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  • 1
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    Perturbation of miR-370-LIN28A-NF-κB regulatory circuit contributes to the development of hepatocellular carcinoma (2013)
    Wiley-Blackwell
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    Publication Date: 2013-06-01
    Description: miR-370 is located within the DLK1/DIO3 imprinting region on human chromosome 14, which has been identified as a cancer-associated genomic region. However, the role of miR-370 in malignances remains controversial. Here we report that miR-370 was repressed in human hepatocellular carcinoma (HCC) tissues and hepatoma cell lines. Using gain-of-function and loss-of-function experiments, we demonstrated that miR-370 inhibited the malignant phenotype of HCC cells in vitro . Overexpression of miR-370 inhibited the growth and metastasis of HCC cells in vivo . Moreover, the RNA-binding protein LIN28A was identified as a direct functional target of miR-370, which in turn blocked the biogenesis of miR-370 by binding to its precursor. LIN28A also mediated the suppressive effects of miR-370 on migration and invasion of HCC cells by post-transcriptionally regulating RelA/p65, which is an important effector of the canonical nuclear factor κB (NF-κB) pathway. Interleukin 6 (IL6), a well-known NF-κB downstream inflammatory molecule, reduced miR-370 but increased LIN28A levels in HCC. Furthermore, miR-370 levels were inversely correlated with LIN28A and IL-6 mRNA levels, whereas LIN28A mRNA expression was positively correlated with IL-6 expression in human HCC samples. Interestingly, reduction of miR-370 expression was associated with the development of HCC in rats, as well as with aggressive tumor behavior and short survival in HCC patients. Conclusions: These data demonstrate the involvement of a novel regulatory circuit consisting of miR-370, LIN28A, RelA/p65 and IL-6 in HCC progression. Manipulating this feedback loop may have beneficial effect in HCC treatment. (H EPATOLOGY 2013.)
    Print ISSN: 0270-9139
    Electronic ISSN: 1527-3350
    Topics: Medicine
    Published by Wiley-Blackwell on behalf of The American Association for the Study of Liver Diseases.
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  • 2
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    Ceftriaxone modulates uptake activity of glial glutamate transporter-1 against global brain ischemia in rats (2014)
    Wiley-Blackwell
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    Publication Date: 2014-10-03
    Description: Ceftriaxone(Cef) selectively increases expression of glial glutamate transporter-1 (GLT-1), which was thought to be neuroprotective in some circumstances. However, the effect of Cef on glutamate uptake of GLT-1 was assayed using in vitro studies such as primary neuron/astrocyte cultures or brain slices. In addition, the effect of Cef on neurons in different ischemic models was still discrepant. Therefore, the present study was undertaken to observe the effect of Cef on neurons in global brain ischemia in rats, and especially to provide direct evidence of the upregulation of GLT-1 uptake for glutamate contributing to the neuronal protection of Cef against brain ischemia. Neuropathological evaluation indicated administration of Cef, especially pre-treatment protocols, significantly prevented delayed neuronal death in hippocampal CA1 subregion normally induced by global brain ischemia. Simultaneously, pre-administration of Cef significantly upregulated the expression of GLT-1. Particularly, GLT-1 uptake assay with 3 H-glutamate in living cells from adult rats showed that upregulation in glutamate uptake accompanied upregulated GLT-1 expression. Inhibition of GLT-1 by antisense oligodeoxynucleotides or dihydrokainate significantly inhibited the Cef-induced upregulation in GLT-1 uptake and the neuroprotective effect against global ischemia. Thus, we may conclude that Cef protects neurons against global brain ischemia via upregulation of the expression and glutamate uptake of GLT-1. This article is protected by copyright. All rights reserved.
    Print ISSN: 0022-3042
    Electronic ISSN: 1471-4159
    Topics: Medicine
    Published by Wiley-Blackwell on behalf of The International Society for Neurochemistry.
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  • 3
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    Oct2 and Bob1 are sensitive and specific markers in lineage determination of B-cell lymphomas with no expression of conventional B-cell markers (2016)
    Wiley-Blackwell
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    Publication Date: 2016-06-21
    Description: Aims Rare cases of B-cell lymphomas do not express conventional B-cell markers (CD20, CD79a, and Pax5), and these types of lymphomas include ALK-positive large B-cell lymphoma, plasmablastic lymphoma, primary effusion lymphoma, and the solid variant of primary effusion lymphoma, extracavitary HHV8-positive large B-cell lymphoma. Establishing accurate diagnoses of these B-cell lymphomas can be challenging, and often requires a large panel of immunohistochemical stains, molecular assays, and cytogenetic studies. B-cell specific transcription factors, Oct2 and Bob1, have been shown to be consistently expressed in most, if not all, B-cell lymphomas; and therefore we investigated the utility of Oct2 and Bob1 immunohistochemistry in lineage determination of the B-cell lymphomas aforementioned. Methods and results We selected 34 cases of previously diagnosed B-cell lymphomas with no or weak expression of CD20, CD79a and Pax5. Oct2 and Bob1 were positive in 74% (25/34) and 85% (29/34) of the cases, respectively. When we combined the results of these two immunostains, 94% (32/34) cases expressed at least one of these 2 markers. We also included 51 control cases of non-B-cell neoplasms, and none of them expressed either Oct2 or Bob1. Conclusions Oct2 and Bob1 are very reliable in determining B-cell lineage in the absence of expression of other pan-B-cell markers, and it should provide great diagnostic benefit of including both of them in a panel of immunohistochemistry to assess undifferentiated malignant neoplasms. This article is protected by copyright. All rights reserved.
    Print ISSN: 0309-0167
    Electronic ISSN: 1365-2559
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 4
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    First Total Synthesis of Prionoid E, A Bioactive Rearranged Secoabietane Diterpene Quinone from Salvia prionitis (2011)
    Wiley-Blackwell
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    Publication Date: 2011-07-19
    Description: The first total synthesis of prionoid E ( 1 ), a rearranged secoabietane diterpene quinone isolated from Salvia prionitis , was achieved efficiently by means of Wacker oxidation ( Scheme 5 ) and aldol condensation ( Scheme 7 ) as the key steps in the synthetic sequence. Thus 1 was prepared in 15 steps in 3.7% yield starting on one hand from anisole (=methoxybenzene) and methylsuccinic anhydride (=dihydro-3-methylfuran-2,5-dione) via 4 ( Scheme 3 and 5 ), and on the other hand from 2-hydroxy-2-methylpropanoic acid via 5 ( Scheme 6 ).
    Print ISSN: 0018-019X
    Electronic ISSN: 1522-2675
    Topics: Chemistry and Pharmacology
    Published by Wiley-Blackwell
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  • 5
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    Association of Total Cholesterol, Low-Density Lipoprotein Cholesterol, and Non-High-Density Lipoprotein Cholesterol with Atherosclerotic Cardiovascular Disease and Cancer in a Chinese Male Population (2017)
    Wiley-Blackwell
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    Publication Date: 2017-11-10
    Description: Objective The objective of this study was to investigate the association between total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) with atherosclerotic cardiovascular disease (ASCVD) or cancer in a male population in the Kailuan cohort of China. Methods This prospective study included 68,769 Chinese male adults from Kailuan cohort of China who had a standardized medical examination between 2006 and 2007 and were followed up for approximately 8 years until occurrence of ASCVD, cancer or death or until December 31, 2014. Cox regression models were used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs). Multivariable analysis was adjusted for age, cigarette smoking, alcohol consumption, physical activity, hypertension, diabetes mellitus and BMI at baseline. Results During follow-up, 2,916 males developed ASCVD and 1,884 developed cancer. Compared with the lowest quartile, the upper-most quartiles of TC, LDL-C and non-HDL-C were all associated with increased ASCVD risk (HR 1.53, 95% CI 1.37-1.70; HR 1.16, 95% CI 1.05-1.28; HR 1.55, 95% CI 1.39-1.72); however, the upper-most quartiles of TC, LDL-C and non-HDL-C were all negatively associated with cancer (HR 0.84, 95% CI 0.74-0.95; HR 0.82, 95% CI 0.72-0.93; HR 0.80, 95%CI 0.70-0.90) and these associations were present after exclusion of incident cancers during the first 4 years of follow-up. Conclusion In this Kailuan cohort study, we report that high TC, LDL-C and non-HDL-C concentrations increased ASCVD incidence in a male population and that these lipid profiles were inversely associated with total cancer and several individual cancers. This article is protected by copyright. All rights reserved.
    Print ISSN: 0020-7136
    Electronic ISSN: 1097-0215
    Topics: Biology , Medicine
    Published by Wiley-Blackwell
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  • 6
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    A three-dimensional zinc-based coordination polymer built from 5-carboxylato-1-carboxylatomethyl-2-oxidopyridinium with a 4-connected sra topology (2014)
    Wiley-Blackwell
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    Publication Date: 2014-08-07
    Description: A novel three-dimensional Zn II complex, poly[aqua(μ 4 -5-carboxylato-1-carboxylatomethyl-2-oxidopyridinium)zinc(II)], [Zn(C 8 H 5 NO 4 )(H 2 O)] n , has been prepared by hydrothermal assembly of Zn(CH 3 COO) 2 ·2H 2 O and 5-carboxy-1-(carboxymethyl)pyridin-1-ium-2-olate (H 2 ccop). The ccop 2− anions bridge the Zn II cations in a head-to-tail fashion via monodentate aromatic carboxylate and phenolate O atoms to form an extended zigzag chain which runs parallel to the [011] direction. One O atom of the aliphatic carboxylate group of the ccop 2− ligand coordinates to the Zn II atom of a neighbouring chain thereby producing undulating layers which lie parallel to the (01 ) plane. A similar parallel undulating planar structure can be obtained if a path involving the other O atom of the aliphatic carboxylate group is considered. Thus, the aliphatic carboxylate group acts in a bridging bidentate mode to give extended –Zn–O–C–O–Zn– sequences running parallel to [001] which link the layers into an overall three-dimensional framework. The three-dimensional framework can be simplified as a 4-connected sra topology with a Schläfli symbol of 4 2 .6 3 .8 if all the Zn II centres and ccop 2− anions are regarded as tetrahedral 4-connected nodes. The three-dimensional luminescence spectrum was measured at room temperature with excitation and emission wavelengths of 344–354 and 360–630 nm, respectively, at intervals of 0.15 and 2 nm, respectively.
    Print ISSN: 0108-2701
    Electronic ISSN: 1600-5759
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Published by Wiley-Blackwell on behalf of International Union of Crystallography (IUCr).
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  • 7
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    Alternative splicing of the cell-fate determinant Numb in hepatocellular carcinoma (2015)
    Wiley-Blackwell
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    Publication Date: 2015-06-09
    Description: Background : The cell fate determinant Numb is aberrantly expressed in cancer. Numb is alternatively spliced with one isoform containing an extended proline rich region (PRR L ) compared to the other (PRR S ). PRR L was recently reported to enhance proliferation of breast and lung cancer cells. However, the importance of Numb alternative splicing in hepatocellular carcinoma (HCC) remain unexplored. Main Results : We report here that Numb PRR L expression is increased in HCC and is associated with early recurrence and reduced overall survival after surgery. In a panel of HCC cell lines, PRR L generally promotes and PRR S suppresses proliferation, migration, invasion and colony formation. PRR S knockdown leads to increased Akt phosphorylation and c-Myc expression, and Akt inhibition or c-Myc silencing dampens the proliferative impact of Numb PRR S knockdown. In the cell models explored in this study, alternative splicing of Numb PRR isoforms is coordinately regulated by the splicing factor Rbfox2 and the kinase SRPK2. Rbfox2 knockdown causes accumulation of PRR L while SRPK2 knockdown causes accumulation of PRR S . SRPK2 subcellular location is regulated by the molecular chaperone Hsp90, and Hsp90 inhibition or knockdown phenocopies SRPK2 knockdown in promoting accumulation of Numb PRR S . Finally, HCC cell lines that predominately express PRR L are differentially sensitive to Hsp90 inhibition. Conclusion : Our data suggest that alternative splicing of Numb may provide a useful prognostic biomarker in HCC and is pharmacologically tractable. This article is protected by copyright. All rights reserved.
    Print ISSN: 0270-9139
    Electronic ISSN: 1527-3350
    Topics: Medicine
    Published by Wiley-Blackwell on behalf of The American Association for the Study of Liver Diseases.
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  • 8
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    Cloning, characterization, and production of three α-l-fucosidases from Clostridium perfringens ATCC 13124 (2015)
    Wiley-Blackwell
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    Publication Date: 2015-12-12
    Description: α- l -Fucosidases are key enzymes for the degradation of intestinal glycans by gut microbes. In this work, three putative α- l -fucosidases (Afc1, Afc2, and Afc3) genes from Clostridium perfringens ATCC 13124 were cloned and expressed in Escherichia coli . Afc1 had the α- l -fucosidase domain of glycoside hydrolase (GH) 29 family but showed no enzyme activity toward all the substrates examined. The putative acid/base residue of Afc1, Ser205, was replaced by a glutamic acid which is conserved in GH29-B α- l -fucosidases. However, the mutant Afc1-S205E still failed to show enzyme activity. Afc2 and Afc3 were determined to be 1,3-1,4-α- l -fucosidase of GH29-B subfamily and 1,2-α- l -fucosidase of GH95 family, respectively, and both of them could release fucose from porcine gastric mucin (PGM). When C. perfringens ATCC 13124 grew with the presence of PGM, the transcription of afc 1 decreased slightly, while those of afc 2 and afc 3 increased to 2.2-fold and 1.4-fold, respectively, and the enzyme activities of Afc2 and Afc3 in the culture increased to 2.2-fold and 2.6-fold, respectively. These results suggest that Afc2 and Afc3 are involved in the degradation of intestinal fucosyl glycans by C. perfringens ATCC 13124.
    Print ISSN: 0233-111X
    Electronic ISSN: 1521-4028
    Topics: Biology
    Published by Wiley-Blackwell
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  • 9
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    Effect of oxidative phosphorylation signaling pathway on silkworm midgut following exposure to phoxim (2015)
    Wiley-Blackwell
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    Publication Date: 2015-11-27
    Description: ABSTRACT Organophosphate pesticides are applied widely in the world for agricultural purposes, and their exposures often resulted in non-cocooning of Bombyx mori in China. Silkworm midgut is the major organ for digestion and nutrient absorption, importantly it is also a barrier against foreign substances and chemical pesticides. The purpose of this study was to determine the mechanism of oxidative injury in silkworm midgut with phoxim induction. The results showed that the transcription level of oxidative phosphorylation signaling pathway genes of midgut under phoxim stress. Digital gene expression (DGE) analysis revealed that 24 electron transport chain (ETC)-related genes were upregulated. Quantitative real time polymerase chain reaction results indicated that the ETC the genes encoding NADH-CoQ1, Succinic-Q, cyt c reductase-S, cyt c oxidase-S, cytochrome c oxidase polypeptide IV, ATP synthase, and vacuolar H+ ATP synthase were all significantly up-regulated by 1.50-, 1.31-, 1.42-, 1.44-, 1.70-, 2.03- and 1.43-fold, respectively. Phoxim induction enhanced the activity of ETC complex in mitochondria, and induced the accumulation of ROS in midgut. These results indicated that trace phoxim enhanced respiration in midgut, and the imbalance between the activity changes of ETC may led to reactive oxygen species accumulation. The ETC of mitochondria may be potential biomarkers of midgut toxicity in B. mori caused by phoxim exposure. © 2015 Wiley Periodicals, Inc. Environ Toxicol, 2015.
    Print ISSN: 1520-4081
    Electronic ISSN: 1522-7278
    Topics: Energy, Environment Protection, Nuclear Power Engineering
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  • 10
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    Association between TNF-α promoter -308 A/G polymorphism and systemic lupus erythematosus susceptibility: a case-control study and meta-analysis (2016)
    Wiley-Blackwell
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    Publication Date: 2016-12-11
    Description: The tumor necrosis factor- α (TNF- α ) promoter -308 A/G polymorphism plays an important role in the etiology of systemic lupus erythematosus (SLE). Several studies have estimated the association between TNF- α -308 A/G and SLE risk. However, results were inconsistent. A case-control study was carried out to explore the association between TNF- α -308 A/G and the SLE risk in a Chinese Han population. Meta-analysis combining present with previous studies were conducted to further explore the association. Our case-control study included 556 SLE patients along with 570 matched healthy controls. TNF- α -308 A allele was significantly increased in SLE patients compared with controls (OR = 2.184, 95% CI: 1.718-2.778, P 〈 0.001). Genotype AA, AG were associated with the susceptibility to SLE as compared with the GG genotype, as well as the dominant model (AA+AG versus GG), respectively. The meta-analysis included 41 comparative studies involving 4799 patients and 6635 controls. An association between SLE and allele A was found in the overall populations (OR = 1.70, 95%CI: 1.46-1.98, P 〈 0.001). In addition, we discussed the correlation between this polymorphism and lupus nephritis (LN) risk, showing that allele A was significantly related to LN in the overall populations (OR = 1.80, 95%CI: 1.21-2.68, P = 0.004). The results from our case-control study and the meta-analysis indicate that the TNF- α -308 A allele is significantly associated with an increased risk of SLE/LN. This article is protected by copyright. All rights reserved.
    Print ISSN: 0300-9475
    Electronic ISSN: 1365-3083
    Topics: Medicine
    Published by Wiley-Blackwell
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