Evidence is presented for the nuclear presence of a functional heteromeric complex of epidermal growth factor (EGFR), Src and the Signal Transducer and Activator of Transcription (Stat)3 proteins in pancreatic cancer cells. Stat3 remains nuclear and associated with Src or EGFR, respectively, upon the siRNA knockdown of EGFR or Src, demonstrating the resistance of the complex to the modulation of EGFR or Src alone. Significantly, chromatin immunoprecipitation (ChIP) analyses reveal the nuclear EGFR, Src and Stat3 complex is bound to the c-Myc promoter. The siRNA knockdown of EGFR or Src, or the pharmacological inhibition of Stat3 activity only marginally suppressed c-Myc expression. By contrast, the concurrent modulation of Stat3 and EGFR, or Stat3 and Src, or EGFR and Src strongly suppressed c-Myc expression, demonstrating that the novel nuclear heteromeric complex intricately regulates the c-Myc gene. The prevalence of the transcriptionally functional EGFR, Src, and Stat3 nuclear complex provides an additional and novel mechanism for supporting the pancreatic cancer phenotype and explains in part the insensitivity of pancreatic cancer cells to the inhibition of EGFR, Src or Stat3 alone.
Content of individual sugars, organic acids, total phenolics (TPH), some important phenolic compounds (kaempferol, myricetin, quercetin, and ellagic acid) and total antioxidant capacity (TAC) in the fruits of strawberry, raspberry and blackberry were studied. A comparison was made between cultivars and wild relatives of each species (Fragaria vesca L., Rubus idaeus L. and Rubus fruticosus L.). The main sugars found were fructose and glucose both in the fruits of wild species and the studied cultivars. Citric acid was determined to be the major organic acid in most of tested berries with the exception of blackberry cultivars, where malic acid was dominant. The content of individual phenolic compounds varied among the wild species, as well as among the studied cultivars. Ellagic acid content was higher in F. vesca, R. idaeus and R. fruticosus (122.5 mg/g FW, 12.71 mg/g FW and 61.7 mg/g FW, respectively) than that obtained in analyzed cultivars. Overall, TPH expressed higher values in the wild strawberry and blackberry species in comparison to the studied cultivars, and consequently, the highest levels of TAC were recorded in F. vesca (5.78 mg asc/ g FW), followed by R. fruticosus (4.95 mg asc/g FW). PRACTICAL APPLICATIONSIn recent years, both wild and cultivated berries have become very attractive for consumers because of potentially beneficial phytochemicals contained in these fruits. Fruit nutritional quality can be described by standard quality parameters (sugars and organic acids), and the analysis of antioxidant capacity influenced by specific related compounds. The importance of flavonoids and other phenolics have been suggested to play a preventive role in the development of cancer and heart disease. A significant positive correlation observed in this study between total phenolics and total antioxidant capacity indicate the need for the use of wild species in the breeding programs of small fruits, especially strawberry and blackberry, in order to increase their nutritive value and the health benefits. ISSN 0146-9428 Journal of Food Quality
BackgroundGold nanoparticles (AuNPs) scatter light intensely at or near their surface plasmon wavelength region. Using AuNPs coupled with dynamic light scattering (DLS) detection, we developed a facile nanoparticle immunoassay for serum protein biomarker detection and analysis. A serum sample was first mixed with a citrate-protected AuNP solution. Proteins from the serum were adsorbed to the AuNPs to form a protein corona on the nanoparticle surface. An antibody solution was then added to the assay solution to analyze the target proteins of interest that are present in the protein corona. The protein corona formation and the subsequent binding of antibody to the target proteins in the protein corona were detected by DLS.ResultsUsing this simple assay, we discovered multiple molecular aberrations associated with prostate cancer from both mice and human blood serum samples. From the mice serum study, we observed difference in the size of the protein corona and mouse IgG level between different mice groups (i.e., mice with aggressive or less aggressive prostate cancer, and normal healthy controls). Furthermore, it was found from both the mice model and the human serum sample study that the level of vascular endothelial growth factor (VEGF, a protein that is associated with tumor angiogenesis) adsorbed to the AuNPs is decreased in cancer samples compared to non-cancerous or less malignant cancer samples.ConclusionThe molecular aberrations observed from this study may become new biomarkers for prostate cancer detection. The nanoparticle immunoassay reported here can be used as a convenient and general tool to screen and analyze serum proteins and to discover new biomarkers associated with cancer and other human diseases.
This work presents findings, which indicate important role of fructose, fructose 6-phosphate (F6P), and fructose 1,6-bisphosphate (FBP) in preservation of homeostasis in plants under low temperature. Cold combined with light is known to incite increased generation of superoxide in chloroplasts leading to photoinhibition, but also an increased level of soluble sugars. In the present study, oxidative stress in pea leaves provoked by cold/light regime was asserted by the observed decrease of the level of oxidized form of PSI pigment P700 (P700+). Alongside, the increased antioxidative status and the accumulation of fructose were observed. The antioxidative properties of fructose and its phosphorylated forms were evaluated to appraise their potential protective role in plants exposed to chilling stress. Fructose, and particularly F6P and FBP exhibited high capacities for scavenging superoxide and showed to be involved in antioxidative protection in pea leaves. These results combined with previously established links implicate that the increase in level of fructose sugars through various pathways intercalated into physiological mechanisms of homeostasis represents important non-enzymatic antioxidative defense in plants under cold-related stress.
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