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Liver failure is a familiar severe disease, with no good clinical early diagnostic indicators and treatment methods. Studies have shown that non-encoding RNA (ncRNA) characterized by microRNA (miRNA) and long non-coding RNA (lncRNA) can be used not only as an early diagnostic indicator of liver failure, but also play a key regulatory role in an inflammatory response to liver failure, hepatocyte death and hepatocyte regeneration. Simultaneously, the epigenetic regulation of ncRNA also participates in the initiation and progression of liver failure. This article reviews the relationship between miRNA, lncRNA, and liver failure to find new targets for the diagnosis and treatment of liver failure.
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Objective@#To investigate the inhibitory effect of small interference RNA (siRNA) targeted against transforming growth factor β1 (TGFβ1) in mice with hepatic fibrosis infected with Schistosoma japonicum.@*Methods@#Three short hairpin RNAs (shRNA) targeting different positions of TGFβ1 and one unrelated control sequence (HK) were designed and cloned to a plasmid pGenesil-1 respectively to obtain four recombinant expression vectors. Thirty male BALB/c mice were randomly divided into six groups, including normal group, model group, control group (pGenesil-HK) and three treatment groups (pGenesil-TGFβ1-m1, pGenesil-TGFβ1-m2 and pGenesil-TGFβ1-m3) and each group had five mice. The hepatic fibrosis animal models infected with Schistosoma japonicum were constructed. The levels of hydroxyproline (HYP) in liver tissue were examined by biochemistry. Liver histopathology was examined by hematoxylin-eosin and Masson staining. The mRNA expression and protein expression levels of TGFβ1, mothers against decapentaplegic homolog (Smad) 3, Smad 7 and α-smooth muscle actin (α-SMA) in the livers were detected by quantitative real time polymerase chain reaction (RT-qPCR) and Western blot. Two independent samples t test was used to compare the measurement data between groups.@*Results@#The liver fibrogenesis was obviously improved in all treatment groups compared with model group.The levels of HYP of liver tissue in all treatment groups were significantly lower than that in model group (t=14.870, 7.097 and 10.741, respectively, all P<0.01). The mRNA expression levels of TGFβ1, Smad 3 and α-SMA(model group vs pGenesil-TGFβ1-m1 group, t=3.235, 5.141 and 10.026, respectively; model group vs pGenesil-TGFβ1-m2 group, t=3.396, 5.145 and 4.951, respectively; model group vs pGenesil-TGFβ1-m3 group, t=3.511, 5.429 and 6.485, respectively)and protein (model group vs pGenesil-TGFβ1-m1 group, t=8.847, 8.044 and 10.746, respectively; model group vs pGenesil-TGFβ1-m2 group, t=9.709, 7.484 and 10.847, respectively; model group vs pGenesil-TGFβ1-m3 group, t=9.672, 8.766 and 11.508, respectively) were significantly decreased in all treatment groups compared with model group (all P< 0.01), while the levels of Smad 7 mRNA and protein were significantly increased in all treatment groups compared with model group(t=11.742 and 11.211, respectively in pGenesil-TGFβ1-m1 group; t=14.446 and 13.736, respectively in pGenesil-TGFβ1-m2 group; t=10.892 and 10.908, respectively in pGenesil-TGFβ1-m3 group, all P< 0.01).@*Conclusions@#Specific siRNA targeting TGFβ1 could significantly inhibit the liver fibrogenesis in mice infected with Schistosoma japonicum. The anti-fibrosis mechanisms of the siRNA maybe associated with the down-regulation of TGFβ1, Smad 3 and α-SMA expressions and up-regulation of Smad 7 expression in liver tissue, which results in suppressing the activation of hepatic stellate cells.
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Objective To investigate the inhibitory effect of small interference RNA (siRNA) targeted against transforming growth factor β1 (TGFβ1) in mice with hepatic fibrosis infected with Schistosoma japonicum.Methods Three short hairpin RNAs (shRNA) targeting different positions of TGFβ1 and one unrelated control sequence (HK) were designed and cloned to a plasmid pGenesil-1 respectively to obtain four recombinant expression vectors.Thirty male BALB/c mice were randomly divided into six groups,including normal group,model group,control group (pGenesil-HK) and three treatment groups (pGenesil-TGFβ1-m1,pGenesil-TGFβ1-m2 and pGenesil-TGFβ1-m3) and each group had five mice.The hepatic fibrosis animal models infected with Schistosoma japonicum were constructed.The levels of hydroxyproline (HYP) in liver tissue were examined by biochemistry.Liver histopathology was examined by hematoxylin-eosin and Masson staining.The mRNA expression and protein expression levels of TGFβ1,mothers against decapentaplegic homolog (Smad) 3,Smad 7 and α-smooth muscle actin (α-SMA) in the livers were detected by quantitative real time polymerase chain reaction (RT-qPCR) and Western blot.Two independent samples t test was used to compare the measurement data between groups.Results The liver fibrogenesis was obviously improved in all treatment groups compared with model group.The levels of HYP of liver tissue in all treatment groups were significantly lower than that in model group (t =14.870,7.097 and 10.741,respectively,all P ＜ 0.01).The mRNA expression levels of TGFβ1,Smad 3 and α-SMA(model group vs pGenesil-TGFβ1-m1 group,t =3.235,5.141 and 10.026,respectively;model group vs pGenesil-TGFβ1-m2 group,t =3.396,5.145 and 4.951,respectively;model group vs pGenesil-TGFβ1-m3 group,t =3.511,5.429 and 6.485,respectively) and protein (model group vs pGenesil-TGFβ1-m1 group,t =8.847,8.044 and 10.746,respectively;model group vs pGenesil-TGFβ1-m2 group,t =9.709,7.484 and 10.847,respectively;model group vs pGenesil-TGFβ1-m3 group,t =9.672,8.766 and 11.508,respectively) were significantly decreased in all treatment groups compared with model group (all P ＜ 0.01),while the levels of Smad 7 mRNA and protein were significantly increased in all treatment groups compared with model group(t=11.742 and 11.211,respectively in pGenesil-TGFβ1-m1 group;t =14.446 and 13.736,respectively in pGenesil-TGFβ1-m2 group;t =10.892 and 10.908,respectively in pGenesil-TGFβ1-m3 group,all P ＜ 0.01).Conclusions Specific siRNA targeting TGFβ1 could significantly inhibit the liver fibrogenesis in mice infected with Schistosoma japonicum.The anti-fibrosis mechanisms of the siRNA maybe associated with the down-regulation of TGFβ1,Smad 3 and α-SMA expressions and up-regulation of Smad 7 expression in liver tissue,which results in suppressing the activation of hepatic stellate cells.
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Objective@#To investigate the protective effect of ACY1215 (Rocilinostat), a histone deacetylase inhibitor, against brain edema in mice with acute liver failure.@*Methods@#Lipopolysaccharide combined with D-galactosamine was used to establish a mouse model of acute liver failure, and ACY1215 was used for intervention. The effect of ACY1215 on histopathological changes of the liver was observed after 24 hours, as well as the changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood ammonia, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), brain water content, blood-brain barrier structure, NF-κB-p65, histone, acetylated histone, and TNF-α mRNA in brain tissue.@*Results@#The mice with acute liver failure had marked pathological damage in liver tissue, as well as significant increases in the levels of ALT, AST, blood ammonia, TNF-α, and IFN-γ (t≥5.367, all P < 0.05). ACY1215 significantly improved the pathological damage in liver tissue and reduced the serum levels of ALT, AST, blood ammonia, TNF-α, and IFN-γ (t≤-3.515, all P < 0.05). ACY1215 also significantly reduced the expression of NF-κB-p65 (t = -5.871, P = 0.004) and the mRNA expression of TNF-α (t = -11.913, P < 0.01) in brain tissue and brain water content (t = -2.355, P < 0.01). According to the results of electron microscopy, the model group had an abnormal blood-brain barrier structure, and the ACY1215 group had slighter damage than the model group. Compared with the normal group, the model group had significant increases in the acetylation level of histone H3 and H4 in brain tissue (t≥3.009, both P < 0.05), while ACY1215 further upregulated the acetylation levels of histone H3 and H4 (t≥6.682, both P < 0.05).@*Conclusion@#ACY1215 exerts a protective effect against brain edema in mice with acute liver failure, possibly by regulating histone acetylation and inhibiting inflammation.
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OBJECTIVE@#To investigate the clinical efficacy of oral medicine and sodium hyaluronate in prevention of intrauterine adhesions after artificial abortion. @*METHODS@#A total of 572 patients with early pregnancy termination through artificial abortion, who experienced two or more times of abortion, were retrospectively analyzed. Patients were randomly and voluntarily divided into 4 groups: an artificial cycle group, a drospirenone and ethinylestradiol tablets group, a sodium hyaluronate group, and a control group. The thickness of the endometrium, return time of menses, and the status of intrauterine adhesions were observed. @*RESULTS@#The thickness of the endometrium in the artificial period group was greater than that in the control group (P<0.001). It was less in the drospirenone and ethinylestradiol tablets group comparing with that in the control group (P<0.001). There was no significant difference in the thickness of the endometrium between the sodium hyaluronate group and the control group (P=0.717). Return time of menses in the artificial menstrual cycle group and the drospirenone and ethinylestradiol tablets group was shorter than that in the control group (P<0.001). There was no significant difference in return time of menses between the sodium hyaluronate group and the control group (P=0.813). The incidence of intrauterine adhesions could be reduced by the 3 preventive measures (All P<0.01). @*CONCLUSION@#Drugs for artificial cycle and drospirenone and ethinylestradiol tablets medication immediately after artificial abortion can effectively promote endometrial repair and reduce the incidence of intrauterine adhesions. However, for the patients with poor compliance, drospirenoneand ethinylestradiol tablets are the first choice for prevention of intrauterine adhesion.
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Female , Humans , Pregnancy , Abortion, Induced , Androstenes , Pharmacology , Therapeutic Uses , Endometrium , Ethinyl Estradiol , Pharmacology , Therapeutic Uses , Hyaluronic Acid , Pharmacology , Therapeutic Uses , Menstrual Cycle , Menstruation , Tissue AdhesionsABSTRACT
Objective To investigate the effect of MS-275, an histone deacetylase ( HDAC ) inhibitor, on acute liver failure ( ALF ) induced by D-galactosamine and lipopolysaccharide in mice. Methods Thirty specific pathogen free (SPF) C57BL/6 male mice were randomly and equally divided into control, ALF model and MS-275 groups. ALF model was induced by D-galactosamine ( D-Gal ) and lipopolysaccharide (LPS), and the mice in MS-275 group received MS-275 (1 mg/kg) at 2 h before the induction of ALF.Serum and liver samples of mice were obtained at 24 h after ALF induction.The serum levels of ALT, AST, TBil and tumor necrosis factor-alpha ( TNF-α) , interferon γ( IFNγ) , interleukin ( IL )-1β, high mobility group box 1 ( HMGB1 ) were tested by biochemical methods or ELISA kit, respectively.The expression of HDAC1, HDAC3, acetylation of histone H3, H4, P65, acetylation and phosphorylation of P65 in liver were detected by Western blotting.The changes of histology in liver was detected by HE staining, and the translocation of P65 in liver was detected by immunohistochemistry. Comparison of variables among the groups was performed using t test.Results MS-275 inhibited the infiltration of inflammatory cells and improved the pathological changes of liver tissue.Compared with ALF group, serum ALT, AST, TBil levels were decreased in MS-275 group ( t =-22.215, -11.914 and-12.160, all P<0.05), but still higher than those in the control group (t=14.852, 11.692 and 8.333, all P<0.05); serum TNF-α, IFNγ, IL-1β, HMGB1 levels were also significantly decreased in MS-275 group (t=-7.926, -3.427, -2.475 and -5.920, all P<0.05), but TNF-αand IFNγwere still higher than those in the control group (t=5.541 and 5.514, all P<0.05).Compared with control group, the expression of class I HDAC in liver tissue was significantly decreased in MS-275 group ( t=-3.676 and-10.576, P<0.05), while the expressions of acetylation of histone H3, H4 and P65 were significantly increased (t=3.976, 5.559 and 4.588, all P<0.05).MS-275 inhibited the translocation of P65 from cytoplasm to the nucleus.Conclusion MS-275 can protect liver from acute failure in mice through enhancing the acetylation levels of non-histones.
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Objective To investigate changes of regulatory T (Treg) cell proportion and activity in patients with decompensated hepatitis B-related cirrhosis complicated with bacterial infections.Methods Thirty patients with decompensated hepatitis B-related cirrhosis complicated with bacterial infections,20patients with decompensated hepatitis B-related cirrhosis without bacterial infection and 10 healthy controls were recruited in the study from Renmin Hospital of Wuhan University during January 2009 and December 2011.Peripheral blood mononuclear cells (PBMCs) were obtained from blood samples via density gradient centrifugation.The proportion of CD4+ CD25+ CD127low Treg cells in CD4+ cells was detected by flow cytometry.The immune activity of Treg cells isolated from PBMCs was observed by a suppression assay of allogeneic mixed lymphocyte response (MLR).Results Patients with decompensated hepatitis B-related cirrhosis complicated with bacterial infections had significantly lower percentage of Treg cells in CD4 + T cells of PBMCs than the patients with decompensated hepatitis B-related cirrhosis without bacterial infections [(4.07±1.18)％ vs.(9.74 ±3.00)％,t =9.35,P＜0.01].The suppression ability to homologous PBMCs proliferation of Treg cells isolated from patients with decompensated hepatitis B-related cirrhosis complicated with bacterial infections was significantly weakened as demonstrated in MLR assay [ cpm =(22.79 ± 4.94) × 103],which had a statistical difference compared with both the patients with decompensated hepatitis B-related cirrhosis without bacterial infection and the healthy controls [ cpm =(6.43±1.19) × 103 and (5.96 ± 1.25) × 103 respectively; t =16.09 and 16.51,P＜ 0.01].Conclusion There is a decrease of both quantity and activity of Treg cell in the patients with decompensated hepatitis B-related cirrhosis complicated with bacterial infections.
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Objective To investigate the expression of signal transduction molecule STAT-1 in patients with chronic hepatitis B (CHB) who received interferon-alpha (IFNα) treatment with different responses. Methods A total of 13 CHB patients received IFNα treatment, among who 5 demonstrated complete viral response ( Group A) and 8 showed no response ( Group B). All patients underwent liver biopsy before and after the therapy. STAT-1 mRNA of liver tissue was semi-quantified by RT-PCR and levels of STAT-1 protein were detected by Western-blot. Results Absorbance values (A) of STAT-1 mRNA in group A and B were (1. 18±0.06) and (0.21±0.04) respectively (t =35.27, P<0. 01). The levels of STAT-1 protein of liver tissue in group A were also significantly higher than those in group B. Conclusion IFNα resistance may be closely related to the down-regulation of STAT-1.
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Objective To evaluate the therapeutic effects of capsule Huoluoshugan on schistosomal hepatocirrhosis.Methods Ninety-six patients with schistosomal hepatocirrhosis were selected and divided randomly into three groups:Huoluoshugan group,interferon-?(IFN-?)group and control group,and treated with capsule Huoluoshugan,IFN-? and routine therapy,respectively.The course of treatment was 6 months in all groups.Before and after the treatment,the symptoms,physical signs,indexes of liver function and hepatic fibrosis,and changes of B-type ultrasonic images were detected for all the patients.Results The indexes of liver function,hepatic fibrosis and B-type ultrasonic image of the patients in Huoluoshugan group improved obviously compared with the control group after the treatment(P0.05).In addition,there was no obvious adverse reactions during the treatment in the patients of Huoluoshugan group.Conclusion Capsule Huoluoshugan can reduce the indexes of hepatic fibrosis and improve the liver function in patients with schistosomal hepatocirrhosis.