Combining transcriptomics with network pharmacology to explore the mechanism of Yiqi Huoxue decoction against liver fibrosis

by Yao-Yao Mao, Ke Zhang, Dan-Dan Zhao, Jia-Wei Cui, Zhan-Dong Lin, Cong-Yue Zhang, Yue-Min Nan

Background

Clinical practice commonly uses the Yi-qi Huo-xue formula (YQHX), a traditional Chinese herbal medicine comprising eight herbal components, to treat liver fibrosis resulting from various etiologies. Nevertheless, this formula’s specific active constituents and underlying mechanisms of action remain to be fully elucidated.

Methods

The drug components of YQHX and potential targets for liver fibrosis were identified via the screening of the various databases. Qualitative and quantitative identification of chemical components of drug-containing serum by Ultra Performance Liquid Chromatography (UPLC).Liver fibrosis was induced in mice through the intraperitoneal injection of carbon tetrachloride, followed by oral administration of YQHX. RNA-Seq quantified transcriptomic profiles in liver tissue.The degree of liver fibrosis was assessed via histopathology staining, the transcription and expression of relevant proteins were analyzed. Primary cells were isolated for in vitro experiments to validate the influence of YQHX on the associated signaling pathways.

Results

Network pharmacology identified IL-1β, IL-6, and TNF-α as potential targets for YQHX in treating liver fibrosis.The UPLC detected multiple potential active components. In vivo experiments showed that YQHX reduced serum AST and ALT levels in liver fibrosis-induced mice, decreased liverIL-1β, IL-6, and TNF-α levels, and improved liver fibrosis.The results of transcriptomics suggest that YQHX can reduce the expression of “collagen-activated signaling pathway,” “MyD88-dependent toll-like receptor signaling pathway,” “fibrinolysis” and “toll-like receptor 4 signaling pathway”. Furthermore, YQHX reduced the aggregation of M1 macrophages in the portal area and the deposition of α-SMA. Primary bone marrow-derived cells successfully transformed into M1 macrophages after induction, and YQHX reduced the levels of IL-1β, IL-6, and TNF-α in the supernatant of M1 macrophage culture and decreased the activation of primary hepatic stellate cells indirectly co-cultured with the supernatant. Interestingly, TLR4 agonists weakened this inhibitory effect. Both in vitro and in vivo experiments demonstrated that YQHX could inhibit the expression of the TLR4/TRAF6/MyD88 pathway in M1 macrophages.

Conclusion

We reveal here the molecular mechanism and signaling pathway of YQHX in treating liver fibrosis by utilizing network pharmacology in conjunction with in vivo and in vitro experiments. The findings offer insights that may advance the clinical application of YQHX.

Adjuvant Icotinib in EGFR-mutated stage IB non-small cell lung cancer with high-risk factors: A retrospective case series

by Mengzhi Cheng, Jianbin Zhang, Lili Jin, Caihua Yu, Zhonghai Xie, Dong Li, Qinhua Gu, Qibin Shen

Primary results of the CORIN trial indicated that, compared with chemotherapy, icotinib significantly improved 3-year disease-free survival (DFS) in patients with Epidermal Growth Factor Receptor (EGFR)-mutated stage IB non-small cell lung cancer (NSCLC). However, evidence regarding the outcomes of adjuvant icotinib in patients with high-risk factors remains limited. This retrospective study evaluated the efficacy and safety of adjuvant icotinib in patients with EGFR-mutated high-risk stage IB NSCLC. We enrolled 37 patients with completely resected EGFR-mutated high-risk stage IB NSCLC. The median follow-up time was 31 months, and the 3-year DFS rate was 91.4%. Two patients experienced disease recurrence and were successfully switched to osimertinib upon identification of an EGFR (T790M) mutation. Although overall survival (OS) and central nervous system (CNS)-DFS data were not mature, no deaths or central nervous system metastases were observed by the end of follow-up. 29 (78.4%) patients experienced grade 1–2 adverse events (AEs), no grade 3 or higher AEs occurred. This study suggests a potential DFS benefit and well-tolerated profile of adjuvant icotinib in patients with EGFR-mutated high-risk stage IB NSCLC. However, longer-term follow-up is necessary to assess the long-term outcomes.