Mechanism of Molecular Activity of Yolkin-a Polypeptide Complex Derived from Hen Egg Yolk-in PC12 Cells and Immortalized Hippocampal Precursor Cells H19-7.

Food-derived bioactive peptides able to regulate neuronal function have been intensively searched and studied for their potential therapeutic application. Our previous study showed that a polypeptide complex yolkin, isolated from hen egg yolk as a fraction accompanying immunoglobulin Y (IgY), improved memory and cognitive functions in rats. However, the mechanism activated by the yolkin is not explained. The goal of the present study was to examine what molecular mechanism regulating brain-derived neurotrophic factor (BDNF) expression is activated by the yolkin complex, using in vitro models of PC12 cell line and fetal rat hippocampal cell line H19-7. It was shown that yolkin increased the proliferative activity of rat hippocampal precursor cells H19-7 cells and upregulated the expression/production of BDNF in a cyclic adenosine monophosphate (cAMP)-response element-binding protein (CREB)-dependent manner. Additionally the upregulation of carboxypeptidase E/neurotrophic factor-α1 (CPE/(NF-α1) expression was shown. It was also determined that upregulation of CREB phosphorylation by yolkin is dependent on cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt) signaling pathway activation. Moreover, the impact of yolkin on the level of intracellular Ca2+, nitric oxide, and activation of extracellular signal-regulated kinases 1/2 (ERK 1/2 kinase) was excluded. These results emphasize that yolkin can act comprehensively and in many directions and may participate in the regulation of neurons' survival and activity. Therefore, it seems that the yolkin specimen can be used in the future as a safe, bioavailable, natural nutraceutical helping to improve the cognition of older people.

Non-toxic Polymeric Dots with the Strong Protein-Driven Enhancement of One- and Two-Photon Excited Emission for Sensitive and Non-destructive Albumin Sensing.

The need for efficient probing, sensing, and control of the bioactivity of biomolecules (e.g., albumins) has led to the engineering of new fluorescent albumins' markers fulfilling very specific chemical, physical, and biological requirements. Here, we explore acetone-derived polymer dots (PDs) as promising candidates for albumin probes, with special attention paid to their cytocompatibility, two-photon absorption properties, and strong ability to non-destructively interact with serum albumins. The PDs show no cytotoxicity and exhibit high photostability. Their pronounced green fluorescence is observed upon both one-photon excitation (OPE) and two-photon excitation (TPE). Our studies show that both OPE and TPE emission responses of PDs are proteinaceous environment-sensitive. The proteins appear to constitute a matrix for the dispersion of fluorescent PDs, limiting both their aggregation and interactions with the aqueous environment. It results in a large enhancement of PD fluorescence. Meanwhile, the PDs do not interfere with the secondary protein structures of albumins, nor do they induce their aggregation, enabling the PD candidates to be good nanomarkers for non-destructive probing and sensing of albumins.

A Novel Mechanism of Macrophage Activation by the Natural Yolkin Polypeptide Complex from Egg Yolk.

Ageing is accompanied by the inevitable changes in the function of the immune system. It provides increased susceptibility to chronic infections that have a negative impact on the quality of life of older people. Therefore, rejuvenating the aged immunity has become an important research and therapeutic goal. Yolkin, a polypeptide complex isolated from hen egg yolks, possesses immunoregulatory and neuroprotective activity. Considering that macrophages play a key role in pathogen recognition and antigen presentation, we evaluated the impact of yolkin on the phenotype and function of mouse bone marrow-derived macrophages of the BMDM cell line. We determined yolkin bioavailability and the surface co-expression of CD80/CD86 using flow cytometry and IL-6, IL-10, TGF-ß and iNOS mRNA expression via real-time PCR. Additionally, the impact of yolkin on the regulation of cytokine expression by MAPK and PI3K/Akt kinases was determined. The stimulation of cells with yolkin induced significant changes in cell morphology and an increase in CD80/CD86 expression. Using pharmaceutical inhibitors of ERK, JNK and PI3K/Akt, we have shown that yolkin is able to activate these kinases to control cytokine mRNA expression. Our results suggest that yolkin is a good regulator of macrophage activity, priming mainly the M1 phenotype. Therefore, it is believed that yolkin possesses significant therapeutic potential and represents a promising possibility for the development of novel immunomodulatory medicine.

Inverse Correlation Between Alzheimer's Disease and Cancer: Short Overview.

The negative association between Alzheimer's disease (AD) and cancer suggests that susceptibility to one disease may protect against the other. When biological mechanisms of AD and cancer and relationship between them are understood, the unsolved problem of both diseases which still touches the growing human population could be overcome. Actual information about biological mechanisms and common risk factors such as chronic inflammation, age-related metabolic deregulation, and family history is presented here. Common signaling pathways, e.g., p53, Wnt, role of Pin1, and microRNA, are discussed as well. Much attention is also paid to the potential impact of chronic viral, bacterial, and fungal infections that are responsible for the inflammatory pathway in AD and also play a key role to cancer development. New data about common mechanisms in etiopathology of cancer and neurological diseases suggests new therapeutic strategies. Among them, the use of nilotinib, tyrosine kinase inhibitor, protein kinase C, and bexarotene is the most promising.

Comparative Studies of Yolkin Preparations Isolated from Egg Yolks of Selected Bird Species.

The results of our research have proven that yolkin preparations isolated from eggs of different bird species show a high similarity in polypeptide composition. Despite the small differences in protein patterns, all of yolkin preparations showed also strong immunomodulatory activity, comparable with yolkin obtained previously from hen egg yolk. It can therefore be deducted that the presence of this polypeptide complex in the egg is not accidental and performs an important biological function for developing embryo.

The subcellular localization of bHLH transcription factor TCF4 is mediated by multiple nuclear localization and nuclear export signals.

Transcription factor 4 (TCF4) is a class I basic helix-loop-helix (bHLH) transcription factor which regulates the neurogenesis and specialization of cells. TCF4 also plays an important role in the development and functioning of the immune system. Additionally, TCF4 regulates the development of Sertoli cells and pontine nucleus neurons, myogenesis, melanogenesis and epithelial-mesenchymal transition. The ability of transcription factors to fulfil their function often depends on their intracellular trafficking between the nucleus and cytoplasm of the cell. The trafficking is regulated by specific sequences, i.e. the nuclear localization signal (NLS) and the nuclear export signal (NES). We performed research on the TCF4 trafficking regulating sequences by mapping and detailed characterization of motifs potentially acting as the NLS or NES. We demonstrate that the bHLH domain of TCF4 contains an NLS that overlaps two NESs. The results of in silico analyses show high conservation of the sequences, especially in the area of the NLS and NESs. This high conservation is not only between mouse and human TCF4, but also between TCF4 and other mammalian E proteins, indicating the importance of these sequences for the functioning of bHLH class I transcription factors.