3,639 research outputs found
Micheliolide suppresses LPS-induced neuroinflammatory responses.
No full textMicroglia-involved neuroinflammation is thought to promote brain damage in various neurodegenerative disorders. Thus, inhibition of microglial over-activation may have a therapeutic benefit for the treatment of neurodegenerative disorders. Micheliolide (MCL) is a sesquiterpene lactone which inhibits various inflammatory response. However, whether MCL can inhibit neuroinflammation caused by LPS-activated BV2 microglia has not yet been explored. In this study, we demonstrated that treatment of BV2 cells with MCL significantly repressed LPS-stimulated nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, as well as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) induction. MCL also attenuated mRNA levels of multiple pro-inflammatory cytokines and mediators such as iNOS, COX-2, TNF-α, IL-6 and IL-1β. Mechanistic studies revealed that MCL suppressed LPS-stimulated the activation of IκBα/NF-κB pathway and Akt pathway. Moreover, MCL inhibited LPS-induced the activition of c-Jun N-terminal kinase (JNK), p38 MAPK kinase, and extracellular signal-regulated kinases 1/2 (ERK1/2). Meanwhile, MCL markedly promoted antioxidant protein heme oxygenase-1 (HO-1) expression by enhancing NF-E2-related factor 2 (Nrf2) activity. Together, our results imply that MCL may serve as a neuroprotective agent in neuroinflammation-related neurodegenerative disorders
John Tong
No full textabstract: John was ten years old when he left his home. He traveled to Ethiopia with his friends and elders without food or water.
“Lost Boys Found” is an ongoing, interdisciplinary project that is collecting, recording and archiving the oral histories of the Lost Boys/Girls of Sudan. The collection is a work-in-progress, seeking to record the oral history of as many Lost Boys/Girls as are willing, and will be used in a future book.Age: 25Region: BarakazarThis picture and bio was donated to the "Lost Boys Found" oral history project from The Arizona Lost Boys Cente
FOXA1 antagonizes EZH2-mediated CDKN2A repression in carcinogenesis
No full textCDKN2A (p16(INK4a)) is a crucial tumor suppressor involved in many cancers. Our recent investigations revealed that FOXA1 as a forkhead transcription factor mediates CDKN2A activation in cellular senescence. However, the contribution of this axis in carcinogenesis remains unclear. Here, using a comprehensive collection of cancer microarray data, we found FOXA1 is down-regulated in many cancers compared to their normal counterparts and the positive correlation between FOXA1 and CDKN2A could be observed in prostate and breast cancers with lower EZH2 (epigenetic repressor for CDKN2A) expression. Experimentally, epistasis analysis in prostate and breast cancer cells indicated that higher expression of FOXA1 opposes EZH2-mediated CDKN2A repression, as further depletion of FOXA1 reverts the de-silencing of CDKN2A caused by EZH2 inhibition. Concomitantly, EZH2-depletion suppresses cancer cell cycle progression and this regulation is optimized in the presence of FOXA1 and CDKN2A. A further oncogenic transformation assay suggested that overexpression of EZH2 is insufficient to block RAS-induced CDKN2A activation and loss of FOXA1 is mandatory to potentiate EZH2-mediated CDKN2A silencing and to bypass the senescence barrier. Importantly, using an in vitro histone methyltransferase (HMTase) system, we found FOXA1 directly inhibits EZH2's histone methyltransferase activity through its C-terminal histone binding motif. These data support that positive regulation of CDKN2A by FOXA1 counteracts its tumorigenic repression of by EZH2 in cancers. (C) 2014 Elsevier Inc. All rights reserved.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000343634900029&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Biochemistry & Molecular BiologyBiophysicsSCI(E)[email protected]; [email protected]
Waste is "wicked" when we try to solve it. Author's response to Joshua Goldstein's comments
No full textThis is the author's response to Dr. Goldstein's response to our recent article The rise and fall of a Waste cityin the construction of an urban circular economic systenif The changing landscape of waste in Beijingin the February 2016 issue of this publication. (C) 2016 Elsevier B.V. All rights reserved.SCI(E)REVIEW175-17611
Expression of the Leo1-like domain of replicative senescence down-regulated Leo1-like (RDL) protein promotes senescence of 2BS fibroblasts
No full textReplicative senescence is thought to relate to aging in vivo and tumor suppression. In this report, we isolated a gene and designated it as RDL (replicative senescence down-regulated Leo1-like gene). RDL’s expression decreased upon replicative senescence of human diploid 2BS fibroblasts. Overexpression of RDL slightly delayed 2BS fibroblast senescence, whereas suppression of RDL expression imposed no obvious effects on senescence. However, introduction of cDNA fragment encoding the Leo1-like domain of RDLp (Leo) alone shortened the replicative life span of 2BS fibroblasts and promoted several senescent features; the introduction of truncated RDL cDNA fragment resulting from deletion of Leo (RDL-Leo–) significantly prolonged 2BS life span and caused a noticeable delay of these senescent features. We demonstrated that introduction of Leo obviously increased the expression of p16INK4a, p21WAF1, and PTEN, whereas introduction of RDL-Leo– distinctly decreased p16INK4a expression. Taken together, our results suggest that the Leo1-like domain of RDLp is a senescence-associated domain that accelerates the senescence of 2BS fibroblasts and that there should be another counteractive domain in the remaining part of RDLp.—Zhao, L., Tong, T., Zhang, Z. Expression of the Leo1-like domain of replicative senescence down-regulated Leo1-like (RDL) protein promotes senescence of 2BS fibroblasts
The Socio-Cultural Context of Mo Xiang Tong Xiu's Novel “The Founder of the Demon Path” Mo Xiang Tong Xiu
No full textАвтор розкриває стиль, структуру та наратив роману Мосян Тунсю «Засновник демонічного шляху», що сформувалися під впливом літературних тенденцій Китаю 2010-х років.
The author reveals the style, structure, and narrative of Mosiang Tongxiu's Mo Xiang Tong Xiu's novel The Founder of the Demon Path, which were shaped by the literary trends in China in the 2010s
Whose story is it anyway? The ethics of narration and the narration of ethics in Summertime and Die Sneeuslaper
No full textIncludes bibliographical references.This dissertation analyses and compares the narrative strategies in J.M. Coetzee’s Summertime and Marlene van Niekerk’s Die sneeuslaper and considers the implications of these strategies for the authors’ exploration of the ethics of writing. Much has been written about the literary oeuvres of both Coetzee and Van Niekerk, including studies of the translations of Van Niekerk’s Afrikaans novels into English. There are few “interlingual” comparative studies of contemporary works in Afrikaans and English, however, and certainly none to my knowledge which compares the work of Coetzee and Van Niekerk. My contribution to the conversation about Coetzee’s and Van Niekerk’s work, but also to an increasingly multilingual and interconnected South African literary criticism, will be a comparison of one recent work by each of these two authors, written in English and Afrikaans respectively. I draw on the theories of Bakhtin, Barthes and Levinas to consider the ethical dimension of texts in which “double-voicedness”, a questioning not only of existence, but of the self is fore grounded in the content and narrative structure; where there is a shift in focus from the author to the reader (“the birth of the reader”) and “utterances” are made with the response of “the other” in mind
Nucleostemin Knockdown Sensitizes Hepatocellular Carcinoma Cells to Ultraviolet and Serum Starvation-Induced Apoptosis.
No full textNucleostemin (NS) is a GTP-binding protein that is predominantly expressed in embryonic and adult stem cells but not in terminally differentiated cells. NS plays an essential role in maintaining the continuous proliferation of stem cells and some types of cancer cells. However, the role of NS in hepatocellular carcinoma (HCC) remains unclear. Therefore, this study aimed to clarify the role of NS in HCC. First, we demonstrated high expression of NS in most HCC cell lines and liver cancer tissues. NS knockdown induced a severe decline in cell viability of MHCC97H cells as detected by MTT and cell proliferation assays. Next, we used ultraviolet (UV) and serum starvation-induced apoptosis models to investigate whether NS suppression or up-regulation affects HCC cell apoptosis. After UV treatment or serum starvation, apoptosis was strongly enhanced in MHCC97H and Bel7402 cells transfected with small interfering RNA against NS, whereas NS overexpression inhibited UV- and serum-induced apoptosis of HCC cells. Furthermore, after UV irradiation, inhibition of NS increased the expression of pro-apoptosis protein caspase 3 and decreased the expression of anti-apoptosis protein Bcl-2. A caspase 3 inhibitor could obviously prevent NS knockdown-induced apoptosis. In conclusion, our study demonstrated overexpression of NS in most HCC tissues compared with their matched surrounding tissues, and silencing NS promoted UV- and serum starvation-induced apoptosis of MHCC97H and Bel7402 cells. Therefore, the NS gene might be a potential therapeutic target of HCC
基于概率的地图实体匹配方法
No full textAuthor name used in this publication: 童小华, Tong, Xiao-huaAuthor name used in this publication: 邓愫愫Author name used in this publication: SHI Wen-zhong2006-2007 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishedVoR allowe
Characterization of a novel positive transcription regulatory element that differentially regulates the alpha-2-macroglobulin gene in replicative senescence
No full textAlpha-2-macroglobulin (alpha 2M), a protease inhibitor, is implicated in Alzheimer's disease, atherosclerosis, and other age-related diseases. The elevated level of alpha 2M mRNA has been described in replicative senescence and it could be used as a biomarker of the aging cells. However, the mechanism responsible for the up-regulation of its expression is still unclear. This report identified a novel transcriptional regulatory element, the alpha 2M transcription enhancement element (ATEE), within the alpha 2M promoter. This element differentially activates alpha 2M expression in senescent versus young fibroblasts. Electrophoretic mobility shift assays revealed abundant complexes in senescent cell nuclear extracts compared with young cell nuclear extracts. The DNase I footprint revealed the protein-binding core sequence through which the protein binds the ATEE. Mutation within ATEE selectively abolished alpha 2M promoter activity in senescent (but not young) cells. These results indicated the ATEE, as a positive transcription regulatory element, contributes to the up-regulation of alpha 2M during replicative senescence.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000296633300003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Geriatrics & GerontologySCI(E)PubMed3ARTICLE6517-5251
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