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  • 1
    Online Resource
    Online Resource
    A novel synthetic oleanolic acid derivative with amino acid conjugate suppresses tumour growth by inducing cell cycle arrest
    Oxford University Press (OUP) ; 2010
    In:  Journal of Pharmacy and Pharmacology Vol. 59, No. 8 ( 2010-02-18), p. 1087-1093
    Details
    In: Journal of Pharmacy and Pharmacology, Oxford University Press (OUP), Vol. 59, No. 8 ( 2010-02-18), p. 1087-1093
    Abstract: Oleanolic acid (3β-hydroxy-olean-12-en-28-oic acid; OA) has a wide variety of bioactivities and is used for medicinal purposes in many Asian countries. Various derivatives of OA have been synthesized in attempts to improve the potency. Here we describe the anti-tumour activity of a novel OA derivative, N-[(3β)-3-(acetyloxy)-28-oxoolean-12-en-28-yl]-glycine methyl ester (AOA-GMe). AOA-GMe was a more potent inhibitor of the growth of B16 melanoma cells than its parent compound OA, both in-vitro and in-vivo. AOA-GMe also exhibited dose-dependent inhibition of human K562 leukaemia cells, but had almost no toxicity in normal human peripheral blood mononuclear cells. AOA-GMe induced cell cycle arrest in G0/G1 and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D, cyclin-dependent kinase CDK4 and phosphorylated retinoblastoma protein, and increases in the cyclin-dependent kinase inhibitor p15. OA did not show such activities. These results suggest that AOA-GMe may induce growth arrest in tumour cells through regulation of proteins involved in the cell cycle.
    Type of Medium: Online Resource
    ISSN: 0022-3573 , 2042-7158
    URL: Article
    DOI: 10.1211/jpp.59.8.0005
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2010
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    detail.hit.zdb_id: 2050532-2
    SSG: 15,3
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  • 2
    Online Resource
    Online Resource
    The Differentially Expressed Circular RNAs in the Substantia Nigra and Corpus Striatum of Nrf2-Knockout Mice
    S. Karger AG ; 2018
    In:  Cellular Physiology and Biochemistry Vol. 50, No. 3 ( 2018), p. 936-951
    Details
    In: Cellular Physiology and Biochemistry, S. Karger AG, Vol. 50, No. 3 ( 2018), p. 936-951
    Abstract: Background/Aims: The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a protective role in both acute neuronal damage and chronic neurodegeneration-related oxidative stress. Circular RNAs (circRNAs) are involved with various diseases in the central nervous system (CNS). This study aimed to identify the key circRNAs involved in Nrf2-neuroprotection against oxidative stress. Methods: The differentially expressed circRNAs (DEcircRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice were identified by microarray analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was then used to validate the expression of selected DEcircRNAs in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice. Based on our previous microarray analysis of the differentially expressed mRNAs (DEmRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice, the DEcircRNA-miRNA-DEmRNA interaction network was constructed. Functional annotation of DEmRNAs that shared the same binding miRNAs with DEcircRNAs was performed using gene ontology (GO) and pathway analyses. Results: A total of 65 and 150 significant DEcircRNAs were obtained in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, respectively, and seventeen shared DEcircRNAs were found in both these two tissues. The qRT-PCR results were generally consistent with the microarray results. The DEcircRNA-miRNA-DEmRNA interaction network and pathway analysis indicated that mmu_circRNA_34132, mmu_circRNA_017077 and mmu-circRNA-015216 might be involved with Nrf2-mediated neuroprotection against oxidative stress. Mmu_circRNA_015216 and mmu_circRNA_017077 might play roles in the Nrf2-related transcriptional misregulation and Nrf2-mediated processes of rheumatoid arthritis, respectively. In addition to these two processes, mmu_circRNA_34132 may be a potential regulator of Nrf2-mediated protection for diabetes mellitus and Nrf2-mediated defence against ROS in hearts. Conclusion: In conclusion, our study identified the key DEcircRNAs in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, which might provide new clues for further exploring the mechanism of Nrf2-mediated neuroprotection against oxidative stress and other Nrf2-mediated processes.
    Type of Medium: Online Resource
    ISSN: 1015-8987 , 1421-9778
    URL: Article
    DOI: 10.1159/000494478
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2018
    detail.hit.zdb_id: 1482056-0
    SSG: 12
    SSG: 15,3
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  • 3
    Online Resource
    Online Resource
    Reversal of Lipid Metabolism Dysregulation by Selenium and Folic Acid Co-Supplementation to Mitigate Pathology in Alzheimer’s Disease
    MDPI AG ; 2022
    In:  Antioxidants Vol. 11, No. 5 ( 2022-04-24), p. 829-
    Details
    In: Antioxidants, MDPI AG, Vol. 11, No. 5 ( 2022-04-24), p. 829-
    Abstract: Aberrant lipid metabolism is reported to be closely related to the pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease (AD). Selenium (Se) and folate are two ideal and safe nutritional supplements, whose biological effects include regulating redox and homocysteine (Hcy) homeostasis in vivo. Here, to achieve effective multitarget therapy for AD, we combined Se and folic acid in a co-supplementation regimen (Se-FA) to study the therapeutic potential and exact mechanism in two transgenic mouse models of AD (APP/Tau/PSEN and APP/PS1). In addition to a reduction in Aβ generation and tau hyperphosphorylation, a restoration of synaptic plasticity and cognitive ability was observed in AD mice upon Se-FA administration. Importantly, by using untargeted metabolomics, we found that these improvements were dependent on the modulation of brain lipid metabolism, which may be associated with an antioxidant effect and the promotion of Hcy metabolism. Thus, from mechanism to effects, this study systematically investigated Se-FA as an intervention for AD, providing important mechanistic insights to inform its potential use in clinical trials.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox11050829
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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  • 4
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    Online Resource
    Abietane Diterpenoids With Potent Cytotoxic Activities From the Resins of Populus euphratica
    SAGE Publications ; 2019
    In:  Natural Product Communications Vol. 14, No. 5 ( 2019-05), p. 1934578X1985002-
    Details
    In: Natural Product Communications, SAGE Publications, Vol. 14, No. 5 ( 2019-05), p. 1934578X1985002-
    Abstract: A new abietane norditerpenoid, 5-(6-isopropyl-2-methylnaphthalen-1-yl)pentan-2-one (1), with a rare 4,5-seco-19-norabietane skeleton possessing a rearranged angular methyl group at C-5, 2 new naturally occurring compounds, 19-norabieta-4,6,8,11,13-penttaen-3-one (2) and 14-hydroxy-7-oxo ester (3), along with 10 known analogs (4−13) were isolated from the resins of Populus euphratica. The new structures were elucidated by spectroscopic analysis (one-/two-dimensional nuclear magnetic resonance and high-reolution electrospray ionization mass spectrometry). Biological evaluation showed that compounds 1 and 2 display low cytotoxicity against normal cells and appreciable cytotoxicity in cancer cells, with 2 to be more sensitive in HepG2 cells with a half-maximal inhibitory concentration value of 27.0 μM.
    Type of Medium: Online Resource
    ISSN: 1934-578X , 1555-9475
    URL: Article
    DOI: 10.1177/1934578X19850029
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
    detail.hit.zdb_id: 2430442-6
    SSG: 15,3
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