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Highlights • HCC capsule broken leading to tumor invasion • Macrophage-derived MMP-9/MMP-2 were closely related to the rupture of the FC of HCC • MMP-9/MMP-2 was able to discriminate effectively between ruptured FC and intact FC Graphical Abstract

Abstract Background Currently, systemic therapies for patients with advanced-stage hepatocellular carcinoma (HCC) rely mainly on systemic drugs. However, traditional systemic drugs have a high rate of serious adverse events, and the curative effects of some potential anticancer drugs, such as curcumin (CUR) and resveratrol (RSV), are less apparent due to their poor bioavailability. Therefore, it is urgent to develop a highly effective therapy to improve patient prognosis. Herein, an injectable HCC-targeted nanoparticle (NP) was designed to deliver CUR and RSV to hepatoma cells. Results The molecular self-assembled NPs showed higher tumour retention through the enhanced permeability and retention (EPR) effect of the NPs and surface modification with the HCC-specific peptide moiety SP94 to effectively treat HCC. These HCC-targeted NPs led to a significant reduction in the drug dosage, delayed the rate of drug release and improved the bioavailability of the encapsulated drugs. The drug concentrations in the vicinity of the tumour increased, and a good therapeutic effect was observed without obvious side effects. Conclusions These SP94-mediated NPs allowed large amounts of antitumor drugs to accumulate in tumours, providing a novel strategy for innovative HCC therapy. This nanoplatform also offers an idea for exploring other potential chemotherapeutics. Graphical Abstract

Abstract Background Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor originating from the secondary bile duct and its branch epithelium. Among primary liver tumors, the incidence of ICC is second only to hepatocellular carcinoma. Tumor microenvironment can regulate the occurrence and development of tumors. This study is dedicated to finding more markers that can diagnose ICC by finding the differential tumor microenvironment cells between ICC and normal tissues. Methods We wanted to study the infiltration of immune cells between the cholangiocarcinoma of the same patient and its paired non-tumor tissues, to explore the difference of immune cells in the tumor microenvironment and adjacent non-tumor tissues in the same organism. So, we searched the relevant data of patients with ICC from the GEO database and found that the GSE45001 data set meets our research needs. CIBERSORT database is used to calculate immune cell composition. Finally, perform visual analysis and data statistics to find out the differentially expressed immune cells. Results We found that the expression levels of dendritic cells activated, macrophages M2, and T cells regulatory (Tregs) in ICC were higher than normal tissues, and the expression levels of macrophages M1, monocytes, and T cells follicular helper in ICC were lower than normal tissues. Conclusion These 6 types of immune cells are expected to become molecular markers for clinical diagnosis of ICC.

Abstract Background T cell receptor gamma locus antisense RNA 1 (TRG-AS1) has been reported to involve in the progression of glioblastoma, however the role and its underlying molecular mechanism in hepatocellular carcinoma (HCC) remain unknown. Methods Quantitative real-time polymerase chain reaction (RT-qPCR) was applied to detect TRG-AS1 expression in HCC cells. Besides, the proliferation abilities of HCC cells were assessed by colony formation and EdU assays. The migratory and invasive abilities of HCC cells were examined by transwell assays. Imunofluorescence staining (IF) was used to analyze the epithelial–mesenchymal transitions (EMT). The interaction among TRG-AS1, miR-4500 and BTB domain and CNC homolog 1 (BACH1) were proofed by means of RIP and RNA pull down and luciferase reporter assays. Results TRG-AS1 was conspicuously overexpressed in HCC cells. TRG-AS1 silencing apparently suppressed HCC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). Mechanism exploration revealed that TRG-AS1 acted as a molecular sponge of miR-4500 to regulate BACH1. MiR-4500 silencing or BACH1 overexpression in BACH1-downregulated cells fully rescued cell proliferation migration, invasion and EMT progress. Conclusion TRG-AS1 regulates HCC progression by targeting miR-4500/BACH1 axis.