Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
1.
Neurol Sci ; 44(3): 835-843, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36301362

RESUMO

OBJECTIVE: Lipid abnormalities are important risk factors in patients with large atherosclerotic strokes. Recent studies have shown that non-traditional lipid parameters are crucial to the development of atherosclerosis and are closely related to the clinical outcome of acute ischemic stroke (AIS). Therefore, we aimed to investigate the relationship between non-traditional lipid parameters and carotid plaque stability and stenosis degree in patients with large atherosclerotic stroke. METHODS: We retrospectively analyzed 336 patients with AIS. All patients were divided into the non-plaque group, stable plaque group, and vulnerable plaque group according to ultrasound examination. At the same time, the patients were divided into non-stenosis, mild stenosis, moderate stenosis, and severe stenosis groups according to the degree of stenosis. Non-traditional lipid parameters, including residual lipoprotein cholesterol (RLP-C), non-high-density lipoprotein cholesterol (non-HDL-C), non-HDL-C to high-density lipoprotein cholesterol ratio (non-HDL-C/HDL-C), triglyceride to HDL-C ratio (TG/HDL-C), Castelli's risk index (CRI), and the atherogenic index of plasma (AIP). Receiver operating characteristic (ROC) curves and multivariate logistic regression analyses were used to investigate the associations between the non-traditional lipid parameters and carotid plaque vulnerability. Spearman linear correlation analysis was used to test the correlation between variables and the degree of carotid plaque stenosis. RESULTS: This study population included 336 patients with AIS, of whom 294 had a carotid plaque. Multivariate logistic regression model showed that RLP-C (OR, 3.361; 95%CI, 1.311-8.617), non-HDL-C/HDL-C (OR, 1.699; 95%CI, 1.279-2.258), non-HDL-C (OR, 1.704; 95%CI, 1.143-2.540), CRI-I (OR, 1.573; 95%CI, 1.196-2.068), and CRI-II (OR, 2.022; 95%CI, 1.369-2.985) were independent risk factors for carotid plaque vulnerability. In addition, Spearman correlation analysis showed that the values of RLP-C, non-HDL-C/HDL-C, non-HDL-C, TG/HDL-C, CRI-I, CRI-II, and AIP on admission were positively correlated with the degree of carotid plaque stenosis (all P < 0.001). CONCLUSION: This study provides evidence that non-traditional lipid parameters (LP-C, non-HDL-C/HDL-C, non-HDL-C, CRI-I, and CRI-II) were potential predictors of carotid plaque vulnerability in patients with AIS. However, no significant correlation was observed between TG/HDL-C and AIP. RLP-C, non-HDL-C/HDL-C, non-HDL-C, TG/HDL-C, CRI-I, CRI-II, and AIP were closely related to the degree of carotid plaque stenosis. Non-traditional lipid parameters can be used as novel biomarkers of carotid plaque vulnerability and stenosis.


Assuntos
Aterosclerose , Estenose das Carótidas , AVC Isquêmico , Placa Aterosclerótica , Humanos , Estudos Retrospectivos , AVC Isquêmico/etiologia , AVC Isquêmico/complicações , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Artérias Carótidas , Fatores de Risco , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Constrição Patológica
2.
Biol Pharm Bull ; 44(9): 1263-1271, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34162786

RESUMO

Herpes simplex virus-1 (HSV-1) infection of the eyes leads to herpes simplex virus keratitis (HSK), the main cause of infectious blindness in the world. As the current therapeutics for HSV-1 infection are rather limited and prolonged use of acyclovir (ACV)/ganciclovir (GCV) and in immunocompromised patients lead to the rise of drug resistant mutants, it underlines the urgent need for new antiviral agents with distinct mechanisms. Our study attempted to establish ras-related C3 botulinum toxin substrate 1 (Rac1) as a new therapeutic target for HSV-1 infection by using Rac1-specific inhibitors to evaluate the in vitro inhibition of virus growth. Our results showed that increased Rac1 activity facilitated HSV-1 replication and inhibition of Rac1 activity by NSC23766 and Ehop016 significantly reduced HSV-1 replication. Thus, we identified NSC23766 and Ehop016 as possessing potent anti-HSV-1 activities by suppressing the Rac1 activity, suggesting that Rac1 is a potential target for treating HSV-1-related diseases.


Assuntos
Aminoquinolinas/farmacologia , Antivirais/farmacologia , Carbazóis/farmacologia , Herpes Simples/tratamento farmacológico , Pirimidinas/farmacologia , Proteínas rac1 de Ligação ao GTP/antagonistas & inibidores , Aminoquinolinas/uso terapêutico , Animais , Antivirais/uso terapêutico , Carbazóis/uso terapêutico , Chlorocebus aethiops , Avaliação Pré-Clínica de Medicamentos , Células HeLa , Herpes Simples/virologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Humanos , Pirimidinas/uso terapêutico , Células Vero , Replicação Viral/efeitos dos fármacos , Proteínas rac1 de Ligação ao GTP/metabolismo
3.
J Med Virol ; 92(12): 3628-3637, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32356915

RESUMO

Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, was used to protect liver function through antiapoptosis or reducing endoplasmic reticulum stress (ER stress). Previous studies showed that ER stress was modulated by herpes simplex virus types 1 (HSV-1) infection to facilitate viral replication. Here, we investigated the effect of TUDCA on HSV-1 infection of HEC-1-A cells and showed that both replication and multiplication of the virus were inhibited by TUDCA in a dose dependent manner. Unfolded protein response was induced to deliver stress signals from ER to nucleus. We found that TUDCA alleviated activating transcription factor 6 branch inhibition, partially enhanced protein kinase RNA-like ER kinase pathway activation, and repressed inositol-requiring protein 1α arm activation significantly in infected cells. The findings of this study suggest that TUDCA inhibits HSV-1 replication through ER stress pathway, which may provide a potential therapeutic strategy for HSV-1 infection.

4.
J Med Virol ; 92(8): 996-1006, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31663613

RESUMO

The Ebola virus is highly infectious and characterized by hemorrhagic fever, headache, and so on with a high mortality rate. Currently, there are neither therapeutic drugs or vaccines against the Ebola virus nor fast diagnostic methods for the detection of Ebola virus infection. This study reported the induction and isolation of two monoclonal antibodies that specifically recognized the glycoprotein (GP) and secreted glycoprotein (sGP) of the Ebola virus. Plasmids encoding either GP or sGP were constructed and immunized BALB/c mice, accordingly purified sGP was boosted. The antisera were analyzed for binding activity against sGP protein in enzyme-linked immunosorbent assay (ELISA) and neutralization activity in a pseudotyped virus neutralization assay. A number of reactive clones were isolated and two monoclonal antibodies T231 and T242 were identified to react with both GP and sGP. Western blot and ELISA assays showed that the monoclonal antibodies could react with GP and sGP, respectively. Moreover, they could recognize Ebola pseudovirus by cellular immunochemistry assay. We labeled the monoclonal antibody T231 with biotin and analyzed the competitiveness of the two antibodies by the ELISA test. The results showed that the binding epitopes of the two monoclonal antibodies to sGP were partially overlapped. In summary, two GP-specific mAbs were identified, which will be used to detect the Ebola virus or investigate GP.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Ebolavirus/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/isolamento & purificação , Afinidade de Anticorpos , Especificidade de Anticorpos , Western Blotting , Clonagem Molecular , Ensaio de Imunoadsorção Enzimática , Epitopos/imunologia , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Proteínas do Envelope Viral/genética
5.
Int J Mol Sci ; 20(19)2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31575039

RESUMO

Signal transducer and activator of transcription 3 (STAT3) is a multifunctional factor that regulates inflammation and immunity. Knowledge of its regulatory mechanisms is very limited. Here, we showed that enterovirus 71 (EV71) infection induced the phosphorylation of STAT3 and the expression of its downstream inflammatory regulators. Knockdown of STAT3 with siRNAs significantly restricted viral RNA and protein levels, and also reduced viral titers. With further investigation, we found that importin α family member Karyopherin-α1 (KPNA1) was employed by both STAT1 and STAT3 for their nuclear import. The phosphorylated and un-phosphorylated STAT3 competed with STAT1 for binding to the decreased KPNA1 post infection and repressed downstream ISG expression. STAT3 knockdown alleviated the repressed type I IFN-mediated antiviral response upon infection and led to decreased viral replication. Taken together, our data suggested the role of STAT3 in maintaining the balance of inflammation and antiviral responses in the central nervous system (CNS) upon infection.


Assuntos
Interações Hospedeiro-Patógeno , Interferon Tipo I/metabolismo , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Viroses/metabolismo , Transporte Ativo do Núcleo Celular , Técnicas de Silenciamento de Genes , Humanos , Imunidade Inata , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica , Transporte Proteico , Transdução de Sinais , Viroses/virologia
6.
Virol J ; 15(1): 173, 2018 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-30419930

RESUMO

BACKGROUND: The pattern recognition receptors (PPRs) are the earliest phase of the host defense against pathogens in genital epithelium, and toll-like receptors (TLRs) are best characterized PPRs mediating innate immune responses. Herpes simplex virus type 2 (HSV-2), a member of herpesviridae family, causes one of the most prevalent sexually transmitted infection in the world. In this paper, we described that HSV-2 infection would induce activator protein 1 (AP-1) via TLR4-MyD88/TRIF pathway in human genital epithelial cell. METHODS: TLRs expression profiles and changes was investigated in HSV-2-infected cells. The effect of TLR4-MyD88/TRIF on HSV-2-induced AP-1 activation and viral replication was also evaluated. The TLR4 translocation change was examined after viral infection. Finally, viral ICP0 effect on TLR4 signaling and TLR4-promoter regulation were primarily studied. RESULTS: HSV-2-induced AP-1 activation was dependent on TLR4 and downstream adaptor molecules MyD88 and TRIF. And also, TLR4, MyD88 and TRIF was proved to affect HSV-2 replication. AP-1 activation would also be enhanced via overexpression of myeloid differentiation protein 2 (MD2), implicating that it might be a necessary accessory for TLR4 to sense HSV-2 infection. Protein quantification of cytoplasmic and membrane-associated TLR4 revealed that HSV-2 infection increased membrane-anchoring TLR4 level, but not cytoplasmic ones. Viral ICP0 could augment cellular AP-1, TLR4 promoter activation and TLR4 expression level. The specific inhibitor treatment and transcription factor binding site scanning in TLR4 promoter region showed that AP-1 activity was essential for TLR4-promoter activation. CONCLUSIONS: Taken together, HSV-2 infection could stimulate AP-1 activation via TLR4-MyD88/TRIF axis, and then feedback to up-regulate TLR4 expression in human genital epithelial cells.


Assuntos
Células Epiteliais/virologia , Herpesvirus Humano 2/imunologia , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição AP-1/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Linhagem Celular , Genitália/citologia , Herpesvirus Humano 2/genética , Humanos , Imunidade Inata , Fator 88 de Diferenciação Mieloide/metabolismo , Regiões Promotoras Genéticas , Transdução de Sinais , Receptor 4 Toll-Like/genética , Fator de Transcrição AP-1/genética , Replicação Viral
7.
Biochem Biophys Res Commun ; 479(3): 571-577, 2016 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-27666477

RESUMO

As a cytoplasmic parasite, RNA virus develops sophisticated mechanisms to counter host defense and utilize host proteins to facilitate its replication. Here we found Moloney leukemia virus 10 (MOV10), a highly conserved cellular protein belonging to SF1 helicase family, played critical roles in EV71 infection. Silencing cellular MOV10 could restrict EV71 replication, while over-expressing MOV10 resulted in increased viral replication at low dosage and repressed viral replication at high dosage. Further investigation showed that MOV10 exhibited dual functions in EV71 regulation, its C-terminus positively regulated viral replication by binding to EV71 cloverleaf-like structure and the internal ribosome entry site while the N-terminus showed a potential antiviral activity when individually overexpressed. In addition, RNA-dependent interaction between MOV10 and HuR as well as the co-localization of MOV10 and processing bodies were also observed post infection. Taken together, our data indicate a crucial role of MOV10 in EV71 infection for the first time, providing new insights for its roles in EV71 infection.


Assuntos
Regiões 5' não Traduzidas , Enterovirus Humano A/fisiologia , Sítios Internos de Entrada Ribossomal , RNA Helicases/genética , RNA Viral/genética , Replicação Viral , Proteína Semelhante a ELAV 1/metabolismo , Inativação Gênica , Genoma Viral , Células HEK293 , Células HeLa , Humanos , Microscopia de Fluorescência , Ligação Proteica , Domínios Proteicos , RNA/química
8.
Phys Chem Chem Phys ; 18(25): 16621-8, 2016 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-27095305

RESUMO

Ambient-Pressure X-ray Photoelectron Spectroscopy (AP-XPS) and Infrared Reflection Absorption Spectroscopy (AP-IRRAS) have been used to elucidate the active sites and mechanistic steps associated with the ethanol steam reforming reaction (ESR) over Ni-CeO2(111) model catalysts. Our results reveal that surface layers of the ceria substrate are both highly reduced and hydroxylated under reaction conditions while the small supported Ni nanoparticles are present as Ni(0)/NixC. A multifunctional, synergistic role is highlighted in which Ni, CeOx and the interface provide an ensemble effect in the active chemistry that leads to H2. Ni(0) is the active phase leading to both C-C and C-H bond cleavage in ethanol and it is also responsible for carbon accumulation. On the other hand, CeOx is important for the deprotonation of ethanol/water to ethoxy and OH intermediates. The active state of CeOx is a Ce(3+)(OH)x compound that results from extensive reduction by ethanol and the efficient dissociation of water. Additionally, we gain an important insight into the stability and selectivity of the catalyst by its effective water dissociation, where the accumulation of surface carbon can be mitigated by the increased presence of surface OH groups. The co-existence and cooperative interplay of Ni(0) and Ce(3+)(OH)x through a metal-support interaction facilitate oxygen transfer, activation of ethanol/water as well as the removal of coke.

9.
Biochem Biophys Res Commun ; 466(2): 254-9, 2015 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-26363455

RESUMO

Enterovirus 71 is one of the major causative pathogens of HFMD in children. Upon infection, the viral RNA is translated in an IRES-dependent manner and requires several host factors for effective replication. Here, we found that T-cell-restricted intracellular antigen 1 (TIA-1), and TIA-1 related protein (TIAR) were translocated from nucleus to cytoplasm after EV71 infection and localized to the sites of viral replication. We found that TIA-1 and TIAR can facilitate EV71 replication by enhancing the viral genome synthesis in host cells. We demonstrated that both proteins bound to the stem-loop I of 5'-UTR of viral genome and improved the stability of viral genomic RNA. Our results suggest that TIA-1 and TIAR are two new host factors that interact with 5-UTR of EV71 genome and positively regulate viral replication.


Assuntos
Regiões 5' não Traduzidas , Enterovirus Humano A/genética , Enterovirus Humano A/fisiologia , Proteínas de Ligação a Poli(A)/fisiologia , Proteínas de Ligação a RNA/fisiologia , Replicação Viral , Genoma Viral , Humanos , RNA Viral/metabolismo , Antígeno-1 Intracelular de Células T
10.
Neurosci Lett ; 759: 136049, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34126180

RESUMO

Aquaporin-4 (AQP4) is the key water channel protein that regulates brain water homeostasis. Polarized expression of AQP4 on the astroglial endfeet facilitates its role in bi-directional brain water flux control. In the current study, we found that enterovirus 71 (EV71) infection induced depolarization of AQP4 in mouse brain, and demonstrated that ß-dystroglycan (ß-DG), the key component of dystrophin glycoprotein complex (DGC) that anchors AQP4 to the astroglial endfeet, was degraded upon infection. Elevated activity or expression of matrix metalloproteinase 9 (MMP9) upon infection was found in both mouse brains and patient cerebrospinal fluid (CSF) samples. Inhibiting MMP9 activity by SB-3CT rescued the decay of ß-DG and reduced the depolarization of AQP4. Brain edema induced by viral infection was also ameliorated by SB-3CT treatment in mice.


Assuntos
Aquaporina 4/metabolismo , Encéfalo/virologia , Infecções por Enterovirus/metabolismo , Infecções por Enterovirus/virologia , Metaloproteinase 9 da Matriz/metabolismo , Animais , Astrócitos/metabolismo , Astrócitos/virologia , Encéfalo/metabolismo , Edema Encefálico/metabolismo , Edema Encefálico/virologia , Pré-Escolar , Distroglicanas/metabolismo , Enterovirus Humano A , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
11.
Front Microbiol ; 10: 625, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984146

RESUMO

Enterovirus 71 (EV71), the etiological agent of hand-foot-and-mouth disease, has become an increasing public health challenge worldwide. Accumulating evidence suggests that mammalian microRNAs (miRNAs), a class of non-coding RNAs of 18 to 24 nucleotides (nt) with important regulatory roles in cellular processes, participate in host antiviral defense and studies have suggested roles of miRNAs in EV71 replication and pathogenesis. In the current study, we reported that the expression of hsa-miR-17∼92 cluster was significantly downregulated during EV71 infection. Overexpression of hsa-miR-17∼92 inhibited, while inhibition of endogenous hsa-miR-17∼92 facilitated EV71 replication. We identified two sequences located at nt 3024 to 3038 and nt 2838 to 2862 of the EV71 (strain FY0805) genome as potential targets for hsa-miR-17-5p and miR-19a/b, respectively, which were validated by luciferase reporter assays and Western blot. Meanwhile, we identified DNA methylation as a novel mechanism of hsa-miR-17∼92 regulatory roles. The methylation of the miR-17-92 promoter was significantly increased (50%) upon EV71 infection, which appeared to be caused by the increased expression of DNMT3B but not DNMT1 and DNMT3A. Furthermore, we demonstrated that the members of miR-17-92 cluster were decreased in the sera of EV71 infected patients, suggesting the clinical implication and the potential therapeutic application of miR-17-92.

12.
Front Immunol ; 10: 1095, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31156641

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever with a high mortality rate in humans, which is caused by SFTS virus (SFTSV), a novel phlebovirus in the Bunyaviridae family, is tick borne and endemic in Eastern Asia. Previous study found that SFTSV can infect and replicate in macrophages in vivo and in vitro. However, the role of macrophages in virus replication and the potential pathogenic mechanisms of SFTSV in macrophage remain unclear. In this study, we provided evidence that the SFTSV infection drove macrophage differentiation skewed to M2 phenotype, facilitated virus shedding, and resulted in viral spread. We showed evidence that miR-146a and b were significantly upregulated in macrophages during the SFTSV infection, driving the differentiation of macrophages into M2 cells by targeting STAT1. Further analysis revealed that the elevated miR-146b but not miR-146a was responsible for IL-10 stimulation. We also found that SFTSV increased endogenous miR-146b-induced differentiation of macrophages into M2 cells mediated by viral non-structural protein (NSs). The M2 skewed differentiation of macrophages may have important implication to the pathogenesis of SFTS.


Assuntos
Diferenciação Celular/imunologia , Febre/complicações , Macrófagos/imunologia , MicroRNAs/metabolismo , Febre por Flebótomos/complicações , Phlebovirus/imunologia , Trombocitopenia/complicações , Animais , Diferenciação Celular/genética , Modelos Animais de Doenças , Febre/imunologia , Febre/virologia , Células HeLa , Humanos , Ativação de Macrófagos/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Febre por Flebótomos/imunologia , Febre por Flebótomos/virologia , Síndrome , Células THP-1 , Trombocitopenia/imunologia , Trombocitopenia/virologia , Transfecção , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/imunologia
13.
J Microbiol Biotechnol ; 28(8): 1367-1375, 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30301314

RESUMO

Silver nanoparticles have been widely applied for biomedical areas owing to their potent antiviral and antibacterial activities. Synthesis of silver nanoparticles using biomacromolecules is more efficient, environment-friendly, and cost-saving compared with the traditional approach. In this paper, a novel approach was developed to establish a reaction system with Ag+-BH4--sericin to synthesize silver nanoparticles conjugated to sericin (AgNPs-Sericin). Sericin could be as a good dispersant and stabilizing agent, which is able to modify nanoscaled AgNPs, the average diameter of which was only 3.78 ± 1.14nm prepared in a 0.3 mg/ml sericin solution. The characterizations of the AgNPs-Sericin were determined by FTIR, thermogravimetry, and XRD analyses. The results showed that the synthesized AgNPs conjugated with sericin as organic phase. Via SAED and XRD analysis, we showed that these AgNPs formed polycrystalline powder with a face-centered cubic structure of bulk metals. Moreover, we investigated the antiviral and antibacterial activities of AgNPs-Sericin, and the results showed that AgNPs-Sericin exhibited potent anti-HIV-1 activity against CCR5-tropic and CXCR4-tropic strains, but no significant cytotoxicity was found toward human genital epithelial cells compared with free silver ions, which are accepted as a commonly used potent antimicrobial agent. Moreover, its antibacterial activity was determined via flow cytometry. The results showed that AgNPs-Sericin could suppress gram-negative (E. coli) and gram-positive (S. aureus) bacteria, but more was potent for the gram-negative one. We concluded that our AgNPs-Sericin could be a potential candidate as a microbicide or antimicrobial agent to prevent sexually transmitted infections.


Assuntos
Fármacos Anti-HIV/síntese química , Anti-Infecciosos/síntese química , Nanopartículas Metálicas/química , Sericinas/química , Prata/química , Fármacos Anti-HIV/farmacologia , Anti-Infecciosos/farmacologia , Linhagem Celular , Escherichia coli/efeitos dos fármacos , Humanos , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Tamanho da Partícula , Staphylococcus aureus/efeitos dos fármacos
14.
Int Immunopharmacol ; 60: 111-120, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29730555

RESUMO

Enterovirus 71 (EV71) infection of young children can cause neurological manifestations, which is mainly responsible for the fatality. Although a vaccine is recently available for preventing enterovirus 71 infection, its efficacy remains to be seen. Therefore, there is a pressing need for anti-viral agents for the treatment of EV71 infection. By screening a natural compound library for inhibitory activity of EV71 replication, we identified a small molecule, harmine, that inhibited EV71 replication by targeting NF-κB signaling pathway. Harmine is a ß-carboline alkaloid found in the medicinal plant Peganum harmala, which is used as a folk antitumor medicine in China and other parts of the Asia. The estimated EC50 value for harmine to block EV71 infection was 20 µM, while the CC50 was estimated at 500 µM in vitro. Harmine inhibited replication of EV71, as evidenced by its ability to diminish plague formation induced by EV71 and to reduce the level of viral RNA and protein. Mechanistic studies indicated that harmine suppressed EV71 replication through inhibition of NF-κB signaling pathway. Harmine treatment also reduced EV71-induced reactive oxygen species (ROS) formation, which was associated with a decline in EV71-associated NF-κB activation. In addition, the harmine treatment could protect AG129 mice against EV71 replication in vivo. These findings suggest that harmine may present as a candidate antiviral drug for the treatment of EV71 infection.


Assuntos
Antivirais/farmacologia , Enterovirus Humano A/efeitos dos fármacos , Harmina/farmacologia , NF-kappa B/metabolismo , Animais , Antivirais/uso terapêutico , Chlorocebus aethiops , Enterovirus Humano A/fisiologia , Infecções por Enterovirus/tratamento farmacológico , Infecções por Enterovirus/metabolismo , Infecções por Enterovirus/virologia , Harmina/uso terapêutico , Células HeLa , Humanos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Células Vero , Replicação Viral/efeitos dos fármacos
15.
Nat Commun ; 9(1): 3328, 2018 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-30127439

RESUMO

Severe Fever with Thrombocytopenia Syndrome (SFTS), an emerging infectious disease caused by a novel phlebovirus, is associated with high fatality. Therapeutic interventions are lacking and disease pathogenesis is yet to be fully elucidated. The anti-viral immune response has been reported, but humoral involvement in viral pathogenesis is poorly understood. Here we show defective serological responses to SFTSV is associated with disease fatality and a combination of B-cell and T-cell impairment contribute to disruption of anti-viral immunity. The serological profile in deceased patients is characterized by absence of specific IgG to viral nucleocapsid and glycoprotein due to failure of B-cell class switching. Expansion and impairment of antibody secretion is a signature of fatal SFTSV infection. Apoptosis of monocytes in the early stage of infection diminishes antigen-presentation by dendritic cells, impedes differentiation and function of T follicular helper cells, and contributes to failure of the virus-specific humoral response.


Assuntos
Linfócitos B/imunologia , Imunidade Celular , Imunidade Humoral , Phlebovirus/fisiologia , Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Apoptose , Antígeno B7-1/metabolismo , Infecções por Bunyaviridae/sangue , Infecções por Bunyaviridae/imunologia , Diferenciação Celular , Citocinas/metabolismo , Células Dendríticas/metabolismo , Glicoproteínas/sangue , Antígenos HLA-DR/metabolismo , Humanos , Imunoglobulina G/metabolismo , Cinética , Subpopulações de Linfócitos/imunologia , Modelos Biológicos , Monócitos/metabolismo , Proteínas do Nucleocapsídeo/sangue , Fenótipo , Especificidade da Espécie , Análise de Sobrevida , Linfócitos T Auxiliares-Indutores/imunologia , Viremia/sangue , Viremia/imunologia
16.
Spectrochim Acta A Mol Biomol Spectrosc ; 66(4-5): 1175-9, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17289427

RESUMO

The bond polarizabilities of pyrimidine are elucidated from the Raman intensities excited at 632.8 nm by an algorithm proposed by Wu et al. [B. Tian, G. Wu, G. Liu, J. Chem. Phys. 87 (1987) 7300]. The contrast between the bond polarizabilities and the bond electronic densities by RHF/6-31G* calculation shows that, in the excited virtual state, the electrons of the C-N bond which is connected to the C-C bond tend to spread to the most spacious C-H bond, its adjacent C-N bond and possibly, the C-C bond in this nonresonant process.


Assuntos
Pirimidinas/química , Análise Espectral Raman , Eletricidade Estática
17.
DNA Cell Biol ; 36(7): 565-570, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28488892

RESUMO

P-bodies are cytoplasmic foci composed of mRNAs and enzymes involved in mRNA degradation. P-bodies have been found to link to RNA interference and RNA decay mediated by microRNAs (miRNAs) and translational repression. Here, we aim to investigate different effects of overexpressed Dcp1a or GW182 on cytoplasmic aggregates formation and influence on miRNA pathway. Small RNAs were recruited into endogenous foci of P-bodies and aggregates formed by Dcpa1 and GW182 overexpression. However, only overexpressed Dcp1a but not GW182 was colocalized with DDX6, another component of P-bodies and suppressed protein translation. In addition, we investigated the relationship between stress granules and miRNA pathway and found that granules induced by G3BP1 overexpression could recruit small RNAs into the granules and repressed protein translation. As Ago2 is a key component of RNA-induced silencing complex, we also investigated the localization of endogenous Ago2 (edo-Ago2) after Dcp1a and GW182 overexpression, and found that endo-Ago2 did not colocalize with the aggregates induced by overexpression of Dcpla, GW182, and G3BP1. Notably, the ability of miRNA to regulate its target was enhanced by the granules induced by Dcp1a and G3BP1 expression. Our results suggest that overexpressed Dcp1a and GW182 can form different cytoplasmic aggregates and play distinct biological roles in the miRNA pathway.


Assuntos
Autoantígenos/genética , Proteínas de Transporte/genética , Endorribonucleases/genética , MicroRNAs/genética , Interferência de RNA , Proteínas de Ligação a RNA/genética , Transativadores/genética , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Autoantígenos/metabolismo , Proteínas de Transporte/metabolismo , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , DNA Helicases , Endorribonucleases/metabolismo , Células HEK293 , Células HeLa , Humanos , Substâncias Macromoleculares/química , Substâncias Macromoleculares/metabolismo , MicroRNAs/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose , Ligação Proteica , Biossíntese de Proteínas , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA , Estabilidade de RNA , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais , Transativadores/metabolismo
18.
Viruses ; 9(9)2017 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-28832521

RESUMO

In response to the endoplasmic reticulum (ER) stress induced by herpes simplex virus type 1 (HSV-1) infection, host cells activate the unfolded protein response (UPR) to reduce the protein-folding burden in the ER. The regulation of UPR upon HSV-1 infection is complex, and the downstream effectors can be detrimental to viral replication. Therefore, HSV-1 copes with the UPR to create a beneficial environment for its replication. UPR has three branches, including protein kinase RNA (PKR)-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activated transcription factor 6 (ATF6). IRE1α is the most conserved branch of UPR which has both RNase and kinase activities. Previous studies have shown that IRE1α RNase activity was inactivated during HSV-1 infection. However, the effect of the two activities of IRE1α on HSV-1 replication remains unknown. Results in this study showed that IRE1α expression was up-regulated during HSV-1 infection. We found that in HEC-1-A cells, increasing RNase activity, or inhibiting kinase activity of IRE1α led to viral suppression, indicating that the kinase activity of IRE1α was beneficial, while the RNase activity was detrimental to viral replication. Further evidence showed that the kinase activity of IRE1α leads to the activation of the JNK (c-Jun N-terminal kinases) pathway, which enhances viral replication. Taken together, our evidence suggests that IRE1α is involved in HSV-1 replication, and its RNase and kinase activities play differential roles during viral infection.


Assuntos
Endorribonucleases/metabolismo , Endorribonucleases/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/farmacologia , Ribonucleases/metabolismo , Replicação Viral/efeitos dos fármacos , Proteína 1 de Ligação a X-Box/farmacologia , Animais , Antivirais/farmacologia , Linhagem Celular , Chlorocebus aethiops , Replicação do DNA , Estresse do Retículo Endoplasmático , Endorribonucleases/farmacocinética , Regulação da Expressão Gênica , Células HeLa , Herpes Simples/metabolismo , Herpes Simples/virologia , Herpesvirus Humano 1/metabolismo , Herpesvirus Humano 1/patogenicidade , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosforilação/fisiologia , Proteínas Serina-Treonina Quinases/farmacocinética , Splicing de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/análise , Transdução de Sinais/genética , Resposta a Proteínas não Dobradas , Regulação para Cima , Células Vero , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
19.
FEBS Open Bio ; 7(6): 747-758, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28593131

RESUMO

Enterovirus 71 (EV71) is the major causative agent of hand-foot-and-mouth disease in young children and can cause severe cerebral and pulmonary complications and even fatality. This study aimed at elucidating whether and how EV71 infection is regulated by a cellular microRNA, miR-127-5p. We found that miR-127-5p can downregulate the expression of SCARB2, a main receptor of EV71, by targeting two potential sites in its 3' UTR region and inhibit EV71 infection. Meanwhile, miR-127-5p expression was upregulated during EV71 infection. Notably, transfecting cells with miR-127-5p mimics led to a significant decrease in viral replication, while inhibition of endogenous miR-127-5p facilitated viral replication. Furthermore, our evidence showed that miR-127-5p did not affect postentry viral replication. Taken together, these results indicated that miR-127-5p inhibited EV71 replication by targeting the SCARB2 mRNA.

20.
Spectrochim Acta A Mol Biomol Spectrosc ; 62(1-3): 415-9, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16257743

RESUMO

Two adsorbate forms of the monothiocyanate complex of chromium ion on the silver electrode are identified in the surface enhanced Raman scattering. The spectroscopic, especially the electronic, properties of these two forms under different applied voltages on the electrode and under both 632.8 and 514.5 nm excitations are studied by the bond force constants (bond orders) and the bond polarizability derivatives which are retrieved from the Raman intensities by an algorithm developed by Wu and co-workers. The work shows the potential of this approach to the surface enhanced Raman scattering and other fields like resonance Raman that involve vibronic coupling.


Assuntos
Cromo/química , Tiocianatos/química , Adsorção , Eletroquímica , Eletrodos , Cinética , Lasers , Prata , Análise Espectral Raman/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA