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The incidence rate of nonalcoholic fatty liver disease (NAFLD) has been increasing in China in recent years and has reached 11％-15％.At present,the multiple-hit hypothesis is considered the main pathogenesis of NAFLD,yet the specific pathogenesis remains unknown.This article elaborates on the roles of carcinoembryonic antigen-related cell adhesion molecule 1 highly expressed in the liver,vitamin D/vitamin D receptor axis,and psychological factors in the development and progression of NAFLD,in order to provide new directions for the research on the pathogenesis of NAFLD in future.
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Objective To explore the correlation between hyperlipidemia and colorectal polyps by compare the level of serum lipids in patients with colorectal polyps.Methods The levels of total cholesterol (TC),triglyceride (TG) and low density lipoprotein-cholesterol (LDL-C) of 159 patients with colorectal polyps and 138 controls were tested.The serum lipids between colorectal polyps group and control group,of colorectal polyps with different pathological type,of adenomatous polyps with different pathological type,of adenomatous polyps with different location,colorectal polyps of different gender were compared.Chi square test or t test were performed for data analysis.Results The incidence of hyperlipidemia of colorectal polyps group was 41.5％ (66/159),which was higher than that of control group (16.7％,23/138) and the difference was statistically significant (x2 =36.56,P＜0.01),its levels of TG,TC and LDL-C were all higher than those of the latter ((1.52±0.56) mmol/L vs (1.06 ± 0.42) mmol/L,(5.22±0.86) mmol/L vs (4.52±0.96) mmol/L,(2.85±0.66) mmol/L vs (2.52± 0.35) mmol/L; t=4.23,4.02,3.72,all P＜0.01).There were no significant differences in the levels of TC,TG and LDL-C between colorectal polyps with different pathological type (all P＞ 0.05).The incidence of hyperlipidemia of tubular villous adenoma and villous adenoma (progressive adenomas) was 60.0％ (15/25),which was higher than that of tubular adenoma group (33.3％,20/60) and the difference was statistically significant (x2=5.18,P＜0.05).The incidence of hyperlipidemia of left colon and rectal polyps group was 46.2％ (49/106),which was higher than that of right colon polyps group (28.6 ％,12/42) and the difference was statistically significant (x2 =3.87,P＜0.05).The incidence of hyperlipidemia of male colorectal polyps group was 47.2％ (51/108),which was higher than that of female group (29.4％,15/51) and the difference was statistically significant (x2 =4.53,P＜0.05).The level of TG of male colorectal polyps group was higher than that of female group ((1.84 ± 0.73) mmol/L vs (1.55±0.65) mmol/L) and the difference was statistically significant (t=3.98,P＜0.05).Age (r=0.766,P=0.009),TG level (r=0.535,P=0.012) and TClevel (r=0.688,P=0.025) were positively correlated with genesis of colorectal polyps.Conclusion There is a significant correlation between hypertriglyceride,hypercholesteremia and colorectal polyps.
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Objective To investigate the effects of exogenous transforming growth factor-β3 (TGF-β3) on the expression of endogenous TGF-β3 and proliferation of rat hepatic stellate cells (HSC).MethodsRat HSC cells were seeded in 24-well plates and were divided into 2 groups.One group of cells were exposed to TGF-β3 of different concentrations (0.08,0.4,2,10 and 50 ng/ml) for 2 hours and then the cell culture supernatant was collected; the other group of cells were exposed to 10 ng/ml TGF-β3 and the cell culture supernatant was collected at different time point (0.25,0.5,1,2,4,8 and 13 h).The content TGF-β3 was determined by ELISA method.Some other HSC cells were seeded in 96-well plates and divided into 2 groups.One group of cells were cultured in the presence of exogenous TGF-β3 of different concentrations (0.001,0.005,0.02,0.08,0.32,1.25,5,20,100,500 ng/ml) for 24 hours and then the cell proliferation was detected; the other group of cells were treated with 5 ng/ml TGF-β3 for 24 and 48 hours.The cell proliferation was measured by MTT method.The HSC cell morphology of control group and TGF-β3 treated group was observed under inverted microscope. Results The endogenous TGF-β3 expression of HSC cells obviously increased after exogenous TGF β3 treated at 2 ng/ml and reached the peak at 3 hour [(0.845±0.028) ng/ml vs (0.026±0.021) ng/ml,F=210.168,P=0.00].Low concentrations of exogenous TGF-β3 did not affect the proliferation of HSC cells.Above 0.32 ng/ml,exogenous TGF-β3 could promote HSC proliferation.There was no dose-dependent relationship between HSC cell proliferation and the concentration of exogenous TGF-β3 (F=0.68,P=0.57).Under microscope,lhere was no significant difference in HSC cell morphology between control group and TGF-β3 treated group.Conclusions Exogenous TGF-β3 can promote the expression of endogenous TGF-β3 in HSC cells,and can promote HSC cell proliferation.There is no obvious effect of exogenous TGF-β3 on HSC morphology.
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Objective To investigate effect of transforming growth factor β3(TGFβ3)on expression of MMP-9,MMP-2,TIMP-1 and collagen I in rats with liver fibrosis through transduction by recombinant adeno-associated virus 2(rAAV2).Methods Rats were randomly divided into 4 groups:normal control group,model group,negative control group and TGFβ3 group.Liver fibrosis model was induced by hypodermic injection of 40% CCl4.rAAV2-TGFβ3,was injected via vena caudalis of the rats one week before CCl4 Was given.All rats were sacrificed and the liver tissues were taken 8 weeks afler injection of CCl4.The histopathological changes were observed on HE sections;the expressions of MMP-9,MMP-2,TIMP-1 and collagen I were examined by histochemistry and the positive area rates were semi-quantitatively analyzed.Results Compared with the model group and negative control group,the decreases of inflammatory infiltration and collagen fibers hyperplasia were observed in the TGFβ3 group,and the expression of MMP-9 increased(q=23.664,27.746,P<0.01),the expression of collagen I(q=5.503,5.251,P<0.01)and TIMP-1(q=5.800,8.608,P<0.01)decreased,but that of MMP-2 was not changed(q=2.1 08,0.996,P>0.05).Conclusion rAAV2-TGFβ3 can reduce the histological damage and degree of liver fibrosis in rats by inhibiting expression of TIMP-1 and collagen I,and upregulating expression of MMP-9.
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Objective To investigate the effects of transforming growth factorβ1(TGFβ1)and β3 (TGFβ3)gene transfer on MMP-2,MMP-9 and TIMP-1 expression in hepatic stellate cells(HSC-T6).Methods TGFβ1 and TGFβ3 expression plagmids were constructed.The recombinant expression plasmid pcDNA3.1(+)-=TGFβ1 and pcDNA3.1(+).TGFβ3 were transfected or cotransfected into HSC-T6.At 24,48 and 72 h after transfection,the expression of MMP-2,MMP-9 and TIMP-1 mRNA were detected by real-time quantitative PCR,and the expression of MMP-2,MMP-9 and TIMP-1 protein were detected by Western blot.The recombinant expression plasmid pcDNA3.1(+).TGFβ1 was transfected into HSC-T6,and positive clones were selected by G418.The positive clones were transfected by the recombinant expression plasmid pcDNA3.1(+).TGFβ1,and the expression of MMP-2,MMP-9 and TIMP-1 were detected at 48 h after transfection.Results After transfection with peDNA3.1-TGFβ1,MMP-2 and TIMP-1 increaged remarkably in HSC-T6 cells(P＜0.05),but MMP-9 remained at the sanle level;After transfection with pcDNA3.1-TGFβ3,expression levels of MMP-2,MMP-9 and TIMP-1 mRNA were not changed,but TIMP-1 protein increased remarkably(P＜0.05);in cotransfection group,the expression of MMP-2 was higher than that in the blank and the control groups(P＜0.05),but MMP-9 level was not changed and TIMP-1was decreased compared with that in the TGF-β1 transfection group(P＜0.05).After TGFβ3was transfected into positive clones,the change of MMP-2 wag not significant(P＞0.05).but MMP-9 increaged and TIMP-1 decreased significantly at 48 h after transfection(P＜0.05).Conclusions TGFB3 may inhibit liver fibrosis by increase the activity of MMP-2 and MMP-9,and decrease the activity of TIMP-1.
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A persistent infection model was established after human hepatoma cells infected by Japanese encephalitis viruses were subcultured for several times. Viral titers of mutant viruses in persistently infected cells were examined by plaque methods using BHK cells. Nucleotides of the E coding region of two wild and two mutant viruses were amplified by RT-PCR. PCR products were sequenced by ABI-PRSMTM310 sequencing system. Compared to JaGAr-01 wild strains, four amino acids were replaced (E61Tyr→Asp, E219His→Tyr, E384Val→Glu, E418Pro→Ala) in the E sequence of JaGAr-01 persistently-infected mutant strains. Eleven amino acid replacement (E51Arg→Ser, E61Tyr→Asp, E83Lys→Glu, E123Ser→Arg, E209Arg→Lys, E227Pro→Ser, E276Asp→Ser,E290Arg→Lys, E387Lys→Arg, E418Leu→Pro, E454Arg→Gly) was also noted when we compared the E sequence between persistently infected Nakayama and its wild strains. A lot of similarities of amino acid sequence between mutant strains JaGAr-01 and Nakayama were also noted. It was concluded that geno-variation existed in E region of mutant viruses and the mutant protein encoded by E region, especially the mutation of E61 (Tyr→Asp) may contribute to the maintenance of the persistent infection of Japanese encephalitis virus.
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A persistent infection model was established after human hepatoma cells infected by Japanese encephalitis viruses were subcultured for several times. Viral titers of mutant viruses in persistently infected cells were examined by plaque methods using BHK cells. Nucleotides of the E coding region of two wild and two mutant viruses were amplified by RT-PCR. PCR products were sequenced by ABI-PRSM 310 sequencing system. Compared to JaGAr-01 wild strains, four amino acids were replaced (E61Tyr --> Asp, E219His --> Tyr, E384Val --> Glu, E418Pro --> Ala) in the E sequence of JaGAr-01 persistently-infected mutant strains. Eleven amino acid replacement (E51Arg --> Ser, E61Tyr --> Asp, E83Lys --> Glu, E123Ser --> Arg, E209Arg --> Lys, E227Pro --> Ser, E276Asp --> Ser, E290Arg --> Lys, E387Lys --> Arg, E418Leu --> Pro, E454Arg --> Gly) was also noted when we compared the E sequence between persistently infected Nakayama and its wild strains. A lot of similarities of amino acid sequence between mutant strains JaGAr-01 and Nakayama were also noted. It was concluded that geno-variation existed in E region of mutant viruses and the mutant protein encoded by E region, especially the mutation of E61 (Tyr --> Asp) may contribute to the maintenance of the persistent infection of Japanese encephalitis virus.
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In this study, the mechanism by which Suramin inhibits the replication of epidemic encephalitis B virus was explored to provide a theoretical basis for its further application in clinical practice. After viral infection of HepG2 and IMR-32 cells, different concentrations of Suramin were added to the culture media, and then the cultural supernatants and infected cells were collected 48 h later. For the evaluation of the curative effect, cytopathic effect (CPE), virus titers, the expression of viral protein and viral RNA were determined by Western blot, RT-PCR and in vitro RNA synthesis, respectively. At the concentration of 50 microg/ml of Suramin, HepG2 and IMR-32 infected with epidemic encephalitis B virus decreased by 51.8% and 0.03% respectively, as compared with controls. It was suggested that expression of encephalitis B virus proteins NS3 and E was notably reduced by Suramin. This is especially true of E protein. At RNA level, however, no difference in RNA virus was found between Suramin-treated virus and non-treated cells. Our results suggest that Suramin can inhibit viral replication by blocking the production of viral proteins.