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1.
Nanotechnology ; 33(27)2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35299165

RESUMO

Nanoimprint technology has the advantages of low cost, high precision, high fidelity and high yield. The metal nanoparticle fluid is non-Newtonian fluid, which is used as the imprint transfer medium to realize high fidelity of pattern because of its shear thinning effect. In order to functionalize the metal nanoparticles microstructure, the subsequent sintering step is required to form a metal interconnect wire. Metal interconnect wire with fewer grain boundaries and fewer holes have excellent mechanical and electronic properties. In this paper, the pseudoplastic metal nanoparticle fluid was formed by Ag nanoparticle and precursor solution, and then the thermal diffusion process was completed by microwave sintering after interconnects were embossed. The influence of microwave and thermal atmosphere on the microstructure and performance of Ag Interconnect wires was analyzed and discussed, and the Ag Interconnect wires performance was determined under the influence of time and temperature parameters. In our experiments, the interconnects after microwave sintering can achieve 39% of the conductivity of bulk silver. The microwave sintering module might be integrated as the heat treatment module of the metal micro/nano pattern directly imprint lithography.

2.
Appl Opt ; 61(27): 8115-8122, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36255934

RESUMO

Plasmonic lasers, which use the strong confinement of surface plasmon polaritons, are key parts to realize ultracompact coherent light sources at deep subwavelength scales. We propose a plasmonic laser composed of a silicon substrate, ZnO nanowire, dielectric layer, metal layer, and electrode. In this structure, the superimposed coupling of the surface plasmon mode at the metal interface with the high refractive index gain nanowire mode makes the electric field in the spacer layer significantly enhanced. The ZnO nanowire is used as gain material to provide gain compensation. The optical and electrical properties are simulated with the geometric parameters and dielectric layer material. The results show that the structure has strong confinement of the optical field and can realize a deep subwavelength constraint at a lower threshold level. It provides theoretical support for realizing ultracompact coherent light sources.

3.
J Neurosci ; 38(26): 5982-5995, 2018 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-29891731

RESUMO

We developed an innovative biomaterial-based approach to repair the critical neural circuitry that controls diaphragm activation by locally delivering brain-derived neurotrophic factor (BDNF) to injured cervical spinal cord. BDNF can be used to restore respiratory function via a number of potential repair mechanisms; however, widespread BDNF biodistribution resulting from delivery methods such as systemic injection or lumbar puncture can lead to inefficient drug delivery and adverse side effects. As a viable alternative, we developed a novel hydrogel-based system loaded with polysaccharide-BDNF particles self-assembled by electrostatic interactions that can be safely implanted in the intrathecal space for achieving local BDNF delivery with controlled dosing and duration. Implantation of BDNF hydrogel after C4/C5 contusion-type spinal cord injury (SCI) in female rats robustly preserved diaphragm function, as assessed by in vivo recordings of compound muscle action potential and electromyography amplitudes. However, BDNF hydrogel did not decrease lesion size or degeneration of cervical motor neuron soma, suggesting that its therapeutic mechanism of action was not neuroprotection within spinal cord. Interestingly, BDNF hydrogel significantly preserved diaphragm innervation by phrenic motor neurons (PhMNs), as assessed by detailed neuromuscular junction morphological analysis and retrograde PhMN labeling from diaphragm using cholera toxin B. Furthermore, BDNF hydrogel enhanced the serotonergic axon innervation of PhMNs that plays an important role in modulating PhMN excitability. Our findings demonstrate that local BDNF hydrogel delivery is a robustly effective and safe strategy to restore diaphragm function after SCI. In addition, we demonstrate novel therapeutic mechanisms by which BDNF can repair respiratory neural circuitry.SIGNIFICANCE STATEMENT Respiratory compromise is a leading cause of morbidity and mortality following traumatic spinal cord injury (SCI). We used an innovative biomaterial-based drug delivery system in the form of a hydrogel that can be safely injected into the intrathecal space for achieving local delivery of brain-derived neurotrophic factor (BDNF) with controlled dosing and duration, while avoiding side effects associated with other delivery methods. In a clinically relevant rat model of cervical contusion-type SCI, BDNF hydrogel robustly and persistently improved diaphragmatic respiratory function by enhancing phrenic motor neuron (PhMN) innervation of the diaphragm neuromuscular junction and by increasing serotonergic innervation of PhMNs in ventral horn of the cervical spinal cord. These exciting findings demonstrate that local BDNF hydrogel delivery is a safe and robustly effective strategy to maintain respiratory function after cervical SCI.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/administração & dosagem , Medula Cervical/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Recuperação de Função Fisiológica/efeitos dos fármacos , Respiração/efeitos dos fármacos , Traumatismos da Medula Espinal , Animais , Diafragma/efeitos dos fármacos , Feminino , Hidrogéis , Ratos , Ratos Sprague-Dawley
4.
Neurobiol Dis ; 127: 591-604, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31028873

RESUMO

We tested a biomaterial-based approach to preserve the critical phrenic motor circuitry that controls diaphragm function by locally delivering minocycline hydrochloride (MH) following cervical spinal cord injury (SCI). MH is a clinically-available antibiotic and anti-inflammatory drug that targets a broad range of secondary injury mechanisms via its anti-inflammatory, anti-oxidant and anti-apoptotic properties. However, MH is only neuroprotective at high concentrations that cannot be achieved by systemic administration, which limits its clinical efficacy. We have developed a hydrogel-based MH delivery system that can be injected into the intrathecal space for local delivery of high concentrations of MH, without damaging spinal cord tissue. Implantation of MH hydrogel after unilateral level-C4/5 contusion SCI robustly preserved diaphragm function, as assessed by in vivo recordings of compound muscle action potential (CMAP) and electromyography (EMG) amplitudes. MH hydrogel also decreased lesion size and degeneration of cervical motor neuron somata, demonstrating its central neuroprotective effects within the injured cervical spinal cord. Furthermore, MH hydrogel significantly preserved diaphragm innervation by the axons of phrenic motor neurons (PhMNs), as assessed by both detailed neuromuscular junction (NMJ) morphological analysis and retrograde PhMN labeling from the diaphragm using cholera toxin B (CTB). In conclusion, our findings demonstrate that local MH hydrogel delivery to the injured cervical spinal cord is effective in preserving respiratory function after SCI by protecting the important neural circuitry that controls diaphragm activation.


Assuntos
Medula Cervical/lesões , Hidrogéis/uso terapêutico , Minociclina/uso terapêutico , Rede Nervosa/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Medula Cervical/efeitos dos fármacos , Medula Cervical/fisiopatologia , Diafragma/efeitos dos fármacos , Diafragma/fisiopatologia , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Feminino , Hidrogéis/administração & dosagem , Minociclina/administração & dosagem , Rede Nervosa/fisiopatologia , Fármacos Neuroprotetores/administração & dosagem , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Respiração/efeitos dos fármacos , Traumatismos da Medula Espinal/fisiopatologia
5.
J Opt Soc Am A Opt Image Sci Vis ; 36(5): 893-897, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31045018

RESUMO

We propose a technique for generating a sequence of co-axial zero axial irradiance with a so-called dual-type fractal spiral zone plate (DTFSZP). Based on the Fresnel diffraction theory, we simulated the focusing performance of this optical device. The results reveal that DTFSZP has the remarkable ability of generating a sequence of optical vortices with larger depth of focus and high lateral resolution. The central diffracted image rotates in the vicinity of the focal plane. Moreover, the focusing performance follows a modulo-4 transmutation rule. Such optics promises a complementary and versatile high-resolution non-destructive tool for particle manipulation and provides potential application in three-dimensional optical alignment systems.

6.
J Neural Eng ; 21(1)2024 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-38359460

RESUMO

Objective.Abundant lipid-laden macrophages are found at the injury site after spinal cord injury (SCI). These cells have been suggested to be pro-inflammatory and neurotoxic. AdipoRon, an adiponectin receptor agonist, has been shown to promote myelin lipid efflux from mouse macrophage foam cells. While it is an attractive therapeutic strategy, systemic administration of AdipoRon is likely to exert off-target effects. In addition, the pathophysiology after SCI in mice is different from that in humans, whereas rat and human SCI share similar functional and histological outcomes. In this study, we evaluated the effects of AdipoRon on rat macrophage foam cells and developed a drug delivery system capable of providing sustained local release of AdipoRon to the injured spinal cord.Approach.Rat macrophages were treated with myelin debris to generate anin vitromodel of SCI foam cells, and the effects of AdipoRon treatment on myelin uptake and efflux were studied. AdipoRon was then loaded into and released from microparticles made from dextran sulfate and fibrinogen for sustained release.Main results.AdipoRon treatment not only significantly promotes efflux of metabolized myelin lipids, but also inhibits uptake of myelin debris. Myelin debris alone does not appear to be inflammatory, but myelin debris treatment potentiates inflammation when administered along with pro-inflammatory lipopolysaccharide (LPS) and interferon-γ. AdipoRon significantly attenuated myelin lipid-induced potentiation of inflammation. Bioactive AdipoRon can be released in therapeutic doses from microparticles.Significance.These data suggest that AdipoRon is a promising therapeutic capable of reducing lipid accumulation via targeting both myelin lipid uptake and efflux, which potentially addresses chronic inflammation following SCI. Furthermore, we developed microparticle-based drug delivery systems for local delivery of AdipoRon to avoid deleterious side effects. This is the first study to release AdipoRon from drug delivery systems designed to reduce lipid accumulation and inflammation in reactive macrophages after SCI.


Assuntos
Bainha de Mielina , Piperidinas , Traumatismos da Medula Espinal , Ratos , Camundongos , Humanos , Animais , Macrófagos/metabolismo , Macrófagos/patologia , Inflamação/patologia , Lipídeos/farmacologia
7.
Biofabrication ; 16(2)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38447206

RESUMO

Owing to its thermoresponsive and photocrosslinking characteristics, gelatin methacryloyl (GelMA)-based biomaterials have gained widespread usage as a novel and promising bioink for three-dimensional bioprinting and diverse biomedical applications. However, the flow behaviors of GelMA during the sol-gel transition, which are dependent on time and temperature, present significant challenges in printing thick scaffolds while maintaining high printability and cell viability. Moreover, the tunable properties and photocrosslinking capabilities of GelMA underscore its potential for localized drug delivery applications. Previous research has demonstrated the successful incorporation of minocycline (MH) into GelMA scaffolds for therapeutic applications. However, achieving a prolonged and sustained release of concentrated MH remains a challenge, primarily due to its small molecular size. The primary aim of this study is to investigate an optimal extrusion printing method for GelMA bioink in extrusion bioprinting, emphasizing its flow behaviors that are influenced by time and temperature. Additionally, this research seeks to explore the potential of GelMA bioink as a carrier for the sustained release of MH, specifically targeting cellular protection against oxidative stress. The material properties of GelMA were assessed and further optimization of the printing process was conducted considering both printability and cell survival. To achieve sustained drug release within GelMA, the study employed a mechanism using metal ion mediation to facilitate the interaction between MH, dextran sulfate (DS), and magnesium, leading to the formation of nanoparticle complexes (MH-DS). Furthermore, a GelMA-basedin vitromodel was developed in order to investigate the cellular protective properties of MH against oxidative stress. The experimental results revealed that the printability and cell viability of GelMA are significantly influenced by the printing duration, nozzle temperature, and GelMA concentrations. Optimal printing conditions were identified based on a thorough assessment of both printability and cell viability. Scaffolds printed under these optimal conditions exhibited exceptional printability and sustained high cell viability. Notably, it was found that lower GelMA concentrations reduced the initial burst release of MH from the MH-dextran sulfate (MH-DS) complexes, thus favoring more controlled, sustained release profiles. Additionally, MH released under these conditions significantly enhanced fibroblast viability in anin vitromodel simulating oxidative stress.


Assuntos
Bioimpressão , Metacrilatos , Minociclina , Minociclina/farmacologia , Preparações de Ação Retardada/farmacologia , Sulfato de Dextrana , Impressão Tridimensional , Gelatina , Bioimpressão/métodos , Estresse Oxidativo , Hidrogéis , Alicerces Teciduais , Engenharia Tecidual/métodos
8.
J Neurotrauma ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39078323

RESUMO

A major portion of spinal cord injury (SCI) cases occur in the cervical region, where essential components of the respiratory neural circuitry are located. Phrenic motor neurons (PhMNs) housed at cervical spinal cord level C3-C5 directly innervate the diaphragm, and SCI-induced damage to these cells severely impairs respiratory function. In this study, we tested a biomaterial-based approach aimed at preserving this critical phrenic motor circuitry after cervical SCI by locally delivering hepatocyte growth factor (HGF). HGF is a potent mitogen that promotes survival, proliferation, migration, repair, and regeneration of a number of different cell and tissue types in response to injury. We developed a hydrogel-based HGF delivery system that can be injected into the intrathecal space for local delivery of high levels of HGF without damaging the spinal cord. Implantation of HGF hydrogel after unilateral C5 contusion-type SCI in rats preserved diaphragm function, as assessed by in vivo recordings of both compound muscle action potentials and inspiratory electromyography amplitudes. HGF hydrogel also preserved PhMN innervation of the diaphragm, as assessed by both retrograde PhMN tracing and detailed neuromuscular junction morphological analysis. Furthermore, HGF hydrogel significantly decreased lesion size and degeneration of cervical motor neuron cell bodies, as well as reduced levels surrounding the injury site of scar-associated chondroitin sulfate proteoglycan molecules that limit axon growth capacity. Our findings demonstrate that local biomaterial-based delivery of HGF hydrogel to injured cervical spinal cord is an effective strategy for preserving respiratory circuitry and diaphragm function.

9.
Adv Sci (Weinh) ; 11(22): e2310162, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38602439

RESUMO

The inflammatory response is a key factor affecting tissue regeneration. Inspired by the immunomodulatory role of spermidine, an injectable double network hydrogel functionalized with spermidine (DN-SPD) is developed, where the first and second networks are formed by dynamic imine bonds and non-dynamic photo-crosslinked bonds respectively. The single network hydrogel before photo-crosslinking exhibits excellent injectability and thus can be printed and photo-crosslinked in situ to form double network hydrogels. DN-SPD hydrogel has demonstrated desirable mechanical properties and tissue adhesion. More importantly, an "operando" comparison of hydrogels loaded with spermidine or diethylenetriamine (DETA), a sham molecule resembling spermidine, has shown similar physical properties, but quite different biological functions. Specifically, the outcomes of 3 sets of in vivo animal experiments demonstrate that DN-SPD hydrogel can not only reduce inflammation caused by implanted exogenous biomaterials and reactive oxygen species but also promote the polarization of macrophages toward regenerative M2 phenotype, in comparison with DN-DETA hydrogel. Moreover, the immunoregulation by spermidine can also translate into faster and more natural healing of both acute wounds and diabetic wounds. Hence, the local administration of spermidine affords a simple but elegant approach to attenuate foreign body reactions induced by exogenous biomaterials to treat chronic refractory wounds.


Assuntos
Diabetes Mellitus Experimental , Modelos Animais de Doenças , Hidrogéis , Inflamação , Espermidina , Cicatrização , Espermidina/farmacologia , Animais , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Inflamação/tratamento farmacológico , Camundongos , Masculino , Materiais Biocompatíveis
10.
Materials (Basel) ; 16(12)2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37374478

RESUMO

Nickel-based alloys have demonstrated significant promise as structural materials for Gen-IV nuclear reactors. However, the understanding of the interaction mechanism between the defects resulting from displacement cascades and solute hydrogen during irradiation remains limited. This study aims to investigate the interaction between irradiation-induced point defects and solute hydrogen on nickel under diverse conditions using molecular dynamics simulations. In particular, the effects of solute hydrogen concentrations, cascade energies, and temperatures are explored. The results show a pronounced correlation between these defects and hydrogen atoms, which form clusters with varying hydrogen concentrations. With increasing the energy of a primary knock-on atom (PKA), the number of surviving self-interstitial atoms (SIAs) also increases. Notably, at low PKA energies, solute hydrogen atoms impede the clustering and formation of SIAs, while at high energies, they promote such clustering. The impact of low simulation temperatures on defects and hydrogen clustering is relatively minor. High temperature has a more obvious effect on the formation of clusters. This atomistic investigation offers valuable insights into the interaction between hydrogen and defects in irradiated environments, thereby informing material design considerations for next-generation nuclear reactors.

11.
Adv Healthc Mater ; 12(8): e2202270, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36457271

RESUMO

Bacterial infection is one of the most frequent wound complications and has become a major public health concern. Increasing resistance to antibiotics has been noted with these agents broadly used in wound management. It is an urgent demand to develop alternative antibacterial strategies with a reduced chance of resistance. Herein, a Nepenthes-mimicking nanosheet array of MoS2 on carbon fibers (CF-MoS2 ) is proposed to achieve dual bactericidal activities. First, the sharp edges of synthesized surfaces are capable of inducing physical disruption of cell membranes, demonstrating mechanical antibacterial activity like their natural counterparts. Second, in the presence of near-infrared light, bioinspired CF-MoS2 nanosheets are able to cause the death of damaged bacteria owing to their inherent photothermal properties. Such dual-functional modes endow the surfaces with nearly 100% killing efficiency for highly concentrated Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Furthermore, their potential to be applied as wound dressings for photothermal treatment of infectious wounds is also investigated in vivo. Bioinspired CF-MoS2 dressings show advantages of synergistic disinfection and efficient promotion of wound regeneration. It is foreseen that this high-performance and multifunctional CF-MoS2 could afford a feasible broad-spectrum treatment for non-antibiotic disinfection.


Assuntos
Escherichia coli , Infecções Estafilocócicas , Humanos , Fibra de Carbono , Molibdênio/farmacologia , Desinfecção , Staphylococcus aureus , Antibacterianos/farmacologia
12.
Front Immunol ; 14: 1113883, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36776889

RESUMO

Introduction: Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of 25% of the population and is a leading cause of cirrhosis and hepatocellular carcinoma. NAFLD ranges from simple steatosis (non-alcoholic fatty liver) to non-alcoholic steatohepatitis (NASH). Hepatic macrophages, specifically Kupffer cells (KCs) and monocyte-derived macrophages, act as key players in the progression of NAFLD. Caspases are a family of endoproteases that provide critical connections to cell regulatory networks that sense disease risk factors, control inflammation, and mediate inflammatory cell death (pyroptosis). Caspase-11 can cleave gasdermin D (GSDMD) to induce pyroptosis and specifically defends against bacterial pathogens that invade the cytosol. However, it's still unknown whether high fat diet (HFD)-facilitated gut microbiota-generated cytoplasmic lipopolysaccharides (LPS) activate caspase-11 and promote NAFLD. Methods: To examine this hypothesis, we performed liver pathological analysis, RNA-seq, FACS, Western blots, Seahorse mitochondrial stress analyses of macrophages and bone marrow transplantation on HFD-induced NAFLD in WT and Casp11-/- mice. Results and Discussion: Our results showed that 1) HFD increases body wight, liver wight, plasma cholesterol levels, liver fat deposition, and NAFLD activity score (NAS score) in wild-type (WT) mice; 2) HFD increases the expression of caspase-11, GSDMD, interleukin-1ß, and guanylate-binding proteins in WT mice; 3) Caspase-11 deficiency decreases fat liver deposition and NAS score; 4) Caspase-11 deficiency decreases bone marrow monocyte-derived macrophage (MDM) pyroptosis (inflammatory cell death) and inflammatory monocyte (IM) surface GSDMD expression; 5) Caspase-11 deficiency re-programs liver transcriptomes and reduces HFD-induced NAFLD; 6) Caspase-11 deficiency decreases extracellular acidification rates (glycolysis) and oxidative phosphorylation (OXPHOS) in inflammatory fatty acid palmitic acid-stimulated macrophages, indicating that caspase-11 significantly contributes to maintain dual fuel bioenergetics-glycolysis and OXPHOS for promoting pyroptosis in macrophages. These results provide novel insights on the roles of the caspase-11-GSDMD pathway in promoting hepatic macrophage inflammation and pyroptosis and novel targets for future therapeutic interventions involving the transition of NAFLD to NASH, hyperlipidemia, type II diabetes, metabolic syndrome, metabolically healthy obesity, atherosclerotic cardiovascular diseases, autoimmune diseases, liver transplantation, and hepatic cancers.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/patologia , Dieta Hiperlipídica/efeitos adversos , Caspases/metabolismo , Piroptose , Fosforilação Oxidativa , Diabetes Mellitus Tipo 2/metabolismo , Macrófagos , Inflamação/metabolismo , Glicólise
13.
J Colloid Interface Sci ; 612: 194-202, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-34992019

RESUMO

Semiconductor photocatalysis, as a means of utilizing stranded renewable solar resources, is now emerging as a viable and promising approach for increasingly severe water pollution. In this work, a high-performance photocatalytic system has been fabricated by immobilizing spiky TiO2/Au nanohybrids on one side of hydrophobic nanoPE substrate (PE-TiO2/Au) that forces the enabling of air-liquid-solid triphase photocatalytic interface. Such a triphase system allows efficient oxygen access to the photocatalyst surface, which is feasible for charge separation and reactive oxygen species (ROS) production. Two modes of triphase systems with different gas flow paths were constructed, in which PE-TiO2/Au was floating on the aqueous solution surface (exposed mode) or immersing in aqueous phase (immersed mode). It is worth mentioning that the exposed PE-TiO2/Au enables a more efficient oxygen supply, thus leading to a 5.5-fold and 1.8-fold higher reaction kinetics as compared to normal liquid-solid diphase system and immersed PE-TiO2/Au. Meanwhile, PE-TiO2/Au also exerts bactericidal effect under visible light irradiation, which effectively inactivates S.aureus (>99.9%) in a lean period of 30 min. The qualities of high lethality rate and short reaction time are endowed to PE-TiO2/Au due to the co-effect of unique triphase interface microenvironment and elaborate heterojunction of spiky TiO2/Au nanohybrids. In this paper, we have revealed for the first time that the antibacterial efficiency can be effectively improved by increasing the oxygen supply with the construction of three-phase interface, which represents a promising option in designing highly efficient photocatalytic systems for sewage purification applications.


Assuntos
Antibacterianos , Titânio , Antibacterianos/farmacologia , Catálise , Semicondutores , Água
14.
Glia ; 59(6): 981-96, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21456043

RESUMO

Chondroitin sulfate-4,6 (CS-E) glycosaminoglycan (GAG) upregulation in astroglial scars is a major contributor to chondroitin sulfate proteoglycan (CSPG)-mediated inhibition [Gilbert et al. (2005) Mol Cell Neurosci 29:545­558]. However, the role of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S6ST) catalyzed sulfation of CS-E, and its contribution to CSPG-mediated inhibition of CNS regeneration remains to be fully elucidated. Here, we used in situ hybridization to show localized upregulation of GalNAc4S6ST mRNA after CNS injury. Using in vitro spot assays with immobilized CS-E, we demonstrate dose-dependent inhibition of rat embryonic day 18 (E18) cortical neurons. To determine whether selective downregulation of CS-E affected the overall inhibitory character of extracellular matrix produced by reactive astrocytes, single [against (chondroitin 4) sulfotransferase 11 (C4ST1) or GalNAc4S6ST mRNA] or double [against C4ST1 and GalNAc4S6ST mRNA] siRNA treatments were conducted and assayed using quantitative real-time polymerase chain reaction and high-performance liquid chromatography to confirm the specific downregulation of CS-4S GAG (CS-A) and CS-E. Spot and Bonhoeffer stripe assays using astrocyte-conditioned media from siRNA-treated rat astrocytes showed a significant decrease in inhibition of neuronal attachment and neurite extensions when compared with untreated and TGF-treated astrocytes. These findings reveal that selective attenuation of CS-E via siRNA targeting of GalNAc4S6ST significantly mitigates CSPG-mediated inhibition of neurons, potentially offering a novel intervention strategy for CNS injury.


Assuntos
Astrócitos/metabolismo , Córtex Cerebral/enzimologia , Proteoglicanas de Sulfatos de Condroitina/fisiologia , Neurônios/metabolismo , Sulfotransferases/antagonistas & inibidores , Sulfotransferases/biossíntese , Animais , Animais Recém-Nascidos , Astrócitos/enzimologia , Células Cultivadas , Proteoglicanas de Sulfatos de Condroitina/genética , Regulação para Baixo/genética , Marcação de Genes/métodos , Masculino , Inibição Neural/genética , Neurônios/enzimologia , Ratos , Ratos Sprague-Dawley , Sulfotransferases/genética
15.
Neural Regen Res ; 16(2): 247-253, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32859771

RESUMO

Spinal cord injury results in significant loss of motor, sensory, and autonomic functions. Although a wide range of therapeutic agents have been shown to attenuate secondary injury or promote regeneration/repair in animal models of spinal cord injury, clinical translation of these strategies has been limited, in part due to difficulty in safely and effectively achieving therapeutic concentrations in the injured spinal cord tissue. Hydrogel-based drug delivery systems offer unique opportunities to locally deliver drugs to the injured spinal cord with sufficient dose and duration, while avoiding deleterious side effects associated with systemic drug administration. Such local drug delivery systems can be readily fabricated from biocompatible and biodegradable materials. In this review, hydrogel-based strategies for local drug delivery to the injured spinal cord are extensively reviewed, and recommendations are made for implementation.

16.
IEEE Trans Neural Syst Rehabil Eng ; 27(5): 846-856, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30998475

RESUMO

Braided multi-electrode probes (BMEPs) for neural interfaces comprise ultrafine microwire bundles interwoven into tubular braids. BMEPs provide highly flexible probes and tethers, and an open lattice structure with up to 24 recording/stimulating channels in precise geometries, currently all within a [Formula: see text] diameter footprint. This paper compares the long-term tissue effects of BMEPs ( [Formula: see text] wires) versus single conventional 50- [Formula: see text] wires, by testing nearby chronic immune response and neural survival in rat cortex. Four different types of electrodes were implanted in cortex in each of eight rats: 1) BMEP with tether; 2) tethered 50- [Formula: see text] wire; 3) BMEP without a tether; and 4) untethered 50- [Formula: see text] wire. Quantitative immunohistological statistical comparisons after eight weeks using GFAP, ED1, and NeuN staining clearly showed that both BMEP implants had significantly less tissue immune response and more neuronal survival than either of the 50- [Formula: see text] wires ( ) in each of the eight rats. Data strongly indicate that BMEP tissue responses are superior, and that BMEP designs partly alleviate chronic tissue inflammatory responses and neural losses. The flexible body, tether and open braid lattice, and finer wire diameters of BMEP designs may all contribute to reducing the biological long-term response.


Assuntos
Córtex Cerebral/fisiologia , Eletrodos Implantados , Microeletrodos , Próteses Neurais , Neurônios/fisiologia , Animais , Antígenos Nucleares/metabolismo , Sobrevivência Celular , Córtex Cerebral/citologia , Córtex Cerebral/imunologia , Ectodisplasinas/metabolismo , Desenho de Equipamento , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Nanotecnologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/imunologia , Desenho de Prótese , Ratos , Ratos Sprague-Dawley
17.
Nanomaterials (Basel) ; 9(7)2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31266260

RESUMO

In this paper, the effect of electron irradiation fluence on direct current (DC) and radio frequency (RF) of InP-based high electron mobility transistors (HEMTs) was investigated comprehensively. The devices were exposed to a 1 MeV electron beam with varied irradiation fluences from 1 × 1014 cm-2, 1 × 1015 cm-2, to 1 × 1016 cm-2. Both the channel current and transconductance dramatically decreased as the irradiation fluence rose up to 1 × 1016 cm-2, whereas the specific channel on-resistance (Ron) exhibited an apparent increasing trend. These changes could be responsible for the reduction of mobility in the channel by the irradiation-induced trap charges. However, the kink effect became weaker with the increase of the electron fluence. Additionally, the current gain cut-off frequency (fT) and maximum oscillation frequency (fmax) demonstrated a slightly downward trend as the irradiation fluence rose up to 1 × 1016 cm-2. The degradation of frequency properties was mainly due to the increase of gate-drain capacitance (CGD) and the ratio of gate-drain capacitance and gate-source capacitance (CGD/CGS). Moreover, the increase of Ron may be another important factor for fmax reduction.

18.
Food Chem ; 270: 573-578, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30174088

RESUMO

A novel simple, sensitive and reliable sensor based on S1 nuclease, FAM-labeled ssDNA (DNA-F) and graphene oxide (GO) was developed for detecting adenosine triphosphate (ATP) and evaluating the freshness of meat (beef) samples. With S1 nuclease as the cleaver of DNA-F and ATP as the inhibitor of S1 nuclease, the fluorescence of DNA-F could be obviously quenched by GO, which exhibits the fluorescence of system gradually decrease as the increasing ATP concentration. Under the optimal conditions, a linear correlation between the fluorescence and the ATP concentration from 20 µM to 3500 µM is obtained with a detection limit of 3.2 µM. Furthermore, the proposed ATP detection method was applied to the ATP detection in microorganisms in meat samples, which acquired the satisfying results, respectively.


Assuntos
Trifosfato de Adenosina/análise , Carne/análise , Carne/normas , Técnicas Biossensoriais , Fluorescência , Corantes Fluorescentes , Grafite , Limite de Detecção , Óxidos , Espectrometria de Fluorescência
19.
ACS Appl Mater Interfaces ; 11(33): 29512-29521, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31397552

RESUMO

Here we reported a study of metal ions-assisted assembly of DNA-minocycline (MC) complexes and their potential application for controlling MC release. In the presence of divalent cations of magnesium or calcium ions (M2+), MC, a zwitterionic tetracycline analogue, was found to bind to phosphate groups of nucleic acids via an electrostatic bridge of phosphate (DNA)-M2+-MC. We investigated multiple parameters for affecting the formation of DNA-Mg2+-MC complex, including metal ion concentrations, base composition, DNA length, and single- versus double-stranded DNA. For different nitrogen bases, single-stranded poly(A)20 and poly(T)20 showed a higher MC entrapment efficiency of DNA-Mg2+-MC complex than poly(C)20 and poly(G)20. Single-stranded DNA was also found to form a more stable DNA-Mg2+-MC complex than double-stranded DNA. Between different divalent metal ions, we observed that the formation of DNA-Ca2+-MC complex was more stable and efficient than the formation of DNA-Mg2+-MC complex. Toward drug release, we used agarose gel to encapsulate DNA-Mg2+-MC complexes and monitored MC release. Some DNA-Mg2+-MC complexes could prolong MC release from agarose gel to more than 10 days as compared with the quick release of free MC from agarose gel in less than 1 day. The released MC from DNA-Mg2+-MC complexes retained the anti-inflammatory bioactivity to inhibit nitric oxide production from pro-inflammatory macrophages. The reported study of metal ion-assisted DNA-MC assembly not only increased our understanding of biochemical interactions between tetracycline molecules and nucleic acids but also contributed to the development of a highly tunable drug delivery system to mediate MC release for clinical applications.


Assuntos
DNA/química , Íons/química , Minociclina/química , Animais , Anti-Inflamatórios/química , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Macrófagos/metabolismo , Camundongos , Células RAW 264.7
20.
J R Soc Interface ; 5(26): 957-75, 2008 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-18477539

RESUMO

Biomaterials are widely used to help treat neurological disorders and/or improve functional recovery in the central nervous system (CNS). This article reviews the application of biomaterials in (i) shunting systems for hydrocephalus, (ii) cortical neural prosthetics, (iii) drug delivery in the CNS, (iv) hydrogel scaffolds for CNS repair, and (v) neural stem cell encapsulation for neurotrauma. The biological and material requirements for the biomaterials in these applications are discussed. The difficulties that the biomaterials might face in each application and the possible solutions are also reviewed in this article.


Assuntos
Materiais Biocompatíveis/administração & dosagem , Doenças do Sistema Nervoso Central/terapia , Animais , Derivações do Líquido Cefalorraquidiano , Humanos , Hidrogéis , Bombas de Infusão Implantáveis , Próteses e Implantes
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