RESUMEN
The tripartite motif (TRIM)-5 and TRIM22 are involved in innate immune response and show anti-viral activities. The current study aimed at evaluating the association of TRIM5 and TRIM22 polymorphisms with treatment outcomes in patients with chronic hepatitis C virus (CHC). TRIM5 rs3824949 and TRIM22 polymorphisms (rs7113258, rs7935564, and rs1063303) were genotyped using TaqMan polymerase chain reaction (PCR) assay in 425 treatment-naïve CHC patients. Rapid virological response (RVR), early virological response (EVR), and sustained virological response (SVR) were found in 54.1%, 74.8%, and 67.1% of the patients, respectively. RVR and SVR were associated with TRIM5 rs3824949 (GG), TRIM22 rs1063303 (GC), and TRIM22 rs7113258 (AA), while there was a relationship between TRIM5 rs3824949 (GG) and EVR. TRIM5 and TRIM22 single nucleotide polymorphisms (SNPs) were strongly associated with increased odds of RVR, EVR, and SVR after an interferon-based therapy in patients with CHC.
Asunto(s)
Antivirales/uso terapéutico , Proteínas Portadoras/genética , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Antígenos de Histocompatibilidad Menor/genética , Polietilenglicoles/uso terapéutico , Polimorfismo de Nucleótido Simple , Proteínas Represoras/genética , Proteínas de Motivos Tripartitos/genética , Adulto , Factores de Restricción Antivirales , Femenino , Hepatitis C Crónica/genética , Humanos , Irán , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Respuesta Virológica Sostenida , Resultado del Tratamiento , Ubiquitina-Proteína LigasasRESUMEN
The emergence of extensively drug-resistant (XDR) Acinetobacter baumannii strains and the limited number of efficacious antibiotics demonstrate an urgent need to develop novel agents to treat infections caused by this dangerous pathogen. To find antimicrobial peptides against A. baumannii growing either in planktonic or in biofilm mode, biopanning was carried out with a peptide library on five XDR A. baumannii strains grown in the medium containing human blood (blood biopanning) and biofilms formed by these strains (biofilm biopanning). Two groups of peptides were identified, among which two peptides N10 (from blood biopanning) and NB2 (from biofilm biopanning) were selected and synthesized for more assessments. The selected peptides showed significant binding to A. baumannii rather than to the human cell line Caco-2. Both peptides were effective against A. baumannii and showed antibacterial activities (minimum inhibitory concentration (MIC) 500⯵g/ml). In the biofilm inhibition assay, NB2 reduced biofilm more efficiently (75%) than N10 (50%). The combination of the two peptides could function better than each peptide alone to prevent biofilm formation by A. baumannii. Supplementation of conventional therapy with a mixture of peptides targeting A. baumannii or using peptides to deliver antibiotics specifically to the site of infection may be promising to control A. baumannii-related diseases.