RESUMO
The interconversion between electrical and mechanical energies is pivotal to ferroelectrics to enable their applications in transducers, actuators and sensors. Ferroelectric polymers exhibit a giant electric-field-induced strain (>4.0%), markedly exceeding the actuation strain (≤1.7%) of piezoelectric ceramics and crystals. However, their normalized elastic energy densities remain orders of magnitude smaller than those of piezoelectric ceramics and crystals, severely limiting their practical applications in soft actuators. Here we report the use of electro-thermally induced ferroelectric phase transition in percolative ferroelectric polymer nanocomposites to achieve high strain performance in electric-field-driven actuation materials. We demonstrate a strain of over 8% and an output mechanical energy density of 11.3 J cm-3 at an electric field of 40 MV m-1 in the composite, outperforming the benchmark relaxor single-crystal ferroelectrics. This approach overcomes the trade-off between mechanical modulus and electro-strains in conventional piezoelectric polymer composites and opens up an avenue for high-performance ferroelectric actuators.
Assuntos
Eletricidade , Nanocompostos , PolímerosRESUMO
Microplastics (MPs) can enter the reproductive system and can be potentially harmful to human reproductive health. In this study, 13 types of microplastics (MPs) were identified in patient blood, cancer samples, and paracarcinoma samples using Raman spectroscopy, with polyethylene, polypropylene and polyethylene-co-polypropylene being the most abundant polymer types. Futher, cotton was also found in our study. The diversity and abundance of MPs were higher in blood samples than in cancerous tissues, and there was a significant positive correlation between diversity (p < 0.05). Furthermore, the diversity and abundance of MPs in cancerous tissues were higher than in paracancerous tissues. The dimensional sizes of MPs in these samples were also very similar, with the majority of detected MPs being smaller in size. Correlation analysis showed that patient's age correlated with the abundance of MPs in blood samples, body mass index (BMI) correlated with the abundance of MPs in cancerous tissues. Notably, the frequency with which patients consume bottled water and beverages may also increase the abundance of MPs. This study identifies for the first time the presence of MPs and cotton in cancerous and paracancerous tissues of human cervical cancer patients. This provides new ideas and basic data to study the risk relationship between MP exposure and human health.
Assuntos
Microplásticos , Neoplasias do Colo do Útero , Humanos , Feminino , Microplásticos/análise , Neoplasias do Colo do Útero/sangue , Adulto , Pessoa de Meia-Idade , Análise Espectral RamanRESUMO
Electrohydrodynamic (EHD) printing has been considered as a mature strategy to mimic the hierarchical microarchitectures in native extracellular matrix (ECM). Most of the EHD-printed scaffolds possess single-dimensional fibrous structures, which cannot mimic the multi-dimensional architectures for enhanced cellular behaviors. Here we developed a two-nozzle EHD printing system to fabricate hybrid scaffolds involving submicron and microscale features. The polyethylene oxide- polycaprolactone (PEO-PCL) submicron fibers were fabricated via solution-based EHD printing with a width of 527 ± 56 nm. The PCL microscale fibers were fabricated via melt-based EHD printing with a width of 11.2 ± 2.3µm. The hybrid scaffolds were fabricated by printing the submicron and microscale fibers in a layer-by-layer manner. The microscale scaffolds were utilized as a control group. Rat myocardial cells (H9C2 cells) were cultured on the two kinds of scaffolds for the culturing period of 1, 3 and 5 d. Biological results indicated that H9C2 cells showed enhanced adhesion and proliferation behaviors on the hybrid scaffold than those on the pure microscale scaffold. This work offers a facile and scalable strategy to fabricate multiscale synthetic scaffolds, which might be further explored to regulate cellular behaviors in the fields of tissue regeneration and biomedical engineering.
Assuntos
Engenharia Tecidual , Alicerces Teciduais , Ratos , Animais , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Linhagem Celular , Poliésteres/química , Proliferação de Células , Impressão TridimensionalRESUMO
Supramolecular assembly loading drug as biomedical materials is a research hotspot. Herein, we reported a supramolecular electrospun assembly constructed via the hydrophobic and hydrogen bonding interaction. The obtained results showed that the assembly by supramolecular electrospinning not only increased the interactions of multiple antibacterial active species including antibiotics, cationic polymers, and silver to form a flexible membrane with good mechanical strength but also indicated the dual effects of rapid doxycycline and polyethyleneimine release as well as a sustained Ag release. Interestingly, the assembly showed not only good degradability but also a high bacteriostatic efficacy toward Escherichia coli (E. coli) up to 99.9%. More importantly, the in vivo wound healing assay indicated that the assembly could promote the healing of uninfected, E. coli-infected, and even methicillin-resistant staphylococcus aureus-infected wounds. The current research provides a novel approach to construct a supramolecular assembly by electrospinning mechanically induced strong noncovalent interaction.
Assuntos
Staphylococcus aureus Resistente à Meticilina , beta-Ciclodextrinas , Antibacterianos/farmacologia , Escherichia coli , PolímerosRESUMO
Nanomedicine has attracted increasing attention and emerged as a safer and more effective modality in cancer treatment than conventional chemotherapy. In particular, the distinction of tumor microenvironment and normal tissues is often used in stimulus-responsive drug delivery systems for controlled release of therapeutic agents at target sites. In this study, we developed mesoporous silica nanoparticles (MSNs) coated with polyacrylic acid (PAA), and pH-sensitive lipid (PSL) for synergistic delivery and dual-pH-responsive sequential release of arsenic trioxide (ATO) and paclitaxel (PTX) (PL-PMSN-PTX/ATO). Tumor-targeting peptide F56 was used to modify MSNs, which conferred a target-specific delivery to cancer and endothelial cells under neoangiogenesis. PAA- and PSL-coated nanoparticles were characterized by TGA, TEM, FT-IR, and DLS. The drug-loaded nanoparticles displayed a dual-pH-responsive (pHe = 6.5, pHendo = 5.0) and sequential drug release profile. PTX within PSL was preferentially released at pH = 6.5, whereas ATO was mainly released at pH = 5.0. Drug-free carriers showed low cytotoxicity toward MCF-7 cells, but ATO and PTX co-delivered nanoparticles displayed a significant synergistic effect against MCF-7 cells, showing greater cell-cycle arrest in treated cells and more activation of apoptosis-related proteins than free drugs. Furthermore, the extracellular release of PTX caused an expansion of the interstitial space, allowing deeper penetration of the nanoparticles into the tumor mass through a tumor priming effect. As a result, FPL-PMSN-PTX/ATO exhibited improved in vivo circulation time, tumor-targeted delivery, and overall therapeutic efficacy.
Assuntos
Antineoplásicos/uso terapêutico , Trióxido de Arsênio/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel/uso terapêutico , Resinas Acrílicas/química , Resinas Acrílicas/farmacocinética , Resinas Acrílicas/toxicidade , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Trióxido de Arsênio/farmacocinética , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Cetrimônio/química , Cetrimônio/toxicidade , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Células MCF-7 , Camundongos Endogâmicos ICR , Nanopartículas/toxicidade , Oligopeptídeos/química , Oligopeptídeos/farmacocinética , Oligopeptídeos/toxicidade , Paclitaxel/química , Paclitaxel/farmacocinética , Porosidade , Dióxido de Silício/química , Dióxido de Silício/farmacocinética , Dióxido de Silício/toxicidade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Inflammation and oxidative stress are two major factors that are involved in the pathogenesis of atherosclerosis. A smart drug delivery system that responds to the oxidative microenvironment of atherosclerotic plaques was constructed in the present study. Simvastatin (SIM)-loaded biodegradable polymeric micelles were constructed from hyaluronic acid (HA)-coated poly(ethylene glycol)-poly(tyrosine-ethyl oxalyl) (PEG-Ptyr-EO) for the purpose of simultaneously inhibiting macrophages and decreasing the level of reactive oxygen species (ROS) to treat atherosclerosis. HA coating endows the micelle system the ability of targeting CD44-positive inflammatory macrophages. Owing to the ROS-responsive nature of PEG-Ptyr-EO, the micelles can not only be degraded by enzymes, but also consumes ROS by itself at the pathologic sites, upon which the accumulation of pro-inflammatory macrophages is effectively suppressed and oxidative stress is alleviated. Consequently, the cellular uptake experiment demonstrated that SIM-loaded HA-coated micelles can be effectively internalized by LPS-induced RAW264.7 cells and showed high cytotoxicity against the cells, but low cytotoxicity against LO2 cells. In mouse models of atherosclerosis, intravenously SIM-loaded HA-coated micelles can effectively reduce plaque content of cholesterol, resulting in remarkable therapeutic effects. In conclusion, the SIM-loaded micelle system provides a promising and innovative option against atherosclerosis.
Assuntos
Antioxidantes , Aterosclerose/metabolismo , Ácido Hialurônico/química , Inibidores de Hidroximetilglutaril-CoA Redutases , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Modelos Animais de Doenças , Peróxido de Hidrogênio/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Micelas , Polietilenoglicóis/química , Células RAW 264.7 , Sinvastatina/química , Sinvastatina/farmacocinética , Sinvastatina/farmacologiaRESUMO
Panax quinquefolium saponin (PQS) composed of 45% pseudo-ginsenoside F11 (PF11), is a natural mixture of sterol compounds obtained from the American ginseng plant, having numerous promising benefits for health. However, low solubility and permeability limit the development of PQS as a therapeutic agent for oral administration. In this study, PQS liposomes (PQS-Lips) were prepared by thin layer hydration, an in situ single-pass intestinal perfusion (SPIP) model was used to verify the improvement of membrane permeability of PQS-Lips. PQS-Lips had a high encapsulation efficiency (EE) of 65%â¼70%, a particle size about 100.0 nm, and a zeta potential of -60 mV with regular spherical surface. FTIR and DSC showed the PQS in liposomes were amorphous, indicating that hydrogen bonds formed between one or several hydroxyl groups in PQS and C-O group at the phospholipid polar terminal. In addition, PQS-Lips showed sustained release in vitro than PQS at pH 1.2 and pH 6.8, and PQS-Lips had good stability in simulated gastric and intestinal fluid. Then, the absorption rate (K a) and effective permeability coefficient (P eff) of PQS-Lips in the whole small intestine were significantly higher than those in PQS solution (PQS-Sol), which proved that the PQS-Lips could significantly increase the membrane permeability of PQS and promote its absorption in the small intestine. From the experimental results, it could be known that liposome technology could effectively improve the absorption of PQS in the small intestine.
Assuntos
Ginsenosídeos , Saponinas/química , Absorção Intestinal , Lipossomos/químicaRESUMO
Calcium phosphate (CaP)-containing materials, such as hydroxyapatite and brushite, are well studied bone grafting materials owing to their similar chemical compositions to the mineral phase of natural bone and kidney calculi. In recent studies, magnesium phosphate (MgP)-containing compounds, such as newberyite and struvite, have shown promise as alternatives to CaP. However, the different ways in degradation and release of Mg2+ and Ca2+ ions in vitro may affect the biocompatibility of CaP and MgP-containing compounds. In the present paper, newberyite, struvite, and brushite 3D porous structures were constructed by 3D-plotting combining with a two-step cementation process, using magnesium oxide (MgO) as a starting material. Briefly, 3D porous green bodies fabricated by 3D-plotting were soaked in (NH4)2HPO4 solution to form semi-manufactured 3D porous structures. These structures were then soaked in different phosphate solutions to translate the structures into newberyite, struvite, and brushite porous scaffolds. Powder X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectrometry (EDS) were used to characterize the phases, morphologies, and compositions of the 3D porous scaffolds. The porosity, compressive strength, in vitro degradation and cytotoxicity on MC3T3-E1 osteoblast cells were assessed as well. The results showed that extracts obtained from immersing scaffolds in alpha-modified essential media induced minimal cytotoxicity and the cells could be attached merely onto newberyite and brushite scaffolds. Newberyite and brushite scaffolds produced through our 3D-plotting and two-step cementation process showed the sustained in vitro degradation and excellent biocompatibility, which could be used as scaffolds for the bone tissue engineering.
Assuntos
Materiais Biocompatíveis/síntese química , Fosfatos de Cálcio/química , Compostos de Magnésio/química , Óxido de Magnésio/farmacologia , Microtecnologia/métodos , Fosfatos/química , Estruvita/química , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/química , Cimentos Ósseos/síntese química , Cimentos Ósseos/química , Células Cultivadas , Precipitação Química/efeitos dos fármacos , Força Compressiva , Óxido de Magnésio/química , Teste de Materiais , Camundongos , Conformação Molecular , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Polimerização/efeitos dos fármacos , Porosidade , Pós/síntese química , Pós/química , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodosRESUMO
Tanshinone I (TSI) is one of the bioactive compound obtained from the root of Salvia miltiorrhiza which is a well-known traditional Chinese medicine (TCM) used for the treatment of various diseases. Although TSI possesses several pharmacological effects, it has poor water solubility, blood-brain barrier (BBB) permeability and brain bioavailability. Therefore, in the present study, we developed TSI nanoemulsion (TSI-NE) modified with a brain targeting ligand (Lactoferrin (Lf)) to improve the BBB permeability. Pseudo-ternary phase diagrams were used to optimize the formulation. The optimal TSI-NE and TSI-Lf-NE were prepared and characterized. Finally, the uptake of TSI-Lf-NE by mouse brain microvascular endothelial cell line (bEnd.3 cells) was assessed using Coumarin-6 as a fluorescent probe. The results of the study showed that the stable optimal formulation of O/W nanoemulsion was successfully developed and modified with Lf. The cellular uptake study has shown that the fluorescence intensity (FI) increased with time over the incubation period. The FI at all time intervals increased in the following order: Coumarin-6-Solutionï¼Coumarin-6-NEï¼Coumarin-6-Lf-NE. The results suggest that the BBB permeability of Coumarin-6-Lf-NE was better than those of Coumarin-6-NE and Coumarin-6 solution. Lf modified nanoemulsion has great potential for improving the brain delivery of TSI.
Assuntos
Abietanos/química , Abietanos/metabolismo , Encéfalo/metabolismo , Emulsões/química , Lactoferrina/química , Nanopartículas/química , Animais , Disponibilidade Biológica , Transporte Biológico/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Linhagem Celular , Cumarínicos/química , Cumarínicos/metabolismo , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Emulsões/metabolismo , Lactoferrina/metabolismo , Camundongos , Nanopartículas/metabolismo , Tamanho da Partícula , Permeabilidade/efeitos dos fármacos , Polietilenoglicóis/química , Solubilidade , Tiazóis/química , Tiazóis/metabolismo , Distribuição Tecidual/efeitos dos fármacosRESUMO
A novel functional fiber (PAN-CDs) loaded with carbon dots (CDs) with excellent photoreduction and adsorption properties for Cr(VI) was prepared via an amidization reaction between the CDs' carboxyl groups and amine groups on polyacrylonitrile (PAN)-based ion exchange fibers, which could completely preserve the fluorescence properties of the CDs. The photoluminescence (PL), photocatalysis and adsorption properties of PAN-CDs were characterized and analyzed. The PAN-CDs possess high adsorption capacity (297.6â¯mg/g) and excellent kinetic behavior (attaining adsorption equilibrium in 30â¯min) for Cr(VI) adsorption. Furthermore, the residual Cr(VI) (approximately 3â¯mg/L) after adsorption could be removed completely by subsequent photoreduction by the PAN-CDs. The Cr-saturated PAN-CDs could be easily separated by filtering and regenerated, with no observable decay of removal efficiency after five regeneration cycles. In addition, due to the PL quenching action of Cr(VI), the PAN-CDs can also be used as sensor for quantitative detection of trace Cr(VI) in aqueous solution.
Assuntos
Cromo/química , Poluentes Químicos da Água/química , Resinas Acrílicas/química , Adsorção , Carbono/química , Cromo/análise , Pontos Quânticos/química , Poluentes Químicos da Água/análise , Purificação da Água/métodosRESUMO
Laccase was immobilized in polyvinyl alcohol beads containing halloysite nanotubes (PVA/HNTs) to improve the stability and reusability of enzyme. The porous structure of PVA/HNTs beads facilitates the entrapment of enzyme and prevents the leaching of immobilized laccase as well. Halloysite nanotubes act as bridge to connect the adjacent pores, facilitating the electron transfer and enhancing the mechanical properties. PVA/HNTs beads have high laccase immobilization capacity (237.02 mg/g) and activity recovery yield (79.15%), indicating it can be used as potential support for laccase immobilization. Compared with free laccase, the immobilized laccase on hybrid beads exhibits enhanced pH tolerance (even at pH 8.0), good thermal stability (57.5% of the initial activity can be maintained at 75 °C), and excellent storage stability (81.17% of enzyme activity could be retained after storage at 4 °C for 5 weeks compared with that for free enzyme of 60%). Also, the removal efficiency for reactive blue can reach as high as 93.41% in the presence of redox mediator 2,2-azinobis(3-ethylbenzthiazoline-6-sulfonate), in which adsorption and degradation exist simultaneously. The remarkable pH tolerance, thermal and storage stability, and reuse ability imply potential application of porous PVA/HNTs immobilized enzyme in environmental fields.
Assuntos
Silicatos de Alumínio/química , Corantes/química , Enzimas Imobilizadas/química , Lacase/química , Nanotubos/química , Álcool de Polivinil/química , Poluentes Químicos da Água/química , Adsorção , Argila , Porosidade , Eliminação de Resíduos Líquidos/métodosRESUMO
CONTEXT: Fungal keratitis, a corneal fungal infection of the eye caused mainly by Candida species, has become the leading cause of blindness resulting from corneal disease in China. Present limitations in the management of ophthalmic fungal infections include the inability to provide long-term extraocular drug delivery without compromising intraocular structures and/or systemic drug exposure. OBJECTIVE: The aim of this study was to construct amphotericin B (AmB) loaded, chitosan-modified, nanostructured lipid carriers (AmB-CH-NLC) for prolonged ocular application and for the improvement of the targeted delivery of AmB to the ocular mucosa. MATERIALS AND METHODS: The AmB-CH-NLC was produced by the method of emulsion evaporation-solidification at low temperature. The particle size, zeta potential, and encapsulation efficiency, drug-release behavior, and corneal penetration ability were performed in vitro and in vivo. RESULTS AND DISCUSSION: The prepared AmB-CH-NLC nanoparticles exhibited a measured size of 185.4 nm, a zeta potential of 27.1 mV, and an entrapment efficiency of 90.9%. Sustained drug release behavior was observed in vitro. The in vivo ocular pharmacokinetic study indicated improved bioavailability of AmB-CH-NLC. The corneal penetration study showed that the AmB-CH-NLC could successfully penetrate into the cornea with no obvious irritation to the rabbits' eyes. CONCLUSION: The results support that this novel nanomedicine could be a promising system for effective ocular delivery of amphotericin B for fungal keratitis-targeted therapy.
Assuntos
Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Quitosana/química , Infecções Oculares Fúngicas/tratamento farmacológico , Ceratite/tratamento farmacológico , Lipídeos/química , Administração Oftálmica , Anfotericina B/metabolismo , Animais , Antifúngicos/metabolismo , Disponibilidade Biológica , Preparações de Ação Retardada , Composição de Medicamentos , Emulsões , Infecções Oculares Fúngicas/metabolismo , Ceratite/metabolismo , Lipossomos , Masculino , Nanopartículas/química , Tamanho da Partícula , Permeabilidade , CoelhosRESUMO
With the purpose of improving the ultrafiltration (UF) efficiency, anionic polyacrylamide (APAM) has been used as a coagulant aid in the flocculation-UF process. In this study, the impact of APAM on UF efficiency has been investigated with regard to membrane fouling, membrane cleaning and effluent quality. The results indicated that the optimal dosage of APAM had positive impacts on membrane fouling control, membrane cleaning and effluent quality. According to the flux decline curve, scanning electron microscopy and contact angle characterization, the optimal dosage of APAM was determined to be 0.1 mg/L coupled with 2 mg/L (as Al3+) poly-aluminium chloride. Under this optimal condition, membrane fouling can be mitigated because of the formation of a porous and hydrophilic fouling layer. APAM in the fouling layer can improve the chemical cleaning efficiency of 0.5% NaOH due to the disintegration of the fouling layer when APAM is dissolved under strong alkaline conditions. Furthermore, with the addition of APAM in the flocculation-UF process, more active adsorption sites can be formed in the flocs as well as the membrane fouling layer, thus more antipyrine molecules in the raw water can be adsorbed and removed in the flocculation-UF process.
Assuntos
Resinas Acrílicas/química , Ultrafiltração/instrumentação , Adsorção , Hidróxido de Alumínio/química , Ânions/química , Floculação , Membranas Artificiais , Ultrafiltração/métodos , Purificação da Água/métodosRESUMO
Objective: To explore the enzymatic hydrolysis conditions of Xiaoyao-pill herb residues by cellulose. Methods: Based on the single factor test,an Box-Benhnken design was used to optimize the parameters, three factors, including cellulase dosage, enzymolysis time, and solid-liquid ratio were regarded as investigation factors,the yield of enzymatic hydrolysis as index, Xiaoyao-pill herb residues enzymatic hydrolysis catalyzed by cellulase, and a mathematical regression model was established. Results: The optimal parameters were obtained as follows,cellulase dosage was 6%,enzymolysis time was 5. 6 h and solid-liquid ratio was 1 ⶠ12( g / m L). Under this condition,the yield of enzymatic hydrolysis was 43. 89%. Conclusion: The results may provide new reference for further exploring Chinese herbal medicine efficiently.
Assuntos
Medicamentos de Ervas Chinesas/metabolismo , Celulase , Celulose , HidróliseRESUMO
BACKGROUND/AIMS: Of the 35 million human immunodeficiency virus (HIV)-positive patients worldwide, 10-40% are coinfected with chronic hepatitis C virus (HCV). Compared to HCV-monoinfected patients, those coinfected experience decreased spontaneous HCV clearance, accelerated liver fibrosis, and a decreased response to anti-HCV therapy. We conducted a meta-analysis to estimate the efficacy of treating acute HCV in HIV-positive patients with peginterferon and ribavirin combination therapy. METHODS: Two authors independently searched MEDLINE and EMBASE (2014) for English articles, and reviewed bibliographies and abstracts from major liver and HIV conferences (2011-2013). Original studies featuring at least 10 treatment-naive, HIV-positive adults infected with acute HCV and treated with peginterferon and ribavirin were included. Analyses were calculated using a random-effects model. Heterogeneity was assessed using the Cochrane Q test (p < 0.05) and the I(2) statistic (>50%). RESULTS: From 12 studies (450 patients), the pooled sustained virological response (SVR) was 71.4% (95% CI 64.7-77.4; Q statistic = 22.20, p = 0.023, I(2) = 50.44). The rapid virological response (RVR; 7 studies, 196 patients) was 47.4% (95% CI 40.6-54.7), and the early virological response (EVR; 9 studies, 283 patients) was 82.8% (95% CI 67.0-92.0). The probability of an SVR was 93.1% (95% CI 84.9-97.0) in those who obtained an RVR (6 studies, 82 patients) and 85.9% (95% CI 78.7-91.0) if an EVR (7 studies, 168 patients) was reached. CONCLUSION: Peginterferon with ribavirin is an effective option for treating acute HCV in HIV-positive patients, especially if they achieve an RVR or an EVR.
Assuntos
Antivirais/uso terapêutico , Coinfecção , Infecções por HIV/complicações , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Doença Aguda/terapia , Adulto , Quimioterapia Combinada , Genótipo , Soropositividade para HIV , Hepatite C/complicações , Hepatite C/virologia , Humanos , Interferon alfa-2 , RNA Viral/genética , Proteínas Recombinantes/uso terapêuticoRESUMO
BACKGROUND: The zygomycete fungi like Rhizomucor miehei have been extensively exploited for the production of various enzymes. As a thermophilic fungus, R. miehei is capable of growing at temperatures that approach the upper limits for all eukaryotes. To date, over hundreds of fungal genomes are publicly available. However, Zygomycetes have been rarely investigated both genetically and genomically. RESULTS: Here, we report the genome of R. miehei CAU432 to explore the thermostable enzymatic repertoire of this fungus. The assembled genome size is 27.6-million-base (Mb) with 10,345 predicted protein-coding genes. Even being thermophilic, the G + C contents of fungal whole genome (43.8%) and coding genes (47.4%) are less than 50%. Phylogenetically, R. miehei is more closerly related to Phycomyces blakesleeanus than to Mucor circinelloides and Rhizopus oryzae. The genome of R. miehei harbors a large number of genes encoding secreted proteases, which is consistent with the characteristics of R. miehei being a rich producer of proteases. The transcriptome profile of R. miehei showed that the genes responsible for degrading starch, glucan, protein and lipid were highly expressed. CONCLUSIONS: The genome information of R. miehei will facilitate future studies to better understand the mechanisms of fungal thermophilic adaptation and the exploring of the potential of R. miehei in industrial-scale production of thermostable enzymes. Based on the existence of a large repertoire of amylolytic, proteolytic and lipolytic genes in the genome, R. miehei has potential in the production of a variety of such enzymes.
Assuntos
Genoma Fúngico , Rhizomucor/genética , Transcriptoma , Metabolismo dos Carboidratos , Celulose/metabolismo , Cromossomos Fúngicos , Esterases/genética , Esterases/metabolismo , Perfilação da Expressão Gênica , Genômica , Lipase/genética , Lipase/metabolismo , Dados de Sequência Molecular , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Filogenia , Rhizomucor/classificação , Rhizomucor/enzimologiaRESUMO
Candida albicans morphogenesis and gastrointestinal colonization are closely associated with the pathogenicity of this pathogen. This study investigated the in vitro and in vivo effect of verapamil, a calcium channel blocker, on these processes. Exposure to ≥ 10 µg mL(-1) verapamil led to a significant decrease of C. albicans hyphal cells. The ability to adhere to a polystyrene surface and buccal epithelial cells was inhibited by exposure to ≥ 20 µg mL(-1) verapamil. Detection of the Hwp1-green fluorescent protein fusion protein showed that verapamil inhibited expression and transport of Hwp1, indicating its activity against both the regulation network of morphogenesis-associated proteins and the secretory pathway in C. albicans. Moreover, treatment with verapamil at 10 mg (kg day)(-1) led to a remarkable decrease in gastrointestinal-colonizing fungal cells. This study revealed the inhibitory effect of verapamil on C. albicans hyphal development, adhesion and gastrointestinal colonization, which is relevant to decreased expression and abnormal transport of the proteins required for morphogenesis. Therefore, verapamil may be taken into account when choosing an antifungal therapy against C. albicans colonization and infection.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Hifas/efeitos dos fármacos , Verapamil/farmacologia , Animais , Antifúngicos/administração & dosagem , Candida albicans/crescimento & desenvolvimento , Candida albicans/fisiologia , Células Cultivadas , Células Epiteliais/microbiologia , Proteínas Fúngicas/antagonistas & inibidores , Humanos , Hifas/crescimento & desenvolvimento , Hifas/fisiologia , Glicoproteínas de Membrana/antagonistas & inibidores , Camundongos Endogâmicos ICR , Poliestirenos , Verapamil/administração & dosagemRESUMO
Free-standing polymer films that adhere strongly to tissue and can codeliver multiple therapeutic agents in a controlled manner are useful as medical plasters. In this study, a bilayer polymer film comprising a drug reservoir layer and a supporting layer is fabricated by spin-coating poly(lactic-co-glycolic acid) (PLGA) on top of a layer-by-layer assembled film of poly(ß-amino esters) (PAE), alginate sodium (ALG), and recombinant human basic fibroblast growth factor (bFGF). Apart from bFGF, the bilayer film can also load antibiotic drug ceftriaxone sodium (CTX) by a postdiffusion process. The PLGA supporting layer facilitates the direct peeling of the bilayer film from substrate to produce a robust and flexible free-standing film with excellent adhesion onto the human skin and porcine liver. The excellent adhesion of the bilayer film originates from the ALG component in the drug reservoir layer. CTX is quickly released by easily breaking its electrostatic interaction with the drug reservoir layer, whereas the sustained release of bFGF is due to the slow degradation of PAE component in the drug reservoir layer. Wounds can be synergetically treated by fast release of CTX to effectively eradicate invasive bacteria and by sustained release of bFGF to accelerate wound healing. Our results serve as a basis for designing multifunctional free-standing films with combination therapy for biomedical applications.
Assuntos
Antibacterianos , Bacillus subtilis/efeitos dos fármacos , Ceftriaxona , Escherichia coli/crescimento & desenvolvimento , Fator 2 de Crescimento de Fibroblastos , Membranas Artificiais , Adesivos Teciduais , Alginatos/química , Alginatos/farmacologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Ceftriaxona/química , Ceftriaxona/farmacologia , Linhagem Celular , Fator 2 de Crescimento de Fibroblastos/química , Fator 2 de Crescimento de Fibroblastos/farmacologia , Ácido Glucurônico/química , Ácido Glucurônico/farmacologia , Ácidos Hexurônicos/química , Ácidos Hexurônicos/farmacologia , Humanos , Ácido Láctico/química , Ácido Láctico/farmacologia , Camundongos , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Suínos , Adesivos Teciduais/química , Adesivos Teciduais/farmacologiaRESUMO
A temperature/pH dual sensitive hydrogel with a semi-interpenetrating network (semi-IPN) structure was synthesized through an aqueous amino-succinimide reaction between water-soluble polysuccinimide and polyethyleneimine in the presence of thermosensitive cellulose derivatives. Single-factor experiments were carried out to optimize the preparation conditions of the semi-IPN hydrogel. The swelling behavior and cytotoxicity assay of the hydrogel were tested. Finally, taking 5- fluorouracil (5-Fu) as a model drug, the release performance of the 5-Fu-loaded hydrogel was investigated. The results indicated that the swelling ratio (SR) first decreased and then increased when the pH of the solutions ascended from 2 to 10. The SR decreased with the increase in temperature. In addition, the swelling behavior of the hydrogel was reversible and reproducible under different pH values and temperatures. The prepared hydrogels had good cytocompatibility. The release behavior of 5-Fu was most consistent with the Korsmeyer-Peppas model and followed the case II diffusion. The acidic environment was beneficial for the release of 5-Fu. The preparation process of the semi-IPN hydrogel is simple and the reaction can proceed quickly in water. The strategy introduced here has great potential for application in the preparation of drug carriers.
Assuntos
Celulose , Fluoruracila , Hidrogéis , Succinimidas , Temperatura , Hidrogéis/química , Hidrogéis/síntese química , Celulose/química , Celulose/análogos & derivados , Concentração de Íons de Hidrogênio , Fluoruracila/química , Fluoruracila/farmacologia , Succinimidas/química , Água/química , Liberação Controlada de Fármacos , Portadores de Fármacos/química , HumanosRESUMO
To reduce the white pollution, the eco-friendly biodegradable poly (butylene adipate-co-terephthalate) (PBAT)-based films had attracted increasing interests worldwide. However, the high-cost of the PBAT had limited the large-scale development and application. In this work, 10 wt% low-cost lignin was introduced into the PBAT to prepare composite films by melt blending and blow molding, and the POSS(epoxy)8 was selected as the compatibilizer to improve the compatibility of PBAT and lignin. The maximum tensile strength and the nominal strain at break subsequently increased by 48.2 % and 21.4 % respectively, while the water vapor permeability enhanced by 9.9 %. Furthermore, the UV aging resistance of PBAT/lignin films were significantly improved, with only 1 wt% POSS(epoxy)8 content. This work provides an efficient strategy to foster the end-user confidence in the low-cost and eco-friendly biodegradable polymer materials with efficient performance.