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排序方式: 共有978条查询结果,搜索用时 109 毫秒
81.
da Silva LE Joussef AC Pacheco LK da Silva DG Steindel M Rebelo RA Schmidt B 《Bioorganic & medicinal chemistry》2007,15(24):7553-7560
In the present paper 12 N-quinolin-8-yl-arylsulfonamides synthesized by coupling 8-aminoquinolines with various arylsulfonylchlorides were assayed in vitro against Leishmania amazonensis, Leishmania chagasi and Trypanosoma cruzi strains. This series of new compounds were found to be selective for Leishmania spp. promastigote and amastigote forms. The most active compound was the N-(8-quinolyl)-3,5-difluoro-benzenesulfonamide 10 with an IC50 against L. amazonensis and L. chagasi of 2.12 and 0.45 μM, respectively. The less cytotoxic biphenyl derivative 7 was very effective against intracellular L. amazonensis with a reduction of macrophage cell infection of 82.1% at 25 μM. In addition, a copper complex 17 of an inactive ligand was readily synthesized and showed high leishmanicidal and trypanocidal activity against both extra and intracellular forms. 相似文献
82.
Overexpression of MMP9 in macrophages attenuates pulmonary fibrosis induced by bleomycin 总被引:1,自引:0,他引:1
Cabrera S Gaxiola M Arreola JL Ramírez R Jara P D'Armiento J Richards T Selman M Pardo A 《The international journal of biochemistry & cell biology》2007,39(12):2324-2338
Pulmonary fibrosis is a common response to a variety of lung injuries, characterized by fibroblast/myofibroblast expansion and abnormal accumulation of extracellular matrix. An increased expression of matrix metalloprotease 9 (MMP9) in human and experimental lung fibrosis has been documented, but its role in the fibrotic response is unclear. We studied the effect of MMP9 overexpression in bleomycin-driven lung fibrosis using transgenic mice expressing human MMP9 in alveolar macrophages (hMMP9-TG). At 8 weeks post-bleomycin, the extent of fibrotic lesions and OH-proline content were significantly decreased in the TG mice compared to the WT mice. The decreased fibrosis in hMMP9-TG mice was preceded by a significant reduction of neutrophils and lymphocytes in bronchoalveolar lavage (BAL) at 1 and 4 weeks post-bleomycin, respectively, as well as by significantly less TIMP-1 than the WT mice. From a variety of cytokines/chemokines investigated, we found that BAL levels of insulin-like growth factor binding protein-3 (IGFBP3) as well as the immunoreactive protein in the lungs were significantly lower in hMMP9-TG mice compared with WT mice despite similar levels of gene expression. Using IGFBP-3 substrate zymography we found that BAL from TG mice at 1 week after bleomycin cleaved IGFBP-3. Further, we demonstrated that MMP9 degraded IGFBP-3 into lower molecular mass fragments. These findings suggest that increased activity of MMP9 secreted by alveolar macrophages in the lung microenvironment may have an antifibrotic effect and provide a potential mechanism involving IGFBP3 degradation. 相似文献
83.
Elizabeth D. Hughes Yun Yan Qu Suzanne J. Genik Robert H. Lyons Christopher D. Pacheco Andrew P. Lieberman Linda C. Samuelson Igor O. Nasonkin Sally A. Camper Margaret L. Van Keuren Thomas L. Saunders 《Mammalian genome》2007,18(8):549-558
Genetically modified mouse strains derived from embryonic stem (ES) cells are powerful tools for gene function analysis. ES
cells from the C57BL/6 mouse strain are not widely used to generate mouse models despite the advantage of a defined genetic
background. We assessed genetic variation in six such ES cell lines with 275 SSLP markers. Compared to C57BL/6, Bruce4 differed
at 34 SSLP markers and had significant heterozygosity on three chromosomes. BL/6#3 and Dale1 ES cell lines differed at only
3 SSLP makers. The C2 and WB6d ES cell lines differed at 6 SSLP markers. It is important to compare the efficiency of producing
mouse models with available C57BL/6 ES cells relative to standard 129 mouse strain ES cells. We assessed genetic stability
(the tendency of cells to become aneuploid) in 110 gene-targeted ES cell clones from the most widely used C57BL/6 ES cell
line, Bruce4, and 710 targeted 129 ES cell clones. Bruce4 clones were more likely to be aneuploid and unsuitable for ES cell-mouse
chimera production. Despite their tendency to aneuploidy and consequent inefficiency, use of Bruce4 ES cells can be valuable
for models requiring behavioral studies and other mouse models that benefit from a defined C57BL/6 background.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
84.
Piccinini Alexandre Oliveira Mariana Pacheco Silva Mariella Reinol Bett Gabriela Souza Becker Isabel Borges Mendes Talita Farias Salla Daniéle Hendler Silva Larissa Espindola Vilela Thais Ceresér Moraes Fernanda Mendes Moterle Diego Damiani Adriani Paganini Dagostin Lígia Salvan Tietbohl Lariani Tamires Bittencourt João Vitor Silvano Biehl Erica Denicol Tais Luise Bonfante Sandra Regina Andrade Vanessa Moraes Silveira Paulo Cesar Lock Prophiro Josiane Somariva Ferreira Gabriela Kozuchovski Petronilho Fabricia Kanis Luiz Alberto Rezin Gislaine Tezza 《Neurochemical research》2022,47(7):1888-1903
Neurochemical Research - This study aimed to evaluate the effect of Cynara cardunculus leaf ethanol extract on inflammatory and oxidative stress parameters in the hypothalamus, prefrontal cortex,... 相似文献
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88.
Remedios Castello-Cros Gloria Bonuccelli Alex Molchansky Franco Capozza Agnieszka K Witkiewicz Ruth C Birbe Anthony Howell Richard G Pestell Diana Whitaker-Menezes Federica Sotgia Michael P Lisanti 《Cell cycle (Georgetown, Tex.)》2011,10(12):2021-2034
We have previously demonstrated that loss of stromal caveolin-1 (Cav-1) in cancer-associated fibroblasts is a strong and independent predictor of poor clinical outcome in human breast cancer patients. However, the signaling mechanism(s) by which Cav-1 downregulation leads to this tumor-promoting microenvironment are not well understood. To address this issue, we performed an unbiased comparative proteomic analysis of wild-type (WT) and Cav-1-/- null mammary stromal fibroblasts (MSFs). Our results show that plasminogen activator inhibitor type 1 and type 2 (PAI-1 and PAI-2) expression is significantly increased in Cav-1-/- MSFs. To establish a direct cause-effect relationship, we next generated immortalized human fibroblast lines stably overexpressing either PAI-1 or PAI-2. Importantly, PAI-1/2(+) fibroblasts promote the growth of MDA-MB-231 tumors (a human breast cancer cell line) in a murine xenograft model, without any increases in angiogenesis. Similarly, PAI-1/2(+) fibroblasts stimulate experimental metastasis of MDA-MB-231 cells using an in vivo lung colonization assay. Further mechanistic studies revealed that fibroblasts overexpressing PAI-1 or PAI-2 display increased autophagy (“self-eating”) and are sufficient to induce mitochondrial biogenesis/activity in adjacent cancer cells, in co-culture experiments. In xenografts, PAI-1/2(+) fibroblasts significantly reduce the apoptosis of MDA-MB-231 tumor cells. The current study provides further support for the “Autophagic Tumor Stroma Model of Cancer” and identifies a novel “extracellular matrix”-based signaling mechanism, by which a loss of stromal Cav-1 generates a metastatic phenotype. Thus, the secretion and remodeling of extracellular matrix components (such as PAI-1/2) can directly regulate both (1) autophagy in stromal fibroblasts and (2) epithelial tumor cell mitochondrial metabolism. 相似文献
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90.
Aldo S. Pacheco Maria Teresa González Julie Bremner Marcelo Oliva Olaf Heilmayer Jürgen Laudien José M. Riascos 《Helgoland Marine Research》2011,65(3):413-424
Benthic communities show changes in composition and structure across different environmental characteristics and habitats.
However, incorporating species biological traits into the analysis can provide a better understanding of system functioning
within habitats. We compare the functional diversity of macrobenthic communities from a contrasting shallow (15 m) and deep
(50 m) sublittoral soft-sediment habitats in northern Chile, using biological traits analysis. Our aim was to highlight the
biological characteristics responsible for differences between habitats and the implications for ecosystem functioning. Trait
analysis showed that the deep habitat was restricted in providing functionally important biogenic structure and bioturbation
and supports less diverse feeding-related energy pathways. The shallow habitat is characterized by more diverse energy pathways
and a higher potential for matter exchange through bioturbation. We provide support to the predictions of transfer of energy
from the benthos to upper trophic levels in the shallow, which is characterized mainly by normoxia and little organic matter
content in the sediment. In the deep habitat, characterized by hypoxia and more organic matter, energy appears to be transferred
to microbial components. We suggest that trait analysis should be added to the traditional approaches based on species diversity,
because it provides indicators of ecosystem stress. 相似文献