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1.
Virol Sin ; 39(2): 290-300, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38331038

RESUMO

Coxsackievirus B3 (CVB3) is the pathogen causing hand, foot and mouth disease (HFMD), which manifests across a spectrum of clinical severity from mild to severe. However, CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis, failing to replicate human HFMD symptoms. Although several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys, there is no comprehensive data on CVB3. In this study, we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes. The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip, leading to nasopharyngeal colonization, acute severe pathological injury, and typical HFMD symptoms. Notably, the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage. In the subsequent study, rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms, viral excretion, serum antibody conversion, viral nucleic acids and antigens, and the specific organ damages, particularly in the heart. Surprisingly, there were no significant differences in myocardial enzyme levels, and the clinical symptoms resembled those often associated with common, mild infections. In summary, the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced HFMD. These models could serve as a basis for understanding the disease pathogenesis, conducting pre-trial prevention and evaluation, and implementing post-exposure intervention.


Assuntos
Modelos Animais de Doenças , Enterovirus Humano B , Doença de Mão, Pé e Boca , Macaca mulatta , Mesocricetus , Animais , Doença de Mão, Pé e Boca/virologia , Doença de Mão, Pé e Boca/patologia , Enterovirus Humano B/patogenicidade , Anticorpos Antivirais/sangue , Cricetinae , Feminino , Eliminação de Partículas Virais , Nasofaringe/virologia , Masculino
2.
Curr Drug Deliv ; 20(2): 192-200, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35410599

RESUMO

INTRODUCTION: High mortality and limited therapeutic efficacy of clinical treatment make breast cancer a stubborn disease in women. The hypovascular issue is the main challenge needed to be overcome in breast cancer treatment. METHODS: For this purpose, hyperthermia-sensitive liposomes containing indocyanine green (ICG) and brucea javanica oil (BJO) (LP(BJO/ICG)) were constructed for near-infrared (NIR) laser-induced photothermal- /chemo-antitumor therapy. ICG, an FDA-approved photothermal agent, was employed in this study to perform photothermal therapy (PTT) effect as well as relieve hypovascular conditions in breast cancer tissue. RESULTS: BJO triggered release from the hyperthermia-sensitive LP (BJO/ICG) due to disassembly of liposomes under the PTT effect caused by ICG under NIR laser irradiation. It was found that mice in LP (BJO/ICG) group showed the slowest tumor growth under NIR laser irradiation, illustrating the strongest antitumor effect among all groups. CONCLUSION: This responsive-release drug delivery platform can be a promising candidate for the treatment of breast cancer.


Assuntos
Hipertermia Induzida , Neoplasias , Animais , Feminino , Camundongos , Brucea javanica , Sistemas de Liberação de Medicamentos , Verde de Indocianina/farmacologia , Verde de Indocianina/uso terapêutico , Lipossomos , Neoplasias/tratamento farmacológico , Terapia Fototérmica , Óleos de Plantas/química
3.
Virol Sin ; 37(4): 610-618, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35777657

RESUMO

Coxsackievirus A10 (CV-A10) is one of the etiological agents associated with hand, foot and mouth disease (HFMD) and also causes a variety of illnesses in humans, including pneumonia, and myocarditis. Different people, particularly young children, may have different immunological responses to infection. Current CV-A10 infection animal models provide only a rudimentary understanding of the pathogenesis and effects of this virus. The characteristics of CV-A10 infection, replication, and shedding in humans remain unknown. In this study, rhesus macaques were infected by CV-A10 via respiratory or digestive route to mimic the HFMD in humans. The clinical symptoms, viral shedding, inflammatory response and pathologic changes were investigated in acute infection (1-11 day post infection) and recovery period (12-180 day post infection). All infected rhesus macaques during acute infection showed obvious viremia and clinical symptoms which were comparable to those observed in humans. Substantial inflammatory pathological damages were observed in multi-organs, including the lung, heart, liver, and kidney. During the acute period, all rhesus macaques displayed clinical signs, viral shedding, normalization of serum cytokines, and increased serum neutralizing antibodies, whereas inflammatory factors caused some animals to develop severe hyperglycemia during the recovery period. In addition, there were no significant differences between respiratory and digestive tract infected animals. Overall, all data presented suggest that the rhesus macaques provide the first non-human primate animal model for investigating CV-A10 pathophysiology and assessing the development of potential human therapies.


Assuntos
Enterovirus Humano A , Doença de Mão, Pé e Boca , Animais , Anticorpos Neutralizantes , Benzenoacetamidas , Pré-Escolar , Humanos , Macaca mulatta , Piperidonas
4.
J Pharm Pharmacol ; 61(6): 713-9, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19505361

RESUMO

OBJECTIVES: Polymeric nanoparticles have been extensively studied as drug carriers. Chitosan and its derivatives have attracted significant attention in this regard but have limited application because of insolubility in biological solution. In this work, we attempted to utilize cholesterol-modified glycol chitosan (CHGC) self-aggregated nanoparticles to increase aqueous solubility, and to reduce side effects and enhance the antitumour efficacy of the anticancer drug doxorubicin. Methods CHGC nanoparticles were loaded with doxorubicin by a dialysis method, and their characteristics were determined by transmission electron microscopy examination, light-scattering study, in-vitro drug-release study, pharmacokinetic study in rats and in-vivo antitumour activity in mice. KEY FINDINGS: The resulting doxorubicin-loaded CHGC nanoparticles (DCNs) formed self-assembled aggregates in aqueous medium. From the observation by transmission electron microscopy, DCNs were almost spherical in shape. The mean diameters of these nanoparticles determined by dynamic light scattering were in the range of 237-336 nm as the doxorubicin-loading content increased from 1.73% to 9.36%. In-vitro data indicated that doxorubicin release from DCNs was much faster in phosphate-buffered saline at pH 5.5 than at pH 6.5 and 7.4, and the release rate was dependent on the loading content of doxorubicin in these nanoparticles. It was observed that DCN-16 (drug loaded content: 9.36%) exhibited prolonged circulation time in rat plasma and showed higher antitumour efficacy against S180-bearing mice than free doxorubicin. CONCLUSIONS: These results indicated that CHGC nanoparticles had potential as a carrier for insoluble anticancer drugs in cancer therapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Quitosana/química , Colesterol/química , Doxorrubicina/administração & dosagem , Nanopartículas/química , Polímeros/química , Animais , Antibióticos Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Quitosana/farmacocinética , Quitosana/uso terapêutico , Colesterol/farmacocinética , Colesterol/uso terapêutico , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapêutico , Portadores de Fármacos , Composição de Medicamentos , Luz , Masculino , Camundongos , Camundongos Endogâmicos ICR , Microscopia Eletrônica de Transmissão , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Tamanho da Partícula , Polímeros/farmacocinética , Polímeros/uso terapêutico , Ratos , Ratos Sprague-Dawley , Espalhamento de Radiação , Solubilidade , Ensaios Antitumorais Modelo de Xenoenxerto
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