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2.
Oncol Lett ; 18(5): 4403-4414, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31611949

RESUMO

Pancreatic cancer is a highly malignant cancer associated with high expression levels of sonic hedgehog signaling molecule (Shh), patched 1 (Ptch1), smoothened frizzled class receptor (Smo) and glioma-associated oncogene family zinc finger 1 (Gli1) in the hedgehog (Hh) signaling pathway. Inhibition of the Hh signaling pathway is a potential therapeutic target for pancreatic cancer. The aim of the present study was to investigate the effects of dauricine in a pancreatic cancer BxPC-3 ×enograft animal model and examine the underlying molecular mechanisms through Hh signaling pathway. High-and low-dose dauricine treatment significantly suppressed tumor growth with no concomitant effect on the spleen index. In addition, dauricine induced apoptosis and cell cycle arrest in pancreatic cancer BxPC-3 cells. The inhibitory effects of dauricine on pancreatic cancer may be mediated by the suppression of the Hh signaling pathway, as indicated by the decreases in the gene and protein expression levels of Shh, Ptch1, Smo and Gli1. The effects of dauricine were similar to those of 5-fluorouracil. Dauricine, a naturally occurring alkaloid, may be a potential anticancer agent for the treatment of pancreatic cancer.

3.
J Exp Clin Cancer Res ; 38(1): 237, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171015

RESUMO

BACKGROUND: Liver cancer stem cells (LCSCs) are a small subset of cells characterized by unlimited self-renewal, cell differentiation, and uncontrollable cellular growth. LCSCs are also resistant to conventional therapies and are thus believed to be held responsible for causing treatment failure of hepatocellular carcinoma (HCC). It has been recently found that long non-coding RNAs (lncRNAs) are important regulators in HCC. This present study aims to explore the underlying mechanism of how lncRNA DLX6-AS1 influences the development of LCSCs and HCC. METHODS: A microarray-based analysis was performed to initially screen differentially expressed lncRNAs associated with HCC. We then analyzed the lncRNA DLX6-AS1 levels as well as CADM1 promoter methylation. The mRNA and protein expression of CADM1, STAT3, CD133, CD13, OCT-4, SOX2, and Nanog were then detected. We quantified our results by evaluating the spheroid formation, proliferation, and tumor formation abilities, as well as the proportion of tumor stem cells, and the recruitment of DNA methyltransferase (DNMT) in LCSCs when lncRNA DLX6-AS1 was either overexpressed or silenced. RESULTS: LncRNA DLX6-AS1 was upregulated in HCC. The silencing of lncRNA DLX6-AS1 was shown to reduce and inhibit spheroid formation, colony formation, proliferation, and tumor formation abilities, as well as attenuate CD133, CD13, OCT-4, SOX2, and Nanog expression in LCSCs. Furthermore, downregulation of lncRNA DLX6-AS1 contributed to a reduction in CADM1 promoter methylation via suppression of DNMT1, DNMT3a, and DNMT3b in LCSCs and inactivating the STAT3 signaling pathway. CONCLUSION: This study demonstrated that down-regulated lncRNA DLX6-AS1 may inhibit the stem cell properties of LCSCs through upregulation of CADM1 by suppressing the methylation of the CADM1 promoter and inactivation of the STAT3 signaling pathway.


Assuntos
Molécula 1 de Adesão Celular/genética , Transformação Celular Neoplásica/genética , Metilação de DNA , Proteínas de Homeodomínio/genética , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Animais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Xenoenxertos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Modelos Biológicos , Células-Tronco Neoplásicas/metabolismo
4.
Biosci Biotechnol Biochem ; 82(1): 57-64, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29191087

RESUMO

Alzheimer's disease (AD) is the most common cause of dementia among elderly population. Deranged ß-amyloid (Aß) trafficking across the blood-brain barrier is known to be a critical element in the pathogenesis of AD. In the vascular endothelial cells of hippocampus, Aß transport is mainly mediated by low-density lipoprotein-associated protein 1 (LRP1) and the receptor for advanced glycation end (RAGE) products; therefore, LRP1 and RAGE endothelial cells are potential therapeutic targets for AD. In this study, we explored the effects of Formononetin (FMN) on learning and memory improvement in APP/PS1 mice and the related mechanisms. We found that FMN significantly improved learning and memory ability by suppressing Aß production from APP processing, RAGE-dependent inflammatory signaling and promoted LRP1-dependent cerebral Aß clearance pathway. Moreover, FMN treatment alleviated ultrastructural changes in hippocampal vascular endothelial cells. In conclusion, we believe that FMN may be an efficacious and promising treatment for AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Isoflavonas/uso terapêutico , Fármacos Neuroprotetores , Animais , Humanos , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Camundongos , Fármacos Neuroprotetores/uso terapêutico , Receptor para Produtos Finais de Glicação Avançada/efeitos dos fármacos , Receptores de LDL/efeitos dos fármacos , Proteínas Supressoras de Tumor/efeitos dos fármacos
5.
Molecules ; 21(8)2016 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-27527137

RESUMO

Blumea balsamifera, also named Ainaxiang, is widely used as an ancient medicinal herb in tropical and subtropical Asia. It is rich in essential oils. In this work the essential oils of B. balsamifera from different plant organs and in different months were extracted, and then analyzed by gas chromatography-mass spectrometry. The results showed that essential oil yield of young leaves was the highest (0.65 mL/100 g), followed by mature leaves (0.57 mL/100 g), and the oil yield was higher in October (0.47 mL/100 g) than other months. A total of 44 compounds were identified, representing 92.64%-96.71% of the oil. Eighteen common chemical components were found among the six plant organs, representing >80% of the oil constituents. l-borneol was the main ingredient in leaves, and its content was the highest in senescent leaves and in December. In the essential oils of young shoots and young stems, the main component was dimethoxydurene. Antioxidant activity was also determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ß-carotene bleaching (BCB) assays. The results indicated that the ß-carotene bleaching activity was far stronger than the DPPH radical-scavenging capacity, and the young leaves and young shoots showed stronger antioxidant activity. Dimethoxydurene, ß-caryophyllene, and α-caryophyllene play a positive role in good antioxidant activity, while ß-eudesmol, phytol, and tetradecanal play a negative role. The antioxidant activity revealed in this study might help in developing this promising bioresource for use in the medicinal and cosmetic industries.


Assuntos
Antioxidantes/farmacologia , Asteraceae/crescimento & desenvolvimento , Óleos Voláteis/farmacologia , Antioxidantes/química , Asteraceae/química , Cromatografia Gasosa-Espectrometria de Massas , Óleos Voláteis/química , Oxirredução/efeitos dos fármacos , Folhas de Planta/química , Folhas de Planta/crescimento & desenvolvimento , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Brotos de Planta/química , Brotos de Planta/crescimento & desenvolvimento , Caules de Planta/química , Caules de Planta/crescimento & desenvolvimento
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