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1.
Curr Med Chem ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38486385

RESUMO

BACKGROUND: Traditional Oriental Medicines (TOMs) formulated using a variety of medicinal plants have a low risk of side effects. In previous studies, five TOMs, namely Dangguijakyaksan, Hwanglyeonhaedoktang, Ukgansan, Palmijihwanghwan, and Jowiseungchungtang have been commonly used to treat patients with Alzheimer's disease. However, only a few studies have investigated the effects of these five TOMs on tau pathology. OBJECTIVE: This study aimed to examine the effect of five TOMs on various tau pathologies, including post-translational modifications, aggregation and deposition, tau-induced neurotoxicity, and tau-induced neuroinflammation. METHODS: Immunocytochemistry was used to investigate the hyperphosphorylation of tau induced by okadaic acid. In addition, the thioflavin T assay was used to assess the effects of the TOMs on the inhibition of tau K18 aggregation and the dissociation of tau K18 aggregates. Moreover, a water-soluble tetrazolium-1 assay and a quantitative reverse transcription polymerase chain reaction were used to evaluate the effects of the TOMs on tau-induced neurotoxicity and inflammatory cytokines in HT22 and BV2 cells, respectively. RESULTS: The five TOMs investigated in this study significantly reduced okadaic acid-induced tau hyperphosphorylation. Hwanglyeonhaedoktang inhibited the aggregation of tau and promoted the dissociation of tau aggregates. Dangguijakyaksan and Hwanglyeonhaedoktang attenuated tau-induced neurotoxicity in HT22 cells. In addition, Dangguijakyaksan, Hwanglyeonhaedoktang, Ukgansan, and Palmijihwanghwan reduced tauinduced pro-inflammatory cytokine levels in BV2 cells. CONCLUSION: Our results suggest that five TOMs are potential therapeutic candidates for tau pathology. In particular, Hwanglyeonhaedoktang showed the greatest efficacy among the five TOMs in cell-free and cell-based screening approaches. These findings suggest that Hwanglyeonhaedoktang is suitable for treating AD patients with tau pathology.

2.
Biomed Pharmacother ; 172: 116226, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301421

RESUMO

Alzheimer's disease (AD) is characterized by the presence of two critical pathogenic factors: amyloid-ß (Aß) and tau. Aß and tau become neurotoxic aggregates via self-assembly, and these aggregates contribute to the pathogenesis of AD. Therefore, there has been growing interest in therapeutic strategies that simultaneously target Aß and tau aggregates. Although neferine has attracted attention as a suitable candidate agent for alleviating AD pathology, there has been no study investigating whether neferine affects the modulation of Aß or tau aggregation/dissociation. Herein, we investigated the dual regulatory effects of neferine on Aß and tau aggregation/dissociation. We predicted the binding characteristics of neferine to Aß and tau using molecular docking simulations. Next, thioflavin T and atomic force microscope analyses were used to evaluate the effects of neferine on the aggregation or dissociation of Aß42 and tau K18. We verified the effect of neferine on Aß fibril degradation using a microfluidic device. In addition, molecular dynamics simulation was used to predict a conformational change in the Aß42-neferine complex. Moreover, we examined the neuroprotective effect of neferine against neurotoxicity induced by Aß and tau and their fibrils in HT22 cells. Finally, we foresaw the pharmacokinetic properties of neferine. These results demonstrated that neferine, which has attracted attention as a potential treatment for AD, can directly affect Aß and tau pathology.


Assuntos
Doença de Alzheimer , Benzilisoquinolinas , Síndromes Neurotóxicas , Humanos , Simulação de Acoplamento Molecular , Peptídeos beta-Amiloides , Doença de Alzheimer/tratamento farmacológico , Dispositivos Lab-On-A-Chip , Tecnologia
3.
Int J Biol Macromol ; 263(Pt 2): 130516, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423419

RESUMO

Tau is a microtubule-associated protein that plays a critical role in the stabilization and modulation of neuronal axons. Tau pathology is stronger associated with cognitive decline in patients with Alzheimer's disease (AD) than amyloid beta (Aß) pathology. Hence, tau targeting is a promising approach for the treatment of AD. Previous studies have demonstrated that the non-saponin fraction with rich polysaccharide (NFP) from Korean red ginseng (KRG) can modulate tau aggregation and exert a therapeutic effect on AD. Therefore, we investigated the efficacy of NFP isolated from KRG on tau pathology in experimental models of AD. Our results showed that NFP from KRG ameliorated deposition and hyperphosphorylation of tau in the brain of 3xTg mice. Moreover, NFP from KRG modulated the aggregation and dissociation of tau K18 in vitro. We demonstrated the alleviatory effects of NFP from KRG on hyperphosphorylated tau and tau kinase in okadaic acid-treated HT22 cells. Furthermore, NFP from KRG mitigated Aß deposition, neurodegeneration, and neuroinflammation in 3xTg mice. We revealed the neuroprotective effects of NFP from KRG on tau-induced neuronal loss in HT22 cells. Our results indicate that NFP extracted from KRG is a novel therapeutic agent for the treatment of AD associated with tau pathology.


Assuntos
Doença de Alzheimer , Panax , Humanos , Camundongos , Animais , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas tau/metabolismo , Panax/metabolismo , Camundongos Transgênicos , Modelos Animais de Doenças
4.
Colloids Surf B Biointerfaces ; 234: 113729, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38160475

RESUMO

Biofilms formed owing to the attachment of bacteria to surfaces have caused various problems in industries such as marine transportation/logistics and medicine. In response, many studies have been conducted on bactericidal surfaces, and nanostructured surfaces mimicking cicada and dragonfly wings are emerging as candidates for mechano-bactericidal surfaces. In specific circumstances involving mechano-bactericidal activity, certain nanostructured surfaces could exhibit their bactericidal effects by directly deforming the membranes of bacteria that adhere to these nanostructures. Additionally, in most cases, debris of bacterial cells may accumulate on these nanostructured surfaces. Such accumulation poses a significant challenge: it diminishes the mechano-bactericidal effectiveness of the surface, as it hinders the direct interaction between the nanostructures and any new bacteria that attach subsequently. In specific circumstances involving mechano-bactericidal activity, certain nanostructured surfaces could exhibit their bactericidal effects by directly deforming the membranes of bacteria that adhere to these nanostructures. Additionally, in most cases, debris of bacterial cells may accumulate on these nanostructured surfaces. Such accumulation poses a significant challenge: it diminishes the mechano-bactericidal effectiveness of the surface, as it hinders the direct interaction between the nanostructures and any new bacteria that attach subsequently.In other words, there is a need for strategies to remove the accumulated bacterial debris in order to sustain the mechano-bactericidal effect of the nanostructured surface. In this study, hierarchical micro/nano-structured surface (echinoid-shaped nanotextures were formed on Al micro-particle's surfaces) was fabricated using a simple pressure-less sintering method, and effective bactericidal efficiency was shown against E. coli (97 ± 3.81%) and S. aureus (80 ± 9.34%). In addition, thermal cleaning at 500 °C effectively eliminated accumulated dead bacterial debris while maintaining the intact Al2O3 nanostructure, resulting in significant mechano-bactericidal activity (E. coli: 89 ± 6.86%, S. aureus: 75 ± 8.31%). As a result, thermal cleaning maintains the intact nanostructure and allows the continuance of the mechano-bactericidal effect. This effect was consistently maintained even after five repetitive use (E. coli: 80 ± 16.26%, S. aureus: 76 ± 12.67%).


Assuntos
Nanoestruturas , Odonatos , Animais , Staphylococcus aureus/fisiologia , Escherichia coli , Nanoestruturas/química , Bactérias , Antibacterianos/farmacologia , Antibacterianos/química , Propriedades de Superfície
5.
Biomed Pharmacother ; 168: 115770, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37865990

RESUMO

Alzheimer's disease (AD) is characterized by the aggregation of disordered proteins, such as amyloid beta (Aß) and tau, leading to neurotoxicity and disease progression. Despite numerous efforts, effective inhibitors of Aß and tau aggregates have not been developed. Thus, we aimed to screen natural small molecules from crude extracts that target various pathologies and are prescribed for patients with neurological diseases. In this study, we screened 162 natural small molecules prescribed for neurological diseases and identified genipin and pyrogallol as hit compounds capable of simultaneously regulating the aggregation of Aß and tau K18. Moreover, we confirmed the dual modulatory effects of these compounds on the reduction of amyloid-mediated neurotoxicity in vitro and the disassembly of preformed Aß42 and tau K18 fibrils. Furthermore, we observed the alleviatory effects of genipin and pyrogallol against AD-related pathologies in triple transgenic AD mice. Molecular dynamics and docking simulations revealed the molecular interaction dynamics of genipin and pyrogallol with Aß42 and tau K18, providing insights into their suppression of aggregation. Our findings suggest the therapeutic potential of genipin and pyrogallol as dual modulators for the treatment of AD by inhibiting aggregation or promoting dissociation of Aß and tau.


Assuntos
Doença de Alzheimer , Humanos , Camundongos , Animais , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Pirogalol/farmacologia , Proteínas tau/metabolismo , Camundongos Transgênicos
6.
BMB Rep ; 56(9): 520-525, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37482752

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline. Several recent studies demonstrated that impaired adult neurogenesis could contribute to AD-related cognitive impairment. Adult subventricular zone (SVZ) neurogenesis, which occurs in the lateral ventricles, plays a crucial role in structural plasticity and neural circuit maintenance. Alterations in adult SVZ neurogenesis are early events in AD, and impaired adult neurogenesis is influenced by the accumulation of intracellular Aß. Although Aß-overexpressing transgenic 5XFAD mice are an AD animal model well representative of Aß-related pathologies in the brain, the characterization of altered adult SVZ neurogenesis following AD progression in 5XFAD mice has not been thoroughly examined. Therefore, we validated the characterization of adult SVZ neurogenesis changes with AD progression in 2-, 4-, 8-, and 11-monthold male 5XFAD mice. We first investigated the Aß accumulation in the SVZ using the 4G8 antibody. We observed intracellular Aß accumulation in the SVZ of 2-month-old 5XFAD mice. In addition, 5XFAD mice exhibited significantly increased Aß deposition in the SVZ with age. Next, we performed a histological analysis to investigate changes in various phases of adult neurogenesis, such as quiescence, proliferation, and differentiation, in SVZ. Compared to age-matched wild-type (WT) mice, quiescent neural stem cells were reduced in 5XFAD mice from 2-11 months of age. Moreover, proliferative neural stem cells were decreased in 5XFAD mice from 2 to 8 months of age. Furthermore, differentiations of neuroblasts were diminished in 5XFAD mice from 2-11 months of age. Intriguingly, we found that adult SVZ neurogenesis was reduced with aging in healthy mice. Taken together, our results revealed that impairment of adult SVZ neurogenesis appears with aging or AD progression. [BMB Reports 2023; 56(9): 520-525].


Assuntos
Doença de Alzheimer , Células-Tronco Neurais , Doenças Neurodegenerativas , Camundongos , Masculino , Animais , Doença de Alzheimer/patologia , Neurogênese , Células-Tronco Neurais/patologia , Camundongos Transgênicos , Modelos Animais de Doenças , Peptídeos beta-Amiloides
7.
Polymers (Basel) ; 14(24)2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36559894

RESUMO

In the use of the medical devices, it is essential to prevent the attachment of bacteria to the device surface or to kill the attached bacteria. To kill bacteria, many researchers have used antibiotics or studied nanostructure-based antibacterial surfaces, which rely on mechanical antibacterial methods. Several polymers are widely used for device fabrication, one of which is polycaprolactone (PCL). PCL is biocompatible, biodegradable, easy to fabricate using 3D printing, relatively inexpensive and its quality is easily controlled; therefore, there are various approaches to its use in bio-applications. In addition, it is an FDA-approved material, so it is often used as an implantable material in the human body. However, PCL has no inherent antibacterial function, so it is necessary to develop antibacterial functions in scaffold or film-based PCL medical devices. In this study, process parameters for nanopillar fabrication were established through a simple thermal imprinting method with PCL. Finally, a PCL film with a flexible and transparent nanopillar structure was produced, and the mechano-bactericidal potential was demonstrated using only one PCL material. PCL with nanopillars showed bactericidal ability against Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) bacteria cultured on its surface that resulted in membrane damage and death due to contact with nanopillars. Additionally, bacteriostatic results were shown to inhibit bacterial growth and activity of Staphylococcus aureus (S. aureus) on PCL nanostructured columns. The fabricated nanopillar structure has confirmed that mechanically induced antibacterial function and can be applied to implantable medical devices.

8.
ACS Appl Mater Interfaces ; 14(34): 39478-39488, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-35959590

RESUMO

Over the past few decades, extensive research efforts have been devoted to developing surfaces with unique functionalities, such as controlled wettability, antibiofouling, antifogging, and anti-icing behavior, for applications in a wide range of fields, including biomedical devices, optical instruments, microfluidics, and energy conservation and harvesting. However, many of the previously reported approaches have limitations with regard to eco-friendliness, multifunctionality, long-term stability and efficacy, and cost effectiveness. Herein, we propose a scalable bifunctional surface that simultaneously exhibits excellent antifogging and antibiofouling properties based on the synergistic integration of an eco-friendly and bio-friendly polyethylene glycol (PEG) hydrogel, oleamide (OA), and nanoscale architectures in a single flexible platform. We demonstrate that the PEG-OA-nanostructure hybrid exhibits excellent antifogging performance owing to its enhanced water absorption and spreading properties. We further show that the triple hybrid exhibits notable biofilm resistance without the use of toxic biocides or chemicals by integrating the "fouling-resistant" mechanism of the PEG hydrogel, the "fouling-release" mechanism of OA, and the "foulant-killing" mechanism of the nanostructures.

9.
ACS Appl Bio Mater ; 5(6): 3006-3012, 2022 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-35609304

RESUMO

Antibacterial surfaces are one of the most important surfaces in the medical and marine industries. Many researchers are studying antibacterial surfaces to kill bacteria or prevent adhesions. Various materials and structures are applied to the surface to inhibit the adhesion of bacteria or kill the adhered bacteria. Nowadays, a dual strategy is preferred rather than a single strategy. In this study, nanopillar structures were fabricated using polyethylene glycol dimethacrylate (PEGDMA), which has an antifouling effect. Afterward, the fabricated nanostructured PEGDMA was assessed to confirm the intrinsic antibacterial effect and mechanically induced antibacterial functions. The adhesion of Gram-negative and Gram-positive bacteria can be effectively reduced by the PEG hydration layer formation, steric repulsion, and flexible chain, and the nanostructure can damage the bacterial membrane. In addition, we performed antibacterial experiments on a nanopillar-structured surface made of PEGDMA. Furthermore, we revealed that the mechanical robustness of the nanopillared surface was superior to that of the nanocone-structured surface using computational analysis. Nanopillar structures fabricated using PEGDMA are promising candidates for antifouling and antibacterial surfaces and can be applied in various industries.


Assuntos
Aderência Bacteriana , Nanoestruturas , Antibacterianos/farmacologia , Bactérias , Metacrilatos , Nanoestruturas/química , Polietilenoglicóis/farmacologia , Propriedades de Superfície
10.
Soft Matter ; 17(7): 1715-1723, 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33538288

RESUMO

Biofouling of tubular fluidic devices limits the stability, accuracy, and long-term uses of lab-on-a-chip systems. Healthcare-associated infection by biofilm formations on body-indwelling and extracorporeal tubular medical devices is also a major cause of mortality and morbidity in patients. Although diverse antifouling techniques have been developed to prevent bacterial contamination of fluidic devices based on antimicrobial materials or nanoscale architectures, they still have limitations in biocompatibility, long-term activity, and durability. In this study, a new conceptual tubular fluidic device model that can effectively suppress bacterial contamination based on dynamic surface motions without using bactericidal materials or nanostructures is proposed. The fluidic device is composed of a magneto-responsive multilayered composite. The composite tube can generate dynamic surface deformation with controlled geometries along its inner wall in response to a remote magnetic field. The magnetic field-derived surface wave induces the generation of vortices near the inner wall surface of the tube, enabling sweeping of bacterial cells from the surface. As a result, the dynamic composite tube could effectively prevent biofilm formation for an extended time of 14 days without surface modification with chemical substances or nanostructures.


Assuntos
Anti-Infecciosos , Incrustação Biológica , Nanoestruturas , Antibacterianos , Bactérias , Biofilmes , Incrustação Biológica/prevenção & controle , Humanos
11.
J Ren Nutr ; 31(6): 593-601, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33323326

RESUMO

OBJECTIVE: Although dietary modification is a critical component of chronic kidney disease (CKD) management, compliance with dietary recommendations is often suboptimal. This prospective intervention study was conducted to evaluate the effects and adherence of intensive, individualized nutrition counseling in CKD patients from a single nation Asian ethnic group. METHODS: Patients with Stages 3 and 4 CKD were recruited from a tertiary hospital outpatient clinic in Korea. The intensive group received 3 monthly sessions of individualized intensive nutrition counseling. The control group received a one-time group program. The intensive group was compared with the control group at 3 months. RESULTS: A total of 59 patients were enrolled, and 42 (71.2%) completed the study (23/32 of the intensive group; 19/27 of the control group). The mean age of the patients was 64.7 ± 12.5 years, and 81% were male. The most common nutritional diagnosis was an excessive intake of sodium (Na, 97.6%), followed by potassium (K, 78.6%), protein (52.4%), and phosphorus (P, 31.0%). After 3 months of nutrition counseling, K and P intakes decreased significantly in both the intensive group (K, 2,760.9 ± 677.4 vs. 1,500.7 ± 398.5 mg/d, P < .001; P, 1,010.5 ± 247.4 vs. 631.3 ± 178.1 mg/d, P < .001) and the control group (K, 2,090.8 ± 765.3 vs. 1,703.9 ± 490.0 mg/d, P = .036; P, 807.2 ± 163.8 vs. 679.1 ± 175.9 mg/d, P = .044). Meanwhile, protein (68.3 ± 21.8 vs. 45.4 ± 10.1 g/d, P = .001), Na (4,009.8 ± 1,418.2 vs. 2,224.6 ± 759.8 mg/d, P < .001), and energy intakes (1,857.1 ± 411.5 vs. 1,273.7 ± 231.5 kcal, P < .001) decreased in the intensive group, but were comparable in the control group. Notably, BMI decreased (BMI, 25.4 ± 2.5 vs. 24.9 ± 2.9 kg/m2, P = .014) while eGFR (43.1 ± 11.8 vs. 48.9 ± 13.7 mL/min/1.73m2, P = .002) improved significantly in the intensive group only. CONCLUSION: Intensive individualized nutrition counseling results in better adherence to dietary recommendations and improvement in kidney function in CKD patients.


Assuntos
Estado Nutricional , Insuficiência Renal Crônica , Idoso , Aconselhamento , Humanos , Rim , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia
12.
Sci Adv ; 5(11): eaax8935, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31819902

RESUMO

Diverse bioinspired antifouling strategies have demonstrated effective fouling-resistant properties with good biocompatibility, sustainability, and long-term activity. However, previous studies on bioinspired antifouling materials have mainly focused on material aspects or static architectures of nature without serious consideration of kinetic topographies or dynamic motion. Here, we propose a magnetically responsive multilayered composite that can generate coordinated, undulatory topographical waves with controlled length and time scales as a new class of dynamic antifouling materials. The undulatory surface waves of the dynamic composite induce local and global vortices near the material surface and thereby sweep away foulants from the surface, fundamentally inhibiting their initial attachment. As a result, the dynamic composite material with undulating topographical waves provides an effective means for efficient suppression of biofilm formation without surface modification with chemical moieties or nanoscale architectures.

13.
ACS Nano ; 13(10): 11181-11193, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31518110

RESUMO

Vertically aligned nanomaterials, such as nanowires and nanoneedles, hold strong potential as efficient platforms onto which living cells or tissues can be interfaced for use in advanced biomedical applications. However, their rigid mechanical properties and complex fabrication processes hinder their integration onto flexible, tissue-adaptable, and large-area patch-type scaffolds, limiting their practical applications. In this study, we present a highly flexible patch that possesses a spiky hydrogel nanostructure array as a transplantable platform for enhancing the growth and differentiation of stem cells and efficiently suppressing biofilm formation. In vitro studies show that the hydrogel nanospike patch imposes a strong physical stimulus to the membranes of stem cells and enhances their osteogenic, chondrogenic, and adipogenic differentiation and the secretion of crucial soluble factors without altering cell viability. At the same time, the array exhibits effective bactericidal properties against Gram-positive and Gram-negative bacteria. In vivo studies further demonstrate that the flexible hydrogel patch with its spiky vertical nanostructures significantly promotes the regeneration of damaged cranial bone tissues while suppressing pathogenic bacterial infections in mouse models.


Assuntos
Antibacterianos/farmacologia , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/citologia , Nanoestruturas/química , Animais , Antibacterianos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/patogenicidade , Humanos , Hidrogéis/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Osteogênese/efeitos dos fármacos , Engenharia Tecidual , Alicerces Teciduais/química
14.
Int J Mol Sci ; 20(16)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426329

RESUMO

It is widely known that the degeneration of neural circuits is prominent in the brains of Alzheimer's disease (AD) patients. The reciprocal connectivity of the medial septum (MS) and hippocampus, which constitutes the septo-hippocampo-septal (SHS) loop, is known to be associated with learning and memory. Despite the importance of the reciprocal projections between the MS and hippocampus in AD, the alteration of bidirectional connectivity between two structures has not yet been investigated at the mesoscale level. In this study, we adopted AD animal model, five familial AD mutations (5XFAD) mice, and anterograde and retrograde tracers, BDA and DiI, respectively, to visualize the pathology-related changes in topographical connectivity of the SHS loop in the 5XFAD brain. By comparing 4.5-month-old and 14-month-old 5XFAD mice, we successfully identified key circuit components of the SHS loop altered in 5XFAD brains. Remarkably, the SHS loop began to degenerate in 4.5-month-old 5XFAD mice before the onset of neuronal loss. The impairment of connectivity between the MS and hippocampus was accelerated in 14-month-old 5XFAD mice. These results demonstrate, for the first time, topographical evidence for the degradation of the interconnection between the MS and hippocampus at the mesoscale level in a mouse model of AD. Our results provide structural and functional insights into the interconnectivity of the MS and hippocampus, which will inform the use and development of various therapeutic approaches that target neural circuits for the treatment of AD.


Assuntos
Doença de Alzheimer/patologia , Hipocampo/patologia , Septo do Cérebro/patologia , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Modelos Animais de Doenças , Feminino , Hipocampo/metabolismo , Humanos , Masculino , Camundongos Transgênicos , Mutação , Vias Neurais/metabolismo , Vias Neurais/patologia , Presenilina-1/genética , Septo do Cérebro/metabolismo
15.
Int J Mol Sci ; 20(12)2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234321

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by neurodegeneration and cognitive deficits. Amyloid beta (Aß) peptide is known to be a major cause of AD pathogenesis. However, recent studies have clarified that mitochondrial deficiency is also a mediator or trigger for AD development. Interestingly, red ginseng (RG) has been demonstrated to have beneficial effects on AD pathology. However, there is no evidence showing whether RG extract (RGE) can inhibit the mitochondrial deficit-mediated pathology in the experimental models of AD. The effects of RGE on Aß-mediated mitochondrial deficiency were investigated in both HT22 mouse hippocampal neuronal cells and the brains of 5XFAD Aß-overexpressing transgenic mice. To examine whether RGE can affect mitochondria-related pathology, we used immunohistostaining to study the effects of RGE on Aß accumulation, neuroinflammation, neurodegeneration, and impaired adult hippocampal neurogenesis in hippocampal formation of 5XFAD mice. In vitro and in vivo findings indicated that RGE significantly improves Aß-induced mitochondrial pathology. In addition, RGE significantly ameliorated AD-related pathology, such as Aß deposition, gliosis, and neuronal loss, and deficits in adult hippocampal neurogenesis in brains with AD. Our results suggest that RGE may be a mitochondria-targeting agent for the treatment of AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Mitocôndrias/efeitos dos fármacos , Panax , Preparações de Plantas/uso terapêutico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Linhagem Celular , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Panax/química , Preparações de Plantas/química
17.
ACS Appl Bio Mater ; 2(10): 4242-4248, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-35021439

RESUMO

The eggshell membrane (ESM) is usually regarded as an agricultural byproduct waste, even though it has unique properties as a biomaterial. In particular, the ESM has a flexible and highly pure microfibrous network structure that can be used as an artificial extracellular matrix (ECM) platform for engraftment or as a tissue-engineered scaffold. In this study, flexible and functional scaffolds were constructed using an ESM and graphene, and their applicability for stem cell and tissue engineering was analyzed. The graphene-layered ESM (GEM) scaffolds show enhanced characteristics, such as ECM-like hierarchical micro- and nanostructures and better mechanical and hydrophilic properties than those of a raw ESM. The GEM scaffolds can control the adhesion properties of stem cells, enhancing the proliferation and osteogenic properties of the cells compared with the effects of a raw ESM. Additionally, the GEM scaffolds can improve the secretion of growth factors from stem cells, possibly through enhanced cell-substrate interactions, thereby promoting the proliferation and differentiation of these cells.

18.
ACS Macro Lett ; 8(1): 64-69, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35619411

RESUMO

Despite extensive efforts toward developing antibiofilm materials, efficient prevention of biofilm formation remains challenging. Approaches based on a single strategy using either bactericidal material, antifouling coatings, or nanopatterning have shown limited performance in the prevention of biofilm formation. This study presents a hybrid strategy based on a lipid-hydrogel-nanotopography hybrid for the development of a highly efficient and durable biofilm-resistant material. The hybrid material consists of nanostructured antifouling, biocompatible polyethylene glycol-based polymer grafted with an antifouling zwitterionic polymer of 2-methacryloyloxyethyl phosphorylcholine. Based on the unique composite nanostructures, the lipid-hydrogel-nanostructure hybrid exhibits superior dual functionalities of antifouling and bactericidal activities against Gram-negative and Gram-positive bacteria, compared with those of surfaces with simple nanostructures or antifouling coatings. Additionally, it preserves the robust antibiofilm activity even when the material is damaged under external mechanical stimuli thanks to the polymeric composite nanostructure.

19.
Small ; 14(52): e1803411, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30417603

RESUMO

Low-dimensional nanomaterials are widely adopted as active sensing elements for electronic skins. When the nanomaterials are integrated with microscale architectures, the performance of the electronic skin is significantly altered. Here, it is shown that a high-performance flexible and stretchable electronic skin can be produced by incorporating a piezoresistive carbon nanotube composite into a hierarchical topography of micropillar-wrinkle hybrid architectures that mimic wrinkles and folds in human skin. Owing to the unique hierarchical topography of the hybrid architectures, the hybrid electronic skin exhibits versatile and superior sensing performance, which includes multiaxial force detection (normal, bending, and tensile stresses), remarkable sensitivity (20.9 kPa-1 , 17.7 mm-1 , and gauge factor of 707 each for normal, bending, and tensile stresses), ultrabroad sensing range (normal stress = 0-270 kPa, bending radius of curvature = 1-6.5 mm, and tensile strain = 0-50%), sensing tunability, fast response time (24 ms), and high durability (>10 000 cycles). Measurements of spatial distributions of diverse mechanical stimuli are also demonstrated with the multipixel electronic skin. The stress-strain behavior of the hybrid structure is investigated by finite element analysis to elucidate the underlying principle of the superior sensing performance of the electronic skin.

20.
ACS Macro Lett ; 6(5): 561-565, 2017 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35610879

RESUMO

We present rheological and mechanical behaviors of a partially cured photopolymer. When an ultraviolet (UV)-curable resin is exposed to UV light in atmospheric conditions, a partially cured layer is formed on the top of the resin owing to inhibitory effects of oxygen. Interestingly, such a partially cured resin behaves like a Bingham plastic with a yield stress, being a rigid solid at low shear stress and a viscous liquid at high stress. Unlike typical Bingham plastic materials, however, deformation rate saturation is observed with an increase in applied stress, which is attributed to the gradient in the degree of photopolymerization of the resin (termed "gradient Bingham plastic"). This gradient Bingham plastic can be utilized for the robust fabrication of diverse 3D, multiscale structures.

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