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1.
PLoS Pathog ; 20(2): e1011999, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38306394

RESUMEN

Hepatitis B virus (HBV) chronically infects 296 million people worldwide, posing a major global health threat. Export of HBV RNAs from the nucleus to the cytoplasm is indispensable for viral protein translation and genome replication, however the mechanisms regulating this critical process remain largely elusive. Here, we identify a key host factor embryonic lethal, abnormal vision, Drosophila-like 1 (ELAVL1) that binds HBV RNAs and controls their nuclear export. Using an unbiased quantitative proteomics screen, we demonstrate direct binding of ELAVL1 to the HBV pregenomic RNA (pgRNA). ELAVL1 knockdown inhibits HBV RNAs posttranscriptional regulation and suppresses viral replication. Further mechanistic studies reveal ELAVL1 recruits the nuclear export receptor CRM1 through ANP32A and ANP32B to transport HBV RNAs to the cytoplasm via specific AU-rich elements, which can be targeted by a compound CMLD-2. Moreover, ELAVL1 protects HBV RNAs from DIS3+RRP6+ RNA exosome mediated nuclear RNA degradation. Notably, we find HBV core protein is dispensable for HBV RNA-CRM1 interaction and nuclear export. Our results unveil ELAVL1 as a crucial host factor that regulates HBV RNAs stability and trafficking. By orchestrating viral RNA nuclear export, ELAVL1 is indispensable for the HBV life cycle. Our study highlights a virus-host interaction that may be exploited as a new therapeutic target against chronic hepatitis B.


Asunto(s)
Virus de la Hepatitis B , ARN Viral , Animales , Humanos , Virus de la Hepatitis B/metabolismo , Transporte Activo de Núcleo Celular , ARN Viral/genética , ARN Viral/metabolismo , Drosophila/genética , Replicación Viral/genética , Proteínas Nucleares/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Proteína 1 Similar a ELAV/genética , Proteína 1 Similar a ELAV/metabolismo
2.
J Nanosci Nanotechnol ; 17(2): 884-92, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29671467

RESUMEN

In this study, poly(D,L-lactic acid)­polyethylene glycol­poly(D,L-lactic acid), hereafter referred to as PDLLA­PEG­PDLLA, triblock copolymer membranes were prepared by electrospinning. Scanning electron microscopy images revealed the morphology of the microfibers, which had a diameter ranging from 300 to 900 nm. Fourier transform infrared spectroscopy was employed for structural analysis of the PDLLA­PEG­PDLLA/florfenicol (FF) membranes, which exhibited three absorption peaks at 3455, 1684, and 1533 cm−1, respectively, indicating that the triblock copolymer and FF are very well blended in the composite membranes. Differential scanning calorimetry revealed that weak interaction possibly decreased the activity of the segment and elevated the T g from 43 °C to 46 °C. From the in vitro dissolution tests, PDLLA as a biodegradable and biocompatible polymer can improve the solubility of FF. The rate of drug release increased with increasing PEG proportion. Furthermore, tensile and nanoindentation tests demonstrated that nanofibers exhibit mechanical properties such as tensile stress (700­2800 KPa), strain (40­120%), and good toughness (0.28­0.98 GPa). In conclusion, PDLLA­PEG­PDLLA nanofibers as a carrier improve the solubility of FF and control drug release.


Asunto(s)
Portadores de Fármacos/química , Técnicas Electroquímicas/métodos , Membranas Artificiales , Nanofibras/química , Poliésteres/química , Polietilenglicoles/química , Ensayo de Materiales , Tianfenicol/análogos & derivados , Tianfenicol/química , Tianfenicol/farmacocinética
3.
J Nanosci Nanotechnol ; 21(3): 1549-1559, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33404418

RESUMEN

Cellulose acetate (CA) fibrous membranes blended with poly-(γ-glutamic acid) (γ-PGA) and ZnO were produced via electrospinning. The performance of the obtained composite membrane was investigated by scanning electron microscopy (SEM), Fourier transform IR spectroscopy, tensile test, water contact angle, and thermogravimetric analysis. The corn plant height, leaf area and SPAD (soil and plant analyzer development) were compared with plants covered with CA/γ-PGA and CA/γ-PGA/ZnO fibrous membranes at room temperature. Simultaneously, the water absorption and degradation rate were also studied. The results obtained indicate the potential use of these fibrous membranes for mulching film applications. The fibrous membranes could also find potential use as a material for food packing, facial mask and as antimicrobial films for wound dressing.

4.
RSC Adv ; 8(48): 27304-27317, 2018 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-35539979

RESUMEN

Poly(ether ether ketone)/zinc oxide (PEEK/ZnO) composites were manufactured by using the injection molding technique. Before blending with the PEEK resin matrix, some ZnO nanoparticles were modified by γ-aminopropyltriethoxylsilane (APTES). The effect of surface modification of ZnO nanoparticles by amino groups and Si-O bonds was investigated. PEEK/ZnO composites were characterized by scanning electron microscopy (SEM), thermogravimetric analysis, and X-ray diffraction. The scanning electron micrographs showed that ZnO nanoparticles were encapsulated in the PEEK phase; within this phase, the nanoparticles were homogeneously dispersed. Mechanical and tribological properties were measured by tensile strength, flexural strength, coefficient of friction, and wear rate. It was shown that the interfacial compatibility between ZnO nanoparticles and PEEK matrix was significantly enhanced due to the amino and Si-O bonds decorated on the ZnO nanoparticles. More importantly, the thermal stability of PEEK improved upon the incorporation of ZnO nanoparticles into this matrix. Cell viability studies with mouse osteoblasts demonstrated that cell growth on PEEK and PEEK/ZnO was significantly enhanced. On the basis of the obtained results, PEEK/ZnO composites are recommended as promising candidates for orthopaedic materials and trauma implants.

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