RESUMEN
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. The outcomes of both spontaneous HCV clearance and response to therapy depend on both viral and host factors. To investigate the influence of polymorphisms of IL-28B rs12979860 and TBX21 rs17250932, rs4794067 as well as viral factors (HCV genotype, F protein) on the outcome of HCV infection, we genotyped 565 patients with chronic HCV infection, 191 patients spontaneously resolved from HCV infection, 359 healthy controls and 383 treatment-naïve CHC patients with pegylated interferon-α and ribavirin (PEG IFN-α/RBV). Results showed that TBX21 rs4794067 variant genotypes significantly correlated with increased risk of HCV chronic infection (dominant model: OR = 5.690, 95% CI = 2.024-16.000) and susceptibility (dominant model: OR = 5.658, 95% CI = 2.514-12.735). We also found that the rs12979860, rs2227982 and rs36084323 polymorphisms showed no significant associations with susceptibility or spontaneous clearance of HCV in the anti-F antibody subgroup; however, the anti-F antibody positive subgroup might show an increased risk of N-SVR (all P < 0.001). Our results demonstrate that variant factors in both the host and pathogen are commonly important for HCV clearance. In addition rs4794067 and F protein status may be strong predictive markers in the Chinese population.
Asunto(s)
Hepatitis C Crónica/genética , Hepatitis C Crónica/virología , Interleucinas/genética , Polimorfismo de Nucleótido Simple , Proteínas de Dominio T Box/genética , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/sangre , Antivirales/uso terapéutico , Pueblo Asiatico/genética , China , Susceptibilidad a Enfermedades , Quimioterapia Combinada , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Hepacivirus/genética , Hepacivirus/inmunología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/etnología , Humanos , Interferón-alfa/uso terapéutico , Interferones , Masculino , Persona de Mediana Edad , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Respuesta Virológica Sostenida , Proteínas del Núcleo Viral/inmunología , Adulto JovenRESUMEN
The 18-mer oligodeoxynucleotides (ODNs) that can inhibit survivin gene expression were selected as a model gene drug to study hepatic-targeting drug delivery system. Novel galactosylated polymers (cholesteryloxycarbonylamino) ethylamine-alpha,beta-polyasparthydrazied (CHE-PAHy-Lacs), which target asialoglycoprotein receptor on hepatic parenchymal cells (PC), were designed and synthesized as non-toxic, non-antigenic and non-teratogenic ligands for liposomes. The liposomes incorporating different CHE-PAHy-Lacs were prepared and characterized by zeta potential and particle size analyzer. The drug encapsulation efficiency was measured by gel filtration method. 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate was used as a marker for all the liposome preparations in the in vivo experiments. The CHE-PAHy-Lac liposomes produced a significant improvement in the encapsulation efficiency of ODNs (28.73-51.37%) compared with conventional liposomes (9.88%). The in vivo results showed that the liposomes incorporating CHE-PAHy-Lac, which contained about 30% (w/w) galactosyl residues, exhibited marked accumulation in the liver and hepatic PC. These results suggest that the novel galactosylated polymers used for liposomes have a great potential as a gene delivery system for hepatic targeting.
Asunto(s)
Receptor de Asialoglicoproteína/metabolismo , Liposomas , Hígado/metabolismo , Oligodesoxirribonucleótidos/administración & dosificación , Polímeros/administración & dosificación , Animales , Galactosa/química , Masculino , Ratones , Polímeros/síntesis química , Ratas , Ratas Wistar , Distribución TisularRESUMEN
Lignin impedes the digestion of corn stover when used as an animal feed. Phanerochaete chrysosporium is an efficient lignindegrader. Geotrichum candidum can be used to produce single-cell protein. In this study, protoplasts of the two fungi were prepared and fused. After screening, one of the fusants, Fusant R1, was selected for corn stover fermentation. It decreased lignin from 109 to 54 g/kg and increased protein from 48 to 67 g/kg in corn stover. Comparison with their parental strains indicated that the fusant obtained the lignin-degrading ability from P. chrysosporium and the protein-accumulating ability from G. candidium.