The function role of HIGD1A in nonalcoholic steatohepatitis from chronic hepatitis B.

BACKGROUND: Accompanied by the growing prevalence of nonalcoholic fatty liver disease (NAFLD), the coexistence of chronic hepatitis B (CHB) and NAFLD has increased. In the context of CHB, there is limited understanding of the factors that influence the development of NASH. METHODS: We enrolled CHB combined NAFLD patients who had liver biopsy and divided them to NASH vs. non-NASH groups. A whole transcriptome chip was used to examine the expression profiles of long noncoding RNAs (lncRNAs) and mRNA in biopsied liver tissues. The function analysis of HIGD1A were performed. We knocked down or overexpressed HIGD1A in HepG2.2.15 cells by transient transfection of siRNA-HIGD1A or pcDNA-HIGD1A. In vivo investigations were conducted using hepatitis B virus (HBV) transgenic mice. RESULTS: In 65 patients with CHB and NAFLD, 28 were patients with NASH, and 37 were those without NASH. After screening 582 differentially expressed mRNAs, GO analysis revealed differentially expressed mRNAs acting on nicotinamide adenine dinucleotide phosphate (NADPH), which influenced redox enzyme activity. KEGG analysis also shown that they were involved in the NAFLD signaling pathway. The function analysis revealed that HIGD1A was associated with the mitochondrion. Then, both in vivo and in vitro CHB model, HIGD1A was significantly higher in the NASH group than in the non-NASH group. HIGD1A knockdown impaired mitochondrial transmembrane potential and induced cell apoptosis in HepG2.2.15 cells added oleic acid and palmitate. On the contrary, hepatic HIGD1A overexpression ameliorated free fatty acids-induced apoptosis and oxidative stress. Furthermore, HIGD1A reduced reactive oxygen species (ROS) level by increasing glutathione (GSH) expression, but Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/Acetyl-CoA carboxylase (ACC) pathway was not involved. CONCLUSION: Both in vivo and in vitro CHB model, an upward trend of HIGD1A was observed in the NASH-related inflammatory response. HIGDIA played a protective role in cells against oxidative stress. Our data suggested that HIGD1A may be a positive regulator of NASH within the CHB context.

Clinical Features of Non-Alcoholic Fatty Liver Disease in the Non-Lean Population.

INTRODUCTION: The prevalence of non-alcoholic fatty liver disease (NAFLD) in non-lean patients is significantly increased, and obesity significantly increases the risk of cirrhosis and HCC in NAFLD patients. However, whether there is a difference in clinical manifestations of NAFLD between overweight and obesity remains unclear. The objective of this study was to assess the clinical and histological features of NAFLD among a non-lean population. METHODS: Current study enrolled consecutive non-lean (body mass index [BMI] >23 kg/m2) patients with NAFLD and available liver biopsy results. Patients were stratified by BMI into two groups for the comparison of their clinical and histological variables, which included the overweight (BMI 23∼<28 kg/m2) and the obese (BMI ≥28 kg/m2). Risk factors for moderate to severe fibrosis (stage >1) were also analyzed through the logistic regression model. RESULTS: Among 184 non-lean patients with metabolic-associated fatty liver disease enrolled, 65 and 119 were overweight and obese, respectively. Patients in the obesity group had a significantly lower level of gamma-glutamyl transpeptidase, higher levels of platelet, glucose, prothrombin time, and more common of moderate to severe inflammatory activity when compared to those in the overweight group. However, a significant low frequency of moderate to severe fibrosis was found in the obesity group versus the overweight group (19.33% vs. 40.00%, p = 0.002). Binary logistics regression analysis of fibrosis found that aspartate transaminase (AST), BMI, alanine transaminase (ALT), and cholesterol (CHOL) were independent predictors for moderate to severe fibrosis in non-lean patients with NAFLD. Compared with the traditional fibrosis-4 (AUC = 0.77) and aminotransferase to platelet ratio index (AUC = 0.79) indexes, the combined index based on AST, BMI, ALT, and CHOL was more accurate in predicting moderate to severe fibrosis in non-lean patients with NAFLD (AUC = 0.87). CONCLUSIONS: Clinical and histological features differed between obesity and overweight patients with NAFLD. When compared to the traditional serum markers, the combination index including AST, BMI, ALT, and CHOL provided a better model to predict moderate to severe fibrosis in non-lean patients with NAFLD.

The identify role and molecular mechanism of the MALAT1/hsa-mir-20b-5p/TXNIP axis in liver inflammation caused by CHB in patients with chronic HBV infection complicated with NAFLD.

BACKGROUND/AIMS: To identify the inflammatory damage caused by chronic hepatitis B (CHB) in patients of chronic hepatitis B virus (HBV) infection complicated with non-alcoholic fatty liver disease (NAFLD), then guiding clinicians to carry out antiviral treatment. METHODS: According to the pathological features of liver biopsy, treatment-naïve obese patients of chronic HBV infection complicated with NAFLD who had elevated alanine transaminase (ALT) were divided into CHB group and NASH group. Transcriptome chips were used to analyze the expression profiles of long non-coding RNA (lncRNA) and mRNA in liver puncture tissues from the two groups. The chip data of CHB and NASH groups were analyzed for differential expression analysis, gene function analysis, signal pathway analysis, target gene prediction and competing endogenous RNAs (ceRNA) network analysis. RESULTS: By comparing CHB group with NASH group, a total of 44 differentially expressed lncRNAs and 567 differentially expressed mRNAs were screened. GO analysis predicted that the differentially expressed mRNAs may affect monooxygenase activity and oxidoreductase activity. KEGG analysis predicted that the differentially expressed mRNAs may be related to signaling pathways involved in oxidative phosphorylation, phagosomes, and NAFLD. Differential analysis of lncRNA shown that the expression of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in CHB group was significantly upregulated. Subsequently, through target gene prediction and ceRNA network analysis, we found thioredoxin interacting protein (TXNIP), which was significantly upregulated in the CHB group and had a ceRNA relationship with MALAT1. It is predicted that there may be a ceRNA regulation relationship of MALAT1/hsa-miR- 20b-5p/TXNIP. CONCLUSION: The MALAT1/hsa-miR-20b-5p/TXNIP axis may mediate CHB-induced inflammatory damage in chronic HBV infection complicated with NAFLD, and the mechanism may be related to the activation of NLRP3 inflammatory bodies and downstream inflammatory responses.

Clinical features of hepatitis B patients at immune-tolerance phase with basal core promoter and/or precore mutations.

Little data exist on basal core promoter/precore (BCP/PC) mutations in chronic hepatitis B (CHB) patients at the immune-tolerance (IT) phase. We studied consecutive treatment-naïve, CHBe-antigen (HBeAg)-positive patients who had undergone liver biopsy and genotyping. Those in the IT phase or immune-clearance (IC) phase were enrolled for comparison of the frequency of BCP/PC mutations and their clinical presentations. Subgroup analyses for the IT group were also performed between patients with and without mutations, and IC patients between fibrosis stages ≤2 vs fibrosis >2. Among 301 patients enrolled, 88/301 (29.24%) and 213/301 (70.76%) were at the IT and IC phase, respectively. The frequency of BCP/PC mutations in IT phase was significantly lower than those in IC phase (15.91% vs 64.79%, P < .001). The BCP mutation only was significantly more frequent than the PC mutation in both groups and also in all IC subgroups. IT patients with BCP/PC mutations had significantly higher quantitative anti-HBc levels compared with those of patients with wild-type virus (P < .05). They also had significantly lower mean levels of alanine transaminase, aspartate transaminase, total bilirubin and qAnti-HBc compared with those of IC patients (all P < .05). Additionally, they were significantly younger in mean age, had higher platelet count, higher levels of HBV DNA and surface antigen, as well as higher frequency of genotype B than those of IC patients with fibrosis >2 (all P < .05). BCP/PC mutations were found in IT patients with CHB. They had distinct clinical characteristics when compared with patients with wild-type or at IC phase. Further studies are needed to understand their natural history and treatment outcomes.

Correlation between Myocardial Velocity Measured using Tissue Doppler Imaging in the Left Ventricular Lead-Implanted Segment and Response to Cardiac Resynchronization Therapy.

OBJECTIVES: This study investigated whether tissue Doppler imaging parameters, especially the peak systolic velocity of the left ventricular lead-implanted segment (Ss), affect cardiac resynchronization therapy response. METHODS: In this case-control study, 110 enrolled patients were divided into cases (responder group, n=65) and controls (nonresponder group, n=45) based on whether their left ventricular end-systolic volume was reduced by ≥15% at 6 months after surgery. Preoperative clinical and echocardiographic data were collected. Multivariate logistic regression models were used to analyze the factors affecting the response to cardiac resynchronization therapy, and receiver operating characteristic curves were plotted to evaluate their diagnostic values. RESULTS: The proportion of patients with left bundle branch block in the case group was higher than that in the control group. The control group showed a higher left atrial volume index, E/A ratio and E/Em ratio but lower Ss than that of the case group. A multivariate regression analysis showed that left bundle branch block, Ss, and an E/Em ratio>14 were independent risk factors affecting the response to cardiac resynchronization therapy. Ss=4.1 cm/s was the best diagnostic threshold according to the receiver operating characteristic curve. CONCLUSIONS: Ss is an important factor affecting the response to cardiac resynchronization therapy. Patients with heart failure associated with Ss<4.1 cm/s have a higher risk of nonresponse.

Correlation between myocardial velocity measured using tissue doppler imaging in the left ventricular lead-implanted segment and response to cardiac resynchronization therapy

OBJECTIVES: This study investigated whether tissue Doppler imaging parameters, especially the peak systolic velocity of the left ventricular lead-implanted segment (Ss), affect cardiac resynchronization therapy response. METHODS: In this case-control study, 110 enrolled patients were divided into cases (responder group, n=65) and controls (nonresponder group, n=45) based on whether their left ventricular end-systolic volume was reduced by ≥15% at 6 months after surgery. Preoperative clinical and echocardiographic data were collected. Multivariate logistic regression models were used to analyze the factors affecting the response to cardiac resynchronization therapy, and receiver operating characteristic curves were plotted to evaluate their diagnostic values. RESULTS: The proportion of patients with left bundle branch block in the case group was higher than that in the control group. The control group showed a higher left atrial volume index, E/A ratio and E/Em ratio but lower Ss than that of the case group. A multivariate regression analysis showed that left bundle branch block, Ss, and an E/Em ratio>14 were independent risk factors affecting the response to cardiac resynchronization therapy. Ss=4.1 cm/s was the best diagnostic threshold according to the receiver operating characteristic curve. CONCLUSIONS: Ss is an important factor affecting the response to cardiac resynchronization therapy. Patients with heart failure associated with Ss<4.1 cm/s have a higher risk of nonresponse.

Molecular cloning, tissue expression and regulation of nutrition and temperature on Δ6 fatty acyl desaturase-like gene in the red claw crayfish (Cherax quadricarinatus).

Desaturase enzymes play an important role in the synthesis of unsaturated fatty acids. In this study, a complete cDNA sequence of a Δ6 desaturase-like gene was cloned from the hepatopancreas of the red claw crayfish, Cherax quadricarinatus. The full-length 1885 bp sequence comprises a 5' UTR of 254 bp, 3' UTR of 234 bp, and an open reading frame (ORF) of 1377 bp encoding a 458 amino acid polypeptide (GenBank accession no. MF497442). Bioinformatics analysis revealed three conserved histidine-rich regions, a cytochrome b5 domain at the N-terminus, and a haem binding site (HPGG) in the cytochrome b5 domain, all of which are typical of Δ6 desaturases. Quantitative real-time PCR demonstrated significantly higher expression in the hepatopancreas than other tissues. After feeding crayfish four formulated diets in which fish oil was replaced by 0, 33, 67, or 100% highly unsaturated soybean oil for 8 weeks, Δ6 desaturase-like mRNA expression and enzyme activity were higher than in the fish oil only group. Additionally, a 4-week low temperature treatment at 25, 20, 15, or 9 °C increased Δ6 desaturase mRNA expression and enzyme activity with decreasing water temperature. These results may help us better understand the biosynthesis of unsaturated fatty acids in C. quadricarinatus.

Fabrication and characterization of cellular iron nanocrystalline film.

Cellular iron nanocrystalline film was fabricated on carbon substrate by electron beam chemical vapor deposition (EB-CVD). The film was made up of single alpha-iron cubes with {100} facets ranging from several tens to 200 nm. The thickness and distribution of the film could be controlled by adjusting the irradiation position and duration of the electron beam. The integration of well-faceted nanocrystals enables the film to have a high ratio of free surfaces, which are essential for applications in chemical catalysis and energy absorption. The application of this film as a substrate for further nanofabrication was demonstrated.

Sensitivity of key factors and uncertainties in health risk assessment of benzene pollutant.

Predicting long-term potential human health risks from contaminants in the multimedia environment requires the use of models. However, there is uncertainty associated with these predictions of many parameters which can be represented by ranges or probability distributions rather than single value. Based on a case study with information from an actual site contaminated with benzene, this study describes the application of MMSOILS model to predict health risk and distributions of those predictions generated using Monte Carlo techniques. A sensitivity analysis was performed to evaluate which of the random variables are most important in producing the predicted distributions of health risks. The sensitivity analysis shows that the predicted distributions can be accurately reproduced using a small subset of the random variables. The practical implication of this analysis is the ability to distinguish between important versus unimportant random variables in terms of their sensitivity to selected endpoints. This directly translates into a reduction in data collection and modeling effort. It was demonstrated that how correlation coefficient could be used to evaluate contributions to overall uncertainty from each parameter. The integrated uncertainty analysis shows that although drinking groundwater risk is similar with inhalation air risk, uncertainties of total risk come dominantly from drinking groundwater route. Most percent of the variance of total risk comes from four random variables.

[Uncertainty analysis of health risk assessment caused by benzene contamination in a contaminated site].

Lots of uncertainties lie in the procedure of environmental risk assessment (ERA) and how to analyze them exactly is studied comprehensively. Based on the investigation of petroleum contamination in a contaminated site, the representative benzene contaminant in soil was selected to analyze uncertainty of environmental risk resulting from drinking and inhalation exposure routes, using the Monte-Carlo simulations. According to the analysis results, the total health risk average value caused by benzene contamination from the alkene factory is 1.18 x 10(-4) for the people living on the district A, which is more than the risk limit of U.S. EPA 10(-6) and means contamination hazard to health. In four different areas of the alkene factory, the main source of risk comes from the cracking equipments with 1.17 x 10(-4). With the impact factors of the uncertainty, the contamination harm to the human health's probability is different referring to the different risk level, which is a criteria value meaning no harm to health issued by different institution. The study results provide an important foundation of effective control and remediation actions of contaminated sites.

Detection of iron-oxide layer on the surface of iron nitride using high-resolution electron microscopy and Fourier filtering.

High-resolution electron microscopy (HREM) was used to detect the surface Fe3O4 iron-oxide layer formed on [011] Fe4N iron nitride due to electron irradiation in the transmission electron microscope. The existence of a surface oxide layer was confirmed by both image processing and through-focus observation. Images of the iron oxide were revealed using the process of fast Fourier transformation (FFT) of experimental HREM images, filtering of the FFT patterns and inverse FFT. By through-focus observation, HREM images of iron oxide were obtained based on the tuning of contrast transfer function. Fourier filtering is effective for examining the beginning of phase transformation, because at this stage the diffraction spots of iron oxide are too weak to be detected. At the time when the iron oxide layer has developed to some extent, through-focus observation is useful to obtain an image of oxide layers.