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  • 1
    In: Stem Cells International, Hindawi Limited, Vol. 2018 ( 2018-07-11), p. 1-17
    Abstract: Mesenchymal stem cells- (MSCs-) based therapies show different degrees of efficacies for the treatment of various diseases, including lipogenesis. We evaluated the adipogenic differentiation ability of human umbilical cord blood-derived MSCs (hUCB-MSCs) from different donors and examined the contribution of the intracellular calcium (Ca 2+ ) level to this diversity. hUCB-MSCs treated with Ca 2+ or the Ca 2+ chelator BAPTA-AM increased and decreased adipogenic differentiation, respectively. Canonical Wnt5a/ β -catenin expression decreased during adipogenic differentiation of hUCB-MSCs. Treatment with Wnt5a blocked the adipogenic differentiation of hUCB-MSCs and activated the Wnt pathway, with a decrease in the adipogenesis markers PPAR γ and leptin, and reduced lipid vacuole-associated Oil red O activity. In contrast, inhibition of the Wnt pathway with dickkopf-1 and β -catenin small interfering RNA transfection promoted the adipogenic potential of hUCB-MSCs. Interestingly, the Ca 2+ -based system exhibited a synergic effect on adipogenic potential through the Wnt5a/ β -catenin pathway. Our data suggest that the variable adipogenic differentiation potential of hUCB-MSCs from different lots is due to variation in the intracellular Ca 2+ level, which can be used as a marker to predict hUCB-MSCs selection for lipogenesis therapy. Overall, these results demonstrate that exogenous calcium treatment enhanced the adipogenic differentiation of hUCB-MSCs via negatively regulating the Wnt5a/ β -catenin signaling pathway.
    Type of Medium: Online Resource
    ISSN: 1687-966X , 1687-9678
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2018
    detail.hit.zdb_id: 2573856-2
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  • 2
    In: Mediators of Inflammation, Hindawi Limited, Vol. 2012 ( 2012), p. 1-8
    Abstract: Nanostructured, self-assembling peptides hold promise for a variety of regenerative medical applications such as 3D cell culture systems, accelerated wound healing, and nerve repair. The aim of this study was to determine whether the self-assembling peptide K5 can be applied as a carrier of anti-inflammatory drugs. First, we examined whether the K5 self-assembling peptide itself can modulate various cellular inflammatory responses. We found that peptide K5 significantly suppressed the release of tumor-necrosis-factor- (TNF-) α and prostaglandin E 2 (PGE 2 ) from RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Similarly, there was inhibition of cyclooxygenase- (COX-) 2 mRNA expression assessed by real-time PCR, indicating that the inhibition is at the transcriptional level. In agreement with this finding, peptide K5 suppressed the translocation of the transcription factors activator protein (AP-1) and c-Jun and inhibited upstream inflammatory effectors including mitogen activated protein kinase (MAPK), p38, and mitogen-activated protein kinase kinase 3/6 (MKK 3/6). Whether this peptide exerts its effects via a transmembrane or cytoplasmic receptor is not clear. However, our data strongly suggest that the nanostructured, self-assembling peptide K5 may possess significant anti-inflammatory activity via suppression of the p38/AP-1 pathway.
    Type of Medium: Online Resource
    ISSN: 0962-9351 , 1466-1861
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2008065-7
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  • 3
    In: Mediators of Inflammation, Hindawi Limited, Vol. 2014 ( 2014), p. 1-9
    Abstract: 21-O-Angeloyltheasapogenol E3 (ATS-E3) is a triterpenoid saponin recently isolated from the seeds of the tea tree Camellia sinensis (L.) O. Kuntze. ATS-E3 has several beneficial properties including anti-inflammatory, antidiabetic, antiatherosclerotic, and anticancer effects. Unlike other phenolic compounds isolated from tea plants, there are no studies reporting the pharmacological action of ATS-E3. In this study, we therefore aimed to explore the cellular and molecular inhibitory activities of ATS-E3 in macrophage-mediated inflammatory responses. ATS-E3 remarkably diminished cellular responses of macrophages such as FITC-dextran-induced phagocytic uptake, sodium nitroprusside- (SNP-) induced radical generation, and LPS-induced nitric oxide (NO) production. Analysis of its molecular activity showed that this compound significantly suppressed the expression of inducible NO synthase (iNOS), nuclear translocation of nuclear factor- (NF-) κ B subunits (p50 and p65), phosphorylation of inhibitor of κ B kinase (IKK), and the enzyme activity of AKT1. Taken together, the novel triterpenoid saponin compound ATS-E3 contributes to the beneficial effects of tea plants by exerting anti-inflammatory and antioxidative activities in an AKT/IKK/NF- κ B-dependent manner.
    Type of Medium: Online Resource
    ISSN: 0962-9351 , 1466-1861
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2014
    detail.hit.zdb_id: 2008065-7
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  • 4
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2014 ( 2014), p. 1-12
    Abstract: The inhibitory activities of the Cordyceps pruinosa butanol fraction (Cp-BF) were investigated by determining inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells and by evaluating HCl/ethanol (EtOH)-triggered gastric ulcers in mice. The molecular mechanisms of the inhibitory effects of Cp-BF were investigated by identifying target enzymes using biochemical and molecular biological approaches. Cp-BF strongly inhibited the production of NO and TNF- α , release of reactive oxygen species (ROS), phagocytic uptake of FITC-dextran, and mRNA expression levels of interleukin (IL)-6, inducible NO synthase (iNOS), and tumour necrosis factor-alpha (TNF)- α in activated RAW264.7 cells. Cp-BF also strongly downregulated the NF- κ B pathway by suppressing IKK β according to luciferase reporter assays and immunoblot analysis. Furthermore, Cp-BF blocked both increased levels of NF- κ B-mediated luciferase activities and phosphorylation of p65/p50 observed by IKK β overexpression. Finally, orally administered Cp-BF was found to attenuate gastric ulcer and block the phosphorylation of I κ B α induced by HCl/EtOH. Therefore, these results suggest that the anti-inflammatory activity of Cp-BF may be mediated by suppression of IKK α and its downstream NF- κ B activation. Since our group has established the mass cultivation conditions by developing culture conditions for Cordyceps pruinosa , the information presented in this study may be useful for developing new anti-inflammatory agents.
    Type of Medium: Online Resource
    ISSN: 1741-427X , 1741-4288
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2014
    detail.hit.zdb_id: 2148302-4
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  • 5
    In: Mediators of Inflammation, Hindawi Limited, Vol. 2017 ( 2017), p. 1-9
    Abstract: To address how interleukin-1 receptor-associated kinase 1 (IRAK1) is controlled by other enzymes activated by toll-like receptor (TLR) 4, we investigated the possibility that spleen tyrosine kinase (Syk), a protein tyrosine kinase that is activated at an earlier stage during TLR4 activation, plays a central role in regulating the functional activation of IRAK1. Indeed, we found that overexpression of myeloid differentiation primary response gene 88 (MyD88), an adaptor molecule that drives TLR signaling, induced IRAK1 expression and that piceatannol, a Syk inhibitor, successfully suppressed the MyD88-dependent upregulation of IRAK1 under LPS treatment conditions. Interestingly, in Syk-knockout RAW264.7 cells, IRAK1 activity was almost completely blocked after LPS treatment, while providing a Syk-recovery gene to the knockout cells successfully restored IRAK1 expression. According to our measurements of IRAK1 mRNA levels, the transcriptional upregulation of IRAK1 was induced by LPS treatment between 4 and 60 min, and this can be suppressed in Syk knockout cells, providing an effect similar that that seen under piceatannol treatment. The overexpression of Syk reverses this effect and leads to a significantly higher IRAK1 mRNA level. Collectively, our results strongly suggest that Syk plays a critical role in regulating both the activity and transcriptional level of IRAK1.
    Type of Medium: Online Resource
    ISSN: 0962-9351 , 1466-1861
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2017
    detail.hit.zdb_id: 2008065-7
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  • 6
    In: Mediators of Inflammation, Hindawi Limited, Vol. 2014 ( 2014), p. 1-12
    Abstract: In this study, we aimed to examine the cellular and molecular mechanisms of lancemaside A from Codonopsis lanceolata (Campanulaceae) in the inflammatory responses of monocytes (U937 cells) and macrophages (RAW264.7 cells). Lancemaside A significantly suppressed the inflammatory functions of lipopolysaccharide- (LPS-) treated RAW264.7 cells by suppressing the production of nitric oxide (NO), the expression of the NO-producing enzyme inducible NO synthase (iNOS), the upregulation of the costimulatory molecule CD80, and the morphological changes induced by LPS exposure. In addition, lancemaside A diminished the phagocytic activity of RAW264.7 cells and boosted the neutralizing capacity of these cells when treated with the radical generator sodium nitroprusside (SNP). Interestingly, lancemaside A strongly blocked the adhesion activity of RAW264.7 cells to plastic culture plates, inhibited the cell-cell and cell-fibronectin (FN) adhesion of U937 cells that was triggered by treatment with an anti- β 1-integrin (CD29) antibody and immobilized FN, respectively. By evaluating the activation of various intracellular signaling pathways and the levels of related nuclear transcription factors, lancemaside A was found to block the activation of inhibitor of κ B kinase (IKK) and p65/nuclear factor- (NF-) κ B. Taken together, our findings strongly suggest that the anti-inflammatory function of lancemaside A is the result of its strong antioxidative and IKK/NF- κ B inhibitory activities.
    Type of Medium: Online Resource
    ISSN: 0962-9351 , 1466-1861
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2014
    detail.hit.zdb_id: 2008065-7
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  • 7
    In: BioMed Research International, Hindawi Limited, Vol. 2018 ( 2018), p. 1-6
    Abstract: Objective. Angiotensin II (Ang II) plays a profibrotic role in the kidneys. Although many pathways of Ang II have been discovered, the morphological and mechanical aspects have not been well investigated. We observed the changes in tubular epithelial cells (TECs) after Ang II treatment with or without Ang II receptor blockers (ARBs) using atomic force microscopy (AFM). Methods. TECs were stimulated with Ang II with or without telmisartan, PD123319, and blebbistatin. AFM was performed to measure the cellular stiffness, cell volume, and cell surface roughness. Epithelial to mesenchymal transition markers were determined via immunocytochemistry. Results. After Ang II stimulation, cells transformed to a flattened and elongated mesenchymal morphology. Cell surface roughness and volume significantly increased in Ang II treated TECs. Ang II also induced an increase in phospho-myosin light chain and F-actin and a decrease in E-cadherin. Ang II coincubation with either telmisartan or blebbistatin attenuated these Ang II-induced changes. Conclusion. We report, for the first time, the use of AFM in directly observing the changes in TECs after Ang II treatment with or without ARBs. Simultaneously, we successfully measured the selective effect of PD123319 or blebbistatin. AFM could be a noninvasive evaluating strategy for cellular processes in TECs.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2018
    detail.hit.zdb_id: 2698540-8
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  • 8
    Online Resource
    Online Resource
    Hindawi Limited ; 2016
    In:  Mediators of Inflammation Vol. 2016 ( 2016), p. 1-11
    In: Mediators of Inflammation, Hindawi Limited, Vol. 2016 ( 2016), p. 1-11
    Abstract: Protein arginine methyltransferases (PRMTs) mediate the methylation of a number of protein substrates of arginine residues and serve critical functions in many cellular responses, including cancer development, progression, and aggressiveness, T-lymphocyte activation, and hepatic gluconeogenesis. There are nine members of the PRMT family, which are divided into 4 types (types I–IV). Although most PRMTs do not require posttranslational modification (PTM) to be activated, fine-tuning modifications, such as interactions between cofactor proteins, subcellular compartmentalization, and regulation of RNA, via micro-RNAs, seem to be required. Inflammation is an essential defense reaction of the body to eliminate harmful stimuli, including damaged cells, irritants, or pathogens. However, chronic inflammation can eventually cause several types of diseases, including some cancers, atherosclerosis, rheumatoid arthritis, and periodontitis. Therefore, inflammation responses should be well modulated. In this review, we briefly discuss the role of PRMTs in the control of inflammation. More specifically, we review the roles of four PRMTs (CARM1, PRMT1, PRMT5, and PRMT6) in modulating inflammation responses, particularly in terms of modulating the transcriptional factors or cofactors related to inflammation. Based on the regulatory roles known so far, we propose that PRMTs should be considered one of the target molecule groups that modulate inflammatory responses.
    Type of Medium: Online Resource
    ISSN: 0962-9351 , 1466-1861
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2016
    detail.hit.zdb_id: 2008065-7
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  • 9
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2015 ( 2015), p. 1-10
    Abstract: The Cordyceps species have been widely used for treating various cancer diseases. Although the Cordyceps species have been widely known as an alternative anticancer remedy, which compounds are responsible for their anticancer activity is not fully understood. In this study, therefore, we examined the anticancer activity of 5 isolated compounds derived from the butanol fraction (Cb-BF) of Cordyceps bassiana . For this purpose, several cancer cell lines such as C6 glioma, MDA-MB-231, and A549 cells were employed and details of anticancer mechanism were further investigated. Of 5 compounds isolated by activity-guided fractionation from BF of Cb-EE, KTH-13, and 4-isopropyl-2,6-bis(1-phenylethyl)phenol, Cb-BF was found to be the most potent antiproliferative inhibitor of C6 glioma and MDA-MB-231 cell growth. KTH-13 treatment increased DNA laddering, upregulated the level of Annexin V positive cells, and altered morphological changes of C6 glioma and MDA-MB-231 cells. In addition, KTH-13 increased the levels of caspase 3, caspase 7, and caspase 9 cleaved forms as well as the protein level of Bax but not Bcl-2. It was also found that the phosphorylation of AKT and p85/PI3K was also clearly reduced by KTH-13 exposure. Therefore, our results suggest KTH-13 can act as a potent antiproliferative and apoptosis-inducing component from Cordyceps bassiana , contributing to the anticancer activity of this mushroom.
    Type of Medium: Online Resource
    ISSN: 1741-427X , 1741-4288
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2015
    detail.hit.zdb_id: 2148302-4
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  • 10
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2021 ( 2021-5-11), p. 1-10
    Abstract: Yijin-tang is an oriental traditional herb used to treat inflammatory diseases. In the present study, we investigated the protective effects of Yijin-tang water extract (YTE) using an ovalbumin- (OVA-) induced asthma model, focusing on the antioxidant and anti-inflammatory properties of the herb. BALB/c mice were intraperitoneally injected with OVA on days 0 and 14 and then challenged with OVA on days 21, 22, and 23. The animals were orally administered YTE (200 and 400 mg/kg) from days 18 to 23, and this was found to significantly decrease airway hyperresponsiveness and release of inflammatory cells, cytokines, and OVA-specific immunoglobulin E in mice with asthma. In addition, YTE was associated with a marked reduction in airway inflammation and mucus production in lung tissue of mice with asthma. Furthermore, YTE suppressed the expression of matrix metalloproteinase-9 and phosphorylation of ERK in the lungs, which in turn led to a reduction in inducible nitric oxide synthases and an elevation in reduced glutathione and heme oxygenase-1. In conclusion, YTE effectively suppressed allergic responses in mice with asthma and the effect was closely related to antioxidant and anti-inflammatory properties of the herb. Our results indicate that YTE may be a potential agent for the treatment of allergic asthma.
    Type of Medium: Online Resource
    ISSN: 1741-4288 , 1741-427X
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2148302-4
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