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1.
Nat Commun ; 12(1): 5740, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593806

RESUMO

NG2 glia, also known as oligodendrocyte precursor cells (OPCs), play an important role in proliferation and give rise to myelinating oligodendrocytes during early brain development. In contrast to other glial cell types, the most intriguing aspect of NG2 glia is their ability to directly sense synaptic inputs from neurons. However, whether this synaptic interaction is bidirectional or unidirectional, or its physiological relevance has not yet been clarified. Here, we report that NG2 glia form synaptic complexes with hippocampal interneurons and that selective photostimulation of NG2 glia (expressing channelrhodopsin-2) functionally drives GABA release and enhances inhibitory synaptic transmission onto proximal interneurons in a microcircuit. The mechanism involves GAD67 biosynthesis and VAMP-2 containing vesicular exocytosis. Further, behavioral assays demonstrate that NG2 glia photoactivation triggers anxiety-like behavior in vivo and contributes to chronic social defeat stress.

2.
Mar Biotechnol (NY) ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34595589

RESUMO

Aquaporin (aqp) proteins are a group of small integral membrane proteins that play crucial roles as pore channels for the transport of water and other small solutes across the cell membrane. In our study, we identified 17 aqp genes from the spotted sea bass (Lateolabrax maculatus) genomic database. Gene organization, motif distribution, and selection pressure analyses were performed to investigate their evolutionary characteristics. The aqp mRNA displayed tissue-specific expression pattern in ten selected tissues of healthy spotted sea bass. To investigate the potential involvement of spotted sea bass aqps in osmoregulation, the expression profiles of aqp genes in gills were examined during freshwater (FW) acclimation using qRT-PCR. The mRNA level of aqp3a was dramatically induced during 1-3 day of the FW transition period (77-fold and 15-fold upregulated on 1 day and 3 day than in the control group), indicating that aqp3a may play an important hypo-osmoregulatory role in spotted sea bass. In addition, the expression levels of aqp1aa, aqp1ab, aqp3b, aqp7, and aqp9b increased to various degrees at 1 day after transferring to FW, suggesting their potential involvement in the FW acclimation process. Our study provides a valuable foundation for future studies aimed at uncovering the specific roles of aqp genes during salinity acclimation in spotted sea bass and other teleost species.

3.
Cell ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34644528

RESUMO

Retrotransposons mediate gene regulation in important developmental and pathological processes. Here, we characterized the transient retrotransposon induction during preimplantation development of eight mammals. Induced retrotransposons exhibit similar preimplantation profiles across species, conferring gene regulatory activities, particularly through long terminal repeat (LTR) retrotransposon promoters. A mouse-specific MT2B2 retrotransposon promoter generates an N-terminally truncated Cdk2ap1ΔN that peaks in preimplantation embryos and promotes proliferation. In contrast, the canonical Cdk2ap1 peaks in mid-gestation and represses cell proliferation. This MT2B2 promoter, whose deletion abolishes Cdk2ap1ΔN production, reduces cell proliferation and impairs embryo implantation, is developmentally essential. Intriguingly, Cdk2ap1ΔN is evolutionarily conserved in sequence and function yet is driven by different promoters across mammals. The distinct preimplantation Cdk2ap1ΔN expression in each mammalian species correlates with the duration of its preimplantation development. Hence, species-specific transposon promoters can yield evolutionarily conserved, alternative protein isoforms, bestowing them with new functions and species-specific expression to govern essential biological divergence.

4.
Cancer Res ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645609

RESUMO

The histone demethylase KDM6A controls gene expression by the epigenetic regulation of H3K27 methylation and functions in diverse processes, including differentiation, development, and cancer. Here, we investigated the role of KDM6A in prostate cancer (PCa). Specific homozygous deletion of KDM6A in the adult mouse prostate epithelium strongly inhibited tumor progression initiated by the homozygous loss of PTEN. Mechanistically, KDM6A promoted prostate tumorigenesis and lipid metabolism by binding to the SREBP1c promoter to increase SREBP1c transcription. USP7 deubiquitinated KDM6A to increase its expression. KDM6A was significantly up-regulated in PCa and positively associated with USP7 expression. Furthermore, targeting KDM6A stability by inhibiting USP7 in conditional knockout mice and xenograft models markedly suppressed PCa growth and significantly enhanced KDM6A inhibitor efficacy. Collectively, these findings indicate that KDM6A regulates prostate lipid metabolism and is essential for prostate tumorigenesis initiated by PTEN loss. Targeting USP7/KDM6A could be a valuable strategy to ameliorate prostate cancer progression and therapeutic resistance.

5.
Comp Biochem Physiol B Biochem Mol Biol ; 257: 110677, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34653596

RESUMO

Prostaglandins are a series of unsaturated fatty acids that play critical roles in regulating reproductive events. The prostaglandins endoperoxide H synthases-1/2 (PGHS-1/2; also named cyclooxygenases-1/2, COX-1/2) catalyse the commitment step in prostaglandin synthesis. However, the of the cox genes in teleosts, especially ovoviviparous teleosts, is still unclear. The aim of the present study was to determine the potential role of cox genes in mating and parturition behaviour using black rockfish (Sebastes schlegelii) as a model species. Two transcripts, cox1 and cox2, were cloned. The phylogenetic analysis results revealed that both cox genes were closely related to mammalian coxs. qPCR analyses of their tissue distribution showed that cox1 was mainly expressed in the heart in both sexes, while cox2 was mainly expressed in the testis and ovary. Detection of cox expression in samples from reproductive-related stages further showed that both cox genes may play important roles in mating and parturition processes. In situ hybridization further detected positive cox mRNA signals in the testis and ovary, where they are known to be involved in mating and parturition behaviour. These data suggest that cox1 and cox2 are crucial in inducing mating, gonad regeneration and parturition behaviour.

6.
Food Chem ; 372: 131211, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34601423

RESUMO

In this study, the interaction of ovalbumin with lutein dipalmitate and the effect of ovalbumin on marigold lutein esters extracts were investigated. Lutein dipalmitate quenched the fluorescence of ovalbumin by static quenching. Binding and thermodynamic parameters proved that lutein dipalmitate bound to ovalbumin spontaneously by van der Waals force and hydrogen bond, and the complex stoichiometry was 1:1. Through three-dimensional fluorescence spectroscopy, Fourier transform infrared spectroscopy and circular dichroism experiments, the conformation of ovalbumin was unfolded, and alteration in the ovalbumin secondary structure induced by lutein dipalmitate was observed. The results of transmission electron microscopy and particle size revealed that there were spherical and nano-sized aggregates in the ovalbumin-lutein dipalmitate system, indicating the lutein dipalmitate not only could bind to ovalbumin at molecular level, but also promote the aggregation of ovalbumin. Additionally, the addition of ovalbumin had a positive effect on the stability of marigold lutein esters extracts.

7.
Ren Fail ; 43(1): 1394-1407, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34629011

RESUMO

BACKGROUND: New evidence from studies on risk factors for mortality in hemodialysis (HD) patients with COVID-19 became available. We aimed to review the clinical risk factors for fatal outcomes in these patients. METHODS: We performed meta-analysis using the PubMed, EMBASE, and Cochrane databases. A fixed- or random-effects model was used for calculating heterogeneity. We used contour-enhanced funnel plot and Egger's tests to assess potential publication bias. RESULTS: Twenty-one studies were included. The proportion of males was lower in the survivor group than in the non-survivor group (OR = 0.75, 95% CI [0.61, 0.94]). The proportion of respiratory diseases was significantly lower in the survivor group than in the non-survivor group (OR = 0.42, 95% CI [0.29, 0.60]). The proportion of patients with fever, cough, and dyspnea was significantly lower in the survivor group (fever: OR = 0.53, 95% CI [0.31, 0.92]; cough: OR = 0.50, 95% CI [0.38, 0.65]; dyspnea: OR = 0.25, 95% CI [0.14, 0.47]) than in the non-survivor group. Compared with the non-survivor group, the survivor group had higher albumin and platelet levels and lower leucocyte counts. CONCLUSIONS: Male patients might have a higher risk of developing severe COVID-19. Comorbidities, such as respiratory diseases could also greatly influence the clinical prognosis of COVID-19. Clinical features, such as fever, dyspnea, cough, and abnormal platelet, leucocyte, and albumin levels, could imply eventual death. Our findings will help clinicians identify markers for the detection of high mortality risk in HD patients at an early stage of COVID-19.

8.
BMC Ecol Evol ; 21(1): 165, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488647

RESUMO

BACKGROUND: Domestication alters several phenotypic, neurological, and physiological traits in domestic animals compared to those in their wild ancestors. Domestic ducks originated from mallards, and some studies have shown that spot-billed ducks may have also made minor genetic contributions to domestication. Compared with the two ancestral species, domestic ducks generally differ in body size and bone morphology. In this study, we performed both genomic and transcriptomic analyses to identify candidate genes for elucidating the genetic mechanisms underlying phenotypic variation. METHODS: In this study, the duck genome data from eight domestic breeds and two wild species were collected to study the genetic changes during domestication. And the transcriptome data of different tissues from wild ducks and seven domestic ducks were used to reveal the expression difference between wild and domestic ducks. RESULTS: Using fixation index (Fst) algorithm and transcriptome data, we found that the genes related to skeletal development had high Fst values in wild and domestic breeds, and the differentially expressed genes were mainly enriched in the ossification pathway. Our data strongly suggest that the skeletal systems of domestic ducks were changed to adapt to artificial selection for larger sizes. In addition, by combining the genome and transcriptome data, we found that some Fst candidate genes exhibited different expression patterns, and these genes were found to be involved in digestive, immune, and metabolic functions. CONCLUSIONS: A wide range of phenotypic differences exists between domestic and wild ducks. Through both genome and transcriptome analyses, we found that genes related to the skeletal system in domestic ducks were strongly selected. Our findings provide new insight into duck domestication and selection effects during the domestication.

9.
Comput Intell Neurosci ; 2021: 8387382, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475949

RESUMO

Image style transfer can realize the mutual transfer between different styles of images and is an essential application for big data systems. The use of neural network-based image data mining technology can effectively mine the useful information in the image and improve the utilization rate of information. However, when using the deep learning method to transform the image style, the content information is often lost. To address this problem, this paper introduces L1 loss on the basis of the VGG-19 network to reduce the difference between image style and content and adds perceptual loss to calculate the semantic information of the feature map to improve the model's perceptual ability. Experiments show that the proposal in this paper improves the ability of style transfer, while maintaining image content information. The stylization of the improved model can better meet people's requirements for stylization, and the evaluation indexes of structural similarity, cosine similarity, and mutual information value have increased by 0.323%, 0.094%, and 3.591%, respectively.


Assuntos
Sistemas de Dados , Redes Neurais de Computação , Humanos , Semântica
10.
J Nucl Cardiol ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34476776

RESUMO

BACKGROUND: Previous studies proved the efficacy of cardiac shock wave therapy (CSWT) for coronary artery disease (CAD) patients who are not candidate for reperfusion therapy. Randomized control trials are limited. We try to explore the efficacy and safety of CSWT for patients with severe CAD. METHODS: Thirty patients with severe CAD who had obvious ischemia on myocardial perfusion imaging (MPI) were enrolled and randomly assigned to the CSWT group or the control group. They had received optimal medication treatment for at least three months. Nine sessions of shock wave therapy were conducted over 3 months. CSWT group received the real treatment, while the control group received the pseudo-treatment. Clinical symptom, imaging outcomes and safety parameters were compared between two groups. RESULTS: After treatment, regional stress score (P = .023), improvement rate (IR) of ischemic area (IA) stress (P < .001) and IR of IA difference (P < .001) were significantly favor CSWT group. The interaction of summed rest score (P < .001), summed stress score (P = .004), summed difference score (P = .036) were significantly improved in the CSWT group compared to the control group. Seattle angina questionnaire, quality of life (QOL) and the distance of six-minute walking test (6MWT) were improved in both groups without significant difference between them. Hemodynamic parameters were stable during procedure. Myocardial injury markers showed no changes in two groups. CONCLUSIONS: Our study demonstrated CSWT could effectively and safely improve myocardial perfusion in patients with severe CAD. Clinical symptom, QOL and 6MWT were all improved after treatment, but no significant difference between two groups.

11.
Sci Total Environ ; 805: 150270, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34536863

RESUMO

Polychlorinated biphenyls (PCBs), together with 11 other organic compounds, were initially listed as persistent organic pollutants (POPs) by the Stockholm Convention because of their potential threat to ecosystems and humans. In China, many monitoring studies have been undertaken to reveal the level of PCBs in environment since 2005 due to the introduced stricter environmental regulations. However, there are still significant gaps in understanding the overall spatial and temporal distributions of PCBs in China. This review systematically discusses the occurrence and distribution of PCBs in environmental matrices, organisms, and humans in China. Results showed that PCB contamination in northern and southern China was not significantly different, but the PCB levels in East China were commonly higher than those in West China, which might have been due to the widespread consumption of PCBs and intensive human activities in East China. Serious PCB contamination was found in e-waste disassembling areas (e.g., Taizhou of Zhejiang Province and Qingyuan and Guiyu of Guangdong Province). Higher PCB concentrations were also chronicled in megalopolises and industrial clusters. The unintentionally produced PCBs (UP-PCBs) formed during industrial thermal processes may play an increasingly significant role in PCB pollution in China. Low PCB levels were recorded in rural and underdeveloped districts, particularly in remote and high-altitude localities such as the Tibetan Plateau and the South China Sea. However, these data are limited. Human exposure to PCBs is closely related to the characteristics of environmental pollution. This review also discusses existing issues and future research prospects on PCBs in China. For instance, the accumulation characteristics and migration regularities of PCBs in food webs should be further studied. More investigations should be undertaken to assess the quantitative relationship between external and internal exposure to PCBs. For example, bioaccessibility and bioavailability studies should be supplemented to evaluate human health risks more accurately.

13.
Interact J Med Res ; 10(3): e24831, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581676

RESUMO

BACKGROUND: Research on Graves ophthalmopathy has increased remarkably over the last 2 decades; however, few statistical analyses of the data presented in these publications have been conducted. OBJECTIVE: This study aims to detect and analyze emerging trends and collaboration networks in Graves ophthalmopathy research. METHODS: Graves ophthalmopathy-related publications from 1999 to 2019 were collected from the Web of Science Core Collection Database. Collected publications were restricted by category (article or review) and language (English). Bibliometric analyses included changes in the annual numbers of publications, journals, authors, countries, institutions, keywords, and references. RESULTS: In total, 3051 publications that met the criteria were collected. The number of annual publications has exhibited an increasing trend over the last 20 years. The journal Thyroid ranked first, publishing 183 Graves ophthalmopathy-related studies. There was no evidence of a relationship between impact factor (IF) and the number of publications (P=.69). The author Smith TJ had the largest number of publications on Graves ophthalmopathy (n=83). Of the countries that had published Graves ophthalmopathy-related articles, the United States had the largest number (n=784) and the highest centrality (0.18). Among institutions, the University of Pisa (Italy) contributed the most Graves ophthalmopathy-related articles (n=114). The most recent burst keywords (proliferation, rituximab, and selenium) and references may provide clues on emerging trends in research and clinical practice. CONCLUSIONS: This bibliometric analysis highlights countries, institutions, and authors who contributed to Graves ophthalmopathy-related publications. Emerging trends in Graves ophthalmopathy research, based on burst keywords and references, may provide clues relevant to clinical practice and future research.

14.
PLoS Pathog ; 17(9): e1009918, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34529741

RESUMO

Under RNA virus infection, retinoic acid-inducible gene I (RIG-I) in host cells recognizes viral RNA and activates the expression of type I IFN. To investigate the roles of protein methyltransferases and demethylases in RIG-I antiviral signaling pathway, we screened all the known related enzymes with a siRNA library and identified LSD1 as a positive regulator for RIG-I signaling. Exogenous expression of LSD1 enhances RIG-I signaling activated by virus stimulation, whereas its deficiency restricts it. LSD1 interacts with RIG-I, promotes its K63-linked polyubiquitination and interaction with VISA/MAVS. Interestingly, LSD1 exerts its function in antiviral response not dependent on its demethylase activity but through enhancing the interaction between RIG-I with E3 ligases, especially TRIM25. Furthermore, we provide in vivo evidence that LSD1 increases antiviral gene expression and inhibits viral replication. Taken together, our findings demonstrate that LSD1 is a positive regulator of signaling pathway triggered by RNA-virus through mediating RIG-I polyubiquitination.

15.
BMC Plant Biol ; 21(1): 410, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493227

RESUMO

BACKGROUND: Water deficit is an abiotic stress that retards plant growth and destabilizes crop production. Long non coding RNAs (lncRNAs) are a class of non-coding endogenous RNAs that participate in diverse cellular processes and stress responses in plants. lncRNAs could function as competing endogenous RNAs (ceRNA) and represent a novel layer of gene regulation. However, the regulatory mechanism of lncRNAs as ceRNA in drought stress response is yet unclear. RESULTS: In this study, we performed transcriptome-wide identification of drought-responsive lncRNAs in rice. Thereafter, we constructed a lncRNA-mediated ceRNA network by analyzing competing relationships between mRNAs and lncRNAs based on ceRNA hypothesis. A drought responsive ceRNA network with 40 lncRNAs, 23 miRNAs and 103 mRNAs was obtained. Network analysis revealed TCONS_00021861/miR528-3p/YUCCA7 regulatory axis as a hub involved in drought response. The miRNA-target expression and interaction were validated by RT-qPCR and RLM-5'RACE. TCONS_00021861 showed significant positive correlation (r = 0.7102) with YUCCA7 and negative correlation with miR528-3p (r = -0.7483). Overexpression of TCONS_00021861 attenuated the repression of miR528-3p on YUCCA7, leading to increased IAA (Indole-3-acetic acid) content and auxin overproduction phenotypes. CONCLUSIONS: TCONS_00021861 could regulate YUCCA7 by sponging miR528-3p, which in turn activates IAA biosynthetic pathway and confer resistance to drought stress. Our findings provide a new perspective of the regulatory roles of lncRNAs as ceRNAs in drought resistance of rice.


Assuntos
Oryza/genética , RNA Longo não Codificante/genética , Desidratação/genética , Secas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Células do Mesofilo/ultraestrutura , MicroRNAs/genética , Folhas de Planta/genética , RNA Mensageiro/genética , RNA de Plantas , Espécies Reativas de Oxigênio/metabolismo
16.
Math Biosci Eng ; 18(5): 6652-6671, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34517550

RESUMO

The image super-resolution reconstruction method can improve the image quality in the Internet of Things (IoT). It improves the data transmission efficiency, and is of great significance to data transmission encryption. Aiming at the problem of low image quality in image super-resolution using neural networks, a self-attention-based image reconstruction method is proposed for secure data transmission in IoT environment. The network model is improved, and the residual network structure and sub-pixel convolution are used to extract the feature of the image. The self-attention module is used extract detailed information in the image. Using generative confrontation method and image feature perception method to improve the image reconstruction effect. The experimental results on the public data set show that the improved network model improves the quality of the reconstructed image and can effectively restore the details of the image.


Assuntos
Processamento de Imagem Assistida por Computador , Internet das Coisas , Redes Neurais de Computação
17.
Med Educ Online ; 26(1): 1981198, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34569433

RESUMO

The purpose of this scoping review is to update the recent progress of EPAs research in GME, focusing on the topical concern of EPAs effectiveness, and to provide a reference for medical researchers in countries/regions interested in introducing EPAs. Guided by Arksey and O'Malley's framework regarding scoping reviews, the researchers, in January 2021, conducted a search in five databases to ensure the comprehensiveness of the literature. After the predetermined process, 29 articles in total were included in this study. The most common areas for the implementation and evaluation of EPAs were Surgery (n = 7,24.1%), Pediatric (n = 5,17.2%) and Internal medicine (n = 4,13.8%), a result that shows a relatively large change in the research trend of EPAs in the last two years. Prior to 2018, EPAs research focused on internal medicine, psychiatry, family medicine, and primary care. The articles in the category of EPAs implementation and evaluation had four main themes: (1) validation of EPAs (n = 16,55.2%); (2) describing the experience of implementing EPAs (n = 11,37.9%); (3) examining the factors and barriers that influence the implementation and evaluation of EPAs (n = 6,20.6%); and (4) researching the experiences of faculty, interns, and other relevant personnel in using EPAs. Training programs were the most common EPAs implementation setting (n = 26,89.6%); direct observation and evaluation (n = 12,41.4%), and evaluation by scoring reports (n = 5,17.2%) were the two most common means of assessing physicians' EPA levels; 19 papers (65.5%) used faculty evaluation, and nine of these papers also used self-assessment (31.0%); the most frequently used tools in the evaluation of EPAs were mainly researcher-made instruments (n = 37.9%), assessment form (n = 7,24.1%), and mobile application (n = 6,20.7%). Although EPAs occupy an increasingly important place in international medical education, this study concludes that the implementation and diffusion of EPAs on a larger scale is still difficult.


Assuntos
Educação Baseada em Competências , Internato e Residência , Criança , Competência Clínica , Educação de Pós-Graduação em Medicina , Humanos , Medicina Interna/educação
18.
Alzheimers Dement ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34569707

RESUMO

INTRODUCTION: Tumor necrosis factor (TNF) inhibitors are widely used to treat rheumatoid arthritis (RA) and their potential to retard Alzheimer's disease (AD) progression has been reported. However, their long-term effects on the dementia/AD risk remain unknown. METHODS: A propensity scored matched retrospective cohort study was conducted among 40,207 patients with RA within the US Veterans Affairs health-care system from 2000 to 2020. RESULTS: A total of 2510 patients with RA prescribed TNF inhibitors were 1:2 matched to control patients. TNF inhibitor use was associated with reduced dementia risk (hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.52-0.80), which was consistent as the study period increased from 5 to 20 years after RA diagnosis. TNF inhibitor use also showed a long-term effect in reducing the risk of AD (HR: 0.57, 95% CI: 0.39-0.83) during the 20 years of follow-up. CONCLUSION: TNF inhibitor use is associated with lower long-term risk of dementia/AD among US veterans with RA.

19.
Nat Commun ; 12(1): 5305, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489447

RESUMO

Mitochondrial dysfunction is a common hallmark of neurological disorders, and reducing mitochondrial damage is considered a promising neuroprotective therapeutic strategy. Here, we used high-throughput small molecule screening to identify CHIR99021 as a potent enhancer of mitochondrial function. CHIR99021 improved mitochondrial phenotypes and enhanced cell viability in several models of Huntington's disease (HD), a fatal inherited neurodegenerative disorder. Notably, CHIR99201 treatment reduced HD-associated neuropathology and behavioral defects in HD mice and improved mitochondrial function and cell survival in HD patient-derived neurons. Independent of its known inhibitory activity against glycogen synthase kinase 3 (GSK3), CHIR99021 treatment in HD models suppressed the proteasomal degradation of calpastatin (CAST), and subsequently inhibited calpain activation, a well-established effector of neural death, and Drp1, a driver of mitochondrial fragmentation. Our results established CAST-Drp1 as a druggable signaling axis in HD pathogenesis and highlighted CHIR99021 as a mitochondrial function enhancer and a potential lead for developing HD therapies.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Dinaminas/genética , Doença de Huntington/genética , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Calpaína/genética , Calpaína/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Modelos Animais de Doenças , Dinaminas/metabolismo , Regulação da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Doença de Huntington/tratamento farmacológico , Doença de Huntington/metabolismo , Doença de Huntington/patologia , Injeções Intraperitoneais , Masculino , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Cultura Primária de Células , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Transdução de Sinais
20.
Nat Prod Res ; : 1-8, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542359

RESUMO

A new glyoxylate-containing benzene derivative, methyl 2-(4-hydroxy-3-(3'-methyl-2'-butenyl)phenyl)-2-oxoacetate (1), together with ten known compounds (2-11), were isolated from the marine algicolous fungus, Aspergillus sp. SCSIO 41304. Their planar structures and absolute configurations were elucidated by detailed NMR, MS spectroscopic analysis and comparing with literature data. Compound 1 was isolated as a new fungal secondary metabolite, possessing a methyl glyoxylate moiety R-CO-CO-OCH3, which is rare in natural sources. All the isolated compounds (1-11) were tested for their antibacterial and enzyme inhibitory activities against acetylcholinesterase (AChE) and pancreatic lipase (PL). Among these compounds, aspulvinone H (4) showed moderate inhibition against AChE and PL with IC50 values of 25.95 and 47.06 µM, respectively. Further molecular docking simulation exhibited that compound 4 could well bind to the catalytic pockets of the AChE and PL.

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