Liver fibrosis is a wound-healing response following chronic liver injury caused by hepatitis virus infection,obesity,or excessive alcohol.It is a dynamic and reversible process characterized by the activation of hepa...Liver fibrosis is a wound-healing response following chronic liver injury caused by hepatitis virus infection,obesity,or excessive alcohol.It is a dynamic and reversible process characterized by the activation of hepatic stellate cells and excess accumulation of extracellular matrix.Advanced fibrosis could lead to cirrhosis and even liver cancer,which has become a significant health burden worldwide.Many studies have revealed that noncoding RNAs(ncRNAs),including microRNAs,long noncoding RNAs and circular RNAs,are involved in the pathogenesis and development of liver fibrosis by regulating signaling pathways including transforming growth factor-βpathway,phosphatidylinositol 3-kinase/protein kinase B pathway,and Wnt/β-catenin pathway.NcRNAs in serum or exosomes have been reported to tentatively applied in the diagnosis and staging of liver fibrosis and combined with elastography to improve the accuracy of diagnosis.NcRNAs mimics,ncRNAs in mesenchymal stem cell-derived exosomes,and lipid nanoparticles-encapsulated ncRNAs have become promising therapeutic approaches for the treatment of liver fibrosis.In this review,we update the latest knowledge on ncRNAs in the pathogenesis and progression of liver fibrosis,and discuss the potentials and challenges to use these ncRNAs for diagnosis,staging and treatment of liver fibrosis.All these will help us to develop a comprehensive understanding of the role of ncRNAs in liver fibrosis.展开更多
Viruses can alter the expression of host microRNAs(miRNA s) and modulate the immune response during a persistent infection. The dysregulation of host miRNA s by hepatitis B virus(HBV) contributes to the proinflammator...Viruses can alter the expression of host microRNAs(miRNA s) and modulate the immune response during a persistent infection. The dysregulation of host miRNA s by hepatitis B virus(HBV) contributes to the proinflammatory and profibrotic changes within the liver. Multiple studies have documented the differential regulation of intracellular and circulating miRNA s during different stages of HBV infection. Circulating miRNA s found in plasma and/or extracellular vesicles can integrate data on viral-host interactions and on the associated liver injury. Hence, the detection of circulating miRNA s in chronic HBV hepatitis could offer a promising alternative to liver biopsy, as their expression is associated with HBV replication, the progression of liver fibrosis,and the outcome of antiviral treatment. The current review explores the available data on miRNA involvement in HBV pathogenesis with an emphasis on their potential use as biomarkers for liver fibrosis.展开更多
Liver fibrosis is a repair process in response to damage in the liver; however, severe and chronic injury promotes the accumulation of fibrous matrix, destroying the normal functions and architecture of liver. Hepatic...Liver fibrosis is a repair process in response to damage in the liver; however, severe and chronic injury promotes the accumulation of fibrous matrix, destroying the normal functions and architecture of liver. Hepatic stellate cells(HSCs) are quiescent in normal livers, but in damaged livers, they transdifferentiate into myofibroblastic HSCs, which produce extracellular matrix proteins. Hedgehog(Hh) signaling orchestrates tissue reconstruction in damaged livers and contributes to liver fibrogenesis by regulating HSC activation. Micro RNAs(mi RNAs), endogenous small non-coding RNAs interfering with RNA post-transcriptionally, regulate various cellular processes in healthy organisms. The dysregulation of mi RNAs is closely associated with diseases, including liver diseases. Thus, mi RNAs are good targets in the diagnosis and treatment of various diseases, including liver fibrosis; however, the regulatory mechanisms of mi RNAs that interact with Hh signaling in liver fibrosis remain unclear. We review growing evidence showing the association of mi RNAs with Hh signaling. Recent studies suggest that Hh-regulating mi RNAs induce inactivation of HSCs, leading to decreased hepatic fibrosis. Although mi RNAdelivery systems and further knowledge of interacting mi RNAs with Hh signaling need to be improved for the clinical usage of mi RNAs, recent findings indicate that the mi RNAs regulating Hh signaling are promising therapeutic agents for treating liver fibrosis.展开更多
Liver fibrosis is a common pathological consequence of a variety of chronic stimuli, including viral, autoimmune, drug-induced, cholestatic and metabolic diseases. Fibrosis is driven by a dynamic process involving inc...Liver fibrosis is a common pathological consequence of a variety of chronic stimuli, including viral, autoimmune, drug-induced, cholestatic and metabolic diseases. Fibrosis is driven by a dynamic process involving increased synthesis of matrix components and a failure of physiological mechanisms of matrix turnover. Activation of hepatic stellate cells(HSCs) remains a central event in fibrosis. HSCs are the main source of extracellular matrix(ECM). Transforming growth factor-beta(TGF-β), which is the fibrogenic master cytokine, can induce the activation of HSCs to produce a large amount of ECM, and is capable of inducing apoptosis of liver cells. RNA interference(RNAi) is a novel gene disruption technology. Studies have shown that small interfering RNA(si RNA) targeting TGF-β1 may inhibit the activation and proliferation of HSCs, suppress ECM synthesis and block liver fibrosis. TGF-β1 si RNA-mediated gene silencing therapy provides a new avenue for liver fibrosis. This review summarizes recent progresses in research on HSCs, TGF-β1 and TGF-β1 si RNA in liver fibrosis.展开更多
BACKGROUND: Previous studies have shown that transforming growth factor-beta 1 (TGF-beta 1) is the most potent means of stimulating liver fibrogenesis by myofibroblast-like cells derived from hepatic stellate cells. T...BACKGROUND: Previous studies have shown that transforming growth factor-beta 1 (TGF-beta 1) is the most potent means of stimulating liver fibrogenesis by myofibroblast-like cells derived from hepatic stellate cells. Thus, TGF-beta 1 could be a target for treating hepatic fibrosis. This study aimed to investigate the inhibitory effects of specific TGF-beta 1 small interference RNA (siRNA) on immune hepatic fibrosis induced by Concanavalin A (Con A) in mice. METHODS: Three short hairpin RNAs targeting different positions of TGF-beta 1 were designed and cloned to the plasmid pGenesil-1 to obtain three recombinant expression vectors (pGenesil-TGF-beta 1-ml, pGenesil-TGF-beta 1-m2 and pGenesil-TGF-beta 1-m3). Thirty male Kunming mice were randomly divided into 6 groups: normal, model, control, and three treatment groups. The immune hepatic fibrosis models were constructed by injecting Con A via the tail vein at 8 mg/kg per week for 6 weeks. At weeks 2, 4 and 6, pGenesil-TGF-beta 1-ml, pGenesil-TGF-beta 1-m2 or pGenesi1-TGF-beta 1-m3 was injected by a hydrodynamics-based transfection method via the tail vein at 0.8 ml/10 g within 24 hours after injection of Con A in each of the three treatment groups. The mice in the control group were injected with control plasmid pGenesil-HK at the same dose. All mice were sacrificed at week 7. The levels of hydroxyproline in liver tissue were determined by biochemistry. Liver histopathology was assessed by Van Gieson staining. The expression levels and localization of TGF-beta 1, Smad3, and Smad7 in liver tissue were detected by immunohistochemistry. The expression of TGF-beta 1, Smad3, Smad7 and alpha-smooth muscle actin (alpha-SMA) mRNAs in the liver were assessed by semi-quantitative RT-PCR. RESULTS: The levels of hydroxyproline in the liver tissue of the treatment groups were lower than those of the model group (P<0.01). Histopathologic assay showed that liver fibrogenesis was clearly improved in the treatment groups compared with the model group. The expression levels of TGF-beta 1 and Smad3 of liver tissue were also markedly lower in the treatment groups than in the model group (P<0.01), while the levels of Smad7 were higher in the treatment groups than in the model group (P<0.01). RT-PCR further showed that the expression of TGF-beta 1, Smad3 and alpha-SMA mRNA was significantly inhibited in the treatment groups compared with the model group, while the levels of Smad7 were increased. There was no difference in the above parameters among the three treatment groups or between the control and model groups (P>0.05), but the inhibitory effect of pGenesil-TGF-beta 1-ml was the highest among the treatment groups. CONCLUSIONS: Specific siRNA targeting of TGF-beta 1 markedly inhibited the fibrogenesis of immune hepatic fibrosis induced by Con A in mice. The anti-fibrosis mechanisms of siRNAs may be associated with the down-regulation of TGF-beta 1, Smad3 and alpha-SMA expression and up-regulation of Smad7 expression in liver tissue, which resulted in suppressing the activation of hepatic stellate cells. (Hepatobiliary Pancreat Dis Int 2009; 8: 300-308)展开更多
AIM: To investigate whether expression of selected mi RNAs obtained from fibrotic liver biopsies correlate with fibrosis stage.METHODS: Altogether, 52 patients were enrolled in the study representing various etiologic...AIM: To investigate whether expression of selected mi RNAs obtained from fibrotic liver biopsies correlate with fibrosis stage.METHODS: Altogether, 52 patients were enrolled in the study representing various etiologic backgrounds of fibrosis: 24 cases with chronic hepatitis infections(types B, C), 19 with autoimmune liver diseases(autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, overlapping syndrome cases), and 9 of mixed etiology(alcoholic and nonalcoholic steatosis, cryptogenic cases). Severity of fibrosis was determined by both histologic staging using the METAVIR scoring system and noninvasive transient elastography. Following RNAisolation, expression levels of mi R-21, mi R-122, mi R-214, mi R-221, mi R-222, and mi R-224 were determined using Taq Man Micro RNA Assays applying mi R-140 as the reference. Selection of mi RNAs was based on their characteristic up- or downregulation observed in hepatocellular carcinoma. Relative expression of mi RNAs was correlated with fibrosis stage and liver stiffness(LS) value measured by transient elastography, as well as with serum alanine aminotransferase(ALT) level.RESULTS: The expression of individual mi RNAs showed deregulated patterns in stages F1-F4 as compared with stage F0, but only the reduced level of mi R-122 in stage F4 was statistically significant(P < 0.04). When analyzing mi RNA expression in relation to fibrosis, levels of mi R-122 and mi R-221 showed negative correlations with fibrosis stage, and mi R-122 was found to correlate negatively and mi R-224 positively with LS values(all P < 0.05). ALT levels displayed a positive correlation with mi R-21(P < 0.04). Negative correlations were observed in the fibrosis samples of mixed etiology between mi R-122 and fibrosis stage and LS values(P < 0.05), and in the samples of chronic viral hepatitis, between mi R-221 and fibrosis stage(P < 0.01), whereas mi R-21 showed positive correlation with ALT values in the samples of autoimmune liver diseases(P < 0.03). The results also revealed a strong correlation between fibrosis stage and LS values(P < 0.01) when etiology of fibrosis was not taken into account.CONCLUSION: Reduced expression of mi R-122 in advanced fibrosis and its correlation with fibrosis stage and LS values seem to be characteristic of hepatic fibrosis of various etiologies.展开更多
BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important r...BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis.AIM To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.METHODS This prospective study included 208 patients and 82 age-and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring.RESULTS The ADC value decreased significantly with the progression of fibrosis, from controls(F0) to patients with early fibrosis(F1 and F2) to those with late fibrosis(F3 and F4)(median 1.92, 1.53, and 1.25 × 10^(-3) mm^2/s, respectively)(P = 0.001).The cut-off ADC value used to differentiate patients from controls was 1.83 × 10^(-3) mm^2/s with an area under the curve(AUC) of 0.992. Combining ADC and miR-200 b revealed the highest AUC(0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10^(-3) mm^2/s with an AUC of 0.866. The combination of ADC and miR-200 b revealed the best AUC(0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200 b(r =-0.61, P = 0.001), miR-21(r =-0.62, P = 0.001), and miR-29(r = 0.52,P = 0.001).CONCLUSION Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.展开更多
Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver failure.It’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoh...Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver failure.It’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver diseases.However,current treatment options are limited,highlighting the urgent need for the development of new therapies.As a reversible regulatory mechanism,epigenetic modification is implicated in many biological processes,including liver fibrosis.Exploring the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases,although the current evidence is still controversial.This review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications,including DNA methylation,histone modification,and RNA modification,in liver fibrotic diseases.The potential cooperation of different epigenetic modifications in promoting fibrogenesis was also highlighted.Finally,available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were discussed.In summary,elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.展开更多
基金Supported by Science and Technology Innovation Talent Project of Sichuan Province,No.2022JDRC0047the Central Government-directed Special Funds for Local Science and Technology Development Project,No.2021ZYD0085+1 种基金Natural Science Foundation of China,No.82102383Qin Chuangyuan Recruited High-level Innovation and Entrepreneurship Talents Project of Science and Technology Department of Shaanxi Province,No.QCYRCXM-2022-56.
文摘Liver fibrosis is a wound-healing response following chronic liver injury caused by hepatitis virus infection,obesity,or excessive alcohol.It is a dynamic and reversible process characterized by the activation of hepatic stellate cells and excess accumulation of extracellular matrix.Advanced fibrosis could lead to cirrhosis and even liver cancer,which has become a significant health burden worldwide.Many studies have revealed that noncoding RNAs(ncRNAs),including microRNAs,long noncoding RNAs and circular RNAs,are involved in the pathogenesis and development of liver fibrosis by regulating signaling pathways including transforming growth factor-βpathway,phosphatidylinositol 3-kinase/protein kinase B pathway,and Wnt/β-catenin pathway.NcRNAs in serum or exosomes have been reported to tentatively applied in the diagnosis and staging of liver fibrosis and combined with elastography to improve the accuracy of diagnosis.NcRNAs mimics,ncRNAs in mesenchymal stem cell-derived exosomes,and lipid nanoparticles-encapsulated ncRNAs have become promising therapeutic approaches for the treatment of liver fibrosis.In this review,we update the latest knowledge on ncRNAs in the pathogenesis and progression of liver fibrosis,and discuss the potentials and challenges to use these ncRNAs for diagnosis,staging and treatment of liver fibrosis.All these will help us to develop a comprehensive understanding of the role of ncRNAs in liver fibrosis.
基金Ministerul Cercetarii si Inovarii,Programul 1,subprogramul 1.2.Performanta institutionala,No.PFE_23/2018。
文摘Viruses can alter the expression of host microRNAs(miRNA s) and modulate the immune response during a persistent infection. The dysregulation of host miRNA s by hepatitis B virus(HBV) contributes to the proinflammatory and profibrotic changes within the liver. Multiple studies have documented the differential regulation of intracellular and circulating miRNA s during different stages of HBV infection. Circulating miRNA s found in plasma and/or extracellular vesicles can integrate data on viral-host interactions and on the associated liver injury. Hence, the detection of circulating miRNA s in chronic HBV hepatitis could offer a promising alternative to liver biopsy, as their expression is associated with HBV replication, the progression of liver fibrosis,and the outcome of antiviral treatment. The current review explores the available data on miRNA involvement in HBV pathogenesis with an emphasis on their potential use as biomarkers for liver fibrosis.
基金Supported by the National Research Foundation of Korea funded by the Korean Government(MEST)to Jung YNo.2013R1A2A2A01068268
文摘Liver fibrosis is a repair process in response to damage in the liver; however, severe and chronic injury promotes the accumulation of fibrous matrix, destroying the normal functions and architecture of liver. Hepatic stellate cells(HSCs) are quiescent in normal livers, but in damaged livers, they transdifferentiate into myofibroblastic HSCs, which produce extracellular matrix proteins. Hedgehog(Hh) signaling orchestrates tissue reconstruction in damaged livers and contributes to liver fibrogenesis by regulating HSC activation. Micro RNAs(mi RNAs), endogenous small non-coding RNAs interfering with RNA post-transcriptionally, regulate various cellular processes in healthy organisms. The dysregulation of mi RNAs is closely associated with diseases, including liver diseases. Thus, mi RNAs are good targets in the diagnosis and treatment of various diseases, including liver fibrosis; however, the regulatory mechanisms of mi RNAs that interact with Hh signaling in liver fibrosis remain unclear. We review growing evidence showing the association of mi RNAs with Hh signaling. Recent studies suggest that Hh-regulating mi RNAs induce inactivation of HSCs, leading to decreased hepatic fibrosis. Although mi RNAdelivery systems and further knowledge of interacting mi RNAs with Hh signaling need to be improved for the clinical usage of mi RNAs, recent findings indicate that the mi RNAs regulating Hh signaling are promising therapeutic agents for treating liver fibrosis.
基金Supported by National Natural Science Foundation of China(81373465)
文摘Liver fibrosis is a common pathological consequence of a variety of chronic stimuli, including viral, autoimmune, drug-induced, cholestatic and metabolic diseases. Fibrosis is driven by a dynamic process involving increased synthesis of matrix components and a failure of physiological mechanisms of matrix turnover. Activation of hepatic stellate cells(HSCs) remains a central event in fibrosis. HSCs are the main source of extracellular matrix(ECM). Transforming growth factor-beta(TGF-β), which is the fibrogenic master cytokine, can induce the activation of HSCs to produce a large amount of ECM, and is capable of inducing apoptosis of liver cells. RNA interference(RNAi) is a novel gene disruption technology. Studies have shown that small interfering RNA(si RNA) targeting TGF-β1 may inhibit the activation and proliferation of HSCs, suppress ECM synthesis and block liver fibrosis. TGF-β1 si RNA-mediated gene silencing therapy provides a new avenue for liver fibrosis. This review summarizes recent progresses in research on HSCs, TGF-β1 and TGF-β1 si RNA in liver fibrosis.
文摘BACKGROUND: Previous studies have shown that transforming growth factor-beta 1 (TGF-beta 1) is the most potent means of stimulating liver fibrogenesis by myofibroblast-like cells derived from hepatic stellate cells. Thus, TGF-beta 1 could be a target for treating hepatic fibrosis. This study aimed to investigate the inhibitory effects of specific TGF-beta 1 small interference RNA (siRNA) on immune hepatic fibrosis induced by Concanavalin A (Con A) in mice. METHODS: Three short hairpin RNAs targeting different positions of TGF-beta 1 were designed and cloned to the plasmid pGenesil-1 to obtain three recombinant expression vectors (pGenesil-TGF-beta 1-ml, pGenesil-TGF-beta 1-m2 and pGenesil-TGF-beta 1-m3). Thirty male Kunming mice were randomly divided into 6 groups: normal, model, control, and three treatment groups. The immune hepatic fibrosis models were constructed by injecting Con A via the tail vein at 8 mg/kg per week for 6 weeks. At weeks 2, 4 and 6, pGenesil-TGF-beta 1-ml, pGenesil-TGF-beta 1-m2 or pGenesi1-TGF-beta 1-m3 was injected by a hydrodynamics-based transfection method via the tail vein at 0.8 ml/10 g within 24 hours after injection of Con A in each of the three treatment groups. The mice in the control group were injected with control plasmid pGenesil-HK at the same dose. All mice were sacrificed at week 7. The levels of hydroxyproline in liver tissue were determined by biochemistry. Liver histopathology was assessed by Van Gieson staining. The expression levels and localization of TGF-beta 1, Smad3, and Smad7 in liver tissue were detected by immunohistochemistry. The expression of TGF-beta 1, Smad3, Smad7 and alpha-smooth muscle actin (alpha-SMA) mRNAs in the liver were assessed by semi-quantitative RT-PCR. RESULTS: The levels of hydroxyproline in the liver tissue of the treatment groups were lower than those of the model group (P<0.01). Histopathologic assay showed that liver fibrogenesis was clearly improved in the treatment groups compared with the model group. The expression levels of TGF-beta 1 and Smad3 of liver tissue were also markedly lower in the treatment groups than in the model group (P<0.01), while the levels of Smad7 were higher in the treatment groups than in the model group (P<0.01). RT-PCR further showed that the expression of TGF-beta 1, Smad3 and alpha-SMA mRNA was significantly inhibited in the treatment groups compared with the model group, while the levels of Smad7 were increased. There was no difference in the above parameters among the three treatment groups or between the control and model groups (P>0.05), but the inhibitory effect of pGenesil-TGF-beta 1-ml was the highest among the treatment groups. CONCLUSIONS: Specific siRNA targeting of TGF-beta 1 markedly inhibited the fibrogenesis of immune hepatic fibrosis induced by Con A in mice. The anti-fibrosis mechanisms of siRNAs may be associated with the down-regulation of TGF-beta 1, Smad3 and alpha-SMA expression and up-regulation of Smad7 expression in liver tissue, which resulted in suppressing the activation of hepatic stellate cells. (Hepatobiliary Pancreat Dis Int 2009; 8: 300-308)
基金Supported by Grant from the National Scientific Research Fund,OTKA K101435 and K108548
文摘AIM: To investigate whether expression of selected mi RNAs obtained from fibrotic liver biopsies correlate with fibrosis stage.METHODS: Altogether, 52 patients were enrolled in the study representing various etiologic backgrounds of fibrosis: 24 cases with chronic hepatitis infections(types B, C), 19 with autoimmune liver diseases(autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, overlapping syndrome cases), and 9 of mixed etiology(alcoholic and nonalcoholic steatosis, cryptogenic cases). Severity of fibrosis was determined by both histologic staging using the METAVIR scoring system and noninvasive transient elastography. Following RNAisolation, expression levels of mi R-21, mi R-122, mi R-214, mi R-221, mi R-222, and mi R-224 were determined using Taq Man Micro RNA Assays applying mi R-140 as the reference. Selection of mi RNAs was based on their characteristic up- or downregulation observed in hepatocellular carcinoma. Relative expression of mi RNAs was correlated with fibrosis stage and liver stiffness(LS) value measured by transient elastography, as well as with serum alanine aminotransferase(ALT) level.RESULTS: The expression of individual mi RNAs showed deregulated patterns in stages F1-F4 as compared with stage F0, but only the reduced level of mi R-122 in stage F4 was statistically significant(P < 0.04). When analyzing mi RNA expression in relation to fibrosis, levels of mi R-122 and mi R-221 showed negative correlations with fibrosis stage, and mi R-122 was found to correlate negatively and mi R-224 positively with LS values(all P < 0.05). ALT levels displayed a positive correlation with mi R-21(P < 0.04). Negative correlations were observed in the fibrosis samples of mixed etiology between mi R-122 and fibrosis stage and LS values(P < 0.05), and in the samples of chronic viral hepatitis, between mi R-221 and fibrosis stage(P < 0.01), whereas mi R-21 showed positive correlation with ALT values in the samples of autoimmune liver diseases(P < 0.03). The results also revealed a strong correlation between fibrosis stage and LS values(P < 0.01) when etiology of fibrosis was not taken into account.CONCLUSION: Reduced expression of mi R-122 in advanced fibrosis and its correlation with fibrosis stage and LS values seem to be characteristic of hepatic fibrosis of various etiologies.
基金Science and Technology Development Foundation(STDF),Project NO.3457(TC/4/Health/2010/hep-1.6)
文摘BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis.AIM To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.METHODS This prospective study included 208 patients and 82 age-and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring.RESULTS The ADC value decreased significantly with the progression of fibrosis, from controls(F0) to patients with early fibrosis(F1 and F2) to those with late fibrosis(F3 and F4)(median 1.92, 1.53, and 1.25 × 10^(-3) mm^2/s, respectively)(P = 0.001).The cut-off ADC value used to differentiate patients from controls was 1.83 × 10^(-3) mm^2/s with an area under the curve(AUC) of 0.992. Combining ADC and miR-200 b revealed the highest AUC(0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10^(-3) mm^2/s with an AUC of 0.866. The combination of ADC and miR-200 b revealed the best AUC(0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200 b(r =-0.61, P = 0.001), miR-21(r =-0.62, P = 0.001), and miR-29(r = 0.52,P = 0.001).CONCLUSION Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.
基金supported by the National Key Research and Development Program on Modernization of Traditional Chinese Medicine(Grant No.2022YFC3502104,China)supports from VA Merit Award 5 I01 BX005730+2 种基金National Institutes of Health Grant R01 R01DK-057543 to Huiping Zhou(USA)National High-Level Talents Special Support Program to Xiaojiaoyang Li(China)Fundamental Research Funds for the Central Universities(Grant No.2023-JYBJBZD-046 to Xiaojiaoyang Li,China)。
文摘Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver failure.It’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver diseases.However,current treatment options are limited,highlighting the urgent need for the development of new therapies.As a reversible regulatory mechanism,epigenetic modification is implicated in many biological processes,including liver fibrosis.Exploring the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases,although the current evidence is still controversial.This review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications,including DNA methylation,histone modification,and RNA modification,in liver fibrotic diseases.The potential cooperation of different epigenetic modifications in promoting fibrogenesis was also highlighted.Finally,available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were discussed.In summary,elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.
