Correlation Between Adiponectin Gene rs1501299 Polymorphism and Nonalcoholic Fatty Liver Disease Susceptibility: A Systematic Review and Meta-Analysis.

BACKGROUND Metabolic related nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases around the world. A single nucleotide polymorphism (SNP) rs1501299 (+276G>T) in the adiponectin gene has been recently revealed to be responsible for susceptibility to NAFLD. This meta-analysis intended to assess the association risk of NAFLD and rs1501299 polymorphism. MATERIAL AND METHODS We conducted a literature search on PubMed, Embase, and Cochrane Library databases. All involved studies were selected based on our search criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to quantify the strength of the association. Subgroup analysis considered the effects of ethnicity, subject scope, and source of control. Publication bias was assessed by Begg's tests. RESULTS Eight qualified case-control studies with 1639 patients and 1426 controls demonstrated a significant correlation between rs1501299 polymorphism in adiponectin and NAFLD under the dominant model (OR=1.18, 95% CI=1.02-1.36), allelic contrast (OR=1.21, 95% CI=1.09-1.36), homozygote comparison (OR=1.63, 95% CI=1.26-2.01) and the recessive allele model (OR=1.58, 95% CI=1.23-2.02) with evident heterogeneity. No association was observed between the risk of NAFLD and the genotypic variants in heterozygote comparison (OR=1.11, 95% CI=0.95-1.29) without heterogeneity. Subgroup analysis suggested that the sample size could be the potential source of heterogeneity. Source of control was not the reason for between-study heterogeneity and further sensitivity analysis and publication bias revealed good consistency and symmetry in the pooling studies. CONCLUSIONS Results from our current meta-analysis gave insight into the correlation between rs1501299 polymorphism and the risk of NAFLD, indicating the variant of rs1501299 might be related to increased NAFLD susceptibility.

Adenovirus-mediated dual gene expression of human interleukin-10 and hepatic growth factor exerts protective effect against CCl4-induced hepatocyte injury in rats.

BACKGROUND: Hepatocyte injury is a common pathological cause of various liver diseases. Due to a lack of an effective preventive treatment, gene therapy has become an interesting approach to prevent and alleviate liver injury. AIMS: A protective effect of adenovirus-mediated dual gene expression of human interleukin-10 (hIL-10) and human hepatocyte growth factor (hHGF) was investigated against tetrachloromethane (CCl(4))-induced hepatocyte injury in rats. METHODS: An adenoviral vector carrying the hIL-10 and hHGF genes was constructed, and its protective effect against rat hepatocyte injury was investigated both in vivo and in vitro. RESULTS: In the in vitro CCl(4)-induced cell injury model, simultaneous transfection of hIL-10 and hHGF genes via an adenoviral vector resulted in production of anti-hepatocyte biological factors by an autocrine mechanism, then significantly improved hepatocyte viability. In the in vivo rat model, synergistic effects of these two gene products protected hepatocytes from damage by reducing the CC1(4)-induced hepatocyte degeneration, hepatic fibrosis, and intrahepatic inflammatory cell infiltration, thereby preserving liver function. CONCLUSION: Adenovirus-mediated dual gene expression of hIL-10 and hHGF effectively protected against liver damage by likely regulating immune responses to reduce hepatocyte injury and by promoting hepatocyte regeneration. The hIL-10 and hHGF dual gene expression vector has significant potential in the field of liver disease therapeutics and constitutes one of the most promising current strategies for gene therapy.

Expression profile of microRNAs in serum: a fingerprint for esophageal squamous cell carcinoma.

BACKGROUND: Sensitive and specific biomarkers for the early detection of esophageal squamous cell carcinoma (ESCC) are urgently needed to reduce the high morbidity and mortality of the disease. The discovery of serum microRNAs (miRNAs) and their unique concentration profiles in patients with various diseases makes them attractive, novel noninvasive biomarkers for tumor diagnosis. In this study, we investigated the serum miRNA profile in ESCC patients to develop a novel diagnostic ESCC biomarker. METHODS: Serum samples were taken from 290 ESCC patients and 140 age- and sex-matched controls. Solexa sequencing technology was used for an initial screen of miRNAs in serum samples from 141 patients and 40 controls. A hydrolysis probe-based stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and verification phases to confirm the concentrations of selected miRNAs in serum samples from 149 patients and 100 controls. RESULTS: The Solexa sequencing results demonstrated marked upregulation of 25 serum miRNAs in ESCC patients compared with controls. RT-qPCR analysis identified a profile of 7 serum miRNAs (miR-10a, miR-22, miR-100, miR-148b, miR-223, miR-133a, and miR-127-3p) as ESCC biomarkers. The area under the ROC curve for the selected miRNAs ranged from 0.817 to 0.949, significantly higher than for carcinoembryonic antigen (0.549; P < 0.0005). More importantly, this panel of 7 miRNAs clearly distinguished stage I/II ESCC patients from controls. CONCLUSIONS: This panel of 7 serum miRNAs holds promise as a novel blood-based biomarker for the diagnosis of ESCC.

RRM2 is a potential prognostic biomarker with functional significance in glioma.

Glioma is one of the most common brain tumors, suggesting the importance of investigating the molecular mechanism of gliomas. We studied the roles of Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) in glioma. Expressions of RRM2 are higher in glioma tissues evidenced by TCGA data, western blot and immunohistochemistry. RRM2 is negatively correlated with glioma patient's survival. RNA-seq showed that genes involved in apoptosis, proliferation, cell adhesion and negative regulation of signaling were up-regulated upon RNAi-mediated knock-down of RRM2. Cell phenotypes specific for stably knocking down RRM2 were determined using stable transfection in vitro. In an in vivo model, knock-down of RRM2 inhibited tumor growth and caused suppression of AKT and ERK1/2 signalings. Interfering RRM2 also down-regulated the expression of cyclin A, cyclin B1, cyclin D1, Vimentin, and N-cadherin, and elevated E-cadherin expression. Moreover, overexpression of RRM2 failed to increase the expression of cyclin B1, cyclin D1, and N-cadherin when phosphorylation of AKT and ERK1/2 was suppressed by LY294002 or PD98059. These findings indicated that RRM2 is a positive regulator of glioma progression which contributes to the migration and proliferation of glioma cells through ERK1/2 and AKT signalings and might be a novel prognostic indicator for glioma patients.

PSMB8 regulates glioma cell migration, proliferation, and apoptosis through modulating ERK1/2 and PI3K/AKT signaling pathways.

Glioma has been considered as one of the most aggressive and popular brain tumors of patients. It is essential to explore the mechanism of glioma. In this study, we established PSMB8 as a therapeutic target for glioma treatment. Expression of PSMB8 as well as Ki-67 was higher in glioma tissues demonstrated by western blot and immunohistochemistry. Then, the role of PSMB8 in migration and proliferation of glioma cells was investigated by conducting wound-healing, trans-well assay, cell counting kit (CCK)-8, flow cytometry assay and colony formation analysis. The data showed that interfering PSMB8 may inhibit the migration and proliferation of glioma cells by reducing expression of cyclin A, cyclin B1, cyclin D1, Vimentin, and N-cadherin, and by increasing expression of E-cadherin. Additionally, interfering PSMB8 may induce apoptosis of glioma cells by upregulating caspase-3 expression. Furthermore, these in vitro findings were validated in vivo and the ERK1/2 and PI3k/AKT signaling pathways were involved in PSMB8-triggered migration and proliferation of glioma cells. In an in vivo model, downregulation of PSMB8 suppressed tumor growth. In conclusion, PSMB8 is closely associated with migration, proliferation, and apoptosis of glioma cells, and might be considered as a novel prognostic indicator in patients with gliomas.

Involvement of xanthine oxidase and paraoxonase 1 in the process of oxidative stress in nonalcoholic fatty liver disease.

Xanthine oxidase (XOD) and paraoxonase 1 (PON1) are important enzymes in redox reactions in vivo, and are predominantly synthesized by the liver. The aim of the present study was to investigate the redox state in nonalcoholic fatty liver disease, and determine the association between the activities of XOD and PON1 and the severity of NAFLD. Sprague­Dawley rats were randomly divided into control, model and α­lipoic acid (high and low dose) groups. The rats in the NAFLD model were induced by feeding a high fat diet for 12 weeks and the in vitro cell model of hepatocyte steatosis was induced by treating L­02 cells with oleic acid for 24 h. The body weight, liver function, lipid and oxidative stress indices, and histological features of the liver were examined in the rats. Compared with the control group, the rats in the NAFLD model group showed impaired liver function, lipid disorders and damage from oxidative stress. The serum activity of XOD increased significantly from the 4th week and was markedly higher, compared with that in the control group, reaching a peak in the 12th week. The activity of PON1 was negatively correlated with that of XOD. Compared with the control cells, the activity of XOD and levels of free­fatty acids were significantly higher, and the activity of PON1 was significantly lower in the NAFLD L­02 cell model. All the above indicators were significantly improved by treatment with the antioxidant, α­lipoic acid. The activities of XOD and PON1 may be promising as markers in a noninvasive approach for detecting the severity of NAFLD clinically. α­lipoic acid had protective effects on the NAFLD rats, and the potential mechanism may be associated with the inhibition of oxidative stress and lipid peroxidation.