Background: Hepatocellular carcinoma (HCC), the third most prevalent cause of cancer-related death, is a frequent primary liver cancer with a high rate of morbidity and mortality. T-cell depletion (TEX) is a progressive decline in T-cell function due to continuous stimulation of the TCR in the presence of sustained antigen exposure. Numerous studies have shown that TEX plays an essential role in the antitumor immune process and is significantly associated with patient prognosis. Hence, it is important to gain insight into the potential role of T cell depletion in the tumor microenvironment. The purpose of this study was to develop a trustworthy TEX-based signature using single-cell RNA-seq (scRNA-seq) and high-throughput RNA sequencing, opening up new avenues for evaluating the prognosis and immunotherapeutic response of HCC patients.Methods: The International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases were used to download RNA-seq information for HCC patients. The 10x scRNA-seq. data of HCC were downloaded from GSE166635, and UMAP was used for clustering descending, and subgroup identification. TEX-related genes were identified by gene set variance analysis (GSVA) and weighted gene correlation network analysis (WGCNA). Afterward, we established a prognostic TEX signature using LASSO-Cox analysis. External validation was performed in the ICGC cohort. Immunotherapy response was assessed by the IMvigor210, GSE78220, GSE79671, and GSE91061cohorts. In addition, differences in mutational landscape and chemotherapy sensitivity between different risk groups were investigated. Finally, the differential expression of TEX genes was verified by qRT-PCR.Result: 11 TEX genes were thought to be highly predictive of the prognosis of HCC and substantially related to HCC prognosis. Patients in the low-risk group had a greater overall survival rate than those in the high-risk group, according to multivariate analysis, which also revealed that the model was an independent predictor of HCC. The predictive efficacy of columnar maps created from clinical features and risk scores was strong.Conclusion: TEX signature and column line plots showed good predictive performance, providing a new perspective for assessing pre-immune efficacy, which will be useful for future precision immuno-oncology studies.

Ginsenoside Rg1 (G-Rg1) is a bioactive phytochemical that has been found to be beneficial for the treatment of several diseases including nonalcoholic fatty liver disease (NAFLD). But there is a lack of literature reporting the effect of G-Rg1 on lipid metabolism balance in NAFLD. We investigated the effect and mechanism of G-Rg1 on lipid metabolism in vitro. We found that G-Rg1 decreased the levels of TG, TC, and MDA, and increased activity of SOD. Results of RT-PCR and western blotting showed that supplementation with G-Rg1 downregulated the expression of PPAR γ, FABP1, FATP2/5, CD36, SREBP1 c, and FASN, while the expression of PPAR ɑ, CPT1, ACOX1, MTTP, and ApoB100 was upregulated, after induction by a free fatty acid. Taken together, we conclude that G-Rg1 inhibits lipid synthesis and lipid uptake, and enhances lipid oxidation and lipid export to reduce hepatic steatosis of HepG2 cells by regulating PPAR ɑ and PPAR γ expression. The pathway of G-Rg1 ameliorate lipid accumulation in hepatocytes in vitro.

Background: Tissue-nonspecific alkaline phosphatase (TNAP) expression increases after liver injury, but its role in liver fibrosis remains unclear. This study investigated the effect of TNAP on liver fibrosis and its mechanism in regulating TGF-β1 signaling. Methods: Human liver samples and a CCl₄-induced liver fibrosis mouse model with adv-TNAP and a TNAP inhibitor (tetramisole, Tetra) were used to study the function of TNAP in liver fibrosis. Primary HSCs were used to study the mechanism of TNAP in regulating the TGF-β1 signal. Results: Elevated TNAP expression was observed in human and murine fibrotic liver tissues, correlating with increased fibrotic markers. In vivo experiments using TNAP overexpression and inhibition in a CCl₄-induced liver fibrosis mouse model demonstrated that TNAP exacerbated, while its inhibition alleviated, liver fibrosis. In vitro studies revealed that TNAP regulated TGF-β1 conversion and HSCs activation through the TGF-β1/SMAD pathway. TNAP facilitated TGF-β1 conversion by promoting the interaction between CD47 and thrombospondin-1 (TSP1). Membrane expression of CD47 modulated by TNAP might contribute to the binding effect of CD47 and TSP1. Conclusions: TNAP plays a critical regulatory role in TGF-β1-mediated liver fibrosis, probably by promoting the binding of CD47/TSP1. Targeting TNAP-mediated pathways may offer new therapeutic strategies for liver fibrosis.