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1.
Biofabrication ; 16(2)2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38176079

RESUMO

Human induced pluripotent stem cell (iPSC)-derived brain organoids have potential to recapitulate the earliest stages of brain development, serving as an effectivein vitromodel for studying both normal brain development and disorders. However, current brain organoid culture methods face several challenges, including low throughput, high variability in organoid generation, and time-consuming, multiple transfer and encapsulation of cells in hydrogels throughout the culture. These limitations hinder the widespread application of brain organoids including high-throughput assessment of compounds in clinical and industrial lab settings. In this study, we demonstrate a straightforward approach of generating multiple cerebral organoids from iPSCs on a pillar plate platform, eliminating the need for labor-intensive, multiple transfer and encapsulation steps to ensure the reproducible generation of cerebral organoids. We formed embryoid bodies in an ultra-low attachment 384-well plate and subsequently transferred them to the pillar plate containing Matrigel, using a straightforward sandwiching and inverting method. Each pillar on the pillar plate contains a single spheroid, and the success rate of spheroid transfer was in a range of 95%-100%. Using this approach, we robustly generated cerebral organoids on the pillar plate and demonstrated an intra-batch coefficient of variation below 9%-19% based on ATP-based cell viability and compound treatment. Notably, our spheroid transfer method in combination with the pillar plate allows miniaturized culture of cerebral organoids, alleviates the issue of organoid variability, and has potential to significantly enhance assay throughput by allowingin situorganoid assessment as compared to conventional organoid culture in 6-/24-well plates, petri dishes, and spinner flasks.


Assuntos
Células-Tronco Pluripotentes Induzidas , Humanos , Organoides , Encéfalo , Técnicas de Cultura de Células/métodos
2.
Health Commun ; 39(5): 937-944, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37038244

RESUMO

Applying fuzzy trace theory to misinformation related to COVID-19, the present study (a) examines the roles of gist knowledge in predicting misinformation acceptance, and (b) further examines whether a gist cue in fact checking scales affects the level of gist knowledge. Study 1 (a survey) showed that categorical gist knowledge was negatively related to misinformation acceptance, whereas ordinal gist knowledge was not, when both types of knowledge were included in the model. In addition, Study 2 (an experiment) showed that fact checking scales containing a categorical gist cue resulted in greater categorical gist knowledge.


Assuntos
Comunicação , Humanos , Inquéritos e Questionários
3.
Biotechnol Bioeng ; 121(2): 489-506, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38013504

RESUMO

Brain organoids are self-organized, three-dimensional (3D) aggregates derived from pluripotent stem cells that have cell types and cellular architectures resembling those of the developing human brain. The current understanding of human brain developmental processes and neurological disorders has advanced significantly with the introduction of this in vitro model. Brain organoids serve as a translational link between two-dimensional (2D) cultures and in vivo models which imitate the neural tube formation at the early and late stages and the differentiation of neuroepithelium with whole-brain regionalization. In addition, the generation of region-specific brain organoids made it possible to investigate the pathogenic and etiological aspects of acquired and inherited brain disease along with drug discovery and drug toxicity testing. In this review article, we first summarize an overview of the existing methods and platforms used for generating brain organoids and their limitations and then discuss the recent advancement in brain organoid technology. In addition, we discuss how brain organoids have been used to model aspects of neurodevelopmental and neurodegenerative diseases, including autism spectrum disorder (ASD), Rett syndrome, Zika virus-related microcephaly, Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD).


Assuntos
Transtorno do Espectro Autista , Células-Tronco Pluripotentes Induzidas , Doenças do Sistema Nervoso , Infecção por Zika virus , Zika virus , Humanos , Encéfalo , Organoides
4.
Sensors (Basel) ; 23(23)2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38067755

RESUMO

This paper describes a signal quality classification method for arm ballistocardiogram (BCG), which has the potential for non-invasive and continuous blood pressure measurement. An advantage of the BCG signal for wearable devices is that it can easily be measured using accelerometers. However, the BCG signal is also susceptible to noise caused by motion artifacts. This distortion leads to errors in blood pressure estimation, thereby lowering the performance of blood pressure measurement based on BCG. In this study, to prevent such performance degradation, a binary classification model was created to distinguish between high-quality versus low-quality BCG signals. To estimate the most accurate model, four time-series imaging methods (recurrence plot, the Gramain angular summation field, the Gramain angular difference field, and the Markov transition field) were studied to convert the temporal BCG signal associated with each heartbeat into a 448 × 448 pixel image, and the image was classified using CNN models such as ResNet, SqueezeNet, DenseNet, and LeNet. A total of 9626 BCG beats were used for training, validation, and testing. The experimental results showed that the ResNet and SqueezeNet models with the Gramain angular difference field method achieved a binary classification accuracy of up to 87.5%.


Assuntos
Algoritmos , Balistocardiografia , Balistocardiografia/métodos , Frequência Cardíaca/fisiologia , Artefatos , Movimento (Física)
5.
ACS Appl Mater Interfaces ; 15(48): 55466-55485, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37991753

RESUMO

Despite the effectiveness and selectivity of natural enzymes, their instability has paved the way for developing nanozymes with high peroxidase activity using a straightforward technique, thereby expanding their potential for multifunctional applications. Herein, meso-copper-Prussian blue microcubes (Meso-Cu-PBMCs) nanozymes were successfully prepared via a cost-effective hydrothermal route. It was found that the Cu-PBMCs nanozymes, with three-dimensional (3D) mesoporous cubic morphologies, exhibited an excellent peroxidase-like property. Based on the high affinity of Meso-Cu-PBMCs toward H2O2 (Km = 0.226 µM) and TMB (Km = 0.407 mM), a colorimetric sensor for in situ H2O2 detection was constructed. On account of the high catalytic activity, affinity, and cascade strategy, the Meso-Cu-PBMCs nanozyme generated rapid multicolor displays at varying H2O2 concentrations. Under optimized conditions, the proposed sensor exhibits a preferable sensitivity of 18.14 µA µM-1, a linear range of 10 nM-25 mM, and a detection limit of 6.36 nM (S/N = 10). The reliability of the sensor was verified by detecting H2O2 in spiked human blood serum and milk samples, as well as by detecting in situ H2O2 generated from the neuron cell SH-SY5Y. Besides, the Meso-Cu-PBMCs nanozyme facilitated the catalysis of H2O2 in cancer cells, generating •OH radicals that induce the death of cancer cells (HCT-116 colon cancer cells), which holds substantial potential for application in chemodynamic therapy (CDT). This proposed strategy holds promise for simple, rapid, inexpensive, and effective intracellular biosensing and offers a novel approach to improve CDT efficacy.


Assuntos
Peróxido de Hidrogênio , Neuroblastoma , Humanos , Glucose , Cobre , Colorimetria/métodos , Reprodutibilidade dos Testes , Peroxidase/metabolismo , Peroxidases
6.
Res Sq ; 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37790478

RESUMO

Background: Despite thousands of variants identified by genome-wide association studies (GWAS) to be associated with autism spectrum disorder (ASD), it is unclear which mutations are causal because most are noncoding. Consequently, reliable diagnostic biomarkers are lacking. RNA-seq analysis captures biomolecular complexity that GWAS cannot by considering transcriptomic patterns. Therefore, integrating DNA and RNA testing may reveal causal genes and useful biomarkers for ASD. Methods: We performed gene-based association studies using an adaptive test method with GWAS summary statistics from two large Psychiatric Genomics Consortium (PGC) datasets (ASD2019: 18,382 cases and 27,969 controls; ASD2017: 6,197 cases and 7,377 controls). We also investigated differential expression for genes identified with the adaptive test using an RNA-seq dataset (GSE30573: 3 cases and 3 controls) and DESeq2. Results: We identified 5 genes significantly associated with ASD in ASD2019 (KIZ-AS1, p = 8.67×10- 10; KIZ, p = 1.16×10- 9; XRN2, p = 7.73×10- 9; SOX7, p = 2.22×10- 7; LOC101929229 (also known as PINX1-DT), p = 2.14×10- 6). Two of the five genes were replicated in ASD2017: SOX7 (p = 0.00087) and LOC101929229 (p = 0.009), and KIZ was close to the replication boundary of replication (p = 0.06). We identified significant expression differences for SOX7 (p = 0.0017, adjusted p = 0.0085), LOC101929229 (p = 5.83×10- 7, adjusted p = 1.18×10- 5), and KIZ (p = 0.00099, adjusted p = 0.0055). SOX7 encodes a transcription factor that regulates developmental pathways, alterations in which may contribute to ASD. Limitations: The limitation of the gene-based analysis is the reliance on a reference population for estimating linkage disequilibrium between variants. The similarity of this reference population to the population of study is crucial to the accuracy of many gene-based analyses, including those performed in this study. As a result, the extent of our findings is limited to European populations, as this was our reference of choice. Future work includes a tighter integration of DNA and RNA information as well as extensions to non-European populations that have been under-researched. Conclusions: These findings suggest that SOX7 and its related SOX family genes encode transcription factors that are critical to the downregulation of the canonical Wnt/ß-catenin signaling pathway, an important developmental signaling pathway, providing credence to the biologic plausibility of the association between gene SOX7 and autism spectrum disorder.

7.
bioRxiv ; 2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37905145

RESUMO

Human induced pluripotent stem cell (iPSCs)-derived brain organoids have potential to recapitulate the earliest stages of brain development, serving as an effective in vitro model for studying both normal brain development and disorders. However, current brain organoid culture methods face several challenges, including low throughput, high variability in organoid generation, and time-consuming, multiple transfer and encapsulation of cells in hydrogels throughout the culture. These limitations hinder the widespread application of brain organoids including high-throughput assessment of compounds in clinical and industrial lab settings. In this study, we demonstrate a straightforward approach of generating multiple cerebral organoids from iPSCs on a pillar plate platform, eliminating the need for labor-intensive, multiple transfer and encapsulation steps to ensure the reproducible generation of cerebral organoids. We formed embryoid bodies (EBs) in an ultra-low attachment (ULA) 384-well plate and subsequently transferred them to the pillar plate containing Matrigel, using a straightforward sandwiching and inverting method. Each pillar on the pillar plate contains a single spheroid, and the success rate of spheroid transfer was in a range of 95 - 100%. By differentiating the EBs on the pillar plate, we achieved robust generation of cerebral organoids with a coefficient of variation (CV) below 19%. Notably, our spheroid transfer method in combination with the pillar plate allows miniaturized culture of cerebral organoids, alleviates the issue of organoid variability, and has potential to significantly enhance assay throughput by allowing in situ organoid assessment as compared to conventional organoid culture in 6-/24-well plates, petri dishes, and spinner flasks.

8.
bioRxiv ; 2023 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-37292933

RESUMO

Background: Genome-wide association studies and next generation sequencing data analyses based on DNA information have identified thousands of mutations associated with autism spectrum disorder (ASD). However, more than 99% of identified mutations are non-coding. Thus, it is unclear which of these mutations might be functional and thus potentially causal variants. Transcriptomic profiling using total RNA-sequencing has been one of the most utilized approaches to link protein levels to genetic information at the molecular level. The transcriptome captures molecular genomic complexity that the DNA sequence solely does not. Some mutations alter a gene's DNA sequence but do not necessarily change expression and/or protein function. To date, few common variants reliably associated with the diagnosis status of ASD despite consistently high estimates of heritability. In addition, reliable biomarkers used to diagnose ASD or molecular mechanisms to define the severity of ASD do not exist. Objectives: It is necessary to integrate DNA and RNA testing together to identify true causal genes and propose useful biomarkers for ASD. Methods: We performed gene-based association studies with adaptive test using genome-wide association studies (GWAS) summary statistics with two large GWAS datasets (ASD 2019 data: 18,382 ASD cases and 27,969 controls [discovery data]; ASD 2017 data: 6,197 ASD cases and 7,377 controls [replication data]) which were obtained from the Psychiatric Genomics Consortium (PGC). In addition, we investigated differential expression for genes identified in gene-based GWAS with a RNA-seq dataset (GSE30573: 3 cases and 3 controls) using the DESeq2 package. Results: We identified 5 genes significantly associated with ASD in ASD 2019 data (KIZ-AS1, p=8.67×10-10; KIZ, p=1.16×10-9; XRN2, p=7.73×10-9; SOX7, p=2.22×10-7; PINX1-DT, p=2.14×10-6). Among these 5 genes, gene SOX7 (p=0.00087), LOC101929229 (p=0.009), and KIZ-AS1 (p=0.059) were replicated in ASD 2017 data. KIZ (p=0.06) was close to the boundary of replication in ASD 2017 data. Genes SOX7 (p=0.0017, adjusted p=0.0085), LOC101929229 (also known as PINX1-DT, p=5.83×10-7, adjusted p=1.18×10-5), and KIZ (p=0.00099, adjusted p=0.0055) indicated significant expression differences between cases and controls in the RNA-seq data. SOX7 encodes a member of the SOX (SRY-related HMG-box) family of transcription factors pivotally contributing to determining of the cell fate and identity in many lineages. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins leading to autism. Conclusion: Gene SOX7 in the transcription factor family could be associated with ASD. This finding may provide new diagnostic and therapeutic strategies for ASD.

9.
Int J Numer Method Biomed Eng ; 39(7): e3733, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37221673

RESUMO

The cerebrovascular blood vessels feed necessary agents such as oxygen, glucose, and so forth. to the brain which maintains the smooth functioning of the human body. However, the blood-brain barrier as a vascular border restricts the entry of drugs that can be necessary for the treatment of neurological disorders. The fluid shear stress in the cerebrovascular blood vessels may regulate the drug delivery in the interface between the cerebrovascular blood vessels and the brain. The intensity of influence by various factors that affects the shear stress in the cerebrovascular blood vessels is scarcely addressed in the present study. A hybrid approach of computational fluid dynamics and Taguchi analysis is proposed to evaluate the influence of various geometrical and operating factors on the shear stress in the microfluidic cerebrovascular channel. Furthermore, the non-Newtonian behavior of blood flow is considered to evaluate the shear stress in the microfluidic cerebrovascular channel. The Newtonian and six non-Newtonian fluids models of Carreau, Carreau-Yasuda, Casson, Cross, Ostwald-de Waele, and Herschel-Bulkley are numerically tested under various conditions of the flow rate, width, and height of the channel to find the viscosity influence on the shear stress. The Taguchi analysis consisting of range and variance analyses is applied to the L16 orthogonal array to evaluate the effect of various factors on shear stress in terms of influence order, range, F value, and percentage contribution. The parameters for the considered six non-Newtonian fluid models are proposed to accurately map the viscosity behavior with shear strain compared to the actual blood flow behavior. The Newtonian, Carreau, and Carreau-Yasuda non-Newtonian fluid models are found accurately with maximum errors between the experimental and numerical shear stress results as 2.17%, 1.30%, and 1.48%, respectively. The shear stress decreases with an increase in the width and height of the channel and a decrease in the viscosity for all flow rates. The porosity is evaluated as a highly influential factor followed by the flow rate, width, and height of the channel in decreasing order based on their effects on the shear stress. The modified shear stress equation is proposed with an accuracy of 0.96 by integrating the effect of porosity in addition to width, height, flow rate, and viscosity. The in-vitro microfluidic cerebrovascular model could be designed and manufactured based on the proposed results on influence order, F value, and percentage contribution of various factors in direction of achieving the in-vivo level shear stress.


Assuntos
Hidrodinâmica , Microfluídica , Humanos , Estresse Mecânico , Hemodinâmica , Artérias/fisiologia , Modelos Cardiovasculares , Velocidade do Fluxo Sanguíneo/fisiologia
10.
Lab Chip ; 23(12): 2819-2828, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37212601

RESUMO

Degenerative cascades of the intervertebral disc (IVD) are characterized by the presence of immune cells like monocytes, macrophages, and leukocytes, which contribute to inflammation. Previous in vitro studies on monocyte chemotaxis in the presence of chemical or mechanical stimulation were unable to establish the effects of endogenous stimulating factors from resident IVD cells, or fully understand macrophage and monocyte differentiation pathways in IVD degeneration. Our study simulates monocyte extravasation using a fabricated microfluidic chemotaxis IVD organ-on-a-chip (IVD organ chip), which models the geometry of IVD, chemoattractant diffusion, and infiltration of immune cells. Additionally, the fabricated IVD organ chip mimics stepwise monocyte infiltration and differentiation into macrophages in the degenerative nucleus pulposus (NP) induced by IL-1ß. We find that naïve NP cells do not recruit THP-1 monocyte-like cells, but degenerative NP cells recruit and accumulate macrophages through chemo-gradient channels. Furthermore, the differentiated and migrated THP-1 cells show phagocytic activity around inflammatory NP cells. Our in vitro model of monocyte chemotaxis with degenerative NP on an IVD organ chip depicts the sequential processes of monocyte migration/infiltration, monocyte-to-macrophage differentiation, and accumulation. Using this platform to gain a deeper understanding of monocyte infiltration and differentiation processes can provide insights into the pathophysiology of the immune response in degenerative IVD.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Núcleo Pulposo/metabolismo , Monócitos , Degeneração do Disco Intervertebral/metabolismo , Sistemas Microfisiológicos , Disco Intervertebral/metabolismo
11.
Int J Mol Sci ; 24(7)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37047329

RESUMO

With advances in nanotechnology, nanoparticles have come to be regarded as carriers of therapeutic agents and have been widely studied to overcome various diseases in the biomedical field. Among these particles, mesoporous silica nanoparticles (MSNs) have been investigated as potential nanocarriers to deliver drug molecules to various target sites in the body. This review introduces the physicochemical properties of MSNs and synthesis procedures of MSN-based nanoplatforms. Moreover, we focus on updating biomedical applications of MSNs as a carrier of therapeutic or diagnostic cargo and review clinical trials using silica-nanoparticle-based systems. Herein, on the one hand, we pay attention to the pharmaceutical advantages of MSNs, including nanometer particle size, high surface area, and porous structures, thus enabling efficient delivery of high drug-loading content. On the other hand, we look through biosafety and toxicity issues associated with MSN-based platforms. Based on many reports so far, MSNs have been widely applied to construct tissue engineering platforms as well as treat various diseases, including cancer, by surface functionalization or incorporation of stimuli-responsive components. However, even with the advantageous aspects that MSNs possess, there are still considerations, such as optimizing physicochemical properties or dosage regimens, regarding use of MSNs in clinics. Progress in synthesis procedures and scale-up production as well as a thorough investigation into the biosafety of MSNs would enable design of innovative and safe MSN-based platforms in biomedical fields.


Assuntos
Nanopartículas , Neoplasias , Humanos , Portadores de Fármacos/química , Dióxido de Silício/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Porosidade
12.
Cyberpsychol Behav Soc Netw ; 26(3): 214-220, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36827589

RESUMO

In this research, we tested (a) the effects of augmented reality (AR) and (b) how the effects of AR could be moderated by privacy perceptions. We used a 2 eyewear app type (AR vs. non-AR) by 2 privacy priming (prime vs. no prime) between-subject experimental design, and 114 Korean adults participated in the experiment. Results showed that AR had a main effect on perceived ease of use but not on perceived usefulness. Instead, the effect of AR on perceived usefulness was moderated by privacy priming such that the positive effect of AR on perceived usefulness was weaker when privacy concern was salient. Moreover, the results provided support for a moderated mediation model in which the indirect effect of AR on intent to use the app via perceived usefulness was moderated by privacy priming. Theoretical and practical implications are discussed.


Assuntos
Realidade Aumentada , Aplicativos Móveis , Adulto , Humanos , Privacidade , Tecnologia , Intenção
13.
Health Commun ; 38(3): 585-593, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34376089

RESUMO

The present study tests and extends the RISP model (a) by applying the model in the context of COVID-19 in South Korea and (b) by examining the impacts of information seeking and processing on misinformation exposure and acceptance. Based on a survey of 346 Korean adults, this study showed that information avoidance, but not information seeking, was a positive predictor of misinformation exposure. In addition, heuristic processing, but not systematic processing, moderated the relationship between misinformation exposure and misinformation acceptance, such that the relationship between misinformation exposure and misinformation acceptance was stronger among those who showed greater tendency for heuristic processing. In addition, information insufficiency was a negative predictor of both information avoidance and heuristic processing. Theoretical and practical implications are discussed.


Assuntos
COVID-19 , Adulto , Humanos , Comunicação , Inquéritos e Questionários , República da Coreia
14.
J Affect Disord ; 324: 8-15, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36566932

RESUMO

BACKGROUND: We investigated the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, on a depression-like phenotype in mice exposed to chronic unpredictable stress (CUS). Learning and memory were also assessed using the Morris water maze (MWM) test. METHODS: Liraglutide (0.3 mg/kg/day for 21 days) was administered to mice with or without exposure to CUS. After 21 days of CUS, the forced swim test (FST) was performed to assess its antidepressant effect. To evaluate cognitive function, liraglutide was administered to mice under stress-free conditions for 21 days, and then the MWM test was performed on 6 consecutive days. RESULTS: Chronic liraglutide treatment reduced FST immobility in mice with and without CUS. In the probe trial of the Morris water maze test, the search error rate was reduced and the time spent and path length in the target quadrant and the number of platform crossings were increased. LIMITATION: Additional animal model experiments and molecular level studies are needed to support the results obtained in this study. CONCLUSIONS: Liraglutide appears to exert antidepressant effects and could improve cognitive function. Based on these results, GLP-1 agonists could have potential as novel antidepressants.


Assuntos
Liraglutida , Teste do Labirinto Aquático de Morris , Camundongos , Animais , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Depressão/tratamento farmacológico , Aprendizagem em Labirinto , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Cognição , Peptídeo 1 Semelhante ao Glucagon , Modelos Animais de Doenças , Comportamento Animal , Estresse Psicológico
15.
Health Commun ; 38(12): 2742-2749, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-35968837

RESUMO

Based on the Risk Information Seeking and Processing Model, the present study examines whether COVID-19 message fatigue leads to greater information avoidance and heuristic processing, and consequently greater acceptance of misinformation. We conducted a survey of 821 Korean adults regarding their information seeking and processing regarding COVID-19 vaccination. Results of SEM analyses showed that COVID-19 message fatigue was (a) negatively related to information insufficiency and (b) positively related to information avoidance and heuristic processing. Information avoidance and heuristic processing were subsequently related to greater levels of misinformation acceptance. Theoretical and practical implications are discussed.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Comunicação , Comportamento de Busca de Informação , Adulto , Humanos , Povo Asiático/psicologia , COVID-19/epidemiologia , COVID-19/psicologia , Fadiga/psicologia
16.
Int J Mol Sci ; 23(12)2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35742857

RESUMO

In several rodent models, acute administration of the metabotropic glutamate 2/3 (mGlu2/3) receptor antagonist LY341495 induced antidepressant-like effects via a mechanism of action similar to that of ketamine. However, the effects of chronic mGlu2/3 antagonism have not yet been explored. Therefore, we investigated the effects of chronic LY341495 treatment on the mechanistic target of rapamycin complex 1 (mTORC1) signaling and the levels of synaptic proteins in mice subjected to chronic unpredictable stress (CUS). LY341495 (1 mg/kg) was administered daily for 4 weeks to mice with and without CUS exposure. After the final treatment, the forced swimming test (FST) was used to assess antidepressant-like effects. The hippocampal levels of mTORC1-related proteins were derived by Western blotting. Chronic LY341495 treatment reversed the CUS-induced behavioral effects of FST. CUS significantly reduced the phosphorylation of mTORC1 and downstream effectors [eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP-1) and small ribosomal protein 6 (S6)], as well as the expression of synaptic proteins postsynaptic density-95 (PSD-95) and AMPA receptor subunit GluR1 (GluA1) in the hippocampus. However, chronic LY341495 treatment rescued these deficits. Our results suggest that the activation of hippocampal mTORC1 signaling is related to the antidepressant effect of chronic LY341495 treatment in an animal model of CUS-induced depression.


Assuntos
Antidepressivos , Depressão , Aminoácidos , Animais , Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Depressão/etiologia , Hipocampo/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Estresse Psicológico , Xantenos
17.
Micromachines (Basel) ; 12(11)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34832700

RESUMO

Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP) in the lumbar spine. This phenomenon is caused by several processes, including matrix degradation in IVD tissues, which is mediated by matrix metalloproteinases (MMPs) and inflammatory responses, which can be mediated by interactions among immune cells, such as macrophages and IVD cells. In particular, interleukin (IL)-1 beta (ß), which is a master regulator secreted by macrophages, mediates the inflammatory response in nucleus pulposus cells (NP) and plays a significant role in the development or progression of diseases. In this study, we developed a custom electrical stimulation (ES) platform that can apply low-constant-current stimulation (LCCS) signals to microfluidic chips. Using this platform, we examined the effects of LCCS on IL-1ß-mediated inflammatory NP cells, administered at various currents (5, 10, 20, 50, and 100 µA at 200 Hz). Our results showed that the inflammatory response, induced by IL-1ß in human NP cells, was successfully established. Furthermore, 5, 10, 20, and 100 µA LCCS positively modulated inflamed human NP cells' morphological phenotype and kinetic properties. LCCS could affect the treatment of degenerative diseases, revealing the applicability of the LCCS platform for basic research of electroceuticals.

18.
Biosens Bioelectron ; 183: 113197, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33819903

RESUMO

Most of the compounds are impermeable to the blood-brain barrier (BBB), which poses a significant challenge in the development of therapeutics for the treatment of neurological diseases. Most of the existing in vitro BBB models are not capable of mimicking the in vivo conditions and functions. The numerical approach-based simulation model was proposed to accurately predict the in vivo level shear stress for the microfluidic BBB-on-a-chip. The in vivo level shear stress was predicted for various conditions of volume flow rates, porosities of the polycarbonate membrane of the BBB model, and dimensions of the microfluidic channel. The in vivo shear stress of the microfluidic BBB model increased with a decrease in the dimension of the microfluidic channel and a decrease in the porosity. The in vivo shear stress predicted by the optimized numerical approach-based simulation was validated within 2.17% error with the experimental in vivo level of shear stress at the porosity of 0.01% and all volume flow rates. The shear stress value, according to the volume flow rate of the microfluidic BBB chip with the optimal microfluidic channel size, was effective for the successful formation of tight junctions in primary endothelial cell culture. In this regard, the proposed method provided a standard for the development of various microfluidic organ-on-chip devices that replicate the in vivo conditions and shear stress.


Assuntos
Técnicas Biossensoriais , Técnicas Analíticas Microfluídicas , Barreira Hematoencefálica , Dispositivos Lab-On-A-Chip , Estresse Mecânico
19.
J Nanosci Nanotechnol ; 21(7): 4093-4097, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33715752

RESUMO

The purpose of this study is to produce nanostructured lipid carrier (NLC) that can solubilize poorly water-soluble velutin and verify an improved tyrosinase synthesis inhibition. A solubility test for velutin was conducted. Cetyl palmitate and caprylic/capric triglyceride were selected as solubilizer. The lipid matrix was produced using the ultrasound dispersion method. The morphology and size distribution of the produced NLC was analyzed through scanning electron microscopy (SEM) and dynamic light scattering (DLS), and the release and tyrosinase inhibition of velutin was evaluated through the Franz diffusion cell method and tyrosinase inhibition assay. Lipid matrix nanoparticles showed an average size of approximately 250 nm and polydispersity of 0.2, and it was confirmed that the velutin incorporated within nanoparticles sustained release at a constant rate over 36 hours. Due to extremely low aqueous solubility, the tyrosinase synthesis inhibition of velutin suspension was 0%, and the value of velutin incorporated within the NLC formulation was greatly improved 56.5% (40 µg/mL). As a result, it was verified that lipid-based NLC nanoparticles are an efficient formulation for the topical delivery of poorly water-soluble flavonoids such as velutin.


Assuntos
Nanopartículas , Nanoestruturas , Varredura Diferencial de Calorimetria , Portadores de Fármacos , Flavonas , Lipídeos , Monofenol Mono-Oxigenase , Tamanho da Partícula
20.
Cyberpsychol Behav Soc Netw ; 24(3): 188-193, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33646021

RESUMO

This research examines (a) the negative impact of disinformation including a deepfake video and (b) the protective effect of media literacy education. We conducted an experiment using a two disinformation message type (deepfake video present vs. absent) by three media literacy education (general disinformation vs. deepfake-specific vs. no literacy) factorial design. In the general disinformation (vs. deepfake-specific) literacy condition, participants were informed about (a) the definition of disinformation (vs. deepfake), (b) some examples of disinformation (vs. deepfake), and (c) the social consequences of disinformation (vs. deepfake). Results showed that disinformation messages including a deepfake video resulted in greater vividness, persuasiveness, credibility, and intent to share the message. Media literacy education reduced the effects of disinformation messages.


Assuntos
Comunicação , Informação de Saúde ao Consumidor , Letramento em Saúde , Mídias Sociais , Gravação em Vídeo , Enganação , Feminino , Humanos , Intenção , Masculino , Comunicação Persuasiva , Adulto Jovem
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