[Research progress on the mechanism of action of mitophagy in the occurrence and development of liver cancer].

Mitophagy, as an important link in maintaining mitochondrial homeostasis and environmental homeostasis in the liver, can remove damaged mitochondria and provide energy through autophagy and other processes. Additionally, it plays a dual role in the occurrence and development of liver cancer and can affect the therapeutic effect of liver cancer through a variety of signaling pathways. This article reviews the relationship between mitophagy and hepatitis B virus infection, liver cancer occurrence and development, liver cancer stem cells, mitochondrial division and fusion, therapeutic resistance and invasiveness of liver cancer, and other aspects.

Effect of microRNA-7 on proliferation, invasion, migration and EMT of hepatoma cell line SMMC-7721.

OBJECTIVE: This study aimed to observe the effect of microRNA-7 on the proliferation and migration of human hepatocellular carcinoma cell line SMMC-7721 and its effect on epithelial-mesenchymal transition (EMT). PATIENTS AND METHODS: Eukaryotic expression vector pcDNA3.1(-)-pri-miR-7(p-miR-7) was used to instantaneously transfect human liver cancer cells of SMMC-7721 cells in vitro. The expression of microRNA-7 was detected by RT-qPCR. Western blot was used to detect the expression of EMT marker proteins E-cadherin, ß-catenin, N-cadherin and Vimentin. The proliferation of SMMC-7721 cells was detected by CCK-8 assay, and the invasion and migration ability of cells was detected by transwell assay. RESULTS: Compared with the normal group, the expressions of E-cadherin and ß-catenin in SMMC-7721 cells transfected with miR-7 were significantly increased (p<0.05), while the expressions of N-cadherin and Vimentin were significantly decreased (p<0.05). Meanwhile, the proliferation, invasion and migration ability of the cells were significantly weakened (p<0.05). CONCLUSIONS: The miR-7 can inhibit the proliferation and invasion of human hepatocellular carcinoma cell line SMMC-7721, and its mechanism may be related to upregulation of E-cadherin, ß-catenin protein, and downregulation of N-cadherin and Vimentin proteins.

The toxic effects and fate of intravenously administered zearalenone in goats.

To clarify the toxic effects and fate of zearalenone (ZEA) in ruminants, we studied histopathological changes and toxicokinetic profiles in goats administered with a single intravenous (iv) injection of ZEA at doses of 2.4 mg/kg bw and 1.2 mg/kg bw, respectively. The expression of the mRNA of estrogen receptor (ER) alpha and beta in tissues was also investigated. The histopathological study revealed that ZEA caused hepatocellular swelling and lymphocytic infiltration in the liver, kidney, and uterus. The expression of ERalpha mRNA was enhanced by ZEA in association with the histopathological changes, indicating the possible involvement of ERalpha in the toxic effects of ZEA. For toxicokinetic profiles, blood plasma, urine, and feces were collected consecutively after iv injection of ZEA and analyzed for ZEA and its metabolites with high performance liquid chromatography (HPLC). alpha-Zearalenol (ZOL) and beta-ZOL were detected with ZEA, but alpha-zearalanol (ZAL), beta-ZAL, and zearalanone were below the detection limits. The distribution half-life (t(1/2alpha)) and elimination half-life (t(1/2beta)) of ZEA were 3.15 and 28.58h, respectively. ZEA, alpha-ZOL, and beta-ZOL were excreted in urine and feces, with beta-ZOL being the predominant metabolite. The ZEA and ZOL in urine were largely in their glucuronide and/or sulphate conjugated forms, while those in feces were largely in their free forms. This study showed the toxic effect of zearalenone and its metabolites, and their pharmacokinetic characteristics in goats.

The effect of feeding piglets with the diet containing green tea extracts or coumarin on in vitro metabolism of aflatoxin B1 by their tissues.

To clarify whether enzymes involved in aflatoxin B1 (AFB1) metabolism in pigs respond to antioxidant agents, the effect of feeding piglets with diets containing green tea extracts (Sunphenon) and coumarin on in vitro AFB1 metabolism by their liver and intestinal tissues was studied. The results showed that coumarin reduced AFB1-DNA adduct formation by both liver and intestinal microsomes, while Sunphenon did not have any effects. Both coumarin and Sunphenon enhanced the glutathione S-transferase (GST) activity to conjugate AFB1 to glutathione GSH in the intestine, although no effects were noted in the liver. Changes of the expression of mRNA of GSTA2 and GSTO1 were not in parallel with the observed changes of GST activity, suggesting that other GST subtypes are involved in the GST activity toward AFB1. As for lipophilic-free AFB1 metabolites, coumarin reduced the liver microsomal conversion of AFB1 to aflatoxin M1 (AFM1) and aflatoxin Q1 (AFQ1), but Sunphenon exerted no effects. Both coumarin and Sunphenon enhanced the conversion of AFB1 to aflatoxicol in the liver. All the results suggest that feeding with a diet containing coumarin affects AFB1 metabolism to enhance AFB1 detoxification through the suppression of P450 enzyme activity in the liver and the enhancement of GST activity in the intestine. Feeding with a diet containing Sunphenon enhances AFB1 detoxification, but the effects are noted mainly in the intestine.

Comparative activities of glutathione-S-transferase and dialdehyde reductase toward aflatoxin B1 in livers of experimental and farm animals.

In order to gain a better understanding of the relative activities of glutathione-S-transferase (GST) and aldehyde reductase toward aflatoxin B1 (AFB1) in relation to the variation of species susceptibilities, we studied the in vitro cytosolic GST and reductase activities in liver tissues from male Fischer rats, ICR mice and golden hamsters, adult male rainbow trouts and female piglets. The GST activity was determined by incubating the liver cytosol with glutathione (GSH) and AFB1 in the presence of the hamster liver microsomes to metabolize AFB1 to AFB1-8, 9-epoxide. The reaction product, AFB1 and GSH conjugate (AFB1-GSH), was quantified with HPLC. The reductase activity was determined by incubating liver cytosol with AFB1-dialdehyde, followed by the quantification of the metabolic product, AFB1-dialcohol, with HPLC. All the animal species possessed the GST activities, and AFB1-GSH formed increasingly with the increase of the AFB1 concentration according to the model of first-order enzyme reaction kinetics. The V(max) and K(m) values of the GST activities in rodent species were higher and lower, respectively, than those in the trout and pig, being consistent with the relative susceptibilities to AFB1 of these animal species. However, no relationship was noted between the reductase activity and species susceptibility. Thus, the result of this study shows that GST toward AFB1, but not aldehyde reductase, is a determinant of the variation of species susceptibilities.