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1.
Bioengineered ; 12(1): 310-324, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33446013

RESUMO

In clinical practice, we found that microRNA (miR)-146a-5p is significantly up-regulated in peripheral blood mononuclear cells (PBMCs) of primary sjögren's syndrome (pSS) patients. In vitro experiments confirmed that miR-146a-5p promotes T helper 17 (Th17) cell differentiation, but the specific mechanism is still unknown. To solve this problem, 20 pSS patients and 20 healthy subjects were enrolled in this study and PBMCs were isolated from their blood. The expression of the membrane IL-23 R (mIL-23 R) in PBMCs was determined. CD3+ T cells were also isolated and used to further analyze the relationship between the ectodomain shedding of mIL-23 R and a disintegrin and metalloprotease 17 (ADAM17). Finally, miR-146a-5p inhibitor and mimics were transfected into PBMCs to evaluate the relationship between ADAM17 and mIL-23 R, and explore the role of mIL-23 R and ADAM17 in Th17 cell differentiation. Our results revealed a significantly increased expression of miR-146a-5p in PBMCs from pSS patients and significantly increased percentage of Th17 cells compared to PBMCs from healthy controls. Under polarization culture conditions, pSS patient-derived PBMCs can more easily differentiate into Th17 cells, which was, to a great extent, attributable to the increased expression of mIL-23 R. Moreover, ADAM17, an ectodomain sheddase of mIL-23 R, was targeted and negatively regulated by miR-146a-5p, which reduced the ectodomain shedding of mIL-23 R. Overall, our results suggested that miR-146a-5p could promote Th17 cell differentiation through targeting and negatively regulating ADAM17. Thus, these results might offer a new approach in the treatment of pSS.

2.
Exp Ther Med ; 17(3): 1817-1824, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30783454

RESUMO

Previous studies using microRNA (miRNA or miR) microarrays have demonstrated that miR-1273g-3p is upregulated in patients with hepatitis C virus (HCV)-associated fibrosis. As miRNAs have been suggested to be promising non-invasive biomarkers, the aim of the present study was to assess whether miR-1273g-3p may be useful as a potential indicator of fibrosis progression in patients with HCV. Liver biopsies were performed on 112 patients with chronic hepatitis C (CHC) and liver stiffness measurements (LSM) were performed using FibroTouch. Liver fibrosis was determined based on Meta-analysis of Histological Data in Viral Hepatitis classification, and the aspartate aminotransferase (AST)-to-platelet count (PLT) ratio index (APRI) and Fibrosis-4 score (FIB-4) were calculated. The diagnostic performance of miR-1273g-3p, LSM, APRI and FIB-4 in predicting fibrosis stage were evaluated and compared by receiver operating characteristic (ROC) analysis. It was demonstrated that miR-1273g-3p levels were significantly positively correlated with the liver fibrosis stage (r=0.657, P<0.001). The results of LSM, APRI and FIB-4, the three non-invasive diagnostic methods, had good consistency with liver biopsy results, and their correlation coefficients with fibrosis staging were 0.815, 0.417 and 0.522, respectively. The areas under the ROC curves of miR-1273g-3p for F≥2 and F=4 stage samples were 0.841 and 0.933, respectively, which were lower than LSM (0.890 and 0.937), and higher than FIB-4 (0.791 and 0.766) and APRI (0.719 and 0.760). Spearman analysis demonstrated that serum miR-1273g-3p levels were significantly positively correlated with age, body mass index, alanine aminotransferase, AST and total bilirubin (all P<0.05), and negatively correlated with PLT (P<0.05). However, no significant correlation was observed between miR-1273g-3p levels, baseline HCV RNA loads and genotype. Therefore, the results demonstrated that miR-1273g-3p levels, as a novel non-invasive test, may be a useful and easy method for predicting the stage of liver fibrosis in patients with CHC, and has a better diagnostic performance than FIB-4 and APRI. Further prospective studies are required to validate the efficacy of miR-1273g-3p as a predictor of liver fibrosis.

3.
Cell Death Dis ; 8(5): e2792, 2017 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-28518142

RESUMO

Nonalcoholic fibrosing steatohepatitis is a uniform process that occurs throughout nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) have been shown to be involved in the biological processes, but the role and molecular mechanism of miRNAs in NAFLD are not entirely clear. In this study, we observed a significant reduction in the expression of miR-130a-3p in livers of a mouse model with fibrosis induced by a methionine-choline-deficient diet, of NAFLD patients, and in activated hepatic stellate cells (HSCs). A dual-luciferase activity assay confirmed that transforming growth factor-beta receptors (TGFBRs) 1 and 2 were both the target genes of miR-130a-3p. The hepatic expression of TGFBR1 and TGFBR2 was significantly increased. Moreover, the overexpression of miR-130a-3p in HSCs inhibited HSC activation and proliferation, concomitant with the decreased expression of TGFBR1, TGFBR2, Smad2, Smad3, matrix metalloproteinase-2 (MMP-2), MMP-9, type I collagen (Col-1), and Col-4. In addition, the overexpression of miR-130a-3p promoted HSC apoptosis by inducing the expression of caspase-dependent apoptosis genes. Transfection with si-TGFBR1 and si-TGFBR2 revealed effects on HSC function that were consistent with those of miR-130a-3p. TGFBR1 and TGFBR2 rescued the miR-130a-3p-mediated reductions in the mRNA and protein expression levels of Smad2, Smad3, Col-1, and Col-4. In conclusion, our findings suggest that miR-130a-3p might play a critical role in negatively regulating HSC activation and proliferation in the progression of nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1 and TGFBR2 via the TGF-ß/SMAD signaling pathway.


Assuntos
Apoptose , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Regiões 3' não Traduzidas/genética , Adulto , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colágeno/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/genética , Feminino , Técnicas de Silenciamento de Genes , Ontologia Genética , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptor do Fator de Crescimento Transformador beta Tipo II , Reprodutibilidade dos Testes , Fator de Crescimento Transformador beta/farmacologia
5.
Discov Med ; 22(119): 29-42, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27585228

RESUMO

Long non-coding RNA (LncRNA)-activated by transforming growth factor-beta (LncRNA-ATB) is a key regulator of transforming growth factor-beta (TGF-ß) signaling pathway, and is positively correlated with the development of liver cirrhosis and vascular invasion of hepatocellular carcinoma (HCC). However, the role of LncRNA-ATB in hepatitis C virus (HCV)-related liver fibrosis remains largely unknown. In the present study, we confirmed a high expression level of LncRNA-ATB in the liver tissues and plasma samples of patients with HCV-related hepatic fibrosis, and the plasma level of LncRNA-ATB was significantly correlated with liver fibrosis stages. Furthermore, increased expression level of LncRNA-ATB was also present in activated hepatic stellate cells (HSCs), and knockdown of LncRNA-ATB inhibited the expression of alpha-smooth muscle actin (α-SMA) and alpha-1 type I collagen (Col1A1). LncRNA-ATB was found to share the common miRNA responsive element of miR-425-5p with TGF-ß type II receptor (TGF-ßRII) and SMAD2. Ectopic expression of LncRNA-ATB in HSCs could upregulate the protein expression of TGF-ßRII and SMAD2 by inhibiting the endogenous miR-425-5p. Moreover, overexpression of miR-425-5p could partly abrogate the expression of TGF-ßRII and SMAD2 induced by LncRNA-ATB. Hence, we conclude that LncRNA-ATB promotes HCV-induced liver fibrogenesis by activating HSCs and increasing collagen I production through competitively binding to miR-425-5p. LncRNA-ATB may be a novel diagnostic biomarker and a potential therapeutic target for HCV-related hepatic fibrosis.


Assuntos
Hepacivirus/patogenicidade , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , RNA Longo não Codificante/metabolismo , Adulto , Western Blotting , Linhagem Celular , Proliferação de Células/genética , Proliferação de Células/fisiologia , Feminino , Células HEK293 , Humanos , Imuno-Histoquímica , Hibridização In Situ , Cirrose Hepática/virologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase em Tempo Real
6.
Int J Mol Sci ; 17(7)2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27428948

RESUMO

Interleukin-23 (IL-23) and its downstream factor IL-17 are the key cytokines involved in immune and inflammatory response in chronic liver diseases. This study aimed to investigate the role and molecular mechanisms of the IL-23/Th17 axis in chronic hepatitis C virus (HCV) infection, and the efficacy of IL-23/Th17 modulation in response to anti-HCV therapy. Sixty-six HCV-infected patients and 20 healthy controls were enrolled. The patients received PegIFNa-2a and ribavirin therapy for at least 48 weeks. The plasma level of IL-23 and the number of IL-17A-, IFN-γ-, and IL-21-producing peripheral blood mononuclear cells (PBMCs) at baseline and 12, 24, and 48 weeks following treatment were determined. The mRNA level of Th17 immune-associated molecules in PBMCs was evaluated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) following treatment with IL-23 agonist or antagonist. Our data showed that, compared to healthy controls, HCV-infected patients had an increased plasma level of IL-23 and increased frequencies of IL-17A- and IFN-γ-producing PBMCs, whereas the HCV patients exhibited a reduced number of IL-21-producing PBMCs. However, the baseline frequencies of IL-21-producing PBMCs were markedly higher in HCV patients who achieved rapid virological response (RVR) than those without RVR. Additionally, the mRNA expressions of IL-21, IFN-γ, myxovirus resistance protein A (MxA), and suppressor of cytokine signaling 3 (SOCS3) were significantly upregulated in PBMCs, while FoxP3 expression was suppressed by IL-23 agonist. Thus, the IL-23/Th17 axis plays an important role in development of chronic HCV infection and antiviral response. IL-23 may enhance the antiviral activity of interferon-based therapy by modulating the expression of Th17 cells-associated molecules in HCV-infected patients.


Assuntos
Antivirais/farmacologia , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/farmacologia , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Polietilenoglicóis/farmacologia , Ribavirina/farmacologia , Adolescente , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Hepacivirus/fisiologia , Hepatite C Crônica/metabolismo , Hepatite C Crônica/patologia , Humanos , Interleucina-17/genética , Interleucina-23/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Recombinantes/farmacologia , Adulto Jovem
7.
FEBS Lett ; 590(16): 2709-24, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27423040

RESUMO

MicroRNA (miRNA) play a pivotal role in the development of liver fibrosis. However, the functions of miRNA in hepatitis C virus (HCV)-related liver fibrosis remain unclear. In this study, we systematically analyzed the microarray data of the serum miRNA in patients with HCV-induced hepatic fibrosis. Among 41 dysregulated miRNA, miR-1273g-3p was the most significantly upregulated miRNA and correlated with the stage of liver fibrosis. Overexpression of miR-1273g-3p could inhibit translation of PTEN, increase the expression of α-SMA, Col1A1, and reduce apoptosis in HSCs. Hence, we conclude that miR-1273g-3p might affect the activation and apoptosis of HSCs by directly targeting PTEN in HCV-related liver fibrosis.


Assuntos
Apoptose/genética , Cirrose Hepática/genética , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Actinas/metabolismo , Proliferação de Células/genética , Colágeno Tipo I/metabolismo , Hepacivirus/metabolismo , Hepacivirus/patogenicidade , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/virologia , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática/virologia , MicroRNAs/biossíntese , PTEN Fosfo-Hidrolase/metabolismo
8.
J Int Med Res ; 44(4): 806-16, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27329385

RESUMO

OBJECTIVE: To investigate the regulation mechanism of T cell immunoglobulin and mucin domain-3 (Tim-3) combined with toll-like receptor 3 (TLR3) or TLR4 on antiviral immune and inflammatory response in patients with chronic hepatitis C virus (HCV) infection. METHODS: Patients with chronic HCV infection and healthy control subjects were recruited. Patients received interferon (IFN)-α based therapy. Plasma galectin-9 (Gal-9) was quantitated. Peripheral blood mononuclear cells (PBMCs) were cultured with TLR3 or TLR4 agonists, alone or in combination with Tim-3 antagonist. Levels of IFN-α, TNF-α, and 2'-5' oligoadenylate synthetase (2'-5'OAS), myxovirus resistance protein A (MxA) and suppressor of cytokine 1 (SOCS1) RNA in PBMC cultures were evaluated. RESULTS: Plasma Gal-9 levels were increased in patients (n = 52) compared with controls (n = 20) and significantly declined at treatment week 12 and 24 weeks post-treatment. IFN-α, 2'-5'OAS, MxA, TNF-α and SOCS1 were upregulated by TLR3 and TLR4 agonists. TNF-α and SOCS1 levels were suppressed by the addition of Tim-3 antagonist. CONCLUSIONS: Tim-3 blockade in combination with TLR activation induces the expression of antiviral molecules without a significant increase in TNF-α or SOCS1.


Assuntos
Antivirais/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Hepatite C Crônica/imunologia , Receptor 3 Toll-Like/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Demografia , Feminino , Galectinas/sangue , Hepatite C Crônica/sangue , Humanos , Imunidade , Fatores Imunológicos/sangue , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Mol Med Rep ; 13(3): 2159-66, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26781175

RESUMO

Activation of the innate immune system is involved in the development of chronic liver diseases, including nonalcoholic steatohepatitis. Toll­like receptor 4 (TLR4) is one of the sensors of the innate immune system. The aim of the present study was to elucidate the role of the TLR4­dependent signaling pathway, and examine the effect of pioglitazone on hepatic fibrosis, through modulation of the TLR4 pathway in a mouse model of nutritional fibrotic steatohepatitis. Male C57BL/6J mice were fed a methionine­choline deficient (MCD) diet for 8 weeks to induce nonalcoholic fibrotic steatohepatitis. The PPARγ agonist, pioglitazone, and PPARγ inhibitor, GW9662, were administered to the mice, respectively. The effects of the induction of PPARγ on liver biochemistry and histology, the modulation of TLR4 and its downstream pathway, and the expression levels of inflammatory and fibrogenic genes were assessed using reverse transcription­quantitative polymerase chain reaction and Western blot analyses. The MCD­fed mice exhibited progressive hepatic steatosis, necrotic inflammation and fibrosis, along with increase levels of serum alanine aminotransferase and aspartate aminotransferase, accompanied by the upregulation of TLR4, the TLR4­myeloid differentiation primary response gene 88­dependent pathway and downstream genes, and proinflammatory and profibrotic genes; and downregulation of basic membrane protein and activin membrane­bound inhibitor. The administration of pioglitazone was found to reverse hepatic nutritional fibrosis via restoration of the expression levels of proinflammatory and profibrotic genes in the MCD­fed mice. The results of the present study provide novel evidence supporting the protective role of pioglitazone in ameliorating nutritional fibrotic steatohepatitis, through modulation of the TLR4­mediated signaling pathway.


Assuntos
Colina/administração & dosagem , Cirrose Hepática/tratamento farmacológico , Metionina/deficiência , Substâncias Protetoras/uso terapêutico , Tiazolidinedionas/uso terapêutico , Receptor 4 Toll-Like/metabolismo , Animais , Quimiocinas/genética , Quimiocinas/metabolismo , Dieta , Regulação para Baixo/efeitos dos fármacos , Fibrose , Inflamação/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/genética , Masculino , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , PPAR gama/metabolismo , Pioglitazona , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Tiazolidinedionas/farmacologia , Receptor 4 Toll-Like/genética
10.
J Int Med Res ; 44(6): 1302-1313, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28322102

RESUMO

Objective To evaluate whether gamma-glutamyl transpeptidase to platelet ratio index (GPRI) can diagnose the extent of liver fibrosis in Chinese patients with chronic hepatitis B (CHB) infection. Methods This prospective observational study used liver biopsy results as the gold standard to evaluate the ability of GPRI to predict hepatic fibrosis compared with two other markers, the aspartate aminotransferase (AST) to platelet ratio index (APRI) and fibrosis-4 score (FIB-4). The clinical and demographic factors that affected GPRI, independent of liver fibrosis, were assessed using multivariate linear regression analyses. Results This study enrolled 312 patients with CHB. GPRI had a significantly positive correlation with liver fibrosis stage and the correlation coefficient was higher than that for APRI and FIB-4. The areas under the receiver operating curves for GPRI for significant fibrosis, bridging fibrosis, and cirrhosis were 0.728, 0.836, and 0.842, respectively. Of the three indices, GPRI had the highest diagnostic accuracy for bridging fibrosis and cirrhosis. Age, elevated AST and elevated total bilirubin levels were independent determinants of increased GPRI. Conclusion GPRI was a more reliable laboratory marker than APRI and FIB-4 for predicting the stage of liver fibrosis in Chinese patients with CHB.


Assuntos
Plaquetas/patologia , Hepatite B Crônica/diagnóstico , Cirrose Hepática/diagnóstico , Fígado/patologia , gama-Glutamiltransferase/sangue , Adolescente , Adulto , Idoso , Área Sob a Curva , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Plaquetas/metabolismo , Feminino , Vírus da Hepatite B/patogenicidade , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/sangue , Hepatite B Crônica/enzimologia , Hepatite B Crônica/patologia , Humanos , Fígado/enzimologia , Cirrose Hepática/sangue , Cirrose Hepática/enzimologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Contagem de Plaquetas , Estudos Prospectivos , Índice de Gravidade de Doença
11.
Int J Clin Exp Med ; 8(9): 14871-84, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26628969

RESUMO

Combination therapy comprising pegylated interferon-alpha (PegIFNα) and ribavirin (RBV) has been the standard of care for the chronic hepatitis C patients for more than a decade. Recently, direct antiviral agents show better efficacy, tolerance, and shorter treatment duration. However, the prohibitive costs of the regimens limit their use in developing countries where most of the HCV infection exists. Optimizing the treatment and understanding the host- and virus-factors associated with viral clearance were necessary for individualizing therapy to maximize sustained virologic response. To explore individualized antiviral strategies with PegIFNα-2a/IFNα-2b plus ribavirin for CHC patients, and to clarify predictive factors for virological response. A cohort of 314 patients were included in this open-label, prospective clinical trial, which received individualized doses of PegIFNα-2a or IFNα-2b combined with RBV according to body weight, disease status and complications, with the duration of 44 weeks after HCV RNA undetectable. All the IL-28B (rs8099917), IL-17A (rs8193036), IL-17B (rs2275913) and PD-1.1 SNPs were genotyped using the TaqMan system. The sustained virological response (SVR) in PegIFNα-2a group was significantly higher than that in IFNα-2b (85.8% vs 75.0%, P = 0.034), especially in HCV genotype 1 (84.0% vs 64.3%, P = 0.022). However, no significant differences were found in rapid virological response (RVR), complete early virological response (cEVR) and SVR between PegIFNα-2a and IFNα-2b according to different doses, respectively. The genotype frequency of IL-28B TT in patients with cEVR, SVR was higher than that in non-responsed patients (93.8% vs 78.1%, χ(2) = 7.827, P = 0.005; 95.9% vs 80.4%, χ(2) = 9.394, P = 0.002). No significant correlation between the genotype distribution of IL-17A, IL-17B and PD-1.1 with virological response. Individualized regimens of PegIFNα-2a/RBV and IFNα-2b/RBV could achieve satisfied virological response in Chinese HCV patients. The IL-28B (rs8099917) TT genotype is a clinical usefully marker for cEVR and SVR.

12.
Sci Rep ; 5: 16163, 2015 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-26537990

RESUMO

Nonalcoholic fibrosing steatohepatitis is a uniform process throughout nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) have been suggested to modulate cellular processes in liver diseases. However, the functional role of miRNAs in nonalcoholic fibrosing steatohepatitis is largely unclear. In this study, we systematically analyzed the hepatic miRNAs by microarray analysis in nonalcoholic fibrosing steatohepatitis in C57BL/6J mice induced by methionine-choline deficient (MCD) diet. We identified 19 up-regulated and 18 down-regulated miRNAs in liver with fibrosis. Among these dysregulated miRNAs, miR-146a-5p was the most significant down-regulated miRNA. Luciferase activity assay confirmed that Wnt1 and Wnt5a were both the target genes of miR-146a-5p. Hepatic miR-146a-5p was down-regulated in fibrosing steatohepatitis, but its target genes Wnt1 and Wnt5a and their consequent effectors α-SMA and Col-1 were significantly up-regulated. In addition, miR-146a-5p was downregulated, whilst Wnt1 and Wnt5a were up-regulated in the activated primary hepatic stellate cells (HSCs) compared to the quiescent primary HSCs. Overexpression of miR-146a-5p in HSCs inhibited HSC activation and proliferation, which concomitant with the decreased expressions of Wnt1, Wnt5a, α-SMA and Col-1. In conclusion, miR-146a-5p suppresses activation and proliferation of HSCs in the progress of nonalcoholic fibrosing steatohepatitis through targeting Wnt1 and Wnt5a and consequent effectors α-SMA and Col-1.


Assuntos
Proliferação de Células/genética , Fibrose/genética , Células Estreladas do Fígado/metabolismo , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/genética , Proteínas Wnt/genética , Proteína Wnt1/genética , Animais , Regulação para Baixo/genética , Fibrose/metabolismo , Fígado/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ativação Transcricional/genética , Regulação para Cima/genética , Proteína Wnt-5a
13.
Zhonghua Gan Zang Bing Za Zhi ; 23(4): 265-9, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-26133817

RESUMO

OBJECTIVE: To explore the clinical application and related factors of FibroTouch in the diagnosis of liver fibrosis in patients with chronic liver disease through comparison of the specificity and sensitivity of FibroTouch and multi-parameter models, and to identify whether FibroTouch is a more accurate and safe method in diagnosis of liver fibrosis and evaluation of the therapeutic effect. METHODS: A total of 190 patients with chronic liver disease were performed liver biopsy and underwent liver stiffness measurement (LSM) using FibroTouch in department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University from January 2014 to February 2015. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were tested by enzymic method with automatic biochemistry analyzer. Blood platelet counts were detected by automatic blood cell analyzer. AST-to-PLT ratio index (APRI) and fibrosis index based on the 4 factor (FIB-4) were calculated. The diagnostic values of FibroTouch, APRI and FIB-4 for liver fibrosis degree were calculated and compared by receiver operating characteristic (ROC) curves. The related factors of LSM were analyzed by Spearman analysis. RESULTS: There was significant correlation between LSM and histological fibrosis (r=0.804, P=0.000). The area under ROC curve of LSM for S(≥2, S≥3 and S=4 was 0.894, 0.938 and 0.961, respectively, which was significantly higher than APRI (0.678, 0.698 and 0.658) and FIB-4 (0.765, 0.785 and 0.775). On Spearman analysis, LSM was positively correlated with age, ALT, AST, TBIL ((≥2×ULN) and the grade of liver inflammation (r=0.309, 0.558, 0.504, 0.492 and 0.532, respectively) but negatively with PLT (r=-0.444), (all P<0.05). CONCLUSIONS: LSM is a convenient and reliable approach for diagnosis of liver fibrosis in patients with chronic liver disease. The sensitivity and specificity of Fibrotouch in diagnosis of hepatic fibrosis is superior to APRI and FIB-4, and age, high level ofALT, AST and TBIL (≥2×ULN) were independent predictors of LSM inaccuracy.


Assuntos
Cirrose Hepática , Alanina Transaminase , Aspartato Aminotransferases , Bilirrubina , Biomarcadores , Biópsia , Doença Crônica , Humanos , Contagem de Plaquetas , Curva ROC
14.
Mol Med Rep ; 10(6): 3080-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25269746

RESUMO

Mounting evidence indicates that dysregulated microRNAs (miRNAs) are important in the etiology and pathogenesis of steatohepatitis. However, the functions of miRNAs in the pathophysiological process of non-alcoholic steatohepatitis (NASH) are poorly understood. In this study, C57BL/6J mice were fed a methionine-choline­deficient (MCD) diet for eight weeks in order to induce hepatic steatohepatitis. Using reverse transcription polymerase chain reaction, the hepatic expression levels of miR-199a-5p, miR-122 and miR-221 in the mice were examined. Bioinformatic analysis of dysregulated miR-199a-5p was performed to predict the potential role of miR­199a­5p in NASH. The MCD diet was found to significantly reduce miR-122 expression levels and significantly increase miR­199a-5p expression levels in mouse livers, compared with those of mice fed a control diet. In the bioinformatic analysis, miR­199a­5p was identified to be predominantly involved in transcription, protein serine/threonine kinase activity, insulin signaling, and the Wnt and mitogen­activated protein kinase signaling pathways. The regulation of nuclear receptor corepressor 1 (NCOR1) by miR­199a-5p was also examined by silencing and overexpressing this miRNA in LX-2 cells. The data revealed that NCOR1 protein levels were significantly reduced and enhanced by miR-199a-5p mimic and inhibitor, respectively. These findings suggest a key role for miR-199a-5p in the progression of NASH through inhibition of NCOR1 translation, and provide novel insights into NASH pathogenesis.


Assuntos
MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/genética , Correpressor 1 de Receptor Nuclear/genética , Biossíntese de Proteínas/genética , Regulação para Cima/genética , Animais , Proliferação de Células/genética , Biologia Computacional/métodos , Insulina/genética , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais/genética , Ativação Transcricional/genética , Via de Sinalização Wnt/genética
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