National Science Centre
The aim of the planned research is therefore to check whether Arg-1 actually plays a role in the inhibition of an effective immune response and thus in the progression of myeloma. In our research, we will use genetically modified strains of mice, including animals lacking the Arg-1 gene and strains of transgenic mice, which will allow us to study a specific immune response. We will examine whether the lack of Arg-1 or pharmacological inhibition of this enzyme activity affects the progression of myeloma and the development of the immune response. We will also investigate whether an Arg-1 inhibitor may enhance the anti-tumor effects of bortezomib and reduce its cardiotoxicity in animals. The knowledge gained from this research will provide a better understanding of the molecular mechanisms involved in the development of myeloma, the anti-cancer immune response and the side effects of drugs used in oncology. We hope that the research results will also enable the identification of new research areas that can be used in the development of immunology, cardiooncology and experimental oncology.
Given the significant prognostic value offered by the knowledge of the DIRC3 genotype, we anticipate that understanding the biological basis of a predisposition to DTC associated with this gene will allow the detection of oncogenic aberrations of even greater clinical importance. This may enable the identification of new diagnostic markers of the disease and allow the identification of high-risk DTC patients requiring closer supervision and more radical treatment. The results of the project will be published in the scientific press and will form the basis of the project lead's doctoral dissertation.
The obtained results will allow to broaden the current state of knowledge regarding factors related to the formation of hernias after abdominal surgeries performed with transverse cuts, which differ significantly from midline cuts in terms of the anatomy of the cut structures, blood supply to the wound edges and the forces acting on it. Currently available data do not allow any reliable evaluation of the importance of the technique of abdominal wall closure with transverse incisions within the epigastric region. Apart from very preliminary results, the results obtained so far do not allow to determine the importance of glycation end-products in the pathogenesis of postoperative hernias, and the results of studies on the influence of changes in the collagen content remain inconclusive. In addition to improving the current knowledge, the results obtained may in the future lead to the development of a strategy for more effective assessment and reduction of the risk of hernia formation.
The aim of the project is to assess the content and profile of COPs in products available on the Polish market and the impact of selected technological processes on the level of these contaminants in ready-to-eat food.
The scope of the project will include the following topics:
[1] Optimization and full validation of the method for determining the content and COPs profile in food.
[2] Assessment of the content and profile of COPs in food available on the Polish market, including
traditional products.
[3] Influence of technological processes (baking, frying, smoking; red meat / fish) and maturation time (dairy products) on the content and profile of COPs.
The research material will be market products from three groups: [1] dairy products, [2] red meat and its products, [3] fish and their products. Determination of oxysterols will be carried out using high-performance liquid chromatography with UV and RID detectors, but the obtained results will be confirmed by mass spectrometry. The following compounds will be marked in the products: 7-ketocholesterol, 7α-hydroxycholesterol, 7β-hydroxycholesterol, 5-6α-epoxycholesterol, 5-6β-epoxycholesterol, 25-hydroxycholestrol, cholestanetriol and others. Estimated number of attempts (problems 2 + 3) approx. 650.
This project is only a preliminary study for subsequent works. The future project submitted to the National Science Center will cover [1] the assessment of the exposure of the Polish population to food contamination of animal origin resulting from technological processes (including maturation, thermal processes), with particular emphasis on COPs and biogenic amines, in the context of the pathogenesis of selected diseases non-infectious and [2] to learn about the factors determining the formation of these compounds in food in order to create prognostic models determining their level depending on the product composition and applied technological parameters, within three product groups: dairy products, red meat and its products, fish and their products.
The results obtained under the project will be published in at least two articles in reputable scientific journals (List A of the Ministry of Science and Higher Education), which will be included in the series of publications constituting the basis for initiating the habilitation procedure.
The aim of the project is to determine whether and to what extent the metabolites of ellagotanoids and flavan-3-ol-urolithin and 5- (3 ', 4', 5'-trihydroxyphenyl) -g-valerolactone produced by the intestinal microbiome can contribute to the beneficial effects of rich preparations in polyphenols, such as pomegranate preparations and green tea, in prostate cancer. During the project implementation, the effect of the above-mentioned metabolites and their mixtures with drugs used in the conventional treatment of prostate cancer, the anti-androgen bicalutamide and the chemotherapeutic agent docetaxel, on the proliferation and survival of prostate cancer cells will be investigated. Two prostate cancer cell lines differing in their sensitivity to bicalutamide and docetaxel, LNCaP and DU-145, will serve as in vitro models of neoplastic cells, while the PZ-HPV-7 immortalized cell line will be a model of normal prostate cells. The first stage of the work will investigate the proliferation and apoptosis of cells after incubation with the test compounds and their mixtures. The results of proliferation studies will be used to determine whether there are pharmacodynamic interactions between polyphenol metabolites and drugs and, if appropriate, to determine their nature (synergism, additivity, antagonism). The second stage of the project will focus on determining the influence of the test compounds and their mixtures on the previously selected signal transduction pathways and molecular targets that play an important role and often malfunction in the course of prostate cancer: androgen receptor, signal transducer and activator 3 (STAT3), Akt kinase and NF-kB transcription factor and expression of proteins controlling cell survival (Bcl-2, Bax, survivin). Prostate neoplasms are among the most common and among the leading causes of cancer death in men in the world. About 30% of prostate cancer patients use supplements, often containing plant-based ingredients, to improve disease control. Moreover, it was found that patients with more advanced disease were significantly more likely to use complementary and alternative medicine (CAM). Preparations containing polyphenols from pomegranate fruit and green tea are commonly used by patients with prostate cancer. While the use of phytotherapeutic drugs is generally safe for the general population, it may not be safe for pharmacotherapy of cancer. Many compounds of plant origin interact with drugs used in cancer therapy, limiting their effectiveness or increasing toxicity. Despite the encouraging results of studies on the effect of processed pomegranates and green tea on animal models of prostate cancer in vivo, it is difficult to explain the observed results by the direct action of the polyphenols present in them. The polyphenols present in green tea and pomegranate have poor bioavailability after oral administration. On the other hand, the products of their biotransformation by the intestinal microbiome are easily absorbed in the intestines and reach concentrations at least several times higher in body fluids than their parent compounds. Determining the role of polyphenol metabolites produced by the intestinal microbiome in the systemic action of polyphenols after oral administration will provide useful information on the combined effects of the intestinal microbiome and phytotherapeutic agents, and will contribute to a better understanding of the mechanisms of beneficial outflow of the use of a diet or preparations rich in polyphenols.
The increase in the incidence of malignant neoplasms made it necessary to look for means saving the lives of patients. The interest of scientists was aroused by mushroom extracts, which have been used in the Far East for 2,000 years as alternative components of natural medicine. Currently, research is conducted on the antitumor and immunomodulatory activity of polysaccharides of fungal origin. Conclusions resulting from the analysis of research works of these compounds are promising, because several isolates, derived from the mycelium or fruiting bodies of fungi belonging to the Basidiomycota type, have been approved for treatment in some countries as dietary supplements and as an anti-cancer drug. In Japan, lentinan, a licensed anti-cancer drug that has been used since 1985 by the Japanese pharmaceutical company Ajinomoto, remains in the top ten of the most used anticancer drugs. Lentinan is a highly purified exopolysacchardide fraction, showing a high level of immunomodulatory activity. It was first isolated in 1970 by Chihara from Lentinula edodes (Shii-take mushroom) and is still extracted by the same method to this day. Unfortunately, the cultivation time of L.edodes fruiting bodies is relatively long, and the complex isolation procedure results in low yield and a very high price of the obtained medicinal preparation. Selenium also has an anti-cancer effect. A similar pharmacological effect caused by polysaccharides of fungal origin (β-glucans) and selenium compounds, despite the difference in the mechanism of action, suggests a synergism of both components. Selenium added to the medium may increase the immunomodulatory effect of polysaccharides from the culture medium. The aim of the project is to investigate the mechanism of selenium incorporation into the structure of exopolysaccharides secreted into the substrate in submerged culture of mycelium of the medicinal fungus Lentinula edodes in a liquid medium enriched with sodium selenate (IV) and to determine the impact of this process on the biological activity of these compounds. The project foresees to compare the structure of the intended selenium ego-polysaccharide fractions with reference fractions isolated from non-selenium enriched culture. The research carried out in the project should answer the following questions:
• Does the incorporation of selenium into the structure of exopolysaccharides affect the immunomodulatory, cytotoxic and antioxidant activity of the fraction?
• What is affected by the binding of immune system receptors to β-glucans?
• Could L.edodes breeding in the future contribute to the design of an immunomodulatory drug that would be much cheaper and less toxic than those available on the pharmaceutical market today?
Head and neck squamous cell cancer (HNSCC) is a group of cancers that affect the mouth, pharynx, larynx, nose and paranasal sinuses. They represent over 90% of all malignant neoplasms in this region. In 2012, over 600,000 new cases of HNSCC were registered worldwide, making these cancers the seventh most common human cancer. Despite multicentre research on HNSCC, as well as the development of new therapeutic concepts and diagnostic methods, the average 5-year survival has remained below 50% for 4 decades. Thus, there is an urgent need to identify novel biomarkers and therapeutic approaches for HNSCC. Adequate vascularization is essential for the growth of solid tumors such as HNSCC. Tumor angiogenesis is based on the mechanisms of classical angiogenesis. Tumors are able to increase their own vascularity by producing angiogenic factors or use tumor cells to migrate close to existing vascular structures and mimic endothelial cells (ECs) or differentiate into ECs. Recent years of research into the effects of cancer on its own microenvironment and the host's immune system focuses on micro-vesicles (EVs), which are spherical structures 30-150 nm in diameter, also known as 'exosomes.' EVs are produced by all types of cells but tumor cells are particularly active producers of tumor-derived exosomes (TEX). Exosomes contain a whole panel of different particles such as DNA, mRNA and microRNA (miR), enzymes, growth factors, etc. Research in recent years has shown that TEX play an important role in suppressing the immune system in the tumor microenvironment (TME) which promotes tumor progression. Moreover, the influence of TEX on the development of blood vessels and angiogenesis is also suspected. Therefore, based on our preliminary research results and literature data, we hypothesize that TEX influence the proliferation of ECs and angiogenesis in the HNSCC microenvironment. Therefore, the aim of the present project is to investigate the role of TEX in the angiogenesis and progression of HNSCC and to investigate the mechanisms underlying this process using in vitro, in vivo and ex vivo models.
The study concerns the cognitive functioning of people suffering from schizophrenia. Schizophrenia is one of the most severe mental illnesses. It usually begins at a young age, and its chronic course and strong influence on functioning often necessitate long-term treatment and rehabilitation.
Despite the dynamic development of pharmacotherapy over several decades, a large proportion of patients still experience unpleasant symptoms of the disease - delusions or hallucinations. The productive symptoms of schizophrenia have been the subject of research for many years. Scientists dealing with psychological concepts of psychotic symptoms point out that the cognitive distortions often observed in people suffering from schizophrenia may be a mechanism that triggers or maintains psychotic symptoms. The association of positive symptoms of schizophrenia with such cognitive distortions as: attribution errors (assigning blame for failure to other people), too hasty decision-making ("jumping to conclusions"), deficits in the theory of mind (difficulties in understanding the intentions and emotions of other people) has been shown.
Currently, more and more attention in schizophrenia is devoted to cognitive distortion, which consists in incorrectly assigning the source of information origin - source monitoring processes. The term source monitoring refers to the cognitive processes involved in attributing the origin of memories, knowledge, or beliefs. In everyday life, this ability plays a significant role and enables, among others, distinguishing whether an event really happened to us, or whether we just imagined it or whether someone told us about it. Disturbed source monitoring process can cause interpersonal conflicts or false memories. However, little is known about the mechanisms underlying the above-mentioned difficulties. The extent to which the increased number of source monitoring errors and other cognitive distortions may be affected by neuropsychological deficits in attention, memory, and executive functions has not yet been determined.
The aim of the study is to find out if and how cognitive distortions are related to neuropsychological functioning (e.g. attention, direct memory, verbal memory, executive functions) in people diagnosed with schizophrenia. In order to answer the research question, a study was designed in which 80 people suffering from schizophrenia and 80 healthy people will participate. Participants will be subjected to tests to assess the severity of symptoms, neuropsychological assessment, experimental tasks assessing cognitive distortions and self-report questionnaires.
Establishing the relationship between cognitive distortions and neuropsychological functioning will allow to supplement the existing knowledge and may contribute to the creation of cognitive-behavioral therapeutic interventions aimed at reducing the cognitive distortions committed.
Non-specific inflammatory bowel disease and colon cancer are an extremely serious health problem in the human population. The aim of the research is to design and/validate a new form of therapy of non-specific inflammatory diseases and colon cancer with the use of innovative gold complexes. The research is in line with the current trend in designing anti-inflammatory and anti-cancer compounds based on metal particles, enriching this group with lipid derivatives. The project aims to characterize the anti-inflammatory and anti-cancer properties of the parent compound - TGS, which is a gold (III) complex, in animal models.. The next stage of the research will consist in designing derivatives of the starting compound in which the gold (III) complex will be combined with lipid fragments. From among the newly synthesized compounds, based on the ex vivo test designed specifically for this project, 1-2 derivatives with potential anti-inflammatory activity will be selected for further research, and their anti-inflammatory and anti-tumor efficacy will also be confirmed in animal models. The last stage of the research involves in vitro and in silico tests, the aim of which will be to try to determine the mechanism of action of the new complexes. The results of the conducted research will allow to create the basis for a new form of therapy of inflammatory and neoplastic diseases of the large intestine based on innovative gold (III) complexes by our Consortium. An added value will be the development of a new ex vivo diagnostic test that will allow for a quick and reliable assessment of the potential anti-inflammatory properties of various compounds. The results will also be used to develop the scientific career of one of the researchers participating in the project, constituting the basis for his doctoral dissertation.