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951.
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The extract of the strain Aspergillus flavipes DL‐11 exerted antibacterial activities against six Gram‐positive bacteria. During the following bioassay‐guided separation, ten diphenyl ethers ( 1 – 10 ), two benzophenones ( 11 – 12 ), together with two xanthones ( 13 – 14 ) were isolated. Among them, 4′‐chloroasterric acid ( 1 ) was a new chlorinated diphenyl ether. Their structures were elucidated by extensive spectroscopic data analysis, including IR, HR‐ESI‐MS, NMR experiments, and by comparison with the literature data. All compounds showed moderate to strong antibacterial effects on different Gram‐positive bacteria with MIC values that ranged from 3.13 to 50 μg/mL, but none of the compounds exhibited activity against Gram‐negative bacteria Vibrio parahaemolyticus ATCC17802 (MIC>100 μg/mL). In particular, the MICs of some compounds are at the level of positive control. 相似文献
954.
Head and neck squamous cell carcinoma (HNSCC) represents more than 5% of all cancers diagnosed annually in United States and around the world. Despite advances in the management of patients with this disease, the survival has not been significantly improved, and the search for potential alternative therapies is encouraging. Here we demonstrate that deguelin administration causes a significant HNSCC cell death. Deguelin induces both cell apoptosis and autophagy by modulating multiple signaling pathways in cultured HNSCC cells. Deguelin inhibits Akt signaling, and down-regulates survivin and cyclin-dependent kinase 4 (Cdk4) expressions, by disrupting their association with heat shock protein-90 (Hsp-90). Deguelin induces ceramide production through de novo synthase pathway to promote HNSCC cell death. Importantly, increased ceramide level activates AMP-activated protein kinase (AMPK), which then directly phosphorylates Ulk1 and eventually leads to cell autophagy. We found that a low dose of deguelin sensitized HNSCC cells to 5-FU. Finally, using a nude mice Hep-2 xenograft model, we also showed a significant anti-tumor ability of deguelin in vivo. Together, we suggest that deguelin may represent a novel and effective chemo-agent against HNSCC. 相似文献
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956.
Jie Zhu Hong Wang Shuo Yang Liqiao Guo Zhen Li Wei Wang Suhan Wang Wenting Huang Liping Wang Tan Yang Qiang Ma Yongyi Bi 《PloS one》2013,8(8)
Benzene is an occupational toxicant and an environmental pollutant that potentially causes hematotoxicity and leukemia in exposed populations. Epidemiological studies suggest an association between an increased incidence of childhood leukemia and benzene exposure during the early stages of pregnancy. However, experimental evidence supporting the association is lacking at the present time. It is believed that benzene and its metabolites target hematopoietic stem cells (HSCs) to cause toxicity and cancer in the hematopoietic system. In the current study, we compared the effects of hydroquinone (HQ), a major metabolite of benzene in humans and animals, on mouse embryonic yolk sac hematopoietic stem cells (YS-HSCs) and adult bone marrow hematopoietic stem cells (BM-HSCs). YS-HSCs and BM-HSCs were isolated and enriched, and were exposed to HQ at increasing concentrations. HQ reduced the proliferation and the differentiation and colony formation, but increased the apoptosis of both YS-HSCs and BM-HSCs. However, the cytotoxic and apoptotic effects of HQ were more apparent and reduction of colony formation by HQ was more severe in YS-HSCs than in BM-HSCs. Differences in gene expression profiles were observed in HQ-treated YS-HSCs and BM-HSCs. Cyp4f18 was induced by HQ both in YS-HSCs and BM-HSCs, whereas DNA-PKcs was induced in BM-HSCs only. The results revealed differential effects of benzene metabolites on embryonic and adult HSCs. The study established an experimental system for comparison of the hematopoietic toxicity and leukemogenicity of benzene and metabolites during mouse embryonic development and adulthood. 相似文献
957.
Yang Peng Xiaohua Ye Ying Li Tao Bu Xiaofeng Chen Jiaqi Bi Junli Zhou Zhenjiang Yao 《PloS one》2013,8(11)
Objective
To evaluate whether teicoplanin could be an alternative to vancomycin for treatment of MRSA infection in Chinese population using a meta-analysis in randomized controlled trials.Methods
The following databases were searched: Chinese Biomedical Literature database (CBM), Chinese Journal Full-text database (CNKI), Wanfang database, Medline database, Ovid database and Cochrane Library. Articles published from 2002 to 2013 that studied teicoplanin in comparison to vancomycin in the treatment of MRSA infected patients were collected. Overall effects, publishing bias analysis and sensitivity analysis on clinical cure rate, microbiologic eradication rate and adverse events rate were performed by using Review Manager 5.2 and Stata 11.0 softwares.Results
Twelve articles met entry criteria. There was no statistically significant difference between the two groups regarding the clinical cure rate (risk ratio [RR], teicoplanin vs vancomycin, 0.94; 95% CI, 0.74∼1.19; P = 0.60), microbiological cure rate (risk ratio [RR], teicoplanin vs vancomycin, 0.99; 95% CI, 0.91∼1.07; P = 0.74) and adverse event rate (risk ratio [RR], teicoplanin vs vancomycin, 0.86; 95% CI, 0.40∼1.84; P = 0.70).Conclusions
The meta-analysis results indicate that the two therapies are similar in both efficacy and safety, thus teicoplanin can act as an effective alternative to vancomycin for treating patients infected by MRSA. 相似文献958.
David A. G. Skibinski Brendon J. Hanson Yufang Lin Veronika von Messling Andrea Jegerlehner Jason Boon Sern Tee De Hoe Chye Steven K. K. Wong Amanda A. P. Ng Hui Yin Lee Bijin Au Bernett T. K. Lee Lucia Santoso Michael Poidinger Anna-Marie Fairhurst Alex Matter Martin F. Bachmann Philippe Saudan John E. Connolly 《PloS one》2013,8(10)
Influenza pandemics can spread quickly and cost millions of lives; the 2009 H1N1 pandemic highlighted the shortfall in the current vaccine strategy and the need for an improved global response in terms of shortening the time required to manufacture the vaccine and increasing production capacity. Here we describe the pre-clinical assessment of a novel 2009 H1N1 pandemic influenza vaccine based on the E. coli-produced HA globular head domain covalently linked to virus-like particles derived from the bacteriophage Qβ. When formulated with alum adjuvant and used to immunize mice, dose finding studies found that a 10 µg dose of this vaccine (3.7 µg globular HA content) induced antibody titers comparable to a 1.5 µg dose (0.7 µg globular HA content) of the licensed 2009 H1N1 pandemic vaccine Panvax, and significantly reduced viral titers in the lung following challenge with 2009 H1N1 pandemic influenza A/California/07/2009 virus. While Panvax failed to induce marked T cell responses, the novel vaccine stimulated substantial antigen-specific interferon-γ production in splenocytes from immunized mice, alongside enhanced IgG2a antibody production. In ferrets the vaccine elicited neutralizing antibodies, and following challenge with influenza A/California/07/2009 virus reduced morbidity and lowered viral titers in nasal lavages. 相似文献
959.
Yu Bai Huifang Xue Kun Wang Lifeng Cai Jiayin Qiu Shuangyu Bi Luhua Lai Maosheng Cheng Shuwen Liu Keliang Liu 《Amino acids》2013,44(2):701-713
Covalent inhibitors form covalent adducts with their target, thus permanently inhibiting a physiological process. Peptide fusion inhibitors, such as T20 (Fuzeon, enfuvirtide) and C34, interact with the N-terminal heptad repeat of human immunodeficiency virus type 1 (HIV-1) gp41 glycoprotein to form an inactive hetero six-helix bundle (6-HB) to prevent HIV-1 infection of host cells. A covalent strategy was applied to peptide fusion inhibitor design by introducing a thioester group into C34-like peptide. The modified peptide maintains the specific interaction with its target N36. After the 6-HB formation, a covalent bond between C- and N-peptides was formed by an inter-helical acyl transfer reaction, as characterized by various biophysical and biochemical methods. The covalent reaction between the reactive C-peptide fusion inhibitor and its N-peptide target is highly selective, and the reaction greatly increases the thermostability of the 6-HB. The modified peptide maintains high potency against HIV-1-mediated cell–cell fusion and infection. 相似文献
960.
Ke Bi Tyler Linderoth Dan Vanderpool Jeffrey M. Good Rasmus Nielsen Craig Moritz 《Molecular ecology》2013,22(24):6018-6032
Natural history museum collections provide unique resources for understanding how species respond to environmental change, including the abrupt, anthropogenic climate change of the past century. Ideally, researchers would conduct genome‐scale screening of museum specimens to explore the evolutionary consequences of environmental changes, but to date such analyses have been severely limited by the numerous challenges of working with the highly degraded DNA typical of historic samples. Here, we circumvent these challenges by using custom, multiplexed, exon capture to enrich and sequence ~11 000 exons (~4 Mb) from early 20th‐century museum skins. We used this approach to test for changes in genomic diversity accompanying a climate‐related range retraction in the alpine chipmunks (Tamias alpinus) in the high Sierra Nevada area of California, USA. We developed robust bioinformatic pipelines that rigorously detect and filter out base misincorporations in DNA derived from skins, most of which likely resulted from postmortem damage. Furthermore, to accommodate genotyping uncertainties associated with low‐medium coverage data, we applied a recently developed probabilistic method to call single‐nucleotide polymorphisms and estimate allele frequencies and the joint site frequency spectrum. Our results show increased genetic subdivision following range retraction, but no change in overall genetic diversity at either nonsynonymous or synonymous sites. This case study showcases the advantages of integrating emerging genomic and statistical tools in museum collection‐based population genomic applications. Such technical advances greatly enhance the value of museum collections, even where a pre‐existing reference is lacking and points to a broad range of potential applications in evolutionary and conservation biology. 相似文献