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1.
J Infect Chemother ; 30(6): 571-578, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38036028

RESUMO

INTRODUCTION: The prevalence and infection of the Zika virus (ZIKV) have recently posed a major threat to global public health security. However, there is currently a lack of specific vaccines and effective antiviral drugs for ZIKV infection. METHODS: Theaflavins TF1 and TF2 were selected by evaluating the anti-Zika virus activity of four kinds of theaflavins in vitro. Subsequently, in vivo, we investigated the effects of TF1 and TF2 on weight, survival, tissue viral load, and cytokines in ZIKV-infected mice. RESULTS: We compared the anti-ZIKV activity of four theaflavins (TFs) in cells and found that TF1 and TF2b significantly inhibited the replication of ZIKV/Z16006 toxic strain in BHK and Vero cells by inhibiting the replication and release of ZIKV, while no similar effects were observed for TF2a and TF3. In vivo assay, we only found that TF2b improved the survival rate of infected mice. In tissues of ZIKV-infected mice, the viral load was higher in spleen and blood, followed by liver, epididymis, and testis, the lowest in muscle. Additionally, TF2b treatment significantly reduced the expression of cytokines (IL-6, IL-1ß, TNF-α) and chemokines (CCL2, CCL5, CXCL10) induced by ZIKV infection. CONCLUSIONS: These findings suggest that TF2b has a potent antiviral effect and can be used as a potential candidate for the treatment of ZIKV infection.

2.
Chin Med ; 18(1): 144, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919750

RESUMO

BACKGROUND: Influenza viruses, especially Influenza A virus and Influenza B virus, are respiratory pathogens and can cause seasonal epidemics and pandemics. Severe influenza viruses infection induces strong host-defense response and excessive inflammatory response, resulting in acute lung damage, multiple organ failure and high mortality. Isoquercitrin is a Chinese medicine monomer, which was reported to have multiple biological activities, including antiviral activity against HSV, IAV, SARS-CoV-2 and so on. Aims of this study were to assess the in vitro anti-IAV and anti-IBV activity, evaluate the in vivo protective efficacy against lethal infection of the influenza virus and searched for the more optimal method of drug administration of isoquercitrin. METHODS: In vitro infection model (MDCK and A549 cells) and mouse lethal infection model of Influenza A virus and Influenza B virus were used to evaluate the antiviral activity of isoquercitrin. RESULTS: Isoquercitrin could significantly suppress the replication in vitro and in vivo and reduced the mortality of mouse lethal infection models. Compared with virus infection group, isoquercitrin mitigated lung and multiple organ damage. Moreover, isoquercitrin blocked hyperproduction of cytokines induced by virus infection via inactivating NF-κB signaling. Among these routes of isoquercitrin administration, intramuscular injection is a better drug delivery method. CONCLUSION: Isoquercitrin is a potential Chinese medicine monomer Against Influenza A Virus and Influenza B Virus infection.

3.
Eur J Pharmacol ; 938: 175332, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36265612

RESUMO

Severe pathological damage caused by the influenza virus is one of the leading causes of death. However, the prevention and control strategies for influenza virus infection have certain limitations, and the exploration for new influenza antiviral drugs has become the major research direction. This study evaluated the antiviral activities of four theaflavin derivatives (TFs). Cytopathic effect (CPE) reduction assay revealed that theaflavin-3'-gallate (TF2b) and theaflavin (TF1) could effectively inhibit the replication of influenza viruses H1N1-UI182, H1N1-PR8, H3N2, and H5N1, and TF2b exhibited the most significant antiviral activity in vivo. Intraperitoneal injection of TF2b at 40 mg/kg/d effectively alleviated viral pneumonia, maintained body weight, and improved the survival rate of mice infected with a lethal dose of H1N1-UI182 to 55.56%. Hematological analysis of peripheral blood further showed that TF2b increased the number of lymphocytes and decreased the number of neutrophils, monocytes, and platelets in the blood of infected mice. RT-qPCR results showed that TF2b reduced the mRNA expression levels of inflammatory cytokines (IL-6, TNF-α, and IL-1ß), chemokines (CXCL-2 and CCL-3), and interferons (IFN-α and IFN-γ) after influenza virus infection. In addition, TF2b significantly down-regulated the expression levels of TLR4, p-p38, p-ERK, and cytokines IL-6, TNF-α, IL-1ß, and IL-10. These results suggest that TF2b not only significantly inhibits viral replication and proliferation in vitro, but also alleviates pneumonia injury in vivo. Its antiviral effect might be attributed to the down-regulation of influenza virus-induced inflammatory cytokines by regulating the TLR4/MAPK/p38 signaling pathway.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Virus da Influenza A Subtipo H5N1 , Infecções por Orthomyxoviridae , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Citocinas/metabolismo , Vírus da Influenza A Subtipo H3N2 , Virus da Influenza A Subtipo H5N1/metabolismo , Interleucina-6 , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Infecções por Orthomyxoviridae/tratamento farmacológico
4.
World J Microbiol Biotechnol ; 38(1): 6, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837116

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that poses a significant risk to global health today. In S. aureus, α-hemolysin is an important virulence factor as it contributes to the capacity of the bacteria to infect the host. Here, we showed that biochanin A (bioA), an isoflavone present in red clover, cabbage and alfalfa, effectively inhibited hemolytic activity at a dose as low as 32 µg/mL. Further, western blot and RT-qPCR data showed that bioA reduced the production and expression of MRSA hemolysin in a dose-dependent manner. In addition, when different concentrations of bioA were added to a coculture system of A549 cells and S. aureus, it could significantly decrease cell injury. Importantly, the in vivo study showed that bioA could protect mice from pneumonia caused by a lethal dose of MRSA, as evidenced by improving their survival and reducing the number of bacterial colonies in lung tissues, the secretion of hemolysin into alveolar lavage fluid and the degree of pulmonary edema. In conclusion, biochanin A protected the host from MRSA infection by inhibiting the expression of the hemolysin of MRSA, which may provide experimental evidence for its development to a potential anti-MRSA drug.


Assuntos
Antibacterianos/administração & dosagem , Genisteína/administração & dosagem , Proteínas Hemolisinas/metabolismo , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pneumonia/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Células A549 , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Genisteína/farmacologia , Proteínas Hemolisinas/genética , Hemólise/efeitos dos fármacos , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos , Pneumonia/microbiologia , Infecções Estafilocócicas/microbiologia
5.
Phys Chem Chem Phys ; 22(45): 26306-26311, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33175931

RESUMO

The ionic transport properties of solid electrolyte LaF3 were systematically studied under high pressures up to 30.6 GPa with alternate-current impedance spectra measurements and first-principles calculations. From the impedance spectra measurements, LaF3 was found to transform from pure ionic conduction to mixed ionic and electronic conduction at 15.0 GPa, which results from the pressure-induced structural phase transition from a tysonite-type structure to an anti-Cu3Ti-type structure. F- ion migration can be suppressed by pressure, causing a decrease of the ionic conductivity of LaF3. By first-principles calculations, the pressure-dependent diffusion behaviors of the F- ions can be understood. The increased overlap of electron clouds at the interstitial site between rigid La3+ and liquid F- lattices leads to the appearance of electronic conduction in anti-Cu3Ti-type structured LaF3.

6.
Virology ; 486: 180-6, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26453960

RESUMO

While the 2009 pandemic H1N1 virus has become established in the human population as a seasonal influenza virus, continued adaptation may alter viral virulence. Here, we passaged a 2009 pandemic H1N1 virus (A/Changchun/01/2009) in mice. Serial passage in mice generated viral variants with increased virulence. Adapted variants displayed enhanced replication kinetics in vitro and vivo. Analysis of the variants genomes revealed 6 amino acid changes in the PB1 (T296R), PA (I94V), HA (H3 numbering; N159D, D225G, and R226Q), and NP (D375N). Using reverse genetics, we found that a PB1-T296R substitution found in all adapted viral variants enhanced viral replication kinetics in vitro and vivo, increased viral polymerase activity in human cells, and was sufficient for enhanced virulence of the 2009 pandemic H1N1 virus in mice. Therefore, we defined a novel influenza pathogenic determinant, providing further insights into the pathogenesis of influenza viruses in mammals.


Assuntos
Substituição de Aminoácidos , Vírus da Influenza A Subtipo H1N1/enzimologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/virologia , Proteínas Virais/genética , Proteínas Virais/metabolismo , Animais , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/epidemiologia , Camundongos , Camundongos Endogâmicos BALB C , Mutação de Sentido Incorreto , Virulência
7.
Int J Clin Exp Pathol ; 8(10): 12455-63, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26722432

RESUMO

MicroRNAs (miRNAs) are classes of small, non-coding RNAs that regulate the translation of target mRNA transcripts. In this study, we demonstrated that miR-592 was downregulated in human hepatocellular carcinoma (HCC) and could suppress growth of the human HCC cell line HepG2. A tumor oncogene, DEK, was identified as a direct target of miR-592. Luciferase report assay indicated miR-592 regulates DEK expression though bind to its 3'UTR. Furthermore, knockdown of DEK also suppressed cell proliferation of HepG2 cells, which was consist with miR-592. At last, we suggested that DEK was upregulated in HCC tissues inversely with miR-592. These results demonstrated that miR-592 targets DEK transcript and suppresses HCC cell growth, and may provide potential therapeutic target in human HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Proteínas Cromossômicas não Histona/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Proteínas Oncogênicas/genética , Western Blotting , Carcinoma Hepatocelular/genética , Proliferação de Células/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Proteínas de Ligação a Poli-ADP-Ribose , Reação em Cadeia da Polimerase , Transfecção
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