Exosome-Related FTCD Facilitates M1 Macrophage Polarization and Impacts the Prognosis of Hepatocellular Carcinoma.

BACKGROUND: Exosomes are essential for hepatocellular carcinoma (HCC) progression and have garnered significant interest as novel targets for diagnostic, prognostic, and therapeutic approaches. This study aims to identify potential exosome-related biomarkers for the development of useful strategies for HCC diagnosis and therapy. METHODS: Three datasets obtained from the Gene Expression Omnibus (GEO) were utilized to identify differentially expressed genes (DEGs) in HCC. Through Gene Ontology (GO) analysis and protein-protein interaction (PPI) network, overall survival (OS) analysis, Cox analyses, and diethylnitrosamine (DEN)-induced HCC mouse model detection, exosome-related hub gene was screened out, followed by a prognostic value assessment and immune-correlates analysis based on the Cancer Genome Atlas (TCGA) dataset. The hub gene-containing exosomes derived from Hepa1-6 cells were isolated and characterized using differential ultracentrifugation, transmission electron microscopy scanning, and Western blot. Ultrasound-guided intrahepatic injection, cell co-culture, CCK-8, and flow cytometry were performed to investigate the effects of the hub gene on macrophage infiltration and polarization in HCC. RESULTS: A total of 83 DEGs enriched in the extracellular exosome term, among which, FTCD, HRA, and C8B showed the strongest association with the progression of HCC. FTCD was independently associated with a protective effect in HCC and selected as the hub gene. The presence of FTCD in exosomes was confirmed. FTCD-stimulated macrophages were polarized towards the M1 type and suppressed HCC cells proliferation. CONCLUSIONS: FTCD is a potential exosome-related biomarker for HCC diagnosis, prognosis, and treatment. The crosstalk between FTCD-containing exosomes and macrophages in HCC progression deserves further investigation.

Human placental mesenchymal stem cells regulate inflammation via the NF­κB signaling pathway.

Emerging evidence has indicated that mesenchymal stem cells (MSCs) are involved in the modulation of inflammation. Human placenta-derived (HPL)-MSCs exist in sufficient quantities and play a role in immune regulation. However, the exact roles of HPL-MSCs in inflammation and the specific underlying mechanisms are not well defined. In the present study, HPL-MSCs were obtained from human fetal placentas, and further purified using a commercial kit. Using ELISA, reverse transcription-quantitative PCR, western blot, NO detection and other assays, the present study revealed that HPL-MSCs may improve lipopolysaccharide-induced macrophage inflammation by regulating macrophage polarization. Further mechanistic studies demonstrated that HPL-MSCs attenuated the NF-κB signaling pathway by regulating the expression of toll-like receptor 4 and the phosphorylation of IκBα and p65, which resulted in a reduction in the levels of inflammation. The present study indicated that HPL-MSCs may act as a novel target for the treatment of inflammation-related diseases.