ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) has become the main cause of end-stage liver disease. Probiotics have the potential effect of alleviating NAFLD. The aim of this study was to explore functional probiotics and their underlying mechanisms. The bile salt hydrolase (BSH) activity in thirty-four strains was determined in vitro. Then, C57BL/6 mice were used to explore the effects of probiotics on NAFLD. Body weight and food intake were measured, and serum lipid concentrations, oxidative stress and proinflammatory cytokines levels were determined using commercial kits. The expressions of intestinal bile acid pathway genes were evaluated via real-time PCR. The results showed that Lactobacillus casei YRL577 and L. paracasei X11 had higher BSH activity. L. casei YRL577 significantly reduced liver weight and liver index and could regulate the levels of lipid metabolism, oxidative stress and proinflammatory cytokines as compared with L. paracasei X11. Furthermore, the results indicated that L. casei YRL577 up-regulated the mRNA levels of farnesoid X receptor and fibroblast growth factor 15, whereas down-regulated the mRNA level of apical Na-dependent bile acid transporter. These findings suggested that L. casei YRL577 modified genes in the intestinal bile acid pathway which might contribute to the alleviation of NAFLD.
Subject(s)
Bile Acids and Salts/metabolism , Gene Expression/physiology , Intestinal Mucosa/metabolism , Lacticaseibacillus casei/physiology , Non-alcoholic Fatty Liver Disease/therapy , Probiotics/administration & dosage , Amidohydrolases/genetics , Amidohydrolases/metabolism , Animals , Bile Acids and Salts/genetics , Biomarkers/blood , Cholesterol/analysis , Cytokines/blood , Lipid Metabolism , Liver/chemistry , Liver/pathology , Male , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/metabolism , Organ Size , Oxidative Stress , Triglycerides/analysisABSTRACT
OBJECTIVE: To evaluate the efficacy and safety of raltitrexed plus oxaliplatin-based transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). METHODS: A total of 123 patients with unresectable HCC were recruited into the prospective cohort study. Raltitrexed plus oxaliplatin-based TACE was performed according to the traditional method at monthly intervals and was repeated for up to 4 cycles if no disease progression or intolerable toxicity occurred. The primary efficacy endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and tumor response rate. The Cox proportional-hazards regression model was used to assess the independent prognostic factors of OS. Adverse events were also observed. RESULTS: The median OS time and PFS were 623 days (95% CI: 461, 785) and 338 days (95% CI: 302, 704), respectively. The disease control rate was 95.5% (118/123). The Cox proportional-hazards regression model indicated that age, ECOG performance status and response to TACE as independent prognostic factors of OS. No treatment-related mortality occurred within 30 days of treatment procedure. The most common complications included postembolization syndrome, liver dysfunction and hematological toxicity. Grade 3 pain, transglutaminase abnormality and thrombocytopenia were observed in 16 (13%), 15 (12.2%) and 3 (2.4%) patients, respectively. No grade 4 adverse events were observed. CONCLUSION: Raltitrexed plus oxaliplatin-based TACE led to high tumor response rate and promising PFS and OS, and was considered safe and tolerable in patients with unresectable HCC.
ABSTRACT
Effects of interventional embolotherapy on the expression of fragile histidine triad (FHIT) and p16 in hepatocellular carcinoma (HCC) patients were investigated. Patients with primary HCC who were definitely diagnosed and treated in the Department of Gastroenterology in Qingdao Central Hospital from March 2014 to March 2016 were selected, and they underwent interventional embolotherapy. HCC and cancer-adjacent tissues of the patients were harvested for immunohistochemical staining. The correlation between the expression levels of FHIT and p16 was analyzed at the gene and protein level. Clinical data were collected, and whether they were correlated with the expression of FHIT and p16 was investigated. The expression levels of FHIT and p16 in primary HCC tissues were remarkably lower than that in cancer-adjacent tissues (P<0.05). In HCC tissues, FHIT expression was obviously positively correlated with p16 expression (Spearman's correlation coefficient, r=0.308; P=0.025). FHIT was related to HCC tumor-node-metastasis (TNM) staging, the differentiation degree in Edmondson-Steiner grading, lymph node metastasis and portal vein thrombosis (P<0.05 in all comparisons), whereas, p16 was associated with tumor size and the differentiation degree in Edmondson-Steiner grading (P<0.05 in all comparisons). The expression of FHIT and p16 genes and proteins in HCC tissues were obviously lower than those in cancer-adjacent tissues (P<0.05 in all comparisons). FHIT and p16 genes, as tumor suppressor genes, inhibit the proliferation of HCC, and there is a positive correlation between them. The proteins of the FHIT and p16 can be used as new indicators for clinical detection, thus providing a new method for clinical diagnosis.
