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Background and Aims: Accumulated studies have evaluated the effects of glucokinase regulatory protein (GCKR) gene polymorphisms on the risk of nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD), but the association of GCKR polymorphisms with the risk of NAFLD and CAD in the Chinese Han population have remained unclear. The aim of this study was to investigate the association between GCKR gene polymorphisms (rs780094 and rs1260326) and the risk of NAFLD and CAD in NAFLD patients in a Chinese Northern Han population. Methods: GCKR rs780094 and rs1260326 gene polymorphisms were genotyped by polymerase chain reaction sequencing for B-type ultrasonography-proven NAFLD patients with (n = 82) or without (n = 142) CAD, and in healthy controls (n = 152). Serum lipid profiles’ levels were determined using biochemical methods. Statistical analyses were conducted using SPSS 22.0 statistical software. Results: As the results showed, significant differences in the serum lipid profiles existed between each group. No significant differences were observed in the distributions of genotypes and alleles of GCKR rs780094 and rs1260326 in each group. The GCKR rs780094 T and rs1260326 T allele carriers possessed decreased body mass index value, and serum fasting plasma glucose and TG levels in the overall subjects, respectively. In addition, the GCKR rs780094 T allele carriers possessed decreased serum fasting plasma glucose level in the controls and NAFLD + CAD patients. Conclusions: GCKR rs780094 and rs1260326 polymorphisms were found to be not associated with the risk of NAFLD nor of CAD in NAFLD patients in this Chinese Northern Han population. GCKR rs780094 T and rs1260326 T alleles could affect the body mass index value and serum fasting plasma glucose and triglyceride levels.

Objective To investigate the relationship between angiotensin (AGT) rs2493132 gene polymorphism and the risk of developing non-alcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) in the Chinese Han population. Methods Polymerase chain reaction was performed to determine AGT genotypes. Anthropometric and clinical data were investigated and statistically analyzed in the clinical laboratory department of Qingdao Municipal Hospital. Results The AGT rs2493132 CT + TT genotype was an important risk factor for CAD in patients with NAFLD and NAFLD + CAD in healthy controls. The AGT rs2493132 T allele increased the risk of NAFLD + CAD in healthy controls. The AGT rs2493132 CT + TT genotype and T allele also significantly increased the risk of CAD in patients with NAFLD after adjustments for age, sex, and body mass index. In addition, AGT rs2493132 T allele carriers showed higher total cholesterol (TC) and low-density lipoprotein (LDL) levels compared with non-carriers. Conclusions The AGT rs2493132 CT + TT genotype and T allele significantly increased the risk of developing CAD in patients with NAFLD in the Chinese Han population. The AGT rs2493132 T allele was associated with increased serum TC and LDL levels.

Background and aims The therapeutic effect of tenofovir alafenamide fumarate (TAF), tenofovir disoproxil fumarate (TDF) and entecavir (ETV) on chronic hepatitis B (CHB) patients remains inconsistent. The aim of this study was to explore the differences in virological responses to TAF, TDF and ETV in patients with CHB. Methods Literature searches were conducted of the PubMed, EMBASE, and the Cochrane Library databases to identify randomized controlled trials and observational studies published up to July 21, 2020. Statistical comparisons of virological response between TDF, ETV, and TAF were carried out with pooled odds ratio (OR) values. Results The virological response in TDF-treated CHB patients was notably superior to that of the ETV-treated CHB patients after 12-weeks [OR=1.12, 95% confidence interval (CI): 0.89-1.41], 24-weeks (OR=1.33, 95% CI: 1.11-1.61), 48-weeks (OR=1.62, 95% CI: 1.16-2.25), 72-weeks (OR=1.43, 95% CI: 0.78-2.62), and 96-weeks (OR=1.56, 95% CI: 0.87-2.81) treatment. No significant difference was observed for the virological responses in CHB patients after 48-weeks treatment with TAF or TDF. The virological response in TDF+ETV-treated CHB patients was superior to that of TDF-treated CHB patients after 24-weeks, 48-weeks (OR=1.54, 95% CI: 1.17-2.02), 96-weeks, and 144-weeks. Conclusions The virological response in TDF-treated CHB patients was superior to that in ETV-treated CHB patients, but there was no significant difference between TAF and TDF. In addition, the therapeutic effect of TDF+ETV was superior to TDF alone.

Background CHD is reported to be the primary cause of death in patients with NAFLD. Genetic susceptibility genes contribute to the developmental risk of NAFLD or CHD. Whether the genetic factors could affect the risk of CHD in NAFLD patients is not clear. The aim of this study was to investigate the association of PNPLA3 I148M and TM6SF2 E167K variants with the risk of CHD in NAFLD patients in Chinese Han population. Patients and methods PNPLA3 I148M and TM6SF2 E167K variants were genotyped in a cohort of 189 patients with NAFLD and CHD, as well as 242 patients with NAFLD and 242 healthy controls by gene sequencing. Additionally, serum lipids profiles were determined by standard clinical laboratory methods. Results The minor allele frequency of PNPLA3 I148M and TM6SF2 E167K were 0.39 and 0.06 in this cohort, respectively. The distributions of PNPLA3 I148M genotypes and alleles were significant different in NAFLD group vs controls and in NAFLD+CHD group vs NAFLD group (all P P = 0.01). In addition, PNPLA3 I148M and TM6SF2 E167K possess the joint correlation with the decreased risk of CHD in NAFLD patients with the increased number of risk alleles. Besides, PNPLA3 I148M and TM6SF2 E167K variants associated with the decreased serum lipid levels in overall series. Conclusions There was a joint protective correlation of PNPLA3 I148M and TM6SF2 E167K variants with the developmental risk of CHD in NAFLD patients. PNPLA3 I148M and TM6SF2 E167K variants might correlated with the decreased risk of CHD in NAFLD patients by associated with the reduced serum lipid levels.

The transmembrane 6 superfamily member 2 (TM6SF2) gene E167K variant (rs58542926) was identified by exome-wide association study as a nonsynonymous single nucleotide polymorphism associated with nonalcoholic fatty liver disease. The TM6SF2 E167K variant features a C-to-T substitution at nucleotide 499, encoding a glutamate with lysine change at codon 167 (E167K). TM6SF2 is markedly expressed in the liver, small intestine and kidney, and has been proposed as an important risk factor for diseases associated with lipid metabolism. Subsequently, multifunctional studies of the TM6SF2 E167K variant have been carried out in a spectrum of liver diseases, such as nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, fibrosis, cirrhosis, and viral hepatitis. This review summarizes the research status of the TM6SF2 E167K variant in different liver diseases and specific populations, and discusses the potential mechanisms of the TM6SF2 E167K variant's role in the progression of various liver diseases.

Objective Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases. However, the pathogenesis of NAFLD is largely unknown. Here, we investigated the specific role of miR-499-5p in NAFLD. Methods Free fatty acid was used to induce HL-7702 cell line to establish a NAFLD cell model, and animal models of NAFLD were constructed by feeding C57BL/6 mice with a high-fat diet. Expression levels of miR-499-5p in the HL-7702 cells and C57BL/6 mice were determined by quantitative real-time polymerase chain reaction. In addition, functional experiments were carried out through transfecting miR-499-5p inhibitor into NAFLD cells, and injecting NAFLD mice with a lentiviral vector with the miR-499-5p inhibitor. Furthermore, the effects of miR-499-5p on lipidation and inflammation were investigated by oil red O staining, hematoxylin-eosin staining, and biochemical analysis. Results Compared with normal controls, the expression of miR-499-5p was significantly up-regulated in NAFLD cells and tissues in mouse. After NAFLD cells transfected by miR-499-5p inhibitor, the expression of miR-499-5p was inhibited, the lipid deposition and content of triglycerides (TGs) were reduced, and the lipidation was improved. Simultaneously, after NAFLD mice were injected with the miR-499-5p lentiviral vector, the degree of lipid droplet deposition and content of TGs were also reduced. In addition, it decreased the levels of total cholesterol and aspartate aminotransferase in serum, and improved hepatic lipid metabolism. Conclusions Inhibition of miR-499-5p expression improved NAFLD in mice, which provided a new direction for the treatment of NAFLD.

Nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis to NAFLD-related liver cirrhosis and is a main cause of chronic liver diseases. Patients with nonalcoholic steatohepatitis and fibrosis are at a great risk of the progression to cirrhosis or hepatocellular carcinoma, both of which are tightly associated with liver-related mortality. Liver biopsy is still the gold standard for the diagnosis of NAFLD, but some defects, such as serious complications, sampling error and variability in histologic evaluation among pathologists, remain problematic. Therefore, noninvasive, repeatable and accurate diagnostic methods are urgently needed. Ultrasonography is a well-established and lower-cost imaging technique for the diagnosis of hepatic steatosis, especially suitable for population census, but limited by its low sensitivity to diagnose mild steatosis and being highly operator-dependent. Computed tomography also lacks the sensitivity to detect mild steatosis and small changes in fat content, and presents a potential radiation hazard. Controlled attenuation parameter based on the FibroScan® technology is a promising tool for noninvasive semiquantitative assessment of liver fat content, but the accuracy rate depends on the operator’s expertise and is affected by age, width of the intercostal space, skin capsular distance and body mass index. Magnetic resonance imaging and magnetic resonance spectroscopy are regarded as the most accurate quantitative methods for measuring liver fat content in clinical practice, especially for longitudinal follow up of NAFLD patients. In this review, we mainly introduce the current imaging methods that are in use for evaluation of liver fat content and we discuss the advantages and disadvantages of each method.

Objective To investigate the relationship between angiotensin ( AGT) rs2493132 gene polymorphism and the risk of developing non-alcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) in the Chinese Han population. Methods Polymerase chain reaction was performed to determine AGT genotypes. Anthropometric and clinical data were investigated and statistically analyzed in the clinical laboratory department of Qingdao Municipal Hospital. Results The AGT rs2493132 CT + TT genotype was an important risk factor for CAD in patients with NAFLD and NAFLD + CAD in healthy controls. The AGT rs2493132 T allele increased the risk of NAFLD + CAD in healthy controls. The AGT rs2493132 CT + TT genotype and T allele also significantly increased the risk of CAD in patients with NAFLD after adjustments for age, sex, and body mass index. In addition, AGT rs2493132 T allele carriers showed higher total cholesterol (TC) and low-density lipoprotein (LDL) levels compared with non-carriers. Conclusions The AGT rs2493132 CT + TT genotype and T allele significantly increased the risk of developing CAD in patients with NAFLD in the Chinese Han population. The AGT rs2493132 T allele was associated with increased serum TC and LDL levels.

Contribution of host genetic backgrounds in the development of gastric microbiota has not been clearly defined. This study was aimed to characterize the biodiversity, structure and composition of gastric microbiota among twins. A total of four pairs of twins and eight unrelated individuals were enrolled in the study. Antral biopsies were obtained during endoscopy. The bacterial 16S rRNA gene was amplified and pyrosequenced. Sequences were analyzed for the composition, structure, and α and β diversities of gastric microbiota. Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, and Fusobacteria were the most predominant phyla of gastric microbiota. Each individual, twins as well as unrelated individuals, harbored a microbiota of distinct composition. There was no evidence of additional similarity in the richness and evenness of gastric microbiota among co-twins as compared to unrelated individuals. Calculations of θYC and PCoA demonstrated that the structure similarity of gastric microbial community between co-twins did not increase compared to unrelated individuals. In contrast, the structure of microbiota was altered enormously by Helicobacter pylori infection. These results suggest that host genetic backgrounds had little effect in shaping the gastric microbiota. This property of gastric microbiota could facilitate the studies discerning the role of microbiota from genetic grounds in the pathogenesis.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases. However, the pathogenesis of NAFLD is largely unknown. Here, we investigated the specific role of miR-499-5p in NAFLD. Method: Free fatty acid (FFA) was used to induce HL-7702 cell line to establish a NAFLD cell model, and animal models of NAFLD were constructed by feeding C57BL/6 mice with high fat diet (HFD). Expression levels of miR-499-5p in the HL-7702 cells and C57BL/6 mice were determined by RT-qPCR. In addition, functional experiments were carried out through transfecting miR-499-5p inhibitor into NAFLD cells, and injecting NAFLD mice with a lentiviral vector with knock down the miR-499-5p . Furthermore, the effects of miR-499-5p inhibition on lipidation and inflammation were investigated by oil red O staining, HE staining, and biochemical analysis. Results: Compared with normal controls, the expression of miR-499-5p was significantly up-regulated in NAFLD cells and tissues in mouse (P < 0.05). After NAFLD cells transfected by miR-499-5p inhibitor, the expression of miR-499-5p was inhibited, the lipid deposition and content of TG were reduced, and the lipidation was improved (P < 0.05). Simultaneously, after NAFLD mice were injected with knocked down the miR-499-5p lentiviral vector, the degree of lipid droplet deposition and content of TG were also reduced. Besides, it also decreased the levels of TC and AST in serum, and improved hepatic lipid metabolism (P < 0.05). Conclusion: Inhibition of miR-499-5p expression improved NAFLD in mice, which provided a new direction for the treatment of NAFLD.

Background Dysregulation of the lipid homeostasis is an independent risk factor for non-alcoholic fatty liver disease (NAFLD). Some studies had demonstrated that TRIB1 gene polymorphisms affect the plasma lipids metabolism, but no related data was available for TRIB1 gene polymorphisms in the lipids metabolism in Chinses Han population. The present study was conducted to investigate the association between TRIB1 gene polymorphisms (rs17321515 and rs2954029) and the risk of NAFLD in Chinese Han population and their effects on serum lipid profiles. Patients and methods TRIB1 rs17321515 and rs2954029 gene polymorphisms were genotyped using the polymerase chain reaction (PCR) in B-type ultrasonography-proven NAFLD patients (n = 146) and healthy controls (n = 175). Serum lipid profiles were determined using biochemical methods. Statistical analyses were performed using SPSS 22.0 statistical software. Results The allele distributions of TRIB1 rs17321515 A and rs2954029 A were significant different between the NAFLD patients and healthy controls (P = 0.026, P = 0.045, respectively). The genotype distribution of TRIB1 rs17321515 was significant different between NAFLD patients and healthy controls (P = 0.038). The TRIB1 rs17321515 GA + AA genotype and TRIB1 rs2954029 TA + AA genotype markedly increase the NAFLD risk (OR = 1.885; 95%CI: 1.157–3.070; OR = 1.627; 95%CI: 1.011–2.619, respectively), after adjusted for age, gender, and body mass index, the NAFLD risk still significant (OR = 2.240; 95%CI: 1.196–4.197; OR = 2.050; 95%CI: 1.110–3.786, respectively). In addition, TRIB1 rs17321515 A and rs2954029 A carriers possess the higher lipid profiles in the included subjects. Conclusions TRIB1 rs17321515 and rs2954029 were significant associated with the risk of NAFLD in Chinese Han population. The rs17321515 A and rs2954029 A allele increases the serum lipid profiles in Chinese Han population.

Background and Aims: Colorectal cancer is associated with non-alcoholic fatty liver disease (NAFLD) and other metabolic syndromes, such as obesity, abnormal blood glucose, and dyslipidemia. The relationship of NAFLD and colorectal adenoma, which is the precursor of colorectal cancer, is worthy of discussion. The aim of this study was to investigate the association between colorectal adenoma and NAFLD, colorectal adenoma and metabolic syndrome in a Chinese Han population. Methods: This retrospective study analyzed the relationship between NAFLD and colorectal adenoma in 1089 patients in Qingdao municipal hospital. Subjects were divided into a colorectal adenoma group (n = 267) and a control group (n = 822). NAFLD and the controlled attenuation parameter (CAP) value were determined by abdominal ultrasound and FibroScan. Results: Patients with NAFLD in the colorectal adenoma group and the control group represented 142 cases (53.2%) and 360 cases (43.8%), respectively. The mean CAP value in the colorectal adenoma group was significantly higher than that in the control group. The values of body mass index, triglyceride, high-density lipoprotein cholesterol, aspartate aminotransferase, fasting plasma glucose, and uric acid were also significantly higher in the colorectal adenoma group than in the control group. Multifactor logistic regression analysis showed that the sex, NAFLD, CAP, body mass index, triglyceride, aspartate aminotransferase, and fasting plasma glucose were significant risk factors for colorectal adenoma. Besides, NAFLD and CAP value were significant risk factors for colorectal adenoma in males but not in females. Conclusions: NAFLD and metabolic syndrome were tightly associated with the risk of colorectal adenoma in this Chinese Han population. The effect of NAFLD on colorectal adenoma was prominent in males rather than in females.

Background Genetic factors affect the risk of non-alcoholic fatty liver disease (NAFLD) and colorectal adenoma (CRA) importantly. Transmembrane protein 6 superfamily member 2 (TM6SF2) rs58542926 is a significant genetic susceptibility site for NAFLD. The relationships of TM6SF2 rs58542926 with the risk of NAFLD and CRA in Chinese Han population were unclear. The aim of this study was to investigate the association of TM6SF2 rs58542926 with the risk of NAFLD and CRA, and the effect of CRA on TM6SF2 rs58542926 carried NAFLD patients. Results A total of 839 Chinese Han population were included in this retrospective study. TM6SF2 rs58542926 polymorphism was genotyped in B-type ultrasonography proven NAFLD patients with or without CRA, CRA patients and healthy controls, using polymerase chain reaction. Serum lipid profiles were determined using biochemical methods. Statistical analyses were performed using SPSS statistical software, version 16.0 for mac. There was a significant difference in the distribution of genotype and allele of TM6SF2 rs58542926 in NAFLD and NAFLD&CRA patients compared to controls. The CT + TT genotypes were tightly associated with the risk of NAFLD and NAFLD&CRA. TM6SF2 rs58542926 T allele promotes the abnormal regulation of lipids metabolism and liver injury in NAFLD patients and NAFLD&CRA patients. CRA aggravates the clinical performance of NAFLD in T allele carriers. Conclusions We demonstrated the significant association between TM6SF2 rs58542926 polymorphism and the risk of NAFLD and NAFLD&CRA in a Chinese Han population. The TM6SF2 rs58542926 T allele promotes the abnormal regulation of lipid profiles and liver injury in NAFLD patients, NAFLD&CRA patients, and overall subjects.

Non-alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver disease in the world, is affected by numerous extrinsic and intrinsic factors, including lifestyle, environment, diet, genetic susceptibility, metabolic syndrome and gut microbiota. Accumulating evidence has proven that gut dysbiosis is significantly associated with the development and progression of NAFLD, and several highly variable species in gut microbiota have been identified. The gut microbiota contributes to NAFLD by abnormal regulation of the liver-gut axis, gut microbial components and microbial metabolites, and affects the secretion of bile acids. Due to the key role of the gut microbiota in NAFLD, it has been regarded as a potential target for the pharmacological and clinical treatment of NAFLD. The present review provides a systematic summary of the characterization of gut microbiota and the significant association between the gut microbiota and NAFLD. The possible mechanisms of how the gut microbiota is involved in promoting the development and progression of NAFLD were also discussed. In addition, the potential therapeutic methods for NAFLD based on the gut microbiota were summarized.

Hepatitis B virus (HBV) is a significant global pathogen and efficient cure for HBV patients is still a challenging goal. We previously reported that acidic mucopolysaccharide from stichopus japonicus selenka (SJAMP) could inhibit HBsAg and HBeAg expression in vitro. However, the potential anti-HBV effects of SJAMP in vivo have not yet been explored. In this study, we show that SJAMP exhibits potent anti-HBV activity in HBV transgenic mice in a dose-dependent manner. Specifically, sixty HBV transgenic male BALB/c mice were randomly selected to receive the treatment of PBS, low dose SJAMP (30 mg kg−1), middle dose SJAMP (40 mg kg−1), high dose SJAMP (50 mg kg−1) and IFN (45 IU kg−1) for 30 d. SJAMP treatment suppressed serum HBV-DNA, and liver HBsAg and HBcAg levels in HBV-transgenic mice. The present study highlights the potential application of SJAMP in HBV therapy.

Background: Non-alcoholic fatty liver disease (NAFLD) as a severe health problem is the leading cause of morbidity and mortality from the chronic liver disease worldwide. NAFLD is tightly associated with dyslipidemia although the etiology is still unclear. ATP binding cassette subfamily A member 1 (ABCA1) is involved in cholesterol efflux, fatty acid oxidation, and inflammation. Although some reports show that the ABCA1 polymorphisms affect the lipids metabolism and severity of clinical liver diseases, the effects of ABCA1 polymorphisms on the development of NAFLD are unknown. Objectives: The current study was performed to investigate the association between the ABCA1 polymorphisms and the development of NAFLD and the effect of the four ABCA1 SNPs on the serum lipid levels. Methods: The ABCA1 polymorphisms (rs1800977, rs2066714, rs2066715, and rs2230808) were determined in 265 NAFLD patients and 126 healthy controls using the sequencing and polymerase chain reaction analysis. Serum lipid profiles and liver enzymes were examined using standard clinical laboratory methods. Results: There was a significant difference (P < 0.05) in the genotype of the ABCA1 rs1800977 G/A polymorphisms between NAFLD patients and healthy controls. No significant differences were found in genotypes and allele frequencies of the ABCA1 rs2066714T/C, rs2066715T/C, and rs2230808C/T between NAFLD patients and healthy controls. The ABCA1 rs1800977 A was independently associated with NAFLD after adjusting for the effects of age, gender, and BMI. Compared to the noncarriers in NAFLD patients, the carriers of ABCA1 rs2066714 C showed a significantly higher level of LDL (P = 0.045) and the carriers of ABCA1 rs2230808 T showed a significantly lower level of HDL (P = 0.039). Conclusions: We first demonstrated the association between the ABCA1 polymorphisms and the risk of NAFLD in a Chinese Han population. The ABCA1 rs1800977 may be a protective factor against the development of NAFLD. The ABCA1 rs2066714 C allele could increase the serum LDL cholesterol level, and the ABCA1 rs2230808 T allele could decrease the serum HDL cholesterol level in NAFLD patients.

Background: Cytokeratin-18 Neoepitope M30 (CK-18 M30) has been reported to be associated with chronic HBV infection and severity of liver injury; however, the results of these studies are inconsistent. Objectives: We sought to investigate the association between serum CK-18 M30 levels and the severity of liver injury in chronic hepatitis B (CHB) patients. Methods: A systematic literature search was performed in PubMed, Embase, and Cochrane Library databases for relevant studies published in English up to August 2017. Heterogeneity among individual studies was investigated for summarizing all the studies. The standard mean difference (SMD) and 95% confidence interval (CI) were calculated using a random-effects model or fixed-effects model. Finally, the sensitivity analysis and publication bias were performed to evaluate the accuracy of this meta-analysis. Statistical analysis was conducted using Review Manager 5.3 and Stata 12.0. Results: Five case-control studies were included in the ultimate analysis, recruiting 488 CHB patients, 276 inactive carriers, and 193 healthy controls. The major results of the meta-analysis revealed significantly elevated serum CK-18 M30 levels in chronic HBV infected patients including CHB patients with severe liver injury and inactive HBV carriers when compared to healthy controls (SMD = 1.13, 95% CI: 0.75 - 1.50, P < 0.001; SMD = 0.63, 95% CI: 0.38 - 0.89, P < 0.001, respectively). Furthermore, the serum CK-18 M30 levels were significantly higher in CHB patients with severe liver injury than in inactive carriers (SMD =1.29, 95% CI: 0.60 - 1.98, P < 0.001). The sensitivity and publication bias analysis verified the stability and reliability of our analysis. Conclusions: The elevated serum CK-18 M30 levels could be regarded as a useful non-invasive biomarker for the diagnosis of chronic HBV infection, and were associated with the severity of liver injury in chronic Hepatitis B patients. The serum CK-18 M30 levels could reflect the liver inflammation in inactive carriers, representing the early stage of chronic HBV infection.

Background Some studties reported that the polymorphism of TM6SF2 gene E167K affects the occurrence and the progression of hepatocytes carcinoma (hepatocellular, HCC). In oeder to investigate the effects of the polymorphism of TM6SF2 gene E167K in the pathogenesis of HCC, we explored its influence on the cell cycle in hepatocellular carcinoma cell HEPA1-6. Methods HEPA 1–6 cells which could respectively overexpress TM6SF2 wild type and E167K variant were cultured and HEPA 1–6 cells with zero load plasmids were used as matched control. Flow cytometry was used to detect the cell cycles of these 3 type of HEPA 1–6 cells. Realtime fluores-cence quantitative PCR and western blot were used to analyzed the expression of regulatory factors (Cyclin D1、p53、P16、P27、P21 and Rb) of cell cycle. T-test was used in statistical analysis. Results Cell cycle phase distribution was presented by the proportion of cells in each phases (%). Compared with the control group, the cell cycle phase distribution (G1 phase 57.36 ± 0.21%, G2/M phase 25.61 ± 0.36%,S phases 19.31 ± 0.25%) had no differences in wild type group (G1 phase 57.63 ± 0.28%, G2/M phase 25.77 ± 0.51%, S phases 19.54 ± 0.25%; P 0.05). P16 and P21 expression showed no statistical sigtfificance in any of these three groups (P > 0.05). Conclusion E167K polymorphism of TM6SF2 gene affects cell cycles of HEPA1–6 cells via up-regulating CyclinD1、P53 and Rb and down-regulating P27.

Context An optimal therapeutic strategy has not yet been identified for the pharmacological treatment of intrahepatic cholestasis of pregnancy (ICP). The aim of this study was to evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) and S-adenosylmethionine (SAMe) in the treatment of ICP, both individually and in combination. Evidence Acquisition A meta-analysis of all randomized controlled trials (RCTs) comparing UDCA, SAMe, and combination therapy was performed. We carried out a literature search using pubmed, embase, the cochrane register of controlled trials, and the science citation index of web of science. The maternal clinical and biochemical responses, including pruritus scores, total bilirubin, total bile acids, alanine aminotransferase, and aspartate transaminase, were evaluated. Safety assessments, including preterm delivery, cesarean section, and meconium-stained amniotic fluid, were also analyzed. Results Five RCTs including 311 patients were evaluated. In comparison to SAMe, UDCA significantly reduced the pruritus score (OR = -0.45, 95% confidence interval [CI]: -0.66 to -0.25, P < 0.0001) and improved the levels of total bile acids (TBAs; OR = -0.59, 95% CI: -0.99 to –0.30, P < 0.0001) and alanine aminotransferase (ALT; OR = -0.38, 95% CI: -0.66 to -0.09, P = 0.01). UDCA was associated with significantly lower preterm delivery rates than SAMe (RR = 0.48, 95% CI: 0.32–0.72, P = 0.0004). Interestingly, combination therapy significantly reduced total bilirubin (TB; vs. SAMe, OR = -0.41, 95% CI, -0.74 to -0.08, P = 0.02), aspartate transaminase (AST; vs. UDCA, OR = -0.40, 95% CI, -0.74 to –0.06, P = 0.02), and the rate of preterm delivery (vs. SAMe, OR = 0.62, 95% CI, 0.42 - 0.91, P = 0.02), in comparison with either drug administered alone. Conclusions UDCA decreased the pruritus score, TBA, and ALT levels more effectively than SAMe, reducing the rate of preterm delivery for ICP.

Background: Cardiovascular events are an independent risk factor for nonalcoholic fatty liver disease (NAFLD), which is the leading cause of mortality in NAFLD patients. Several recent studies demonstrated that adiponectin (Ad) polymorphisms were involved in the progression of NAFLD and coronary artery disease (CAD). However, reports on the association between Ad polymorphisms and the risk of developing CAD in NAFLD patients are lacking in a Northern Han Chinese population. Objectives: The present study was designed to evaluate the association between Ad gene polymorphisms (rs266729 and rs2241766) and the risk of developing CAD in Northern Han Chinese patients with NAFLD. Materials and Methods: In this case-control study, using the polymerase chain reaction (PCR), Adrs266729 and rs2241766 gene polymorphisms were genotyped in B-type ultrasonography-proven NAFLD patients, with (n = 246) or without (n = 247) CAD and in healthy controls (n = 304). Serum lipid profiles were determined using biochemical methods. Statistical analyses were performed using SPSS 17.0 statistical software. Results: There were significant differences in the Adrs266729 G allele between the NAFLD patients with and without CAD (P < 0.05). In addition, there was a significant difference in the Adrs2241766 G allele of the NAFLD patients compared with that of the controls (P < 0.05). In the NAFLD CAD population, carriers of the G allele of Adrs266729 had higher serum triglycerides (TG), total cholesterol (TC), fasting plasma glucose (FPG), and low-density lipoprotein (LDL) levels and a lower Ad level than their noncarrier counterparts (P = 0.031, P = 0.034, P = 0.007, P < 0.001, and P < 0.001, respectively). NAFLD patients without CAD had higher TG and serum FPG values and a lower Ad level than their noncarrier counterparts (P = 0.014, P = 0.038, and P < 0.001, respectively). In the NAFLD patients with/without CAD, the carriers of the G allele of Adrs2241766 had higher TG levels (P = 0.039 and P = 0.042, respectively) than those of their noncarrier counterparts. Conclusions: In this Northern Chinese Han population, the Adrs266729 and rs2241766 G alleles were closely associated with the occurrence of NAFLD. However, only NAFLD patients who carried the Adrs266729 G allele had an increased risk of developing CAD.

Background Cardiovascular disease (CAD) responsible and nonalcoholic fatty liver disease (NAFLD) are both metabolic diseases, and they are mostly influenced by genetic factors. The aim of our study is to evaluate the relationship between angiotensin II type-1 receptor (AGTR1) gene rs3772622 polymorphisms and the risk of developing coronary artery disease (CAD) in Chinese patients with NAFLD. Methods Genotype for AGTR1 rs3772622 in 574 NAFLD patients with CAD or 589 NAFLD patients without CAD, 332 CAD patients exclude NAFLD and 338 health control subjects were determined by sequencing and polymerase chain reaction analysis. Relevant statistical methods were employed to analyze the genotypes, alleles and the clinical date. Inter-group differences and associations were assessed statistically using t-tests and Chi square and logistic analyses. The relative risk of AGTR1 rs3772622 for NAFLD was estimated by logistic regression analysis. Results No significant difference in genotype and allele frequency of AGTR1 rs3772622 was found between the NAFLD without CAD population and the controls (P > 0.05). However, makeable difference was found when compared the CAD in patients with NAFLD and CAD free NAFLD patients (P

To investigate the role and mechanism of action of fibroblast growth factor-21 (FGF-21) in reducing triglyceride (TG) in the in vitro and in vivo models of nonalcoholic fatty liver disease (NAFLD).(1) A mixture of free fatty acids was used to establish a model of steatosis in L02 cells, and the cells were treated with various concentrations of FGF-21 or fenofibrate. Twenty-four hours later, oil red O staining was performed to observe the degree of steatosis, and intracellular TG content was determined. RT-PCR and Western blot were applied to measure the mRNA and protein expression of sterol regulatory element-binding protein-1c (SREBP-1c). (2) High-fat diet was used to establish a mouse model of steatosis, and these mice were intraperitoneally injected with FGF-21 or fenofibrate. Eight weeks later, whole blood and liver samples were collected, and HE staining was performed to observe steatosis. Meanwhile, the serum levels of TG, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured, and TG content in the liver was also measured. One-way analysis of variance was used for comparison of data between multiple groups, and the least significant difference t-test was used for comparison between any two groups.(1) Compared with the control group, the model group showed significant steatosis, with significant increases in intracellular lipid droplets and TG content (t = -20.57, P0.01), while FGF-21 reduced the number of intracellular lipid droplets and TG content (F = 98.16, P0.01) in a dose-dependent manner. In addition, the model group had significantly increased mRNA and protein expression of SREBP-1c compared with the control group (t = -10.73 and -0.1006, both P0.01), while FGF-21 down-regulated the mRNA and protein expression of SREBP-1c (F = 161.35 and 36.72, both P0.01). (2) Compared with the mice in the control group, those in the model group showed significant steatosis and had significant increases in serum TG level and TG content in the liver (t = -18.84 and 15.71, both P0.01). FGF-21 relieved hepatic steatosis and reduced the serum TG level and TG content in the liver (t = 18.11 and 9.46, both P0.01). Moreover, FGF-21 reduced the serum levels of ALT and AST in NAFLD mice (t = 25.93 and 12.50, both P0.01).FGF-21 can inhibit the synthesis of TG through suppressing the expression of SREBP-1c, which further confirms the potential therapeutic effect of FGF-21 in the treatment of NAFLD. This may provide new ideas for the treatment of NAFLD.

Background: Recent genome-wide association studies (GWAS) identified that gene Lysophospholipase-like 1 ( LYPLAL1) rs12137855 associated with non-alcoholic fatty liver disease (NAFLD). No research has been performed regarding the association between LYPLAL1 and NAFLD in China. Objectives: The aim of the present study was to investigate the association between the gene LYPLAL1 rs12137855 and NAFLD, and the effect on serum lipid profiles in a Chinese Han population. Patients and Methods: LYPLAL1 rs12137855 gene was genotyped in 184 patients with NAFLD and 114 healthy controls using sequencing and polymerase chain reaction analysis (PCR). We tested serum lipid profiles using biochemical methods. Results: No significant differences in genotype and allele frequencies of LYPLAL1 rs12137855 was found between the NAFLD group and the controls group (P > 0.05). Subjects with the variant LYPLAL1 rs12137855 CC genotype had a higher mean weight, body mass index (BMI) and low density lipoprotein (LDL). Conclusions: Our results showed for the first time that LYPLAL1 gene is not associated with a risk of NAFLD development in the Chinese Han population. The variant carriers of overall subjects significantly increased weight, BMI and LDL.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic stress-induced liver disease that is closely related not only to genetic susceptibility but also to insulin resistance and highly linked with metabolic syndrome. In recent years, the prevalence of NAFLD has increased rapidly, paralleling the epidemic of type 2 diabetes mellitus and obesity leading to cardiovascular disease. It has been demonstrated that NAFLD is highly associated with atherosclerosis. With recently gained knowledge, it appears that NAFLD may induce insulin resistance, dyslipidemia, oxidative stress, inflammation, and fluctuation of adipokines associated with atherosclerosis. In this review, we aimed to summarize recent discoveries related to both NAFLD and atherosclerosis, and to identify possible mechanisms linking them.

Context: The objective of the current study was to evaluate the association between the I148M variant of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and the presence of Chronic Hepatitis C (CHC) across different populations. Evidence Acquisition: This study was a meta-analysis of all relevant researches published in the literature from year 2000 to 2015. The odds ratios (ORs) of PNPLA3 allele distributions in CHC patients were analyzed and compared with healthy controls. The meta-analysis Revman 5.2 software was applied for investigating heterogeneity among individual studies and for summarizing all the studies. The meta-analysis was carried out according to the Cochrane Reviewers’ Handbook recommendations. A total of 120 clinical trials or reports were retrieved, yet only five trials met the study selection criteria. Results: Five hospital-based case-control studies were included in the final analysis. The overall frequency of PNPLA3 gene polymorphisms was 20.4% (205/1005) in CHC and 10.23% (53/518) in controls. The summary odds ratio for the association of gene polymorphisms of PNPLA3 with the risk for CHC was determined as 2.20 (95% CI: 1.56 -3.11) and was statistically significant (P < 0.05). Conclusions: The current meta-analysis showed an association between frequency of GG genotype of PNPLA3 and the risk of development of CHC in various populations throughout the world.

Background: Leptin receptor (LEPR) polymorphisms have been reported to be associated with lipid metabolism and insulin re- sistance in various populations. However, whether LEPR polymorphisms are associated with the risks of non-alcoholic fatty liver disease (NAFLD) and coronary atherosclerosis in the Chinese Han population remains unknown. Objectives: To investigate the association of LEPR polymorphisms at Q223R and K109R with the risks of NAFLD and coronary atherosclerosis in the Chinese Han population. Patients and Methods: Genotypes of LEPRQ223R and K109R were determined by polymerase chain reaction followed by sequenc- ing in patients with NAFLD (n = 554), coronary atherosclerosis (n = 421), and healthy controls (n = 550). Serum lipid profiles were determined using biochemical methods. Pearson's 2 test was used to check for Hardy-Weinberg equilibrium and to analyze the distributions of genotypes' alleles between groups. Baseline characteristics were analyzed using student's t-test, paired-samples t-test, or the 2 test where appropriate. Results: TheLEPRQ223R A allele significantly reduced the risks of both NAFLD and coronary atherosclerosis (OR = 0.683, 95% CI: 0.527 - 0.884, P = 0.004 and OR = 0.724, 95% CI: 0.548 - 0.955, P = 0.022, respectively). Compared to controls, no significant dierences in the genotype and allele frequencies of K109R were found in the NAFLD and coronary atherosclerosis populations, respectively. However, there was a significantly increased risk of coronary atherosclerosis in NAFLD patients who carried the K109R A allele (OR = 2.283, 95% CI: 1.556 - 3.348, P < 0.001). Conclusions: LEPR Q223R polymorphisms may confer a significant risk of NAFLD and coronary atherosclerosis. The A allele in the K109R polymorphism might be considered an independent risk factor for coronary atherosclerosis in NAFLD patients.

To investigate the relationship between SREBP-1c and the risk of liver disease associated with the triacylglyceride lipase PNPLA3 I148M variant using a human hepatoma cell line model transfected with recombinant lentiviruses.Huh7 cells were transfected with control lentivirus or lentivirus containing the PNPLA3 I148M variant (variant). The two cell groups were compared to assess differences in triglyceride content (using oil red O staining), levels of triglyceride and cholesterol (using automated biochemical analyzer), expression of SREBP-lc mRNA (using fluorescence quantitative PCR), and expression of SREBP-1c protein (using western blot.Cells expressing the PNPLA3 I148M variant showed higher triglyceride content (0.54+/-0.03 mmol/L vs. control cells: 0.23+/-0.02 mmol/L; t=22.58, P0.001), cholesterol level (0.28+/-0.03 mmol/L vs. control cells: 0.13+/-0.02 mmol/L; t =11.83, P0.001), SREBP-1cmRNA expression (13.59+/-0.60 vs. 11.81+/-0.82; [The abstract and text in the paper say variant increases, but the data shown says the higher value is in the control cells. Please correct to properly express the data.] P=0.001), and SREBP-1c protein expression. The level of SREBP-1c was positively correlated with serum triglyceride in the cells expressing the PNPLA3 I148M variant (r=0.912, P0.01).The risk of liver disease associated with the PNPLA3 I148M variant, which increases lipogenesis, may involve SREBP-1c and a pathway that increases triglycerides.

Background: Genome-wide association studies have shown that rs738491, rs2143571, and rs3761472 in the sorting and assembly machinery component 50 homolog (SAMM50) gene are significantly associated with susceptibility to nonalcoholic fatty liver disease (NAFLD). Objectives: The present study evaluated the association between the three genetic variants in the SAMM50 gene and susceptibility to NAFLD in a Chinese Han population. Patients and Methods: Genotypes for 3 single nucleotide polymorphisms (SNPs), viz rs738491, rs2143571, and rs3761472, in the SAMM50 gene were determined using an improved multiplex ligation detection reaction technique in 340 B-type ultrasonography-diagnosed NAFLD patients and 452 healthy controls. Meanwhile, serum lipid profiles and liver enzymes were estimated using standard clinical laboratory methods. The SNP-SNP interactions were analyzed by performing multifactor dimensionality reduction (MDR) and generalized multifactor dimensionality reduction (GMDR). Results: The genotype and allele frequencies of the SAMM50 polymorphisms between the NAFLD group and the control group were significantly different (all Ps < 0.05). In the multivariate analysis adjusted for gender, age, and body mass index, the carriers of the rs738491 T allele, rs2143571 A allele, and rs3761472 G allele had significantly increased susceptibility to NAFLD (OR, 1.507; 95% CI, 1.035 to 2.195; P = 0.032; OR, 1.761; 95% CI, 1.232 to 2.517; P = 0.002; OR, 1.483; 95% CI, 1.039 to 2.115; P = 0.030, respectively). Moreover, the rs738491 T allele carriers had significantly higher levels of alanine aminotransferase (ALT) (P = 0.017) than did the noncarriers. However, differences in the levels of serum triglyceride (TG) and aspartate aminotransferase (AST) were not statistically significant (P = 0.123; P = 0.107). The Rs2143571 A allele and the rs3761472 G allele were both deeply associated with increased levels of serum TG, ALT, and AST (all Ps < 0.05). Furthermore, the MDR and GMDR showed that a synergistic relationship might exist between rs738491, rs2143571, and rs3761472 in the SAMM50 gene and the pathophysiology and genetics of NAFLD. Conclusions: We first demonstrated that the rs738491 T allele, rs2143571 A allele, and rs3761472 G allele in the SAMM50 gene created susceptibility to NAFLD in a Chinese Han population. The combination of the three SNPs in the SAMM50 gene may have synergism to predict the predisposition to NAFLD.

To investigate the cell cycle of Huh-7 cells affected by I148M polymorphism of PNPLA3 gene and the possible mechanisms.Huh-7 cells which could respectively overexpress PNPLA3 wild type and I148M variant were cultured and Huh-7 cells with zero load plasmids were used as matched control, Flow cytometry was conducted to detect the cell cycles of these 3 type of Huh-7 cells and western blot and realtime fluorescence quantitative PCR were applied to investigate the expression of regulatory factors (Cyclin D1 and p53) of cell cycle. t-test was used in statistical analysis.Cell cycle phase distribution was presented by the proportion of cells in each phases (%), compared with the control group, the cell cycle phase distribution (G1 phase 59.27 ± 0.15, G2/M phase 24.23 ± 0.31, S phases 16.50 ± 0.26) had no differences in wild type group (G1 phase 58.53 ± 0.35, G2/M phase 24.87 ± 0.60, S phases 16.60 ± 0.26; Probability value less than 0.05). While between variant type group and wild type group, G1 phase was significantly decreased (variant type group G phase 38.37 ± 0.21, Probability value less than 0.05), S phase and G2/M phase were increased (variant type group S phase 27.47 ± 0.35, P less than 0.05; G2/M phase 34.17 ± 0.15, P less than 0.05), respectively. compared with control group, the relative expression of P53 mRNA in variant type group was significantly upregulated (control group 1.06 ± 0.41, variant type group 6.54 ± 0.34; Probability value less than 0.05) and there was no statistical significance in wild type group (1.66 ± 0.30, P more than 0.05); Cyclin D1 expression showed no statistical significance in any of these three groups, control group 1.00 ± 0.10, wild type group 1.06 ± 0.03, variant type group, 1.11 ± 0.04; P0.05).I148M polymorphism of PNPLA3 gene affects cell cycles of Huh-7 cells via up-regulatating P53.

Context: The PNPLA3 I148M variant has been recognized as a genetic determinant of liver fat content and a genetic risk factor of liver damage progression associated with steatohepatitis. The I148M variant is associated with many chronic liver diseases. However, its potential association with inflammatory and autoimmune liver diseases has not been established. Evidence Acquisition: We systemically reviewed the potential associations of I148M variant with chronic viral hepatitis, autoimmune liver diseases and the outcome of liver transplantation, explored the underlying molecular mechanisms and tried to translate them into more individualized decision-making and personalized medicine. Results: There were associations between I148M variant and chronic viral hepatitis and autoimmune liver diseases and differential associations of I148M variant in donors and recipients with post-liver transplant outcomes. I148M variant may activate the development of steatosis caused by host metabolic disorders in chronic viral hepatitis, but few researches were found to illustrate the mechanisms in autoimmune liver diseases. The peripherally mediated mechanism (via extrahepatic adipose tissue) may play a principal role in triglyceride accumulation regardless of adiponutrin activity in the graft liver. Conclusions: Evidences have shown the associations between I148M variant and mentioned diseases. I148M variant induced steatosis may be involved in the mechanism of chronic viral hepatitis and genetic considered personalized therapies, especially for PSC male patients. It is also crucial to pay attention to this parameter in donor selection and prognosis estimation in liver transplantation.

Background: Cardiovascular events account for the main cause of death in patients with non-alcoholic fatty liver disease (NAFLD), and are largely influenced by genetic factors. Although multiple studies showed that tumor necrosis factor-alpha (TNF-α) polymorphisms are risk factors in the progression of NAFLD, few papers on the association of the polymorphisms and the developing coronary artery disease (CAD) in NAFLD patients have been reported. Objectives: The present study was designed to evaluate the association of TNF-α polymorphisms at residues -238 and -308, with the risk of developing CAD in Chinese patients with NAFLD. Patients and Methods: The TNF-α polymorphisms at residues 238 and 308 were genotyped in B-type ultrasonography proven NAFLD patients with (n = 246), without (n = 247) CAD and healthy controls (n = 304), using polymerase chain reaction (PCR). Serum lipid profiles were determined using biochemical methods. Statistical analyses were performed using SPSS statistical software, version 20.0 for Mac. Results: We found a significant association between TNF-α-238 guanine to alanine (GA) polymorphism and carriers of variant allele A between NAFLD patients with and without CAD (P < 0.05). Carriers of the A allele of TNF-α-238 had higher serum triglycerides (TG) and low density lipoprotein (LDL) levels in NAFLD patients with CAD (P = 0.025 and 0.001, respectively) and a higher TG level in NAFLD patients without CAD (P = 0.017), than their non-carrier counterparts. Conclusions: In the Chinese Han population that we studied, NAFLD patients who carry the TNF-α-238 GA polymorphism have an increased risk of developing CAD. Mechanisms underlying this potentially important association require further investigation.

To investigate the association between two polymorphisms of the APOC3 gene (T-455C and C-482T) and hereditary risk of non-alcoholic fatty liver disease (NAFLD).A total of 287 patients with NAFLD and 310 control subjects were genotyped by PCR and direct sequencing. Serum lipid profiles were also detected by standard biochemicalOne-hundred-and-eighty of the study participants were used to measure the APOC3 content by enzyme-linked immunosorbent assay. Inter-group differences and associations were assessed statistically using Chi square and t tests and logistic and linear regression analyses.The frequencies of neither the genotypes or alleles were significantly different between the NAFLD cases and the controls. Compared with the most common genotypes-455TT or-482CC, none of the variants showed a significant increase in risk of NAFLD or for the clinical and biochemical parameters. The adjusted odds ratios (with 95% confidence intervals) of NAFLD were 1.25 (0.79-1.96) and 1.20 (0.76-1.89) for carriers of the APOC3-455C and-482 T variants respectively (P more than 0.05).The T-455C and C-482T polymorphisms of the APOC3 gene are not associated with risk of NAFLD, pathogenic changes in lipid profiles, or insulin resistance in Han Chinese.

To investigate the association between the PNPLA3 rs738409 polymorphism and chronic hepatitis B (CH[B) in a Han Chinese population residing in Qingdao.Peripheral blood samples were collected from 185 CHB patients and 164 healthy controls and subjected to polymerase chain reaction (PCR) and DNA sequencing to determine the PNPLA3 genotypes. The relative risk of the rs738409 polymorphism for CHB was estimated by calculating the odds ratio (OR) and 95% confidence interval.The rs738409 G allele frequency was significantly different between the CHB and control groups (31.9% vs.21.9% respectively, P less than 0.05). Compared to he rs738409 C allele, the G allele was associated with an increased risk of developing CHB (OR =1.67, 95% CI:1.18-2.34, P =0.003). Logistic regression model analysis, with adjustment for confounding factors, indicated that carriers of the PNPLA3 rs738409 GG + GC genotype had increased risk of CHB than carriers of the CC genotype (OR =1.76 ,95% CI:1.14-2.71, P =0.011).Qingdao Han Chinese who are carriers of the rs738409 G allele are at increased risk of CHB.

Context: Our objective was to evaluate the effect of gene polymorphisms of apolipoprotein C3 (APOC3) on the development of non-alcoholic fatty liver disease (NAFLD) in different populations. Evidence Acquisition: We performed a meta-analysis of all relevant studies published in the literature. A total of 115 clinical trials or reports were identified, but only seven trials met our inclusion criteria. A meta-analysis was performed according to the Cochrane Reviewers’ Handbook recommendations. Results: Five hospital-based and two population-based case-control studies were included in the final analysis. The overall frequency of APOC3 gene polymorphisms was 67.5% (1177/1745) in NAFLD and 68.8% (988/1437) in controls. The summary odds ratio for the association of gene polymorphisms of APOC3 and the risk of NAFLD was 1.03 (95% CI: 0.89-1.22),which was not statistically significant (P > 0.05). Conclusions: Our meta-analysis, while not ruling out possible publication bias, showed no association between gene polymorphisms of APOC3 and the risk of NAFLD development in different populations in the world.

Renal cell carcinoma (RCC), one of the most common kidney cancers, has a poor prognosis. Epithelial to mesenchymal transition (EMT) is a hallmark of carcinoma invasion and metastasis. Several studies have examined the molecular regulation of EMT, but the relationship between histone demethylases and EMT is little understood. In this study, we investigated the role of retinoblastoma-binding protein-2 (RBP2), a histone demethylase that is highly expressed in RCC and is positively correlated with poor RCC prognosis in the regulation of EMT. We found that ectopic overexpression of RBP2 can induce cancer stem cell-like (CSC) phenotypes through EMT in RCC cells by converting them to a more mesenchymal phenotype. This results in increased resistance to apoptosis, which leads to enhanced tumor growth in xenograft models. Together, our data show that RBP2 is an epigenetic regulator that has an important role in the initiation of CSC phenotypes through EMT, leading to tumor progression. RBP2 is also a novel biomolecule for RCC diagnosis, and prognosis and may be a therapeutic target.

e12500 Background: Analysis of ctDNA has the potential to revolutionize detection and monitoring of tumors. It’s difficult to identify tumor driving genes in advanced non small cell lung carcinoma ...

Background Recently genome-wide association studies identified that NCAN rs2228603 polymorphism was associated with non-alcoholic fatty liver disease (NAFLD) mainly in subjects of European ancestry. While no research have been conducted to demonstrate the relationship between NCAN rs2228603 and NAFLD in Chinese Han adults. The aim of this study was to investigate whether NCAN rs2228603 is associated with NAFLD in Chinese population. Methods Gene NCAN rs2228603 was genotyped in 182 patients with NAFLD and 195 healthy controls. The expression of NCAN was tested according to polymerase chain reaction analysis (PCR) and serum lipids were performed by biology techniques. Results No significant difference was found in genotype and allele frequencies of NCAN rs2228603 between the NAFLD group and the controls (P > 0.05). Subjects with the NCAN rs2228603 CT genotype showed a higher level of alkaline phosphatase (AKP) (P = 0.017) and a higher high-density lipoprotein (HDL) (P

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease which represents a wide spectrum of hepatic damage. Several studies have reported that NAFLD is a strong independent risk factor for coronary artery disease (CAD). And patients with NAFLD are at higher risk and suggested undergoperiodic cardiovascular risk assessment. Cardiovascular disease (CVD) is responsible for the main cause of death in patients with NAFLD, and is mostly influenced by genetic factors. Both NAFLD and CAD are heterogeneous disease. Common pathways involved in the pathogenesis of NAFLD and CAD includes insulin resistance (IR), atherogenic dyslipidemia, subclinical inflammation, oxidative stress, etc. Genomic characteristics of these two diseases have been widely studied, further research about the association of these two diseases draws attention. The gene polymorphisms of adiponectin-encoding gene (ADIPOQ), leptin receptor (LEPR), apolipoprotein C3 (APOC3), peroxisome proliferator-activated receptors (PPAR), sterol regulatory elementbinding proteins (SREBP), transmembrane 6 superfamily member 2 (TM6SF2), microsomal triglyceride transfer protein (MTTP), tumor necrosis factors-alpha (TNF-α) and manganese superoxide dismutase (MnSOD) have been reported to be related to NAFLD and CAD. In this review, we aimed to provide an overview of recent insights into the genetic basis of NAFLD and CAD.