Advances in experimental animal models of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor with insidious early symptoms, easy metastasis, postoperative recurrence, poor drug efficacy, and a high drug resistance rate when surgery is missed, leading to a low 5-year survival rate. Research on the pathogenesis and drugs is particularly important for clinical treatment. Animal models are crucial for basic research, which is conducive to studying pathogenesis and drug screening more conveniently and effectively. An appropriate animal model can better reflect disease occurrence and development, and the process of anti-tumor immune response in the human body. This review summarizes the classification, characteristics, and advances in experimental animal models of HCC to provide a reference for researchers on model selection.

Liver Injury in Patients with COVID-19: A Retrospective Study.

Objectives: The objective of this study is to explore the incidence, characteristics, risk factors, and prognosis of liver injury in patients with COVID-19. Methods: We collected clinical data of 384 cases of COVID-19 and retrospectively analyzed the incidence, characteristics, and risk factors of liver injury of the patients. In addition, we followed the patient two months after discharge. Results: A total of 23.7% of the patients with COVID-19 had liver injury, with higher serum AST (P < 0.001), ALT (P < 0.001), ALP (P = 0.004), GGT (P < 0.001), total bilirubin (P = 0.002), indirect bilirubin (P = 0.025) and direct bilirubin (P < 0.001) than the control group. The median serum AST and ALT of COVID-19 patients with liver injury were mildly elevated. Risk factors of liver injury in COVID-19 patients were age (P = 0.001), history of liver diseases (P = 0.002), alcoholic abuse (P = 0.036), body mass index (P = 0.037), severity of COVID-19 (P < 0.001), C-reactive protein (P < 0.001), erythrocyte sedimentation rate (P < 0.001), Qing-Fei-Pai-Du-Tang treatment (P = 0.032), mechanical ventilation (P < 0.001), and ICU admission (P < 0.001). Most of the patients (92.3%) with liver injury were treated with hepatoprotective drugs. 95.6% of the patients returned to normal liver function tests at 2 months after discharge. Conclusions: Liver injury was commen in COVID-19 patients with risk factors, most of them have mild elevations in transaminases, and conservative treatment has a good short-term prognosis.

Effect of intestinal microbiota transplantation on cerebral ischemia reperfusion injury in aged mice via inhibition of IL-17.

OBJECTIVES: This study investigates the effects and mechanisms of intestinal microbiota transplantation on cerebral ischemia reperfusion injury in aged mice. METHODS: We constructed a middle cerebral artery occlusion model after fecal microbiota transplantation from young C57 mice to aged C57 mice for 30 consecutive days via enema. The neurological deficit score, cerebral infarction volume, fecal flora composition, and IL-17 levels in the colon, brain, and serum were evaluated in young mice, aged mice, and aged mice that received fecal microbiota transplantation. Moreover, we administered rIL-17A through caudal vein injection to verify its effect on cerebral ischemia reperfusion injury in aged mice. RESULTS: We find that aged mice exhibited larger cerebral infarction volume and more severe neurological deficit than young mice after middle cerebral artery occlusion. Bacteroidetes increased and firmicutes decreased significantly in the feces of aged mice after microbiota transplantation. Furthermore, the transplanted mice showed improved neurological function and reduced infarction volume after middle cerebral artery occlusion compared with the control aged mice. We also find that the neuroprotective effect of the microbiota transplantation was reversed by pre-treatment of rIL-17A. CONCLUSION: In summary, intestinal microbiota transplantation can alleviate cerebral ischemia reperfusion injury in aged mice by restoring their microbiota environment and inhibiting IL-17 in the gut, serum, and brain tissue.

Revaluation of the efficacy of magnetic sphincter augmentation for treating gastroesophageal reflux disease.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a prevalent disease which severely impacts the quality of life of the patients. The surgical options are limited to such patients who are not satisfied with medical therapies. Magnetic sphincter augmentation (MSA) is a new antireflux surgical technique for treating GERD, which could physiologically reinforce the lower esophageal sphincter by magnetic force. Many clinical and animal studies have focused on this new therapy. The purpose of this work was to review the feasibility, efficacy and safety of MSA as a new treatment for GERD. METHODS: We performed a PubMed database search for the MSA and GERD-related studies between 2008 and September 22, 2015. One animal study, two case reports and fifteen clinical studies were identified in this review. RESULTS: The MSA device reinforces the lower esophageal sphincter to antireflux via magnetic force. The feasibility of this laparoscopic technique has been proved by the experimental and clinical studies. The clinical studies demonstrate that MSA treatment could effectively reduce the percent time of esophageal acid exposure (pH < 4) and improve the GERD health-related quality of life score. The operation time of MSA is shorter than that of the Nissen fundoplication, and the efficacy of MSA treatment is equal to that of fundoplication. The most frequent postoperative complication is dysphagia, and the majority of them could be self-resolved with conservative treatment. CONCLUSION: MSA (or LINX) devices provide an alternative surgical option for the patients who had failed in medical therapy. This review of the current literatures demonstrates that MSA is as effective as the medical and conventional surgical therapies. In the future, MSA will play a more important role in the treatment of GERD because of its unique advantage.

Chemopreventive effect of saikosaponin-d on diethylinitrosamine-induced hepatocarcinogenesis: involvement of CCAAT/enhancer binding protein ß and cyclooxygenase-2.

Cyclooxygenase-2 (COX-2) and CCAAT/enhancer binding protein ß (C/EBPß) have been shown to be involved in inflammation and carcinogenesis, and our previous study revealed that they were co-overexpressed in human hepatocellular carcinoma (HCC) tissue and a positive correlation was found. Saikosaponin-d (SSD), a triterpene saponin extracted from Bupleurum falcatum L. (Umbelliferae), is known to exert inhibitory effects on COX-2 expression, together with inflammation and hepatic fibrosis. These findings prompted us to investigate the chemopreventive potential of SSD against hepatocarcinogenesis and its possible molecular mechanism in vivo. An experimental model with diethylinitrosamine (DEN)-treated Sprague Dawley rats was used in the present study. DEN (50 mg/kg body weight) and SSD (2 mg/kg body weight) were intraperitoneally injected weekly and daily, respectively. Administration of SSD alone had no side effects. The liver nodule formation, tumorous invasion to surrounding organs and increased cellular atypia induced by DEN were markedly reduced by SSD in the SSD + DEN group compared with the DEN group. On the other hand, immunohistochemical staining demonstrated that the expression of COX-2 and C/EBPß proteins was significantly increased in tumor cells and macrophages of liver tissue from DEN-treated rats, whereas the expression of the two proteins was markedly lowered in the SSD + DEN group. Overall, our results suggest that SSD prevents DEN-induced hepatocarcinogenesis in rats through inhibition of C/EBPß and COX-2, providing indispensable experimental evidence for the clinical application of SSD as a novel chemopreventive agent against HCC in the future.

Effects of extract from Ginkgo biloba on carbon tetrachloride-induced liver injury in rats.

AIM: To study the effects of extract from Ginkgo biloba (EGb) containing 22% flavonoid and 5% terpenoid on chronic liver injury and liver fibrosis of rats induced by carbon tetrachloride (CCl(4)). METHODS: All rats were randomly divided into control group, CCl(4)-treated group, colchicine-treated group and EGb-protected group. Chronic liver injury was induced in experimental groups by subcutaneous injection of CCl(4) and fed with chows premixed with 79.5% corn powder, 20% lard and 0.5% cholesterol (v/v). EGb-protected group was treated with EGb (0.5 g/kg body weight per day) for 7 wk. At the end of wk 8, all the rats were killed. Liver function, liver fibrosis, oxidative stress and expression of transforming growth factor beta1 (TGF-beta1), a-smooth muscle actin (alpha-SMA) and type I collagens in liver were determined. In addition, pathology changes of liver tissue were observed under light microscope. RESULTS: The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin (Alb) in EGb-protected group were notably improved as compared with the CCl(4)-treated group (P < 0.01). The contents of serum hyaluronic acid (HA), type III procollagen (PCIII), type IV collagen (CIV) and the expression of hepatic tissue TGF-beta1, alpha-SMA and type I collagen in EGb-protected group were significantly lower than those in CCl(4)-treated groups (P < 0.05, P < 0.01). The degrees of liver fibrosis in EGb-protected groups were lower than those in CCl(4)-treated groups (6.58 +/- 1.25 vs 9.52 +/- 2.06, P < 0.05). Compared to the CCl(4)-treated group, the levels of plasma glutathoine peroxidase (Se-GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA) were strikingly improved also in EGb-protected group (P < 0.05, P < 0.01). CONCLUSION: EGb resists oxidative stress and thereby reduces chronic liver injury and liver fibrosis in rats with liver injury induced by CCl(4).

Effects of selenium on peripheral blood mononuclear cell membrane fluidity, interleukin-2 production and interleukin-2 receptor expression in patients with chronic hepatitis.

AIM: To study the effect of selenium on peripheral blood mononuclear cell (PBMC) membrane fluidity and immune function in patients with chronic hepatitis. METHODS: PBMCs were pretreated with selenium (1.156x10(-7) mol/L) for 6 h in vitro or extracted directly from patients after administration of selenium-yeast continuously for 8-12 wk (200 microg/d), and then exposed to Con-A for 48 h. The membrane fluidity, interleukin-2 (IL-2) production and interleukin-2 receptor (IL-2R) expression in PBMCs and malondialdehyde (MDA) concentration in medium and lipid peroxide (LPO) in plasma were determined. RESULTS: The PBMC membrane fluidity, IL-2 production and IL-2R expression in patients with chronic hepatitis were significantly lower than those in healthy blood donators (particle adhesive degree R, 0.17+/-0.01 vs 0.14+/-0.01, P<0.01; IL-2, 40.26+/-9.55 vs 72.96+/-11.36, P<0.01; IL-2R, 31.05+/-5.09 vs 60.58+/-10.56, P<0.01), and the MDA concentration in medium in patients with chronic hepatitis was significantly higher than that in healthy blood donators (1.44+/-0.08 vs 0.93+/-0.08, P<0.01). Both in vitro and in vivo administration of selenium could reverse the above parameters. CONCLUSION: Supplement of selenium can suppress lipid peroxidation, and improve PBMC membrane fluidity and immune function in patients with chronic hepatitis.