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131.
Background
Mapping the expression changes during breast cancer development should facilitate basic and translational research that will eventually improve our understanding and clinical management of cancer. However, most studies in this area are challenged by genetic and environmental heterogeneities associated with cancer.Methodology/Principal Findings
We conducted proteomics of the MCF10AT breast cancer model, which comprises of 4 isogenic xenograft-derived human cell lines that mimic different stages of breast cancer progression, using iTRAQ-based tandem mass spectrometry. Of more than 1200 proteins detected, 98 proteins representing at least 20 molecular function groups including kinases, proteases, adhesion, calcium binding and cytoskeletal proteins were found to display significant expression changes across the MCF10AT model. The number of proteins that showed different expression levels increased as disease progressed from AT1k pre-neoplastic cells to low grade CA1h cancer cells and high grade cancer cells. Bioinformatics revealed that MCF10AT model of breast cancer progression is associated with a major re-programming in metabolism, one of the first identified biochemical hallmarks of tumor cells (the “Warburg effect”). Aberrant expression of 3 novel breast cancer-associated proteins namely AK1, ATOX1 and HIST1H2BM were subsequently validated via immunoblotting of the MCF10AT model and immunohistochemistry of progressive clinical breast cancer lesions.Conclusion/Significance
The information generated by this study should serve as a useful reference for future basic and translational cancer research. Dysregulation of ATOX1, AK1 and HIST1HB2M could be detected as early as the pre-neoplastic stage. The findings have implications on early detection and stratification of patients for adjuvant therapy. 相似文献132.
Denice S. Feig Baiju R. Shah Lorraine L. Lipscombe C. Fangyun Wu Joel G. Ray Julia Lowe Jeremiah Hwee Gillian L. Booth 《PLoS medicine》2013,10(4)
Background
Women with preeclampsia (PEC) and gestational hypertension (GH) exhibit insulin resistance during pregnancy, independent of obesity and glucose intolerance. Our aim was to determine whether women with PEC or GH during pregnancy have an increased risk of developing diabetes after pregnancy, and whether the presence of PEC/GH in addition to gestational diabetes (GDM) increases the risk of future (postpartum) diabetes.Methods and Findings
We performed a population-based, retrospective cohort study for 1,010,068 pregnant women who delivered in Ontario, Canada between April 1994 and March 2008. Women were categorized as having PEC alone (n = 22,933), GH alone (n = 27,605), GDM alone (n = 30,852), GDM+PEC (n = 1,476), GDM+GH (n = 2,100), or none of these conditions (n = 925,102). Our main outcome was a new diagnosis of diabetes postpartum in the following years, up until March 2011, based on new records in the Ontario Diabetes Database. The incidence rate of diabetes per 1,000 person-years was 6.47 for women with PEC and 5.26 for GH compared with 2.81 in women with neither of these conditions. In the multivariable analysis, both PEC alone (hazard ratio [HR] = 2.08; 95% CI 1.97–2.19) and GH alone (HR = 1.95; 95% CI 1.83–2.07) were risk factors for subsequent diabetes. Women with GDM alone were at elevated risk of developing diabetes postpartum (HR = 12.77; 95% CI 12.44–13.10); however, the co–presence of PEC or GH in addition to GDM further elevated this risk (HR = 15.75; 95% CI 14.52–17.07, and HR = 18.49; 95% CI 17.12–19.96, respectively). Data on obesity were not available.Conclusions
Women with PEC/GH have a 2-fold increased risk of developing diabetes when followed up to 16.5 years after pregnancy, even in the absence of GDM. The presence of PEC/GH in the setting of GDM also raised the risk of diabetes significantly beyond that seen with GDM alone. A history of PEC/GH during pregnancy should alert clinicians to the need for preventative counseling and more vigilant screening for diabetes. Please see later in the article for the Editors'' Summary 相似文献133.
The mechanism for the production of hydroxyl radical by lignin peroxidase from the white rot fungus Phanerochaete chrysosporium was investigated. Ferric iron reduction was demonstrated in reaction mixtures containing lignin peroxidase isozyme H2 (LiPH2), H2O2, veratryl alcohol, oxalate, ferric chloride, and 1,10-phenanthroline. The rate of iron reduction was dependent on the concentration of oxalate and was inhibited by the addition of superoxide dismutase. The addition of ferric iron inhibited oxygen consumption in reaction mixtures containing LiPH2, H2O2, veratryl alcohol, and oxalate. Thus, the reduction of ferric iron was thought to be dependent on the LiPH2-catalyzed production of superoxide in which veratryl alcohol and oxalate serve as electron mediators. Oxalate production and degradation in nutrient nitrogen-limited cultures of P. chrysosporium was also studied. The concentration of oxalate in these cultures decreased during the period in which maximum lignin peroxidase activity (veratryl alcohol oxidation) was detected. Electron spin resonance studies using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide were used to obtain evidence for the production of the hydroxyl radical in reaction mixtures containing LiPH2, H2O2, veratryl alcohol, EDTA, and ferric chloride. It was concluded that the white rot fungus might produce hydroxyl radical via a mechanism that includes the secondary metabolites veratryl alcohol and oxalate. Such a mechanism may contribute to the ability of this fungus to degrade environmental pollutants. 相似文献
134.
Faruque SM Chowdhury N Khan R Hasan MR Nahar J Islam MJ Yamasaki S Ghosh AN Nair GB Sack DA 《Applied and environmental microbiology》2003,69(12):7028-7031
Shigella dysenteriae type 1 is the causative agent of the most severe form of bacillary dysentery, which occurs as epidemics in many developing countries. We isolated a bacteriophage from surface water samples from Bangladesh that specifically lyses strains of S. dysenteriae type 1. This phage, designated SF-9, belongs to the Podoviridae family and has a 41-kb double-stranded DNA genome. Further screening of water samples for the prevalence of the phage revealed 9 of 71 (12.6%) water samples which were positive for the phage. These water samples were also positive in PCR assays for one or more S. dysenteriae type 1-specific genes, including ipaBCD and stx1, and live S. dysenteriae type 1 was isolated from three phage-positive samples. The results of this study suggest that phage SF-9 may have epidemiological applications in tracing the presence of S. dysenteriae type 1 in environmental waters. 相似文献
135.
Aman Shah Abdul Majid Amin Malik Shah Abdul Majid Zheng Qin Yin Dan Ji 《Neurochemical research》2013,38(7):1375-1393
Hydrogen sulphide (H2S) is one of three gaseous signaling molecules after nitric oxide and carbon monoxide. Various H2S donor compounds have been synthesized to study its physiological function. Among these compounds sodium hydrosulphide (NaHS), a donor of releasing H2S rapidly have shown to be protective in certain neuronal cell line but several in vivo studies have generated conflicting data. Furthermore several slow releasing H2S donors have been shown to have positive effects on cells in culture. The intracellular concentration of H2S and hence its rate of production may be a factor in keeping the balance between its neuroprotective and toxic effects. The present study was undertaken to deduce how a rapid releasing H2S donor (NaHS) as opposed to a slow releasing donor (ADTOH), affect oxidative stress related intracellular components and survival of RGC-5 cells. It was concluded that when RGC-5 cells are exposed to the toxic effects of glutamate in combination with buthionine sulfoxime (Glu/BSO), ADTOH was more efficacious in inhibiting apoptosis, scavenging reactive oxygen species (ROS), stimulation of glutathione (GSH) and gluthathione-S-transferase (GST). Western blot and qPCR analysis showed ADTOH increased the levels of Nrf2, HO-1, PKCα, p-Akt, Bcl-2 and XIAP but caused a decrease of Nfκβ and xCT greater than NaHS. This study is first to compare the efficacy of two H2S donor drugs as potential neuroprotectants and demonstrate that slow regulated release of H2S to cell culture can be more beneficial in inhibiting oxidative stress induced cell death. 相似文献
136.
137.
Trivedi A Vaghasiya S Dholariya B Dodiya D Shah V 《Journal of enzyme inhibition and medicinal chemistry》2010,25(6):893-899
Various pyrazolo[3,4-d]pyrimidines carrying a variety of substituents in the 6-position have been synthesised and their ability to inhibit growth of Mycobacterium tuberculosis in vitro has been determined. Compounds 5a, 5b, 6c, 7a, 7b, 8d, 8e and 8f demonstrated a minimum inhibitory concentration (MIC) of <6.25?μg/mL and were found to be active against Mycobacterium tuberculosis strain H(37)RV. Compound 8d was found to be the most active compound in vitro with a MIC of <6.25?μg/mL and inhibitory concentration IC(90) of 1.53?μg/mL. 相似文献
138.
Javed Nawab Mohammad Tahir Shah Kifayatullah Khan Roshan Ali 《International journal of phytoremediation》2015,17(9):801-813
Several anthropogenic and natural sources are considered as the primary sources of toxic metals in the environment. The current study investigates the level of heavy metals contamination in the flora associated with serpentine soil along the Mafic and Ultramafic rocks northern-Pakistan. Soil and wild native plant species were collected from chromites mining affected areas and analyzed for heavy metals (Cr, Ni, Fe, Mn, Co, Cu and Zn) using atomic absorption spectrometer (AAS-PEA-700). The heavy metal concentrations were significantly (p < 0.01) higher in mine affected soil as compared to reference soil, however Cr and Ni exceeded maximum allowable limit (250 and 60 mg kg?1, respectively) set by SEPA for soil. Inter-metal correlations between soil, roots and shoots showed that the sources of contamination of heavy metals were mainly associated with chromites mining. All the plant species accumulated significantly higher concentrations of heavy metals as compared to reference plant. The open dumping of mine wastes can create serious problems (food crops and drinking water contamination with heavy metals) for local community of the study area. The native wild plant species (Nepeta cataria, Impatiens bicolor royle, Tegetis minuta) growing on mining affected sites may be used for soil reclamation contaminated with heavy metals. 相似文献
139.
Plant defensins are small cysteine-rich antimicrobial proteins. Their three-dimensional structures are similar in that they consist of an α-helix and three anti-parallel β-strands stabilized by four disulfide bonds. Plant defensins MsDef1 and MtDef4 are potent inhibitors of the growth of several filamentous fungi including Fusarium graminearum. However, they differ markedly in their antifungal properties as well as modes of antifungal action. MsDef1 induces prolific hyperbranching of fungal hyphae, whereas MtDef4 does not. Both defensins contain a highly conserved γ-core motif (GXCX(3-9)C), a hallmark signature present in the disulfide-stabilized antimicrobial peptides, composed of β2 and β3 strands and the interposed loop. The γ-core motifs of these two defensins differ significantly in their primary amino acid sequences and in their net charge. In this study, we have found that the major determinants of the antifungal activity and morphogenicity of these defensins reside in their γ-core motifs. The MsDef1-γ4 variant in which the γ-core motif of MsDef1 was replaced by that of MtDef4 was almost as potent as MtDef4 and also failed to induce hyperbranching of fungal hyphae. Importantly, the γ-core motif of MtDef4 alone was capable of inhibiting fungal growth, but that of MsDef1 was not. The analysis of synthetic γ-core variants of MtDef4 indicated that the cationic and hydrophobic amino acids were important for antifungal activity. Both MsDef1 and MtDef4 induced plasma membrane permeabilization; however, kinetic studies revealed that MtDef4 was more efficient in permeabilizing fungal plasma membrane than MsDef1. Furthermore, the in vitro antifungal activity of MsDef1, MsDef1-γ4, MtDef4 and peptides derived from the γ-core motif of each defensin was not solely dependent on their ability to permeabilize the fungal plasma membrane. The data reported here indicate that the γ-core motif defines the unique antifungal properties of each defensin and may facilitate de novo design of more potent antifungal peptides. 相似文献
140.