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.

Immunity transfer from a mother to the newborn does not depend exclusively on immunoglobulins. Peptides, which are characterized by immunoregulatory properties that accompany IgG2, known as proline- rich polypeptide complex (PRP), have been discovered for the first time in ovine colostrum. In this report we present new data showing that some immunoregulatory peptides associated with the main immunoglobulin class, IgY, are also present in the avian immune system. Cytokine-inducing activity of particular fractions obtained from ovine colostrum, IgG+ (IgG2 containing PRP), IgG− (IgG2 free of PRP), and purified PRP, was compared with that of crude egg yolk IgY (IgY+), additionally purified egg yolk IgY (IgY−), and polypeptides accompanying IgY named Yolkin (Y), using an ex vivo model of whole human blood cells. It was shown that both IgG+ fraction and PRP, but not IgG−, stimulated the whole blood cells to release tumor necrosis factor-α and interleukin-1β cytokines. Similar experiments performed with hen's egg IgY preparations showed that IgY+ and Y samples showed higher cytokine-inducing activity than samples additionally purified with the use of size exclusion chromatography (IgY−). The IgY+ at a dose of 100 μg was even more active than the positive lipopolysaccharide control. It was also found that Y is able to stimulate macrophage cell line J774.2 to release nitric oxide. The results obtained suggest that IgY, the main chicken immunoglobulin fraction, is accompanied by additional polypeptides and plays a role of a transporter of biologically active substances, which was observed in the case of colostral IgG.

The protein mixture of cytokine-inducing activity accompanying chicken immunoglobulin Y, named yolkin, consists of several peptides of molecular weight (MW) ranging from over 1 to 35 kDa. Yolkin and its constituent peptides were found to be efficient inducers of interleukin (IL)-1β, IL-6 and IL-10 secretion. N-terminal amino acid sequences of eight of the electrophoretically purified yolkin constituents revealed that all of them are homological to some fragments of the C-terminal domain of vitellogenin II. The fractions of MW about 4 and 12 kDa are free of carbohydrates and start at position 1732 in the vitellogenin amino acid sequence; whereas the other fractions (MW about 16, 19, 23, 29, 32 and 35 kDa) appeared to be glycoproteins corresponding to the amino acid sequence of vitellogenin starting at position 1572. From these data, it is concluded that yolkin most likely represents vitellogenin-derived peptides that possess cytokine-inducing activity and are, at least partially, responsible for such properties of separated immunoglobulin Y preparation. This finding reveals a new role for vitellogenin as a reservoir of polypeptides that may play an important role in the innate immune system of the developing embryo.

Cel pracy: Nadal istnieje zapotrzebowanie na nowe, efektywne biologiczne interwencje terapeutyczne w epizodach depresyjnych i zaburzeniu depresyjnym nawracającym. Krioterapia ogólnoustrojowa (WBC), będąca formą stymulacji ogólnoustrojowej temperaturami kriogenicznymi, jest coraz częściej stosowaną metodą leczniczą w schorzeniach neurologicznych oraz w reumatologii. Badanie miało na celu określenie skuteczności krioterapii ogólnoustrojowej jako augmentacji leczenia epizodu depresyjnego.Metoda: Do badania obserwacyjnego zrekrutowano 30 dorosłych pacjentów leczonych ambulatoryjnie z powodu epizodu depresyjnego. 21 osób (17 kobiet, 81%) ze średnią wieku 46,1 (±16,7) lat ukończyło badanie. Do określenia nasilenia objawów depresyjnych u badanych użyto Skali Depresji Hamiltona oraz Inwentarza Depresji Becka. Jakość życia oceniano WHOQoL-Bref a poziom anhedonii skalą SHAPS. W okresie 2 tygodni przeprowadzono 10 dwuminutowych sesji ekspozycji na skrajnie niskie temperatury (od -110 do -135 stopni Celsjusza).Wyniki: Po cyklu kriostymulacji ogólnoustrojowej stwierdzono znaczącą poprawę w postaci redukcji ogólnej punktacji w skalach oceniających objawy depresyjne HDRS między T1 (16,94±4,3) i T4 (4,50±4,2) (p<0.00001) oraz BDI (T1: 13,48±4,6; T4: 6,14±6.7, p<0,03), nasilenie anhedonii w skali SHAPS (p=0,011), oraz wyższe wyniki w skali jakości życia w domenach: poczucie zdrowia fizycznego (p=0,024), poczucie zdrowia psychicznego (p=0,016) oraz w domenie środowiskowej (p=0,003). Zauważono istotny wzrost samodzielnie ocenianego samopoczucia przy użyciu skali VAS przed i po przebytych zabiegach (p0,05).Wnioski: Krioterapia ogólnoustrojowa okazała się efektywną, bezpieczną oraz dobrze tolerowaną dodatkową interwencją terapeutyczną wśród pacjentów z epizodem depresyjnym. Dalsze randomizowane badania z grupą kontrolną powinny zostać przeprowadzone.

One of the goals of biomedical sciences is to search and identify natural compounds that are safe, have no side effects, and possess immunostimulatory activity. It has been proven that medicines of natural origin can be effective agents, supporting the therapy of many diseases, not only in the weakened immune system of the body but also in the prevention of many diseases in healthy people. It has been shown that yolkin, a polypeptide complex isolated from hen egg yolk as a fraction accompanying immunoglobulin Y (IgY), possesses potential biological activity. However, the mechanism of its action has not been explained. The objective of this investigation was to examine the molecular mechanisms of innate immune response, activated in response to yolkin, in murine bone marrow-derived macrophages (BMDM). It was shown that yolkin induced phosphorylation of extracellular signal-kinases (ERK1/2) and c-Jun N-terminal kinase (JNK) and upregulated expression and production of type I interferons, TNF-α (tumor necrosis factor α), and nitric oxide (NO), in BMDM cells. Using pharmacological inhibitors of ERK 1/2 and JNK kinases, we revealed that the JNK signaling cascade is required for yolkin-induced inducible NOS expression and upregulation of NO production in mouse macrophages. Using the TLR4-deficient BMDM cell line, we established that yolkin can activate macrophages in a TLR4-dependent manner. It was also shown that NO, TNF-α, and type I IFNs (α/β) produced by BMDM cells in response to yolkin triggered antiviral activity. These data indicate that yolkin affects the regulation of the immune system and antiviral response; therefore, it can be used as an effective immunostimulator of the innate immunity or as a supplement of the conventional therapy of immunodeficiency.