ABSTRACT
Human enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD) cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 μg/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1β, IL-6, IL-8, and TNF-α significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of pro-inflammatory cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.
Subject(s)
Humans , Antiviral Agents/pharmacology , Enterovirus A, Human/drug effects , Naphthoquinones/pharmacology , Rhabdomyosarcoma/virology , Blotting, Western , Cell Line, Tumor , Cytokines/analysis , Dose-Response Relationship, Drug , Real-Time Polymerase Chain Reaction , Toxicity Tests , Viral Plaque Assay , Virus Replication/drug effectsABSTRACT
RESUMO: Objetivo: Descrever as principais doenças crônicas não transmissíveis (DCNT) no país segundo as informações coletadas em indivíduos de 18 anos ou mais de idade. Métodos: Foram utilizados dados da Pesquisa Nacional de Saúde (PNS), 2013, estudo transversal de base populacional. As proporções de cada DCNT foram calculadas e apresentadas segundo sexo, com intervalo de confiança de 95% (IC95%), com os valores absolutos. Resultados: Do total de entrevistados, 45,1% referiram ter pelo menos uma DCNT. A Região com maior prevalência de DCNT foi a Sul (52,1%). A hipertensão arterial apresentou a maior prevalência dentre as DCNT, com 21,4%, seguida por problema crônico de coluna (18,5%), depressão (7,6%), artrite (6,4%) e diabetes (6,2%). O grau de limitação intenso/muito intenso apresentou maiores prevalências para outra doença mental (37,6%) e acidente vascular cerebral (AVC) (25,5%). Conclusão: A melhoria dos serviços de saúde é indispensável para uma resposta efetiva à dupla carga de adoecimento de países de média e baixa renda.
ABSTRACT: Objective: To describe the major noncommunicable diseases (NCDs) in Brazil, according to the information collected from individuals aged 18 years or older. Methods: Data from the National Health Survey (PNS), 2013, a transversal population-based study, were used. The proportions of each NCD were calculated and presented according to sex, with a 95% confidence interval (95%CI), with the absolute values. Results: Of the total respondents, 45.1% reported presenting at least one NCD. The region with the highest prevalence of NCDs was the South (52.1%). Hypertension showed the highest prevalence among NCDs, with 21.4%, followed by chronic back problem (18.5%), depression (7.6%), arthritis (6.4%), and diabetes (6.2%). The intense/very intense degree of limitation showed a higher prevalence of other mental illnesses (37.6%) and cerebrovascular accident (25.5%). Conclusion: The improvement of health services is essential for an effective response to the double burden of illness in the middle- and low-income countries.