Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, leading to a large global cancer burden. Hepatocyte growth factor (HGF) and its highaffinity receptor, mesenchymal epithelial transition factor (c-Met), are closely related to the onset, progression, and metastasis of multiple tumors. The HGF/c-Met axis is involved in cell proliferation, movement, differentiation, invasion, angiogenesis, and apoptosis by activating multiple downstream signaling pathways. In this review, we focus on the function of the HGF/c-Met axis in HCC. The HGF/c-Met axis promotes the onset, proliferation, invasion, and metastasis of HCC. Moreover, it can serve as a biomarker for diagnosis and prognosis, as well as a therapeutic target for HCC. In addition, it is closely related to drug resistance during HCC treatment.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. The prognosis of HCC remains very poor; thus, an effective treatment remains urgent. Herein, a type of nanomedicine is developed by conjugating Fe@Fe 3 O 4 nanoparticles with ginsenoside Rg3 (NpRg3), which achieves an excellent coupling effect. In the dimethylnitrosamineinduced HCC model, NpRg3 application significantly prolongs the survival of HCC mice. Further research indicates that NpRg3 application significantly inhibits HCC development and eliminates HCC metastasis to the lung. Notably, NpRg3 application delays HCC-induced ileocecal morphology and gut microbial alterations more than 12 weeks during HCC progression. NpRg3 administration elevates the abundance of Bacteroidetes and Verrucomicrobia, but decreases Firmicutes. Twenty-nine predicted microbial gene functions are enriched, while seven gene functions are reduced after NpRg3 administration. Moreover, the metabolomics profile presents a significant progression during HCC development, but NpRg3 administration corrects tumor-dominant metabolomics. NpRg3 administration decreases 3-indolepropionic acid and urea, but elevates free fatty acids. Importantly, NpRg3 application remodels the unbalanced correlation networks between gut microbiota and metabolism during HCC therapy. In conclusion, nanoparticle conjugation of ginsenoside Rg3 inhibits HCC development and metastasis via the remodeling of unbalanced gut microbiota and metabolism in vivo, providing an antitumor therapy strategy.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.

Objective: The intestinal microbiome is associated with various autoimmune diseases. Regional difference is the main influencing factor of intestinal microbial difference. This study aimed to identify the differences in fecal microbiome between autoimmune hepatitis (AIH) patients and healthy controls (HCs) in Central China, and to validate the efficacy of fecal microbiome as a diagnostic tool for AIH. Design: We collected 115 fecal samples from AIH patients (N = 37) and HCs (N = 78) in Central China and performed gene sequencing. Fecal microbiomes were characterized and microbial markers for AIH were identified. Results: Fecal microbial diversity showed a downward trend in AIH compared with HCs. Fecal microbial communities significantly differed between both groups. At the phylum level, Verrucomicrobia abundance was significantly increased, while Lentisphaerae and Synergistetes were significantly decreased in the AIH patients vs. the HCs. Compared to the HCs, 15 genera, including Veillonella, Faecalibacterium, and Akkermansia, were enriched, while 19 genera, such as Pseudobutyrivibrio, Lachnospira, and Ruminococcaceae, were decreased in the AIH patients. Ten genera, including Veillonella, Faecalibacterium, and Akkermansia, predominated in the AIH patients. Five microbial biomarkers were deemed optimal diagnostic tools for AIH. The probability of disease was significantly increased in AIH group vs. HCs, achieving 83.25% value of area under the curve. Lou et al. Fecal Microbiome in Autoimmune Hepatitis Conclusion: We present the characteristics of AIH patients in Central China for the first time. Five microbial biomarkers, including Lachnospiraceae, Veillonella, Bacteroides, Roseburia, and Ruminococcaceae, achieved a high potential distinguishing AIH patients from HCs.

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