential clinical implication. Ex vivo [isolated jejunal segment (IJS) of rat], in vitro, andin vivo assays were used in the study. The results indicatedthat genistin (5–80 lmol/L) inhibited the contraction of IJSin a dose-dependent manner and inhibited the increasedcontractilityof IJS induced by acetylcholine (ACh), histamine,high Ca2?, and erythromycin, respectively. Theinhibitory effects of genistin were correlated with thestimulation of alpha adrenergic and beta adrenergicreceptors since these inhibitory effects were significantlyblocked in the presence of phentolamine and propranololrespectively. No further inhibitory effects of genistin wereobserved in the presence of verapamil or in Ca2?-freecondition, indicating genistin-induced inhibitory effects areCa2?-dependent. Genistin decreased myosin light chainkinase (MLCK) protein contents and MLCK mRNAexpression in IJS, and inhibited both phosphorylation andMg2?-ATPase activity of purified myosin, implicating thatthe decrease of MLCK contents and inhibition of MLCKactivity are involved in the genistin-induced inhibitoryeffects. The study suggests the potential clinical implicationsof genistin in relieving intestinal hypercontractility.

Characteristics of Diprophylline-Induced Bidirectional Modulation on Rat Jejunal Contractility

Liu, Fang-Fei,Chen, Da-Peng,Xiong, Yong-Jian,Lv, Bo-Chao,Lin, Yuan The Korean Society of Pharmacology 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.1

In this study, we propose that diprophylline exerts bidirectional modulation (BM) on the isolated rat jejunal segment depending on its contractile state. The results supported the hypothesis. Diprophylline ($20{\mu}M$) exerted stimulatory effects on the contractility of jejunal segment in six low contractile states while inhibitory effects in six high contractile states, showing the characteristics of BM. Diprophylline-induced stimulatory effect was significantly blocked by atropine, indicating the correlation with cholinergic activation. Diprophylline-induced inhibitory effect was partially blocked by phentolamine, propranolol, and L-N-Nitro-Arginine respectively, indicating their correlation with sympathetic activation and nitric oxide-mediated relaxing mechanisms. Diprophylline-induced BM was abolished by tetrodotoxin or in a $Ca^{2+}$ free condition or pretreated with tyrosine kinase inhibitor imatinib, suggesting that diprophylline-induced BM is $Ca^{2+}$ dependent, and that it requires the presence of enteric nervous system as well as pacemaker activity of interstitial cells of Cajal. Diprophylline significantly increased the reduced MLCK expression and myosin extent in constipation-prominent rats and significantly decreased the increased MLCK expression and myosin extent in diarrhea-prominent rats, suggesting that the change of MLCK expression may also be involved in diprophylline-induced BM on rat jejunal contractility. In summary, diprophylline-exerted BM depends on the contractile states of the jejunal segments, requires the presence of $Ca^{2+}$, enteric nervous system, pacemaker activity of interstitial cells of Cajal, and MLCK-correlated myosin phosphorylation. The results suggest the potential implication of diprophylline in relieving alternative hypo/hyper intestinal motility.