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Exosomes are nano-sized phospholipid bilayer vesicles containing abundant and complex biomolecules, such as DNA, mRNAs, microRNAs (miRNAs), lipids, and proteins. Exosomes can be secreted and ingested by most types of cells to transfer information through intercellular transport. After uptake by recipient cells, exosomes release bioactive substances to regulate the biological processes of recipient cells, such as promoting tumor growth and metastasis. Changes of exosomes and their contents are associated with a variety of diseases. In recent years, the role of exosomal miRNAs in the development and progression of hepatocellular carcinoma (HCC) caused by viral hepatitis has attracted wide attention, and exosomal miRNAs from different sources play different roles in this process. This article briefly reviews the research on the role of exosomal miRNAs in the development and progression of viral hepatitis-related HCC and proposes that exosomal miRNAs may be the targets for immunotherapy for HCC microenvironment.
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Objective:To explore the effects of Rougan Huaxian Granules combined with nucleoside antiviral drugs on liver and kidney function, portal hemodynamics, vascular activity, antiviral indexes and aspartate transaminase-platelet ratio index in patients with hepatitis B decompensated cirrhosis.Methods:A case-control study was conducted on 150 patients with hepatitis B decompensated cirrhosis who were hospitalized in Tangshan Infectious Disease Institute and Affiliated Hospital of North China University of Science and Technology from June 2017 to December 2019 were enrolled. The patients were divided into control group and observation group by computer random random number method, with 75 cases in each group. The control group was given routine liver protection and antiviral treatment; the observation group was given Rougan Huaxian granules on the basis of the control group treatment. Observe the changes of liver and kidney function, portal vein system hemodynamics, vascular activity, antiviral index and aspartate transaminase-platelet ratio index in the two groups. Independent sample T test was used to compare the measurement data between the two groups, paired T test was used for comparison between the same groups before and after treatment, and χ2 test was used for counting data. Results:There were no significant differences in gender, age, course of cirrhosis, Child grade of liver function and baseline data of indexes before treatment between 2 groups (ALL P>0.05). After treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen, creatinine,diameter of portal vein (Dpv), diameter of splenic vein (Dsv), endothelin-1, nitric oxide, glucagon (GLA), APRI,were all lower than before treatment. Comparison between groups, observation group ALT (51.60±15.97) U/L, AST (62.65±26.28) U/L, urea nitrogen (10.25±1.65) mmol/L, creatinine (78.54±14.09) μmol/L, Dpv (10.20±1.10) mm, Dsv (8.08±0.68) mm, endothelin-1 (31.93±6.35) ng/L, nitric oxide (41.38±8.06) μg/L, GLA (69.54±12.14) mg/L, APRI (3.14±1.35), were significantly lower than those of control group ((97.49±30.87) U/L, (96.03±25.63) U/L, (17.49±2.55) mmol/L, (116.43±22.77) μmol/L, (13.42±1.26) mm, (10.44±0.83) mm, (44.34+11.88) ng/L, (63.47±15.50) μg/L, (107.11+25.29) mg/L, (5.91±1.93)), the differences were statistically significant ( t values were respectively 11.43, 7.87, 20.64, 12.26, 16.62, 18.99, 7.98, 10.96, 11.60, 10.23, all P<0.05). After treatment, albumin, portal vein velocity (Vpv), and velocity of splenic vein blood flow (Vsv) were all higher in the two groups than before treatment. However, there was no significant difference in Vsv of the control group before and after treatment ( t=0.51, P=0.613). Comparison between groups, albumin (39.42±7.35) g/L, Vpv ((25.72±4.06) cm/s), Vsv ((24.22±6.15) cm/s) in the observation group were significantly higher than those in the control group (34.66±7.95) g/L, (19.38±3.46) cm/s, (19.54±5.88) cm/s ( t values were 3.81, 10.28, 4.76, all P<0.05). After treatment, the total effective rate (96.00%(72/75) vs. 86.67%(65/75), χ2=4.13, P=0.042), HBV DNA negative conversion rate (76.00%(57/75) vs. 58.67%(44/75), χ2=5.12, P=0.024), HBeAg negative conversion rate (50.67%(38/75) vs. 30.67%(23/75), χ2=6.22, P=0.013) and serum HBeAg/HBeAb conversion (28.00%(21/75) vs. 13.33%(10/75), χ2=4.92, P=0.027) in observation group were higher than those in control group, and the differences were statistically significant ( P<0.05). HBsAg negative rate (8.00%(6/75) vs. 5.33%(4/75), χ2=0.43, P=0.513) was higher than that of control group, but the difference was not statistically significant ( P>0.05). Conclusion:Rougan Huaxian Granules combined with nucleoside antiviral drugs has significant effect on patients with decompensated liver cirrhosis of hepatitis B, improve liver and kidney function, liver fibrosis and hemodynamics of the portal vein system, increase vascular activity function, and reduce hepatitis B virus (HBV) DNA load, HBV replication, aspartate transaminase-platelet ratio index, APRI, Toll-like receptor (TLR-4) and transforming growth factor β1 (TGF-β1) levels and improves the body′s immune status.
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Objective To investigate the rebleeding rate after endoscopic selective variceal devascularization (ESVD) and the predictive factors for rebleeding in patients with hepatitis B cirrhosis and esophageal variceal bleeding (EVB). Methods The patients with hepatitis B cirrhosis and EVB who attended Beijing Ditan Hospital, Capital Medical University, from October 2010 to December 2019 and underwent ESVD for the first time were enrolled, and a total of 442 patients were screened out based on inclusion and exclusion criteria. Routine clinical indices, laboratory markers, imaging findings, and endoscopic findings were compared between patients, and the patients were followed up to observe rebleeding. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to describe rebleeding and survival status, and a Cox regression analysis was used to determine the independent risk factors for variceal rebleeding. Results The 1-, 2-, 3-, 4-, and 5-year cumulative rebleeding rates after first ESVD treatment were 25.11%, 33.94%, 39.82%, 42.08%, and 45.02%, respectively. The univariate analysis showed that age, systolic pressure, duration of antiviral therapy ≥1 year, ascites, white blood cell count, neutrophil, and direct bilirubin were associated with rebleeding (all P < 0.05), and the multivariate analysis showed that duration of antiviral therapy ≥1 year (hazard ratio [ HR ]=0.504, 95% confidence interval [ CI ]: 0.357-0.711, P < 0.001) and ascites ( HR =1.424, 95% CI : 1.184-1.714, P < 0.001) were independent influencing factors for variceal rebleeding. Conclusion ESVD has a low rebleeding rate in the treatment of hepatitis B cirrhosis with EVB, and presence of ascites and a short duration of antiviral therapy are independent risk factors for rebleeding after treatment.
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Objective To investigate the role of r-aminobutyric acid B receptor in the development of liver fibrosis.Methods Thirty-two Sprague-Dawley (SD) rats were divided into four groups including a control group,a model group,a baclofen group,and a CGP35348 group.Liver fibrosis was then induced by carbon tetrachloride (CCl4).Baclofen and CGP35348 treatment were carried out after the formation of liver fibrosis,followed by complete extraction of the eyeball to obtain blood sample to test liver function.Liver tissue specimens were cut and stored for histological staining,histochemistry,real-time polymerase chain-reaction (RT-PCR),and western blot analysis.Results Histological staining indicated that the degree of liver fibrosis was more severe in the CGP35348 group than in the baclofen group (P＜0.001).The levels of alanine transaminase (ALT),aspartate aminotransferase (AST),gamma-glutamyl transferase (GGT),total bilirubin (TBil),and direct bilirubin (DBil) were significantly lower in the baclofen group than in the CGP35348 group (P＜0.01).The levels of ALT,AST,GGT,TBil,and DBil were significantly higher in the CGP35348 group than in the model group (P＜0.05).Immunofluorescence results show that the hepatic cell migration was inhibited in the baclofen group.Western blot results showed that the expression levels of α-SMA protein were significantly lowered in the baclofen group when compared to that of the CGP35348 group and model group (P＜0.01).Conclusion GABAB receptor might play a role in the liver protection by inhibition of migration of hepatic cells in liver fibrosis.Further studies into the mechanism behind this function are further needed and may be a potential source of future anti-fibrotic treatment.
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<p><b>OBJECTIVE</b>To examine the expression changes of activin beta A, beta C, beta E and follistatin mRNA in the development of rat hepatic fibrosis induced by carbon tetrachloride (CCl(4)).</p><p><b>METHODS</b>Hepatic fibrosis was induced in rats by subcutaneous injections of 40% carbon tetrachloride oily solution for a period of 1 to 7 weeks. After carbon tetrachloride injection of 1, 2, 3, 4, 5, 6, and 7 weeks, the 6-12 rats were killed every time. The kinetics of activin beta A, beta C, beta E and follistatin mRNA expression were assessed by the semi-quantity RT-PCR.</p><p><b>RESULTS</b>Activin beta A, beta C, beta E and follistatin mRNA could be detected in normal rat livers. After CCl(4) injection for 2 or 3 weeks, beta A mRNA was transiently decreased and became undetectable, then increased gradually. After CCl injection for 6 and 7 weeks, beta A mRNA level was significantly higher than controls (P<0.01). beta C mRNA could be detected after CCl(4) injection for 1 to 4 weeks and was significantly increased after 5 weeks over controls (P<0.05). beta E mRNA could not be detected after CCl(4) injection for 1 to 5 weeks, but significantly increased after CCl(4) injection for 6 or 7 weeks compared with controls (P<0.01). Except for normal rat liver, no follistatin mRNA was detected in rats after CCl(4) injection.</p><p><b>CONCLUSIONS</b>Activins and follistatin have different expression changes in the development of hepatic fibrosis and the imbalance of activins and follistatin expression may involve in the formation of hepatic fibrosis.</p>
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Animals , Male , Rats , Activins , Genetics , Carbon Tetrachloride , Follistatin , Gene Expression , Inhibin-beta Subunits , Genetics , Liver Cirrhosis, Experimental , Genetics , Pathology , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Objective Recently, a series of studies demonstrated that activation of local renin angiotensin system (RAS) may be related to tissue fibrosis, but the role of RAS in hepatic fibrogenesis has not been evaluated. The present study was designed: (1) to assess the effect of angiotensin converting enzyme (ACE) inhibitor and angiotensin Ⅱ type 1 (AT1) receptor antagonist in preventing hepatic fibrosis induced by CCl 4 administration in rats; (2) to investigate whether or not there are expression of AT1 receptors on hepatic stellate cells. Methods Study was conducted in male Sprague Dawley rats. Except for control group, three treated groups, either enalapril (10 mg/kg), losartan (10 mg/kg) or a combination of enalapril and losartan were given to the fibrotic rats (daily gavage), and saline vehicle was given to the control rats. After 6 weeks, liver fibrosis was assessed directly by hepatic morphometric analysis, which have been considered the gold standard for the quantitative measurement of fibrosis. The expression of AT1 receptors and ? smooth muscle actin (? SMA) in liver tissue were detected by immunohistochemical techniques. Results Compared to the rats of control groups, either enalapril or losartan, or a combination of two drugs can limit the expansion of the interstitium ( P 0.05). Expression of AT1 receptors was found in abundance in hepatic fibrotic interstitium of fibrotic rats, whereas only limited in vasculature in rats of control group to a very slight degree. Conclusions The present results demonstrated that: (1) activation of RAS is related to hepatic fibrosis induced by CCl 4; (2) angiotensin converting enzyme inhibitor and AT1 blocker might slow the propression of hepatic fibrosis; (3) activated hepatic stellate cell expresses AT1 receptors.
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Objective To investigate the effects of different doses of angiotensin Ⅱ(Ang Ⅱ) on hepa tic stellate cells(HSC) proliferation and collagen synthesis in rats. Methods The pronase E and collagen Ⅰ were used to isolate HSC, 3H TdR, 3H Leu and 3H Pro incorporation methods were used to evaluate the effects of different doses of AngⅡ on HSC DNA, protein and proline synthesis. Results It showed that 10 -9 ～10 -6 mol/L AngⅡ could significantly increase the 3H TdR incorporation rate of HSC ( P
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AIM: To investigate the effects of octreotide (Oct) on the proliferation and extracellular matrix (ECM) synthesis in hepatic stellate cells (HSCs). METHODS: HSCs were isolated from normal male Sprague-Dawley rat liver by a combination of pronase-collagenase perfusion and density gradient centrifugation. The concentration of 2.5 ?g/L transforming growth factor ?1 (TGF?1) was used in all the experiment settings. Oct at concentrations of 0.01 mg/L ,0.1 mg/L,1 mg/L and 10 mg/L,respectively,or 0.01 mg/L Oct + TGF?1,0.1 mg/L Oct+TGF?1,1 mg/L Oct+TGF?1,10 mg/L Oct+TGF?1 were respectively added to the cultured HSCs. Effects of Oct on HSC proliferation and ECM synthesis were respectively determined by MTT method,-TdR and -proline incorporation,or radioimmunoassay. RESULTS: Oct inhibited MTT intake by cultured hepatic stellate cells and down-regulated -TdR incorporation,compared with control group. The concentrations of hyaluronic acid,laminin,collagen type IV in the culture supernatant and -proline incorporation in HSCs were decreased by Oct. TGF?1 obviously up-regulated proliferation and ECM synthesis in cultured HSCs,and Oct significantly blocked these actions. CONCLUSION: Oct inhibited proliferation and ECM synthesis in cultured HSCs,and elicited the effects of anti-hepatofibrogenesis.