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. 2019 Mar 13;9(1):4335.
doi: 10.1038/s41598-019-40356-5.

Multiomics analysis profile acute liver injury module clusters to compare the therapeutic efficacy of bifendate and muaddil sapra

Ainiwaer Talifu  1   2   3 , Refuhati Saimaiti  2 , Yusufu Maitinuer  2 , Geyu Liu  1 , Miernisha Abudureyimu  1   2   3 , Xuelei Xin  4
Affiliations

Multiomics analysis profile acute liver injury module clusters to compare the therapeutic efficacy of bifendate and muaddil sapra

Ainiwaer Talifu et al. Sci Rep. .

Abstract

The pathogenesis of acute liver injury has been plagued by biologists and physicians. We know little about its therapeutic mechanism. Therefore, this study explored the mechanism of bifendate and muaddil sapra in the treatment of acute liver injury. Firstly, co-expression and cluster analysis of disease-related genes were carried out, and the Go function and KEGG pathway of modules and related genes were identified. Secondly, pivot analysis of modules can identify key regulators. On the other hand, based on the acute liver injury induced by CCl4, we use the combined analysis of proteomics and transcriptome to find therapeutic targets and related mechanisms of drugs. A total of 21 dysfunction modules were obtained, which were significantly involved in immune system, hepatitis and other related functions and pathways. Transcriptome analysis showed 117 targets for bifendate treatment, while 119 for muaddil sapra. Through exploring the mechanism, we found that the two drugs could modulate the module genes. Moreover, bifendate regulate the dysfunction module through ncRNA (SNORD43 and RNU11). Muaddil sapra can mediate dysfunction modules not only by regulating ncRNA (PRIM2 and PIP5K1B), but also by regulating TF (STAT1 and IRF8), thus having a wider therapeutic potential. On the other hand, proteome analysis showed that bifendate mainly regulated Rac2, Fermt3 and Plg, while muaddil sapra mainly regulated Sqle and Stat1. In addition, muaddil sapra regulates less metabolic related proteins to make them more effective. Overall, this study not only provides basic theory for further study of the complex pathogenesis of acute liver injury, but also provides valuable reference for clinical use of bifendate and muaddil sapra in the treatment of acute liver injury.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Co-expression modules.
Figure 2
Figure 2
Enrichment analysis.
Figure 3
Figure 3
ncRNA and TF-pivot of regulatory module.
Figure 4
Figure 4
Identification of drug treatment targets.
Figure 5
Figure 5
Target proteins of drugs.
Figure 6
Figure 6
Interaction Network of Drug Target Proteins.
See this image and copyright information in PMC

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