RESUMEN
Fish interferon (IFN)-mediated antiviral innate immunity is the first line of defense against virus invasion. In the present study, we identify two fish IFN genes (here tentatively named IFNa and IFNc) with different-sized 3' UTRs from clone F strain of gibel carp Carassius auratus gibelio. Carp IFNa has a relatively short 3'UTR without AU-rich elements (AREs) but IFNc has a long one with 9 AREs. Functionally, carp IFNa and IFNc display significantly antiviral potential to viral infection, likely through induction of downstream IFN-stimulated genes (ISGs). Both carp IFN genes are induced by viral infection, poly(I:C) treatment and IRF3/7, which are ascribed to the IFN-sensitive response elements (ISRE) within their promoters. Carp IFN genes are also induced by each other and by themselves, indicating existence of a positive feedback loop in fish IFN-mediated antiviral immune response. Comparative analyses of 3'UTR-mediated expression regulation at mRNA and protein levels show that the ARE-containing 3'UTR of carp IFNc rather than the short 3'UTR of carp IFNa promotes mRNA decay but instead results in high-level protein expression, indicating that 3'UTR of fish IFN mRNAs might be a potential factor for regulation of IFN-mediated antiviral immune response. Considering a fact that a given protein function is largely related to its protein level, these results suggest that both promoter and 3'UTR contribute to the transcription and translation of fish IFN genes, thus shaping their eventually antiviral potential.
Asunto(s)
Regiones no Traducidas 3' , Enfermedades de los Peces/genética , Carpa Dorada/genética , Interferones/genética , Regulación hacia Arriba , Elementos Ricos en Adenilato y Uridilato , Animales , Línea Celular , Enfermedades de los Peces/inmunología , Infecciones por Herpesviridae/genética , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/virología , Especificidad de la EspecieRESUMEN
Our goals were to examine the dual-directional regulation effects of resveratrol (1) in vitro by using MCF-7 cells (estradiol receptor-positive cells), study its mechanism of action, and give a systematical analysis of the regulatory networks of each related factor. An MTT test and growth curve showed that the proliferation of MCF-7 cells was inhibited by a high concentration of 1, and that its IC(50) was 8.70 x 10(-5) +/- 0.23 mol/l. However, 1 induced the proliferation of MCF-7 cells at 10(-7)-10(-5) mol/l, and resulted in a peak proliferation at 1.0 x 10(-7) mol/l. A high concentration of 1 arrested cell cycle progression at the G(1) phase, and a typical "sub-G(1) peak" of apoptotic cells was also observed by flow cytometry. The proliferation index of MCF-7 cells increased significantly with a low concentration of 1 (p < 0.05). 1 in high concentrations induced Bax, caspase-3, and cyclin-dependent kinase (CDK) inhibitor P21 expression, whereas the expressions of cyclin CDK2, Bcl-2, and proliferating cell nuclear antigen (PCNA) were decreased by 1 treatment. Conversely, treatment with low concentrations of 1 decreased the expression of P21 and Bax, while the expressions of cyclin CDK2, Bcl-2, and PCNA were increased. These results suggest that 1 had a dual-regulatory effect on MCF-7 cells. CDK-associated protein was a key factor at both the high and low concentrations used in this study.
Asunto(s)
Ciclo Celular/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/efectos de los fármacos , Estilbenos/farmacología , Caspasa 3/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/efectos de los fármacos , Femenino , Humanos , Estructura Molecular , Resveratrol , Estilbenos/química , Células Tumorales CultivadasRESUMEN
OBJECTIVE: To explore the public health situation and needs in Anxian after Wenchuan earthquake so as to make an effective strategy for disease control and prevention. METHODS: 69 concentrated settlements with 100 residents were investigated. Probability proportion to size was adopted for sampling of 2200 residents from 687 scattered households (about 440 000 scattered residents). The content of this survey included drinking water, food hygiene, environment sanitation, planning immunity and medical health service, disease surveillance and so on. SPSS 16.0 was used for data analysis, and statistical interpretation was used to describe the results. RESULTS: 90.9% (31/66) resettled residents in Anxian lived in tents, 7.6% (5/66) lived in the movable-plate house, 93.3% (621/666) scattered households lived in tents and 71.9% (446/621) of them lived in tents which were built by residents themselves; the rate of drinking water disinfection in resettlement sites and scattered households were 97.1% (66/68) and 94.6% (650/687); 12.8% scattered residents had mouldy or food; 50% of resettlement sites raised animals; 43.6% (17/39) medical station didn't have bacterin inoculation service; 66.7% (10/15) lacked sufficient disinfection equipment; register rate was 50.0% (33/66) and report rate of symptoms and infectious diseases was 56.1% (37/66). CONCLUSION: There was still some risk of enteric and vector-borne diseases in Anxian, therefore, some tailored measures should be very important.
Asunto(s)
Desastres , Terremotos , Necesidades y Demandas de Servicios de Salud , Monitoreo del Ambiente , Encuestas de Atención de la Salud , Servicios de Salud , Humanos , Abastecimiento de AguaRESUMEN
OBJECTIVE: To explore the mental health status of residents scattered living in Anxian after Wenchuan earthquake so as to provide scientific basis for further mental health intervention. METHODS: A face to face interview was conducted among the scattered residents with designed questionnaire, which had three parts of the physical and emotional reaction, the relax methods and the social care and supports expected. Two-stage probability proportional to size (PPS) sample method was performed to sample 2184 from 0.44 million scattered residents in Anxian. On the basis of statistical description, mental health of different characteristics groups was compared. RESULTS: Three main symptoms of posttraumatic stress disorders in 2184 residents (11.23+/-3.44) were higher than the 103 fire victims in Hunan in 2003 (10.06+/-3.26), three factor scores of SCL-90 (5.76+/-1.74) were higher than normal in 1998 repair mode (n=23 891) (4.72+/-1.44), and the statistical difference was observed (t=10.77, P<0.05; t=706.04, P<0.05). Comparing the mental health of different groups, some significant differences were found by age, gender and education background. CONCLUSION: The earthquake disaster brought prevalent physical and emotional reaction. Elderly people, female, junior students need mental intervention immediately. Therefore, strengthen the mental education and assistance (especially in high risk groups) would be of more significance.
Asunto(s)
Desastres , Terremotos , Salud Mental , Trastornos por Estrés Postraumático/psicología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Muestreo , Trastornos por Estrés Postraumático/epidemiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) is a member of the basic helix-loop-helix/PER-ARNT-SIM (bHLH/PAS) transcription factor family. ARNT2 heterodimerizes with several members of the family, including single-minded homolog-1 (SIM1) and neuronal PAS domain protein 4 (NPAS4), primarily in neurons of the central nervous system. We screened 64,424 third-generation germline mutant mice derived from N-ethyl-N-nitrosourea (ENU)-mutagenized great-grandsires for weight abnormalities. Among 17 elevated body weight phenotypes identified and mapped, one strongly correlated with an induced missense mutation in Arnt2 using a semidominant model of inheritance. Causation was confirmed by CRISPR/Cas9 gene targeting to recapitulate the original ENU allele, specifying Arg74Cys (R74C). The CRISPR/Cas9-targeted (Arnt2R74C/R74C) mice demonstrated hyperphagia and increased adiposity as well as hepatic steatosis and abnormalities in glucose homeostasis. The mutant ARNT2 protein showed decreased transcriptional activity when coexpressed with SIM1. These findings establish a requirement for ARNT2-dependent genes in the maintenance of the homeostatic feeding response, necessary for prevention of obesity and obesity-related diseases.