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1.
Small ; 18(34): e2202405, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35908156

RESUMEN

The development of high-efficiency enzyme mimics is of great significance in the field of biocatalysis. However, it remains challenging to design novel enzyme mimics with multiple enzyme-like activities, excellent stability, and good reusability. Herein, a facile molecular assembly strategy to construct dialdehyde cellulose (DAC) templated Cu-doped polydopamine (DAC@PDA/Cu) membrane with dual enzyme-like activities is presented. The Schiff base bonds formed between polydopamine (PDA) and DAC can not only accelerate the adhesion of PDA thin layer but also contribute to Cu-loading and high stability of DAC@PDA/Cu membrane. Importantly, the assembled DAC@PDA/Cu membrane exhibits a remarkable catalytic activity that is superior to the natural laccase along with high stability and excellent reusability. Moreover, the DAC@PDA/Cu membrane also demonstrates peroxidase-like activity, and it is successfully applied in the sensitive detection of ascorbic acid (AA). This work will provide a new paradigm methodology for rational design and practical applications of enzyme mimics based on bioinspired molecular assemblies.


Asunto(s)
Indoles , Polímeros , Celulosa/química , Indoles/química , Polímeros/química
2.
Nanotechnology ; 33(3)2021 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-34649224

RESUMEN

In this work, a novel composite carrier system for loading essential oils was developed by using tetraethyl orthosilicate (TEOS) and (3-aminopropyl) triethoxysilane (APTES) as silica precursors and cetyl trimethyl ammonium bromide (CTAB) as a template, and the resultant aminated mesoporous silica was further chemically modified by polyacrylic acid (PAA). The obtained composite carriers exhibited a high loading capability toward tea tree oil (TTO), and they also significantly improved the release behavior of TTO due to the steric hindrance of silica mesopore and the polymer restriction. Besides, it was found that the release behavior followed the First-Order kinetic model, revealing that the release of TTO was driven by the concentration gradient. In addition, these composite carriers with essential oil-loaded demonstrated remarkable antibacterial performance againstE. coliandS. aureus, and they could retain antibacterial performance even after 50 d. Moreover, the antibacterial mechanism was also elucidated with the assistance of nucleic acid and conductivity measurements. Therefore, this work provides a facile and environmentally friendly approach to preparing effective composite carriers for improving the sustained release of essential oils, and the long-term antibacterial performance of these essential oil-loaded composite carriers makes them tremendously potential for practical applications.


Asunto(s)
Antibacterianos/química , Portadores de Fármacos/química , Nanocompuestos/química , Aceites Volátiles/química , Dióxido de Silicio/química , Resinas Acrílicas/química , Antibacterianos/farmacología , Cetrimonio/química , Preparaciones de Acción Retardada , Liberación de Fármacos , Escherichia coli/efectos de los fármacos , Aceites Volátiles/farmacología , Porosidad , Propilaminas/química , Silanos/química , Staphylococcus aureus/efectos de los fármacos
3.
Macromol Rapid Commun ; 42(6): e2000610, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33345361

RESUMEN

Providing access to highly diverse polymer structures by multicomponent reactions is highly desirable; efficient Meldrum's acid-based multicomponent reactions, however, have been rarely highlighted in polymer chemistry. Here, the three-component reaction of Meldrum's acid, indole, and aldehyde is introduced into polymer synthesis. Direct multicomponent polymerization of Meldrum's acid, dialdehyde, and diindole can perform under mild conditions, resulting in complex Meldrum's acid-containing polymers with well-defined structures, and high molecular weights. Additionally, nearly quantitative postpolymerization modification can also perform via this Meldrum's acid-based multicomponent reaction. These results indicate that Meldrum's acid-based multicomponent reaction will be a potential tool to prepare novel polymers.


Asunto(s)
Dioxanos , Polímeros , Aldehídos , Polimerizacion
4.
J Mater Sci Mater Med ; 32(3): 24, 2021 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-33675428

RESUMEN

The in vivo fast degradation and poor biocompatibility are two major challenges of the magnesium alloys in the field of artificial bone materials. In this study, graphene oxide (GO) was first functionalized by chitosan (GOCS) and then immobilized on the magnesium alloy surface, finally the complex of heparin and bone morphogenetic protein 2 was incorporated on the modified surface to synergistically improve the corrosion resistance, anticoagulation, and osteogenesis. Apart from an excellent hydrophilicity after the surface modification, a sustained heparin and BMP2 release over 14 days was achieved. The corrosion resistance of the modified magnesium alloy was significantly better than that of the control according to the results of electrochemical tests. Moreover, the corrosion rate was also significantly reduced in contrast to the control. The modified magnesium alloy not only had excellent anticoagulation, but also can significantly promote osteoblast adhesion and proliferation, upregulate the expression of alkaline phosphatase and osteocalcin, and enhance mineralization. Therefore, the method of the present study can be used to simultaneously improve the corrosion resistance and biocompatibility of the magnesium alloys targeted for the orthopedic applications.


Asunto(s)
Aleaciones/química , Proteína Morfogenética Ósea 2/química , Heparina/química , Magnesio/química , Osteogénesis/efectos de los fármacos , Anticoagulantes , Materiales Biocompatibles , Plaquetas , Adhesión Celular , Corrosión , Espectroscopía Dieléctrica , Electroquímica , Humanos , Concentración de Iones de Hidrógeno , Ensayo de Materiales
5.
J Am Chem Soc ; 142(41): 17318-17322, 2020 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-32981318

RESUMEN

Thermoelectric conversion of low temperature, delocalized, and abundant thermal sources is crucial for the development of the Internet of Things (IoT) and/or a carbon-free society. Thermocells are of great interest in thermoelectric conversion of low-temperature heat due to the low cost and flexibility of components. However, significant improvement of the conversion efficiency is required for the practical use of the cells. Here, we report thermo-electrochemical cells driven by volume phase transition (VPT) of hydrogel nanoparticles (NPs). Entropically driven VPT of poly(N-isopropylacrylamide) NPs containing carboxylic acids and amines generates a pH gradient of up to 0.049 and -0.053 pH K-1, respectively, around physiological temperature. The pH gradient triggers the proton-coupled electron transfer (PCET) reactions of quinhydrone on the electrodes, resulting in the highly efficient thermoelectric conversion with a Seebeck coefficient (Se) of -6.7 and +6.1 mV K-1. Thermocells driven by phase transition of hydrogels provide a nontoxic, flexible, and inexpensive charger that harvests carbon-free energy from abundant energy sources such as solar, body and waste heat.


Asunto(s)
Resinas Acrílicas/química , Hidrogeles/química , Nanopartículas/química , Aminas/química , Benzoquinonas/química , Ácidos Carboxílicos/química , Suministros de Energía Eléctrica , Técnicas Electroquímicas , Transporte de Electrón , Concentración de Iones de Hidrógeno , Oxidación-Reducción , Transición de Fase , Temperatura de Transición
6.
Small ; 14(37): e1802403, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30129176

RESUMEN

Chemotherapy is well recognized to induce immune responses during some chemotherapeutic drugs-mediated tumor eradication. Here, a strategy involving blocking programmed cell death protein 1 (PD-1) to enhance the chemotherapeutic effect of a doxorubicin nanoprodrug HA-Psi-DOX is proposed and the synergetic mechanism between them is further studied. The nanoprodrugs are fabricated by conjugating doxorubicin (DOX) to an anionic polymer hyaluronic acid (HA) via a tumor overexpressed matrix metalloproteinase sensitive peptide (CPLGLAGG) for tumor targeting and enzyme-activated drug release. Once accumulated at the tumor site, the nanoprodrug can be activated to release antitumor drug by tumor overexpressed MMP-2. It is found that HA-Psi-DOX nanoparticles can kill tumor cells effectively and initiate an antitumor immune response, leading to the upregulation of interferon-γ. This cytokine promotes the expression of programmed cell death protein-ligand 1 (PD-L1) on tumor cells, which will cause immunosuppression after interacting with PD-1 on the surface of lymphocytes. The results suggest that the therapeutic efficiency of HA-Psi-DOX nanoparticles is significantly improved when combined with checkpoint inhibitors anti-PD-1 antibody (α-PD1) due to the neutralization of immunosuppression by blocking the interaction between PD-L1 and PD-1. This therapeutic system by combining chemotherapy and immunotherapy further increases the link between conventional tumor therapies and immunotherapy.


Asunto(s)
Antineoplásicos/farmacología , Doxorrubicina/farmacología , Inmunoterapia , Nanopartículas/química , Polímeros/química , Profármacos/farmacología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Animales , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Doxorrubicina/farmacocinética , Femenino , Ácido Hialurónico/síntesis química , Ácido Hialurónico/química , Interferón gamma/metabolismo , Melanoma Experimental/patología , Ratones Endogámicos C57BL , Nanopartículas/ultraestructura , Metástasis de la Neoplasia , Profármacos/farmacocinética , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T Citotóxicos/efectos de los fármacos
7.
Small ; 13(37)2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28783253

RESUMEN

Tumor hypoxia severely limits the efficacy of traditional photodynamic therapy (PDT). Here, a liposome-based nanoparticle (designated as LipoMB/CaO2 ) with O2 self-sufficient property for dual-stage light-driven PDT is demonstrated to address this problem. Through a short time irradiation, 1 O2 activated by the photosensitizer methylene blue (MB) can induce lipid peroxidation to break the liposome, and enlarge the contact area of CaO2 with H2 O, resulting in accelerated O2 production. Accelerated O2 level further regulates hypoxic tumor microenvironment and in turn improves 1 O2 generation by MB under another long time irradiation. In vitro and in vivo experiments also demonstrate the superior competence of LipoMB/CaO2 to alleviate tumor hypoxia, suppress tumor growth and antitumor metastasis with low side-effect. The O2 self-sufficient LipoMB/CaO2 nanoplatform with dual-stage light manipulation is a successful attempt for PDT against hypoxic tumor.


Asunto(s)
Luz , Nanopartículas/química , Oxígeno/química , Fotoquimioterapia , Hipoxia Tumoral , Animales , Apoptosis , Peso Corporal , Compuestos de Calcio/química , Línea Celular Tumoral , Liposomas , Azul de Metileno , Ratones , Nanopartículas/ultraestructura , Necrosis , Óxidos/química , Carga Tumoral , Difracción de Rayos X
8.
Arch Virol ; 161(7): 1945-7, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27020571

RESUMEN

To investigate the epidemiological data on coxsackievirus B3 (CVB3) infection and its incidence in infants and children, a prospective cohort study was carried out from 2012 to 2014 in Jiangsu Province, China. According to the results of seropositive rates and NTAb titers of CVB3, an epidemic of CVB3 infection was found, and a dynamic change in CVB3 neutralizing antibody was also observed. One case was recorded with CVB3-associated hand, foot and mouth disease (HFMD), and the isolates belonged to the CVB3 D2 subtype. Our data help us to better understand the epidemic characteristics of CVB3 infection in infants and children.


Asunto(s)
Infecciones por Coxsackievirus/virología , Enterovirus Humano B/aislamiento & purificación , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Preescolar , China/epidemiología , Infecciones por Coxsackievirus/sangre , Infecciones por Coxsackievirus/epidemiología , Enterovirus Humano B/clasificación , Enterovirus Humano B/genética , Femenino , Humanos , Lactante , Masculino , Estudios Prospectivos
9.
RNA Biol ; 13(3): 343-52, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26717154

RESUMEN

Eucheuma denticulatum, an economically and industrially important red alga, is a valuable marine resource. Although microRNAs (miRNAs) play an essential role in gene post-transcriptional regulation, no research has been conducted to identify and characterize miRNAs in E. denticulatum. In this study, we identified 134 miRNAs (133 conserved miRNAs and one novel miRNA) from 2,997,135 small-RNA reads by high-throughput sequencing combined with bioinformatics analysis. BLAST searching against miRBase uncovered 126 potential miRNA families. A conservation and diversity analysis of predicted miRNA families in different plant species was performed by comparative alignment and homology searching. A total of 4 and 13 randomly selected miRNAs were respectively validated by northern blotting and stem-loop reverse transcription PCR, thereby demonstrating the reliability of the miRNA sequencing data. Altogether, 871 potential target genes were predicted using psRobot and TargetFinder. Target genes classification and enrichment were conducted based on Gene Ontology analysis. The functions of target gene products and associated metabolic pathways were predicted by Kyoto Encyclopedia of Genes and Genomes pathway analysis. A Cytoscape network was constructed to explore the interrelationships of miRNAs, miRNA-target genes and target genes. A large number of miRNAs with diverse target genes will play important roles for further understanding some essential biological processes in E. denticulatum. The uncovered information can serve as an important reference for the protection and utilization of this unique red alga in the future.


Asunto(s)
Biología Computacional/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , MicroARNs/genética , Rhodophyta/genética , Análisis de Secuencia de ARN/métodos , Regulación de la Expresión Génica de las Plantas , Ontología de Genes , Redes Reguladoras de Genes , ARN de Planta/genética , Alineación de Secuencia , Homología de Secuencia de Ácido Nucleico
10.
J Med Virol ; 87(12): 2009-17, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26010334

RESUMEN

Epidemiological data from active surveillance on human enterovirus, which could cause hand, foot, and mouth disease, were limited. An active surveillance system was used to investigate the enterovirus spectrum and the incidence of different enteroviruses in infants aged 6-35 months in Jiangsu Province from 2012 to 2013. Fifty-nine infants were randomly selected from 522 non-EV-A71/CV-A16 HFMD patients. We collected 173 throat swabs and 174 rectal swabs from these infants. RT-PCR was used to amplify 5'-UTR and VP1 regions of enteroviruses and the serotypes were determined by the sequence comparison using BLAST. Twenty-one non-EV-A71/CA16 enterovirus serotypes were detected in those infants. E16, E18 were firstly reported in HFMD patients. The four top common non-EV-A71/CV-A enteroviruses among infants were CV-B3, CV-A10, CV-A6, and E9 with the HFMD incidence rates at 1.4%, 0.84%, 0.56%, and 0.47%, respectively. Over 20.8% patients were co-infected with multiple enteroviruses. Neither the course of sickness nor clinical symptoms of the co-infected patients was more severe than those infected with single enterovirus. Two patients were infected different enterovirus successively within 2 months. Several new enterovirus serotypes and multiple models of infection associated with HFMD were discovered through the active surveillance system. These data provide a better understanding of the viral etiology of HFMD.


Asunto(s)
Enterovirus/clasificación , Enterovirus/aislamiento & purificación , Monitoreo Epidemiológico , Enfermedad de Boca, Mano y Pie/epidemiología , Enfermedad de Boca, Mano y Pie/virología , Preescolar , China/epidemiología , Coinfección/epidemiología , Coinfección/virología , Enterovirus/genética , Heces/virología , Femenino , Genotipo , Enfermedad de Boca, Mano y Pie/prevención & control , Humanos , Incidencia , Lactante , Epidemiología Molecular , Faringe/virología , ARN Viral/genética , Análisis de Secuencia de ADN , Serogrupo , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Vacunas Virales/administración & dosificación , Vacunas Virales/inmunología
11.
Sensors (Basel) ; 15(9): 22473-89, 2015 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-26404303

RESUMEN

In this paper, vertically aligned Pt nanowire arrays (PtNWA) with different lengths and surface roughnesses were fabricated and their electrochemical performance toward hydrogen peroxide (H2O2) detection was studied. The nanowire arrays were synthesized by electroplating Pt in nanopores of anodic aluminum oxide (AAO) template. Different parameters, such as current density and deposition time, were precisely controlled to synthesize nanowires with different surface roughnesses and various lengths from 3 µm to 12 µm. The PtNWA electrodes showed better performance than the conventional electrodes modified by Pt nanowires randomly dispersed on the electrode surface. The results indicate that both the length and surface roughness can affect the sensing performance of vertically aligned Pt nanowire array electrodes. Generally, longer nanowires with rougher surfaces showed better electrochemical sensing performance. The 12 µm rough surface PtNWA presented the largest sensitivity (654 µA·mM⁻¹·cm⁻²) among all the nanowires studied, and showed a limit of detection of 2.4 µM. The 12 µm rough surface PtNWA electrode also showed good anti-interference property from chemicals that are typically present in the biological samples such as ascorbic, uric acid, citric acid, and glucose. The sensing performance in real samples (river water) was tested and good recovery was observed. These Nafion-free, vertically aligned Pt nanowires with surface roughness control show great promise as versatile electrochemical sensors and biosensors.


Asunto(s)
Técnicas Electroquímicas/instrumentación , Polímeros de Fluorocarbono/química , Nanocables/química , Carbono/química , Electrodos , Vidrio/química , Peróxido de Hidrógeno/análisis , Nanocables/ultraestructura , Platino (Metal) , Espectrometría por Rayos X , Propiedades de Superficie , Agua/química
12.
Lancet ; 381(9882): 2024-32, 2013 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-23726161

RESUMEN

BACKGROUND: A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. METHODS: We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247. FINDINGS: 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33). INTERPRETATION: EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity. FUNDING: China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological.


Asunto(s)
Enterovirus Humano A/inmunología , Infecciones por Enterovirus/prevención & control , Vacunas Virales/inmunología , Adyuvantes Inmunológicos/efectos adversos , Compuestos de Alumbre , Anticuerpos Antivirales/sangre , Preescolar , Método Doble Ciego , Infecciones por Enterovirus/inmunología , Femenino , Humanos , Inmunidad Activa/fisiología , Lactante , Estimación de Kaplan-Meier , Masculino , Vacunas de Productos Inactivados/efectos adversos , Vacunas de Productos Inactivados/inmunología , Vacunas Virales/efectos adversos
13.
J Colloid Interface Sci ; 676: 626-635, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39053410

RESUMEN

Chemodynamic therapy (CDT) via Fenton-like reaction is greatly attractive owing to its capability to generate highly cytotoxic •OH radicals from tumoral hydrogen peroxide (H2O2). However, the antitumor efficacy of CDT is often challenged by the relatively low radical generation efficiency and the high levels of antioxidative glutathione (GSH) in tumor microenvironment. Herein, an innovative photothermal Fenton-like catalyst, Fe-chelated polydopamine (PDA@Fe) nanoparticle, with excellent GSH-depleting capability is constructed via one-step molecular assembly strategy for dual-modal imaging-guided synergetic photothermal-enhanced chemodynamic therapy. Fe(III) ions in PDA@Fe nanoparticles can consume the GSH overexpressed in tumor microenvironment to avoid the potential •OH consumption, while the as-produced Fe(II) ions subsequently convert tumoral H2O2 into cytotoxic •OH radicals through the Fenton reaction. Notably, PDA@Fe nanoparticles demonstrate excellent near-infrared light absorption that results in superior photothermal conversion ability, which further boosts above-mentioned cascade catalysis to yield more •OH radicals for enhanced CDT. Taken together with T1-weighted magnetic resonance imaging (MRI) contrast enhancement (r1 = 8.13 mM-1 s-1) and strong photoacoustic (PA) imaging signal of PDA@Fe nanoparticles, this design finally realizes the synergistic photothermal-chemodynamic therapy. Overall, this work offers a new promising paradigm to effectively accommodate both imaging and therapy functions in one well-defined framework for personalized precision disease treatment.


Asunto(s)
Indoles , Rayos Infrarrojos , Hierro , Polímeros , Indoles/química , Indoles/farmacología , Polímeros/química , Polímeros/farmacología , Catálisis , Humanos , Hierro/química , Animales , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Terapia Fototérmica , Supervivencia Celular/efectos de los fármacos , Nanopartículas/química , Tamaño de la Partícula , Ensayos de Selección de Medicamentos Antitumorales , Propiedades de Superficie , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Fototerapia , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos
14.
J Hazard Mater ; 478: 135534, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39151359

RESUMEN

Cigarette butts have become one of the most common and persistent forms of debris in marine coastal areas, where they pose significant toxicity risks. This study investigated cigarette butt pollution along beaches of the Yellow Sea and used laboratory experiments to assess the toxicity of their leachate and fibers on the euryhaline rotifer Brachionus plicatilis. A pollution index confirmed pollution by this debris across all eight beaches surveyed, where the density of cigarette butts averaged 0.23 butts/m2. In controlled laboratory experiments, both the fibers and leachates from cigarette butts exhibited negative impacts on the development, reproduction, and population growth of rotifers. Unique abnormalities observed under different exposure treatments indicated toxicity specific to certain chemicals and particles. Continuous exposure to cigarette butts initially reduced rotifer fecundity, but this effect diminished over successive generations. However, the exposure induced transgenerational reproductive toxicity in the rotifers. Adaptive responses in rotifers after repeated exposure led to relative reduction in reproductive inhibition in the F3 and F4 generations. Furthermore, rotifers were capable of ingesting and accumulating cigarette butts, and maternal transfer emerged as an alternative pathway for uptake of this material in the offspring. These results increase our understanding of the ecological risks posed by cigarette butts in aquatic environments.


Asunto(s)
Microplásticos , Reproducción , Rotíferos , Contaminantes Químicos del Agua , Animales , Rotíferos/efectos de los fármacos , Reproducción/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Microplásticos/toxicidad , Productos de Tabaco/toxicidad , Monitoreo del Ambiente
15.
Acta Biomater ; 181: 176-187, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38719158

RESUMEN

Bacterial infections are among the most critical global health challenges that seriously threaten the security of human. To address this issue, a biocompatible engineered living hydrogel patch was developed by co-embedding engineered photothermal bacteria (EM), photosensitizer (porphyrin) and reactive oxygen species amplifier (laccase) in a protein hydrogel. Remarkably, the genetice engineered bacteria can express melanin granules in vivo and this allows them to exhibit photothermal response upon being exposed to NIR-II laser (1064 nm) irradiation. Besides, electrostatically adhered tetramethylpyridinium porphyrin (TMPyP) on the bacterial surface and encapsulated laccase (Lac) in protein gel can generate highly toxic singlet oxygen (1O2) and hydroxyl radical (·OH) in the presence of visible light and lignin, respectively. Interestingly, the engineered bacteria hydrogel patch (EMTL@Gel) was successfully applied in synergistic photothermal, photodynamic and chemodynamic therapy, in which it was able to efficiently treat bacterial infection in mouse wounds and enhance wound healing. This work demonstrates the concept of "fighting bacteria with bacteria" combining bacterial engineering and material engineering into an engineered living hydrogel path that can synergistically boost the therapeutic outcome. STATEMENT OF SIGNIFICANCE: Genetically engineered bacteria produce melanin granules in vivo, exhibiting remarkable photothermal properties. These bacteria, along with a photosensitizer (TMPyP) and a reactive oxygen species amplifier (laccase), are incorporated into a biocompatible protein hydrogel patch. Under visible light, the patch generates toxic singlet oxygen (1O2) and hydroxyl radical (·OH), demonstrates outstanding synergistic effects in photothermal, photodynamic, and chemodynamic therapy, effectively treating bacterial infections and promoting wound healing in mice.


Asunto(s)
Hidrogeles , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Hidrogeles/química , Hidrogeles/farmacología , Ratones , Infecciones Bacterianas/tratamiento farmacológico , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Lacasa/química , Porfirinas/química , Porfirinas/farmacología , Escherichia coli/efectos de los fármacos
16.
Arthritis Rheumatol ; 76(1): 18-31, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37527031

RESUMEN

OBJECTIVE: We previously reported an increased expression of microRNA-155 (miR-155) in the blood monocytes of patients with rheumatoid arthritis (RA) that could be responsible for impaired monocyte polarization to anti-inflammatory M2-like macrophages. In this study, we employed two preclinical models of RA, collagen-induced arthritis and K/BxN serum transfer arthritis, to examine the therapeutic potential of antagomiR-155-5p entrapped within PEGylated (polyethylene glycol [PEG]) liposomes in resolution of arthritis and repolarization of monocytes towards the anti-inflammatory M2 phenotype. METHODS: AntagomiR-155-5p or antagomiR-control were encapsulated in PEG liposomes of 100 nm in size and -10 mV in zeta potential with high antagomiR loading efficiency (above 80%). Mice were injected intravenously with 1.5 nmol/100 µL PEG liposomes containing antagomiR-155-5p or control after the induction of arthritis. RESULTS: We demonstrated the biodistribution of fluorescently tagged PEG liposomes to inflamed joints one hour after the injection of fluorescently tagged PEG liposomes, as well as the liver's subsequent accumulation after 48 hours, indicative of hepatic clearance, in mice with arthritis. The injection of PEG liposomes containing antagomiR-155-5p decreased arthritis score and paw swelling compared with PEG liposomes containing antagomiR-control or the systemic delivery of free antagomiR-155-5p. Moreover, treatment with PEG liposomes containing antagomiR-155-5p led to the restoration of bone marrow monocyte defects in anti-inflammatory macrophage differentiation without any significant functional change in other immune cells, including splenic B and T cells. CONCLUSION: The injection of antagomiR-155-5p encapsulated in PEG liposomes allows the delivery of small RNA to monocytes and macrophages and reduces joint inflammation in murine models of RA, providing a promising strategy in human disease.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , MicroARNs , Humanos , Ratones , Animales , Antagomirs/metabolismo , Antagomirs/uso terapéutico , Liposomas/metabolismo , Liposomas/uso terapéutico , Distribución Tisular , Macrófagos , Antiinflamatorios/uso terapéutico , MicroARNs/metabolismo
17.
Hum Vaccin Immunother ; 19(1): 2164140, 2023 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-36600518

RESUMEN

Coxsackievirus A6 (CA6) is one of the major causative agents of herpangina and hand-foot-mouth disease (HFMD). Since 2008, CA6 has circulated widely around the world. Especially in Asia-Pacific region CA6 had even replaced enterovirus A71 (EV71) and coxsackievirus A16 (CA16) as the main prevalent strain of HFMD. In the recent 10 years, monovalent and multivalent vaccines against CA6 have been researched and developed by manufacturers from China, Korea, and the USA. The neutralizing antibody titer is a key indicator for accurately evaluating immunogenicity of vaccine. However, so far, the World Health Organization international standard for CA6 neutralizing antibody has not been available. In order to meet the needs of evaluating the immunogenicity of vaccines against CA6, the first Chinese national standard for CA6 neutralizing antibody was established, which was conducted to ensure that methods used to measure the neutralizing antibody titers against CA6 are accurate, reliable, and comparable. Three lyophilized candidate standards (29#, 39# and 44#) were produced with 0.40 ml/vial from plasma samples donated by healthy individuals. The collaborative study showed that the 29# candidate standard could effectively minimize the variability in neutralization titers between labs and across challenging viruses of different genotypes (A, D1, and D3). Therefore, the 29# candidate sample was established as the first Chinese national standard for CA6 neutralizing antibody test. This standard has good long-term stability and was assigned a potency of 150 units per milliliter (U/ml) of CA6 neutralizing antibody. It will contribute to ensure uniformity of potency or activity of vaccines and potentially therapeutic antibody preparations.


Asunto(s)
Enterovirus Humano A , Enterovirus , Enfermedad de Boca, Mano y Pie , Humanos , Enterovirus/genética , Anticuerpos Antivirales , Anticuerpos Neutralizantes , Vacunas Combinadas
18.
Emerg Microbes Infect ; 12(1): 2149352, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36395069

RESUMEN

Coxsackievirus A16 (CA16), a main causative agent of hand, foot, and mouth disease (HFMD), has become a serious public health concern in the Asia-Pacific region. Here, we generated an anti-CA16 monoclonal antibody, DMA2017, derived from an epidemic strain CA16. Surprisingly, although DMA2017 could not neutralize the original and circulating CA16 strains in vitro, the passive transfer of DMA2017 (10 µg/g) could protect suckling mice from a lethal challenge with CA16 in vivo. Then, we confirmed the protective effect of DMA2017 relies on the Fc-dependent effector functions, such as antibody-dependent cellular cytotoxicity (ADCC). The linear epitope of DMA2017 was mapped by phage display technique to a conserved patch spanning residues 143-148 (NSHPPY) of the VP2 EF-loop of CA16. DMA2017 could inhibit the binding of the antibodies present in the sera of naturally infected children to CA16, indicating that the epitope of DMA2017 is immunodominant for CA16. Our results confirm, for the first time, that a potential preventive and therapeutic effect could be mediated by a non-neutralizing antibody elicited against CA16. These findings bring a hitherto understudied protective role of non-neutralizing antibodies during viral infections into the spotlight and provide a new perspective on the design and evaluation of CA16 vaccines.


Asunto(s)
Enterovirus Humano A , Enterovirus , Enfermedad de Boca, Mano y Pie , Vacunas Virales , Animales , Ratones , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Enfermedad de Boca, Mano y Pie/prevención & control , Epítopos , Anticuerpos Monoclonales
19.
Adv Healthc Mater ; 12(21): e2203252, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37154112

RESUMEN

Gene therapy holds great promise as an effective treatment for many diseases of genetic origin. Gene therapy works by employing cationic polymers, liposomes, and nanoparticles to condense DNA into polyplexes via electronic interactions. Then, a therapeutic gene is introduced into target cells, thereby restoring or changing cellular function. However, gene transfection efficiency remains low in vivo due to high protein binding, poor targeting ability, and substantial endosomal entrapment. Artificial sheaths containing PEG, anions, or zwitterions can be introduced onto the surface of gene carriers to prevent interaction with proteins; however, they reduce the cellular uptake efficacy, endosomal escape, targeting ability, thereby, lowering gene transfection. Here, it is reported that linking dipicolylamine-zinc (DPA-Zn) ions onto polyplex nanoparticles can produce a strong hydration water layer around the polyplex, mimicking the function of PEGylation to reduce protein binding while targeting cancer cells, augmenting cellular uptake and endosomal escape. The polyplexes with a strong hydration water layer on the surface can achieve a high gene transfection even in a 50% serum environment. This strategy provides a new solution for preventing protein adsorption while improving cellular uptake and endosomal escape.


Asunto(s)
Neoplasias , Zinc , Unión Proteica , Polímeros/metabolismo , ADN/metabolismo , Cationes , Transfección , Técnicas de Transferencia de Gen , Polietilenglicoles/metabolismo , Neoplasias/terapia
20.
Zootaxa ; 5200(4): 321-343, 2022 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37045033

RESUMEN

A brief preliminary revision of the genus Scelimena Serville, 1838 (Tetrigidae: Scelimeninae: Scelimenini) from PR China is presented. Scelimena pyrroma Lao, Kasalo, Gao, Deng et Skejo sp. nov. is described from Hainan, Ding'an, based on a female holotype and a male paratype, and an additional photograph of a female in the natural habitat from Wuzhi National Nature Reserve (Wuzhi-shan Mountain). Specimens of this new species were hitherto reported from Hainan as S. dentiumeris (Hancock, 1907), a species endemic to Borneo. The new species is easily distinguished from its congeners by the presence of prominent yellow humeral tubercles and by the lateral pronotal spines directed forwards. The new species from Hainan and S. chinensis (Hancock, 1915) from Vietnam are assigned to Scelimena producta species group based on the similarity with S. producta (Serville, 1838), which is characterized by the humeral angles with tubercles, wide vertex, and toothed ventral margins of hind femora, while S. boettcheri Günther, 1938 from Palawan is assigned to Scelimena discalis species group, based on the tuberculated median carina. Scelimena dammermanni Günther, 1938, stat. nov., hitherto regarded as a subspecies of S. producta, is elevated to a species level because it lacks ventral spines on the hind legs, present in all S. producta individuals. New synonymy is established: Scelimena melli Günther, 1938, =Scelimena brevispina Cao et Zheng, 2011, syn. nov.; =Scelimena wulingshana Zheng, 1993, syn. nov.; =Eufalconoides guizhouensis Zheng et Shi, 2006, syn. nov. Scelimena melli, S. guangxiensis Zheng et Jiang, 1994 from southern China and S. kempi (Hancock, 1915) from NE India are assigned to S. bellula species group on the basis of similarity to S. bellula Storozhenko et Dawwrueng, 2015. Further research should determine whether S. spicupennis Zheng & Ou, 2003 represents a valid species or a synonym of another Scelimena species, as well as if S. nitidogranulosa Günther, 1938 and S. guangxiensis Zheng & Jiang, 1994 represent separate species or whether they are conspecific. Specimens of S. nitidogranulosa from Hainan reported by Liang & Zheng in 1998 are in fact Platygavialidium sinicum Günther, 1939. Scelimena songkrana Zha et Wen, 2017 is recorded from China for the first time. A key to Scelimena species found in PR China is also provided.


Asunto(s)
Ortópteros , Femenino , Masculino , Animales , Ecosistema
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