ABSTRACT
BACKGROUND: Gut probiotic depletion is associated with non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC). Here, we investigated the prophylactic potential of Lactobacillus acidophilus against NAFLD-HCC. METHODS: NAFLD-HCC conventional and germ-free mice were established by diethylnitrosamine (DEN) injection with feeding of high-fat high-cholesterol (HFHC) or choline-deficient high-fat (CDHF) diet. Orthotopic NAFLD-HCC allografts were established by intrahepatic injection of murine HCC cells with HFHC feeding. Metabolomic profiling was performed using liquid chromatography-mass spectrometry. Biological functions of L. acidophilus conditional medium (L.a CM) and metabolites were determined in NAFLD-HCC human cells and mouse organoids. FINDINGS: L. acidophilus supplementation suppressed NAFLD-HCC formation in HFHC-fed DEN-treated mice. This was confirmed in orthotopic allografts and germ-free tumourigenesis mice. L.a CM inhibited the growth of NAFLD-HCC human cells and mouse organoids. The protective function of L. acidophilus was attributed to its non-protein small molecules. By metabolomic profiling, valeric acid was the top enriched metabolite in L.a CM and its upregulation was verified in liver and portal vein of L. acidophilus-treated mice. The protective function of valeric acid was demonstrated in NAFLD-HCC human cells and mouse organoids. Valeric acid significantly suppressed NAFLD-HCC formation in HFHC-fed DEN-treated mice, accompanied by improved intestinal barrier integrity. This was confirmed in another NAFLD-HCC mouse model induced by CDHF diet and DEN. Mechanistically, valeric acid bound to hepatocytic surface receptor GPR41/43 to inhibit Rho-GTPase pathway, thereby ablating NAFLD-HCC. INTERPRETATION: L. acidophilus exhibits anti-tumourigenic effect in mice by secreting valeric acid. Probiotic supplementation is a potential prophylactic of NAFLD-HCC. FUNDING: Shown in Acknowledgments.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Pentanoic Acids , Probiotics , Humans , Animals , Mice , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/etiology , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/complications , Lactobacillus acidophilus , Liver Neoplasms/drug therapy , Liver Neoplasms/etiology , Liver/metabolism , Cell Transformation, Neoplastic/metabolism , Carcinogenesis/pathology , Diet, High-Fat , Choline/metabolism , Probiotics/pharmacology , Probiotics/therapeutic use , Mice, Inbred C57BLABSTRACT
The incidence of short-term complications after laparoscopic surgery for gastric cancer is higher. Whether ω-3 fish oil fat emulsion can reduce short-term complications of gastric cancer after laparoscopic surgery is controversial. The purpose of this study was to explore the effect of ω-3 fish oil fat emulsion on postoperative recovery of patients with gastric cancer after laparoscopic surgery. A total of 111 patients were included in this study. These patients were given parenteral nutrition for 5 day or more after surgery. We used univariate analysis and multivariate analysis to determine whether ω-3 fish oil fat emulsion could affect the incidence of short-term complications after gastric cancer laparoscopic surgery. The incidence of postoperative short-term complications in patients with parenteral nutrition supplemented with ω-3 fish oil fat emulsion was significantly lower than that in patients without ω-3 fish oil fat emulsion (12/51 VS 26/60, P = 0.027). ω-3 fish oil fat emulsion is an independent risk factor for short-term postoperative complications in patients with gastric cancer (OR = 0.393, CI:0.155-0.996, P = 0.049). In conclusion, the addition of ω-3 fish oil fat emulsion to parenteral nutrition after operation can effectively reduce the incidence of short-term complications in patients with gastric cancer after laparoscopic surgery.
Subject(s)
Fatty Acids, Omega-3 , Laparoscopy , Stomach Neoplasms , Fat Emulsions, Intravenous/therapeutic use , Fish Oils , Humans , Parenteral Nutrition , Soybean Oil , Stomach Neoplasms/etiologyABSTRACT
The particle characterization from the influent and effluent of a chemical-biological flocculation (CBF) process was studied with a laser diffraction device. Water samples from a chemically enhanced primary treatment (CEPT) process and a primary sediment tank process were also analyzed for comparison. The results showed that CBF process was not only effective for both the big size particles and small size particles removal, but also the best particle removal process in the three processes of CBF process, CEPT process, and PST process (primary sediment tanks). The results also indicated that CBF process was superior to CEPT process in the heavy metals removal. The high and non-selective removal for heavy metals might be closely related to its strong ability to eliminate small particles. Samples from different locations in CBF reactors showed that small particles were easier to aggregate into big ones and those disrupted flocs could properly flocculate again along CBF reactor because of the biological flocculation.