Objective: The study aimed to explore the protective mechanism of Ganoderic acid A (GAA) in renal fibrosisand to verify that GAA can ameliorate renal fibrosis by regulating the Niemann-pick C1-like 1 (NPC1L1) gene. Meth...Objective: The study aimed to explore the protective mechanism of Ganoderic acid A (GAA) in renal fibrosisand to verify that GAA can ameliorate renal fibrosis by regulating the Niemann-pick C1-like 1 (NPC1L1) gene. Methods:Transforming growth factor beta1 (TGF-β1) was used to treat Human Kidney-2 (HK-2) cells to establish a renal fibrosismodel. The differentially expressed genes in the control (CTRL) group, TGF-β1 group, and TGF-β1 + GAA group werescreened via transcriptome sequencing technology and verified by qPCR and Western blot experiments. The NPC1L1gene overexpression plasmid was constructed. The expression levels of N-cad, E-cad, and Slug-related proteins inCTRL, TGF-β1, TGF-β1+GAA (25 μg/mL), and TGF-β1+GAA (25 μg/mL) + NPC1L1 Overexpression (OE) groupswere detected by qPCR and Western blot analysis. Western blot analysis was used to identify the extracellular matrixassociated proteins Tenascin-C, α-SMA, and fibrosis-related protein Collagen I. Fibrosis marker protein Fibronectinwas detected and quantified by immunofluorescence. Results: Transcriptomic sequencing revealed that TGF-β1stimulation led to 267 differentially regulated genes, with 118 up-regulated and 149 down-regulated, while furthermodulation of 213 genes, comprising 112 up-regulated and 101 down-regulated genes, was observed in the GAAintervention group. The target gene in these processes was found to be NPC1L1 by investigations using GeneOntology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). qPCR and Western blot resultsconfirmed that TGF-β1 increased NPC1L1 expression, which was attenuated by GAA. Additionally, TGF-β1upregulated N-cad and Slug. However, GAA reversed this effect and NPC1L1 overexpression partially rescued theGAA effect. TGF-β1 also decreased E-cad expression, reversed by GAA, and NPC1L1 overexpression antagonized thisreversal. Furthermore, TGF-β1 promoted Collagen I, α-SMA, and Tenascin-C expression, and GAA reduced theselevels, effects that were reversed by NPC1L1 overexpression. Immunofluorescence results showed that TGF-β1increased fibronectin expression, which was decreased by GAA, and increased by NPC1L1 overexpression.Conclusion: GAA ameliorates renal fibrosis by antagonizing NPC1L1 gene expression inhibiting epithelialmesenchymal transition and reducing extracellular matrix formation.展开更多
Liver fibrosis is the formation of extracellular matrix deposits due to excessive repair of chronic liver damage.Liver fi brosis is a necessary stage in the progression of cirrhosis,and timely intervention reverses th...Liver fibrosis is the formation of extracellular matrix deposits due to excessive repair of chronic liver damage.Liver fi brosis is a necessary stage in the progression of cirrhosis,and timely intervention reverses the pathogenesis.Liver fi brosis is a dynamic and highly integrated molecular,cellular and organisational process.Currently,no specifi c drug is used to treat liver fi brosis,and liver transplantation is the main clinical treatment for cirrhosis.Chemical drugs are often designed to target individual genes or proteins,with kinds of side eff ects.Food polyphenols,which are available and safe,have unique advantages and great potential in the treatment with the liver fibrosis.This review summarizes the pathogenesis of liver fi brosis and provides examples of food polyphenols’anti-liver fi brosis mechanisms that have been identifi ed in recent studies,and provides some sights for the development of anti-liver fi brosis drugs.展开更多
AIM:To construct and evaluate a new non-invasive fibrosis index for assessment of the stage of liver f ibrosis. METHODS:A new f ibrosis index (Fibro-Stiffness index) was developed in 165 of 285 patients with chronic h...AIM:To construct and evaluate a new non-invasive fibrosis index for assessment of the stage of liver f ibrosis. METHODS:A new f ibrosis index (Fibro-Stiffness index) was developed in 165 of 285 patients with chronic hepatitis C, and was validated in the other 120 patients where liver biopsy was performed. Its usefulness was compared with liver stiffness (LS) measured by FibroScan, the aminotransferase-to-platelet ratio index, the Forns index and the FibroIndex. RESULTS: The Fibro-Stiffness index consists of LS,platelet count and prothrombin time. The values of the Fibro-Stiffness index differed signif icantly between neighboring f ibrosis stages except F0-F1. The area under the receiver operating characteristics curves of the Fibro-Stiffness index for prediction of F≥2 (0.90), F≥ 3 (0.90) and F= 4(0.92) in the estimation group and those for F≥ 3 (0.93) and F =4 (0.97) in the validation group were the highest among the 5 methods examined. The accuracy of the Fibro-Stiffness index had highest values for F≥2, F≥3 and F=4 in both the estimation and validation groups. The diagnostic performance for F= 4 was improved by a combination of the Fibro-Stiffness index with serum hyaluronic acid level. CONCLUSION: The Fibro-Stiffness index was constructed and validated. It showed superior diagnostic performance to other indices for F ≥ 2,3 and 4.展开更多
AIM: To examine whether hepatitis C virus (HCV)-infected patients who carry hypercoagulable mutationssuffer from increased rates of liver fi brosis. METHODS: We analyzed DNA samples of 168 HCV patients for three commo...AIM: To examine whether hepatitis C virus (HCV)-infected patients who carry hypercoagulable mutationssuffer from increased rates of liver fi brosis. METHODS: We analyzed DNA samples of 168 HCV patients for three common hypercoagulable gene mutations: prothrombin 20210 (PT20210), factor V Leiden (FV Leiden) and methylene tetrahydrofolate reductase (MTHFR). The patients were consecutively recruited as part of the prospective "Fibroscore Study" in France. The effect of the various mutations on the rate of fi-brosis was analyzed statistically and was correlated with epidemiological, clinical and biochemical data such as grade and stage of liver biopsies, patients' risk factors for liver cirrhosis, and timing of infection. RESULTS: Fifty two of the patients were categorized as "fast fi brosers" and 116 as "slow fi brosers"; 13% of the "fast fi brosers" carried the PT20210 mutation as compared with 5.5% of the "slow fi brosers", with an odds ratio of 4.76 (P = 0.033; 95% CI: 1.13-19.99) for "fast" liver fibrosis. Carriage of MTHFR or FV Leiden mutations was not associated with enhanced liver fi brosis. CONCLUSION: Carriage of the PT20210 mutation is related to an increased rate of liver fi brosis in HCV patients.展开更多
Hypertrophic cardiomyopathy(HCM)is a type of hereditary cardiomyopathy caused by gene mutation.Its histological features include cardiomyocyte hypertrophy and disarray as well as myocardial fi brosis.Gene mutation,abn...Hypertrophic cardiomyopathy(HCM)is a type of hereditary cardiomyopathy caused by gene mutation.Its histological features include cardiomyocyte hypertrophy and disarray as well as myocardial fi brosis.Gene mutation,abnormal signal transduction,and abnormal energy metabolism are considered the main mechanisms of myocardial fi brosis.There is a strong correlation between myocardial fi brosis and the occurrence,development,and prognosis of HCM.We review the application of myocardial fi brosis in the diagnosis and treatment of HCM,focusing on research progress and the application of magnetic resonance imaging on the basis of the characteristics of fi brosis in the diagnosis and prognosis of HCM.展开更多
The aim of this study was to explore the expression of integrin-β1 in different stages of hepaticfibrosis and intervention of resveratrol as well as the way by which integrin-β1 promoted hepaticfibrosis.Hepaticfibrosis...The aim of this study was to explore the expression of integrin-β1 in different stages of hepaticfibrosis and intervention of resveratrol as well as the way by which integrin-β1 promoted hepaticfibrosis.Hepaticfibrosis models of male Sprague Dawley(SD)rats were created and intragastric administration of resveratrol was given in low(40 mg/kg),middle(120 mg/kg)and high(200 mg/kg)dose groups.The expression of integrin-β1,transforming growth factor-β(TGF-β)and tissue inhibitor of metalloproteinase-1(TIMP-1)in different stages of hepaticfibrosis was detected by using RT-PCR.The expression of hexadecenoic acid(HA)and precollagen III(pc III)was assayed by radioimmunoassay.The expression of integrin-β1,TGF-βand TIMP-1 was determined in each group.Liver function and pathological sections of each group in different stages of hepaticfibrosis was tested to judge the therapeutic efficacy of resveratrol at different doses.The expression of integrin-β1 in normal control group was low and steady and was not increased with the development of hepaticfibrosis,but it was increased in other groups.The expression levels of integrin-β1 in the model control group(0.878±0.03,P<0.01)and low dose group(0.855±0.04,P<0.01)were higher than other groups,but there was no difference between model control group and low dose group(P>0.05).The expression levels of integrin-β1 and TGF-βin middle dose group and high dose group were higher than other groups(P<0.01).The expression levels of integrin-β1 and TGF-βin model control group and low dose group were lower than the normal control group(P<0.01).The expression levels of TIMP-1 in the model control and low dose groups were higher than the other groups(P<0.01).The expression levels of TIMP-1 in the middle dose group and the high dose group were lower than the normal control group(P<0.01).The expression of integrin-β1 existed in all stages of hepaticfibrosis of SD rats,and it was increased with the development of hepaticfibrosis.The expression of TGF-βand TIMP-1 was consistent with that of integrin-β1 in different stages of hepaticfibrosis.Resveratrol could improve the degree of hepaticfibrosis of SD rats and decrease the expression of integrin-β1 markedly at a dose of 120 mg/kg.展开更多
Combined hepatocellular carcinoma(HCC)and cholangiocarcinoma(CC)is a rare tumor entity.In this report,we describe a case of a young patient who developed a liver tumor in a cirrhotic liver caused by cystic fi brosis.A...Combined hepatocellular carcinoma(HCC)and cholangiocarcinoma(CC)is a rare tumor entity.In this report,we describe a case of a young patient who developed a liver tumor in a cirrhotic liver caused by cystic fi brosis.All diagnostic fi ndings suggested that this tumor was an HCC.We performed living donor liver transplantation.Histological examination of the tumor revealed combined HCC and CC as an incidental fi nding.Two years after the transplantation,the patient is in good clinical condition and is disease-free.展开更多
T1 mapping using cardiovascular magnetic resonance(CMR)introduces novel techniques for myocardial tissue characterization to detect and quantify disease processes occurring at the microscopic level.Even though T1 mapp...T1 mapping using cardiovascular magnetic resonance(CMR)introduces novel techniques for myocardial tissue characterization to detect and quantify disease processes occurring at the microscopic level.Even though T1 mapping has limited spatial resolution,cellular and molecular changes occurring within each voxel can affect the aggregate T1 signal rendering them quantifi able.The estimated T1-based parameters quantifi ed on a“map”demonstrate the spatial localization of these changes whereby each pixel expresses the quantitative value of that parameter.This quantifi cation permits detection of diffuse disease even if it is not directly visible.Rather than relying on nonspecifi c functional measures,T1 mapping focuses on intrinsic changes of myocardial composition that advances understanding about specifi c disease pathways.These changes in myocardial tissue composition inform diagnosis and prognosis.T1 mapping encompasses two key parameters:native(i.e.,precontrast)T1 and extracellular volume fraction(ECV)derived from additional postcontrast T1 and blood T1 measurements.These advances introduce new tools to detect focal and diffuse myocardial derangements occurring in cardiac disease that can be otherwise diffi cult to detect.T1 and ECV mapping foster precision medicine and personalized care,promising to improve patient outcomes through targeted therapy.Capitalizing on the opportunities introduced by T1 mapping and ECV requires further investigation.展开更多
基金sponsored by KeyResearch and Development Project of Science andTechnology Department of Tibet (No. XZ202201ZY0033G).
文摘Objective: The study aimed to explore the protective mechanism of Ganoderic acid A (GAA) in renal fibrosisand to verify that GAA can ameliorate renal fibrosis by regulating the Niemann-pick C1-like 1 (NPC1L1) gene. Methods:Transforming growth factor beta1 (TGF-β1) was used to treat Human Kidney-2 (HK-2) cells to establish a renal fibrosismodel. The differentially expressed genes in the control (CTRL) group, TGF-β1 group, and TGF-β1 + GAA group werescreened via transcriptome sequencing technology and verified by qPCR and Western blot experiments. The NPC1L1gene overexpression plasmid was constructed. The expression levels of N-cad, E-cad, and Slug-related proteins inCTRL, TGF-β1, TGF-β1+GAA (25 μg/mL), and TGF-β1+GAA (25 μg/mL) + NPC1L1 Overexpression (OE) groupswere detected by qPCR and Western blot analysis. Western blot analysis was used to identify the extracellular matrixassociated proteins Tenascin-C, α-SMA, and fibrosis-related protein Collagen I. Fibrosis marker protein Fibronectinwas detected and quantified by immunofluorescence. Results: Transcriptomic sequencing revealed that TGF-β1stimulation led to 267 differentially regulated genes, with 118 up-regulated and 149 down-regulated, while furthermodulation of 213 genes, comprising 112 up-regulated and 101 down-regulated genes, was observed in the GAAintervention group. The target gene in these processes was found to be NPC1L1 by investigations using GeneOntology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). qPCR and Western blot resultsconfirmed that TGF-β1 increased NPC1L1 expression, which was attenuated by GAA. Additionally, TGF-β1upregulated N-cad and Slug. However, GAA reversed this effect and NPC1L1 overexpression partially rescued theGAA effect. TGF-β1 also decreased E-cad expression, reversed by GAA, and NPC1L1 overexpression antagonized thisreversal. Furthermore, TGF-β1 promoted Collagen I, α-SMA, and Tenascin-C expression, and GAA reduced theselevels, effects that were reversed by NPC1L1 overexpression. Immunofluorescence results showed that TGF-β1increased fibronectin expression, which was decreased by GAA, and increased by NPC1L1 overexpression.Conclusion: GAA ameliorates renal fibrosis by antagonizing NPC1L1 gene expression inhibiting epithelialmesenchymal transition and reducing extracellular matrix formation.
基金supported by the People’s Livelihood Plan Project of Department of Science and Technology of Liaoning Province(No.2021JH2/10300074)Department of Education of Liaoning Province(No.LJKMZ20221367)Career Development Support Plan for Young and Middleaged Teachers in Shenyan。
文摘Liver fibrosis is the formation of extracellular matrix deposits due to excessive repair of chronic liver damage.Liver fi brosis is a necessary stage in the progression of cirrhosis,and timely intervention reverses the pathogenesis.Liver fi brosis is a dynamic and highly integrated molecular,cellular and organisational process.Currently,no specifi c drug is used to treat liver fi brosis,and liver transplantation is the main clinical treatment for cirrhosis.Chemical drugs are often designed to target individual genes or proteins,with kinds of side eff ects.Food polyphenols,which are available and safe,have unique advantages and great potential in the treatment with the liver fibrosis.This review summarizes the pathogenesis of liver fi brosis and provides examples of food polyphenols’anti-liver fi brosis mechanisms that have been identifi ed in recent studies,and provides some sights for the development of anti-liver fi brosis drugs.
文摘AIM:To construct and evaluate a new non-invasive fibrosis index for assessment of the stage of liver f ibrosis. METHODS:A new f ibrosis index (Fibro-Stiffness index) was developed in 165 of 285 patients with chronic hepatitis C, and was validated in the other 120 patients where liver biopsy was performed. Its usefulness was compared with liver stiffness (LS) measured by FibroScan, the aminotransferase-to-platelet ratio index, the Forns index and the FibroIndex. RESULTS: The Fibro-Stiffness index consists of LS,platelet count and prothrombin time. The values of the Fibro-Stiffness index differed signif icantly between neighboring f ibrosis stages except F0-F1. The area under the receiver operating characteristics curves of the Fibro-Stiffness index for prediction of F≥2 (0.90), F≥ 3 (0.90) and F= 4(0.92) in the estimation group and those for F≥ 3 (0.93) and F =4 (0.97) in the validation group were the highest among the 5 methods examined. The accuracy of the Fibro-Stiffness index had highest values for F≥2, F≥3 and F=4 in both the estimation and validation groups. The diagnostic performance for F= 4 was improved by a combination of the Fibro-Stiffness index with serum hyaluronic acid level. CONCLUSION: The Fibro-Stiffness index was constructed and validated. It showed superior diagnostic performance to other indices for F ≥ 2,3 and 4.
文摘AIM: To examine whether hepatitis C virus (HCV)-infected patients who carry hypercoagulable mutationssuffer from increased rates of liver fi brosis. METHODS: We analyzed DNA samples of 168 HCV patients for three common hypercoagulable gene mutations: prothrombin 20210 (PT20210), factor V Leiden (FV Leiden) and methylene tetrahydrofolate reductase (MTHFR). The patients were consecutively recruited as part of the prospective "Fibroscore Study" in France. The effect of the various mutations on the rate of fi-brosis was analyzed statistically and was correlated with epidemiological, clinical and biochemical data such as grade and stage of liver biopsies, patients' risk factors for liver cirrhosis, and timing of infection. RESULTS: Fifty two of the patients were categorized as "fast fi brosers" and 116 as "slow fi brosers"; 13% of the "fast fi brosers" carried the PT20210 mutation as compared with 5.5% of the "slow fi brosers", with an odds ratio of 4.76 (P = 0.033; 95% CI: 1.13-19.99) for "fast" liver fibrosis. Carriage of MTHFR or FV Leiden mutations was not associated with enhanced liver fi brosis. CONCLUSION: Carriage of the PT20210 mutation is related to an increased rate of liver fi brosis in HCV patients.
文摘Hypertrophic cardiomyopathy(HCM)is a type of hereditary cardiomyopathy caused by gene mutation.Its histological features include cardiomyocyte hypertrophy and disarray as well as myocardial fi brosis.Gene mutation,abnormal signal transduction,and abnormal energy metabolism are considered the main mechanisms of myocardial fi brosis.There is a strong correlation between myocardial fi brosis and the occurrence,development,and prognosis of HCM.We review the application of myocardial fi brosis in the diagnosis and treatment of HCM,focusing on research progress and the application of magnetic resonance imaging on the basis of the characteristics of fi brosis in the diagnosis and prognosis of HCM.
基金supported by the Natural Science Foundation of Shanghai(No.06ZR14090).
文摘The aim of this study was to explore the expression of integrin-β1 in different stages of hepaticfibrosis and intervention of resveratrol as well as the way by which integrin-β1 promoted hepaticfibrosis.Hepaticfibrosis models of male Sprague Dawley(SD)rats were created and intragastric administration of resveratrol was given in low(40 mg/kg),middle(120 mg/kg)and high(200 mg/kg)dose groups.The expression of integrin-β1,transforming growth factor-β(TGF-β)and tissue inhibitor of metalloproteinase-1(TIMP-1)in different stages of hepaticfibrosis was detected by using RT-PCR.The expression of hexadecenoic acid(HA)and precollagen III(pc III)was assayed by radioimmunoassay.The expression of integrin-β1,TGF-βand TIMP-1 was determined in each group.Liver function and pathological sections of each group in different stages of hepaticfibrosis was tested to judge the therapeutic efficacy of resveratrol at different doses.The expression of integrin-β1 in normal control group was low and steady and was not increased with the development of hepaticfibrosis,but it was increased in other groups.The expression levels of integrin-β1 in the model control group(0.878±0.03,P<0.01)and low dose group(0.855±0.04,P<0.01)were higher than other groups,but there was no difference between model control group and low dose group(P>0.05).The expression levels of integrin-β1 and TGF-βin middle dose group and high dose group were higher than other groups(P<0.01).The expression levels of integrin-β1 and TGF-βin model control group and low dose group were lower than the normal control group(P<0.01).The expression levels of TIMP-1 in the model control and low dose groups were higher than the other groups(P<0.01).The expression levels of TIMP-1 in the middle dose group and the high dose group were lower than the normal control group(P<0.01).The expression of integrin-β1 existed in all stages of hepaticfibrosis of SD rats,and it was increased with the development of hepaticfibrosis.The expression of TGF-βand TIMP-1 was consistent with that of integrin-β1 in different stages of hepaticfibrosis.Resveratrol could improve the degree of hepaticfibrosis of SD rats and decrease the expression of integrin-β1 markedly at a dose of 120 mg/kg.
文摘Combined hepatocellular carcinoma(HCC)and cholangiocarcinoma(CC)is a rare tumor entity.In this report,we describe a case of a young patient who developed a liver tumor in a cirrhotic liver caused by cystic fi brosis.All diagnostic fi ndings suggested that this tumor was an HCC.We performed living donor liver transplantation.Histological examination of the tumor revealed combined HCC and CC as an incidental fi nding.Two years after the transplantation,the patient is in good clinical condition and is disease-free.
文摘T1 mapping using cardiovascular magnetic resonance(CMR)introduces novel techniques for myocardial tissue characterization to detect and quantify disease processes occurring at the microscopic level.Even though T1 mapping has limited spatial resolution,cellular and molecular changes occurring within each voxel can affect the aggregate T1 signal rendering them quantifi able.The estimated T1-based parameters quantifi ed on a“map”demonstrate the spatial localization of these changes whereby each pixel expresses the quantitative value of that parameter.This quantifi cation permits detection of diffuse disease even if it is not directly visible.Rather than relying on nonspecifi c functional measures,T1 mapping focuses on intrinsic changes of myocardial composition that advances understanding about specifi c disease pathways.These changes in myocardial tissue composition inform diagnosis and prognosis.T1 mapping encompasses two key parameters:native(i.e.,precontrast)T1 and extracellular volume fraction(ECV)derived from additional postcontrast T1 and blood T1 measurements.These advances introduce new tools to detect focal and diffuse myocardial derangements occurring in cardiac disease that can be otherwise diffi cult to detect.T1 and ECV mapping foster precision medicine and personalized care,promising to improve patient outcomes through targeted therapy.Capitalizing on the opportunities introduced by T1 mapping and ECV requires further investigation.
