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1.
Oncol Lett ; 18(6): 6126-6142, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788087

RESUMO

The prognostic value and molecular mechanism of microRNA-100-5p (miR-100-5p) in hepatocellular carcinoma (HCC) are still unclear. To explore the prognostic value and the mechanism of miR-100-5p in HCC, the present study analyzed the results of 18 previous studies and bioinformatic datasets. The clinical significance of miR-100-5p and its targets in HCC were investigated using The Cancer Genome Atlas and the Gene Expression Omnibus, as well as relevant literature. In total, 12 online tools were used to predict the target genes of miR-100-5p. Bioinformatics analysis and Spearman correlation analysis were performed, and genomic alterations of the hub genes were evaluated. A meta-analysis with 1,258 samples revealed that miR-100-5p was significantly downregulated in HCC [standard mean difference (SMD), -0.94; 95% confidence interval (CI), -1.14 to -0.74; I2, 35.2%]. Lower miR-100-5p expression was associated with poorer clinical characteristics and a poorer prognosis for patients with HCC. Additionally, bioinformatics analysis revealed that the 'regulation of transcription', 'chromatin remodeling complex', 'transcription regulator activity', 'pathways in cancer' and 'heparan sulfate biosynthesis' were the most enriched terms. Furthermore, expression of histone deacetylase (HDAC)2, HDAC3, SHC-transforming protein 1 (SHC1), Ras-related protein Rac1 (RAC1) and E3 ubiquitin-protein ligase CBL (CBL) was negatively correlated with miR-100-5p expression. Among these, upregulated HDAC2 [hazard ratio (HR), 1.910; 95% CI, 1.309-2.787; P=0.0007], HDAC3 (HR, 1.474; 95% CI, 1.012-2.146; P=0.0435), SHC1 (HR, 1.52; 95% CI, 1.043-2.215; P=0.0281) and RAC1 (HR, 1.817; 95% CI, 1.248-2.645; P=0.0022) were associated with shorter survival. Alterations in HDAC2, SHC1, RAC1 and IGF1R were linked with a poorer outcome for HCC, and alternative splicing of SHC and RAC1 were significantly decreased and increased in HCC, respectively. In summary, the downregulation of miR-100-5p may be involved in the progression and prognosis of HCC. The upregulation of HDAC2, HDAC3, SHC1 and RAC1 may indicate a poorer survival rate for patients with HCC. Thus, miR-100-5p and these 4 potential target genes may provide novel therapeutic targets and prognostic predictors for patients with HCC.

2.
World J Gastroenterol ; 25(33): 4835-4849, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31543677

RESUMO

Liver fibrosis is the common pathological basis of all chronic liver diseases, and is the necessary stage for the progression of chronic liver disease to cirrhosis. As one of pathogenic factors, inflammation plays a predominant role in liver fibrosis via communication and interaction between inflammatory cells, cytokines, and the related signaling pathways. Damaged hepatocytes induce an increase in pro-inflammatory factors, thereby inducing the development of inflammation. In addition, it has been reported that inflammatory response related signaling pathway is the main signal transduction pathway for the development of liver fibrosis. The crosstalk regulatory network leads to hepatic stellate cell activation and proinflammatory cytokine production, which in turn initiate the fibrotic response. Compared with the past, the research on the pathogenesis of liver fibrosis has been greatly developed. However, the liver fibrosis mechanism is complex and many pathways involved need to be further studied. This review mainly focuses on the crosstalk regulatory network among inflammatory cells, cytokines, and the related signaling pathways in the pathogenesis of chronic inflammatory liver diseases. Moreover, we also summarize the recent studies on the mechanisms underlying liver fibrosis and clinical efforts on the targeted therapies against the fibrotic response.

3.
Biomed Pharmacother ; 117: 109110, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31252263

RESUMO

Resveratrol has been suggested to mediate liver fibrosis. The switch from classically M(LPS) to alternatively activated M(IL-4) macrophages shows to protect organs from fibrosis. However, the mechanisms remain unclear. The study aimed to investigate whether resveratrol inhibited liver fibrosis by delivering IL-10 to promote the macrophage polarization in vitro and in vivo. We observed that resveratrol improved CCL4-induced liver fibrosis, upregulated Kupffer cells, increased the expression of IL-10 and M(IL-4) marks including Mrc1, Mrc2, CD163 and Arg1, whereas it slightly suppressed the level of M(LPS) including iNOS, TNF-α and MCP1. In vitro, resveratrol promoted the M(LPS) switch to M(IL-4) macrophage and elevated the expression of CD206 and iNOS as well. Meanwhile, IL-10 increased in both M(IL-4) and M(LPS). We concluded that resveratrol relieved liver fibrosis by producing more IL-10 to promote the polarization of M(LPS) to M(IL-4)-like macrophages.


Assuntos
Interleucina-4/farmacologia , Lipopolissacarídeos/farmacologia , Cirrose Hepática/genética , Macrófagos/metabolismo , Resveratrol/farmacologia , Regulação para Cima/efeitos dos fármacos , Animais , Tetracloreto de Carbono , Polaridade Celular/efeitos dos fármacos , Inflamação/patologia , Interleucina-10/metabolismo , Macrófagos do Fígado/efeitos dos fármacos , Macrófagos do Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fenótipo , Células RAW 264.7
4.
Oncol Lett ; 16(4): 5389-5397, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30250609

RESUMO

T helper (Th)22 and Th17 cells are implicated in the pathogenesis of a number of types of cancer. However, the function of Th22 and Th17 cells in malignant ascites (MA) remains unknown. The present study aimed at examining the distribution, phenotypes, recruitment, and prognostic value of Th22 and Th17 cells in MA from patients with hepatocellular carcinoma (HCC). A total of 26 patients with HCC with MA and 15 healthy controls were included in the present study. The proportion of Th22 cells, Th17 cells, C-C motif chemokine receptor (CCR)4, CCR6 and CCR10 were examined using flow cytometry. Interleukin (IL-)22, IL-17, C-C motif chemokine ligand (CCL)20, CCL22 and CCL27 were investigated using ELISA. In addition, the chemoattractant activity of chemokines for Th22 and Th17 cells in vitro were examined via a chemotaxis assay. The results of the present study demonstrated that Th22 cells, Th17 cells, IL-22 and IL-17 were significantly increased in MA compared with the corresponding blood and peripheral blood from healthy controls. Additionally, Th22 cells expressed increased concentrations of CCR6, CCR4 and CCR10, and Th17 cells expressed increased concentrations of CCR4 and CCR6 in MA compared with the corresponding blood. The chemotaxis assay revealed that CCL20/CCR6, CCL22/CCR4 and CCL27/CCR10 were responsible for the recruitment of Th22 cells into MA, whereas CCL22/CCR4 was responsible for the recruitment of Th17 cells. Furthermore, the patients with an increased number of Th17 cells exhibited an increased survival time compared with patients with a limited number of Th17 cells. Th22 and Th17 cells serve an important function in the development of MA, and the accumulation of Th22 and Th17 cells in MA may be due to a local increase in proinflammatory cytokines and chemokines. Increased Th17 cell numbers in MA may indicate the improvement of patient survival.

5.
Medicine (Baltimore) ; 96(42): e8261, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29049217

RESUMO

BACKGROUND: Gene alterations are crucial to the molecular pathogenesis of pancreatic cancer. The present study was designed to identify the potential candidate genes in the pancreatic carcinogenesis. METHODS: Gene Expression Omnibus database (GEO) datasets of pancreatic cancer tissue were retrieval and the differentially expressed genes (DEGs) from individual microarray data were merged. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) networks, and gene coexpression analysis were performed. RESULTS: Three GEO datasets, including 74 pancreatic cancer samples and 55 controls samples were selected. A total of 2325 DEGs were identified, including 1383 upregulated and 942 downregulated genes. The GO terms for molecular functions, biological processes, and cellular component were protein binding, small molecule metabolic process, and integral to membrane, respectively. The most significant pathway in KEGG analysis was metabolic pathways. PPI network analysis indicated that the significant hub genes including cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1), mitogen-activated protein kinase 3 (MAPK3), and phospholipase C, gamma 1 (PLCG1). Gene coexpression network analysis identified 4 major modules, and the potassium channel tetramerization domain containing 10 (KCTD10), kin of IRRE like (KIRREL), dipeptidyl-peptidase 10 (DPP10), and unc-80 homolog (UNC80) were the hub gene of each modules, respectively. CONCLUSION: Our integrative analysis provides a comprehensive view of gene expression patterns associated with the pancreatic carcinogenesis.


Assuntos
Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pancreáticas/genética , Proteínas de Transporte/genética , Estudos de Casos e Controles , Citocromo P-450 CYP2E1/genética , Bases de Dados Genéticas , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Humanos , Proteínas de Membrana/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Fosfolipase C gama/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Mapas de Interação de Proteínas , Transdução de Sinais/genética
6.
Biomed Res Int ; 2017: 2831056, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28349057

RESUMO

Background. Both IL-9 and miR-200a are involved in the pathogenesis of cancers; however, the role of IL-9 in pancreatic cancer and the possible underlying mechanisms remain unknown. The aim of this study was to investigate the effect of IL-9 on pancreatic cancer cells and its interaction with miR-200a. Methods. Pancreatic cancer cells (PANC-1 and AsPC-1) were treated with IL-9 and the expression of miR-200a and ß-catenin in pancreatic cancer cells was measured. ß-Catenin was examined as a target gene of miR-200a in pancreatic cancer cells. The interaction between IL-9 and miR-200a in pancreatic cancer cells was determined by infecting miR-200a mimics prior to IL-9 treatment and then measuring miR-200a and ß-catenin expression. Results. IL-9 significantly promoted the proliferation, invasion, and migration of pancreatic cancer cells; however, the effect on pancreatic cancer cell apoptosis was insignificant. ß-Catenin was verified as a target gene of miR-200a in pancreatic cancer cells. Overexpression of miR-200a in pancreatic cancer cells significantly attenuated proliferation and metastasis and reduced ß-catenin expression. IL-9 treatment of pancreatic cancer cells decreased miR-200a expression and increased ß-catenin expression. The effect of miR-200a on pancreatic cancer cells decreased following IL-9 treatment. Conclusions. IL-9 promotes proliferation and metastasis in pancreatic cancer cells; this effect may partly involve regulation of the miR-200a/ß-catenin axis.


Assuntos
Interleucina-9/genética , Interleucina-9/metabolismo , MicroRNAs/biossíntese , Neoplasias Pancreáticas/genética , beta Catenina/biossíntese , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-9/administração & dosagem , MicroRNAs/genética , Neoplasias Pancreáticas/patologia , Transdução de Sinais , beta Catenina/genética
7.
Sci Rep ; 6: 36436, 2016 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-27819314

RESUMO

IL-22 ameliorates liver fibrosis by inhibiting hepatic stellate cells (HSC), and loss of miR-200a is associated with the development of liver fibrosis. The study aimed to investigate the interplay between IL-22 and miR-200a in regulating liver fibrosis in vivo and in vitro. We observed that IL-22 significantly reduced the proliferation of HSC and increased the expression of p-STAT3. ß-catenin was identified as a target gene of miR-200a by luciferase reporter assay, and upregulation of miR-200a significantly attenuated the proliferation of HSC and reduced ß-catenin expression. IL-22 treatment increased expression of miR-200a and decreased expression of ß-catenin in HSC. The expression of p-STAT3 and miR-200a was elevated while ß-catenin was decreased in fibrotic rat liver after IL-22 treatment. Expression levels of ß-catenin and p-STAT3 were inversely correlated in fibrotic rat liver and HSC. Upregulation of ß-catenin suppressed expression of p-STAT3 in HSC. We concluded that IL-22 inhibits HSC activation and ameliorates liver fibrosis through enhancing expression of miR-200a and reducing expression of ß-catenin, suggesting there may be a crosstalk between IL-22/STAT3 and ß-catenin pathway.


Assuntos
Proteínas do Domínio Armadillo/metabolismo , Interleucinas/uso terapêutico , Cirrose Hepática/prevenção & controle , MicroRNAs/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Actinas/análise , Animais , Antagomirs/metabolismo , Apoptose/efeitos dos fármacos , Proteínas do Domínio Armadillo/antagonistas & inibidores , Proteínas do Domínio Armadillo/genética , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/análise , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Interleucinas/farmacologia , Cirrose Hepática/patologia , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Alinhamento de Sequência , Fator de Crescimento Transformador beta1/farmacologia , Regulação para Cima/efeitos dos fármacos
8.
Sci Rep ; 6: 18694, 2016 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-26728971

RESUMO

T helper 9 (Th9) cells, a recently recognized Th cell subset, are involved in autoimmune diseases. We aimed to investigate the role of Th9/interleukin-9 (IL-9) in the pathogenesis of hepatic fibrosis. Th9 and Th17 cells were quantified in chronic hepatitis B (CHB) patients with hepatic fibrosis, HBV-associated liver cirrhosis (LC) patients and healthy controls (HC). The percentages of Th9 and Th17 cells, concentrations of IL-9 and IL-17, as well as expression of IL-17, TNF-α, IL-6, IL-4, IL-21, TGF-ß1 and IFN-γ were significantly increased in plasma of CHB and LC patients compared with those in HC. Splenic Th9 and Th17 cells, plasma concentrations and liver expression of IL-9 and IL-17A were significantly elevated in mice with hepatic fibrosis compared with controls. Neutralization of IL-9 in mice ameliorated hepatic fibrosis, attenuated the activation of hepatic stellate cells, reduced frequencies of Th9, Th17 and Th1 cells in spleen, and suppressed expression of IL-9, IL-17A, IFN-γ, TGF-ß1, IL-6, IL-4 and TNF-α in plasma and liver respectively. Our data suggest a deleterious role of Th9/IL-9 in increasing hepatic fibrosis and exacerbating disease endpoints, indicating that Th9/IL9 based immunotherapy may be a promising approach for treating hepatic fibrosis.


Assuntos
Interleucina-9/metabolismo , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Subpopulações de Linfócitos T , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Adolescente , Adulto , Idoso , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/farmacologia , Estudos de Casos e Controles , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/metabolismo , Humanos , Imunofenotipagem , Interleucina-17/antagonistas & inibidores , Interleucina-17/sangue , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucina-9/antagonistas & inibidores , Interleucina-9/sangue , Interleucina-9/genética , Cirrose Hepática/patologia , Contagem de Linfócitos , Masculino , Camundongos , Pessoa de Meia-Idade , RNA Mensageiro/genética , Baço/imunologia , Baço/metabolismo , Baço/patologia , Células Th17/imunologia , Células Th17/metabolismo , Adulto Jovem
9.
Medicine (Baltimore) ; 94(31): e1238, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26252284

RESUMO

CD44v6 is a cell adhesion molecule that plays an important role in the development and progression of esophageal cancer. However, the prognostic value and clinical significance of CD44v6 in esophageal cancer remains controversial. In the present study, we aimed to clarify these relationships through a meta-analysis.We performed a comprehensive search of studies from PubMed, EMBASE, Ovid library database, Google scholar, and Chinese National Knowledge Infrastructure databases that were published before June 2015. The odds ratio (OR) and pooled hazard ratio (HR) with the 95% confidence intervals (CI) were used to estimate the effects.Twenty-one studies including 1504 patients with esophageal cancer were selected to assess the prognostic value and clinical significance of CD44v6 in these patients. The results showed that the expression of CD44v6 was higher in esophageal cancer tissue than in normal colorectal tissue (OR=9.19, 95% CI=6.30-13.42). Moreover, expression of CD44v6 was higher in patients with lymphoid nodal metastasis, compared to those without (OR=6.91, 95% CI=4.81-9.93). The pooled results showed that CD44v6 was associated with survival in patients with esophageal cancer (HR = 2.47, 95% CI = 1.56-3.92). No significant difference in CD44v6 expression was found in patients with different histological types and tumor stages (both P>0.05). Moreover, no publication bias was found among the studies (all P > 0.05).This meta-analysis demonstrates that CD44v6 is associated with the metastasis of esophageal cancer and a poor prognosis, but is not associated with the histological types and tumor stages.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/metabolismo , Receptores de Hialuronatos/metabolismo , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Humanos , Modelos Estatísticos , Metástase Neoplásica , Estadiamento de Neoplasias , Razão de Chances , Prognóstico
10.
World J Gastroenterol ; 21(14): 4323-33, 2015 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-25892884

RESUMO

AIM: To evaluate the utility of carbohydrate antigen 19-9 (CA19-9) for differential diagnosis of pancreatic carcinoma and chronic pancreatitis. METHODS: We searched the literature for studies reporting the sensitivity, specificity, and other accuracy measures of serum CA19-9 levels for differentiating pancreatic carcinoma and chronic pancreatitis. Pooled analysis was performed using random-effects models, and receiver operating characteristic (ROC) curves were generated. Study quality was assessed using Standards for Reporting Diagnostic Accuracy and Quality Assessment for Studies of Diagnostic Accuracy tools. RESULTS: A total of 34 studies involving 3125 patients with pancreatic carcinoma and 2061 patients with chronic pancreatitis were included. Pooled analysis of the ability of CA19-9 level to differentiate pancreatic carcinoma and chronic pancreatitis showed the following effect estimates: sensitivity, 0.81 (95%CI: 0.80-0.83); specificity, 0.81 (95%CI: 0.79-0.82); positive likelihood ratio, 4.08 (95%CI: 3.39-4.91); negative likelihood ratio, 0.24 (95%CI: 0.21-0.28); and diagnostic odds ratio, 19.31 (95%CI: 14.40-25.90). The area under the ROC curve was 0.88. No significant publication bias was detected. CONCLUSION: Elevated CA19-9 by itself is insufficient for differentiating pancreatic carcinoma and chronic pancreatitis, however, it increases suspicion of pancreatic carcinoma and may complement other clinical findings to improve diagnostic accuracy.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Carcinoma/sangue , Neoplasias Pancreáticas/sangue , Pancreatite Crônica/sangue , Área Sob a Curva , Carcinoma/diagnóstico , Diagnóstico Diferencial , Humanos , Razão de Chances , Neoplasias Pancreáticas/diagnóstico , Pancreatite Crônica/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Regulação para Cima
11.
World J Gastroenterol ; 21(5): 1531-45, 2015 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-25663772

RESUMO

AIM: To investigate the effect of interleukin (IL)-22 on hepatic fibrosis in mice and the possible mechanism involved. METHODS: Liver fibrosis was induced in male BALB/c mice by CCl4. Recombinant IL-22 (rmIL-22) was administered intraperitoneally in CCl4-treated mice. Fibrosis was assessed by histology and Masson staining. The activation of hepatic stellate cells (HSCs) was investigated by analysis of α-smooth muscle actin expression. The frequencies of T helper (Th) 22 cells, Th17 cells and Th1 cells, the expression of inflammatory cytokines [IL-22, IL-17A, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-6, IL-1ß] and transcription factors [aryl hydrocarbon receptor (AHR), RAR-related orphan receptor (RORγt), T-bet] mRNA in the liver were investigated. In addition, the plasma levels of IL-22, IL-17A, IFN-γ, TNF-α, IL-6 and IL-1ß were evaluated. RESULTS: Significant elevations in circulating Th22 cells, Th17 cells, Th1 cells, IL-22, IL-17A, and IFN-γ were observed in the hepatic fibrosis group compared with the control group (P < 0.01). Treatment with rmIL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis, which was confirmed by lower hepatic fibrosis pathological scores (P < 0.01). RmIL-22 decreased the frequencies of Th22 cells (6.71% ± 0.97% vs 8.09% ± 0.74%, P < 0.01), Th17 cells (4.34% ± 0.37% vs 5.71% ± 0.24%, P < 0.01), Th1 cells (3.09% ± 0.49% vs 4.91% ± 0.73%, P < 0.01), and the levels of IL-22 (56.23 ± 3.08 vs 70.29 ± 3.01, P < 0.01), IL-17A (30.74 ± 2.77 vs 45.68 ± 2.71, P < 0.01), and IFN-γ (74.78 ± 2.61 vs 124.89 ± 2.82, P < 0.01). Down-regulation of IL-22, IL-17A, IFN-γ, TNF-α, IL-6, IL-1ß, AHR RORγt, and T-bet gene expression in the liver was observed in the rmIL-22 group (P < 0.01). CONCLUSION: The frequencies of Th22, Th17 and Th1 cells are elevated in hepatic fibrosis. RmIL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines, thereby ameliorating liver fibrogenesis.


Assuntos
Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Células Estreladas do Fígado/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Interleucinas/farmacologia , Cirrose Hepática Experimental/prevenção & controle , Fígado/efeitos dos fármacos , Animais , Tetracloreto de Carbono , Citocinas/genética , Citocinas/imunologia , Células Estreladas do Fígado/imunologia , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Mediadores da Inflamação/imunologia , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/genética , Cirrose Hepática Experimental/imunologia , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , Masculino , Camundongos Endogâmicos BALB C , RNA Mensageiro/metabolismo , Proteínas Recombinantes/farmacologia , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th17/metabolismo , Fatores de Tempo
12.
Tumour Biol ; 36(3): 2033-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25387810

RESUMO

Interleukin (IL)-22 has been implicated in inflammation and tumorigenesis. To date, no studies have investigated the role of IL-22 polymorphism in the carcinogenesis of gastric cancer (GC). In this study, we aimed to investigate the association of IL-22 polymorphisms with the risk of GC in a Chinese population. One hundred eight GC patients and 110 healthy controls were included in the study. IL-22 rs1179251, rs2227485, and rs2227473 polymorphisms were determined by PCR amplification and DNA sequencing. Haplotypes were constructed, and a possible association of these haplotypes with GC was assessed. The distribution of IL-22 rs1179251 polymorphism with clinical parameters was also analyzed. The IL-22 rs1179251 polymorphism was significantly associated with an increased risk of GC (p < 0.05). Stratified analysis revealed that rs1179251 was associated with advanced stages, lymph node metastases, and distant metastases of GC (p < 0.05). No associations were found between rs2227485 and rs2227473 and the risk of GC (p > 0.05). Three possible haplotypes (C(rs1179251)-C(rs2227485)-G(rs2227485), C(rs1179251)-T(rs2227485)-G(rs2227485), and G(rs1179251)-T(rs2227485)-A(rs2227485)) were identified, but no associations were found between these and the risk of GC (p > 0.05). In summary, our study demonstrates that the rs1179251 polymorphism of IL-22 was associated with an increased risk of GC and may influence the progression of GC. Future larger studies with other ethnic populations are required to confirm these findings.


Assuntos
Interleucinas/genética , Neoplasias Gástricas/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Risco , Neoplasias Gástricas/imunologia
13.
Hum Immunol ; 75(10): 1062-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25223469

RESUMO

BACKGROUND: The association between ADIPOQ polymorphisms and the risk of obesity remains controversial. We perform a comprehensive meta-analysis to clarify the current understanding of this association. METHODS: We searched for relevant studies in PubMed, Embase and Cochrane library before February 2014. The strengths of the association between ADIPOQ polymorphisms and obesity risk were estimated by odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Eighteen case-control studies analyzing four SNPs (rs17300539, rs266729, rs1501299 and rs2241766) of ADIPOQ gene were eligible for the present meta-analysis. The pooling results showed that rs17300539 (2GG+GA vs. 2AA+GA: OR=0.78, 95%CI=0.69-0.89) and rs1501299 (2GG+GA vs. 2AA+GA: OR=0.89, 95%CI=0.80-0.98) were associated with obesity risk in Caucasian ethnicity. The rs266729 were associated with obesity risk in Asian ethnicity (2CC+CG vs. 2GG+GCG: OR=0.77, 95%CI=0.65-0.92). However, there were no associations between rs2241766 and the obesity risk (P>0.05). No publication bias was found among these studies (all P>0.05). CONCLUSIONS: This study suggests that ADIPOQ rs17300539 and rs1501299 are associated with risk of obesity in Caucasian ethnicity, and the rs266729 is associated with obesity risk in Asian ethnicity. However, there is no association between rs2241766 and obesity risk.


Assuntos
Adiponectina/genética , Grupo com Ancestrais do Continente Asiático , Grupo com Ancestrais do Continente Europeu , Obesidade/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único , Risco
14.
PLoS One ; 9(9): e108762, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25259861

RESUMO

BACKGROUND: The diagnostic efficiency of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology varies widely depending on the treatment method of the specimens. The present study aimed to evaluate the diagnostic efficacy of cell block (CB) immunohistochemistry, smear cytology (SC), and liquid-based cytology (LBC) in patients with pancreatic lesions without consulting an on-site cytopathologist. METHODS: This study prospectively enrolled 72 patients with pancreatic lesions. The EUS-FNA specimens were examined by SC, LBC, and CB immunohistochemistry. The diagnostic efficacy of the 3 methods was then compared. Patients' final diagnosis was confirmed by surgical resection specimens, diagnostic imaging, and clinical follow-up. RESULTS: Our results included 60 malignant and 12 benign pancreatic lesions. The diagnostic sensitivity (90%), negative predictive value (66.7%), and accuracy (91.7%) of CB immunohistochemistry were significantly higher than those of SC (70.0%, 30.0%, and 75.0%, respectively) and LBC (73.3%, 31.6%, and 77.8%, respectively) (all P<0.05). The combination of CB and SC, or CB and LBC, did not significantly increase the efficacy compared to CB immunohistochemistry alone. CONCLUSION: Our findings suggest that in the absence of an on-site cytopathologist, CB immunohistochemistry on EUS-FNA specimens offers a higher diagnostic efficacy in patients with pancreatic lesions than does SC and LBC.


Assuntos
Citodiagnóstico/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Imuno-Histoquímica/métodos , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Adulto Jovem
15.
Medicine (Baltimore) ; 93(14): e85, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25255024

RESUMO

Surgical resection is a standard treatment for insulinomas; however, it is associated with a high risk of complications and limited to specific suitable candidates. In recent years, endoscopic ultrasound (EUS)-guided ethanol ablation of insulinomas has emerged as a new therapeutic option, especially for elderly patients and candidates unfit for surgery. We aimed to evaluate the feasibility and safety of this technique for insulinomas. Four patients diagnosed with insulinomas based on EUS-fine-needle aspiration and immunohistochemistry results underwent EUS-guided 95% ethanol ablation. A comprehensive literature review was performed to understand the current status of the feasibility, safety, and effects of EUS-guided ethanol ablation of insulinomas. EUS-guided ethanol ablation of insulinomas was successfully completed in all the 4 patients. There were no perioperative or postoperative complications. The patients were discharged at 3 days after the procedure. No recurrence of hypoglycemia or tumors was noted during follow-up (range, 3-6 months). Literature review showed 8 patients with insulinomas who underwent EUS-guided ethanol ablation. All the procedures were successful, with no need for further surgical treatment. Among these reviewed cases, 6 patients had no post-procedural complications, while other 2 patients showed a mild increase in the serum levels of lipase and/or pancreatic enzymes within 48 h post-procedure; furthermore, 1 of these 2 patients presented at a later date with medically controllable hematoma and ulceration. During follow-up, 6 patients remained asymptomatic and normoglycemic, while the 2 patients who presented post-procedural complications developed occasional mild confusion. EUS-guided ethanol ablation of insulinomas is an effective and safe modality, with an acceptable level of post-procedural complications. However, the long-term effects of this new therapeutic option need to be validated in a large randomized controlled trial with longer follow-up.


Assuntos
Técnicas de Ablação/métodos , Endossonografia/métodos , Etanol/uso terapêutico , Insulinoma/cirurgia , Neoplasias Pancreáticas/cirurgia , Idoso , China , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapêutica
16.
Zhonghua Gan Zang Bing Za Zhi ; 22(2): 136-41, 2014 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-24735597

RESUMO

OBJECTIVE: To investigate the role of activated hepatocyte growth factor (HGF) in apoptosis of hepatic stellate cells (HSCs) and in modulating the Rho signaling pathway. METHODS: HSCs were divided into the following groups: blank control, consisting of HSCs without treatment; two treatment controls, consisting of HSCs exposed to exogenous HGF at 50 ng/ml and HSCs exposed to exogenous HGF activator (HGFA) at 70 ng/ml; three experimental groups, consisting of HSCs exposed to both exogenous HGF and HGFA, HSCs pre-incubated with the HGF inhibitor c-met at 500 ng/ml for 6 hours and then exposed to exogenous HGF and HGFA, and HSCs pre-incubated with the Rho pathway inhibitor Y-27632 at 10 ng/ml and then exposed to exogenous HGF and HGFA. Activation status of the cultured HSCs was determined by change in expression of alpha-smooth muscle actin (SMA). The optimal intervention concentration of Y-27632 was determined by MTT assay. The apoptotic status of HSCs was determined by flow cytometry. Expression of the HGF-alpha chain was detected by immunofluorescence. The expression of RhoA was evaluated by PCR (for mRNA) and by immunohistochemical staining and Western blot analysis (for protein). RESULTS: Exposure to 10 mumol/L Y-27632 led to obvious growth inhibition of HGF + HGFA-induced HSCs, compared with the other concentrations tested (P less than 0.05). HGF + HGFA induced the expression of the HGF-alpha chain in a time-dependent manner (P less than 0.01); however, the increases in expression of HGF-alpha chain induced by HGF alone and HGFA alone were not significantly different from the level in the blank controls (P more than 0.05). Exposure to HGF alone and HGFA alone led to a time-dependent increase in apoptosis (24 h, 48 h, 72 h) but exposure to HGF + HGFA led to the highest levels of apoptosis (P less than 0.05). Exposure to HGF + HGFA led to a time-dependent decrease in RhoA mRNA and protein expression (P less than 0.01). CONCLUSION: Activation of hepatocyte growth factor promotes apoptosis of hepatic stellate cells by suppressing RhoA expression and down-regulating the Rho signaling pathway.

17.
Diagn Microbiol Infect Dis ; 79(1): 102-7, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24629577

RESUMO

The diagnosis of tuberculosis (TB) ascites using standard diagnostic tools is difficult. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of adenosine deaminase (ADA) levels in ascites for diagnosing TB ascites. A systematic review was performed of English language publications prior to April 2013. Sensitivity, specificity, and other measures of the accuracy of ADA for the diagnosis of TB ascites using ascites fluid were summarized using a random-effects model or a fixed-effects model. Receiver operating characteristic curves were used to summarize overall test performance. Seventeen studies involving 1797 subjects were eligible for the analysis. The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the area under cure of overall analysis were: 0.93, 0.94, 13.55, 0.11, 169.83, and 0.976, respectively; the results of sensitivity analysis of studies that used Giusti method were 0.94, 0.94, 12.99, 0.08, 183.18, and 0.977, respectively. Our results suggest that ADA in the ascites can be a sensitive and specific target and a critical criterion for the diagnosis of TB ascites.


Assuntos
Adenosina Desaminase/análise , Líquido Ascítico/química , Peritonite Tuberculosa/diagnóstico , Peritonite Tuberculosa/enzimologia , Biomarcadores/análise , Humanos , Sensibilidade e Especificidade
18.
World J Gastroenterol ; 19(45): 8427-34, 2013 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-24363536

RESUMO

AIM: To establish the role of magnetic resonance cholangiography (MRC) in diagnosis of biliary anatomy in living-donor liver transplantation (LDLT) donors. METHODS: A systematic review was performed by searching electronic bibliographic databases prior to March 2013. Studies with diagnostic results and fulfilled inclusion criteria were included. The methodological quality of the studies was assessed. Sensitivity, specificity and other measures of the accuracy of MRC for diagnosis of biliary anatomy in LDLT donors were summarized using a random-effects model or a fixed-effects model. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Publication bias was assessed using Deek's funnel plot asymmetry test. Sensitivity analysis was adopted to explore the potential sources of heterogeneity. RESULTS: Twelve studies involving 869 subjects were eligible to the analysis. The scores of Quality Assessment of Diagnostic Accuracy Studies for the included studies ranged from 11 to 14. The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic OR of MRC in diagnosis of biliary anatomy in LDLT donor were 0.88 (95%CI: 0.84-0.92), 0.95 (95%CI: 0.93-0.97), 15.33 (95%CI: 10.70-21.95), 0.15 (95%CI: 0.11-0.20) and 130.77 (95%CI: 75.91-225.27), respectively. No significant heterogeneity was detected in all the above four measures. Area under SROC curve was 0.971. Little publication bias was noted across the studies (P = 0.557). Sensitivity analysis excluding a study with possible heterogeneity got a similar overall result, which suggested the little influence of this study on the overall results. CONCLUSION: Our results suggest that MRC is a high specificity but moderate sensitivity technique in diagnosis of biliary anatomy in LDLT donors.


Assuntos
Ductos Biliares/anatomia & histologia , Colangiopancreatografia por Ressonância Magnética , Seleção do Doador , Transplante de Fígado/métodos , Doadores Vivos , Área Sob a Curva , Distribuição de Qui-Quadrado , Humanos , Funções Verossimilhança , Razão de Chances , Valor Preditivo dos Testes , Curva ROC
19.
PLoS One ; 8(9): e72710, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24066025

RESUMO

BACKGROUND: Previous studies have shown inconsistent results on the association between diabetes mellitus (DM) and some clinical outcomes. We conducted a meta-analysis of observational studies to assess effect of DM on clinical outcomes after coronary stenting. METHODS: We searched for studies without language restriction in PubMed, Embase and Cochrane library prior to 2012. The clinical outcomes including in-stent restenosis (ISR), major adverse cardiac events (MACE), stent thrombosis (ST), target lesion revascularization (TLR) and target vessel revascularization (TVR). Adjusted odds ratio (OR), and the corresponding 95% confidence interval (95% CI) was summarized. RESULTS: 55 studies involving 128,084 total patients (38,416 DM patients and 89,668 controls) were eligible for our analysis. Overall, there were significant associations between DM and ISR (OR = 1.70, 95% CI: 1.53-1.89, I(2) = 0.0%), MACE (OR = 1.54, 95% CI: 1.36-1.73, I(2) = 29.0%), ST (OR = 2.01, 95% CI: 1.36-2.97, I(2) = 47.7%), TLR (OR = 1.46, 95% CI: 1.26-1.68, I(2) = 43.3%) as well as TVR (OR = 1.33, 95% CI: 1.17-1.51, I(2) = 48.3). Subgroup analysis showed that the associations were similar between BMS and DES implantation. Moreover, there was no significant association in the ST subgroup after 1-3 years follow-up. CONCLUSIONS: Our meta-analysis suggests that after coronary stent implantation, DM is associated with ISR, MACE, ST, TLR and TVR. DM appears to be a vital risk factor of these clinical outcomes.


Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Diabetes Mellitus/fisiopatologia , Stents Farmacológicos/efeitos adversos , Intervalos de Confiança , Humanos , Fatores de Risco
20.
Yonsei Med J ; 54(4): 832-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23709415

RESUMO

PURPOSE: The association between Helicobacter pylori (H. pylori) and blood ammonia levels in cirrhotic patients is controversial. We aimed to clarify this controvercy by performing a meta-analysis of published studies. MATERIALS AND METHODS: We searched PubMed, EMBASE and Cochrane library for studies which explored the association between H. pylori and blood ammonia levels in cirrhotic patients before May 2012. Six cohort studies involved in 632 H. pylori positive and 396 H. pylori negative cirrhotic patients were eligible for our analysis. The summary estimates were presented as standard means differences (SMD) and 95% confidence intervals (CI) from individual studies. RESULTS: Overall, there was significant association between H. pylori infection and the elevated blood ammonia levels in cirrhotic patients (SMD=0.34, 95% CI=0.21-0.47, I²=42.1%). Sensitivity analysis further confirmed this association. Subgroup analysis showed that the association was found only in Asian ethnicity, but not in Caucasian ethnicity. CONCLUSION: H. pylori infection is associated with elevated blood ammonia levels in cirrhotic patients, and more large scale studies and stratify analysis are warranted in order to further evaluate this association.


Assuntos
Infecções por Helicobacter/sangue , Cirrose Hepática/sangue , Cirrose Hepática/microbiologia , Amônia/sangue , Grupo com Ancestrais do Continente Asiático , Grupo com Ancestrais do Continente Europeu , Helicobacter pylori/patogenicidade , Humanos , Viés de Publicação , Análise de Regressão
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