RESUMO
As one of the highly contagious forms, herpes simplex virus type 2 (HSV-2) commonly caused severe genital diseases and closely referred to the HIV infection. The lack of effective vaccines and drug-resistance proclaimed the preoccupation for alternative antiviral agents against HSV-2. Molecules bearing indole nucleus presented diverse biological properties involving antiviral and anti-inflammatory activities. In this study, one of the indole molecules, arbidol derivative (ARD) was designed and synthesized prior to the evaluation of its anti-HSV-2 activity. Our data showed that the ARD effectively suppressed HSV-2-induced cytopathic effects and the generation of progeny virus, with 50% effective concentrations of 3.386 and 1.717⯵g/mL, respectively. The results of the time-course assay suggested that the ARD operated in a dual antiviral way by interfering virus entry and impairing the earlier period of viral cycle during viral DNA synthesis. The ARD-mediated HSV-2 inhibition was partially attained by blocking NF-κB pathways and down-regulating the expressions of several inflammatory cytokines. Furthermore, in vivo studies showed that oral administration of ARD protected BALB/c mice from intravaginal HSV-2 challenge by alleviating serious vulval lesions and histopathological changes in the target organs. Besides, the treatment with ARD also made the levels of viral protein, NF-κB protein and inflammatory cytokines lower, in consistent with the in-vitro studies. Collectively, ARD unveiled therapeutic potential for the prevention and treatment of HSV-2 infections.
Assuntos
Colo do Útero/patologia , Colo do Útero/virologia , Células Epiteliais/virologia , Herpesvirus Humano 2/efeitos dos fármacos , Indóis/farmacologia , Animais , Antivirais/química , Antivirais/farmacologia , Citocinas/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Humanos , Indóis/química , Indóis/toxicidade , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Receptores Toll-Like/metabolismo , Vagina/efeitos dos fármacos , Vagina/patologia , Vagina/virologia , Replicação Viral/efeitos dos fármacosRESUMO
With the growth of industry, the extensive use of lead, and urban expansion in Northwestern Valley Cities (NVC) China, there is probable reason for presuming an increasing risk of lead exposure. However, little is known about the lead exposure of children less than 6 years old in NVC. As a first investigation, this study uses a survey to systematically determine the influences of various risk factors within the family environment, parents' background, children's behavior, mother's behavior during pregnancy, and parental perception about children's blood lead (CBL). A total of 596 families were recruited from the general population in Urumqi, Lanzhou, Xining and Yan'an. Parents, and their children (<6 years old), were asked about the environment and behaviors which could possibly relate with lead exposure. The results indicated that in the typical NVC of China, children's environment and behavior, parents' education level, and mother's pregnancy behavior, were associated with potential CBL. It was noted that not all parents in NVC China recognized the importance of children's lead exposure. Therefore, children's health care and medical screening campaigns need to be designed to improve family's fundamental knowledge of lead hazards, associated health effects, and prevention in the NVC of China.
Assuntos
Comportamento Infantil , Exposição Ambiental/análise , Chumbo/sangue , Pais/psicologia , Saúde da Criança , Pré-Escolar , China , Cidades , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fatores de Risco , Fatores SocioeconômicosRESUMO
The purpose of this study was to identify the concentration of multi-elements (MEs) in source water (surface and drinking water) and assess their quality for sustainability. A total of 161 water samples including 88 tap drinking waters (DW) and 73 surface waters (SW) were collected from five cities in Xi'an, Yan'an, Xining, Lanzhou, and Urumqi in northwestern China. Eighteen parameters including pH, electrical conductivity (EC), total organic carbon (TOC) total nitrogen (TN), chemical compositions of anions (F-, Cl-, NO3-,HCO3-, SO42-), cations (NH4âº, Kâº, Naâº, Ca2+,Mg2+), and metals (lead (Pb), chromium (Cr), cadmium (Cd), copper (Cu)) were analyzed in the first time at the five cities . The results showed that pH values and concentrations of Cl-, SO42-, Naâº, Kâº, Ca2+, Mg2+ and Cd, Cr, Cu in DW were within the permissible limits of the Chinese Drinking Water Quality Criteria, whereas the concentrations of other ions (F-, NO3-, NH4⺠and Pb) exceeded their permissible values. In terms of the SW, the concentrations of F-, Cl-, NO3-, SO42- were over the third range threshold i.e., water suitable for fishing and swimming of the Surface Water Quality Standards in China. The spatial distributions of most MEs in source water are similar, and there was no clear variation for all ions and metals. The metals in DW may be caused by water pipes, faucets and their fittings. The noncarcinogenic risk of metals in DW for local children are in decreasing order Cr > Cd > Pb > Cu. The carcinogenic risk from Cr exposure was at the acceptable level according to threshold of USEPA. Although the comprehensive index of potential ecological assessment of Cr, Cd, Pb and Cu in SW ranked at low risk level and was in the order of Huang River in Xining > Peaceful Canal in Urumqi > Yan River in Yan'an > Yellow River in Lanzhou, their adverse effects to ecology and human health at a low concentration in local semi-arid and arid areas should not be ignored in the long run.