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1.
Int. j. morphol ; 42(2)abr. 2024.
Article de Anglais | LILACS | ID: biblio-1558139

RÉSUMÉ

SUMMARY: The response of the immune system to harmful stimuli leads to inflammation, and the adverse effects of the toxic hepatitis chemical, thioacetamide (TAA) on the human body are well documented. This article investigated the degree of protection provided by the combined pleotropic drug, metformin (Met) and the plant polyphenolic and the antiinflammatory compound, resveratrol (Res) on liver tissue exposed to TAA possibly via the inhibition of the inflammatory cytokine, tumor necrosis factor-α (TNF-α) / mammalian target of rapamycin (mTOR) axis-mediated liver fibrosis, as well as amelioration of profibrotic gene and protein expression. Rats were either given TAA (200 mg/kg via intraperitoneal injection) for 8 weeks beginning at the third week (experimental group) or received during the first two weeks of the experiment combined doses of metformin (200 mg/kg) and resveratrol (20 mg/kg) and continued receiving these agents and TAA until experiment completion at week 10 (treated group). A considerable damage to hepatic tissue in the experimental rats was observed as revealed by tissue collagen deposition in the portal area of the liver and a substantial increase (p<0.0001) in hepatic levels of the inflammatory marker, tumor necrosis factor-α (TNF-α), as well as blood levels of hepatocellular injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TAA also augmented hepatic tissue levels of the signalling molecule that promotes liver fibrosis (mTOR), and profibrogenic markers; alpha-smooth muscle actin (α-SMA) protein, tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA, and matrix metalloproteinase-9 (MMP-9) mRNA. All these parameters were protected (p≤0.0016) by Met+Res. In addition, a significant correlation was detected between liver fibrosis score and inflammation, liver injury enzymes, mTOR, and profibrogenesis markers. Thus, these findings suggest that Met+Res effectively protect the liver against damage induced by thioacetamide in association with the downregulation of the TNF-α/mTOR/fibrosis axis.


La respuesta del sistema inmunológico a estímulos dañinos conduce a la inflamación y los efectos adversos de la tioacetamida (TAA), una sustancia química tóxica para el hígado, están bien documentadas. Este artículo investigó el grado de protección proporcionado por el fármaco pleotrópico combinado metformina (Met), el polifenólico vegetal y el compuesto antiinflamatorio resveratrol (Res) en el tejido hepático expuesto a TAA, posiblemente a través de la inhibición de la citoquina inflamatoria, factor de necrosis tumoral α (TNF-α)/objetivo de la fibrosis hepática mediada por el eje de rapamicina (mTOR), así como mejora de la expresión de genes y proteínas profibróticas. Las ratas recibieron TAA (200 mg/kg mediante inyección intraperitoneal) durante 8 semanas a partir de la tercera semana (grupo experimental) o recibieron durante las dos primeras semanas del experimento dosis combinadas de metformina (200 mg/kg) y resveratrol (20 mg/kg) y continuaron recibiendo estos agentes y TAA hasta completar el experimento en la semana 10 (grupo tratado). Se observó un daño considerable al tejido hepático en las ratas experimentales, como lo revela el depósito de colágeno tisular en el área portal del hígado y un aumento sustancial (p<0,0001) en los niveles hepáticos del marcador inflamatorio, el factor de necrosis tumoral-α (TNF- α), así como los niveles sanguíneos de biomarcadores de lesión hepatocelular, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). TAA también aumentó los niveles en el tejido hepático de la molécula de señalización que promueve la fibrosis hepática (mTOR) y marcadores profibrogénicos; proteína actina del músculo liso alfa (α- SMA), inhibidor tisular de las metaloproteinasas-1 (TIMP-1) mRNA y matriz metaloproteinasa-9 (MMP-9) mRNA. Todos estos parámetros fueron protegidos (p≤0.0016) por Met+Res. Además, se detectó una correlación significativa entre la puntuación de fibrosis hepática y la inflamación, las enzimas de lesión hepática, mTOR y los marcadores de profibrogénesis. Por lo tanto, estos hallazgos sugieren que Met+Res protege eficazmente el hígado contra el daño inducido por la tioacetamida en asociación con la regulación negativa del eje TNF-α/mTOR/fibrosis.


Sujet(s)
Animaux , Rats , Thioacétamide/toxicité , Resvératrol/pharmacologie , Cirrhose du foie/traitement médicamenteux , Metformine/pharmacologie , Immunohistochimie , Cytokines/antagonistes et inhibiteurs , Facteur de nécrose tumorale alpha , Inhibiteur tissulaire de métalloprotéinase-1 , Sirolimus , Sérine-thréonine kinases TOR , Inflammation , Foie/effets des médicaments et des substances chimiques , Cirrhose du foie/induit chimiquement
2.
Rev. colomb. gastroenterol ; 39(1): 37-43, Jan.-Mar. 2024. tab, graf
Article de Anglais | LILACS-Express | LILACS | ID: biblio-1576290

RÉSUMÉ

Abstract Introduction: The medical record and liver biochemical profile are essential in diagnosing liver diseases. Liver biopsy is the reference parameter for diagnosis, activity evaluation, fibrosis status, or therapeutic response, but it is invasive and carries risks. For fibrosis staging, easily accessible non-invasive tests without resorting to biopsy have been developed. The FIB-4 and APRI indexes are helpful but do not determine the degree of fibrosis in the early and intermediate stages. Fibrosis can be evaluated using elastography, a sensitive technique to differentiate patients without fibrosis from those with advanced fibrosis. Objective: To describe the diagnostic performance of FibroScan in detecting fibrosis compared to the APRI and FIB-4 indexes versus the biopsy in a care center for patients with liver diseases in Bogotá. Methods: A retrospective, cross-sectional cohort study compared the APRI, FIB-4, and Fibroscan with biopsy; diagnostic accuracy measures and an area under the curve (AUROC) analysis were described. Results: The biopsy was positive for fibrosis in 40%. The AUROC was 0.90 (confidence interval [CI]: 0.83-0.97) for FibroScan, 0.52 (CI: 0.35-0.68) for APRI, and 0.52 (CI: 0.37-0.68) for FIB-4. Conclusions: FibroScan helps diagnose and monitor chronic liver disease and should be combined with other tests and the clinical picture. FibroScan was better at detecting advanced stages when discriminating against patients with liver fibrosis than the APRI and FIB-4 indexes.


Resumen Introducción: En el proceso diagnóstico de las enfermedades hepáticas, la historia clínica y el perfil bioquímico hepático son fundamentales. La biopsia hepática es el parámetro de referencia para el diagnóstico, evaluación de la actividad, estado de fibrosis o respuesta terapéutica, pero es invasiva y con riesgos. Para la estadificación de la fibrosis, se han desarrollado pruebas no invasivas de fácil acceso y sin recurrir a la biopsia. Los índices FIB-4 y APRI son útiles, pero no determinan el grado de fibrosis en estadios precoces e intermedios. La fibrosis puede evaluarse mediante elastografía, técnica sensible para diferenciar pacientes sin fibrosis de aquellos con fibrosis avanzada. Objetivo: Describir el desempeño diagnóstico para la detección de fibrosis del FibroScan comparado con los índices APRI y FIB-4 frente a la biopsia de pacientes evaluados en un centro de atención de pacientes con enfermedades hepáticas de Bogotá. Métodos: Estudio de cohorte retrospectivo, transversal, que comparó los índices APRI, FIB-4 y Fibroscan con la biopsia; se describieron las medidas de precisión diagnóstica y un análisis de área bajo la curva (AUROC). Resultados: La biopsia fue positiva para fibrosis en el 40%, FibroScan mostró un AUROC de 0,90 (intervalo de confianza [IC]: 0,83-0,97), índices APRI de 0,52 (IC: 0,35-0,68) y FIB-4 de 0,52 (IC: 0,37-0,68). Conclusiones: FibroScan es útil para el diagnóstico y seguimiento de la enfermedad hepática crónica, y debe utilizarse en combinación con otras pruebas y la clínica. FibroScan mostró un excelente rendimiento en la discriminación de pacientes con fibrosis hepática comparado con los índices APRI y FIB-4, y es mejor para detectar estadios avanzados.

3.
Basic & Clinical Medicine ; (12): 108-113, 2024.
Article de Chinois | WPRIM | ID: wpr-1018580

RÉSUMÉ

Emerging evidence suggests that ferroptosis,an iron-dependent form of regulated cell death,plays a criti-cal role in the genesis of liver fibrosis through inducing hepatic stellate cell(HSC)ferroptosis to inhibit liver fibrosis or inducing hepatic ferroptosis to potentiates liver fibrosis.Pharmacologically targeting at ferroptosis with its inducers can slow down the progression of liver fibrosis in vitro and in vivo model.This review suggests that pharmacological in-duction of HSC ferroptosis might be used as a potential novel targeted therapy for the treatment of liver fibrosis.

4.
Article de Chinois | WPRIM | ID: wpr-1018838

RÉSUMÉ

Objective To compare the effects of CalliSpheres drug-eluting beads transcatheter arterial chemoembolization(DEB-TACE)and conventional TACE(c-TACE)on liver fibrosis and liver function in the treatment of primary hepatocellular carcinoma(HCC).Methods A total of 40 patients diagnosed with HCC at Xuzhou Municipal Cancer Hospital of China between October 2020 and October 2022 were enrolled in this study.According to therapeutic scheme,the patients were divided into DEB-TACE group(n=20)and c-TACE group(n=20).The preoperative,and postoperative 5-day and one-month hyaluronidase(HA),type Ⅲ procollagen peptide(P Ⅲ NP),type Ⅳ collagen(CⅣ)and laminin(LN),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),albumin(Alb),and prothrombin time(PT)were compared between the two groups.Results The technical success rate was 100%in both groups,and tumor staining completely disappeared immediately after TACE in all patients.The postoperative 5-day levels of HA,LN,P Ⅲ NP,and CⅣ in both groups were remarkably higher than the preoperative ones(P<0.05).One month after TACE,HA level in the DEB-TACE group was prominently higher than its preoperative value(P<0.05);HA and LN levels in the c-TACE group were obviously higher than their preoperative values(P<0.05);and the HA and LN levels in c-TACE group were significantly higher than those in DEB-TACE group(P<0.05).Five days after TACE,in the DEB-TACE group the AST and PT levels were higher than their preoperative values while the Alb level was lower than its preoperative value(P<0.05);in the c-TACE group the ALT,AST,TBiL and PT were higher than their preoperative values while the Alb level was lower than its preoperative value(P<0.05);the ALT and AST levels in the c-TACE group were strikingly higher than those in the DEB-TACE group while Alb level was strikingly lower than that in the DEB-TACE group(P<0.05).Conclusion Both CalliSpheres DEB-TACE and c-TACE can aggravate liver fibrosis and cause liver function damage.However,the degree of liver fibrosis and liver function damage caused by CalliSpheres DEB-TACE is less than that caused by c-TACE.(J Intervent Radiol,2024,33:259-263)

5.
Article de Chinois | WPRIM | ID: wpr-1020807

RÉSUMÉ

Objective To study the diagnostic value of miR-571 for liver fibrosis by detecting miR-571 expression in the peripheral blood of patients with liver fibrosis.Methods From December 2022 to September 2023,40 patients with liver fibrosis,40 patients with chronic hepatitis,and 40 healthy controls were chosen as research subjects.The expression level of miR-571 in peripheral blood was detected using a real-time quantitative polymerase chain reaction,and the relative expression of miR-571 in each group was evaluated.The Spearman correlation method was utilized to examine the relationship between miR-571 and clinical detection indices.To assess the capacity of miR-571 and the multivariate diagnostic model to identify liver fibrosis,binary logistic regression was used to create a multivariate diagnostic model,and ROC curves were generated.Results The expression of miR-571 was significantly higher in the liver fibrosis group than in the healthy control and hepatitis groups,and the difference was statistically significant(P<0.001).The expression level of miR-571 was positively connected with ALT,APRI score,and FIB-4 index(r = 0.23,0.30,0.22,P<0.05)and negatively correlated with PLT(r =-0.19,P<0.05)according to Spearman correlation analysis.Logistic regression research revealed that miR-571 and the FIB-4 index were independent risk factors for liver fibrosis.The AUC for miR-571 to diagnose fibrosis was 0.91(95%CI:0.85~0.96),while the AUC for miR-571 paired with the FIB-4 index was 0.94(95%CI:0.90~0.98).Conclusion MiR-571 expression was shown to be considerably higher in the peripheral blood of hepatic fibrosis patients,and the combined FIB-4 index offers some clinical diagnostic value for hepatic fibrosis.

6.
Article de Chinois | WPRIM | ID: wpr-1020834

RÉSUMÉ

Objective There is a Few studies explored the association between vitamin intake and meta-bolic dysfunction-associated fatty liver disease(MAFLD),while the existing results were still contradictory.This study aimed to investigate the association between dietary vitamins and all-cause mortality as well as fibrosis risk in patients with MAFLD.Methods The data were extracted from the third National Health and Nutrition Examination Surveys 1988-1994.Dietary vitamins was assessed using a 24 h diet recall,including vitamin A,vitamin B6,vitamin B12,vitamin C,vitamin D,thiamin,riboflavin,folic acid and α-tocopherol.The non-alcoholic fatty liver disease fibrosis score(NFS)<-1.455 was considered as non-advanced fibrosis,while NFS≥-1.455 was considered as advanced fibrosis.Results A total of 3844 MAFLD participants were included in this study.The median time of follow-up was 310 months.1739 participants(45.3%)were deceased during the follow-up.The intake of thiamin,riboflavin,α-tocopherol,VB6,and VB12 were significantly higher in patients with NFS-determined non-advanced fibrosis(P<0.05).After adjusting,a significantly lower risk of fibrosis was found in patients with the highest quartile(>11.5 mg/d)of α-tocopherol intake compared to the lowest intake group(P = 0.031).Compared to the lowest quartile group,the risk of mortality was reduced by 0.34 folds in the group consuming the highest quartile amount(>130 mg/d)of VC(HRs:0.66,95%CI:0.51~0.85,P = 0.001).Conclusions More α-tocopherol intake reduced fibrosis grade in MAFLD patients.VC intake may reduce all-cause mortality in patients with MAFLD.

7.
Clinical Medicine of China ; (12): 128-132, 2024.
Article de Chinois | WPRIM | ID: wpr-1026705

RÉSUMÉ

The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing year by year, and it has become a serious public health problem that threatens human health.NAFLD patients can progress from simple steatosis to non-alcoholic steatohepatitis (NASH), liver fibrosis, and even cirrhosis without intervention. Therefore, early diagnosis and treatment are particularly important.Liver biopsy is the gold standard for diagnosing NAFLD, but its limitations such as invasion, bleeding, and high cost limit its widespread clinical application. There is an urgent need for sensitive and convenient non-invasive diagnostic methods to achieve early diagnosis and treatment of NAFLD.This article provides a review of the progress in serological diagnostic methods for NAFLD both domestically and internationally in recent years.

8.
Article de Chinois | WPRIM | ID: wpr-1028636

RÉSUMÉ

Objective:To investigate the association of time in range with metabolic associated fatty liver disease(MAFLD) and advanced liver fibrosis in patients with type 2 diabetes.Methods:This study was a retrospective study. A total of 494 type 2 diabetic patients were recruited in the Department of Endocrinololgy of Henan Provincial People′s Hospital from November 2019 to April 2022. Time in range(TIR) was calculated with continuous glucose monitoring data. Abdominal ultrasound scan was used to diagnose fatty liver. Liver stiffness measurement(LSM) by transient elastography was used to evaluate liver fibrosis. Pearson and multivariate linear regression analysis was used to evaluate the association between TIR and LSM. Multivariate logistic regression analysis was used to analyze the association of TIR with risk of MAFLD and advanced liver fibrosis.Results:Pearson correlation analysis showed that LSM was negatively correlated with TIR( r=-0.86, P<0.001) and was positively correlated with homeostasis model assessment for insulin resistance(HOMA-IR; r=0.48, P<0.001). After adjusting for confounding factors, multivariate linear regression analysis showed that TIR significantly negatively predicted LSM( β=-0.75, P<0.001), and HOMA-IR significantly positively predicted LSM( β=0.21, P=0.025). After adjusting for confounding factors, logistic regression analysis showed that compared with TIR Q4 patients, TIR Q1 patients had an increased risk of MAFLD( OR=1.96, 95% CI 1.07-3.62, P=0.027), advanced liver fibrosis( OR=3.82, 95% CI 1.17-12.50, P=0.027), and HOMA-IR was an independent risk factor for MAFLD( OR=1.22, 95% CI 1.04-1.43, P=0.005) and advanced liver fibrosis( OR=1.26, 95% CI 1.03-1.54, P=0.025). Conclusions:TIR and insulin resistance are independent risk factors for MAFLD and advanced liver fibrosis in patients with type 2 diabetes. TIR has a significant predictive value for MAFLD and advanced liver fibrosis.

9.
Article de Chinois | WPRIM | ID: wpr-1032164

RÉSUMÉ

Objective @# To explore the role of long non-coding RNA XR_378418 (LncRNA XR_378418) in the bi- ological behavior of hepatic stellate cells line JS-1 and to probe the potential molecular mechanism of LncRNA XR _378418 involved in liver fibrosis based on transcriptome sequencing.@*Methods @#In this study,the recombinant plasmid of pcDNA-LncRNA XR_378418 and control plasmid pcDNA-NC were constructed and transfected into JS-1 cells respectively.Then,the expression level of LncRNA XR_378418 was analyzed by quantitative real-time PCR (RT-qPCR) .The effect of overexpression of LncRNA XR_378418 on proliferation and migration of JS-1 cells were detected by cell counting kit-8 assay ( CCK-8 ) and scratch assay,respectively. Finally,by high-throughput se- quencing analysis,the effect of XR_378418 on the transcriptomics of JS-1 cells was analyzed. @*Results @#T-qPCR results showed that the expression level of LncRNA XR_378418 in the overexpression group was significantly higher than that in the control group (P<0. 05) .The results of CCK-8 and scratch experiment suggested that the prolifer- ation and migration in the pcDNA-LncRNA XR _ 378418 group significantly increased. Furthermore ,the high- throughput sequencing analysis showed that a total of 248 genes were screened by gene differential analysis ,of which 127 were up-regulated ,and 117 were down-regulated. Gene Ontology ( GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that LncRNA XR_378418 could regulate cell adhesion,autophagy and Ca2 + signaling,etc.@*Conclusion @#LncRNA XR_378418 promotes the proliferation and migration of JS-1 cells and affects the expression of genes related to cell adhesion and calcium signaling in JS-1 cells.

10.
Article de Chinois | WPRIM | ID: wpr-1036316

RÉSUMÉ

Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

11.
China Pharmacy ; (12): 1570-1575, 2024.
Article de Chinois | WPRIM | ID: wpr-1036544

RÉSUMÉ

OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics. METHODS Forty mice were divided into normal control group (0.5% carboxymethyl cellulose sodium solution), model group (0.5% carboxymethyl cellulose sodium solution), and BP low-dose and high-dose groups (50, 100 mg/kg), with 10 mice in each group. Except for the normal control group, the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model; they were given relevant medicine/solution intragastrically, once a day, for consecutive 8 weeks. After the last medication, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected, and liver pathological changes were observed; the expressions of α-smooth muscle actin (α-SMA) and Collagen Ⅰ were detected in liver tissue; the serum of the mice was collected for metabolomics analysis. RESULTS Compared with the model group, serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups (P<0.05), while liver fibrosis was improved significantly. Meanwhile, metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group, of which 18 substances were upregulated and 157 substances were downregulated; the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism, butanoate metabolism, fatty acid synthesis, tyrosine metabolism, β-alanine metabolism, nicotinic acid and nicotinamide metabolism, glutathione metabolism, etc. CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism, butanoate metabolism, glutathione metabolism and so on in rats with liver fibrosis.

12.
Article de Chinois | WPRIM | ID: wpr-1030653

RÉSUMÉ

Liver fibrosis is a repair response to chronic liver injury caused by various etiologies. Its continuous progression can develop into liver cirrhosis or even hepatocellular carcinoma, eventually leading to liver failure. Currently, there is no effective treatment for liver fibrosis. Hepatic macrophages play a key role in intrahepatic inflammatory response, progression and resolution of fibrosis, and have emerged as an important therapeutic target for anti-hepatic fibrosis. The function of hepatic macrophages in the process of liver fibrosis was mainly reviewed and the mode of action of hepatic macrophages from various aspects was discussed to provide ideas for the treatment of liver fibrosis.

13.
Organ Transplantation ; (6): 352-358, 2024.
Article de Chinois | WPRIM | ID: wpr-1016898

RÉSUMÉ

Hepatitis E virus infection is a common cause of acute viral hepatitis. In recent years, the incidence of hepatitis E has shown an increasing trend, which has gradually become an important cause of acute viral hepatitis worldwide. Age, sex, intensity of immunosuppression and socio-economic factors are all risk factors for hepatitis E virus infection. Liver transplant recipients require long-term use of immunosuppressive drugs for anti rejection treatment, prone to hepatitis E virus infection and at the risk of liver fibrosis and cirrhosis due to immunosuppression status. Therefore, special attention should be paid to liver transplant recipients in clinical practice. Meantime, related risk factors should be identified to assist diagnosis and take stricter preventive measures. According to literature review, the etiological characteristics of hepatitis E virus and the epidemiological characteristics, clinical manifestations, diagnosis and treatment of hepatitis E virus infection in liver transplant recipients were reviewed, aiming to properly monitor, treat and prevent hepatitis E virus infection in liver transplant recipients in clinical practice, improving the prognosis of liver transplant recipients.

14.
Article de Chinois | WPRIM | ID: wpr-1017006

RÉSUMÉ

Objective Studies on the expression and location of zinc finger protein A20 (A20) and connective tissue growth factor (CTGF) in liver tissues of patients with chronic hepatitis B were conducted, and the relationship between them and liver fibrosis was determined by FibroScan. Methods Studies on A20 and CTGF in liver tissues of 160 patients with chronic hepatitis B were conducted in accordance with the stage of pathological fibrosis and inflammation of the liver, and quantitative immunohistochemistry test was conducted, and statistical analysis was conducted by FibroScan. Results The expressions of A20 and CTGF in liver tissues increased with the aggravation of liver pathological fibrosis and inflammation, and there were significant differences between each stage and the control group (P0.05). There was positive correlation between liver A20 and CTGF, r=0.796 (P<0.05). Conclusions In patients with chronic hepatitis B, A20, CTGF and FibroScan are positively correlated with the degree of liver fibrosis, and A20 and CTGF are also positively correlated with the degree of liver inflammation, which can be used as indicators to evaluate the degree of liver inflammation and fibrosis, and further guide the anti-inflammatory and anti-fibrosis treatment of patients.

15.
Article de Chinois | WPRIM | ID: wpr-1017234

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Objective To investigate the application value of quantitative parameters MRFDGmax and SUVmax in the stages of hepatitis,liver fibrosis and cirrhosis in rats by whole-body dynamic 18 F-FDG PET/CT Patlak imaging.Methods Twenty-four SD rats were randomly divided into four groups of six rats each,which were the normal group,hepatitis group,liver fibrosis group and cirrhosis group.According to the experimental grouping,rats in each group were induced by the CC14 oil solution complex method.Whole-body dynamic 18 F-FDG PET/CT patlak imaging was performed on each group of rats separately at the completion of induction.After the imaging was com-pleted,the MRFDGmax,SUVmax and CT values of the livers of each group were analyzed;subsequently,the serum of rats in each group was extracted for the detection of liver function indexes(AST,ALT and ALP),and HE staining was performed on the livers of rats in the normal,hepatitis and cirrhosis groups,and Masson staining was performed on those in the liver fibrosis group;the α-SMA expression in the liver tissues of each group was analyzed by immu-nohistochemical method.The data were analyzed by one-way ANOVA,two independent samples t-test and Pearson correlation analysis.Results MRFDGmax,SUVmax values were statistically significant differences among normal,hep-atitis,liver fibrosis and cirrhosis groups(F=84.54,38.35,P<0.001).The difference in CT values between liver fibrosis and cirrhosis groups was not statistically significant(t=-0.407,P=0.693),and the difference was statistically significant when compared between the rest of the groups(F=112.25,P<0.001).Compared with the normal group,AST,ALT and ALP of the experimental group showed a staged increase,and the differences were statistically significant(F=93.32,64.63,145.03,P<0.001).HE staining showed that hepatocytes of the normal group were neatly arranged and structurally intact;a large number of inflammatory cells infiltrated the hepa-titis group with steatosis;pseudo lobe formation was observed in the cirrhosis group.Masson staining of the liver fi-brosis group showed collagen fiber proliferation and thickening of the peritoneum.Immunohistochemistry test results showed that α-SMA expression increased in hepatitis group,liver fibrosis group and cirrhosis group,with a staged increase,and the difference was statistically significant(F=80.57,P<0.001).Correlation analysis showed a positive correlation between SUVmax and MRFDGmax(r=0.967,P<0.01).α-SMA was positively correlated with AST,ALT and ALP in the hepatitis,liver fibrosis and cirrhosis groups,respectively(r=0.924,0.756,0.934,P<0.01).Conclusion Whole-body dynamic 18F-FDG PET/CT Patlak imaging has application value in monitoring hepatitis,liver fibrosis and cirrhosis stages through quantitative parameters MRFDGmax and SUVmax changes.

16.
Article de Chinois | WPRIM | ID: wpr-1014533

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Liver fibrosis is pathological in most chronic liver diseases. Exosomes secreted by mesenchymal stem cells (MSCs) can regulate liver fibrosis through mechanisms such as inhibition of inflammatory response and proliferation of activated hepatic stellate cells, regulation of immune cells and metabolism. Therefore, MSC-derived exosomes can be used as a cell-free therapy for chronic liver disease, expanding new ideas for the treatment of chronic liver disease. Recent researches on MSC-derived exosomes in the treatment of liver fibrosis are reviewed in this article.

17.
Acta Anatomica Sinica ; (6): 55-61, 2024.
Article de Chinois | WPRIM | ID: wpr-1015142

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Objective To investigate the relationship between nuclear factor(NF)-κB signaling pathway and gender differences in alcoholic liver fibrosis. Methods C57BL/6 N mice at 7-8 weeks of age were randomly divided into: male normal group, male model group, female normal group and female model group of 20 mice each. The normal group was fed with control liquid diet for 8 weeks, and the model group was fed with alcoholic liquid diet for 8 weeks combined with 31.5% ethanol gavage (5g/kg twice a week) to establish an alcoholic liver fibrosis model. The mice were executed at the end of 8 weekends, and the alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity, estradiol (E

18.
Article de Chinois | WPRIM | ID: wpr-1003404

RÉSUMÉ

ObjectiveTo explore the mechanism and pathway of Gandou Fumu decoction (GDFMD) in the development of liver fibrosis in Wilson's disease (WD). MethodFirst, 30 TX-j mice were randomly divided into the model group, high-dose, medium-dose, and low-dose GDFMD groups, and penicillamine group, with six mice in each group, and another six wild-type mice were used as the normal group. The high-dose, medium-dose, and low-dose GDFMD groups were intragastrically administered drugs of 13.92, 6.96, 3.48 g·kg-1. In the penicillamine group, 0.1 g·kg-1 of penicillamine was given by intragastric administration. The model group and the normal group were given equal volume of normal saline, once a day, for four consecutive weeks. Samples were collected four weeks after gavage, and enzyme-linked immunosorbent assay (ELISA) was used to detect type Ⅲ procollagen peptide (PCⅢ), collagen type Ⅳ (Col Ⅳ), hyaluronic acid (HA), and laminin (LN). Hematoxylin-eosin (HE), Masson, and picric acid-Sirus red collagen (Sirus Red) staining were used to observe the histopathological changes of liver fibrosis. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), immunohistochemistry, and Western blot were used to observe the expressions of α-smooth muscle actin (α-SMA) and collagen type Ⅰ (Col Ⅰ), which were related to the activation of hepatic stellate cells (HSCs). The expression of miR-29b-3p was observed by Real-time PCR. The expression of Unc-51-like kinase 1 (ULK1) and its downstream-related factors were observed by Western blot. The downstream genes of miR-29b-3p were verified by the dual luciferase reporter gene detection method. ResultCompared with the normal group, the four items of liver fibrosis (PCⅢ, Col Ⅳ, HA, and LN) in the model group were significantly abnormal (P<0.01), and the pathology was significantly abnormal. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ, as well as α-SMA mRNA and Col Ⅰ mRNA was up-regulated (P<0.05, P<0.01), and miR-29b-3p expression was down-regulated (P<0.01). ULK1, p-ULK1, autophagy-related gene 13 (Atg13), p-Atg13, Beclin-1, FAK family kinase-interacting protein of 200 kDa (FIP200), activating molecule in BECN1-regulated autophagy protein 1 (AMBKA1), and microtubule-associated protein 1 light chain 3Ⅱ/Ⅰ(LC3Ⅱ/Ⅰ) were up-regulated (P<0.05, P<0.01). p62 protein expression was down-regulated (P<0.01). Compared with the model group, the four items of liver fibrosis in the high-dose, medium-dose, and low-dose GDFMD groups and the penicillamine group were significantly improve (P<0.01), and the pathological conditions were improved. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ, as well as α-SMA mRNA and Col Ⅰ mRNA was down-regulated (P<0.05, P<0.01), and the expression of miR-29b-3p was up-regulated (P<0.01). ULK1, p-ULK1, Atg13, p-Atg13, Beclin-1, FIP200, AMBKA1, and LC3Ⅱ/Ⅰ were down-regulated (P<0.05, P<0.01), and p62 protein expression was up-regulated (P<0.01). The prediction software predicted that there was a binding site between miR-29b-3p and ULK1. The dual-luciferase reporter gene detection method indicated that the luciferase activity of the ULK1-WT plasmid-transfected cell group was reduced when miR-29b-3p mimics were co-cultured (P<0.01). ConclusionGDFMD can regulate ULK1-mediated autophagy by up-regulating miR-29b-3p and further exert its anti-hepatic fibrosis effect in Wilson's disease.

19.
Chinese Journal of Biologicals ; (12): 183-187, 2024.
Article de Chinois | WPRIM | ID: wpr-1006856

RÉSUMÉ

@#Objective To investigate the effect of glutaminase 1(GLS1)specific inhibitor BPTES[bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide]on the liver fibrosis in the mouse model of liver fibrosis induced by carbon tetrachloride(CCl4).Methods Male C57BL/6J mice were intraperitoneally injected with olive oil(control group),10%CCl4(10 μL/g,model group)or 10% CCl4(10 μL/g)+ BPTES(10 mg/kg,treatment group),with 10 mice in each group,two doses a week for four weeks to establish liver fibrosis model. Collagen deposition in mouse liver tissue was observed by Sirius red staining. The expression levels of actin alpha 2(Acta2),collagen typeⅠalpha 1(Col1a1)GLS1 and GLS1 protein were detected by qRT-PCR and immunohistochemical staining.Results Compared with the control group,the liver tissue of mice in the model group was generally enlarged,the surface was not smooth and granular,and the ratio of liver mass to tibia length significantly increased(t = 2. 979,P < 0. 05);The Sirius red positive area of collagen deposition increased signifi-cantly in the liver tissue of mice in the model group(t = 7. 661,P < 0. 01),the relative expression levels of Acta2 and Col1a1 significantly increased(t = 4. 335 and 5. 319,respectively,each P < 0. 01),and the mRNA and protein levels of GLS1 significantly increased(t = 5. 319 and 9. 725,respectively,each P < 0. 01). However,compared with the model group,the BPTES treatment group had a reduction in liver mass,a significant reduction in the Sirius red positive area of collagen deposition in liver tissue(t = 7. 427,P < 0. 01),and a significant reduction in the relative expressions of Atca2 and Col1a1(t = 3. 713 and 2. 628,respectively,each P < 0. 05).Conclusion Inhibition of GLS1activity can significantly improve the degree of liver fibrosis induced by CCl4,providing a new idea for the treatment of liver fibrosis.

20.
Chinese Herbal Medicines ; (4): 82-93, 2024.
Article de Anglais | WPRIM | ID: wpr-1010743

RÉSUMÉ

OBJECTIVE@#Hepatic fibrosis has been widely considered as a conjoint consequence of almost all chronic liver diseases. Chuanxiong Rhizoma (Chuanxiong in Chinese, CX) is a traditional Chinese herbal product to prevent cerebrovascular, gynecologic and hepatic diseases. Our previous study found that CX extracts significantly reduced collagen contraction force of hepatic stellate cells (HSCs). Here, this study aimed to compare the protection of different CX extracts on bile duct ligation (BDL)-induced liver fibrosis and investigate plausible underlying mechanisms.@*METHODS@#The active compounds of CX extracts were identified by high performance liquid chromatography (HPLC). Network pharmacology was used to determine potential targets of CX against hepatic fibrosis. Bile duct hyperplasia and liver fibrosis were evaluated by serologic testing and histopathological evaluation. The expression of targets of interest was determined by quantitative real-time PCR (qPCR) and Western blot.@*RESULTS@#Different CX extracts were identified by tetramethylpyrazine, ferulic acid and senkyunolide A. Based on the network pharmacological analysis, 42 overlap targets were obtained via merging the candidates targets of CX and liver fibrosis. Different aqueous, alkaloid and phthalide extracts of CX (CXAE, CXAL and CXPHL) significantly inhibited diffuse severe bile duct hyperplasia and thus suppressed hepatic fibrosis by decreasing CCCTC binding factor (CTCF)-c-MYC-long non-coding RNA H19 (H19) pathway in the BDL-induced mouse model. Meanwhile, CX extracts, especially CXAL and CXPHL also suppressed CTCF-c-MYC-H19 pathway and inhibited ductular reaction in cholangiocytes stimulated with taurocholate acid (TCA), lithocholic acid (LCA) and transforming growth factor beta (TGF-β), as illustrated by decreased bile duct proliferation markers.@*CONCLUSION@#Our data supported that different CX extracts, especially CXAL and CXPHL significantly alleviated hepatic fibrosis and bile duct hyperplasia via inhibiting CTCF-c-MYC-H19 pathway, providing novel insights into the anti-fibrotic mechanism of CX.

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