Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Sci Rep ; 10(1): 2971, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060367

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2.
Int J Biol Macromol ; 144: 1004-1012, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31715236

RESUMO

Alzheimer's disease (AD) is the most common degenerative disease of the central nervous system. It is associated with abnormal accumulation of amyloid-ß (Aß) plaques, impaired neurogenesis, and damaged cognitive functions. We have known for a long time that natural compounds and their derivatives have gained increasing attention in AD drug research due to their multiple effects and inherently enormous chemicals. In this study, we will demonstrate that polysaccharides from L. barbarum (LBP1), a traditional natural compound, can reduce Aß level and improve the cognitive functions in APP/PS1 transgenic mouse. LBP1 can enhance neurogenesis as indicated by BrdU/NeuN double labeling. Furthermore, it can restore synaptic dysfunction at hippocampus CA3-CA1 pathway. Additionally, in vitro cell assay indicates that LBP1 may affect Aß processing. In conclusion, our study indicates that LBP1 might be a potential therapeutic agent for the treatment of AD against multiple targets that include synaptic plasticity, Aß pathology and neuropathology.

3.
Neurobiol Aging ; 80: 187-195, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31203190

RESUMO

The abnormal proliferation and neurogenesis of neural progenitor cells (NPCs) is usually associated with the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). Mitochondrial stress is one of the most prominent features of AD and is thought to be involved in the impairment of the neurogenesis and proliferation of NPCs. Thus, restoring mitochondrial function by pharmaceutical intervention may alleviate disease-related defects in neurogenesis and is considered a potential therapeutic strategy for AD. In the present study, we found that the oral administration of PL201A, a designed analog of phenylpropanoids, which are a family of natural products with antiaging effects, promoted the neurogenesis and proliferation of NPCs and ameliorated cognitive impairment in a transgenic mouse model of AD. Furthermore, PL201A attenuated amyloid-ß-induced mitochondrial stress and promoted NPC proliferation in vitro. Further mechanistic studies showed that PL201A restored the activation of AMP-regulated protein kinase-retinoblastoma signaling, which was suppressed by amyloid-ß. Our findings suggest that PL201A may represent a promising regenerative therapeutic agent for cognitive decline in neurodegenerative diseases.

4.
Sci Rep ; 9(1): 3462, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30837577

RESUMO

Glioblastoma (GBM) is the most common and aggressive malignant tumor in adult brain. Even with the current standard therapy including surgical resection followed by postoperative radiotherapy and chemotherapy with temozolomide (Temo), GBM patients still have a poor median survival. Reprogramming of tumor cells into non-malignant cells might be a promising therapeutic strategy for malignant tumors, including GBM. Based on previous studies using small molecules to reprogram astrocytes into neuronal cells, here we further identified a FTT cocktail of three commonly used drugs (Fasudil, Tranilast, and Temo) to reprogram patient-derived GBM cells, either cultured in serum containing or serum-free medium, into neuronal like cells. FTT-treated GBM cells displayed a neuronal like morphology, expressed neuronal genes, exhibited neuronal electrophysiological properties, and showed attenuated malignancy. More importantly, FTT cocktail more significantly suppressed tumor growth and prolonged survival in GBM patient derived xenograft than Temo alone. Our study provided preclinical evidence that the neuronal reprogramming drug cocktail might be a promising strategy to improve the existing treatment for GBM.

5.
Sensors (Basel) ; 18(7)2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29954094

RESUMO

The characteristics of the dual-core photonic crystal fiber (PCF) sensor are studied using the finite element method (FEM), and the structure is improved according to the numerical simulation results. The results show that whether or not the four large air holes far away from the geometry center of the PCF are filled with analyte has no influence on the wavelength sensitivity of the sensor which means those holes can be replaced by small air holes. The wavelength sensitivity can be tuned by adjusting the sizes of the other large air holes which are as for liquid holes. The dynamic detection range of the refractive index (RI) is from 1.33 to 1.51. In particular, high linearity is obtained in the range of 1.44 to 1.51. The sensitivity is as high as 6021 nm/RIU when the liquid holes are the smallest. When liquid holes are tangential with the envelope of first layer air holes, the wavelength sensitivity is 4028 nm/RIU, and the coefficient of determination (R²) is 0.99822 when the RI of the analyte varies from 1.44 to 1.51 which shows that high sensitivity and good linearity are both obtained.

6.
Front Aging Neurosci ; 10: 169, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29922152

RESUMO

Alzheimer's disease (AD) is a multi-factorial neurodegenerative disorder with abnormal accumulation of amyloid-ß (Aß) plaques, neuroinflammation and impaired neurogenesis. Mounting evidences suggest that single-target drugs have limited effects on clinical treatment and alternative or multiple targets are required. In recent decades, natural compounds and their derivatives have gained increasing attention in AD drug discovery due to their inherently enormous chemical and structural diversity. In this study, we demonstrated that naringin dihydrochalcone (NDC), a widely used dietary sweetener with strong antioxidant activity, improved the cognitive function of transgenic AD mice. Pathologically, NDC attenuated Aß deposition in AD mouse brain. Furthermore, NDC reduced periplaque activated microglia and astrocytes, indicating the inhibition of neuroinflammation. It also enhanced neurogenesis as investigated by BrdU/NeuN double labeling. Additionally, the inhibition of Aß level and neuroinflammation by NDC treatment was also observed in an AD cell model or a microglia cell line. Taken together, our study indicated that NDC might be a potential therapeutic agent for the treatment of AD against multiple targets that include Aß pathology, neuroinflammation and neurogenesis.

7.
Sci Rep ; 7(1): 13222, 2017 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-29038567

RESUMO

Mammalian haploid embryonic stem cells (haESCs) provide new possibilities for large-scale genetic screens because they bear only one copy of each chromosome. However, haESCs are prone to spontaneous diploidization through unknown mechanisms. Here, we report that a small molecule combination could restrain mouse haESCs from diploidization by impeding exit from naïve pluripotency and by shortening the S-G2/M phases. Combined with 2i and PD166285, our chemical cocktail could maintain haESCs in the haploid state for at least five weeks without fluorescence-activated cell sorting (FACS) enrichment of haploid cells. Taken together, we established an effective chemical approach for long-term maintenance of haESCs, and highlighted that proper cell cycle progression was critical for the maintenance of haploid state.


Assuntos
Células-Tronco Embrionárias Murinas/metabolismo , Proteínas Quinases/metabolismo , Transdução de Sinais , Animais , Ciclo Celular/genética , Divisão Celular , Linhagem Celular , Citometria de Fluxo , Fase G2 , Haploidia , Camundongos , Camundongos Endogâmicos C57BL , Ploidias , Células-Tronco Pluripotentes , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
8.
Stem Cell Reports ; 8(5): 1124-1134, 2017 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-28457886

RESUMO

The recent establishment of mammalian haploid embryonic stem cells (ESCs) provides new possibilities for genetic screening and for understanding genome evolution and function. However, the dynamics of mitosis in haploid ESCs is still unclear. Here, we report that the duration of mitosis in haploid ESCs, especially the metaphase, is significantly longer than that in diploid ESCs. Delaying mitosis by chemicals increased self-diploidization of haploid ESCs, while shortening mitosis stabilized haploid ESCs. Taken together, our study suggests that the delayed mitosis of haploid ESCs is associated with self-diploidization.


Assuntos
Células-Tronco Embrionárias/citologia , Haploidia , Metáfase , Animais , Linhagem Celular , Diploide , Camundongos , Análise de Célula Única
9.
Stem Cell Reports ; 8(1): 84-94, 2017 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-28076758

RESUMO

Promoting neurogenesis is a promising strategy for the treatment of cognition impairment associated with Alzheimer's disease (AD). Ganoderma lucidum is a revered medicinal mushroom for health-promoting benefits in the Orient. Here, we found that oral administration of the polysaccharides and water extract from G. lucidum promoted neural progenitor cell (NPC) proliferation to enhance neurogenesis and alleviated cognitive deficits in transgenic AD mice. G. lucidum polysaccharides (GLP) also promoted self-renewal of NPC in cell culture. Further mechanistic study revealed that GLP potentiated activation of fibroblast growth factor receptor 1 (FGFR1) and downstream extracellular signal-regulated kinase (ERK) and AKT cascades. Consistently, inhibition of FGFR1 effectively blocked the GLP-promoted NPC proliferation and activation of the downstream cascades. Our findings suggest that GLP could serve as a regenerative therapeutic agent for the treatment of cognitive decline associated with neurodegenerative diseases.


Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Cognição/efeitos dos fármacos , Polissacarídeos Fúngicos/farmacologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Reishi/química , Doença de Alzheimer/tratamento farmacológico , Animais , Proliferação de Células/efeitos dos fármacos , Autorrenovação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Neurogênese/efeitos dos fármacos , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
Aging Cell ; 14(5): 784-96, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26010330

RESUMO

Aberrant neural progenitor cell (NPC) proliferation and self-renewal have been linked to age-related neurodegeneration and neurodegenerative disorders including Alzheimer's disease (AD). Rhizoma Acori tatarinowii is a traditional Chinese herbal medicine against cognitive decline. In this study, we found that the extract of Rhizoma Acori tatarinowii (AT) and its active constituents, asarones, promote NPC proliferation. Oral administration of AT enhanced NPC proliferation and neurogenesis in the hippocampi of adult and aged mice as well as that of transgenic AD model mice. AT and its fractions also enhanced the proliferation of NPCs cultured in vitro. Further analysis identified α-asarone and ß-asarone as the two active constituents of AT in promoting neurogenesis. Our mechanistic study revealed that AT and asarones activated extracellular signal-regulated kinase (ERK) but not Akt, two critical kinase cascades for neurogenesis. Consistently, the inhibition of ERK activities effectively blocked the enhancement of NPC proliferation by AT or asarones. Our findings suggest that AT and asarones, which can be orally administrated, could serve as preventive and regenerative therapeutic agents to promote neurogenesis against age-related neurodegeneration and neurodegenerative disorders.


Assuntos
Acorus/química , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Anisóis/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Fatores Etários , Animais , Anisóis/química , Anisóis/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurogênese/efeitos dos fármacos
11.
J Cell Physiol ; 230(7): 1438-47, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25556830

RESUMO

Baclofen is used clinically as a drug that treats spasticity, which is a syndrome characterized by excessive contraction of the muscles and hyperflexia in the central nervous system (CNS), by activating GABA(B) receptors (GABA(B)Rs). Baclofen was recently reported to desensitize chemokine receptors and to suppress inflammation through the activation of GABA(B)Rs. GABA(B)Rs are expressed in various immune cells, but the functions of these receptors in autoimmune diseases remain largely unknown. In this study, we investigated the effects of baclofen in murine collagen-induced arthritis (CIA). Oral administration of baclofen alleviated the clinical development of CIA, with a reduced number of IL-17-producing T helper 17 (T(H)17) cells. In addition, baclofen treatment suppressed dendritic cell (DC)-primed T(H)17 cell differentiation by reducing the production of IL-6 by DCs in vitro. Furthermore, the pharmacological and genetic blockade of GABA(B)Rs in DCs weakened the effects of baclofen, indicating that GABA(B)Rs are the molecular targets of baclofen on DCs. Thus, our findings revealed a potential role for baclofen in the treatment of CIA, as well as a previously unknown signaling pathway that regulates DC function.


Assuntos
Artrite/induzido quimicamente , Baclofeno/uso terapêutico , Colágeno/toxicidade , Células Dendríticas/efeitos dos fármacos , Agonistas dos Receptores de GABA-B/uso terapêutico , Animais , Baclofeno/farmacologia , Linfócitos T CD4-Positivos/fisiologia , Diferenciação Celular , Sobrevivência Celular , Células Dendríticas/citologia , Células Dendríticas/fisiologia , Agonistas dos Receptores de GABA-B/farmacologia , Antagonistas de Receptores de GABA-B/farmacologia , Regulação da Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Relaxantes Musculares Centrais/farmacologia , Relaxantes Musculares Centrais/uso terapêutico , Receptores de GABA-B/genética , Receptores de GABA-B/metabolismo , Células Th17/citologia , Células Th17/fisiologia
12.
Zhongguo Zhong Yao Za Zhi ; 38(11): 1676-8, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-24010275

RESUMO

In this work, a rapid analysis method basing on ultraviolet spectroscopy was established for the determination of danshensu, protocatechuic aldehyde, rosmarinci acid, lithospermic acid and salvianolic acid B in the extraction process of Danhong injection. In the extraction process of Danshen and Honghua crude drugs, 44 extraction solution samples were collected and the contents of the five components were determined by HPLC analysis. The ultraviolet spectra of the samples were collected. Partial least square regression was used to establish the multivariate calibration models between the ultraviolet spectra and the contents of the five components. The results showed that the established models could predict the contents of the five components in the extraction solution accurately. The ultraviolet spectroscopy method established in this work can be used for rapid analysis of the intermediates of Danhong injection, which may be applied for the quality control in the manufacturing process.


Assuntos
Química Farmacêutica/normas , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/isolamento & purificação , Salvia miltiorrhiza/química , Espectrofotometria Ultravioleta/métodos , Cromatografia Líquida de Alta Pressão , Controle de Qualidade
13.
Proc Natl Acad Sci U S A ; 110(18): 7395-400, 2013 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-23589893

RESUMO

Rheumatoid arthritis (RA) is an inflammatory disease in which interleukin 17 (IL-17)-producing T helper 17 (T(H)17) cells have been critically involved. We show that in patients with RA, the expression of a multifunctional regulator ß-arrestin1 was significantly up-regulated in peripheral and synovial CD4(+) T cells, which correlated well with active phases of RA. In collagen-induced arthritis, deficiency of ß-arrestin1 ameliorated disease with decreased T(H)17 cell differentiation, proinflammatory cytokine production, synovitis, and cartilage and bone destruction. Further mechanistic study reveals that ß-arrestin1 promoted signal transducer and activator of transcription 3 (STAT3) activation required for T(H)17 cell differentiation through scaffolding the interaction of Janus kinase 1 and STAT3. These findings indicate a critical role for ß-arrestin1 in the pathogenesis of collagen-induced arthritis and T(H)17 cell differentiation and suggest ß-arrestin1 as a potential diagnostic biomarker and therapeutic target for RA.


Assuntos
Arrestinas/deficiência , Artrite Experimental/imunologia , Artrite Experimental/patologia , Diferenciação Celular/imunologia , Células Th17/imunologia , Células Th17/patologia , Animais , Arrestinas/metabolismo , Artrite Experimental/metabolismo , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Técnicas de Silenciamento de Genes , Humanos , Interleucina-17/metabolismo , Janus Quinase 1/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator de Transcrição STAT3/metabolismo , Regulação para Cima , beta-Arrestinas
14.
Nucleic Acids Res ; 38(18): 6054-64, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20507910

RESUMO

Dnmt3a and Dnmt3b are paralogous enzymes responsible for de novo DNA methylation but with distinguished biological functions. In mice, disruption of Dnmt3b but not Dnmt3a causes global DNA hypomethylation, especially in repetitive sequences, which comprise the large majority of methylated DNA in the genome. By measuring DNA methylation activity of Dnmt3a and Dnmt3b homologues from five species, we found that mammalian Dnmt3b possessed significantly higher methylation activity on chromatin DNA than Dnmt3a and non-mammalian Dnmt3b. Sequence comparison and mutagenesis experiments identified a single amino acid substitution (I662N) in mammalian Dnmt3b as being crucial for its high chromatin DNA methylation activity. Further mechanistic studies demonstrated this substitution markedly enhanced the binding of Dnmt3b to nucleosomes and hence increased the chromatin DNA methylation activity. Moreover, this substitution was crucial for Dnmt3b to efficiently methylate repetitive sequences, which increased dramatically in mammalian genomes. Consistent with our observation that Dnmt3b evolved more rapidly than Dnmt3a during the emergence of mammals, these results demonstrated that the I662N substitution in mammalian Dnmt3b conferred enhanced chromatin DNA methylation activity and contributed to functional adaptation in the epigenetic system.


Assuntos
Cromatina/enzimologia , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Células Cultivadas , DNA (Citosina-5-)-Metiltransferases/química , Epigênese Genética , Humanos , Camundongos , Dados de Sequência Molecular , Nucleossomos/enzimologia , Ligação Proteica , Sequências Repetitivas de Ácido Nucleico
15.
Nat Immunol ; 10(12): 1252-9, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19838199

RESUMO

Interleukin 17 (IL-17)-producing T helper cells (T(H)-17 cells) are increasingly recognized as key participants in various autoimmune diseases, including multiple sclerosis. Although sets of transcription factors and cytokines are known to regulate T(H)-17 differentiation, the role of noncoding RNA is poorly understood. Here we identify a T(H)-17 cell-associated microRNA, miR-326, whose expression was highly correlated with disease severity in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis (EAE). In vivo silencing of miR-326 resulted in fewer T(H)-17 cells and mild EAE, and its overexpression led to more T(H)-17 cells and severe EAE. We also found that miR-326 promoted T(H)-17 differentiation by targeting Ets-1, a negative regulator of T(H)-17 differentiation. Our data show a critical role for microRNA in T(H)-17 differentiation and the pathogenesis of multiple sclerosis.


Assuntos
Diferenciação Celular , MicroRNAs/genética , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Linfócitos T Auxiliares-Indutores/citologia , Linfócitos T Auxiliares-Indutores/imunologia , Adulto , Animais , Sequência de Bases , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Feminino , Humanos , Interleucina-17/imunologia , Masculino , Camundongos , Esclerose Múltipla/patologia , Proteína Proto-Oncogênica c-ets-1/genética , Proteína Proto-Oncogênica c-ets-1/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Regulação para Cima
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA