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1.
Br J Cancer ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834745

RESUMO

BACKGROUND: Diffuse invasion remains a primary cause of treatment failure in pediatric high-grade glioma (pHGG). Identifying cellular driver(s) of pHGG invasion is needed for anti-invasion therapies. METHODS: Ten highly invasive patient-derived orthotopic xenograft (PDOX) models of pHGG were subjected to isolation of matching pairs of invasive (HGGINV) and tumor core (HGGTC) cells. RESULTS: pHGGINV cells were intrinsically more invasive than their matching pHGGTC cells. CSC profiling revealed co-positivity of CD133 and CD57 and identified CD57+CD133- cells as the most abundant CSCs in the invasive front. In addition to discovering a new order of self-renewal capacities, i.e., CD57+CD133- > CD57+CD133+ > CD57-CD133+ > CD57-CD133- cells, we showed that CSC hierarchy was impacted by their spatial locations, and the highest self-renewal capacities were found in CD57+CD133- cells in the HGGINV front (HGGINV/CD57+CD133- cells) mediated by NANOG and SHH over-expression. Direct implantation of CD57+ (CD57+/CD133- and CD57+/CD133+) cells into mouse brains reconstituted diffusely invasion, while depleting CD57+ cells (i.e., CD57-CD133+) abrogated pHGG invasion. CONCLUSION: We revealed significantly increased invasive capacities in HGGINV cells, confirmed CD57 as a novel glioma stem cell marker, identified CD57+CD133- and CD57+CD133+ cells as a new cellular driver of pHGG invasion and suggested a new dual-mode hierarchy of HGG stem cells.

2.
Plant Cell Physiol ; 61(5): 978-987, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32154879

RESUMO

Eukaryotic chromatin is tightly packed into hierarchical structures, allowing appropriate gene transcription in response to environmental and developmental cues. Here, we provide a chromosome-scale de novo genome assembly of sesame with a total length of 292.3 Mb and a scaffold N50 of 20.5 Mb, containing estimated 28,406 coding genes using Pacific Biosciences long reads combined with a genome-wide chromosome conformation capture (Hi-C) approach. Based on this high-quality reference genome, we detected changes in chromatin architectures between normal growth and dark-treated sesame seedlings. Gene expression level was significantly higher in 'A' compartment and topologically associated domain (TAD) boundary regions than in 'B' compartment and TAD interior regions, which is coincident with the enrichment of H4K3me3 modification in these regions. Moreover, differentially expressed genes (DEGs) induced by dark treated were enriched in the changed TAD-related regions and genomic differential contact regions. Gene Ontology (GO) enrichment analysis of DEGs showed that genes related to 'response to stress' and 'photosynthesis' functional categories were enriched, which corresponds to dark treatment. These results suggested that chromatin organization is associated with gene transcription in response to dark treatment in sesame. Our results will facilitate the understanding of regulatory mechanisms in response to environmental cues in plants.


Assuntos
Cromatina/metabolismo , Escuridão , Genoma de Planta , Sesamum/genética , Regulação da Expressão Gênica de Plantas , Anotação de Sequência Molecular , Transcrição Gênica
3.
Plant Cell Physiol ; 59(12): 2549-2563, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30541045

RESUMO

Jatropha curcas is a promising feedstock for biofuel production because its oil is highly suitable for processing bio-jet fuels and biodiesel. However, Jatropha exhibits a long juvenile stage in subtropical areas. miR172, a conserved small non-protein-coding RNA molecule with 21 nucleotides, regulates a wide range of developmental processes. To date, however, no studies have examined the function of miR172 in Jatropha. There are five miR172 precursors encoding two mature miR172s in Jatropha, which are expressed in all tissues, with the highest expression level in leaves, and the levels are up-regulated with age. Overexpression of JcmiR172a resulted in early flowering, abnormal flowers, and altered leaf morphology in transgenic Arabidopsis and Jatropha. The expression levels of miR172 target genes were down-regulated, and the flower identity genes were up-regulated in the JcmiR172a-overexpressing transgenic plants. Interestingly, we showed that JcmiR172 might be involved in regulation of stem vascular development through manipulating the expression of cellulose and lignin biosynthesis genes. Overexpression of JcmiR172a enhanced xylem development and reduced phloem and pith development. This study helped elucidate the functions of miR172 in perennial plants, a known age-related miRNA involved in the regulation of perennial plant phase change and organ development.


Assuntos
Jatropha/crescimento & desenvolvimento , Jatropha/genética , MicroRNAs/metabolismo , Reprodução/genética , Madeira/crescimento & desenvolvimento , Madeira/genética , Arabidopsis/genética , Sequência de Bases , Tamanho Celular , Flores/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , MicroRNAs/genética , Fenótipo , Fotoperíodo , Folhas de Planta/anatomia & histologia , Caules de Planta/anatomia & histologia , Plantas Geneticamente Modificadas , Sementes/genética , Sementes/crescimento & desenvolvimento , Xilema/crescimento & desenvolvimento
4.
Planta ; 241(4): 823-36, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25502690

RESUMO

MAIN CONCLUSION: The JcUEP promoter is active constitutively in the bio-fuel plant Jatropha curcas , and is an alternative to the widely used CaMV35S promoter for driving constitutive overexpression of transgenes in Jatropha. Well-characterized promoters are required for transgenic breeding of Jatropha curcas, a biofuel feedstock with great potential for production of bio-diesel and bio-jet fuel. In this study, an ubiquitin extension protein gene from Jatropha, designated JcUEP, was identified to be ubiquitously expressed. Thus, we isolated a 1.2 kb fragment of the 5' flanking region of JcUEP and evaluated its activity as a constitutive promoter in Arabidopsis and Jatropha using the ß-glucuronidase (GUS) reporter gene. As expected, histochemical GUS assay showed that the JcUEP promoter was active in all Arabidopsis and Jatropha tissues tested. We also compared the activity of the JcUEP promoter with that of the cauliflower mosaic virus 35S (CaMV35S) promoter, a well-characterized constitutive promoter conferring strong transgene expression in dicot species, in various tissues of Jatropha. In a fluorometric GUS assay, the two promoters showed similar activities in stems, mature leaves and female flowers; while the CaMV35S promoter was more effective than the JcUEP promoter in other tissues, especially young leaves and inflorescences. In addition, the JcUEP promoter retained its activity under stress conditions in low temperature, high salt, dehydration and exogenous ABA treatments. These results suggest that the plant-derived JcUEP promoter could be an alternative to the CaMV35S promoter for driving constitutive overexpression of transgenes in Jatropha and other plants.


Assuntos
Regulação da Expressão Gênica de Plantas , Jatropha/genética , Proteínas de Plantas/genética , Regiões Promotoras Genéticas/genética , Arabidopsis/genética , Sequência de Bases , Flores/citologia , Flores/genética , Genes Reporter , Jatropha/citologia , Dados de Sequência Molecular , Folhas de Planta/citologia , Folhas de Planta/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/citologia , Raízes de Plantas/genética , Plantas Geneticamente Modificadas , Plântula/citologia , Plântula/genética , Análise de Sequência de DNA , Estresse Fisiológico , Transgenes , Ubiquitina/metabolismo
5.
Work ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38217563

RESUMO

BACKGROUND: In the discourse on the heterogeneity of gender and environmental concern, gender equality awareness can further illuminate the complexity of gender and environmental concern across different cultural backgrounds. OBJECTIVE: Differing from prior research, our study focuses on exploring the relationship between different genders, gender equality awareness, and environmental concern, as well as investigating whether gender equality awareness has distinct effects on environmental concern among different genders. METHODS: Utilizing data from the 2021 China General Social Survey (CGSS), we conducted a theoretical investigation into gender differences in environmental concern. First, we used descriptive statistics to observe the differences between the samples. Secondly, in order to compare the influence of gender equality awareness on different genders, we conducted t-tests on gender subgroups. Subsequently, an Ordinary Least Squares (OLS) regression model was employed to examine the effects of gender and gender equality awareness on environmental issues. Finally, gender equality awareness was introduced as a moderating variable to explore its potential interaction with gender and investigate whether a moderation mechanism exists between gender and environmental concern. RESULTS: Findings indicate that 1) male respondents in China exhibit greater concern for the environment compared to female respondents; 2) higher levels of gender equality awareness are positively correlated with higher levels of environmental concern; 3) the influence of gender on environmental concern is moderated by the degree of gender equality awareness. Specifically, when gender equality awareness is strengthened, female respondents exhibit a higher degree of environmental concern. CONCLUSION: Enhancing gender equality awareness contributes to improving both social gender equality and equitable concern for the environment. The findings could provide insights for similar developing countries like China.

6.
Work ; 77(1): 3-21, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37638467

RESUMO

BACKGROUND: Throughout history, the world has faced numerous health challenges and outbreaks, but through the dedication of medical professionals, solutions have been found. Despite this, the emergence of the coronavirus (COVID-19) has presented a new and dangerous threat. Nevertheless, with unwavering commitment, health experts have triumphantly discovered a remedy. OBJECTIVES: The study aimed to examine how religious workers worldwide could contribute positively to ensuring the fair distribution of COVID-19 vaccines, addressing vaccine hesitancy, encouraging people to get vaccinated, and preventing vaccine nationalism. METHOD: Our study employed a refined qualitative content analysis methodology to categorize factual information and pave the way for subsequent policymakers. We meticulously curetted the most trustworthy secondary data sources and utilized them to analyze the study. RESULTS: The content analysis reveals that religious workers played an active role in the global coronavirus vaccination drive by working towards better vaccine distribution, encouraging people to get vaccinated and countering hesitation and nationalism. CONCLUSION: In light of the discoveries, it would be prudent for policymakers to engage religious workers in advancing the cause of public health, regardless of whether the health matters are localized, national, or global in scale. This strategy has the potential to be both alluring and convincing.


Assuntos
COVID-19 , Vacinas , Humanos , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Surtos de Doenças , Programas de Imunização
7.
Nat Biomed Eng ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491329

RESUMO

Dental calculi can cause gingival bleeding and periodontitis, yet the mechanism underlying the formation of such mineral build-ups, and in particular the role of the local microenvironment, are unclear. Here we show that the formation of dental calculi involves bacteria in local mature biofilms converting the DNA in neutrophil extracellular traps (NETs) from being degradable by the enzyme DNase I to being degradation resistant, promoting the nucleation and growth of apatite. DNase I inhibited NET-induced mineralization in vitro and ex vivo, yet plasma DNases were ineffective at inhibiting ectopic mineralization in the oral cavity in rodents. The topical application of the DNA-intercalating agent chloroquine in rodents fed with a dental calculogenic diet reverted NET DNA to its degradable form, inhibiting the formation of calculi. Our findings may motivate therapeutic strategies for the reduction of the prevalence of the deposition of bacteria-driven calculi in the oral cavity.

8.
Artigo em Inglês | MEDLINE | ID: mdl-36767548

RESUMO

Social support can affect an individual's physical activity and activity habitus. This study aims to explore: (1) the correlations between physical activity and parental/peer support among Chinese college students; (2) the differences between the effects of parental/peer support on college students' physical activity. To achieve these aims, we conducted a cross-sectional study from September to December 2021, recruiting 1005 students (479 male respondents) from seven comprehensive universities in western China. Through OLS linear regression and quantile regression, we empirically testify that both parental support and peer support have significant influence on physical activity and activity habitus of Chinese college students, and peer support has greater impact. We also examine such effects of both types of support by grouping the samples into two groups on the bases of their existing physical activity habitus. We posit that as the most intimate interpersonal relationships, parental support and peer support play a key role in college students' physical activity and activity habitus, and peer support has greater impact as they step into college. Our study provides insights into the factors of physical activity and activity habitus and we propose that attention regarding the impact of social support should be paid when we are trying to promote the physical activity of college students.


Assuntos
Exercício Físico , Relações Interpessoais , Humanos , Masculino , Estudos Transversais , Universidades , Apoio Social , Grupo Associado
9.
Artigo em Inglês | MEDLINE | ID: mdl-36901337

RESUMO

Green behavior is traditionally considered as an effective way to ameliorate environmental degradation and requires an individual to make sacrifices of their social resources. However, few studies have focused on its status signaling. In this study, we draw on the theory of social class and the concept of status signaling theory to empirically investigate the effect of objective social class and perceived social status on private-sphere green behavior in China. Using national comprehensive survey data from China General Survey Data (CGSS) in 2021 subjected to ordinary least-square regression model and step regression models, we present the following results: (1) higher-class individuals, both objectively and subjectively, tend to engage in more private-sphere green behavior than their lower-class counterparts; (2) the effect of objective social class on private-sphere green behavior is mediated by individual's perceived social status in the class hierarchy; (3) environmental concern significantly correlates with private-sphere green behavior, and it also mediates the effect between objective social class and private-sphere green behavior. The present research provides insights into how social class and its psychological manifestations (i.e., perceptions of status) correlate with private-green behavior in China. Our results suggest that more social context factors should be considered when identifying the factors promoting pro-environmental behavior in China.


Assuntos
Conservação dos Recursos Naturais , Classe Social , Humanos , China , Inquéritos e Questionários
10.
Front Public Health ; 11: 1268775, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37869184

RESUMO

Background: With the rapid changes in body image construction brought about by the upgrading of consumption in China, trend-seeking college students are faced with mental health problems brought about by the pursuit of the "ideal body type," which cannot be ignored. This study aims to explore the relationship between body image construction and mental health among college students. This study utilized data from the Survey on Physical Activity and Mental Health of College Students. A total of 1,192 students were randomly selected as the survey sample, and 1,044 valid samples were obtained. The mean age of the respondents was 19.34 years. Methods: First, we categorized body image constructs into three categories based on the differences between subjective and objective body image: high acceptance, low acceptance, and consistency. Second, to ensure analytical rigor and minimize potential confounders, we used a generalized propensity score weighting model. Finally, we used a causal mediation framework to investigate the potential causal mechanisms between the independent variable (perceived body image bias) and the dependent variable (mental health) in order to better understand the "net effect." Results: (1) There is a significant correlation between college students' body image perceptual bias and mental health, i.e., the higher the individual's acceptance of his/her own body image, the higher the level of mental health, and vice versa. (2) Students in humanities and social sciences are more likely to have increased psychological burden due to poor negative body image. (3) In the mediation analysis, although the causal mediating effect of physical exercise was not significant, family and peer support in physical exercise played an important mediating role, especially the influence of peers was more significant. Conclusion: The construction of body image is a double-edged sword that can either promote positive individual development or lead to self-depreciation. Creating a positive climate for physical activity has a positive impact on college students' mental health compared to participation in physical activity behaviors. While improving students' media literacy on college campuses, it is important to enhance adaptive guidance to promote their physical and mental health and personal development.


Assuntos
Imagem Corporal , Saúde Mental , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Universidades , Nível de Saúde , Estudantes/psicologia , Inquéritos e Questionários
11.
Front Public Health ; 11: 1108096, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36908418

RESUMO

Background: With the popularization of the Internet, the use of the Internet is becoming more and more important in the daily life of older adults. However, previous research mainly focuses on Internet use and health in general, and the mechanism of this effect remains to be studied. To bridge this gap, this study aims to explore the mediational effects of social support between Internet use and health among older adults in China. Methods: The data used in this article are from the 2021 Chinese General Social Survey (CGSS). Social support is divided into two aspects and four dimensions: informal social support (relatives support, friends support, neighbors support) and formal social support (social insurance). This article uses the nested multivariate OLS regression models to analyze the impact of Internet use on health. Furthermore, Finally, SPSS macro PROCESS is applied to test their mediation effects. Results: Informal social support positively influenced the health status among older adults, while formal social support did not. Among the three types of informal social support, relatives support and friends support significantly affected health status among Chinese older adults. Regarding social support differences between urban and rural areas, it was found that relatives support is a positively significant factor for rural older adults, while friends support is significant for urban older adults. Conclusions: Since Internet use has many ways of impacting health status, social support only plays a partial mediating role in this study. It recommends that the government should take compelling measures to encourage and promote the use of the Internet among older adults and obtain various social support to improve their health status.


Assuntos
Uso da Internet , Apoio Social , Humanos , Idoso , Nível de Saúde , Amigos , China
12.
J Alzheimers Dis ; 92(4): 1341-1355, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37038814

RESUMO

BACKGROUND: Emerging evidence indicates that sleep disorders are the common non-cognitive symptoms of Alzheimer's disease (AD), and they may contribute to the pathogenesis of this disease. OBJECTIVE: In this study, we aim to investigate the effect of chronic sleep deprivation (CSD) on AD-related pathologies with a focus on tau phosphorylation and the underlying DNA methylation regulation. METHODS: AßPPswe/PS1ΔE9 AD mice and their wild-type (WT) littermates were subjected to a two-month CSD followed by electroencephalography and electromyography recording. The mice were examined for learning and memory evaluation, then pathological, biochemical, and epigenetic assessments including western blotting, immunofluorescence, dot blotting, and bisulfite sequencing. RESULTS: The results show that CSD caused sleep disturbances shown as sleep pattern change, poor sleep maintenance, and increased sleep fragmentation. CSD increased tau phosphorylation at different sites and increased the level of tau kinases in AD and WT mice. The increased expression of cyclin-dependent kinase 5 (CDK5) may result from decreased DNA methylation of CpG sites in the promoter region of CDK5 gene, which might be associated with the downregulation of DNA methyltransferase 3A and 3B. CONCLUSION: CSD altered AD-related tau phosphorylation through epigenetic modification of tau kinase gene. The findings in this study may give insights into the mechanisms underlying the effects of sleep disturbances on AD pathology and provide new therapeutic targets for the treatment of this disease.


Assuntos
Doença de Alzheimer , Animais , Camundongos , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Modelos Animais de Doenças , Camundongos Transgênicos , Fosforilação , Privação do Sono/complicações , Privação do Sono/genética , Proteínas tau/genética , Proteínas tau/metabolismo
13.
CNS Neurosci Ther ; 29(7): 1889-1897, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36883266

RESUMO

AIM: The molecular mechanism underlying Alzheimer's disease (AD) pathologies remains unclear. The brain is extremely sensitive to oxygen deprivation, and brief interruptions in oxygen supply may lead to permanent brain damage. The objective here was to access the red blood cell (RBC) physiological alterations and the changes in blood oxygen saturation of an AD model as well as to explore the possible mechanism underlying these pathologies. METHODS: We used female APPswe /PS1ΔE9 mice as AD models. Data were collected at the age of 3, 6, and 9 months. In addition to examining classic features of AD, namely cognitive deficiency and Aß depositions, 24 h blood oxygen saturation was monitored by Plus oximeters in real time. In addition, RBC physiological parameters were measured by blood cell counter using peripheral blood from the epicanthal veins. Furthermore, in the mechanism investigations, the expression of phosphorylated band 3 protein was examined by a series of Western blot analyses, and the levels of soluble Aß40 and Aß42 on the membrane of RBCs were determined by ELISA. RESULTS: Our results showed that the blood oxygen saturation in the AD mice was significantly reduced as early as at 3 months of age, preceding the neuropathological changes and cognitive impairments. Meanwhile, the expression of phosphorylated band 3 protein and levels of soluble Aß40 and Aß42 were all elevated in the erythrocytes of the AD mice. CONCLUSION: APPswe /PS1ΔE9 mice exhibited decreased oxygen saturation together with reduced RBC counts and hemoglobin concentrations at the early stage, which may aid in the development of predictive markers for AD diagnosis. The increased expression of band 3 protein and elevated Aß40 and Aß42 levels may contribute to the deformation of RBCs and, in turn, cause the subsequent AD development.


Assuntos
Doença de Alzheimer , Camundongos , Feminino , Animais , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Camundongos Transgênicos , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Saturação de Oxigênio , Cognição , Eritrócitos/patologia , Oxigênio , Peptídeos beta-Amiloides/metabolismo , Modelos Animais de Doenças , Presenilina-1/genética , Presenilina-1/metabolismo
14.
Elife ; 112022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36378164

RESUMO

Precise synaptic connection of neurons with their targets is essential for the proper functioning of the nervous system. A plethora of signaling pathways act in concert to mediate the precise spatial arrangement of synaptic connections. Here we show a novel role for a gap junction protein in controlling tiled synaptic arrangement in the GABAergic motor neurons in Caenorhabditis elegans, in which their axons and synapses overlap minimally with their neighboring neurons within the same class. We found that while EGL-20/Wnt controls axonal tiling, their presynaptic tiling is mediated by a gap junction protein UNC-9/Innexin, that is localized at the presynaptic tiling border between neighboring dorsal D-type GABAergic motor neurons. Strikingly, the gap junction channel activity of UNC-9 is dispensable for its function in controlling tiled presynaptic patterning. While gap junctions are crucial for the proper functioning of the nervous system as channels, our finding uncovered the novel channel-independent role of UNC-9 in synapse patterning.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Sinapses/metabolismo , Neurônios Motores/metabolismo , Conexinas/genética , Conexinas/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo
15.
Brain Pathol ; 32(3): e13028, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34668266

RESUMO

Circadian disruption is prevalent in Alzheimer's disease (AD) and may contribute to cognitive impairment, psychological symptoms, and neurodegeneration. This study aimed to evaluate the effects of environmental and genetic factors on the molecular clock and to establish a link between circadian rhythm disturbance and AD. We investigated the pathological effects of chronic sleep deprivation (CSD) in the APPswe /PS1ΔE9 transgenic mice and their wild-type (WT) littermates for 2 months and evaluated the expression levels of clock genes in the circadian rhythm-related nuclei. Our results showed that CSD impaired learning and memory, and further exaggerated disease progression in the AD mice. Furthermore, CSD caused abnormal expression of Bmal1, Clock, and Cry1 in the circadian rhythm-related nuclei of experimental mice, and these changes are more significant in AD mice. Abnormal expression of clock genes in AD mice suggested that the expression of clock genes is affected by APP/PS1 mutations. In addition, abnormal tau phosphorylation was found in the retrosplenial cortex, which was co-located with the alteration of BMAL1 protein level. Moreover, the level of tyrosine hydroxylase in the locus coeruleus of AD and WT mice was significantly increased after CSD. There may be a potential link between the molecular clock, Aß pathology, tauopathy, and the noradrenergic system. The results of this study provided new insights into the potential link between the disruption of circadian rhythm and the development of AD.


Assuntos
Doença de Alzheimer , Relógios Circadianos , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Doença de Alzheimer/patologia , Animais , Relógios Circadianos/genética , Camundongos , Camundongos Transgênicos , Privação do Sono/genética
16.
Neurosci Bull ; 37(7): 1010-1024, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34128188

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease, which manifests with both motor and non-motor symptoms. Circadian rhythm dysregulation, as one of the most challenging non-motor features of PD, usually appears long before obvious motor symptoms. Moreover, the dysregulated circadian rhythm has recently been reported to play pivotal roles in PD pathogenesis, and it has emerged as a hot topic in PD research. In this review, we briefly introduce the circadian rhythm and circadian rhythm-related genes, and then summarize recent research progress on the altered circadian rhythm in PD, ranging from clinical features to the possible causes of PD-related circadian disorders. We believe that future comprehensive studies on the topic may not only help us to explore the mechanisms of PD, but also shed light on the better management of PD.


Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Ritmo Circadiano , Humanos
17.
Elife ; 92020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32314960

RESUMO

Slo2 potassium channels play important roles in neuronal function, and their mutations in humans may cause epilepsies and cognitive defects. However, it is largely unknown how Slo2 is regulated by other proteins. Here we show that the function of C. elegans Slo2 (SLO-2) depends on adr-1, a gene important to RNA editing. ADR-1 promotes SLO-2 function not by editing the transcripts of slo-2 but those of scyl-1, which encodes an orthologue of mammalian SCYL1. Transcripts of scyl-1 are greatly decreased in adr-1 mutants due to deficient RNA editing at a single adenosine in their 3'-UTR. SCYL-1 physically interacts with SLO-2 in neurons. Single-channel open probability (Po) of neuronal SLO-2 is ~50% lower in scyl-1 knockout mutant than wild type. Moreover, human Slo2.2/Slack Po is doubled by SCYL1 in a heterologous expression system. These results suggest that SCYL-1/SCYL1 is an evolutionarily conserved regulator of Slo2 channels.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica/fisiologia , Neurônios/metabolismo , Canais de Potássio Ativados por Sódio/metabolismo , Animais , Caenorhabditis elegans , Humanos , Camundongos , Edição de RNA/fisiologia
18.
Aging Dis ; 11(2): 315-326, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32257544

RESUMO

Rapid eye movement sleep behavior disorder (RBD) is a sleep behavior disorder characterized by abnormal behaviors and loss of muscle atonia during rapid eye movement (REM) sleep. RBD is generally considered to be associated with synucleinopathies, such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), and usually precedes years before the first symptom of these diseases. It is believed that RBD predicts the neurodegeneration in synucleinopathy. However, increasing evidences have shown that RBD is also found in non-synucleinopathy neurodegenerative diseases, including Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), etc. Sleep disturbance such as RBD may be an early sign of neurodegeneration in these diseases, and also serve as an assessment of cognitive impairments. In this review, we updated the clinical characteristics, diagnosis, and possible mechanisms of RBD in neurogenerative diseases. A better understanding of RBD in these neurogenerative diseases will provide biomarkers and novel therapeutics for the early diagnosis and treatment of the diseases.

19.
Brain Res Bull ; 153: 334-340, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31580908

RESUMO

Glioblastoma (GBM) is one of the most malignant and aggressive primary brain tumor, with a mean life expectancy of less than 15 months. The malignant nature of GBM prompts the need for further research on its tumorigenesis and novel treatments to improve its outcome. One of the promising research targets is autophagy, a fundamental metabolic process of degrading and recycling cellular components. Interventions to activate or inhibit autophagy have both been proposed as GBM therapies, suggesting a controversial, context-dependent role of autophagy in GBM tumorigenesis. In this review, we highlight the molecular links between GBM and autophagy with the focus on the effects of autophagy on the stemness maintenance, metabolism and proteostasis in GBM tumorigenesis. Understanding the molecular pathways involved in autophagy target is critical for GBM therapy.


Assuntos
Autofagia/fisiologia , Carcinogênese/metabolismo , Glioblastoma/patologia , Animais , Neoplasias Encefálicas/patologia , Glioblastoma/metabolismo , Humanos
20.
ACS Chem Neurosci ; 10(2): 902-909, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30412668

RESUMO

Chronic hypoxia is considered as one of the important environmental factors contributing to the pathogenesis of Alzheimer's disease (AD). Many chronic hypoxia-causing comorbidities, such as obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD), have been reported to be closely associated with AD. Increasing evidence has documented that chronic hypoxia may affect many pathological aspects of AD including amyloid ß (Aß) metabolism, tau phosphorylation, autophagy, neuroinflammation, oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial and synaptic dysfunction, which may collectively result in neurodegeneration in the brain. In this Review, we briefly summarize the effects of chronic hypoxia on AD pathogenesis and discuss the underlying mechanisms. Since chronic hypoxia is common in the elderly and may contribute to the pathogenesis of AD, prospective prevention and treatment targeting hypoxia may be helpful to delay or alleviate AD.


Assuntos
Doença de Alzheimer/patologia , Encéfalo/patologia , Hipóxia/patologia , Estresse Oxidativo/fisiologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Doença Crônica , Humanos , Hipóxia/metabolismo , Proteínas tau/metabolismo
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