The protective effect of glycyrrhizin on hepatic ischemia-reperfusion injury in rats and possible related signal pathway.

OBJECTIVES: To investigate the protective effect of glycyrrhizin (GL) on hepatic ischemia-reperfusion injury (HIRI). MATERIALS AND METHODS: Forty SD rats were randomly divided into sham group, HIRI group, GL 100 mg/kg group, and GL 200 mg/kg group. The pathological alterations of liver tissue in each group were observed. The levels of alanine transaminase (ALT), aspartate aminotransferase (AST), endothelin-1 (ET-l), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were detected. Western blot was used to detect the expression levels of cytoplasmic protein caspase-3, Bax, Bcl-2, heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear protein Nrf2. RESULTS: Compared with the HIRI group, the levels of AST, ALT, ET-1, TNF-α, IL-1ß, and IL-6 in GL groups were lower, serum NO content was higher, MDA content was lower, SOD and GSH-Px activities were significantly increased, apoptosis index was lower (P<0.05), which was more obvious in high-dose GL (200 mg/kg) group. The LC3-II/LC3-I ratio and Beclin-1 protein expression levels in the GL group were significantly lower than the HIRI group, but the expression levels of cytoplasmic protein HO-1 and nuclear protein Nrf2 were significantly higher than those of the HIRI group, which was more obvious in the high-dose GL group (P<0.05). CONCLUSION: GL has a protective effect on the liver of HIRI rats, and its mechanism may be related to activation of the Nrf2/HO-1 signaling pathway, inhibition of oxidative stress, inflammation, autophagy, and apoptosis.

Expression of lncRNA MSC-AS1 in hepatocellular carcinoma cell lines and its effect on proliferation, apoptosis, and migration.

BACKGROUND/AIMS: This study aimed to explore the expression of long non-coding RNA MSC-AS1 in hepatocellular carcinoma (HCC) cells and its effect on the proliferation, migration, and apoptosis of HCC cells. MATERIALS AND METHODS: The expression of MSC-AS1 in HCC cell lines BEL7402, SMMC7721, Huh7, HepG2, MHCC97-H, and normal hepatocyte line L02 was detected by reverse transcriptase polymerase chain reaction. The HCC cells were divided into blank, negative control (NC)-small interfering RNA (siRNA) (transfected with negative siRNA), and MSC-AS1 siRNA (transfected with MSC-AS1 siRNA) groups. Cell counting kit-8 and colony formation assays were used to determine the proliferation, and cell apoptosis, migration, and invasion were detected by flow cytometry, wound healing, and transwell assays, respectively. Western blot was used to detect the expression of related proteins. RESULTS: The expression of MSC-AS1 in HCC cell lines was significantly higher than that in L02. In the MSC-AS1 siRNA group, the proliferation and colony formation of HCC cells were inhibited, whereas the apoptosis rate was significantly higher than that in the blank and NC-siRNA groups. The rate of wound healing and the number of invasion cells in the MSC-AS1 siRNA group were significantly lower than that in the blank and NC-siRNA groups. CONCLUSION: MSC-AS1 was upregulated in HCC cells, and the downregulation of MSC-AS1 could inhibit cell proliferation, migration, and invasion and promote apoptosis of HCC cells.

Baseline Hepatitis B Virus Titer Predicts Initial Postpartum Hepatic Flare: A Multicenter Prospective Study.

BACKGROUND AND GOALS: A series of changes in the immune system occur during pregnancy and puerperium. Currently, we aim to characterize both the natural changes in liver inflammation and its association with hepatitis B viremia during this special period. PATIENTS AND METHODS: Chronic hepatitis B (CHB) gravidas were recruited and followed up to 52 weeks postpartum. Virological and biochemical parameters were assessed throughout the period. RESULTS: A total of 1097 CHB mothers had finished the entire follow-up including 451 accepting telbivudine, 178 accepting tenofovir, and 468 without antiviral therapy. Among the mothers, 11.94% went through hepatic flare in the first trimester and the rate decreased to 2.1% at the time of delivery. Nevertheless, a much higher frequency (19.78%) was observed in the early postpartum. Interestingly, alanine aminotransferase level decreased along with the development of pregnancy and then suddenly increased in the first month of puerperium. In addition, a downward trend was observed on the titer of HBsAg and HBeAg after delivery. Of note, an obvious higher frequency of alanine aminotransferase flare was revealed in mothers with high viremia (>6 log10 IU/mL). With multivariate analysis, only hepatitis B virus titer at baseline was strongly associated with hepatic flare during early postpartum (95% confidence interval, 1.012-3.049, P=0.045). The predictive rates of hepatic flare at baseline viral load of 6, 7, and 8 log10 IU/mL were 16.67%, 28.30%, and 30.60%, respectively. CONCLUSIONS: CHB gravidas with high viremia should be monitored closely during entire pregnancy, and extended antiviral therapy is recommend to those mothers with baseline viremia >7 log10 IU/mL.

Downregulation of microRNA-27b-3p enhances tamoxifen resistance in breast cancer by increasing NR5A2 and CREB1 expression.

Estrogen-dependent breast cancer is often treated with the aromatase inhibitors or estrogen receptor (ER) antagonists. Tamoxifen as a major ER antagonist is usually used to treat those patients with ERα-positive breast cancer. However, a majority of patients with ERα positive fail to respond to tamoxifen due to the presence of intrinsic or acquired resistance to the drug. Altered expression and functions of microRNAs (miRNAs) have been reportedly associated with tamoxifen resistance. In this study, we investigated the role of miR-27b-3p in resistance of breast cancer to tamoxifen. MiR-27b-3p levels were remarkably reduced in the tamoxifen-resistant breast cancer cells compared with their parental cells. In addition, miR-27b-3p was also significantly downregulated in breast tumor tissues relative to adjacent non-tumor tissues. Moreover, the expression levels of miR-27b-3p were lower in the breast cancer tissues from tamoxifen-resistant patients compared with that from untreated-tamoxifen patients. Notably, tamoxifen repressed miR-27b-3p expression, whereas estrogen induced miR-27b-3p expression in breast cancer cells. Besides, we provided experimental evidences that miR-27b-3p enhances the sensitivity of breast cancer cells to tamoxifen in vitro and in vivo models. More importantly, we validated that miR-27b-3p directly targeted and inhibited the expression of nuclear receptor subfamily 5 group A member 2 (NR5A2) and cAMP-response element binding protein 1 (CREB1) and therefore augmented tamoxifen-induced cytotoxicity in breast cancer. Lastly, miR-27b-3p levels were found to be significantly negatively correlated with both NR5A2 and CREB1 levels in breast cancer tissues. Our findings provided further evidence that miR-27b-3p might be considered as a novel and potential target for the diagnosis and treatment of tamoxifen-resistant breast cancer.