Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Front Cell Infect Microbiol ; 11: 790036, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869083

RESUMO

Interferon gamma-inducible protein 16 (IFI16) is a DNA sensor protein, which triggers interferon-beta (IFN-ß) production. However, the role of IFI16 in the innate immunity against hepatitis B virus (HBV) remains controversial. Peripheral blood mononuclear cells (PBMCs) and serum specimens were collected from 20 patients with chronic hepatitis B (CHB) receiving Peg-IFN-α2b therapy. IFI16 mRNA/protein of PBMCs and serum IFI16 at baseline and changes during Peg-IFN-α2b treatment were detected. The interaction between IFI16 and HBV DNA in the PBMCs was analyzed using chromatin immunoprecipitation assay. Leukemic T cell line CEM-C7 and HBV-replicating HepG2.2.15 cells were used to test the effects of interferon treatment and HBV replication on IFI16 expression. Compared with healthy controls, lower levels of IFI16 mRNA but more significant expression of IFI16 protein with heterogeneous degradation were detected in PBMCs of CHB patients. Early changes in IFI16 mRNA, but not IFNB mRNA of PBMCs or serum IFI16, were correlated to HBeAg seroconversion of Peg-IFN-α2b therapy. An interaction between IFI16 and HBV DNA was detected in the PBMCs. In the cultured HepG2.2.15 and CEM-C7 cells, interferons resulted in the translocalization of IFI16 from the cytoplasm to the nucleus and inhibited IFI16 degradation. IFI16 of PBMCs may play a role in sensing HBV infection, and early change in IFI16 mRNA of PBMCs is valuable to predict HBeAg seroconversion in Peg-IFN-α2b treatment. The influences on IFI16 degradation and subcellular location may present a molecular mechanism of antiviral activity of interferon.


Assuntos
Antivirais , Hepatite B , Proteínas Nucleares/imunologia , Fosfoproteínas/imunologia , Antivirais/uso terapêutico , Células Cultivadas , Hepatite B/tratamento farmacológico , Hepatite B/imunologia , Humanos , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Leucócitos Mononucleares , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico
2.
Cell Death Dis ; 11(7): 552, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32690860

RESUMO

Acute promyelocytic leukemia (APL) therapy involves the compounds cytotoxic to both malignant tumor and normal cells. Relapsed APL is resistant to subsequent chemotherapy. Novel agents are in need to kill APL cells selectively with minimal toxicity. DDX5 has been recognized to be a novel target to suppress acute myeloid leukemia (AML). However, the role of DDX5 remains elusive in APL. Here a DDX5-targeting fully human monoclonal autoantibody named after 2F5 was prepared. It is demonstrated that 2F5 selectively inhibited APL cell proliferation without toxicity to normal neutrophil and tissues. Moreover, 2F5 was confirmed to induce G0/G1 phase arrest in APL cells, and promote APL cell differentiation combined with decreased DDX5 expression and increased reactive oxygen species (ROS) production. Knockdown of DDX5 by siRNA also inhibited proliferation, promoted cell differentiation and enhanced ROS production in APL cells. However, the ROS inhibitor reversed the effects of 2F5 on DDX5 and ROS in APL cells. Thus, we conclude that DDX5-targeting 2F5 inhibits APL cell proliferation, and promotes cell differentiation via induction of ROS. 2F5 showed the therapeutic value of fully human monoclonal autoantibody in APL, which provides a novel and valid approach for treatment of relapse/refractory APL.


Assuntos
Anticorpos Monoclonais/farmacologia , Diferenciação Celular/efeitos dos fármacos , RNA Helicases DEAD-box/antagonistas & inibidores , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia , Espécies Reativas de Oxigênio/metabolismo , Acetilcisteína/farmacologia , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Humanos , Leucemia Promielocítica Aguda/genética , Masculino , Camundongos Endogâmicos BALB C , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo
3.
Antiviral Res ; 177: 104765, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32171856

RESUMO

BACKGROUND & AIMS: Quantification of anti-HBs and anti-HBc predicts the risk of HBV reactivation (HBVr) in lymphoma patients receiving rituximab treatment. However, it remains unclear whether the quantification is predictive of HBVr in leukemia patients undergoing immunosuppression. METHODS: and patients: Clinical and laboratory data of the leukemia patients with resolved HBV infection diagnosed between January 2013 and March 2018 were retrospectively collected. Data series of HBV seromarkers and HBV DNA levels before the patients receiving chemotherapy and/or hematopoietic stem cell transplantation (HSCT) and during follow-up duration were analyzed. RESULTS: In total, 533 leukemia patients with resolved HBV infection were included. The incidences of HBVr were 5.7% (25/441) and 2.2% (2/92) in patients receiving HSCT and chemotherapy, respectively. In patients receiving HSCT, acute lymphoid leukemia had a significantly higher incidence of HBVr than acute myeloid leukemia (8.9% vs 3.9%, P < 0.05). The incidence varied almost zero to 40% due to the differences in the profiles of HBV antibodies. High anti-HBs (cut-off of 79.2 IU/L) or low anti-HBc levels (cut-off of 4.475, S/CO) at baseline were associated with a low risk of HBVr. Anti-HBe status did not affect the incidence of HBVr. However, the cut-offs were only predictive of HBVr in the patients who had negative anti-HBe. CONCLUSION: The baseline profiles of HBV antibodies are predictive of the risk of HBVr in leukemia patients undergoing immunosuppression. However, seronegative anti-HBe is a prerequisite for using baseline anti-HBs and anti-HBc quantification to predict HBVr risk.


Assuntos
Anticorpos Anti-Hepatite B/imunologia , Hepatite B/imunologia , Leucemia/imunologia , Ativação Viral , Adolescente , Adulto , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Vírus da Hepatite B/imunologia , Humanos , Leucemia/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab/uso terapêutico , Adulto Jovem
4.
EMBO J ; 36(22): 3325-3335, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28963395

RESUMO

The Hippo pathway plays essential roles in organ size control and cancer prevention via restricting its downstream effector, Yes-associated protein (YAP). Previous studies have revealed an oncogenic function of YAP in reprogramming glucose metabolism, while the underlying mechanism remains to be fully clarified. Accumulating evidence suggests long noncoding RNAs (lncRNAs) as attractive therapeutic targets, given their roles in modulating various cancer-related signaling pathways. In this study, we report that lncRNA breast cancer anti-estrogen resistance 4 (BCAR4) is required for YAP-dependent glycolysis. Mechanistically, YAP promotes the expression of BCAR4, which subsequently coordinates the Hedgehog signaling to enhance the transcription of glycolysis activators HK2 and PFKFB3. Therapeutic delivery of locked nucleic acids (LNAs) targeting BCAR4 attenuated YAP-dependent glycolysis and tumor growth. The expression levels of BCAR4 and YAP are positively correlated in tissue samples from breast cancer patients, where high expression of both BCAR4 and YAP is associated with poor patient survival outcome. Taken together, our study not only reveals the mechanism by which YAP reprograms glucose metabolism, but also highlights the therapeutic potential of targeting YAP-BCAR4-glycolysis axis for breast cancer treatment.


Assuntos
Glucose/metabolismo , Proteínas Hedgehog/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Sequência de Bases , Neoplasias da Mama/genética , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Feminino , Glicólise/genética , Células HEK293 , Hexoquinase/genética , Hexoquinase/metabolismo , Humanos , Modelos Biológicos , Fosfofrutoquinase-2/genética , Fosfofrutoquinase-2/metabolismo , Transcrição Genética , Resultado do Tratamento , Regulação para Cima/genética
5.
Virus Res ; 197: 85-91, 2015 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-25533532

RESUMO

Recent studies have shown that the Moloney leukemia virus 10 (Mov10), a putative RNA helicase, has very broad and potent antiretroviral activities. Hepatitis B virus (HBV) has a reverse transcription process, but the potential role of Mov10 in HBV replication remains unknown. In this study, Mov10 was demonstrated to affect HBV expression in HepG2 and HepG2.2.15 cell lines. The data showed that the over-expression of exogenous Mov10 resulted in an increase of the HBsAg and HBeAg levels in the culture supernatant and HBV mRNA level in transfected cells at a low dose and resulted in a decrease at a high dose, but HBV DNA in culture supernatant was not affected. The knockdown of endogenous Mov10 expression through siRNA treatment could suppress levels of HBsAg, HBeAg and HBV mRNA, but had no effect on HBV DNA. Above results indicate that an appropriate level of exogenous Mov10 is responsible for HBV replication, that any perturbation in the level of Mov10 could affect HBV replication, while the endogenous Mov10 could promote HBV replication in vitro. The precise mechanisms that underlie the action of Mov10 on HBV still need further investigation.


Assuntos
Regulação Viral da Expressão Gênica , Vírus da Hepatite B/fisiologia , Hepatócitos/virologia , Interações Hospedeiro-Patógeno , RNA Helicases/metabolismo , Replicação Viral , Células Hep G2 , Humanos
6.
J Microbiol ; 52(6): 510-4, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24871977

RESUMO

To explore the relationship of the MOV10, A3G, and IFN-α mRNA levels with chronic hepatitis B virus (HBV) infection, Blood samples from 96 patients with chronic hepatitis B (CHB) and 21 healthy individuals as control were collected. HBV DNA load and aminotransferase in the serum were tested using real time PCR and velocity methods, respectively. The MOV10, A3G, and IFN-α mRNA levels in the peripheral blood mononuclear cells (PBMC) were examined through qRT-PCR. The MOV10, A3G, and IFN-α mRNA levels in CHB group was significantly lower than those in the control group (P<0.01, P<0.05, P<0.01, respectively). The A3G mRNA level in the high-HBV DNA load group was lower than that in the low-HBV DNA load group (P<0.05). However, no statistical difference was found in the MOV10 and IFN-α mRNA levels between the two HBV DNA load groups. Furthermore, the MOV10 mRNA level showed positive correlation with IFN-α in the control group. These results indicated that the expression of the innate immune factors MOV10, A3G, and IFN-α is affected by chronic HBV infection.


Assuntos
Hepatite B Crônica/metabolismo , Interferon-alfa/genética , RNA Helicases/genética , RNA Mensageiro/genética , Desaminase APOBEC-3G , Adulto , Citidina Desaminase/genética , DNA Viral/sangue , Feminino , Hepatite B Crônica/sangue , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Carga Viral
7.
Arch Virol ; 158(4): 785-91, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23183771

RESUMO

The treatment of infection with lamivudine-resistant mutants of hepatitis B virus (HBV) with mutations in the YMDD motif has become a crucial issue in the clinic. In this work, the plasmids pcDNA3.1 (+)-HBV/C-YVDD and pcDNA3.1 (+)-HBV/C-YMDD were constructed and injected into BALB/c mice using a hydrodynamics-based procedure to investigate viral replication and expression of HBV lamivudine-resistant YVDD mutants in vivo. Compared with the YMDD group, HBsAg levels were higher in sera of mice in the YVDD group, but HBeAg levels were lower on day 1 after injection. Levels of HBcAg in hepatocytes were higher in the YVDD group on day 1, whereas the HBsAg levels were lower. The levels of HBV mRNA in the liver were higher in mice in the YVDD group on day 1 after injection. The results showed that injection with these plasmids resulted in efficient initiation of replication of HBV in mice and also suggested that the combined mutations in YVDD mutants could affect the replication process.


Assuntos
Modelos Animais de Doenças , Vírus da Hepatite B/genética , Hepatite B/virologia , Hepatite Viral Animal/virologia , Animais , Ensaio de Imunoadsorção Enzimática , Feminino , Regulação Viral da Expressão Gênica/fisiologia , Antígenos de Superfície da Hepatite B/isolamento & purificação , Antígenos E da Hepatite B/isolamento & purificação , Fígado/patologia , Fígado/virologia , Camundongos , Camundongos Endogâmicos BALB C , Mutação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , DNA Polimerase Dirigida por RNA , Organismos Livres de Patógenos Específicos
8.
Virus Res ; 163(1): 197-201, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21963662

RESUMO

To investigate the mechanism and prognosis of occult hepatitis B virus (HBV) infection (OBI) at a molecular level among healthy young adults, the presence of HBV DNA in 1176 sera samples collected from healthy young people after neonatal vaccination was assessed by nested polymerase chain reaction (PCR) using specific primers designed for the X and S regions of the HBV genome. Full-length HBV DNA from 9 patients with OBI (OB1-OB9) was cloned and sequenced. Deletions in the pre-S, basal core promoter (BCP), core (C) and polymerase (P) regions were observed. The data indicate that there is still a substantial risk of OBI in China despite neonatal vaccination. All deletions that were observed in the pre-S, BCP, C and P regions play a direct or indirect role in OBI. The presence of a deletion mutation in the pre-S1 region was considered to play a pivotal role in hepatocarcinogenesis and was found to increase the risk of hepatocellular carcinoma in the cohorts studied.


Assuntos
Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B/virologia , Deleção de Sequência , Adolescente , China , Clonagem Molecular , Análise por Conglomerados , Primers do DNA/genética , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Genótipo , Antígenos de Superfície da Hepatite B/genética , Humanos , Masculino , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Soro/virologia , Transativadores/genética , Proteínas Virais Reguladoras e Acessórias
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...