RESUMEN
Epstein-Barr virus (EBV) is an aetiologic risk factor for the development of multiple sclerosis (MS). However, the role of EBV-infected B cells in the immunopathology of MS is not well understood. Here we characterized spontaneous lymphoblastoid cell lines (SLCLs) isolated from MS patients and healthy controls (HC) ex vivo to study EBV and host gene expression in the context of an individual's endogenous EBV. SLCLs derived from MS patient B cells during active disease had higher EBV lytic gene expression than SLCLs from MS patients with stable disease or HCs. Host gene expression analysis revealed activation of pathways associated with hypercytokinemia and interferon signalling in MS SLCLs and upregulation of forkhead box protein 1 (FOXP1), which contributes to EBV lytic gene expression. We demonstrate that antiviral approaches targeting EBV replication decreased cytokine production and autologous CD4+ T cell responses in this ex vivo model. These data suggest that dysregulation of intrinsic B cell control of EBV gene expression drives a pro-inflammatory, pathogenic B cell phenotype that can be attenuated by suppressing EBV lytic gene expression.
Asunto(s)
Linfocitos B , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Esclerosis Múltiple , Humanos , Herpesvirus Humano 4/genética , Esclerosis Múltiple/virología , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/genética , Esclerosis Múltiple/metabolismo , Linfocitos B/inmunología , Linfocitos B/metabolismo , Linfocitos B/virología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Citocinas/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Linfocitos T CD4-Positivos/metabolismo , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Transcriptoma , Replicación Viral , Regulación Viral de la Expresión Génica , Línea Celular , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Perfilación de la Expresión Génica , Adulto , Femenino , MasculinoRESUMEN
OBJECTIVES: We aimed to examine the current status and trends of food and nutrient intake in the Korean population over the past 20 years using the data from the Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: We conducted a survey of 116,284 subjects over the age of one year in Korea, who participated in the KNHANES between 1998 and 2018. We collected data on the subjects' intake for the day before using the 24-hour recall method. The annual percent change (APC) in the food groups and nutrient intake were calculated using SAS and Joinpoint software. RESULTS: The intake of grains (APC=-0.4, p<0.05) and vegetables (APC=-0.8, p<0.05) was observed to decrease. In contrast, the intake of beverages, meat, dairy, and eggs increased. In particular, beverage intake increased by more than four times (APC=9.2, p<0.05). There was no significant change in energy intake. However, the proportion of energy intake from carbohydrates decreased by approximately 5%p (APC=-0.3, p<0.05), whereas that from fat increased by approximately 5%p (APC= 1.1, p<0.05). Additionally, there were decreases in the proportion of energy intake from breakfast and homemade meals and increases in the energy intake from snacks, dining out, and convenience food. The intake of vitamin C (APC=-3.2, p<0.05) and sodium (APC=-2.3, p<0.05) significantly decreased. CONCLUSIONS: Over the past 20 years, there has been decreases in the intake of grains, vegetables, carbohydrates, sodium, and vitamin C and increases in the intake of beverages, dairy, meat, eggs, and fat. Since nutritional status is an important factor in the prevention and management of chronic diseases, it should be continuously monitored.
Asunto(s)
Dieta/tendencias , Ingestión de Alimentos , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , República de Corea , Adulto JovenRESUMEN
Microhaplotypes (microhaps or MHs) are novel forensically relevant genetic markers that demand large and appropriate allele frequency datasets for their implementation in casework. In this study we report on the allele frequency data of 74 microhap loci (230 SNPs) included in a newly developed 74-plex assay. The panel was tested on the Ion S5 system on a total of 347 samples from four main U.S. population groups of African, European, East Asian and Southwest Hispanic descent. Overall, frequencies of individual alleles at each locus varied considerably among the different population groups. An increase in the average value of gene diversity was also observed as the number of SNPs per locus increased. Most microhap markers showed no significant deviation from Hardy-Weinberg ratios within any of the individual population samples displaying an average power of discrimination between 0.74 and 0.81 and an average probability of exclusion between 0.32 and 0.39. Moreover, the four population groups had no clear genetic affinities with the exception of U.S. European and U.S. Southwest Hispanic populations, which showed the lowest FST value. STRUCTURE and principal component analyses (PCA) analysis resulted in effective clustering of the four populations with the U.S. European and Southwest Hispanic showing some overlap. These results support the potential use of this sequence-based 74plex-microhaplotype assay for ancestry inference in addition to previously reported human identification and mixture deconvolution capabilities.
Asunto(s)
Genética de Población , Haplotipos , Grupos Raciales/genética , Dermatoglifia del ADN , Frecuencia de los Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Polimorfismo de Nucleótido Simple , Análisis de Componente Principal , Análisis de Secuencia de ADN , Estados UnidosRESUMEN
We hypothesized that olive leaf extract might alleviate dyslipidemia resulting from estrogen deficiency. Serum lipid profile and mRNA expression of the related genes in the liver and adipose tissue were analyzed after providing olive leaf extract (200 or 400 mg/kg body weight; n=7 for each group) to ovariectomized rats for 10 weeks. After 10 weeks' administration, the rats in the olive leaf extract-administered groups showed significantly lower levels of serum triglyceride and very-low-density lipoprotein (VLDL)-cholesterol compared with the rats in the control group, whereas the administration of olive leaf extract did not significantly change the elevated low-density lipoprotein cholesterol levels. In addition, administration of high dose of olive leaf extract significantly decreased the liver triglyceride and increased serum estradiol levels. mRNA expressions of peroxisome proliferator-activated receptor alpha (PPAR α) and acyl-CoA oxidase (ACO) were not affected by ovariectomy, however, administration of olive leaf extract significantly increased both PPAR α and ACO mRNA expression. Expression of adiponectin mRNA in adipose tissue was significantly decreased in the ovariectomized control group. Rats administered low-dose olive leaf extract showed significantly elevated adiponectin mRNA expression compared with rats in the ovariectomized control group. Even though dose-dependent effects were not observed in most of the measurements, these results suggest that genes involved in lipid metabolism may be regulated by olive leaf extract administration in ovariectomized rats.