RESUMEN
Membrane fouling is the major obstacle for membrane bioreactors operated at a long sludge retention time to reduce sludge production. In this study, a sludge process reduction (SPR) module, consisting of a microaerobic tank and a settler, was inserted before an anoxic/oxic MBR (AO-MBR) to achieve dual objectives of fouling alleviation and sludge reduction. Three SPR-MBRs were operated to investigate influences of sludge recirculation ratios from the SPR settler to the microaerobic tank on process performance. Compared to AO-MBR, the SPR-MBRs reduced sludge production by 43.1-56.4% by maintaining sludge retention times above 175 d, and decreased foulant layer resistance and pore clogging resistance. Inserting SPR reduced the accumulation of dissolved organic matters and extracellular polymeric substances, enlarged sludge flocs, and decreased sludge viscoelasticity. However, increasing RSPR stimulated outward diffusion of extracellular polymeric substances and increased sludge viscosity. SPR-MBRs achieved effective sludge reduction by enriching hydrolytic (Trichococcus and Aeromonas) and fermentative genera (Lactococcus, Paludibacter, Macellibacteroides, and Acinetobacter) in the SPR, and alleviated membrane fouling by prohibiting the growth of extracellular polymeric substance-secreting bacteria and enriching filamentous bacteria to enlarge particle size. The results revealed that the SPR-MBR maximized sludge reduction with a very long sludge retention time, and alleviated membrane fouling synchronously.
Asunto(s)
Matriz Extracelular de Sustancias Poliméricas , Aguas del Alcantarillado , Reactores Biológicos/microbiología , Fermentación , Bacterias , Membranas ArtificialesRESUMEN
Bacterial biofilms can be programmed to produce living materials with self-healing and evolvable functionalities. However, the wider use of artificial biofilms has been hindered by limitations on processability and functional protein secretion capacity. We describe a highly flexible and tunable living functional materials platform based on the TasA amyloid machinery of the bacterium Bacillus subtilis. We demonstrate that genetically programmable TasA fusion proteins harboring diverse functional proteins or domains can be secreted and can assemble into diverse extracellular nano-architectures with tunable physicochemical properties. Our engineered biofilms have the viscoelastic behaviors of hydrogels and can be precisely fabricated into microstructures having a diversity of three-dimensional (3D) shapes using 3D printing and microencapsulation techniques. Notably, these long-lasting and environmentally responsive fabricated living materials remain alive, self-regenerative, and functional. This new tunable platform offers previously unattainable properties for a variety of living functional materials having potential applications in biomaterials, biotechnology, and biomedicine.
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Bacillus subtilis/fisiología , Materiales Biocompatibles/química , Biopelículas , Bacillus subtilis/genética , Proteínas Bacterianas/genética , Materiales Biocompatibles/metabolismo , Biodegradación Ambiental , Composición de Medicamentos , Elasticidad , Ingeniería Genética/métodos , Nanopartículas/química , Paraoxon/metabolismo , Impresión Tridimensional , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismoRESUMEN
In this work, we investigated the interactions between graphene oxide (GO) and conjugated polyelectrolytes (CPEs) with different backbone and side chain structures. By studying the mechanism of fluorescence quenching of CPEs by GO, we find that the charge and the molecular structure of CPEs play important roles for GO-CPEs interactions. Among them, electrostatic interaction, π-π interaction, and cation-π bonding are dominant driving forces. By using a cationic P2, we have developed a sensitive homogeneous sensor for DNA and RNA detection with a detection limit of 50 pM DNA and RNA, which increased the sensitivity by 40-fold as compared to GO-free CPE-based sensors. This GO-assisted CPE sensing strategy is also generic and shows a high potential for biosensor designs based on aptamers, proteins, peptides, and other biological probes.
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ADN/análisis , Fluorescencia , Grafito/química , Óxidos/química , Polímeros/química , ARN/análisis , Transducción de Señal , Electrólitos/químicaRESUMEN
Cymbidium mosaic virus (CymMV) and Odontoglossum ringspot virus (ORSV) are among the world's most serious and widespread orchid viruses; they often infect orchids, causing devastating losses to the orchid industry. Therefore, it is critical to establish a method that can rapidly and accurately detect viruses in the field using simple instruments, which will largely reduce the further spread of viruses and improve the quality of the orchid industry and is suitable for mass promotion and application at grassroots agrotechnical service points. In this investigation, we established a rapid amplification method for virus detection at 39 °C for 35 min to detect the presence of CymMV and ORSV simultaneously, sensitively, and specifically in orchids. Primers for the capsid protein (CP)-encoding genes of both viruses were designed and screened, and the reaction conditions were optimized. The experimental amplification process was completed in just 35 min at 39 °C. There were no instances of nonspecific amplification observed when nine other viruses were present. The RPA approach had detection limits of 104 and 103 copies for pMD19T-CymMV and pMD19T-ORSV, respectively. Moreover, the duplex RT-RPA investigation confirmed sensitivity and accuracy via a comparison of detection results from 20 field samples with those of a gene chip. This study presents a precise and reliable detection method for CymMV and ORSV using RT-RPA. The results demonstrate the potential of this method for rapid virus detection. It is evident that this method could have practical applications in virus detection processes.
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Orchidaceae , Enfermedades de las Plantas , Potexvirus , Enfermedades de las Plantas/virología , Orchidaceae/virología , Sensibilidad y Especificidad , Proteínas de la Cápside/genética , Potyvirus/genética , Potyvirus/aislamiento & purificación , Potyvirus/clasificación , ARN Viral/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Cartilla de ADN/genéticaRESUMEN
Photothermal therapy (PTT), which utilizes nanomaterials to harvest laser energy and convert it into heat to ablate tumor cells, has been rapidly developed for lung tumor treatment, but most of the PTT-related nanomaterials are not degradable, and the immune response associated with PTT is unclear, which leads to unsatisfactory results of the actual PTT. Herein, we rationally designed and prepared a manganese ion-doped polydopamine nanomaterial (MnPDA) for immune-activated PTT with high efficiency. Firstly, MnPDA exhibited 57.2% photothermal conversion efficiency to accomplish high-efficiency PTT, and secondly, MnPDA can be stimulated by glutathione (GSH) to the release of Mn2+, and it can produce ·OH in a Fenton-like reaction with the overexpressed H2O2 and stimulate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. These two synergistically can effectively remove lung tumor cells that have not been ablated by PTT, resulting in an 86.7% tumor suppression rate under laser irradiation of MnPDA in vivo, and further significantly activated the downstream immune response, as evidenced by an increased ratio of cytotoxic T cells to immunosuppressive Treg cells. Conclusively, the GSH degradable MnPDA nanoparticles can be used for photothermal therapy and cGAS-STING-activated immunotherapy of lung tumors, which provides a new idea and strategy for the future treatment of lung tumors.
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Indoles , Neoplasias Pulmonares , Nanopartículas , Neoplasias , Polímeros , Humanos , Manganeso , Peróxido de Hidrógeno , Terapia Fototérmica , Inmunoterapia , Neoplasias Pulmonares/terapia , GlutatiónRESUMEN
Sorghum is not only an important cereal crop but also a biofuel crop. The sorghum brown midrib mutant 6 (bmr6) has a reduced lignin content in the cell walls and vascular tissues, which could potentially be advantageous for cellulosic biofuel production. Meanwhile, both dry matter yield and plant height were decreased in the bmr6 mutant. To identify genes affected in the mutant, differential gene expression analysis was performed for bmr6 and the wild type. As a result, a total of 1,052 differentially expressed genes were detected between the two samples, of which 166 genes were downregulated and 886 genes were upregulated. Five hundred seventy-nine of the 1,052 differentially expressed genes could be assigned to 154 documented pathways. These pathways mainly included primary and secondary metabolism. Therefore, mutation of the bmr6 gene, which impaired the biosynthesis of lignin, ultimately affected the expression of these genes associated with the growth and development of sorghum. Except for the bmr6 gene, 11 key enzyme genes of monolignols biosynthesis were upregulated. Promoter analysis identified that these genes have common MYB sites. It revealed that a feedback mechanism existed in the pathway and a MYB1 transcription factor (Sb02g031190) could associate with the upregulation of these genes in sorghum. In this study, we investigated gene expressions at a global level in sorghum bmr6 mutant and provided valuable insights into the mechanisms of lignin biosynthesis.
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Mutación , Proteínas de Plantas/metabolismo , Sorghum/genética , Factores de Transcripción/metabolismo , Sitios de Unión , Regulación de la Expresión Génica de las Plantas , Lignina/biosíntesis , Lignina/genética , Redes y Vías Metabólicas , Proteínas de Plantas/química , Proteínas de Plantas/genética , Regiones Promotoras Genéticas , Sorghum/enzimología , Sorghum/metabolismo , Factores de Transcripción/química , Factores de Transcripción/genéticaRESUMEN
Orchids are significant ornamental plants whose viral infection results in substantial economic damage. Cymbidium mosaic virus (CymMV), Odontoglossum ringspot virus (ORSV), and Cymbidium ringspot virus (CymRSV) represent three important and prevalent orchid viruses. The detection system proposed in this study uses a triplex TaqMan quantitative real-time PCR assay to identify CymMV, ORSV, and CymRSV in a simultaneous manner. We designed specific primers and probes for CymMV, ORSV, and CymRSV, with amplified sequences of 156 bp, 148 bp, and 145 bp, respectively. The minimum detection limit of the triplex qRT-PCR assay for CymMV and CymRSV was 1 copy/assay, and the minimum detection limit was 10 copies/assay for ORSV. The minimum stable detection limits for CymMV, ORSV, and CymRSV were 10, 102, and 102 copies/assay, respectively. Therefore, this system exhibited higher sensitivity (approximately 10 to 104-fold) than RT-PCR. The intra-and interassay CVs of Cq values are less than 0.55 and 0.95%, respectively, indicating that the triplex assay is highly reliable and accurate. In addition, 66 samples from five different orchid genera were analyzed using the established assay and gene chip. The detection results demonstrated that the triplex probe qRT-PCR demonstrated higher sensitivity than the gene chip, indicating that the triplex real-time PCR assay could be used for the detection of field samples. Our findings suggest that the triplex real-time RT-PCR detection system represents a rapid, simple, and accurate tool for detecting CymMV, ORSV, and CymRSV on orchids.
RESUMEN
High-entropy multimetallic nanopatterns with controlled morphology, composition and uniformity hold great potential for developing nanoelectronics, nanophotonics and catalysis. Nevertheless, the lack of general methods for patterning multiple metals poses a limit. Here, we develop a DNA origami-based metallization reaction system to prescribe multimetallic nanopatterns with peroxidase-like activities. We find that strong coordination between metal elements and DNA bases enables the accumulation of metal ions on protruding clustered DNA (pcDNA) that are prescribed on DNA origami. As a result of the condensation of pcDNA, these sites can serve as nucleation site for metal plating. We have synthesized multimetallic nanopatterns composed of up to five metal elements (Co, Pd, Pt, Ag and Ni), and obtained insights on elemental uniformity control at the nanoscale. This method provides an alternative pathway to construct a library of multimetallic nanopatterns.
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Aleaciones , Nanopartículas del Metal , Entropía , Metales , ADNRESUMEN
The heavy metal (HM) ion-enzyme interaction is an important research topic in many areas. Using glucose oxidase (GOx) as an example, a comprehensive experimental platform based on quartz crystal microbalance and electroanalysis techniques is developed here to quantitatively study the HM ion-enzyme interactions and amperometric inhibitive assays of HM ions. The effects of some common HM ions on the bioactivities of solution-state GOx (GOx(s)), electrode surface-adsorbed GOx (GOx(ads)), and polymer-entrapped GOx (GOx(e)) are comparatively examined on the basis of anodic amperometric detection of enzymatically generated H(2)O(2). Ag(+) shows the strongest inhibition effect among the HM ions examined, and the inhibitive assays of Ag(+) based on GOx(s), GOx(ads), and GOx(e) entrapped in poly(l-noradrenalin) (PNA) give limits of detection (LOD) of 2.0, 8.0, and 5.0 nM (S/N = 3), respectively. Inhibition effects of Hg(2+), Cu(2+), and Co(2+) are detectable only at 15 µM or higher concentrations, and the other HM ions show undetectable inhibition even at 1.0 mM. The developed experimental platform allows one to quantify the number of the bound HM ions per GOx(ads) molecule at various inhibition percentages. In addition, the electrosynthesized PNA matrix to entrap GOx for an inhibitive assay of Ag(+) shows the lowest competitive affinity to HM ions and gives the highest sensitivity, as compared with several other polymer matrixes commonly used for the inhibitive assay. The suggested experimental platform is recommended for wide applications in enzymatic inhibitive assays and quantitative studies of the inhibition effects of HM ions on many other redox-event-relevant enzymes.
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Electroquímica/métodos , Enzimas Inmovilizadas/antagonistas & inhibidores , Enzimas Inmovilizadas/metabolismo , Glucosa Oxidasa/antagonistas & inhibidores , Glucosa Oxidasa/metabolismo , Plata/metabolismo , Plata/farmacología , Unión Competitiva , Electrodos , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacología , Enzimas Inmovilizadas/química , Glucosa Oxidasa/química , Peróxido de Hidrógeno/metabolismo , Polímeros/química , Unión Proteica , SolucionesRESUMEN
Materials that can regulate the composition and structure of the cell membrane to fabricate engineered cells with defined functions are in high demand. Compared with other biomolecules, DNA has unique advantages in cell membrane engineering due to its excellent programmability and biocompatibility. Especially, the near-atomic scale precision of DNA nanostructures facilitates the investigation of structure-property relations on the cell membrane. In this review, first the state of the art of functional DNA nanostructures is summarized, and then the overview of the use of DNA nanostructures to engineer the cell membrane is presented. Subsequently, applications of DNA nanostructures in modifying cell membrane morphology, controlling ions transport, and synthesizing high precise liposomes are highlighted. Finally, the challenges and outlook on using DNA nanostructures for cell membrane engineering are discussed.
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Nanoestructuras , Membrana Celular , ADN , Ingeniería , Liposomas , NanotecnologíaRESUMEN
Cell-mediated living fabrication has great promise for generating materials with versatile, programmable functions. Here, we demonstrate the engineering of living materials consisting of semi-interpenetrating polymer networks (sIPN). The fabrication process is driven by the engineered bacteria encapsulated in a polymeric microcapsule, which serves as the initial scaffold. The bacteria grow and undergo programmed lysis in a density-dependent manner, releasing protein monomers decorated with reactive tags. Those protein monomers polymerize with each other to form the second polymeric component that is interlaced with the initial crosslinked polymeric scaffold. The formation of sIPN serves the dual purposes of enhancing the mechanical property of the living materials and anchoring effector proteins for diverse applications. The material is resilient to perturbations because of the continual assembly of the protein mesh from the monomers released by the engineered bacteria. We demonstrate the adoption of the platform to protect gut microbiota in animals from antibiotic-mediated perturbations. Our work lays the foundation for programming functional living materials for diverse applications.
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Polímeros/química , Animales , Bacterias/citología , Microbioma Gastrointestinal , Ratones , beta-Lactamasas/químicaRESUMEN
OBJECTIVES: This study aimed to investigate the prevalence of insomnia and risk factors among different job categories of steel workers in China, in order to improve their quality of occupational life. MATERIAL AND METHODS: A cross-sectional face-to-face survey was conducted which involved 5834 steel workers from a large enterprise located in northern China, including front-line, maintenance and inspection, and other auxiliary workers. The Athens Insomnia Scale and the Job Content Questionnaire were used to assess the status of insomnia and job stress/social support, respectively. Multivariable logistic regression was used to identify factors influencing insomnia. RESULTS: The overall prevalence of insomnia was determined at 42.0% (95% confidence interval: 40.7%-43.2%). For front-line, maintenance and inspection, and other auxiliary workers, the prevalence was 42.3%, 39.8%, and 47.9% (p = 0.001), respectively. The participants with high stress and low support, and those who had experienced ≥2 major life events in the past 12 months, compared to those with low stress and high support, and those without major events, displayed an increased risk of insomnia among all 3 job categories (the adjusted odds ratio ranged 1.56-2.38 and 1.30-1.75, respectively). The educational level, shift work, alcohol consumption, and present illness were identified as influencing factors of insomnia for 1 or 2 job categories. CONCLUSIONS: The prevalence of insomnia was the highest in the group of other auxiliary steel workers among the 3 job categories of steel workers under consideration. While the influencing factors of insomnia differed among the groups, job stress and major life events were common risk factors of insomnia among the 3 categories of steel workers. Int J Occup Med Environ Health. 2020;33(2):215-33.
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Empleo/clasificación , Industria Manufacturera , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Acero , Adulto , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estrés Laboral , Prevalencia , Factores de Riesgo , Apoyo SocialRESUMEN
The application of additive manufacturing (AM) technology has been widely used in various medical fields, including craniomaxillofacial surgery. The aim of the present study was to examine the surgical efficiency and post-operative outcomes of patient-specific titanium mandibular reconstruction using AM. Major steps in directly designing and manufacturing 3D customized titanium implants are discussed. Furthermore, pre-operative preparations, surgical procedures and post-operative treatment outcomes were compared among patients who received mandibular reconstruction using a customized 3D titanium implant, titanium reconstruction plates or vascularized autologous fibular grafting. Use of a customized titanium implant significantly improved surgical efficiency and precision. When compared with mandibular reconstruction using the two conventional approaches, patients who received the customized implant were significantly more satisfied with their facial appearance, and exhibited minimal post-operative complications in the 12-month follow-up period. Patients who underwent mandibular reconstruction using a customized titanium implant displayed improved mandibular contour symmetry, restored occlusal function, normal range of mouth opening and no temporomandibular joint related pain; all complications frequently experienced by patients who undergo conventional approaches of mandibular reconstruction.
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Supramolecular hydrogels with stimuli-responsive behaviors under aqueous environments are attractive for their potential applications in controlled drug delivery, clinical diagnostics, and tissue engineering. However, there still remain challenges in developing multicomponent hydrogels as a new generation of "smart" soft materials with multiple intelligent functions toward complex biochemical stimuli. In this work, a three dimensional (3D)-nanostructured supramolecular hydrogel was fabricated using a simple and facile strategy via the self-assembly of graphene oxide (GO) nanosheets, poly(vinyl alcohol) (PVA) chains, and G-quartet/hemin (G4/H) motifs. The as-prepared GO/PVA/G4/H hydrogel exhibited a honeycomb-like 3D GO network architecture as well as excellent mechanical properties. Importantly, the hydrogel demonstrated pH-inducing reversible and cyclic phase transitions between solution and hydrogel states, which could be used as "ink" for injectable 3D printing of different shaped patterns. Also, binary AND and OR logic gates were successfully built by encapsulating enzymes into the hydrogels, which responded to a variety of biochemicals. In addition, the hydrogels showed excellent peroxidase-like activity, achieving the ultrasensitive detection of H2O2 at a concentration as low as 100 nM by their deposition on an electrochemical electrode. The design of multicomponent hydrogels opens up an avenue to fabricate novel "smart" soft matter for biological and medical applications.
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Materiales Biomiméticos/química , Grafito/química , Hidrogeles/química , Peróxido de Hidrógeno/química , Peroxidasa/química , Alcohol Polivinílico/químicaRESUMEN
BACKGROUND: Enterovirus 71 (EV71) is one of the major causative pathogens of hand, foot, and mouth disease (HFMD). Immune cells play a critical role in determining the outcomes of virus infection. We aimed to characterize the lymphocyte subsets and transcriptional levels of T lymphocytes-associated transcription factors in peripheral blood cells of children with EV71 infection. METHODS: Peripheral blood samples from 32 children with EV71 infection and 32 control subjects were included in this study. The frequencies of T-, B-lymphocytes, and their subsets were determined by flow cytometry. The expression of transcription factors, including T-bet, Gata3, ROR γ t, Foxp3, TCF-1, and BCL-6 in the whole blood cells were evaluated by real-time reverse-transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: The frequencies of T cells, helper T cells (Th), cytotoxic T cells (Tc), IFN-γ+ Th1, IFN-γ+ Tc1, and regulatory T (Treg) cells were significantly decreased (P < 0.01) in children with EV71 infection. As for IL-4+ Th2, IL-4+ Tc2, IL-17+ Th17, IL-17+ Tc17, follicular helper T cells (Tfh), CD3+CD8+IL-21+ T cells, CD19+ B cells, and CD19+IL-10+ B10 cells, their frequencies were significantly increased in the EV71 group (P < 0.01). The EV71 group had lower mRNA expressions of T-bet, Gata3, and Foxp3 than the control group (P < 0.05), whereas the expressions of ROR γ t, TCF-1, and BCL-6 showed no significant difference between two groups. CONCLUSIONS: EV71 infection in children caused a decreased frequency of total Th, Tc and Treg cells, and increased percentages of B cell, Th2 and Th17 cells in blood.
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Infecciones por Enterovirus/inmunología , Subgrupos Linfocitarios/inmunología , Factores de Transcripción/metabolismo , Niño , Preescolar , Citocinas/metabolismo , Enterovirus Humano A , Femenino , Citometría de Flujo , Factores de Transcripción Forkhead , Factor de Transcripción GATA3 , Humanos , Lactante , Linfocitos , Masculino , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Factor 1 de Transcripción de Linfocitos T , Proteínas de Dominio T Box , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Células TH1/inmunología , Células Th17/inmunologíaRESUMEN
Electroconductive fibers (E-fibers) with excellent flexibility and elasticity are crucial for the advancement of smart textiles for wearable electronics. However, the current metal-based conductive wires are not capable of satisfying the practical demands attributing to their limited stretchability and inferior antiabrasion ability. Herein, we report a superelastic and electroconductive fiber with a spring-like structure, inspired by the unique coiled tendril structures of climbing plants. The E-fiber is constructed by wrapping a flexible yet conductive carbon nanotube/polydimethylsiloxane (CNT/PDMS) composite yarn onto a polyester filament. In this system, the polyester filament provides mechanical robustness and stretchability, while the coiled CNT/PDMS composite yarn (C/P CY) offers sufficient conductivity. Notably, the as-fabricated E-fiber possesses high stretchability (165%), exceptional tensile force (660 cN), extraordinary antiabrasion ability, and remarkable electrical stability under various deformations. In addition, the great air permeability and electrothermal stability are also achieved, which are essential for comfortable wear and steady conduction. The developed E-fiber based on CNT composite wrapping yarn, together with its exceptional mechanical and electrical performance, provides the material with promising prospects for practical applications in wearable electronics.
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Plantas/química , Polímeros/química , Dispositivos Electrónicos Vestibles , Dimetilpolisiloxanos/química , Elasticidad , Conductividad Eléctrica , Diseño de Equipo , Nanotubos de Carbono/química , Desarrollo de la Planta , Polímeros/síntesis química , Resistencia a la Tracción , Textiles/análisisRESUMEN
Engineering biological interfaces represents a powerful means to improve the performance of biosensors. Here, we developed a DNA-engineered nanozyme interface for rapid and sensitive detection of dental bacteria. We employed DNA aptamer as both molecular recognition keys and adhesive substrates to functionalize the nanozyme. Utilizing different immobilization strategies and DNA designs, a range of DNA nanoscale biointerfaces were constructed to modulate enzymatic and biological properties of the nanozyme systems. These functional biointerfaces improved the accessibility of bacteria to the nanozyme surface, providing large signal change range at optimal DNA probe density. The DNA-functionalized nanozymes demonstrate a rapid, label-free, and highly sensitive direct colorimetric detection of Streptococcus mutans, with a detection limit of 12 CFU mL-1, as well as excellent discrimination from other dental bacteria. We demonstrate the use of this biological nanointerface for identifying dental bacteria in salivary samples, showing its potential in clinical prevention and diagnosis of dental diseases.
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Técnicas Biosensibles , ADN Catalítico/química , Gingivitis/diagnóstico , Gingivitis/microbiología , Nanoestructuras/química , Streptococcus mutans , Colorimetría , HumanosRESUMEN
Clinical need for treating allergic conjunctivitis (AC) is rapidly increasing. However, AC-relevant anti-inflammatory compounds are generally difficult to solubilize in water, thus limiting their therapeutic potential. Solubility-improved eye drop formulations of these compounds have poor bioavailability and a short retention time in ophthalmic tissues. Herein, we report a DNA/poly(lactic-co-glycolicacid) (PLGA) hybrid hydrogel (HDNA) for water-insoluble ophthalmic therapeutic delivery. PLGA pre-encapsulation enables loading of water-insoluble therapeutics. HDNA's porous structure is capable of sustained delivery of therapeutics. Dexamethasone (DEX), with demonstrated activities in attenuating inflammatory symptom in AC, was used as a model system. The designed HDNA hybrid hydrogels significantly improved the DEX accumulation and mediated the gradual DEX release in ophthalmic cells and tissues. Using the HDNA-DEX complexes, potent efficacy in two animal models of AC was acquired. Given this performance, demonstrable biocompatibility, and biodegradability of DNA hydrogel, the HDNA-based ophthalmic therapeutic delivery system enables novel treatment paradigms, which will have widespread applications in the treatment of various eye diseases.
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Conjuntivitis Alérgica/tratamiento farmacológico , ADN/química , Dexametasona/farmacología , Hidrogeles/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Disponibilidad Biológica , Conjuntivitis Alérgica/genética , ADN/farmacología , Dexametasona/química , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Epitelio Corneal/efectos de los fármacos , Ojo/efectos de los fármacos , Ojo/patología , Humanos , Hidrogeles/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacología , Conejos , Solubilidad/efectos de los fármacos , Agua/químicaRESUMEN
Noninvasive drug delivery is a promising treatment strategy for ocular posterior segment diseases. Many physiological and anatomical barriers of the eye considerably restrict effective diffusion of therapeutics to the target site. To overcome this problem, a novel cyclic arginine-glycine-aspartate (RGD) hexapeptide and penetratin (PEN) co-modified PEGylation polyamidoamine (PAMAM) was designed as a nanocarriers (NCs), and its penetrating and targeting abilities were evaluated. In this study, we show that PAMAM-PEG (reaction molar ratio 1:32) has a relatively high grafting efficiency and low cytotoxicity. The particle size was within the range of 15-20 nm after modification with RGD and PEN. Cellular uptake of RGD-modified NCs involved significant affinity toward integrin αvß3, which validated the targeting of neovasculature. An in vitro permeation study indicated that modification with PEN significantly improved penetration of the NCs (1.5 times higher). In vivo ocular distribution studies showed that, the NCs (modified with PEN or co-modified with RGD and PEN) were highly distributed in the cornea and retina (p < .001), and modification extended retinal retention time for more than 12 h. Therefore, these NCs appear to be a promising noninvasive ocular drug delivery system for ocular posterior segment diseases.
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Péptidos de Penetración Celular/administración & dosificación , Péptidos de Penetración Celular/química , Córnea/efectos de los fármacos , Dendrímeros/química , Péptidos Cíclicos/química , Animales , Línea Celular , Córnea/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Humanos , Integrina alfaVbeta3/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Tamaño de la Partícula , Poliaminas/química , Polietilenglicoles/químicaRESUMEN
Graphene-based nanomaterials (GMs) are served as great promising agents for the prevention and therapy of infectious diseases. However, their dental applications remain to be evaluated, especially under the context of the oral microbial community. Here, we examined the exposure-response of salivary bacterial community to two types of GMs, that is, graphene oxide (GO) and GO-silver nanoparticles (AgNPs). Both GO and GO-AgNPs showed lethal effect against salivary bacteria in a concentration-dependent manner, and the antibacterial capacity of GO-AgNPs is superior to GO. Interestingly, the salivary bacterial community enhanced the tolerance to GMs as compared to homogeneous bacteria. High-throughput sequencing revealed that both 80 µg/mL GO and 20 µg/mL GO-AgNPs significantly altered the biodiversity of salivary bacterial community. Especially, they increased the relative abundance of Gram-positive bacteria compared to the untreated sample, notably Streptococcus, suggesting that the bacterial wall structure plays a critical role in resisting the damage of GMs. Although GMs could effectively limit the salivary bacterial activity and cause changes in bacterial community structure, they are not toxic to mammalian cell lines. We envision this study could provide novel insights into the application of GMs as "green antibiotics" in nanomedicine.