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1.
Gastroenterol Rep (Oxf) ; 9(1): 31-37, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33747524

RESUMO

Background: The artificial neural network (ANN) emerged recently as a potent diagnostic tool, especially for complicated systemic diseases. This study aimed to establish a diagnostic model for the recognition of fatty liver disease (FLD) by virtue of the ANN. Methods: A total of 7,396 pairs of gender- and age-matched subjects who underwent health check-ups at the First Affiliated Hospital, College of Medicine, Zhejiang University (Hangzhou, China) were enrolled to establish the ANN model. Indices available in health check-up reports were utilized as potential input variables. The performance of our model was evaluated through a receiver-operating characteristic (ROC) curve analysis. Other outcome measures included diagnostic accuracy, sensitivity, specificity, Cohen's k coefficient, Brier score, and Hosmer-Lemeshow test. The Fatty Liver Index (FLI) and the Hepatic Steatosis Index (HSI), retrained using our training-group data with its original designated input variables, were used as comparisons in the capability of FLD diagnosis. Results: Eight variables (age, gender, body mass index, alanine aminotransferase, aspartate aminotransferase, uric acid, total triglyceride, and fasting plasma glucose) were eventually adopted as input nodes of the ANN model. By applying a cut-off point of 0.51, the area under ROC curves of our ANN model in predicting FLD in the testing group was 0.908 [95% confidence interval (CI), 0.901-0.915]-significantly higher (P < 0.05) than that of the FLI model (0.881, 95% CI, 0.872-0.891) and that of the HSI model (0.885; 95% CI, 0.877-0.893). Our ANN model exhibited higher diagnostic accuracy, better concordance with ultrasonography results, and superior capability of calibration than the FLI model and the HSI model. Conclusions: Our ANN system showed good capability in the diagnosis of FLD. It is anticipated that our ANN model will be of both clinical and epidemiological use in the future.

2.
World J Gastroenterol ; 26(34): 5156-5168, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32982116

RESUMO

BACKGROUND: Efforts should be made to develop a deep-learning diagnosis system to distinguish pancreatic cancer from benign tissue due to the high morbidity of pancreatic cancer. AIM: To identify pancreatic cancer in computed tomography (CT) images automatically by constructing a convolutional neural network (CNN) classifier. METHODS: A CNN model was constructed using a dataset of 3494 CT images obtained from 222 patients with pathologically confirmed pancreatic cancer and 3751 CT images from 190 patients with normal pancreas from June 2017 to June 2018. We established three datasets from these images according to the image phases, evaluated the approach in terms of binary classification (i.e., cancer or not) and ternary classification (i.e., no cancer, cancer at tail/body, cancer at head/neck of the pancreas) using 10-fold cross validation, and measured the effectiveness of the model with regard to the accuracy, sensitivity, and specificity. RESULTS: The overall diagnostic accuracy of the trained binary classifier was 95.47%, 95.76%, 95.15% on the plain scan, arterial phase, and venous phase, respectively. The sensitivity was 91.58%, 94.08%, 92.28% on three phases, with no significant differences (χ 2 = 0.914, P = 0.633). Considering that the plain phase had same sensitivity, easier access, and lower radiation compared with arterial phase and venous phase , it is more sufficient for the binary classifier. Its accuracy on plain scans was 95.47%, sensitivity was 91.58%, and specificity was 98.27%. The CNN and board-certified gastroenterologists achieved higher accuracies than trainees on plain scan diagnosis (χ 2 = 21.534, P < 0.001; χ 2 = 9.524, P < 0.05; respectively). However, the difference between CNN and gastroenterologists was not significant (χ 2 = 0.759, P = 0.384). In the trained ternary classifier, the overall diagnostic accuracy of the ternary classifier CNN was 82.06%, 79.06%, and 78.80% on plain phase, arterial phase, and venous phase, respectively. The sensitivity scores for detecting cancers in the tail were 52.51%, 41.10% and, 36.03%, while sensitivity for cancers in the head was 46.21%, 85.24% and 72.87% on three phases, respectively. Difference in sensitivity for cancers in the head among the three phases was significant (χ 2 = 16.651, P < 0.001), with arterial phase having the highest sensitivity. CONCLUSION: We proposed a deep learning-based pancreatic cancer classifier trained on medium-sized datasets of CT images. It was suitable for screening purposes in pancreatic cancer detection.


Assuntos
Redes Neurais de Computação , Neoplasias Pancreáticas , Humanos , Interpretação de Imagem Assistida por Computador , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X
3.
World J Gastroenterol ; 26(26): 3750-3766, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32774055

RESUMO

BACKGROUND: Conventional Crohn's disease (CD) treatments are supportive rather than curative and have serious side effects. Adipose-derived mesenchymal stem cells (ADSCs) have been gradually applied to treat various diseases. The therapeutic effect and underlying mechanism of ADSCs on CD are still not clear. AIM: To investigate the effect of ADSC administration on CD and explore the potential mechanisms. METHODS: Wistar rats were administered with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish a rat model of CD, followed by tail injections of green fluorescent protein (GFP)-modified ADSCs. Flow cytometry, qRT-PCR, and Western blot were used to detect changes in the Wnt signaling pathway, T cell subtypes, and their related cytokines. RESULTS: The isolated cells showed the characteristics of ADSCs, including spindle-shaped morphology, high expression of CD29, CD44, and CD90, low expression of CD34 and CD45, and osteogenic/adipogenic ability. ADSC therapy markedly reduced disease activity index and ameliorated colitis severity in the TNBS-induced rat model of CD. Furthermore, serum anti-sacchromyces cerevisiae antibody and p-anti-neutrophil cytoplasmic antibody levels were significantly reduced in ADSC-treated rats. Mechanistically, the GFP-ADSCs were colocalized with intestinal epithelial cells (IECs) in the CD rat model. GFP-ADSC delivery significantly antagonized TNBS-induced increased canonical Wnt pathway expression, decreased noncanonical Wnt signaling pathway expression, and increased apoptosis rates and protein level of cleaved caspase-3 in rats. In addition, ADSCs attenuated TNBS-induced abnormal inflammatory cytokine production, disturbed T cell subtypes, and their related markers in rats. CONCLUSION: Successfully isolated ADSCs show therapeutic effects in CD by regulating IEC proliferation, the Wnt signaling pathway, and T cell immunity.


Assuntos
Tecido Adiposo , Colite , Células-Tronco Mesenquimais , Animais , Colite/induzido quimicamente , Colite/terapia , Células Epiteliais , Transplante de Células-Tronco Mesenquimais , Ratos , Ratos Wistar , Regeneração , Linfócitos T , Ácido Trinitrobenzenossulfônico/toxicidade , Via de Sinalização Wnt
4.
J Dig Dis ; 21(1): 52-58, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31837189

RESUMO

OBJECTIVE: The inflammatory bowel disease disability index (IBD-DI) has been used to evaluate functional status for patients with inflammatory bowel diseases (IBD). The study aimed to develop a reliable Chinese version of IBD-DI (C-IBD-DI). METHODS: Consecutive patients with IBD and healthy controls were recruited from June 2016 to July 2017 in the First Affiliated Hospital, College of Medicine, Zhejiang University (Hangzhou, Zhejiang Province, China) to complete an inflammatory bowel disease questionnaire-32 (IBDQ-32), Hamilton's anxiety rating scale (HAMA) and Hamilton's depression rating scale-24 items (HAMD-24). The validation process included item reduction, reliability and validity tests. RESULTS: Altogether 122 patients with IBD completed the validation process. Factor analysis reduced the C-IBD-DI to 13 items. Cronbach's α coefficient was 0.90. The C-IBD-DI scores were correlated with IBDQ-32 score (r = -0.79, P < 0.001), HAMA (r = 0.78, P < 0.001) and HAMD-24 (r = 0.81, P < 0.001). The total score of C-IBD-DI was significantly higher in patients with active IBD than in those in remission. The intraclass correlation coefficient was 0.83 in the stable IBD group, representing a good test-retest reliability. Those with improved disease activity had a significantly lower C-IBD-DI score at the follow-up visit than at baseline. Patients with IBD had worse disability levels and quality of life than the controls, and were more likely to be anxious and depressed, especially those with active IBD. CONCLUSIONS: The validated C-IBD-DI comprising 13 questions has highly acceptable reliability and validity. Multicenter studies including large sample sizes are needed to further confirm our results.


Assuntos
Avaliação da Deficiência , Doenças Inflamatórias Intestinais/diagnóstico , Índice de Gravidade de Doença , Ansiedade/diagnóstico , China , Depressão/diagnóstico , Humanos , Doenças Inflamatórias Intestinais/psicologia , Qualidade de Vida , Reprodutibilidade dos Testes
5.
World J Gastroenterol ; 25(34): 5120-5133, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31558861

RESUMO

BACKGROUND: Allyl isothiocyanate (AITC), a classic anti-inflammatory and antitumorigenic agent, was recently identified as a potential treatment for obesity and insulin resistance. However, little is known about its direct impact on the liver. AIM: To investigate the effect and underlying mechanism of AITC in nonalcoholic fatty liver disease (commonly referred to as NAFLD). METHODS: To establish a mouse and cellular model of NAFLD, C57BL/6 mice were fed a high fat diet (HFD) for 8 wk, and AML-12 cells were treated with 200 µM palmitate acid for 24 h. For AITC treatment, mice were administered AITC (100 mg/kg/d) orally and AML-12 cells were treated with AITC (20 µmol/L). RESULTS: AITC significantly ameliorated HFD-induced weight gain, hepatic lipid accumulation and inflammation in vivo. Furthermore, serum alanine aminotransferase and aspartate aminotransferase levels were markedly reduced in AITC-treated mice. Mechanistically, AITC significantly downregulated the protein levels of sterol regulatory element-binding protein 1 (SREBP1) and its lipogenesis target genes and upregulated the levels of proteins involved in fatty acid ß-oxidation, as well as the upstream mediators Sirtuin 1 (Sirt1) and AMP-activated protein kinase α (AMPKα), in the livers of HFD-fed mice. AITC also attenuated the nuclear factor kappa B (NF-κB) signaling pathway. Consistently, AITC relieved palmitate acid-induced lipid accumulation and inflammation in AML-12 cells in vitro through the Sirt1/AMPK and NF-κB signaling pathways. Importantly, further studies showed that the curative effect of AITC on lipid accumulation was abolished by siRNA-mediated knockdown of either Sirt1 or AMPKα in AML-12 cells. CONCLUSION: AITC significantly ameliorates hepatic steatosis and inflammation by activating the Sirt1/AMPK pathway and inhibiting the NF-κB pathway. Therefore, AITC is a potential therapeutic agent for NAFLD.


Assuntos
Inflamação/tratamento farmacológico , Isotiocianatos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Linhagem Celular , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/imunologia , Hepatócitos/patologia , Humanos , Inflamação/etiologia , Inflamação/imunologia , Isotiocianatos/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/imunologia , Ácido Palmítico/farmacologia , Transdução de Sinais/imunologia , Sirtuína 1/metabolismo , Regulação para Cima/efeitos dos fármacos
6.
Biomed Res Int ; 2019: 8967306, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223623

RESUMO

Background: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habits in the absence of any detectable organic illnesses. Interest in the effect of dietary opponents to the IBS pathogenesis has been increased in recent years. This study aims to review previous studies to determine the relationship between IBS prevalence in community and dietary energy and macronutrients intakes according to the national nutrition surveys. Methods: A literature search was conducted in PubMed and EMBASE to September, 2018, to identify population-based studies that reported the prevalence of IBS. Daily energy intake, daily carbohydrates, and protein and fat percent contribution to energy intake (%) were obtained from study population-based national nutrition survey. The correlations of prevalence of IBS and dietary intakes were obtained by Spearman coefficient or Pearson coefficient. Results: Global prevalence of IBS was 11.7%. There was no correlation between overall prevalence of IBS of individual countries and national energy intake (P = 0.785), protein proportion (P = 0.063), carbohydrates proportion (P = 0.505), or fat proportion (P = 0.384) according to the years when the studies were conducted. No correlations were detected between dietary intake and male or female IBS prevalence. Interestingly, protein proportion was positively correlated with the prevalence of IBS in Rome III criteria (r = 0.569). Conclusion: Our findings demonstrate that dietary energy and macronutrients intake do not play a direct role in prevalence of IBS. However, IBS diagnostic criteria seem to have a bias on the correlation between prevalence of IBS and dietary intake. Further studies are needed to confirm the correlation between prevalence of IBS and specific dietary intake.


Assuntos
Ingestão de Energia , Síndrome do Intestino Irritável , Nutrientes , Feminino , Humanos , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Prevalência
7.
J Nanosci Nanotechnol ; 19(11): 7261-7268, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31039884

RESUMO

A full-cellulose derived hydrogel, composed of carboxymethyl cellulose (CMC) and nanofibrillated cellulose (NFC), was successfully manufactured and immobilized with Pd/Fe bimetallic nanoparticles for the dechlorination of 2,4,6-trichlorophenol. The NFC-reinforced CMC hydrogels with or without loading of bimetallic nanoparticles were characterized by Fourier transform infrared spectroscopy, Transmission electron microscopy, Scanning electron microscopy-energy dispersive X-ray, and X-ray diffraction analyses. The effect of amounts of NFC on the loading capacity of Pd/Fe, mechanical properties and specific Brunauer-Emmett-Teller surface areas of NFC-reinforced CMC hydrogel was also investigated. The experimental results showed that Pd/Fe bimetallic nanoparticles were dispersed and fixed in the hydrogel matrix with the nanosize spherical shape. The hydrogel would protect the Pd/Fe nanoparticles from oxidation, and thus providing long-term stability in comparison with only NFC-coated Pd/Fe nanoparticles. The hydrogel loaded with Pd/Fe nanoparticles, as a soft material catalytic system, was investigated to dechlorinate 2,4,6-trichlorophenol and was found to be very effective.

9.
Biomed Res Int ; 2018: 4304376, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30402478

RESUMO

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Machine learning techniques were introduced to evaluate the optimal predictive clinical model of NAFLD. Methods: A cross-sectional study was performed with subjects who attended a health examination at the First Affiliated Hospital, Zhejiang University. Questionnaires, laboratory tests, physical examinations, and liver ultrasonography were employed. Machine learning techniques were then implemented using the open source software Weka. The tasks included feature selection and classification. Feature selection techniques built a screening model by removing the redundant features. Classification was used to build a prediction model, which was evaluated by the F-measure. 11 state-of-the-art machine learning techniques were investigated. Results: Among the 10,508 enrolled subjects, 2,522 (24%) met the diagnostic criteria of NAFLD. By leveraging a set of statistical testing techniques, BMI, triglycerides, gamma-glutamyl transpeptidase (γGT), the serum alanine aminotransferase (ALT), and uric acid were the top 5 features contributing to NAFLD. A 10-fold cross-validation was used in the classification. According to the results, the Bayesian network model demonstrated the best performance from among the 11 different techniques. It achieved accuracy, specificity, sensitivity, and F-measure scores of up to 83%, 0.878, 0.675, and 0.655, respectively. Compared with logistic regression, the Bayesian network model improves the F-measure score by 9.17%. Conclusion: Novel machine learning techniques may have screening and predictive value for NAFLD.


Assuntos
Aprendizado de Máquina , Modelos Biológicos , Hepatopatia Gordurosa não Alcoólica/sangue , Adulto , Alanina Transaminase/sangue , Índice de Massa Corporal , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Triglicerídeos/sangue , gama-Glutamiltransferase/sangue
10.
Anal Bioanal Chem ; 410(13): 3111-3117, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29552734

RESUMO

This work reports on a simple method for the determination of lysine content by an in situ sample pretreatment and headspace gas chromatographic measurement (HS-GC) technique, based on carbon dioxide (CO2) formation from the pretreatment reaction (between lysine and ninhydrin solution) in a closed vial. It was observed that complete lysine conversion to CO2 could be achieved within 60 min at 60 °C in a phosphate buffer medium (pH = 4.0), with a minimum molar ratio of ninhydrin/lysine of 16. The results showed that the method had a good precision (RSD < 5.23%) and accuracy (within 6.80%), compared to the results measured by a reference method (ninhydrin spectroscopic method). Due to the feature of in situ sample pretreatment and headspace measurement, the present method becomes very simple and particularly suitable to be used for batch sample analysis in lysine-related research and applications. Graphical abstract The flow path of the reaction and HS-GC measurement for the lysine analysis.


Assuntos
Cromatografia Gasosa/instrumentação , Lisina/análise , Dióxido de Carbono/análise , Celulose/química , Cromatografia Gasosa/métodos , Desenho de Equipamento , Limite de Detecção , Ninidrina/química , Bases de Schiff/química
11.
World J Gastroenterol ; 23(43): 7756-7764, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29209116

RESUMO

AIM: To gain knowledge of xanthelasma, a large population-based study was conducted. METHODS: Patients who underwent upper gastrointestinal endoscopy at the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China during Jan 2009 to Nov 2016 were included. General characteristics as well as clinical data were collected, including blood routine, serum biochemical analysis, endoscopic findinds, histological evaluation and comorbiditie. Statistical analyses was performed using SPSS 20.0 software for Windows (IBM Inc., Chicago, IL, United States) using Student's t-test, Mann-Whitney U test, χ2 test, univariable and multivariable logistic analysis. 2-tailed P value less than 0.05 was considered to be statistically significant. RESULTS: A total of 176006 endoscopies were retrieved and we included 1370 xanthelasma participants (703 men, 667 women) in this study. Prevalence of xanthelasma was 0.78% with average age of 56.6 ± 11.2 years. Chief complaint of xanthelasma consisted abdominal pain (24.2%), up-abdominal discomfort (14.1%), abdominal distention (10.1%), dyspepsia (9.1%), et al. Most xanthelasma occurred as single lesion in gastric antrum. Xanthelasma patients witnessed higher Helicobacter pylori (H. pylori) infection rate, more of other gastric lesions including atrophy, intestinal metaplasia and dysplasia (P < 0.01). In xanthelasma patients, serum carcinoembryonic antigen, triglyceride, fasting glucose, neutrophil, neutrophil-to-lymphocyte ratio were significantly higher, and high density lipoprotein-cholesterol, lymphocyte was lower (P < 0.05). Xanthelasma accompanied with more fatty liver disease and hepatic cyst, but fewer gallbladder polyp (P < 0.05). In logistic regression, it revealed that fasting plasma glucose (OR = 3.347, 1.170-9.575, P < 0.05), neutrophil (OR = 1.617, 1.003-2.605, P < 0.05), and carcinoembryonic antigen (OR = 2.011, 1.236-3.271, P < 0.01) were all independent risk factors in xanthelasma. CONCLUSION: Current study described a large xanthelasma cohort in Chinese population, revealed its relationship with H. pylori infection, carcinogenesis, metabolic dysfunction and inflammation as well.


Assuntos
Mucosa Gástrica/patologia , Infecções por Helicobacter/epidemiologia , Antro Pilórico/patologia , Gastropatias/epidemiologia , Xantomatose/epidemiologia , Adulto , Idoso , Atrofia/sangue , Atrofia/diagnóstico por imagem , Atrofia/epidemiologia , Atrofia/patologia , Glicemia/análise , Antígeno Carcinoembrionário/sangue , China/epidemiologia , Feminino , Mucosa Gástrica/diagnóstico por imagem , Gastroscopia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/diagnóstico por imagem , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Metaplasia/sangue , Metaplasia/diagnóstico por imagem , Metaplasia/epidemiologia , Metaplasia/patologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Prevalência , Antro Pilórico/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Gastropatias/sangue , Gastropatias/diagnóstico por imagem , Gastropatias/microbiologia , Xantomatose/sangue , Xantomatose/diagnóstico por imagem , Xantomatose/microbiologia
12.
World J Gastroenterol ; 23(24): 4390-4398, 2017 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-28706421

RESUMO

AIM: To investigate the role of heat shock protein (HSP)-glycoprotein (gp)96 in dendritic cells (DCs) and lymphocytes induction in gastric cancer (GC). METHODS: Human GC cell lines KATOIII, MKN-28 and SGC-7901 were infected with adenovirus gp96 at a multiplicity of infection of 100. gp96-GC antigen peptide complexes were purified. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, lactate dehydrogenase (LDH) release assay and enzyme-linked immunosorbent assay were used to determine allo-reactive T cell stimulation, natural killer (NK) cell activity and expression of cytokines (such as interleukin (IL)-10, IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α), respectively. Effect of cytotoxic T lymphocyte (CTL) on DCs incubated with HSP-gp96 was also evaluated by LDH release. All assays were performed in triplicate and the average values were reported. Comparison between groups was conducted using Student's t test. RESULTS: T cells incubated with HSP-gp96 exhibited a marked increase in proliferation in a dose-dependent manner (P < 0.05). NK cell activity after gp96-GC peptide complex treatment was significantly higher than that after antigen peptide treatment (P < 0.05). The activity of CTLs incubated with DCs from three GC cells lines was obviously higher than that stimulated by GC antigen at ratios of 50: 1, 25: 1, 10: 1, and 5: 1 (P < 0.05). Furthermore, the secretion of TNF-α, IL-10, IL-12 (P70) and IFN-γ markedly increased after incubation with HSP-gp96 (P < 0.05). CONCLUSION: HSP-gp96 promotes T cell response, enhances DC antigen presentation and induces cytokine secretion, as well. HSP-gp96 has potential as immunotherapy for elimination of residual GC cells.


Assuntos
Antígenos de Neoplasias/imunologia , Células Dendríticas/imunologia , Proteínas de Choque Térmico/imunologia , Células Matadoras Naturais/imunologia , Glicoproteínas de Membrana/imunologia , Neoplasias Gástricas/imunologia , Linfócitos T Citotóxicos/imunologia , Adenoviridae/genética , Apresentação do Antígeno/imunologia , Linhagem Celular Tumoral , Proliferação de Células , Técnicas de Cocultura , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Vetores Genéticos , Humanos , Células Matadoras Naturais/metabolismo , Ativação Linfocitária/imunologia , Linfócitos T Citotóxicos/metabolismo
13.
PLoS One ; 12(3): e0174218, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28346483

RESUMO

BACKGROUNDS/AIMS: Mitochondrial dysfunction plays an important role inthe pathogenesis of nonalcoholic steatohepatitis (NASH), where uncoupling protein (UCP) is actively involved. We previously reported the uncoupling activity of HDMCP and its role in liver steatosis. We now aim to investigate the degree and therapeutic effect of HDMCP in NASH and the regulatory role of miR-146 on HDMCP. METHODS: NASH animal model was established by feeding BALB/c mice with MCD diet while L02 cell was cultured with high concentration of fatty acid (HFFA) for 72h to mimic the steatosis and inflammation of NASH in-vitro appearance. The steatosis level was assessed by H-E/oil-red staining and serum/supernatant marker detection. The inflammation activity was evaluated by levels of Hepatic activity index, transwell, apoptosis degree (TUNEL/flow cytometry) and serum/supernatant marker. HDMCP level was detected by western blot and miRNA expression was tested by qRT-PCR. NASH severity change was recorded after RNA interference while the regulatory role of miR-146 on HDMCP was confirmed by dual luciferase report system. The H2O2 and ATP levels were measured for mechanism exploration. RESULTS: Increased HDMCP expression was identified in NASH animal model and HFFA-72h cultured L02 cell. Moreover, under regulation of miR-146, NASH alleviation was achieved after HDMCP downregulation in both in vivo and in vitro, according to the declination of steatosis and inflammation related markers. Though H2O2 and ATP levels were increased and decreased in NASH models, HDMCP down regulation both increased their levels. CONCLUSIONS: The miR-146-HDMCP-ATP/H2O2 pathway may provide novel mechanism and treatment option for NASH.


Assuntos
Fígado/patologia , MicroRNAs/genética , Proteínas de Transporte da Membrana Mitocondrial/genética , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Regulação para Cima , Animais , Apoptose , Linhagem Celular , Modelos Animais de Doenças , Inflamação/genética , Inflamação/patologia , Fígado/metabolismo , Masculino , Camundongos Endogâmicos BALB C
14.
World J Gastroenterol ; 22(36): 8226-33, 2016 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-27688665

RESUMO

AIM: To perform a systematic review to grade guidelines and present recommendations for clinical management of non-alcoholic fatty liver disease (NAFLD). METHODS: A database search was conducted on PubMed for guidelines published before May 2016, supplemented by reviewing relevant websites. The Appraisal of Guidelines for Research and Evaluation (ARGEE) Instrument II was a tool designed to appraise the methodological rigor and transparency in which a clinical guideline is developed and it is used internationally. It was used to appraise the quality of guidelines in this study. The inclusion criteria include: clinical NAFLD guidelines for adults, published in English, and released by governmental agencies or key organizations. RESULTS: Eleven guidelines were included in this study. Since 2007, guidelines have been released in Asia (3 in China, 1 in South Korea, and 1 in Japan), Europe (1 in Italy), America (1 in United States and 1 in Chile) and three international agencies [European associations joint, Asia-Pacific Working Party and World Gastroenterology Organization (WGO)]. Using the ARGEE II instrument, we found US 2012 and Europe 2016 had the highest scores, especially in the areas of rigor of development and applicability. Additionally, Italy 2010 and Korea 2013 also presented comprehensive content, rigorous procedures and good applicability. And WGO 2014 offered various algorithms for clinical practice. Lastly, a practical algorithm for the clinical management was developed, based on the recommended guidelines. CONCLUSION: This is the first systematic review of NAFLD guidelines. It may yield insights for physicians and policy-makers in the development and application of guidelines.


Assuntos
Hepatopatia Gordurosa não Alcoólica/terapia , Guias de Prática Clínica como Assunto , Algoritmos , Medicina Baseada em Evidências , Gastroenterologia/métodos , Gastroenterologia/normas , Humanos , Cooperação Internacional , Resultado do Tratamento
15.
Oncotarget ; 7(41): 66455-66467, 2016 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-27677588

RESUMO

The pathogenesis of nonalcoholic steatohepatitis (NASH) is still unclear, where involvement of circRNA is considered for its active role as "miRNA sponge". Therefore, we aimed to investigate the circRNA expression pattern in NASH and further construct the circRNA-miRNA-mRNA network for in-depth mechanism exploration. Briefly, NASH mice model was established by Methionine and choline deficiency (MCD) diet feeding. Liver circRNA and mRNA profile was initially screened by microarray and ensuing qRT-PCR verification was carried out. The overlapped predicted miRNAs as downstream targets of circRNAs and upstream regulators of mRNAs were verified by qRT-PCR and final circRNA-miRNA-mRNA network was constructed. Gene Ontology (GO) and KEGG pathway analysis were further applied to enrich the huge mRNA microarray data. To sum up, there were 69 up and 63 down regulated circRNAs as well as 2760 up and 2465 down regulated mRNAs in NASH group, comparing with control group. Randomly selected 13 of 14 mRNAs and 2 of 8 circRNAs were successfully verified by qRT-PCR. Through predicted overlapped miRNA verification, four circRNA-miRNA-mRNA pathways were constructed, including circRNA_002581-miR-122-Slc1a5, circRNA_002581- miR-122-Plp2, circRNA_002581-miR-122-Cpeb1 and circRNA_007585-miR-326- UCP2. GO and KEGG pathway analysis also enriched specific mRNAs. Therefore, circRNA profile may serve as candidate for NASH diagnosis and circRNA-miRNA -mRNA pathway may provide novel mechanism for NASH.


Assuntos
MicroRNAs , Hepatopatia Gordurosa não Alcoólica/genética , RNA Mensageiro , RNA , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB C
17.
Nutr. hosp ; 33(2): 303-309, mar.-abr. 2016. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-153178

RESUMO

Background: Betatrophin is a novel adipokine that provokes pancreatic β-cell proliferation and is involved in lipid metabolism. Aims: This study aims to evaluate the role of serum betatrophin in metabolic syndrome (MetS). Methods: A hospital-based, age-/gender-matched case control study was conducted. The serum betatrophin level was evaluated by enzymelinked immunosorbent assay. Serum concentrations of 12 adipokines were measured to assess their associations with serum betatrophin, using commercial Adipokine Magnetic Bead Panel kits. Statistical analyses included bivariate correlation, receiver operating characteristic (ROC) curve, and multivariate stepwise linear regression. Results: Serum betatrophin showed a higher level in MetS patients (997.36 ± 475.92 pg/ml, p = 0.001) compared with controls (735.35 ± 526.51 pg/ml). Compared with the lowest tertile, the highest tertile of serum betatrophin level indicated an association with higher risk of MetS (adjusted odds ratio = 3.521, 95% confidence interval [CI] [1.191-10.413], p = 0.023). ROC curve of betatrophin was developed to predict the presence of MetS (area under ROC = 0.682 [95% CI, 0.597-0.767], p < 0.001). Furthermore, betatrophin correlated with several parameters, e.g. age (r = 0.286, p < 0.001), body mass index (r = 0.160, p = 0.046), waist-to-hip ratio (r = 0.241, p = 0.002), high-density lipoprotein cholesterol (r = -0.167, p = 0.037), low-density lipoprotein cholesterol (r = -0.195, p = 0.015), fasting plasma glucose (r = 0.266, p = 0.001), hemoglobin A1C (r = 0.314, p < 0.001), homeostasis model assessment of insulin resistance (r = 0.272, p = 0.001), and various adipokines, e.g. resistin (r = 0.571, p < 0.001), interleukin-8 (r = 0.435, p < 0.001), tumor necrosis factor-α (r = 0.295, p = 0.011) and lipocalin-2 (r = 0.346, p = 0.003). Conclusions: This study supports that serum betatrophin plays an important role in MetS, involving the regulations of glucose and lipid metabolism and inflammation (AU)


Introducción: la betatrofina es una novedosa adipoquina que provoca la proliferación de células β pancreáticas e interviene en el metabolismo de los lípidos. Objetivos: el propósito de este estudio es evaluar el papel de la betatrofina en el síndrome metabólico. Método: se llevó a cabo un estudio hospitalario de casos y controles según sexo y edad. El nivel de betatrofina en suero fue evaluado mediante ensayo por inmunoabsorción ligado a enzimas. Se midieron las concentraciones en suero de 12 adipoquinas para evaluar las asociaciones con la betatrofina usando los kits comerciales Adipokine Magnetic Bead Panel. Los análisis estadísticos incluyeron correlación bivariada, análisis de curva ROC y análisis de regresión lineal multivariable. Resultados: el nivel de betatrofina en suero fue más elevado en pacientes con síndrome metabólico (997,36 ± 475,92 pg/ml, p = 0,001) que en los controles (735,35 ± 526,51 pg/ml). Frente al tercil más bajo, el tercil más alto del nivel de betatrofina mostró una asociación con mayor riesgo de síndrome metabólico (odds ratio ajustado = 3,521, intervalo de confianza [IC] 95% [1,191-10,413], p = 0,023). Se desarrolló la curva ROC de betatrofina para pronosticar la presencia de síndrome metabólico (área bajo la curva ROC = 0,682 [95% IC, 0,597-0,767], p < 0,001). Además, la betatrofina mostró correlación con distintos parámetros, como edad (r = 0,286, p < 0,001), índice de masa corporal (r = 0,160, p = 0,046), índice cintura-cadera (r = 0,241, p = 0,002), lipoproteína de alta densidad (r = -0,167, p = 0,037), lipoproteína de baja densidad (r = -0,195, p = 0,015), glucosa plasmática en ayunas (r = 0,266, p = 0,001), hemoglobina A1C (r = 0,314, p < 0,001), índice de resistencia a la insulina mediante HOMA (r = 0,272, p = 0,001) y diversas adipoquinas, entre ellas resistina (r = 0,571, p < 0,001), interleucina-8 (r = 0,435, p < 0,001), factor de necrosis tumoral alfa (r = 0,295, p = 0,011) y lipocalina-2 (r = 0,346, p = 0,003). Conclusiones: este estudio demuestra que la betatrofina en suero desempeña una importante labor en el síndrome metabólico, implicando la regulación del metabolismo de la glucosa y los lípidos y la inflamación (AU)


Assuntos
Humanos , Masculino , Feminino , Síndrome Metabólica/fisiopatologia , Adipocinas/sangue , Glucose/metabolismo , Metabolismo dos Lipídeos , Inflamação/fisiopatologia , Estudos de Casos e Controles , Biomarcadores/sangue , Angiopoietinas/análise , Mediadores da Inflamação/análise
18.
J Gastroenterol Hepatol ; 31(8): 1405-13, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27010240

RESUMO

The incidence of obesity is increasing in Asia, with implications on gastrointestinal (GI) and liver diseases. The Gut and Obesity in Asia Workgroup comprises regional experts with the aim of studying relationship between obesity and the GI and liver diseases in Asia. Through literature review and the modified Delphi process, consensus statements examining the impact of obesity on esophageal, gastric, pancreatic, colorectal, and liver diseases, exploring relationship between gut microbiome and obesity, and assessing obesity therapies have been produced by the Gut and Obesity in Asia Workgroup. Sixteen experts participated with 9/15 statements having strong consensus (>80% agreement). The prevalence of obesity in Asia is increasing (100% percentage agreement in brackets), and this increased prevalence of obesity will result in a greater burden of obesity-related GI and liver diseases (93.8%). There was consensus that obesity increases the risk of gastric cancer (75%) and colorectal neoplasia (87.5%). Obesity was also associated with Barrett's esophagus and esophageal adenocarcinoma (66.7%) and pancreatic cancer (66.7%) in Asia. The prevalence of non-alcoholic fatty liver disease (NAFLD) in Asia is on the rise (100%), and the risk of NAFLD in Asia (100%) is increased by obesity. Obesity is a risk factor for the development of hepatocellular carcinoma (93.8%). Regarding therapy, it was agreed that bariatric surgery was an effective treatment modality for obesity (93.8%) but there was less agreement on its benefit for NAFLD (62.5%). These experts' consensus on obesity and GI diseases in Asia forms the basis for further research, and its translation into addressing this emerging issue.


Assuntos
Gastroenteropatias/epidemiologia , Hepatopatias/epidemiologia , Obesidade/epidemiologia , Ásia/epidemiologia , Grupo com Ancestrais do Continente Asiático , Consenso , Técnica Delfos , Medicina Baseada em Evidências , Gastroenteropatias/diagnóstico , Gastroenteropatias/microbiologia , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Humanos , Incidência , Hepatopatias/diagnóstico , Hepatopatias/microbiologia , Obesidade/diagnóstico , Obesidade/microbiologia , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco
19.
World J Gastroenterol ; 22(5): 1884-90, 2016 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-26855548

RESUMO

AIM: To explore the association between serum α-L-fucosidase (AFU) and non-alcoholic fatty liver disease (NAFLD). METHODS: A total of 16473 individuals (9456 men and 7017 women) were included in the current study, who presented for a health examination at the First Affiliated Hospital of Zhejiang University School of Medicine in 2014. The baseline characteristics of the cohort were compared by NAFLD status. Linear regression analysis and stepwise multiple regression analysis were applied to assess the risk factors for NAFLD. Receiver operating characteristic curve was used to determine the sensitivity and specificity of AFU in the diagnosis of NAFLD. RESULTS: The prevalence rates of NAFLD and metabolic syndrome (MetS) were 38.0% and 25.4%, respectively. The NAFLD group had significantly higher AFU levels than the non-NAFLD group (28.7 ± 7.9 U/L vs 26.0 ± 7.3 U/L, P < 0.001) and the prevalence rate of NAFLD increased with progressively higher serum AFU levels. AFU was positively correlated with MetS and its five components: central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, and elevated blood pressure and fasting glucose. Stepwise multiple logistic regression analysis showed that AFU was associated with an increased risk of NAFLD (OR = 1.009, 95%CI: 1.003-1.014, P < 0.001). The best cut-off value of AFU for the diagnosis of NAFLD was 27.5 U/L. The area under the curve (diagnostic efficacy index) was 0.606. The sensitivity and specificity were 54.6% and 61.8%, respectively. CONCLUSION: AFU level is significantly associated with NAFLD, and elevated AFU level is an independent risk factor for NAFLD.


Assuntos
Síndrome Metabólica/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , alfa-L-Fucosidase/sangue , Adulto , Área Sob a Curva , Biomarcadores/sangue , Distribuição de Qui-Quadrado , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/enzimologia , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Análise Multivariada , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Razão de Chances , Valor Preditivo dos Testes , Prevalência , Curva ROC , Reprodutibilidade dos Testes , Fatores de Risco , Regulação para Cima
20.
Endocrine ; 51(1): 91-100, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26362060

RESUMO

Recent animal studies support close associations of Periostin with hepatosteatosis and steatohepatitis. This study is to evaluate the role of serum periostin in non-alcoholic fatty liver disease (NAFLD). A hospital-based age-/sex-matched case-control study was conducted. Binary logistic regression and receiver operating characteristic (ROC) curve were performed. Serum adipokines were measured by Adipokine Magnetic Bead Panel kits. The serum concentration of Periostin in NAFLD (1914.16 [1323.59-2654.88] ng/ml, P < 0.001) was higher than it in control (1244.94 [837.87-2028.55] ng/ml). The frequency of NAFLD grew (29.8, 52.6, and 67.2%, P < 0.001), as Periostin concentration increased among its tertiles. Compared with the 1st tertile, the 2nd and the 3rd tertiles of Periostin indicated significant associations with higher odds of NAFLD [adjusted odds ratio = 2.602 (95% confidence interval (CI) 1.030-6.575), P = 0.043 and 2.819 (95% CI 1.629-4.878), P < 0.001]. ROC curve of Periostin was developed to predict the presence of NAFLD (area under ROC = 0.693 [95% CI 0.614-0.771], P < 0.001). Lastly, Periostin correlated with several adipokines, including Resistin (r = 0.269, P = 0.018), Adiponectin (r = -0.352, P = 0.002), Interleukin (IL)-6 (r = 0.359, P = 0.001), IL-8 (r = 0.364, P = 0.001), Lipocalin-2 (r = 0.623, P < 0.001), Hepatocyte growth factor (r = 0.522, P < 0.001), and Nerve growth factor (r = 0.239, P = 0.036). It suggests Periostin as a potential biomarker in the management of NAFLD.


Assuntos
Biomarcadores/sangue , Moléculas de Adesão Celular/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Curva ROC , Sensibilidade e Especificidade
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