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1.
J Viral Hepat ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670859

RESUMO

The decay rate of hepatitis C virus (HCV) infected cells during therapy has been used to determine the duration of treatment needed to attain a sustained virologic response, but with direct acting antivirals (DAA) this rate has been difficult to estimate. Here we show that it is possible to estimate it, by simultaneously analyzing the viral load and alanine aminotransferase (ALT) kinetics during combination DAA therapy.We modeled the HCV RNA and ALT serum kinetics in 26 patients with chronic HCV genotype 1b infection, under four different sofosbuvir based combination treatments. In all patients, ALT decayed exponentially to a set-point in the normal range by 1-3 weeks after initiation of therapy. The model indicates that the ALT decay rate during the first few weeks after initiation of therapy reflects the death rate of infected cells, with an estimated median half-life of 2.5 days in this patient population. This information allows independent estimation of the rate of loss of intracellular replication complexes during therapy. Our model also predicts that the final ALT set-point is not related to the release of ALT by dying HCV infected cells. Using ALT data, one can separately obtain information about the rate of "cure" of HCV infected cells versus their rate of death, something not possible when analyzing only HCV RNA data. This information can be used to compare the effects of different DAA combinations, and to rationally evaluate their antiviral effects.

2.
Int J Surg ; 70: 93-101, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31494334

RESUMO

BACKGROUND: At present, there is no ideal treatment for postoperative ileus (POI) after abdominal surgery. This meta-analysis aims to evaluate the efficacy of electroacupuncture (EA) and transcutaneous electroacupuncture (TEA) in improving postoperative POI. METHODS: We systematically screened randomized controlled trials (RCTs) from multiple databases and included 15 high quality RCTs. Two investigators independently conducted data extraction, risk of bias assessment and statistical analysis. Meta-analysis was performed by a random- (REM) or fixed-effect (FIXED) model. RESULTS: A total of 15 trials involving 965 participates were included. Meta-analysis results favored EA/TEA treatment for POI by analysis of time to first flatus [mean difference (MD) -11.60 h, I2 = 94%, REM)], time to first defecation (MD -12.94 h, I2 = 90%, REM), time to bowel sound recovery (MD -7.25 h, I2 = 85%, REM), time to first oral feeding (MD -15.76 h, I2 = 47%, REM) and length of hospital stay (MD -1.19 d, I2 = 44%, REM). Subgroup analysis of laparoscopic surgery patients also favored EA/TEA by analysis of time to first flatus (MD -2.46 h, I2 = 0%, FIXED), time to first oral feeding (MD -10.73 h, I2 = 0%, FIXED) and length of hospital stay (MD -1.30 d, I2 = 32%, REM). ST36 (Zusanli), ST37 (Shangjuxu) and ST39 (Xiajuxu) are preferred EA/TEA acupoints for treating POI. There was no significant difference in postoperative analgesic consumption between EA and control groups (P = 0.39). No severe adverse events associated with EA/TEA were reported. CONCLUSION: This meta-analysis suggests that EA/TEA is a safe, effective treatment for POI after abdominal surgeries including laparoscopic surgery, and that EA/TEA does not relieve postoperative pain after abdominal surgery. There is significant heterogeneity of research on this subject, thus, a professional consensus is needed to establish a standard protocol for use of this technique.

3.
Ann Transplant ; 24: 328-340, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31171762

RESUMO

BACKGROUND Allogeneic transplantation remains one of the best therapies for high-risk acute myeloid leukemia (HR-AML). MATERIAL AND METHODS This study retrospectively analyzed 126 patients with HR-AML after allogeneic hematopoietic stem cell transplantation (allo-HCST). RESULTS The disease-free survival (DFS) rates of 1 year and 3 years were 58.83% (95%CI: 50.75-68.20%) and 53.09% (95%CI: 44.59-63.22%) respectively. The cumulative relapse rates of 1 year and 3 years were 21.1% (95%CI: 14.4-28.8%) and 25.9% (95%CI: 18.1-34.5%) respectively. The cumulative incidences of III to IV acute graft-versus-host disease (aGVHD) for 100 days was 8.70% (95%CI: 4.6-14.5%). The cumulative rate of extensive chronic graft-versus-host disease (cGVHD) for 1-year was 4.1% (95%CI: 1.5-8.7%). The cumulative transplantation related mortality rate of 1 year and 3 years were 20.1% (95%CI: 13.6-27.6%) and 21.0% (95%CI: 14.3-28.6%) respectively. Univariate analysis revealed that lower overall survival was correlated with age, bacterial or fungal infection, disease status at transplantation, III-IV aGVHD, post-transplantation lymphoproliferative disorders (PTLD), white blood cell engraftment, and extramedullary involvement (P<0.05). The results of multivariate analysis were that the aforementioned factors were also related to lower overall survival except for PTLD (P<0.05). The results of univariate and multivariate analysis were that extramedullary involvement, III-IV aGVHD, and status pre-transplantation influenced DFS (P<0.05). The risk factors for relapse were status pre-transplantation and extramedullary involvement by univariate and multivariate analysis (P<0.05). CONCLUSIONS HR-AML has inferior prognosis. Our study indicated the necessity of achieving remission status prior to hematopoietic stem cell transplantation, and administration of preventive treatments on high-risk patients after hematopoietic stem cell transplantation. In addition, adequate prevention and treatment of complications are needed.

4.
J Cell Physiol ; 234(8): 12964-12970, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30556902

RESUMO

Hepatocellular carcinoma is one of the most prevalent and fatal cancers. Studying the long noncoding RNA (lncRNA) alterations in hepatocellular carcinoma may lead to new therapeutic strategies. We checked whether there were correlations between The Cancer Genome Atlas expression profiles of the differentially expressed lncRNAs and their DNA methylation status or the copy number variations for hepatocellular carcinoma. We obtained 41 lncRNAs that were differentially expressed between tumor and normal samples, and their DNA methylation status was negatively correlated with the expression levels. We identified five lncRNAs that were recurrently amplified or deleted in tumor samples, but none of them were associated with the messenger RNA (mRNA) expression levels. To obtain the biological function of these lncRNAs, the coexpressed mRNAs in the hepatocellular carcinoma were figured out. A total of 10 lncRNAs were highly correlated with at least one gene. Six out of the ten lncRNAs were already known to be related with cancer previously. LINC01615 had 72 coexpressed genes, and we carried out the gene ontology (GO) term enrichment for these protein-coding genes. The results suggested that these lncRNAs were associated with extracellular matrix organization. To summarize, we identified 41 potentially cancer-related lncRNAs. In particular, we proposed that LINC01615 potentially affected the extracellular matrix and had further impacts on the metastasis of hepatocellular carcinoma.

5.
J Cell Physiol ; 2018 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-30317608

RESUMO

The molecular mechanism of liver fibrosis caused by hepatitis C virus (HCV) is not clear. The aim of this study is to understand the molecular mechanism of liver fibrosis induced by HCV and to identify potential therapeutic targets for hepatic fibrosis. We analyzed gene expression patterns between high liver fibrosis and low liver fibrosis samples, and identified genes related to liver fibrosis. We identified TAF1, HNF4A, and CALM2 were related to the development of liver fibrosis. HNF4A is important for hepatic fibrogenesis, and upregulation of HNF4A is an ideal choice for treating liver fibrosis. The gene expression of CALM2 is significantly lower in liver fibrosis samples than nonfibrotic samples. TAF1 may serve as a biomarker for liver fibrosis. The results were further validated by an independent data set GSE84044. In summary, our study described changes in the gene expression during the occurrence and development of liver fibrosis. The TAF1, HNF4A, and CALM2 may serve as novel targets for the treatment of liver fibrosis.

6.
Int J Hyperthermia ; 34(8): 1351-1358, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29720001

RESUMO

OBJECTIVE: To evaluate the safety and long-term outcomes of microwave ablation (MWA) combined with transarterial chemoembolization (TACE) in a single stage for the treatment of hepatocellular carcinoma (HCC) with a maximum diameter of 5.0-10.0 cm. METHODS: From January 2013 to December 2016, 84 consecutive HCC patients with cirrhosis from two medical centers who underwent MWA-TACE as a first-line treatment for up to three HCCs with maximum diameters of 5.0-10.0 cm were included. Feasibility, safety and effectiveness were evaluated. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Cox regression models were used to identify the prognostic factors. RESULTS: The technique was successfully performed in all the patients. Grade 3 complications consisted of two cases of hemoperitoneum requiring blood transfusions and embolization. The cumulative incidence of local tumor progression was 25.8% at 3 years, with tumor size found to be the only significant predictive factor (p = .007). The cumulative incidence of OS was 81%, 68% and 49% at 1, 2 and 3 years, respectively. According to the Cox proportional hazards model analysis, serum AFP level, Child-Pugh class and tumor number were significant prognostic factors for OS. CONCLUSION: MWA-TACE is a safe, feasible and effective therapy for the treatment of 5.0- to 10.0-cm HCC lesions in patients with cirrhosis.

7.
Hepatol Int ; 12(2): 107-117, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29651701

RESUMO

BACKGROUND AND AIMS: Limited data are available regarding the association of hepatitis B virus (HBV) mutations with liver fibrosis in HBV infection. The study aimed to clarify whether HBV preS deletion mutation is associated with liver fibrosis progression. METHODS: A total of 469 patients were enrolled, including 324 with chronic hepatitis B (CHB), 28 with HBV-related compensated liver cirrhosis (LC), and 117 with HBV-related decompensated LC. All CHB and compensated LC patients received liver biopsy. Fibrosis grade was assessed using METAVIR score. HBV preS deletion was determined by direct sequencing and verified by clonal sequencing. RESULTS: Overall preS deletion was detected in 12.6% (59/469) patients, specifically, in 7.51% (13/173), 10.60% (16/151), and 20.69% (30/145) of patients with no-to-mild liver fibrosis (F0-1), moderate-to-severe liver fibrosis (F2-3), and cirrhosis (F4), respectively (p < 0.01). Patients with preS-deleted HBV had lower serum HBV DNA and albumin levels compared to patients with wild-type HBV. The median length of preS deletion was 39-base pairs (bp) (3-204 bp) and the deletion most frequently emerged in preS2 initial region. Multivariate analysis identified the preS2 deletion rather than preS1 deletion to be an independent risk factor of significant fibrosis, i.e., METAVIR F ≥ 2 (p = 0.007). In addition, preS-deleted viral sequences were detected in the pool of intrahepatic HBV covalently closed circular DNA. CONCLUSIONS: HBV preS deletion is positively associated with liver fibrosis progression in chronic HBV-infected patients. HBV preS2 deletion may serve as a warning indicator for liver fibrosis progression.


Assuntos
Vírus da Hepatite B/genética , Hepatite B Crônica/genética , Cirrose Hepática/genética , Deleção de Sequência/genética , Adulto , Motivos de Aminoácidos/genética , Códon de Iniciação/genética , Estudos Transversais , DNA Circular/genética , DNA Viral/genética , Progressão da Doença , Feminino , Genótipo , Humanos , Masculino , Sequências Repetitivas de Ácido Nucleico/genética , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
8.
Hepatology ; 67(1): 454-455, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29080218
9.
Liver Int ; 37 Suppl 1: 59-66, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28052634

RESUMO

Since the registration of the first effective nucleoside analogue against the hepatitis B virus almost two decades ago, major progress has been made in the management of chronic hepatitis B infection. However, hepatitis B-related morbidity and mortality remain a major global health threat. This is partly due to the escalating costs and the decrease in compliance related to the need for prolonged therapy for most patients who cannot be "cured". New biomarkers such as quantitative hepatitis B surface antigen might help to determine if hepatitis B e antigen negative patients can be taken off nucleos(t)ide analogues. On the other hand, novel compounds that target the viral life cycle or modulate host immune response are in the pipeline. In the next few years, one should expect breakthrough advancement to be made leading to a "cure" for patients with chronic hepatitis B infection by inducing hepatitis surface antigen loss with or without the development of the hepatitis B surface antibody. In addition, attention and necessary actions should also be taken in patients with hepatitis B infection who are being treated with immunosuppressive therapy and direct anti-viral (DAAs) agents for hepatitis C infection to prevent hepatitis from hepatitis B reactivation.


Assuntos
Antivirais/farmacologia , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Imunossupressores/farmacologia , Biomarcadores/sangue , Ensaios Clínicos como Assunto , Desenho de Drogas , Guanina/análogos & derivados , Guanina/uso terapêutico , Vírus da Hepatite B , Humanos , Interferon-alfa/uso terapêutico , Tenofovir/uso terapêutico
10.
Oncotarget ; 8(8): 12784-12791, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-28061463

RESUMO

The 2014-2015 Ebola epidemic was considered to be the largest and most complex outbreak, which caused 11,310 reported deaths. The epidemic disease can cause a mental health crisis, however, there is only a small amount of scientific literature available related to this health issue so far. We evaluated the psychological symptoms of 161 participants including Ebola survivors and healthcare workers in Sierra Leone, analyzed the impact of job classification, education level on psychological status. We found that the order of total general severity index (GSI) scores from high to low was EVD survivors, SL medical staff, SL logistic staff, SL medical students, and Chinese medical staff. There were 5 dimensions (obsession-compulsion, anxiety, hostility, phobic anxiety, and paranoid ideation) extremely high in EVD survivors. GSI were associated with university education negatively. We believed our information is necessary to develop the comprehensive emergency response plan for emerging infectious disease outbreak.


Assuntos
Pessoal de Saúde/psicologia , Doença pelo Vírus Ebola/psicologia , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Sobreviventes/psicologia , Adolescente , Adulto , Criança , Estudos Transversais , Surtos de Doenças , Feminino , Doença pelo Vírus Ebola/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prevalência , Serra Leoa , Adulto Jovem
12.
Med Sci Monit ; 22: 3009-17, 2016 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-27561414

RESUMO

BACKGROUND The overall prognosis of acute myeloid leukemia (AML) patients with mixed-lineage leukemia (MLL) gene-positivity is unfavorable. In this study, we evaluated the expression levels of the MLL gene in AML patients. MATERIAL AND METHODS We enrolled 68 MLL gene-positive patients out of 433 newly diagnosed AML patients, and 216 bone marrow samples were collected. Real-time fluorescence quantitative PCR (RQ-PCR) was used to precisely detect the expression levels of the MLL gene. RESULTS We divided 41 patients into 2 groups according to the variation of MRD (minimal residual disease) level of the MLL gene. Group 1 (n=22) had a rapid reduction of MRD level to ≤10^-4 in all samples collected in the first 3 chemotherapy cycles, while group 2 (n=19) had MRD levels constantly >10^-4 in all samples collected in the first 3 chemotherapy cycles. Group 1 had a significantly better overall survival (p=0.001) and event-free survival (p=0.001) compared to group 2. Moreover, the patients with >10^-4 MRD level before the start of HSCT (hematopoietic stem cell transplantation) had worse prognosis and higher risk of relapse compared to patients with ≤10^-4 before the start of HSCT. CONCLUSIONS We found that a rapid reduction of MRD level to ≤10^-4 appears to be a prerequisite for better overall survival and event-free survival during the treatment of AML. The MRD levels detected by RQ-PCR were basically in line with the clinical outcome and may be of great importance in guiding early allogeneic HSCT (allo-HSCT) treatment.


Assuntos
Histona-Lisina N-Metiltransferase/genética , Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Fluorescência , Transplante de Células-Tronco Hematopoéticas/métodos , Histona-Lisina N-Metiltransferase/biossíntese , Humanos , Leucemia Mieloide Aguda/enzimologia , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Proteína de Leucina Linfoide-Mieloide/biossíntese , Neoplasia Residual , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Recidiva , Transcriptoma
13.
Hepatol Int ; 10(5): 789-98, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27443347

RESUMO

BACKGROUND: Treatment-experienced chronic hepatitis C (CHC) genotype (GT) 1b represents a major medical burden in China. We evaluate the efficacy, safety and cost-effectiveness of ribavirin (RBV)-free pan-oral direct-acting antivirals (DAAs) in treatment-experienced Chinese with GT1b CHC, including patients with cirrhosis. METHODS: One hundred forty treatment-experienced GT1b CHC Chinese with and without cirrhosis were included in this study. Ninety-four patients were treated with either daclatasvir (DCV, 60 mg)-sofosbuvir (SOF, 400 mg) (group 1, n = 46) or ledipasvir (LDV, 90 mg)-SOF (400 mg) (group 2, n = 48) for 12 weeks. Forty-six patients treated with pegylated interferon and RBV therapy for 72 weeks were enrolled as the control group (group 3). Patients were followed at 4-weekly intervals till 24 weeks after the end of treatment. RESULTS: All patients in group 1 (46/46, 100 %) and 2 (48/48, 100 %) had achieved sustained virologic response at 24 weeks after the end of treatment (SVR 24), which was significantly higher than that of group 3 (13/46, 28.3 %) (p < 0.001). The SVR 24 rates of cirrhotic patients in group 1 (27/27, 100 %) and 2 (27/27, 100 %) were also significantly higher than that of group 3 (3/25, 12 %) (p < 0.001). Twelve weeks of RBV-free LDV-SOF and DCV-SOF was either cost-saving or cost-effective. Adverse events were significantly lower in group 1 and 2 compared with group 3 (p < 0.001). CONCLUSION: Compared with standard therapies, 12 weeks of RBV-free DAA therapies is highly effective, well tolerated and cost-effective in treatment-experienced Chinese with GT1b CHC including patients with cirrhosis.


Assuntos
Antivirais/administração & dosagem , Quimioterapia Combinada/economia , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Adolescente , Adulto , Idoso , Antivirais/economia , China , Análise Custo-Benefício , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/economia , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/economia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ribavirina/administração & dosagem , Resultado do Tratamento , Adulto Jovem
14.
PLoS One ; 11(6): e0155934, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27276081

RESUMO

BACKGROUND: Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions. METHODS: A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable. RESULTS: Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US$21,612. It varied by economic regions. The probability of cost-effectiveness was 18% and 47% for treatment-naive and experienced patients, and it ranged from 15% in treatment-naïve patients in Central-China to 64% in treatment-experienced patients in Eastern-China. The price of 12-week sofosbuvir/ledipasvir treatment needs to be reduced by at least 81% to US$18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US$105 to make the regimen affordable in average patients in China. CONCLUSION: Sofosbuvir/ledipasvir regimen is not cost-effective in most Chinese patients with genotype 1b HCV infection. The results vary by economic regions. Drug price of sofosbuvir/ledipasvir needs to be substantially reduced when entering the market in China to ensure the widest accessibility.


Assuntos
Benzimidazóis/economia , Fluorenos/economia , Hepacivirus , Hepatite C/economia , Modelos Econômicos , Sofosbuvir/economia , Grupo com Ancestrais do Continente Asiático , Benzimidazóis/administração & dosagem , China/epidemiologia , Custos e Análise de Custo , Feminino , Fluorenos/administração & dosagem , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Humanos , Masculino , Cadeias de Markov , Sofosbuvir/administração & dosagem
15.
Chin Med J (Engl) ; 129(11): 1355-62, 2016 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-27231175

RESUMO

BACKGROUND: The acute myeloid leukemia 1 (AML1)-eight-twenty-one (ETO) fusion protein generated by the t(8;21)(q22;q22) translocation is considered to display a crucial role in leukemogenesis in AML. By focusing on the anti-leukemia effects of eyes absent 4 (EYA4) gene on AML cells, we investigated the biologic and molecular mechanism associated with AML1-ETO expressed in t(8;21) AML. METHODS: Qualitative polymerase chain reaction (PCR), quantitative reverse transcription PCR (RT-PCR), and Western blotting analysis were used to observe the mRNA and protein expression levels of EYA4 in cell lines. Different plasmids (including mutant plasmids) of dual luciferase reporter vector were built to study the binding status of AML1-ETO to the promoter region of EYA4. Chromatin immunoprecipitation assay was used to study the epigenetic silencing mechanism of EYA4. Bisulfite sequencing was applied to detect the methylation status in EYA4 promoter region. The influence of EYA4 gene in the cell proliferation, apoptosis, and cell clone-forming ability was detected by the technique of Cell Counting Kit-8, flow cytometry, and clonogenic assay. RESULTS: EYA4 gene was hypermethylated in AML1-ETO+ patients and its expression was down-regulated by 6-fold in Kasumi-1 and SKNO-1 cells, compared to HL-60 and SKNO-1-siA/E cells, respectively. We demonstrated that AML1-ETO triggered the epigenetic silencing of EYA4 gene by binding at AML1-binding sites and recruiting histone deacetylase 1 and DNA methyltransferases. Enhanced EYA4 expression levels inhibited cellular proliferation and suppressed cell colony formation in AML1-ETO+ cell lines. We also found EYA4 transfection increased apoptosis of Kasumi-1 and SKNO-1 cells by 1.6-fold and 1.4-fold compared to negative control, respectively. CONCLUSIONS: Our study identified EYA4 gene as targets for AML1-ETO and indicated it as a novel tumor suppressor gene. In addition, we provided evidence that EYA4 gene might be a novel therapeutic target and a potential candidate for treating AML1-ETO+ t (8;21) AML.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Epigênese Genética/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Proteínas de Fusão Oncogênica/metabolismo , Transativadores/metabolismo , Apoptose/genética , Apoptose/fisiologia , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Imunoprecipitação da Cromatina , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Metilação de DNA/genética , Inativação Gênica , Células HL-60 , Humanos , Leucemia Mieloide Aguda/genética , Proteínas de Fusão Oncogênica/genética , RNA Interferente Pequeno/genética , Proteína 1 Parceira de Translocação de RUNX1 , Ensaio de Radioimunoprecipitação , Transativadores/genética
16.
Mol Med Rep ; 13(3): 2511-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26821057

RESUMO

The aim of the current study was to investigate whether intestinal ischemic preconditioning (IP) reduces damage to the liver during hepatic ischemia reperfusion (IR). Sprague Dawley rats were used to model liver IR injury, and were divided into the sham operation group (SO), IR group and IP group. The results indicated that IR significantly increased Bax, caspase 3 and NF­κBp65 expression levels, with reduced expression of Bcl­2 compared with the IP group. Compared with the IR group, the levels of AST, ALT, MPO, MDA, TNF­α and IL­1 were significantly reduced in the IP group. Immunohistochemistry for Bcl­2 and Bax indicated that Bcl­2 expression in the IP group was significantly increased compared with the IR group. In addition, IP reduced Bax expression compared with the IR group. The average liver injury was worsened in the IR group and improved in the IP group, as indicated by the morphological evaluation of liver tissues. The present study suggested that IP may alleviates apoptosis, reduce the release of pro­inflammatory cytokines, ameloriate reductions in liver function and reduce liver tissue injury. To conclude, IP provided protection against hepatic IR injury.


Assuntos
Precondicionamento Isquêmico , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/sangue , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Aspartato Aminotransferases/sangue , Interleucina-1beta/sangue , Intestinos/irrigação sanguínea , Isquemia/sangue , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/sangue , Peroxidase/sangue , Ratos Sprague-Dawley , Traumatismo por Reperfusão/sangue , Fator de Necrose Tumoral alfa/sangue
17.
Dis Markers ; 2015: 325176, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26612965

RESUMO

miRNA-20b has been shown to be aberrantly expressed in several tumor types. However, the clinical significance of miRNA-20b in the prognosis of patients with hepatocellular carcinoma (HCC) is poorly understood, and the exact role of miRNA-20b in HCC remains unclear. The aim of the present study was to investigate the association of the expression of miR-20b with clinicopathological characteristics and overall survival of HCC patients analyzed by Kaplan-Meier analysis and Cox proportional hazards regression models. Meanwhile, the HIF-1α and VEGF targets of miR-20b have been confirmed. We found not only miR-20b regulation of HIF-1α and VEGF in normal but also regulation of miR-20b in hypoxia. This mechanism would help the tumor cells adapt to the different environments thus promoting the tumor invasion and development. The whole study suggests that miR-20b, HIF-1α, and VEGF serve as a potential therapeutic agent for hepatocellular carcinoma.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Carcinoma Hepatocelular/diagnóstico , Feminino , Células Hep G2 , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/genética
18.
Sci Rep ; 5: 12159, 2015 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-26199080

RESUMO

Chronic hepatitis B virus (HBV) infection is a major global health burden. Functional exhaustion and numerical reduction of HBV-specific cytotoxic T lymphocytes (CTLs) in the liver and peripheral blood limit anti-HBV CTL activity in patients with chronic HBV infection (CHB). However, the ongoing anti-HBV CD8(+) T cell responses in the lymphoid organs are largely unknown due to the infeasibility of obtaining lymphoid organs from CHB patients. Here we demonstrate that the percentage of HBV-specific CD8(+) T cells is higher in the spleen of CHB patients than that from peripheral blood and liver. Although they do respond to TCR stimulation and produce IFNγ, the cells proliferate poorly. Furthermore, miR-720 expression is upregulated in HBV-specific CD8(+) T cells. Overexpression of miR-720 in primary human CD8(+) T cells inhibits TCR stimulation-induced proliferation. We also demonstrate that TGFß sustains miR-720 upregulation after TCR stimulation, and blood TGFß levels are associated with the outcome of type I interferon treatment of CHB patients. Thus, therapies targeting miR-720 may help restore impaired immunity in CHB patients.


Assuntos
Hepatite B Crônica/imunologia , MicroRNAs/fisiologia , Linfócitos T Citotóxicos/imunologia , Proteínas de Ciclo Celular/genética , Humanos , Receptores de Antígenos de Linfócitos T/metabolismo , Baço/imunologia , Fator de Crescimento Transformador beta/metabolismo
19.
Liver Int ; 35(11): 2392-400, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25689614

RESUMO

BACKGROUND & AIMS: Controlled attenuation parameter (CAP) is a non-invasive method for evaluating hepatic steatosis. However, larger skin capsular distance (SCD) can affect the accuracy. The aim of this study was to investigate the impact of SCD on the diagnostic performance of CAP and liver stiffness measurement (LSM). METHODS: Of 101 patients with non-alcoholic fatty liver disease (NAFLD) and 280 patients with chronic hepatitis B (CHB) who underwent liver biopsy were prospectively recruited. CAP, LSM and SCD were performed using FibroScan with M probe. The areas under receiver operating characteristics curves (AUROCs) were calculated to determine the diagnostic efficacy. The optimal thresholds were defined by the maximum Youden index. RESULTS: SCD (B 30.34, P < 0.001) and hepatic steatosis (B 23.04, P < 0.001) were independently associated with CAP by multivariate analysis. The AUROCs were slightly higher for SCD <25 mm compared to those for SCD ≥25 mm for steatosis ≥5% (0.88 vs. 0.81), >33% (0.90 vs. 0.85) and >66% (0.84 vs. 0.72). For SCD <25 mm, the optimal CAP cut-offs for differentiating steatosis ≥5%, >33% and >66% were 255.0 dB/m, 283.5 dB/m and 293.5 dB/m. However, cut-offs were elevated by approximately 60-70 dB/m for SCD ≥25 mm. When stratified by fibrosis grade, LSM was significantly affected by SCD ≥25 mm for advanced fibrosis (≥F3) in NAFLD, but not in CHB. CONCLUSION: CAP is a promising tool for detecting and quantifying hepatic steatosis. SCD ≥25 mm may cause overestimation of steatosis. Similarly, SCD ≥25 mm affects the detection of advanced fibrosis by LSM in NAFLD patients.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatite B Crônica/patologia , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Pele/patologia , Adulto , Área Sob a Curva , Biópsia , Índice de Massa Corporal , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Curva ROC , Índice de Gravidade de Doença
20.
Ultrason Sonochem ; 23: 59-65, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25224856

RESUMO

Synthesis of 2,3-disubstituted-2,3-dihydroquinazolin-4(1H)-one derivatives catalyzed by dodecylbenzenesulfonic acid was carried out in 80-92% yields at 40-42 °C within 1-2 h in aqueous media via one-pot three-component condensation of isatoic anhydride, aromatic aldehyde and amine under ultrasound irradiation. Convenient work-up procedures, mild reaction conditions, avoiding the use of organic solvents, and friendly to environment are the salient features of this protocol.

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