| Autor: |
Jun Liu, Dan-Dan Li, Wei Dong, Yu-Qi Liu, Yang Wu, Da-Xuan Tang, Fu-Chun Zhang, Meng Qiu, Qi Hua, Jing-Yu He, Jun Li, Bai Du, Ting-Hai Du, Lin-Lin Niu, Xue-Jun Jiang, Bo Cui, Jiang-Bin Chen, Yang-Gan Wang, Hai-Rong Wang, Qin Yu, Jing He, Yi-Lin Mao, Xiao-Fang Bin, Yue Deng, Yu-Dan Tian, Qing-Hua Han, Da-Jin Liu, Li-Qin Duan, Ming-Jun Zhao, Cui-Ying Zhang, Hai-Ying Dai, Ze-Hua Li, Ying Xiao, You-Zhi Hu, Xiao-Yu Huang, Kun Xing, Xin Jiang, Chao-Feng Liu, Jing An, Feng-Chun Li, Tao Tao, Jin-Fa Jiang, Ying Yang, Yao-Rong Dong, Lei Zhang, Guang Fu, Ying Li, Shu-Wei Huang, Li-Ping Dou, Lan-Jun Sun, Ying-Qiang Zhao, Jie Li, Yun Xia, Fan Liu, Wen-Jin He, Jian-Cong Tan, Yang Lin, Ya-Bin Zhou, Jian-Fei Yang, Guo-Qing Ma, Hui-Jun Chen, He-Ping Liu, Zong-Wu Liu, Jian-Xiong Liu, Xiao-Jia Luo, Xiao-Hong Bin, Ya-Nan Yu, Hai-Xia Dang, Bing Li, Fei Teng, Wang-Min Qiao, Xiao-Long Zhu, Bing-Wei Chen, Qi-Guang Chen, Chun-Ti Shen, Yong-Yan Wang, Yun-Dai Chen, Zhong Wang |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-10 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2059-3635 |
| DOI: |
10.1038/s41392-021-00741-x |
| Popis: |
Abstract It’s a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86–19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82–20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06–15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r 2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316). |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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