ABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC), the most primary malignant liver tumor and is ranked as the fifth most common malignancy worldwide. Despite various therapeutic approaches being used in clinical practice, the overall effectiveness remains insufficient. Stigmasterol, a compound known for its anti-tumor properties and ability to induce apoptosis in tumor cells, has been found to influenced the composition of the intestinal microbiota. However, the mechanism through which stigmasterol influences the intestinal microbial-host crosstalk in HCC remains elusive. PURPOSE: This study was to investigate whether stigmasterol can remodel gut microbiota, and suppress tumor volume by regulating Treg and IFN-γ+ CD8+ cell in the host with HCC. METHOD: Stigmasterol (at dosages of 0, 50, 100, or 200 mg/kg) was orally administered to Balb/c mice with subcutaneous tumor once every 2 days for 3 weeks. RESULTS: We first found that tumors volume in the group treated with 100 mg/kg stigmasterol were significantly decreased compared with those in the control group (P < 0.05), which exhibited a similar effect as the sorafenib treatment in mice with HCC. This resulted in a significant upregulation of Caspase3, Bax, and P53 expressions, as well as a decrease in Cyclin D1 expression, ultimately leading to a reduction in tumor volume. Additionally, stigmasterol can alter the α and ß diversity of the intestinal flora and significantly increase the abundance of Lactobacillus_johnsonii, Lactobacillus_murinus, and Lactobacillus_reuteri (P<0.05), which can lead to a decrease in the ratio of regulatory T cells (Tregs) to CD8+ T cells in the intestinal tract and tumor tissue, and consequently enhance immune response in the tumor microenvironment (TME) in the host with HCC. CONCLUSION: In this study, we initially utilized different dosages of stigmasterol to intervene in mice with HCC and confirmed its inhibitory effects on tumor growth in vivo, and discovered that stigmasterol affected Lactobacillus johnsonii, Lactobacillus murinus, and Lactobacillus reuteri, resulting in an increased proportion of IFN-γ+ CD8+ T cells and Treg cells in both the intestinal mucosa and tumor tissues, and ultimately leading to increased levels of apoptotic proteins and the subsequent death of tumor cells, which shed light on the effect of stigmasterol on host intestinal tissue and intratumoral immune cells by reshaping the intestinal microbiota, and provide a theoretical foundation for the potential clinical application of stigmasterol in the treatment of HCC.
Subject(s)
CD8-Positive T-Lymphocytes , Carcinoma, Hepatocellular , Gastrointestinal Microbiome , Liver Neoplasms , Mice, Inbred BALB C , Stigmasterol , T-Lymphocytes, Regulatory , Animals , Gastrointestinal Microbiome/drug effects , Stigmasterol/pharmacology , T-Lymphocytes, Regulatory/drug effects , Carcinoma, Hepatocellular/drug therapy , CD8-Positive T-Lymphocytes/drug effects , Liver Neoplasms/drug therapy , Mice , Male , Interferon-gamma/metabolism , Apoptosis/drug effects , Caspase 3/metabolism , Cell Line, Tumor , Cyclin D1/metabolism , Tumor Suppressor Protein p53ABSTRACT
PURPOSE: To compare the shaping ability of three rotary Ni-Ti instruments in simulated root canals. METHODS: A total of 30 simulated resin blocks were divided randomly into 3 groups: ProTaper Universal, ProTaper Next and TF Adaptive. Each group consisted of 10 root canals. The preparation time and changes in canal curvature were measured. Pre- and post-instrumentation photograghs were taken by precise camera and superimposed through Photoshop. The material removed from the inner and outer canal walls at 9 points beginning at 0 mm from the foramen were measured with Image Pro Plus. Centering ability was determined accordingly. The data was analyzed with SPSS13.0 software package. RESULTS: During root canal preparation, no instruments fractured. ProTaper Next was much faster than ProTaper Universal(P<0.05). At the apical curvature, transportation was the least with TF Adaptive, followed by Protaper Next (P<0.05). There were no significant differences in 3 groups with respect to coronal curvature transportation (P>0.05). CONCLUSIONS: Under the conditions of this study, ProTaper Next was the most efficient instrument. TF Adaptive and Protaper Next showed better shaping ability. In general, all the instruments respected original canal curvature well and were safe to be used.