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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.
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Anti-Infecciosos , Incrustação Biológica , Nanoestruturas , Antibacterianos , Bactérias , Biofilmes , Incrustação Biológica/prevenção & controle , HumanosRESUMO
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.
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Estado Nutricional , Insuficiência Renal Crônica , Idoso , Aconselhamento , Humanos , Rim , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapiaRESUMO
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.
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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/metabolismoRESUMO
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.
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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/químicaRESUMO
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.
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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%).
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Nanoestruturas , Odonatos , Animais , Staphylococcus aureus/fisiologia , Escherichia coli , Nanoestruturas/química , Bactérias , Antibacterianos/farmacologia , Antibacterianos/química , Propriedades de SuperfícieRESUMO
To date, several off-the-shelf products such as artificial blood vessel grafts have been reported and clinically tested for small diameter vessel (SDV) replacement. However, conventional artificial blood vessel grafts lack endothelium and, thus, are not ideal for SDV transplantation as they can cause thrombosis. In addition, a successful artificial blood vessel graft for SDV must have sufficient mechanical properties to withstand various external stresses. Here, we developed a spontaneous cellular assembly SDV (S-SDV) that develops without additional intervention. By improving the dragging 3D printing technique, SDV constructs with free-form, multilayers and controllable pore size can be fabricated at once. Then, The S-SDV filled in the natural polymer bioink containing human umbilical vein endothelial cells (HUVECs) and human aorta smooth muscle cells (HAoSMCs). The endothelium can be induced by migration and self-assembly of endothelial cells through pores of the SDV construct. The antiplatelet adhesion of the formed endothelium on the luminal surface was also confirmed. In addition, this S-SDV had sufficient mechanical properties (burst pressure, suture retention, leakage test) for transplantation. We believe that the S-SDV could address the challenges of conventional SDVs: notably, endothelial formation and mechanical properties. In particular, the S-SDV can be designed simply as a free-form structure with a desired pore size. Since endothelial formation through the pore is easy even in free-form constructs, it is expected to be useful for endothelial formation in vascular structures with branch or curve shapes, and in other tubular tissues such as the esophagus.
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In this paper, we explore the development of a multi-functional surface designed to tackle the challenges posed by Staphylococcus aureus (S. aureus), a common opportunistic pathogen. Infections caused by S. aureus during surgical procedures highlight the need for effective strategies to inhibit its adhesion, growth, and colonization, particularly on the surfaces of invasive medical devices. Until now, most existing research has focused on nanopillar structures (positive topographies). Uniform nanopillar arrays have been shown to control bacterial behavior based on the spacing between nanopillars. However, nanopillar structures are susceptible to external friction, impact, and force, making it challenging to maintain their antibacterial properties. Therefore, in this study, we investigate the antibacterial behavior of nanohole structures, which offer relatively superior mechanical robustness compared to nanopillars. Moreover, for applications in medical devices such as laparoscopes, there is a pressing need for surfaces that are not only transparent and flexible (or curved) but are also equipped with antibacterial properties. Our study introduces a scalable multi-functional surface that synergistically combines antibacterial and anti-fog properties. This is achieved by fabricating thin films with variously sized holes (ranging from 0.3 µm to 4 µm) using polyurethane acrylate (PUA). We assessed the activity of S. aureus on these surfaces and found that a 1 µm-diameter-hole pattern significantly reduced the presence of live S. aureus, without any detection of dead S. aureus. This bacteriostatic effect is attributed to the restricted proliferation due to the confined area provided by the hole pattern. However, the persistence of some live S. aureus on the surface necessitates further measures to minimize bacterial adhesion and enhance antibacterial effectiveness. To address this challenge, we coated the zwitterionic polymer 2-methacryloyloxyethyl phosphorylcholine (MPC) onto the nanohole pattern surface to reduce S. aureus adhesion. Moreover, in long-term experiments on surfaces, the MPC-coated effectively inhibited the colonization of S. aureus (18 h; 82%, 7 days; 83%, and 14 days; 68% antibacterial rate). By integrating PUA, MPC, and nanohole architectures into a single, flexible platform, we achieved a multi-functional surface catering to transparency, anti-fogging, and anti-biofouling requirements. This innovative approach marks a significant advancement in surface engineering, offering a versatile solution applicable in various fields, particularly in preventing S. aureus contamination in invasive medical devices like laparoscopes. The resultant surface, characterized by its transparency, flexibility, and antibacterial functionality, stands out as a promising candidate for mitigating S. aureus-related risks in medical applications.
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Antibacterianos , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Propriedades de Superfície , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Nanoestruturas/química , Aderência Bacteriana/efeitos dos fármacos , Tamanho da PartículaRESUMO
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.
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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.
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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 DoençasRESUMO
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.
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Doença de Alzheimer , Benzilisoquinolinas , Síndromes Neurotóxicas , Humanos , Simulação de Acoplamento Molecular , Peptídeos beta-Amiloides , Doença de Alzheimer/tratamento farmacológico , Dispositivos Lab-On-A-Chip , TecnologiaRESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanied by irreversible cognitive impairment. A deleterious feedback loop between oxidative stress and neuroinflammation in early AD exacerbates AD-related pathology. Platycodon grandiflorum root extract (PGE) has antioxidant and anti-inflammatory effects in several organs. However, the mechanisms underlying the effects of PGE in the brain remain unclear, particularly regarding its impact on oxidative/inflammatory damage and Aß deposition. Thus, we aim to identify the mechanism through which PGE inhibits Aß deposition and oxidative stress in the brain by conducting biochemical and histological analyses. First, to explore the antioxidant mechanism of PGE in the brain, we induced oxidative stress in mice injected with scopolamine and investigated the effect of PGE on cognitive decline and oxidative damage. We also assessed the effect of PGE on reactive oxygen species (ROS) generation and the expressions of antioxidant enzymes and neurotrophic factor in H2O2- and Aß-treated HT22 hippocampal cells. Next, we investigated whether PGE, which showed antioxidant effects, could reduce Aß deposition by mitigating neuroinflammation, especially microglial phagocytosis. We directly verified the effect of PGE on microglial phagocytosis, microglial activation markers, and pro-inflammatory cytokines in Aß-treated BV2 microglial cells. Moreover, we examined the effect of PGE on neuroinflammation, inducing microglial responses in Aß-overexpressing 5XFAD transgenic mice. PGE exerts antioxidant effects in the brain, enhances microglial phagocytosis of Aß, and inhibits neuroinflammation and Aß deposition, ultimately preventing neuronal cell death in AD. Taken together, our findings indicate that the therapeutic potential of PGE in AD is mediated by its targeting of multiple pathological processes.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Antioxidantes , Microglia , Doenças Neuroinflamatórias , Estresse Oxidativo , Extratos Vegetais , Raízes de Plantas , Platycodon , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Camundongos , Platycodon/química , Peptídeos beta-Amiloides/metabolismo , Masculino , Raízes de Plantas/química , Microglia/efeitos dos fármacos , Microglia/metabolismo , Antioxidantes/farmacologia , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Linhagem Celular , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Modelos Animais de Doenças , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Fagocitose/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Camundongos Transgênicos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologiaRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder associated with behavioral and cognitive impairments. Unfortunately, the drugs the Food and Drug Administration currently approved for AD have shown low effectiveness in delaying the progression of the disease. The focus has shifted to non-pharmacological interventions (NPIs) because of the challenges associated with pharmacological treatments for AD. One such intervention is environmental enrichment (EE), which has been reported to restore cognitive decline associated with AD effectively. However, the therapeutic mechanisms by which EE improves symptoms associated with AD remain unclear. Therefore, this study aimed to reveal the mechanisms underlying the alleviating effects of EE on AD symptoms using histological, proteomic, and neurotransmitter-related analyses. Wild-type (WT) and 5XFAD mice were maintained in standard housing or EE conditions for 4 weeks. First, we confirmed the mitigating effects of EE on cognitive impairment in an AD animal model. Then, histological analysis revealed that EE reduced Aß accumulation, neuroinflammation, neuronal death, and synaptic loss in the AD brain. Moreover, proteomic analysis by liquid chromatography-tandem mass spectrometry showed that EE enhanced synapse- and neurotransmitter-related networks and upregulated synapse- and neurotransmitter-related proteins in the AD brain. Furthermore, neurotransmitter-related analyses showed an increase in acetylcholine and serotonin concentrations as well as a decrease in polyamine concentration in the frontal cortex and hippocampus of 5XFAD mice raised under EE conditions. Our findings demonstrate that EE restores cognitive impairment by alleviating AD pathology and regulating synapse-related proteins and neurotransmitters. Our study provided neurological evidence for the application of NPIs in treating AD.
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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].
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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-AmiloidesRESUMO
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.
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Doença de Alzheimer , Humanos , Camundongos , Animais , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Pirogalol/farmacologia , Proteínas tau/metabolismo , Camundongos TransgênicosRESUMO
This paper presents the fabrication of a thin and flexible polydimethylsiloxane (PDMS) stamp with a thickness of a few tens of um and its application to nanoimprint lithography (NIL). The PDMS material generally has a low elastic modulus and high adhesive characteristics. Therefore, after being treated, the thin PDMS stamp is easily deformed and torn, adhering to itself and other materials. This paper introduces the use of a metal ring around the flange of a thin PDMS stamp to assist with the handling of this material. A PDMS stamp with a motheye pattern in nanometer scale was inserted between a substrate and a microstamp with concave patterns in micrometer scale. Subsequently, three-dimensional (3D) hybrid nano/micropatterns were fabricated by pressing these two stamps and curing the resist. The fabricated hybrid patterns were measured and verified in both the microscale and nanoscale. The process, termed "dual NIL," can be applied to the fabrication of optical components or bio-sensors that require repetitive nanopatterns on micropatterns.
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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.
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Aderência Bacteriana , Nanoestruturas , Antibacterianos/farmacologia , Bactérias , Metacrilatos , Nanoestruturas/química , Polietilenoglicóis/farmacologia , Propriedades de SuperfícieRESUMO
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.
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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.