RESUMEN
Objective: To investigate the application value of reactive oxygen species (ROS) and adiponectin (ADPN) in the judgment of liver inflammation in chronic hepatitis B virus infection combined with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 159 cases with NAFLD (21 cases), chronic hepatitis B virus infection (57 cases), and chronic hepatitis B virus infection combined with NAFLD (81 cases) were collected between June 2016 to December 2018, and the visited patients diagnosis were confirmed by histopathological examination of the liver. ROS and ADPN level retained in serum was determined by enzyme-linked immunosorbent assay. Histopathological examination of liver tissue was used as the gold standard to discuss the diagnostic value of the serum in patients with chronic hepatitis B virus infection combined with NAFLD for the occurrence of nonalcoholic steatohepatitis. One-way analysis of variance was used for the comparison among multiple groups, and LSD-t test was used for pairwise comparison between groups. Measurement data for non-normal distributions were expressed as M (P25, P75). Comparisons between groups were performed using the Mann-Whitney U or Kruskal-Wallis H test. Chi-square test was used to compare the count data between groups. Correlation analysis was performed using Spearman correlation analysis. Histopathological grouping of liver tissue was used as the gold standard, and the area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the regression formula. Results: (1) In patients with chronic hepatitis B virus infection combined with NAFLD, the levels of ROS in the non-hepatic steatosis group and the mild hepatic steatosis group were significantly lower than those in the moderate and severe hepatic steatosis group, while the ADPN level in the non-hepatic steatosis group was significantly higher than liver steatosis group, P < 0.05. (2) The results of correlation analysis showed that ROS was significantly correlated with NAS score, change in the degree of fatty liver and lobular inflammation (all P < 0.05).There was a significant negative correlation between ADPN and the change in the degree of fatty liver (P < 0.05). (3) Logistic regression analysis results showed that the diagnostic formula for chronic hepatitis B virus infection combined with nonalcoholic steatohepatitis was 0.02 × controlled attenuation index + 0.584 × white blood cells/10(9) + 0.587 × ROS-10.982. The area under receiver operating characteristic curve of the subject was = 0.896. The sensitivity, specificity, positive and negative predictive value were 97.1%, 71.2%, 64.2%, and 97.9%. Conclusion: ADPN and ROS have certain reference value in differentiating the change in the degree of fatty liver and inflammation in chronic hepatitis B virus infection combined with NAFLD and the diagnostic formula has higher application value in the diagnosis and exclusion of chronic hepatitis B virus infection combined with nonalcoholic steatohepatitis.
Asunto(s)
Adiponectina/sangre , Hepatitis B Crónica/sangre , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/virología , Especies Reactivas de Oxígeno/sangre , Biopsia , Virus de la Hepatitis B , Hepatitis B Crónica/complicaciones , Humanos , HígadoRESUMEN
The transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1) has crucial roles in the control of plasma cell differentiation and in maintaining survival of plasma cells. However, how Blimp-1 ensures the survival of plasma cell malignancy, multiple myeloma (MM), has remained elusive. Here we identified Aiolos, an anti-apoptotic transcription factor of MM cells, as a Blimp-1-interacting protein by mass spectrometry. ChIP coupled with DNA microarray was used to profile the global binding of Aiolos and Blimp-1 to endogenous targets in MM cells, which revealed their co-binding to a large number of genes, including apoptosis-related genes. Accordingly, Blimp-1 and Aiolos regulate similar transcriptomes in MM cells. Analysis of the binding motifs for Blimp-1 and Aiolos uncovered a partial motif that was similar across sites for both proteins. Aiolos promotes the binding of Blimp-1 to target genes and thereby enhances Blimp-1-dependent transcriptional repression. Furthermore, treatment with an anti-MM agent, lenalidomide, caused ubiquitination and proteasomal degradation of Blimp-1, leading to the de-repression of a new Blimp-1 direct target, CULLIN 4A (CUL4A), and reduced Aiolos levels. Accordingly, lenalidomide-induced cell death was partially rescued by reintroduction of Blimp-1 or knockdown of CUL4A. Thus, we demonstrated the functional impacts and underlying mechanisms of the interaction between Aiolos and Blimp-1 in maintaining MM cell survival. We also showed that interruption of Blimp-1/Aiolos regulatory pathways contributes to lenalidomide-mediated anti-MM activity.
Asunto(s)
Apoptosis , Factor de Transcripción Ikaros/metabolismo , Factor 1 de Unión al Dominio 1 de Regulación Positiva/metabolismo , Inhibidores de la Angiogénesis/farmacología , Anticuerpos/inmunología , Apoptosis/efectos de los fármacos , Secuencia de Bases , Sitios de Unión , Línea Celular Tumoral , Proteínas Cullin/antagonistas & inhibidores , Proteínas Cullin/genética , Proteínas Cullin/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Células HEK293 , Humanos , Factor de Transcripción Ikaros/genética , Factor de Transcripción Ikaros/inmunología , Lenalidomida , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Factor 1 de Unión al Dominio 1 de Regulación Positiva/antagonistas & inhibidores , Factor 1 de Unión al Dominio 1 de Regulación Positiva/genética , Regiones Promotoras Genéticas , Unión Proteica , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Talidomida/análogos & derivados , Talidomida/farmacología , Ubiquitinación/efectos de los fármacosRESUMEN
A one-dimensional model for the spatio-temporal variation of solids fraction in the blanket considering both the hydrodynamic dispersion and the convection effects was proposed in this study. The model equation was a wave equation whose solution presented shock-wave like characteristic. The model output predicted that the distribution of the solids fraction in the blanket would, firstly, evolve to a uniform distribution at a lower solids fraction. Afterward, the blanket would compact itself to another uniform distribution at a higher solids fraction. Experimental works with synthetic raw water coagulated with PACl suspended in a lab-scale suspended bed confirmed the theoretical predictions. The solids flux plot was constructed with underdosed, optimal and overdosed suspensions. Change in coagulant dose would affect the blanket height and the response time. The solids flux curve was shifted accordingly. The "optimal' operational condition for the upflow suspended bed that produced the lowest effluent turbidity was identified and discussed.