Oxidative stress plays an important role in the pathogenesis of liver diseases. N-Acetyl-serotonin (NAS) has been reported to protect against oxidative damage, though the mechanisms by which NAS protects hepatocytes from oxidative stress remain unknown. To determine whether pretreatment with NAS could reduce hydrogen peroxide- (H2O2-) induced oxidative stress in HepG2 cells by inhibiting the mitochondrial apoptosis pathway, we investigated the H2O2-induced oxidative damage to HepG2 cells with or without NAS using MTT, Hoechst 33342, rhodamine 123, Terminal dUTP Nick End Labeling Assay (TUNEL), dihydrodichlorofluorescein (H2DCF), Annexin V and propidium iodide (PI) double staining, immunocytochemistry, and western blot. H2O2 produced dramatic injuries in HepG2 cells, represented by classical morphological changes of apoptosis, increased levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), decreased activity of superoxide dismutase (SOD), and increased activities of caspase-9 and caspase-3, release of cytochrome c (Cyt-C) and apoptosis-inducing factor (AIF) from mitochondria, and loss of membrane potential (ΔΨm). NAS significantly inhibited H2O2-induced changes, indicating that it protected against H2O2-induced oxidative damage by reducing MDA levels and increasing SOD activity and that it protected the HepG2 cells from apoptosis through regulating the mitochondrial apoptosis pathway, involving inhibition of mitochondrial hyperpolarization, release of mitochondrial apoptogenic factors, and caspase activity.

Suppressor of variegation, Enhancer of Zeste, Trithorax and Myeloid-Nervy-DEAF1 domain-containing (SMYD) proteins are a set of lysine methyltransferases involved in a range of diverse biological functions, including gene expression, and regulation of skeletal and cardiac-muscle development. These proteins may additionally serve roles in a number of different types of cancer. However, the roles of the five SMYD proteins, SMYD 1/2/3/4/5, their expression patterns and prognostic value remain unclear. In the present study, the transcriptional expression levels of the five SMYD proteins were compared with the survival data of patients with breast carcinoma (BC) from the ONCOMINE dataset, Breast Cancer Gene-Expression Miner v4.0, Kaplan-Meier Plotter, The Cancer Genome Atlas and cBioPortal. An increase in the SMYD2/3/5 mRNA expression levels and a decrease in SMYD1/4 mRNA expression levels in BC tissues compared with normal tissues were identified. Increased SMYD3 mRNA and decreased SMYD5 mRNA expression levels were associated with decreased levels of histological differentiation, according to the Scarff-Bloom-Richardson grading system. Kaplan-Meier curves demonstrated that the increased SMYD1/4 and decreased SMYD2/3 mRNA expression levels were associated with good relapse-free survival (RFS) in patients with BC. Furthermore, SMYD2 mRNA expression levels were associated with the RFS of patients with BC with metastatic relapse, and SMYD4 may serve as a tumor suppressor in patients with BC, as patients with increased SMYD4 mRNA expression levels had significantly better RFS compared with decreased SMYD4 mRNA expression levels. The present data suggested that SMYD2 and SMYD3 may be potential biomarkers for diagnosis of BC. Additionally, SMYD2 and SMYD4 may be potential prognostic indicators of patients with BC.

No abstract

Objective To describe the surgical procedures of laparoscopic caudate lobectomy and analyze its clinical efficiency for treating cancer. Methods Twelve consecutive patients of hepatocellular carcinoma, hepatic hemangioma, and focal nodular hyperplasia who received laparoscopic caudate lobectomy in Qilu Hospital of Shandong University from January 2013 to January 2017 were included in this study. The clinical data, intraoperative parameters, and postoperative outcomes were assessed. Results All 12 patients received totally laparoscopic technique. The operative time was 140.8 ± 95.34 minutes. The average estimated blood loss was 97.92 ± 90.54 ml, and no blood transfusions were required. The mean duration of hospital stay was 9.17 ± 2.88 days. There was no perioperative complication or patient mortality in this series. Conclusions Laparoscopic caudate lobectomy is safe and feasible in the selected patients.

The purpose of this study was to investigate the possible protective effect of N-acetylserotonin (NAS) against acute hepatic ischemia-reperfusion (I/R) injury in mice. Adult male mice were randomly divided into three groups: sham, I/R, and I/R + NAS. The hepatic I/R injury model was generated by clamping the hepatic artery, portal vein, and common bile duct with a microvascular bulldog clamp for 30 min, and then removing the clamp and allowing reperfusion for 6 h. Morphologic changes and hepatocyte apoptosis were evaluated by hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Activated caspase-3 expression was evaluated by immunohistochemistry and Western blot. The activation of aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD) was evaluated by enzyme-linked immunosorbent assay (ELISA). The data show that NAS rescued hepatocyte morphological damage and dysfunction, decreased the number of apoptotic hepatocytes, and reduced caspase-3 activation. Our work demonstrates that NAS ameliorates hepatic IR injury.

To explore a simple and easy-to-learn procedure for the isolation of human quiescent hepatic stellate cells (HSCs) that requires no advanced training. Thus reducing costs and increasing efficiency. This protocol will provide sufficient primary cells with minimal contaminants for future basic research on diseases associated with human HSCs. Normal liver tissues were isolated from patients undergoing hepatic hemangioma resection, and a single cell suspension of these tissues was prepared using the Gentle MACS tissue processor. By using this method, the difficulty of the procedure was reduced, fewer cells were lost during the preparation treatments, and the maximal activity of single cells was maintained. Following preparation of the cell suspension, the HSCs were further isolated using a Nycodenz density gradient. Cell viability was examined by trypan blue staining, and the purity of the quiescent human HSCs was determined by autofluorescence and oil red O staining. Activated and quiescent human HSCs were identified using immunofluorescence and Western blotting. The cell cycle distribution in activated and quiescent human HSCs was analyzed by flow cytometry.The recovery rate of the HSCs was approximately (2.1 ± 0.23) × 10 6 of tissue, with 94.43 ± 1.89% cell viability and 93.8 ± 1.52% purity. The technique used in this study is a simple, high-yield, and repeatable method for HSC isolation that is worthy of recommendation.

PurposeTo determined KIAA1199 expression and investigate its correlation with the clinicopathologic data and prognosis of hepatocellular carcinoma (HCC), as well as markers of epithelial-mesenchymal transition (EMT); N-cadherin, E-cadherin and vimentin.Materials and methodsWestern blot, quantitative real-time PCR, and immunohistochemical staining were used to measure KIAA1199 expression in human HCC specimens. Subsequently, the correlation between KIAA1199 expression and the pathological characteristics of HCC patients was analyzed. Univariate and multivariate analyses were used to explore the risk factors associated with disease-free survival (DFS) and overall survival (OS).ResultsKIAA1199 expression was remarkably increased in hepatocellular carcinoma tissues compared to paracarcinomatous tissues. This phenomenon was accompanied by aberrant expression of EMT-associated markers. In addition, high KIAA1199 expression was associated with severe pathological symptoms, low DFS, and low OS. Results of the multivariate analysis showed that KIAA1199 expression may be an independent predictor of low disease-free survival and OS of HCC patients.ConclusionKIAA1199 overexpression in HCC patients is associated with aberrant expression of EMT-associated markers and severe clinicopathological symptoms, and thus may function as a marker of poor prognosis in HCC.

Background Although liver retraction using n-butyl-2-cyanoacrylate (NBCA) glue has been applied to laparoscopic upper abdominal surgery in noncirrhotic patients, there is still no consensus on its safety and feasibility for cirrhotic patients. In this study, we aimed to investigate the safety and effectiveness of liver retraction using NBCA glue during laparoscopic splenectomy and azygoportal disconnection (LSD) for gastroesophageal varices and hypersplenism secondary to liver cirrhosis and portal hypertension. Methods Thirty-nine gastroesophageal varices and hypersplenism secondary to liver cirrhosis and portal hypertension patients were included in our study. We performed LSD in the presence of NBCA glue (n = 22, NBCA group) and absence of NBCA glue (n = 17, n-NBCA group), respectively. The operation time, blood loss, postoperative hospitalization, and liver function were compared between the two groups. Results There was no mortality during the operation. One patient in non-NBCA group received open surgery due to parenchyma hemorrhage. Postoperative pleural effusion occurred in 2 cases of the NBCA group and 1 of the non-NBCA group. One showed left subphrenic abscess in the non-NBCA group. No postoperative bleeding occurred after 9-30 months of follow-up. The time of operation in NBCA group was significantly shorter than those in n-NBCA group (198.86±17.86 versus 217.81±20.25min, P<0.01). Blood loss in NBCA group was significantly lower than non-NBCA group (159.09±56.98 versus 212.50±88.51 ml, P<0.05). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased on day 1 after LSD and decreased to normal level on day 7 after LSD in both groups. There was no significant difference in postoperative hospitalization and liver function between the two groups. Conclusion Liver retraction using NBCA glue during LSD for gastroesophageal varices and hypersplenism secondary to liver cirrhosis and portal hypertension is safe, effective, and feasible.