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1.
Front Public Health ; 12: 1328089, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38444441

RESUMEN

Background: Ultraviolet B (UVB) from sunlight represents a major environmental factor that causes toxic effects resulting in structural and functional cutaneous abnormalities in most living organisms. Although numerous studies have indicated the biological mechanisms linking UVB exposure and cutaneous manifestations, they have typically originated from a single study performed under limited conditions. Methods: We accessed all publicly accessible expression data of various skin cell types exposed to UVB, including skin biopsies, keratinocytes, and fibroblasts. We performed biological network analysis to identify the molecular mechanisms and identify genetic biomarkers. Results: We interpreted the inflammatory response and carcinogenesis as major UVB-induced signaling alternations and identified three candidate biomarkers (IL1B, CCL2, and LIF). Moreover, we confirmed that these three biomarkers contribute to the survival probability of patients with cutaneous melanoma, the most aggressive and lethal form of skin cancer. Conclusion: Our findings will aid the understanding of UVB-induced cutaneous toxicity and the accompanying molecular mechanisms. In addition, the three candidate biomarkers that change molecular signals due to UVB exposure of skin might be related to the survival rate of patients with cutaneous melanoma.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/genética , Neoplasias Cutáneas/genética , Secuencia de Bases , Biomarcadores , ARN
2.
Skin Res Technol ; 30(3): e13609, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38419415

RESUMEN

BACKGROUND: Skin aging, characterized by the deterioration of skin density and elasticity, is a common concern among individuals seeking to maintain a youthful appearance. Zinc-α2-glycoprotein (ZAG) is secreted by various body fluids, and is associated with lipolysis and identified as an atopic dermatitis biomarker. This study evaluated the potential of ZAG peptides, which exert multiple benefits such as anti-aging. MATERIALS AND METHODS: We conducted a 4-week clinical trial on patients with noticeable periorbital wrinkles (n = 22) using a ZAG peptide-containing product. The effects of the products on skin density, elasticity, and the depth of periorbital wrinkles were evaluated using Cutometer Dual MPA580, Ultrascan, and Antera 3D CS, respectively. The effect of ZAG peptides on UVB-treated keratinocyte cells was evaluated in vitro to understand the mechanisms underlying its effects against impaired skin barrier function, collagen degradation, and senescence. In addition, the effects of ZAG peptides on cell viability and expression of aging and skin barrier-related genes were assessed using cell counting kit assay and quantitative reverse transcription-polymerase chain reaction, respectively. RESULTS: The patients demonstrated improved skin density, elasticity, and reduced periorbital wrinkles. Further, more than 85% patients scored the product as satisfactory regarding anti-aging effects. Furthermore, ZAG peptides reduced SA-ß-gal staining, downregulated the senescence-related genes, and upregulated the skin barrier function-related genes in UVB-irradiated keratinocyte cells. CONCLUSIONS: Our clinical and in vitro findings showed that ZAG peptides exert anti-aging effects and improve skin barrier functions, suggesting their promising potential as therapeutic agents to combat skin aging and improve skin health.


Asunto(s)
Lipólisis , Zn-alfa-2-Glicoproteína , Humanos , Piel , Envejecimiento , Zinc
3.
Children (Basel) ; 10(8)2023 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-37628414

RESUMEN

This study analyzes the previous literature on the online safety of children and youth under "the 4Cs risk framework" concerning contact, content, conduct, and contract risks. It then conducts a comparative study of Australia, Canada, and the UK, comparing their institutions, governance, and government-led programs. Relevant research in Childhood Education Studies is insufficient both in quantity and quality. To minimize the four major online risks for children and youth in cyberspace, it is necessary to maintain a regulatory approach to the online exposure of children under the age of 13. Moreover, the global society should respond together to these online risks with "multi-level" policymaking under a "multi-stakeholder approach". At the international level, multilateral discussion within the OECD and under UN subsidiaries should continue to lead international cooperation. At the domestic level, a special agency in charge of online safety for children and youth should be established in each country, encompassing all relevant stakeholders, including educators and digital firms. At the school and family levels, both parents and teachers need to work together in facilitating digital literacy education, providing proper guidelines for the online activities of children and youth, and helping them to become more satisfied and productive users in the digital era.

4.
Org Lett ; 25(28): 5389-5394, 2023 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-37413978

RESUMEN

An expedient approach for the synthesis of challenging ß-fluoroamides from readily accessible cyclopropanone equivalents is reported. Following the addition of pyrazole used here as a transient leaving group, silver-catalyzed regiospecific ring-opening fluorination of the resulting hemiaminal leads to a ß-fluorinated N-acylpyrazole intermediate reactive to substitution with amines, ultimately affording ß-fluoroamides. The process could also be extended to the synthesis of ß-fluoroesters and γ-fluoroalcohols via the addition of alcohols or hydrides as terminal nucleophiles, respectively.

5.
Small ; 19(34): e2300290, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37127866

RESUMEN

This study suggests a Ru/ZnO bilayer grown using area-selective atomic layer deposition (AS-ALD) as a multifunctional layer for advanced Cu metallization. As a diffusion barrier and glue layer, ZnO is selectively grown on SiO2 , excluding Cu, where Ru, as a liner and seed layer, is grown on both surfaces. Dodecanethiol (DDT) is used as an inhibitor for the AS-ALD of ZnO using diethylzinc and H2 O at 120 °C. H2 plasma treatment removes the DDT adsorbed on Cu, forming inhibitor-free surfaces. The ALD-Ru film is then successfully deposited at 220 °C using tricarbonyl(trimethylenemethane)ruthenium and O2 . The Cu/bilayer/Si structural and electrical properties are investigated to determine the diffusion barrier performance of the bilayer film. Copper silicide is not formed without the conductivity degradation of the Cu/bilayer/Si structure, even after annealing at 700 °C. The effect of ZnO on the Ru/SiO2 structure interfacial adhesion energy is investigated using a double-cantilever-beam test and is found to increase with ZnO between Ru and SiO2 . Consequently, the Ru/ZnO bilayer can be a multifunctional layer for advanced Cu interconnects. Additionally, the formation of a bottomless barrier by eliminating ZnO on the via bottom, or Cu, is expected to decrease the via resistance for the ever-shrinking Cu lines.

6.
J Cancer Prev ; 28(1): 29, 2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-37033329

RESUMEN

[This corrects the article on p. 199 in vol. 27, PMID: 36713944.].

7.
JMIR Form Res ; 7: e45913, 2023 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-37052992

RESUMEN

BACKGROUND: This study focuses on the potential of health big data in the South Korean context. Despite huge data reserves and pan-government efforts to increase data use, the utilization is limited to public interest research centered in public institutions that have data. To increase the use of health big data, it is necessary to identify and develop measures to meet the various demands for such data from individuals, private companies, and research institutes. OBJECTIVE: The aim of this study was to identify the perceptions of and demands for health big data analysis and use among workers in health care-related occupations and to clarify the obstacles to the use of health big data. METHODS: From May 8 to May 18, 2022, we conducted a web-based survey among 390 health care-related workers in South Korea. We used Fisher exact test and analysis of variance to estimate the differences among occupations. We expressed the analysis results by item in frequency and percentage and expressed the difficulties in analyzing health big data by mean and standard deviation. RESULTS: The respondents who revealed the need to use health big data in health care work-related fields accounted for 86.4% (337/390); 65.6% (256/390) of the respondents had never used health big data. The lack of awareness about the source of the desired data was the most cited reason for nonuse by 39.6% (153/386) of the respondents. The most cited obstacle to using health big data by the respondents was the difficulty in data integration and expression unit matching, followed by missing value processing and noise removal. Thus, the respondents experienced the greatest difficulty in the data preprocessing stage during the health big data analysis process, regardless of occupation. Approximately 91.8% (358/390) of the participants responded that they were willing to use the system if a system supporting big data analysis was developed. As suggestions for the specific necessary support system, the reporting and provision of appropriate data and expert advice on questions arising during the overall process of big data analysis were mentioned. CONCLUSIONS: Our findings indicate respondents' high awareness of and demand for health big data. Our findings also reveal the low utilization of health big data and the need to support health care workers in their analysis and use of such data. Hence, we recommend the development of a customized support system that meets the specific requirements of big data analysis by users such as individuals, nongovernmental agencies, and academia. Our study is significant because it identified important but overlooked failure factors. Thus, it is necessary to prepare practical measures to increase the utilization of health big data in the future.

8.
Heliyon ; 9(4): e14777, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37025807

RESUMEN

The extracellular matrix (ECM) components present within all tissues and organs help to maintain the cytoskeletal architecture and tissue morphology. Although the ECM plays a role in cellular events and signaling pathways, it has not been well studied due its insolubility and complexity. Brain tissue has a higher cell density and weaker mechanical strength than other tissues in the body. When removing cells using a general decellularization method to produce scaffolds and obtain ECM proteins, various problems must be considered because tissues are easily damaged. To retain the brain shape and ECM components, we performed decellularization in combination with polymerization. We immersed mouse brains in oil for polymerization and decellularization via O-CASPER (Oil-based Clinically and Experimentally Applicable Acellular Tissue Scaffold Production for Tissue Engineering and Regenerative Medicine) and then isolated ECM components using sequential matrisome preparation reagents (SMPRs), namely, RIPA, PNGase F, and concanavalin A. Adult mouse brains were preserved with our decellularization method. Western blot and LC-MS/MS analyses revealed that ECM components, including collagen and laminin, were isolated efficiently from decellularized mouse brains using SMPRs. Our method will be useful to obtain matrisomal data and perform functional studies using adult mouse brains and other tissues.

9.
Int J Mol Sci ; 24(4)2023 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-36834821

RESUMEN

Heavy metals are defined as metals with relatively high density and atomic weight, and their various applications have raised serious concerns about the environmental impacts and potential human health effects. Chromium is an important heavy metal that is involved in biological metabolism, but Cr exposure can induce a severe impact on occupational workers or public health. In this study, we explore the toxic effects of Cr exposure through three exposure routes: dermal contact, inhalation, and ingestion. We propose the underlying toxicity mechanisms of Cr exposure based on transcriptomic data and various bioinformatic tools. Our study provides a comprehensive understanding of the toxicity mechanisms of different Cr exposure routes by diverse bioinformatics analyses.


Asunto(s)
Cromo , Metales Pesados , Humanos , Cromo/toxicidad , Toxicogenética , Metales Pesados/toxicidad , Biología Computacional , Perfilación de la Expresión Génica
10.
Front Psychol ; 14: 1229065, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38356997

RESUMEN

Given the increasing importance of early childhood teachers, this study aims to identify whether past maternal parenting is related to burnout through the double mediation of teacher self-compassion and teacher efficacy, using model comparison. To this end, a survey was conducted with 329 early childhood teachers in Korea. The positive maternal parenting perceived by teachers was negatively related to burnout through teachers' self-compassion and efficacy. Positive maternal parenting reduced burnout by increasing self-compassion and consequently teacher efficacy. Teachers' self-compassion was more closely related to burnout than teacher efficacy, which was treated as an important variable in relation to teachers. These results suggest that early childhood teachers' self-compassion is a significant variable in relation to burnout and suggestions are provided for specific support programs to promote teacher self-compassion.

11.
J Cancer Prev ; 28(4): 150-159, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-38205367

RESUMEN

Cadmium (Cd) exposure primarily occurs through inhalation, either by smoking or occupational exposure to contaminated air. Upon inhalation, Cd ultimately reaches the prostate through the bloodstream. In this review, we investigate the carcinogenic potential of Cd in both respiratory organs and the prostate. Specifically, this review examines cellular metabolism, comprehensive toxicity, and carcinogenic mechanisms by exploring gene ontology, biological networks, and adverse outcome pathways. In the respiratory organs, Cd induces lung cancer by altering the expression of IL1B and FGF2, causing DNA damage, reducing cell junction integrity, and promoting apoptosis. In the prostate, Cd induces prostate cancer by modifying the expression of EDN1 and HMOX1, leading to abnormal protein activities and maturation, suppressing tumor suppressors, and inducing apoptosis. Collectively, this review provides a comprehensive understanding of the carcinogenic mechanisms of Cd in two different organs by adopting toxicogenomic approaches. These insights can serve as a foundation for further research on cadmium-induced cancer, contributing to the establishment of future cancer prevention strategies.

12.
ACS Omega ; 7(49): 45004-45013, 2022 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-36530245

RESUMEN

This study presents the effects of surface roughness on the adhesion strength of plasma-treated rubbers that are widely used in soft robotics. The rubbers are designed with 11 molds of different patterns and fabricated from liquid silicones for mutual comparison. Several specimens with nonperiodic and periodic surface waveforms are quantitatively analyzed based on the correlation between surface roughness and adhesion strength. The surface roughness of three-dimensional (3D) printed molds under different printing conditions is compared to that of the standard specimens molded by a smooth acrylic plate and four sandpapers. The surface profiles are measured by a stylus profiler, analyzed using fast Fourier transform, and subsequently quantified using the experimental roughness parameters, R a and R ku *. The kurtosis ratio R ku * is proposed to simultaneously evaluate the sharpness, total height, and peak density to identify contact surfaces. A 90° peel test is also conducted to evaluate the adhesion strength, considering the designed pattern and printing orientation relative to the peeling direction. Microstructural analysis of the specimens is performed to investigate the peeling mechanism and molding quality using scanning electron and digital microscopes. Correlations between adhesion strength and surface roughness are obtained through the evaluation of the plasma-treated silicone specimens. R ku * is significant in determining the surface properties of the effective contact area, particularly for rough surfaces, and further contributes to an effective evaluation when the parameter R a is used simultaneously. The results suggest that the plasma bonding of silicone rubbers fabricated with 3D-printed molds is effective in enhancing the adhesion strength of soft robots or stretchable devices.

13.
Artículo en Inglés | MEDLINE | ID: mdl-36294105

RESUMEN

This study was conducted to identify the relation between children's autonomy and motor development mediated by teacher-child relationships. Are there differences between teacher-child relationships and motor development according to the gender of the child? To answer this question, the fundamental movement skills of 292 children were measured, and teacher-child relationship and children's autonomy data were collected from the teachers. There was a gender difference in locomotion skills; however, there was no difference in object control skills. In the case of girls, a conflict teacher-child relationship mediates the association between autonomy and object control skills. This study highlights the importance of teacher-child relationships, which are mainly discussed in relation to conventional social-emotional development, and provides examples of whole-child development.


Asunto(s)
Relaciones Interpersonales , Maestros , Femenino , Humanos , Maestros/psicología , Factores Sexuales , Desarrollo Infantil , República de Corea
14.
J Lipid Atheroscler ; 11(3): 272-279, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36212750

RESUMEN

Objective: The endothelial inflammatory response plays an important role in atherogenesis by inducing nuclear factor (NF)κB-dependent cell adhesion molecule expression and monocyte recruitment. Here, we screened for natural ligands and investigated the ability of shinjulactone A to inhibit interleukin-1ß (IL-1ß)-induced endothelial inflammatory signaling. Methods: The natural compound library included 880 single compounds isolated from medicinal plants by the Korean Medicinal Material Bank. Primary endothelial cells were pretreated with single compounds before stimulation with IL-1ß to induce endothelial inflammation. Endothelial inflammation was measured by assaying NFκB activation and monocyte adhesion. The endothelial-mesenchymal transition (EndMT) was evaluated using cell type-specific marker protein expression and morphology. Results: Shinjulactone A was identified as an efficient blocker of IL-1ß -induced NFκB activation, with a half-maximal inhibitory concentration of approximately 1 µM, and monocyte recruitment in endothelial cells. However, it did not affect lipopolysaccharide-induced NFκB activation in macrophages. Compared to Bay 11-782, a well-known NFκB inhibitor that shows considerable cytotoxicity during long-term treatment, shinjulactone A did not affect endothelial cell viability. Furthermore, it also significantly inhibited the EndMT, which is known to promote atherosclerosis and plaque instability. Conclusion: We suggest that shinjulactone A may be an effective and safe drug candidate for atherosclerosis because it targets and inhibits both endothelial inflammation and the EndMT, without impairing NFκB-dependent innate immunity in macrophages.

15.
Sci Rep ; 12(1): 9750, 2022 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-35697899

RESUMEN

Although numerous experimental studies have suggested a significant association between ambient particulate matter (PM) and respiratory damage, the etiological relationship between ambient PM and environmental skin diseases is not clearly understood. Here, we aimed to explore the association between PM and skin diseases through biological big data analysis. Differential gene expression profiles associated with PM and environmental skin diseases were retrieved from public genome databases. The co-expression among them was analyzed using a text-mining-based network analysis software. Activation/inhibition patterns from RNA-sequencing data performed with PM2.5-treated normal human epidermal keratinocytes (NHEK) were overlapped to select key regulators of the analyzed pathways. We explored the adverse effects of PM on the skin and attempted to elucidate their relationships using public genome data. We found that changes in upstream regulators and inflammatory signaling networks mediated by MMP-1, MMP-9, PLAU, S100A9, IL-6, and S100A8 were predicted as the key pathways underlying PM-induced skin diseases. Our integrative approach using a literature-based co-expression analysis and experimental validation not only improves the reliability of prediction but also provides assistance to clarify underlying mechanisms of ambient PM-induced dermal toxicity that can be applied to screen the relationship between other chemicals and adverse effects.


Asunto(s)
Contaminantes Atmosféricos , Enfermedades de la Piel , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Humanos , Material Particulado/análisis , Material Particulado/toxicidad , Reproducibilidad de los Resultados , Piel/química , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/genética
16.
Front Hum Neurosci ; 16: 817538, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35250518

RESUMEN

BACKGROUND: Electronic cigarettes (e-cigs) as substitute devices for regular tobacco cigarettes (r-cigs) have been increasing in recent times. We investigated neuronal substrates of vaping e-cigs and smoking r-cigs from r-cig smokers. METHODS: Twenty-two r-cig smokers made two visits following overnight smoking cessation. Functional magnetic resonance imaging (fMRI) data were acquired while participants watched smoking images. Participants were then allowed to smoke either an e-cig or r-cig until satiated and fMRI data were acquired. Their craving levels and performance on the Montreal Imaging Stress Task and a 3-back alphabet/digit recognition task were obtained and analyzed using two-way repeated-measures analysis of variance. Regions-of-interest (ROIs) were identified by comparing the abstained and satiated conditions. Neuronal activation within ROIs was regressed on the craving and behavioral data separately. RESULTS: Craving was more substantially reduced by smoking r-cigs than by vaping e-cigs. The response time (RT) for the 3-back task was significantly shorter following smoking r-cigs than following vaping e-cigs (interaction: F (1, 17) = 5.3, p = 0.035). Neuronal activations of the right vermis (r = 0.43, p = 0.037, CI = [-0.05, 0.74]), right caudate (r = 0.51, p = 0.015, CI = [0.05, 0.79]), and right superior frontal gyrus (r = -0.70, p = 0.001, CI = [-0.88, -0.34]) were significantly correlated with the RT for the 3-back task only for smoking r-cigs. CONCLUSION: Our findings suggest that insufficient satiety from vaping e-cigs for r-cigs smokers may be insignificant effect on working memory function.

17.
J Cancer Prev ; 27(4): 199-207, 2022 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-36713944

RESUMEN

As a principal component of solar radiation, ultraviolet B (UVB) exposure can be harmful depending on the duration and intensity because the human body can easily be exposed to it. Many studies have demonstrated that UVB causes a series of inflammatory and other skin disorders. UVB has been classified as the Group 1 carcinogen by the International Agency for Research on Cancer. Diverse studies have focused on UVB exposure but the complex perspective of acute and chronic UVB exposure is still lacking. This review presents the differences between acute and chronic exposure to UVB and summarizes public information in terms of toxicogenomic characteristics. We also demonstrated the differences between adverse effects of acute and chronic UVB exposure on the skin system. From the published literatures, we compared the biological pathways predict of the adverse effects caused by each UVB exposure type. Furthermore, our review not only clarifies the differences in each UVB exposure network but also suggests major hub genes related to cellular mechanisms and diseases that are thought to be affected by acute and chronic UVB exposure.

18.
Artículo en Inglés | MEDLINE | ID: mdl-34682569

RESUMEN

This study addresses the novel concept of two types of parental academic support (PAS), namely, as a companion and as a manager, and identifies the effect of children's perceived PAS on their psychological attributes and academic achievements. The data include a nationally representative sample of 6836 students from the Korean Education Longitudinal Study 2013. A correlation analysis showed that the two types of PAS had a positive relation with adolescents' development; however, a structural equation model showed a negative effect of PAS as a manager. Children's perceived PAS as managers had no effect on their self-regulation or academic achievement after 3 years, surprisingly, was found to increase their amotivation. Children's perceived PAS as companions had a long-term, positive effect on adolescents' development and academic achievements. The results suggest that parents should recognize their children's autonomy and provide academic support on an equal level. Further multidimensional PAS studies should be conducted with more detailed questions.


Asunto(s)
Éxito Académico , Adolescente , Niño , Humanos , Estudios Longitudinales , Relaciones Padres-Hijo , Responsabilidad Parental , República de Corea
19.
Biomed Res Int ; 2021: 6667623, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33763483

RESUMEN

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is widely used in clinical microbiology laboratories because it is cost-effective, reliable, and fast. This study is aimed at comparing the identification performance of the recently developed Autof ms1000 (Autobio, China) with that of the Bruker Biotyper (Bruker Daltonics, Germany). From January to June 2020, 205 preserved strains and 302 clinical isolates were used for comparison. Bacteria were tested with duplicates of the direct transfer method, and formic acid extraction was performed if the results were not at the species level. Fungi were tested with formic acid extraction followed by ethanol extraction methods. 16S rRNA or ITS region sequence analysis was performed on isolates that could not be identified by any of the instruments and on isolates that showed inconsistent results. The time to result of each instrument was also compared. Among preserved strains, species-level identification results were obtained in 202 (98.5%) strains by the Autof ms1000 and 200 (97.6%) strains by the Bruker Biotyper. Correct identification at the species/complex level was obtained for 200 (97.6%) strains by the Autof ms1000 and for 199 (97.1%) strains by the Bruker Biotyper. Among clinical isolates, species-level identification results were obtained in 301 (99.7%) strains and 300 (99.3%) strains by the Autof ms1000 and Bruker Biotyper, respectively. Correct identification at the species/complex level was achieved for 299 (99.0%) strains by the Autof ms1000 and for 300 (99.3%) strains by the Bruker Biotyper. The time to analyze 96 spots was approximately 14 min for the Autof ms1000 and approximately 27 min for the Bruker Biotyper. The two instruments showed comparable performance for the routine identification of clinical microorganisms. In addition, the Autof ms1000 has a short test time, making it convenient for use in clinical microbiology laboratories.


Asunto(s)
Bacterias , Técnicas de Tipificación Bacteriana , ARN Bacteriano , ARN Ribosómico 16S , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Bacterias/clasificación , Bacterias/genética , Técnicas de Tipificación Bacteriana/instrumentación , Técnicas de Tipificación Bacteriana/métodos , Humanos , ARN Bacteriano/análisis , ARN Bacteriano/genética , ARN Ribosómico 16S/análisis , ARN Ribosómico 16S/genética
20.
Int J Mol Sci ; 22(1)2021 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-33401721

RESUMEN

Mitochondrial dysfunction contributes to neurodegenerative diseases and developmental disorders such as Fragile X syndrome (FXS). The cross-talk between mitochondria and extracellular vesicles (EVs) suggests that EVs may transfer mitochondrial components as intermediators for intracellular communication under physiological and pathological conditions. In the present study, the ability of EVs to transfer mitochondrial components and their role in mitochondrial dysfunction in astrocytes were examined in the brains of Fmr1 knockout (KO) mice, a model of FXS. The amounts of mitochondrial transcription factor NRF-1, ATP synthases ATP5A and ATPB, and the mitochondrial membrane protein VDAC1 in EVs were reduced in cerebral cortex samples and astrocytes from Fmr1 KO mice. These reductions correspond to decreased mitochondrial biogenesis and transcriptional activities in Fmr1 KO brain, along with decreased mitochondrial membrane potential (MMP) with abnormal localization of vimentin intermediate filament (VIF) in Fmr1 KO astrocytes. Our results suggest that mitochondrial dysfunction in astrocytes is associated with the pathogenesis of FXS and can be monitored by depletion of components in EVs. These findings may improve the ability to diagnose developmental diseases associated with mitochondrial dysfunction, such as FXS and autism spectrum disorders (ASD).


Asunto(s)
Astrocitos/metabolismo , Vesículas Extracelulares/metabolismo , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Síndrome del Cromosoma X Frágil/metabolismo , Mitocondrias/metabolismo , Animales , Células Cultivadas , Corteza Cerebral/metabolismo , Modelos Animales de Enfermedad , Vesículas Extracelulares/genética , Vesículas Extracelulares/ultraestructura , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Inmunohistoquímica , Masculino , Potencial de la Membrana Mitocondrial/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Electrónica de Transmisión , Mitocondrias/genética
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