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.

Fetal But Not Maternal Angiotensin Converting Enzyme (ACE)-2 Gene Rs2074192 Polymorphism is Associated with Increased Risk of Being a Small For Gestational Age (SGA) Newborn.

BACKGROUND/AIMS: The maternal and fetal Renin-Angiotensin-System is involved in the control of pregnancy outcomes such as blood pressure control and gestational age. However, very little is known about the impact of the angiotensin converting enzyme 2 (ACE2) on pregnancy outcome. We thus performed a prospective clinical observational study analyzing the association of maternal and fetal ACE2 gene rs2074192 polymorphism with fetal growth during pregnancy. METHODS: 898 singleton pregnant women were prospectively recruited. 739 pregnant women finally participated in the study and were genotyped. 474 women also donated umbilical cord blood for gene analysis of their offspring. All data such as basic demographic information, data from birth records, biochemical and immunological parameters, as well as Doppler ultrasonographic findings during pregnancy were collected. Fetal and maternal ACE2 gene rs2074192 polymorphism was genotyped by DNA sequencing. RESULTS: Our analysis showed that the maternal ACE2 gene rs2074192 polymorphism was not associated with gestational hypertension, gestational diabetes mellitus, anemia, postpartum hemorrhage and fetal growth. However, neonates having rs2074192 T allele were more likely to be born as small for gestational age (SGA) babies. After multivariable logistic regression considering known confounding, we could demonstrate that the neonatal rs2074192 T allele was an independent risk factor for SGA (OR: 22.93, 95%CI: 1.26∼418.77, P< 0.05). CONCLUSION: This is the first study showing that the babies but not their mothers with ACE2 gene rs2074192 T allele had a high risk for SGA, which contributes to metabolic syndrome and cardiovascular diseases in later life.

A Systematic Review and Meta-Analysis of Influenza A Virus Infection During Pregnancy Associated with an Increased Risk for Stillbirth and Low Birth Weight.

BACKGROUND/AIMS: Impaired pregnancy outcomes, such as low birth weight are associated with increased disease risk in later life, however little is known about the impact of common infectious diseases during pregnancy on birth weight. The study had two aims: a) to investigate risk factors of influenza virus infection during pregnancy, and b) to analyze the impact of influenza virus infection on pregnancy outcome, especially birth weight. METHODS: Prospective and retrospective observational studies found in PubMed, MEDLINE, Embase, Google Scholar, and WangFang database were included in this meta analysis. Data of included studies was extracted and analyzed by the RevMan software. RESULTS: Pregnant women with anemia (P=0.004, RR=1.46, 95% CI: 1.13-1.88), obesity (P<0.00001, RR=1.35, 95% CI: 1.25-1.46) and asthma (P<0.00001, RR=1.99, 95% CI: 1.67-2.37) had higher rates of influenza virus infection. Regarding birth outcomes, influenza A virus infection did not affect the likelihood for cesarean section. Mothers with influenza had a higher rate of stillbirth (P=0.04, RR=2.36, 95% CI: 1.05-5.31), and their offspring had low 5-minute APGR Scores (P=0.009, RR=1.39, 95% CI: 1.08-1.79). Furthermore, the rate for birth weight < 2500g (P=0.04, RR=1.71, 95% CI: 1.03-2.84) was increased. CONCLUSION: Results of this study showed that anemia, asthma and obesity during pregnancy are risk factors influenza A virus infection during pregnancy. Moreover, gestational influenza A infection impairs pregnancy outcomes and increases the risk for low birth weight, a known risk factor for later life disease susceptibility.

[HBsAg seroconversion after entecavir therapy for 7 years following a poor response to interferon-α 2b monotherapy in a HBeAg-negative patient with chronic hepatitis B].

We report a rare case of HBsAg seroconversion after 7 years of entecavir therapy in a 48-year-old HBeAg-negative CHB male patient with chronic hepatitis B (CHB). After a poor response to a 48-week interferon-α 2b therapy, the patient received long-term entecavir therapy. Serum ALT levels became normal and HBV DNA viral load was undetectable at the 10th week after commencement of entecavir treatment, and seroconversion of HBsAg was detected after 7 years of entecavir therapy.

Development of a local vasodilator delivery system using fibrin glue to prevent arterial graft from spasm.

The clinical benefits of coronary artery bypass graft operations can be compromised by postoperative vasospasm. Traditionally, local papaverine (PPV) has been employed during the procedure to prevent and counteract vasospasm. But the relatively short action period limited its application. Fibrin glue (FG) might be a potential carrier of PPV for counteracting vasospasm in a longer action period than PPV solution. After FG incorporated with PPV (PPV-FG) was locally administrated in axillary and femoral arteries of dogs, PPV concentrations in artery vessels surrounding the administration sites were compared with the concentrations at the same sites in dogs given PPV solution. The properties of PPV's release in vitro and maintenance in vessel as well as the influence on the mean peripheral blood pressure and drug concentration in peripheral vein after the introduction PPV-FG on the surface of artery in dogs were evaluated. FG was considered to provide a sustained release of PPV and could maintain a high PPV concentration in artery vessel around the administration site. The results suggested that FG was an effective substrate for reserving PPV in the administrated site in a defined period.