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PURPOSE: The Chronic Liver Disease Questionnaire (CLDQ)-Nonalcoholic Fatty Liver Disease (NAFLD) is a disease-specific instrument to assess the health-related quality of life (HRQL) of patients with NAFLD. In order to provide further evidence for the cross-cultural utility of this instrument in the Chinese population, we translated the CLDQ-NAFLD into Chinese and examined its reliability and validity. METHODS: Patients with NAFLD in 90 hospitals across China were enrolled in this multicenter cross-sectional survey. Eligible patients completed the Chinese version of CLDQ-NAFLD at enrollment to assess HRQL. Internal consistency of the questionnaire was assessed using Cronbach's alpha coefficient and split-half reliability. Convergent and discriminant validity were assessed using Spearman correlation coefficient. Factor analysis was used to test the construct validity. RESULTS: Between March and August 2019, 5181 patients with a mean age of 43.8 ± 13.3 years were enrolled. All domains exhibited good internal consistency, with Cronbach's alpha and split-half reliability greater than 0.70. The scaling success rate of all domains was 100% for convergent validity and 99.4% (179/180) for discriminant validity. The inter-scale correlations indicated a significant correlation between all CLDQ-NAFLD domains (r = 0.608 to 0.832, all p < 0.001). Factor analysis of 36 items extracted 6 factors, which explained 69.14% of the total variance. CONCLUSION: The Chinese version of CLDQ-NAFLD is a reliable and valid instrument for assessing the HRQL of Chinese patients with NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Adulto , Pessoa de Meia-Idade , Estudos Transversais , Qualidade de Vida/psicologia , Reprodutibilidade dos Testes , China , Inquéritos e Questionários , PsicometriaRESUMO
Puerarin, a bioactive flavone compound isolated from Pueraria (Wild.), provides hepatoprotection by anti-inflammatory, anti-alcoholism, and regulating mechanistic target of rapamycin (mTOR). Building evidence suggests that the activation of mTOR reduces liver injuries associated with alcohol consumption and metabolism. However, the poor water solubility, low bioavailability, and short half-life of puerarin hinder its clinical application. The utility of mesoporous silicon nanoparticles (MSNs) can improve traditional Chinese medicine limitations. Stober methods were used to fabricate MSNs@Pue, and the size, zeta potentials and drug encapsulation efficiency were characterized by a series of analytical methods. IVIS Imaging System demonstrated liver-targeted bio-distribution, and then high-throughput sequencing, immunoproteomics and ultrastructure methods indicated autophagy related protective mechanism, followed by curative effect evaluation for the treatment efficacy. An acute-on chronic ethanol-drinking according to Gao-binge model induced alcoholic hepatitis (AH) pathology and resulted in hepatic hyper-autophagy, which was improved with MSNs@Pue administration (puerarin: 30 mM, 42 mg/kg; intravenously [i.v.]). Ethanol-fed mice were found to have increased expression of autophagy-related proteins (Atg3, Atg7, LC3 and p62). In contrast, MSNs@Pue administration significantly decreased the expression of these proteins and alleviated fatty droplets infiltration in damaged liver. Furthermore, acute-on-chronic ethanol feeding also resulted in the activiation of ERK activation and mTOR expression, which were reversed with MSNs@Pue administration and better than the usage of puerarin alone. Results point to MSNs@Pue mediated ERK/mTOR signaling pathway activation as a possible protective strategy to improve AH, which provides a strategy and evidence for treating liver disease using an MSN delivery system.
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Hepatite Alcoólica , Nanopartículas , Camundongos , Animais , Silício , Hepatite Alcoólica/tratamento farmacológico , Nanopartículas/química , Autofagia , Serina-Treonina Quinases TOR , Etanol , Dióxido de Silício/químicaRESUMO
BACKGROUND: Health Related Quality of Life (HRQL) is a multi-dimensional construct that can comprehensively evaluate the patient's health status, including physical, emotional, mental and social well-being. In this study, we aimed to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on HRQL in a Chinese population. METHODS: In this national multicenter cross-sectional survey, patients with NAFLD were enrolled. Chronic Liver Disease Questionnaire (CLDQ)-NAFLD was used to qualify HRQL. Univariate and multivariate analysis were used to identify independent risk factors of HRQL. RESULTS: A total of 5181 patients with NAFLD from 90 centers were enrolled in this study (mean age, 43.8 ± 13.3 years; male, 65.8%). The overall CLDQ score was 5.66 ± 0.89. Multivariate logistic regression analysis showed that body mass index (BMI: HR, 1.642; 95% CI, 1.330-2.026), alanine transaminase (ALT: HR, 1.006; 95% CI, 1.001-1.011), triglyceride (HR, 1.184; 95% CI, 1.074-1.305), disease severity (HR, 3.203; 95% CI, 1.418-7.232) and cardiovascular disease (HR, 4.305; 95% CI, 2.074-8.939) were independent risk factors for overall CLDQ score. In the logistic analyses of individual domain, BMI and triglyceride were independent risk factors of all domains. ALT, disease severity, diabetes, depression and cardiovascular disease were influencing factors for the CLDQ score of several domains. CONCLUSIONS: This national multicenter cross-sectional survey in China indicated that the HRQL in patients with NAFLD was impaired. HRQL was found to be significantly associated with sociodemographic and clinical factors. Attention should be paid to the optimally managing care of patients with NAFLD to improve their HRQL.
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Povo Asiático/psicologia , Povo Asiático/estatística & dados numéricos , Nível de Saúde , Hepatopatia Gordurosa não Alcoólica/psicologia , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Inquéritos e Questionários/normas , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is becoming the leading cause of chronic liver disease worldwide. However, treatment of NAFLD is potentially influenced by psychological conditions. Using the simplified version of the University of Rhode Island Change Assessment (URICA-SV) scale, this study aimed to evaluate the stage of psychological change as a prerequisite to refining implementation strategies for psychological change. DESIGN: A multicentre cross-sectional survey. SETTING: Ninety hospitals in China. PARTICIPANTS: 5181 patients with NAFLD were included in this study. OUTCOME MEASURES: All patients completed the URICA-SV questionnaire and were assigned to one of the three stages of change (precontemplation, contemplation or action) according to their readiness scores. A stepwise multivariate logistic regression analysis was used to identify independent factors associated with the stage of psychological change. RESULTS: A total of 4832 (93.3%) patients were included in the precontemplation stage and only 349 (6.7%) considered making a change or preparing to make one. There were significant differences in gender (Cohen's d=0.039, p=0.005), age (Cohen's d=-0.327, p<0.001), waist circumference (Cohen's d=0.143, p=0.003), alanine transaminase (Cohen's d=0.347, p=0.001), triglyceride (Cohen's d=0.351, p=0.002), body mass index (BMI; Cohen's d=0.056, p<0.001), proportion of hyperlipidaemia (Cohen's d=0.068, p<0.001) and cardiovascular disease (Cohen's d=0.032, p=0.029), therapeutic regimen (Cohen's d=0.136, p<0.001), and Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease overall score (Cohen's d=-0.420, p<0.001) between patients with NAFLD in the precontemplation stage and those in the contemplation/action stage. Logistic regression identified BMI (HR 0.659, 95% CI 0.469 to 0.928, p=0.017), cardiovascular disease (HR 2.161, 95% CI 1.089 to 4.287, p=0.027) and triglyceride (HR 0.751, 95% CI 0.591 to 0.955, p=0.020) as independent factors predicting psychological change. CONCLUSIONS: The results demonstrated that very few patients with NAFLD presented psychological condition in the stage of action. Psychological condition was found to be significantly related to BMI, cardiovascular disease and triglyceride factors. Integrated diversity considerations for evaluating psychological change are necessary.
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Doenças Cardiovasculares , Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/etiologia , Estudos Transversais , Doenças Cardiovasculares/complicações , Triglicerídeos , China/epidemiologiaRESUMO
OBJECTIVE: To investigate the effects of melatonin on cellular proliferation and endogenous vascular endothelial growth factor (VEGF) expression in pancreatic carcinoma cells (PANC-1). METHODS: PANC-1 cells were cultured for this study. The secreted VEGF concentration in the culture medium was determined using ELISA method, VEGF production in the tumor cells was detected by immunocytochemistry, and VEGF mRNA expression was determined by RT-PCR. RESULTS: Higher melatonin concentrations significantly inhibited cellular proliferation, with 1 mmol/L concentration exhibiting the highest inhibitory effect (P<0.01). VEGF concentrations in the cell culture supernatants and intra-cellules were all significantly reduced after melatonin (1 mmol/L) incubation (P<0.05). VEGF mRNA expression decreased markedly in a time-dependent manner during the observation period (P<0.05). CONCLUSIONS: High melatonin concentrations markedly inhibited the proliferation of pancreatic carcinoma cells. The endogenous VEGF expression was also suppressed by melatonin incubation.
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OBJECTIVE: To investigate the potential mechanism by which Shugan Huoxue Huayu Fang (SGHXHYF) ameliorates liver fibrosis. METHODS: Liver fibrosis was induced in rats by intraperitoneal injection of carbon tetrachloride (CCl4) in peanut oil solution (40%, 3 mL/kg body weight) twice a week for 8 weeks. A normal control group received the same volume of peanut oil alone. During weeks 5-8, the CCl4-injected rat groups were administered saline (vehicle control), colchicine (0.1 mg/mL, 1 mg/kg, positive control), or SGHXHYF (0.1 mg/mL; 0.3, 0.6 and 1.2 mg/kg) once daily by oral gavage. Rats were sacrificed 24 h after the last treatment. Blood samples were collected for measurement of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), collagen â and collagen â ¢ levels. Liver samples were analyzed by histopathological staining, Masson's staining of extracellular matrix proteins, and immune-ohistochemical staining of αsmooth muscle actin (α-SMA). TGF-ß1/Smad protein and mRNA levels were analyzed by Western blot and quantitative reverse transcription-polymerase chain reaction analysis, respectively. In vitro experiments were also performed using rat hepatic stellate cells (HSCs). RESULTS: Compared with the control animals, CCl4-exposed rats exhibited elevated serum levels of ALT, AST, ALP, collagen I, and collagen III; reduced serum levels of ALB; and increased collagen deposition and αSMA expression in liver sections, reflecting liver fibrosis. CCl4 also increased expression of TGF-ß1 and the activated (phosphorylated) forms of Smad2 and Smad3 but reduced expression of the negative regulator Smad7 in the liver. Notably, concomitant administration of SGHXHYF to CCl4-exposed rats was found to significantly reverse or abolish the pro-fibrotic effects of CCl4 in the liver and reduced serum transferase levels. Analysis of HSCs in vitro confirmed that, mechanistically, SGHXHYF inhibited activation of the TGF-ß1/Smad signaling pathway by downregulating phosphorylated Smad2 and Smad3 and upregulating Smad7 levels. CONCLUSION: SGHXHYF ameliorated CCl4-induced liver fibrosis by inhibiting the TGF-ß1/Smad signaling pathway. These findings suggest that SGHXHYF may have clinical utility for the treatment or prevention of liver fibrosis.
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Tetracloreto de Carbono , Fator de Crescimento Transformador beta1 , Animais , Tetracloreto de Carbono/efeitos adversos , Colágeno Tipo I/metabolismo , Humanos , Fígado , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , Óleo de Amendoim/metabolismo , Óleo de Amendoim/farmacologia , Óleo de Amendoim/uso terapêutico , Ratos , Transdução de Sinais , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
OBJECTIVE: To study the mechanism of how iron-regulatory protein (hepcidin) affect iron overload in alcoholic liver disease (ALD). METHODS: Thirty male wistar rats were randomly divided into 3 groups: Lieber-Decarli liquid without alcohol group (control group), Lieber-Decarli liquid with alcohol (alcohol group) and hepcidin intraperitoneally injected group (hepcidin group), each rat was fed for 6 weeks. The Serum concentration of Alanine Aminotransferase (ALT), Aspartate Amino Transferase (AST), Iron, Total Iron Binding capacity (TIBC), Ferritin, Malonyl Dialdehyde (MDA) and Hepcidin were determined. Hepatic tissue was examined by hematoxylin and eosin staining, prussian blue iron staining and immunohistochemistry staining. RESULTS: (1) Serum concentration of ALT in control group, alcohol group and hepcidin group were (25.2 ± 4.6) U/L, (37.9 ± 14.3) U/L and (40.9 ± 14.1) U/L (F = 4.907, P < 0.05), respectively. Serum AST among three groups were (32.3 ± 13.4) U/L, (55.0 ± 18.6) U/L and (48.3 ± 26.0) U/L (F = 3.742, P < 0.05), respectively. The secretions of ferritin were (224.72 ± 85.49) ng/ml, (345.59 ± 124.75) ng/ml and (339.47 ± 138.47) ng/ml (F = 3.539, P < 0.05). The serum concentrations of TIBC were (147.30 ± 31.98) µmol/L, (148.04 ± 58.74) µmol/L and (143.28 ± 37.38) µmol/L (F = 1.209, P > 0.05), respectively. The serum concentrations of iron were (55.64 ± 13.32) µmol/L, (60.37 ± 25.89) µmol/L and (49.77 ± 17.64) µmol/L (F = 0.651, P > 0.05), respectively. The serum concentration of MDA were (5.84 ± 2.17) nmol/ml, (6.51 ± 2.23) nmol/ml and (4.27 ± 2.68) nmol/ml (F = 2.782, P > 0.05), respectively. The serum concentration of Hepcidin were (155.96 ± 44.91)ng/ml, (124.11 ± 31.98) ng/ml and (114.96 ± 25.81) ng/ml (F = 3.839, P < 0.05), respectively. (2) Significant fat change observed in the liver of alcohol group. The positive granulations of iron staining were (0.8 ± 1.0), (1.2 ± 1.6) and (1.1 ± 1.1) (F = 0.254, P > 0.05), respectively. No differences found of liver iron express among the three groups. Intraperitoneal injection of hepcidin increased hepcidin expression in liver which was inhibited by alcohol (F = 4.139, P < 0.05). CONCLUSIONS: ALD rats with lower hepcidin expression in liver can result in iron metabolism disorder. Ectogenic hepcidin can protect liver against alcohol damage by inhibiting lipid peroxidation.
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Peptídeos Catiônicos Antimicrobianos/metabolismo , Hepatopatias Alcoólicas/metabolismo , Fígado/metabolismo , Alanina Transaminase/sangue , Animais , Hepcidinas , Proteínas Reguladoras de Ferro/metabolismo , Fígado/patologia , Hepatopatias Alcoólicas/patologia , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVE: To explore the stimulation of human hepatic stellate cells by Cytochrome P4502E1-mediated oxidative stress. METHODS: HepG2-line was transfected with human CYP2E1 plasmid (HepG2/CYP2E1) and empty plasmid (HepG2/PCI) respectively. The CYP2E1 expression was evaluated with RT-PCR and Western blot. MDA was measured in culture medium of HepG2 cell lines. LX2 was co-incubated with HepG2/CYP2E1, HepG2/PCI and HepG2 respectively. The level of hydroxyproline in culture medium was examined in 48 hours and the cells were lysated and total RNA and protein were extracted. COL-1 and MMP2 mRNA levels were detected by RT-PCR and analyzed semi-quantitatively. PICP proteins were measured by ELISA. Zymography was performed to investigate MMP2 enzymatic activities. RESULTS: (1) MDA from the HepG2 which (HepG2/CYP2E1)express human CYP2E1 (6.51+/-0.25) was significantly higher than that from the HepG2 which do not (HepG2/PCI) express human CYP2E1 (3.07+/-0.29) and HepG2 alone (2.57+/-0.29). (F=22.66, all P<0.01). (2) After co-incubated for 48 hours,the level of hydroxyproline in culture medium (35.24+/-3.52) excreted from CYP2E1/LX2 could significantly increase (F=58.89, P is less than 0.01). PICP protein (540.01+/-11.38) excreted from CYP2E1/LX2 was significantly increased (F=124.97, P<0.01). Zymography showed MMP2 gene expression and enzymatic activities of MMP2 had no difference among the groups (F=0.29, P>0.05) (F=0.33, P>0.05). CONCLUSIONS: CYP2E1 derived oxidative stress mediated stimulation of collagen I synthesis by hepatic stellate cells. Hydroxyproline excreted by LX2 was increased by CYP2E1. COL-1mRNA had no difference among the groups (F=0.73, P>0.05).
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Citocromo P-450 CYP2E1/metabolismo , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , Estresse Oxidativo , Colágeno Tipo I/biossíntese , Células Hep G2 , Humanos , Hidroxiprolina/metabolismo , Metaloproteinase 2 da Matriz/metabolismoRESUMO
OBJECTIVE: We aimed to investigate the involvement of the endocytosis of occludin, a key component of tight junction (TJ), in the ethanol-induced disassembly of TJ in a model of alcoholic steatohepatitis. METHODS: Wild-type mice were fed an ethanol-containing or isocaloric liquid diet for 8 weeks and then assessed for liver injury (histopathology and measurement of serum enzymes), gut permeability (in vivo lactulose/mannitol and ex vivo dye leakage assays), intestinal epithelium ultrastructure (transmission electron microscopy), and intestinal occludin localization (immunofluorescence microscopy). The human intestinal epithelial cell line Caco-2 was also analyzed in vitro for the effects of ethanol on the barrier function (transepithelial electrical resistance), occludin localization (immunofluorescence microscopy and Western blotting), and endocytosis pathways (double-labeling immunofluorescence microscopy with selective pathway inhibitors). RESULTS: The ethanol-fed mice developed steatohepatitis and displayed intestinal barrier dysfunction, the disruption of intestinal TJ, and enhanced intestinal endocytosis of occluding compared with the control mice. In the Caco-2 monolayers, ethanol treatment decreased transepithelial electrical resistance, disrupted TJ formation, and enhanced occludin endocytosis in a dose- and time-dependent manner. These deleterious events were reversed by pretreating the Caco-2 cells with a selective pharmacological inhibitor of macropinocytosis, but not with the inhibitors of clathrin or caveolin-mediated endocytic pathways. CONCLUSION: Chronic ethanol exposure may increase intestinal permeability by inducing the micropinocytosis of occludin, resulting in the disruption of intestinal TJ.
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Endocitose/fisiologia , Fígado Gorduroso Alcoólico/fisiopatologia , Mucosa Intestinal/fisiopatologia , Ocludina/fisiologia , Animais , Células CACO-2 , Modelos Animais de Doenças , Endocitose/efeitos dos fármacos , Etanol/farmacologia , Fígado Gorduroso Alcoólico/patologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/ultraestrutura , Camundongos Endogâmicos C57BL , Microscopia Eletrônica , Microscopia de Fluorescência , Ocludina/metabolismo , Permeabilidade , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/fisiologia , Junções Íntimas/ultraestruturaRESUMO
Hematopoietic stem cells (HSCs) and mesenchymal stem cell (MSCs) are two main subtypes of bone marrow stem cells. Extensive studies have been carried out to investigate the therapeutic potential of BMSCs in liver disease. A number of animal and human studies demonstrated that either HSCs or MSCs could be applied to therapeutic purposes in certain liver diseases. The diseased liver may recruit migratory stem cells, particularly from the bone marrow, to generate hepatocyte-like cells either by transdifferentiation or cell fusion. Transplantation of BMSCs has therapeutic effects of restoration of liver mass and function, alleviation of fibrosis and correction of inherited liver diseases. There are still controversial results over the potential effects of BMSCs on liver diseases, and some of the discrepancies are thought to be lied in the differences of experimental protocols, differences in individual research laboratory, and the uncertainties of the techniques employed. Several potential approaches for BMSCs delivery in liver diseases have been proposed in animal studies and human trials. BMSCs can be delivered via intraportal vein, systemic infusion, intraperitoneal, intrahepatic, intrasplenic. The optimal stem cells delivery should be easy to perform, less invasive and traumatic, minimum side effects, and with high cells survival rate. In this review, we focus on the up-to-date evidence of therapeutic effects of BMSCs on liver disease, the characteristics of various delivery approaches, and the considerations for future studies.
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Células-Tronco Adultas/transplante , Hepatopatias/terapia , Transplante de Células-Tronco/métodos , Adulto , Células-Tronco Adultas/patologia , Animais , Células da Medula Óssea/patologia , Transplante de Medula Óssea/métodos , Transdiferenciação Celular , Terapia Genética , Células-Tronco Hematopoéticas/patologia , Humanos , Células-Tronco Mesenquimais/patologia , Medicina RegenerativaRESUMO
OBJECTIVE: To assess the efficacy and safety of Moluodan () in treating dysplasia in chronic atrophic gastritis (CAG) patients. METHODS: This was a multi-centered, double-blind, randomized controlled trial. The total of 196 subjects were assigned to receive either Moluodan or folic acid in a 2:1 ratio by blocked randomization. Mucosa marking targeting biopsy (MTB) was used to insure the accuracy and consistency between baseline and after 6-month treatment. Primary outcomes were histological score, response rate of pathological lesions and dysplasia disappearance rate. Secondary endpoints included gastroscopic findings, clinical symptom and patient reported outcome (PRO) instrument. RESULTS: Dysplasia score decreased in Moluodan group (P =0.002), significance was found between groups (P =0.045). Dysplasia disappearance rates were 24.6% and 15.2% in Moluodan and folic acid groups respectively, no significant differences were found (P =0.127). The response rate of atrophy and intestinal metaplasia were 34.6% and 23.0% in Moluodan group, 24.3% and 13.6% in folic acid group. Moluodan could improve erythema (P =0.044), and bile reflux (P =0.059), no significance between groups. Moluodan was better than folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite (P <0.05), with symptom disappearance rates of 37% to 83%. CONCLUSIONS: Moluodan improved dysplasia score in histopathology, and erythema and bile reflux score in endoscopy, and superior to folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite. [ChiCTR-TRC-00000169].
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Medicamentos de Ervas Chinesas/uso terapêutico , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/patologia , Doença Crônica , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Gastrite Atrófica/microbiologia , Gastroscopia , Helicobacter pylori/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To discuss the effect of BRMS1 on the proliferation, migration and adhesion of mouse forestomach carcinoma. METHODS: The constructed pCMV-myc-BRMS1 recombinant plasmid and blank plasmid were transfected into mouse forestomach carcinoma. MTT method was employed to measure the activity of gastric cancer cell; the scratch assay and Transwell assay to measure the migration and invasion of gastric cancer cell; the adhesion assay to measure the adhesion of gastric cancer cell; while the Western blot assay to measure the expression of The NF-κB signal pathway, downstream matrix metalloproteinase (MMP)-2, MMP-9 and osteopontin and E-cadherin in the gastric cancer cell. Besides, the transplanted animal model of gastric cancer in mice was constructed to measure the size of tumor xenograft. RESULTS: Results of MTT assay showed that, compared with the empty vector control group, the activity of gastric cancer cell was not affected in the BRMS1 transfection group. The improved expression of BRMS1 could inhibit the adhesion, migration and invasion of gastric cancer cell (P < 0.01). Besides, compared with the empty vector control group, the phosphorylation of NF-κB p65 and IκBα was reduced in the BRMS1 transfection group, with the decreased expression of MMP-2, MMP-9 and osteopontin and the increased expression of E-cadherin (P < 0.01). Results of animal experiment also showed that the expression of BRMS1 did not affect the transplanted tumor. CONCLUSIONS: The expression of BRMS1 can significantly inhibit the adhesion, migration, invasion and metastasis of mouse forestomach carcinoma gastric cancer cell, which is related to The NF-κB signal pathway.
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AIM: To evaluate the role of the (13)C-methacetin breath test ((13)C-MBT) in the assessment of acute liver injury in a rat model. METHODS: Acute liver injury in rats was induced by a single intraperitoneal injection of D-galactosamine (D-GalN). Forty-eight male Sprague-Dawley rats were randomly assigned to a control group (n = 8) and five model groups (each n = 8), and acute liver injury was assessed at different time points (6, 12, 24, 48 and 72 h) after D-GalN injection. The (13)C-MBT, biochemical tests, 15-min retention rate of indocyanine green (ICGR15), and liver biopsy were performed and compared between the control and model groups. Correlations between parameters of the (13)C-MBT (Tmax, MVmax, CUM120 and DOBmax), biochemical tests, ICGR15 and liver necrosis score were also analyzed using Spearman's correlation analysis. RESULTS: Tmax, MVmax, CUM120 and DOBmax, as well as most of the traditional methods, correlated with the liver necrosis score (r = 0.493, P < 0.05; r = -0.731, P < 0.01; r = -0.618, P < 0.01; r = -0.592, P < 0.01, respectively). MVmax, CUM120 and DOBmax rapidly decreased and were lower than those in the controls as early as 6 h after D-GalN injection (3.84 ± 0.84 vs 5.06 ± 0.78, P < 0.01; 3.35 ± 0.72 vs 4.21 ± 1.44, P < 0.05; 52.3 ± 20.58 vs 75.1 ± 9.57, P < 0.05, respectively) and reached the lowest point 24 h after D-GalN injection. MVmax, CUM120 and DOBmax returned to normal levels 72 h after D-GalN injection and preceded most of the traditional methods, including liver biopsy. CONCLUSION: The (13)C-MBT is a sensitive tool for the timely detection of acute liver injury and early prediction of recovery in a rat model. Further clinical studies are warranted to validate its role in patients with acute liver injury.
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Testes Respiratórios/métodos , Dióxido de Carbono/metabolismo , Isótopos de Carbono , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Fígado/metabolismo , Oxifenônio , Doença Aguda , Animais , Biomarcadores/metabolismo , Biópsia , Isótopos de Carbono/farmacocinética , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Corantes Fluorescentes , Galactosamina , Verde de Indocianina , Fígado/patologia , Masculino , Oxifenônio/farmacocinética , Ratos Sprague-DawleyRESUMO
AIM: To evaluate the esophageal motility and abnormal acid and bile reflux incidence in cirrhotic patients without esophageal varices (EV). METHODS: Seventy-eight patients with liver cirrhosis without EV confirmed by upper gastroesophageal endoscopy and 30 healthy control volunteers were prospectively enrolled in this study. All the patients were evaluated using a modified protocol including Child-Pugh score, upper gastrointestinal endoscopy, esophageal manometry, simultaneous ambulatory 24-h esophageal pH and bilirubin monitoring. All the patients and volunteers accepted the manometric study. RESULTS: In the liver cirrhosis group, lower esophageal sphincter pressure (LESP, 15.32 ± 2.91 mmHg), peristaltic amplitude (PA, 61.41 ± 10.52 mmHg), peristaltic duration (PD, 5.32 ± 1.22 s), and peristaltic velocity (PV, 5.22 ± 1.11 cm/s) were all significantly abnormal in comparison with those in the control group (P < 0.05), and LESP was negatively correlated with Child-Pugh score. The incidence of reflux esophagitis (RE) and pathologic reflux was 37.18% and 55.13%, respectively (vs. control, P < 0.05). And the incidence of isolated abnormal acid reflux, bile reflux and mixed reflux was 12.82%, 14.10% and 28.21% in patients with liver cirrhosis without EV. CONCLUSION: Cirrhotic patients without EV presented esophageal motor disorders and mixed acid and bile reflux was the main pattern; the cirrhosis itself was an important causative factor.
Assuntos
Transtornos da Motilidade Esofágica/etiologia , Varizes Esofágicas e Gástricas/etiologia , Esôfago/fisiopatologia , Refluxo Gastroesofágico/etiologia , Cirrose Hepática/complicações , Adolescente , Adulto , Idoso , Bilirrubina/metabolismo , Transtornos da Motilidade Esofágica/fisiopatologia , Feminino , Refluxo Gastroesofágico/fisiopatologia , Humanos , Concentração de Íons de Hidrogênio , Masculino , Manometria , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Previous studies have confirmed that serum concentrations of actin-free Gc globulin (Af-Gc globulin) may provide prognostic information in patients withacute liver failure (ALF). However, until now the relation between plasma Af-Gc globulin levels and chronic or acute-on-chronic liver failure (CLF or ACLF) caused by HBV is unknown. METHODS: Plasma Af-Gc globulin in 56 patients with liver failure, in 23 patients with compensated liver cirrhosis (CR), and in 25 healthy controls were measured using enzyme-linked immunosorbent assay (ELISA). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), choline esterase (CHE), Albumin (ALB), total bilirubin (TBIL), palsma international normalized ratio of prothrombin time (INR), and platelet (PLT) were also detected. The Child-Pugh score was calculated for each patient on admission. RESULTS: Plasma Af-Gc globulin levels in CLF, ACLF and CR were significantly lower than that of healthy controls (P < 0.001, respectively). The median (range) Af-Gc globulin level at admission for the liver failure (CLF or ACLF) was significantly reduced compared with that of CR group (P ≤ 0.001); additionally, there was significant difference between CLF and ACLF patients (P < 0.001). In liver failure cohort, plasma Af-Gc globulin was significantly positive correlated with ALB, ALT, AST and CHE (P was 0.001, 0.001, 0.001, < 0.001, respectively). Meanwhile, there was significantly negative correlation between plasma Af-Gc globulin and Child-Pugh score (P = 0.02). The level of Af-Gc globulin in ascites or hydrothorax-infected liver failure patients were markedly lower than that of non-infected (P = 0.015), the levels of Af-Gc in encephalopathy presence were lower than in encephalopathy absence. No significant difference of Af-Gc was noted between non-survivors and survivors during the follow-up period in liver failure patients. CONCLUSIONS: Plasma Af-Gc globulin levels in liver failure patients are significantly reduced compared with compensated liver cirrhosis patients and healthy controls, however, it might not be used in the prognosis of liver failure.
RESUMO
Diphenyl dimethyl bicarboxylate (DDB) has been used in some countries as hepatoprotectant adjuvant in the treatment of liver diseases, such as chronic viral hepatitis, chemical or drug induced hepatic damage. Its early confirmed efficacy is to normalize elevated blood alanine aminotransferase (ALT) from different etiologies, however, it can rarely affect the rest hepatic enzymes. In addition, the lowering or normalization of ALT in most cases occurs during DDB treatment, withdrawal of DDB administration results in ALT re-elevated. Hence, for a long time, it has been only used as adjuvant of liver disease therapy. It is still controversial that whether DDB can be beneficial to liver histology. The normalization of ALT in hepatitis does not indicate therapeutic efficacy if without substantial liver histology improvement. In recent years, more studies showed that DDB might have new therapeutical potentials in liver diseases, it may have the effect of anti-viral, anti-malignancy. These new findings were mostly based on the in vitro or animal experiments, more basic studies and clinical trials are needed to ascertain these efficacies, prior to that stage, it is recommended to be cautious to apply DDB clinically for anti-virus and anti-malignancy purposes.