National Science Centre

The project aims to find a justification for the traditional use of witch hazel bark as a topical agent used in skin
infections, inflammation, and skin regeneration. Wound healing is negatively affected by lifestyle diseases of metabolic
or cardiovascular background, socioeconomic factors, and availability of therapy. As it continues to pose an increasing
economic burden and significantly affects the quality of life among the patients afflicted, new and diverse therapeutic
interventions aimed at facilitating skin regeneration and antimicrobial treatment should be considered. For years
phytotherapy was the main available treatment for dermatological conditions. However, the application of herbal
remedies has been based largely on historical or anecdotal evidence. More credible data obtained in comprehensive
research, as well as approaching both the efficacy and safety of traditionally used remedies is required. The evidencebased
reintroduction of previously used herbal remedies, which antibiotics had replaced, may be a promising strategy.
Evidence linking chemically identified compounds with activity in specific indications would be a foundation for
sufficient standardization and quality control of plant-based products. Moreover, in recent years there has been an
expansion in the research, which progressively incorporates the influence of xenobiotics on the microbiome or the
microbiome on the xenobiotics. Rediscovery of the importance of microbiota will furtherly result in deepening
comprehension of the complex interplay between disease-related processes, characteristics of microbial communities
and the use of xenobiotics. Addressing these issues in the pre-clinical phases of research on medicinal plant materials
would be the first step for effective quality control, design of reliable clinical research with reproducible results, as well
as recognizing the relevance of phytotherapy by evidence-based medicine.

The purpose of this research activity is to use metabolomics (the so-called metabolic footprint
finger) to determine the effect of active substances of drugs present in bottom sediments on metabolism
Heterocypris incongruens, including the selection of metabolic pathways affected by API exposure.

The subject of this research activity is to carry out anatomical research
concerning the white matter pathways of the brain in relation to the results of imaging diagnostics and
neurophysiology, in order to improve the planning process of surgical treatment of patients with
drug-resistant epilepsy.

Celem niniejszego projektu jest poszerzenie wiedzy na temat sygnałowania purynergicznego w
komórkach białaczkowych w tym ocena udziału receptora P2X4 w procesach proliferacji, adhezji
oraz profilu metabolicznego ludzkich komórek przewlekłej białaczki szpikowej in vitro. Dla
realizacji projektu zamierzam użyć linie komórkowe ludzkich białaczek różnego typu: Hel 92.1.7,
NALM-1, K562 oraz KG-1a.

The goal of the project is to obtain
innovative knowledge of the etiology of infections, variability, microbial function in relation to
conventional microbiological methods.

The main aim of this study will be an attempt to evaluate sIgE in the nasal lavage in the nasal passages
provocation test with egg allergens in the investigated group - adults (18-45 years old). The research
is a breakthrough in the area of ​​understanding the mechanisms of the IgE-dependent reaction (within the
nasal mucosa) in food allergy. Assessment options at various levels of reaction including
cellular levels: the determination of sIgE in nasal lavage is evidence of the innovative nature of the
project and, consequently, will constitute (the results of obtained during the implementation of this project will be used in a future project) a continuation under the project of the National Science Center - OPUS carried out on the population
children 6-14 years old. The intranasal allergen challenge test is a method that mimics
the body's response to the action of the allergenic factor. Used in the assessment of membrane reactivity
mucosa to common environmental allergens, it is characterized by high specificity, sensitivity and
test safety [1]. As of today, the literature on the subject shows that there is a need to work on
this issue due to the promising research results and the expansion of new opportunities of assessment. Three currently promising works including: a mouse model [2] and the use of egg allergens
chicken [3] and peanuts [4] prove the need for further research in this area. It must be noted that the assessment of the degree of response to a provoked allergen was based on the technique that
goes beyond the traditional scheme of nasal challenge assessment - vision thermograph, but
significant differences were observed in relation to the assessed values ​​- head and nasal cavity temperature
(Mann-Whitney test: 18.2 ° Cmin (range 4.7-80.8) vs control group 4.8 ° C min (0-24.7); p =
0.0006) [4]. Importantly, EAACI Position paper on the standardization of nasal allergen challenges
points to a new premise for indications for nasal attempts with a clear accent of
the need for further research in this area [1]. The applicant is the first in the world to intend
implementation of a qualified assessment as an objective assessment in the form of an sIgE assay in the nasal washings
directed against egg proteins after intranasal application of the allergen. The research hypothesis
assumes that as a result of local allergen provocation, there will be observed
a significant increase in the level of sIgE in the nasal lavage, which will translate into a typical picture of
early phase of an allergic reaction, i.e. nasal blockage, sneezing, discharge of watery secretions.
Material and method. 50 patients will be qualified for the study, including: 25 people allergic to
chicken egg allergens (positive clinical history, skin tests, serum sIgE) and 25 people aged 18-45 years as a control group. Patients will be diagnosed at the University Clinical Center of the Medical University of Warsaw. The method we will use in the study will be intranasal provocation test with egg allergen. The 10 μg (extract) allergen suspended in 100
μg of saline will be administered as per standard [1] through an atomizer to both nostrils.
The dose used in the provocation test following the research pattern is 50% of the extract used in
oral nutritional tests [4]. The examination will be carried out in two stages: after local
acclimatization to the conditions in the research laboratory, the first test will be performed (after
topical application with a saline atomizer in which allergen will be suspended),
in which patients will undergo nasal lavage for the determination of sIgE in the lavage, and then this
procedure will be repeated in the first 30 minutes of the early phase of the allergic reaction. Material
for testing purposes obtained after prior centrifugation of the nasal washes at a speed of 1,000 rpm, for
a period of 15 minutes was stored at -70 ° C and then subjected to treatment
enzyme-linked immunosorbent biochemical test (UniCAP, Pharmacia, Sweden) at the recommended
sensitivity threshold of 1.0μg / l. At the same time, we will make a subjective evaluation of the nasal washings with
visual and analog scale of the reported complaints in the field of: nasal cavity blockage,
itching, discharge of watery secretions.
 

On December 2, 2010, the Council of the European Union, based on the report of the European Commission of August 3, 2010, decided to subject mephedrone to control measures and to subject it to criminal sanctions provided for by national legislation in the European Union (20101759 / EU). Despite the introduction of appropriate statutory regulations, the number of hospitalizations of patients taking mephedrone with other psychoactive substances is increasing year by year in Poland [1]. The articles published by me in the last 2 years indicate that one of the factors increasing the risk of subsequent hospitalization may be liver dysfunction [2]. The conducted analyzes showed, among others, that it is not mephedrone but HCV infection in this group of patients that is a factor that increases the level of liver enzymes. As a result of taking mephedrone with other drugs, and the concomitant HCV infection, the parenchymal cells of the liver are damaged. This results in increased release of transaminases from the liver into the blood and an increase in their concentration [3]. However, they are non-specific markers of liver damage because they are found in many types of cells, and they increase with damage to almost any organ. For this reason, more specific markers of hepatotoxicity should be investigated, such as: keratin 18 (K18), glutamate dehydrogenase GLDH, α-glutathione-transferase (αGST), tumor necrosis factor alpha (TNF-α) and interleukin 1-Beta [4]. Patients with no co-infection with HCV taking mephedrone with alcohol or mephedrone with heroin (15 in each group) would be enrolled in the study. My research to date shows that patients do not take mephedrone alone, but combine it with other psychoactive substances [1]. For this reason, the comparison group would consist of patients addicted to heroin alone (n = 30), alcohol (n = 30), as well as healthy people (n = 30). The study would exclude patients with disease entities that could affect the obtained results of liver parameters, which would be measured in biological material collected immediately after admission to the hospital. Future studies would include a larger group of people, including patients with HCV co-infection. The obtained preliminary results would also allow the identification of groups of patients for whom supplementation with liver regenerating preparations, i.e. containing S-Adenosylmethionine (SAM), would be necessary.  S-adenosylmethionine affects the metabolism of important neurotransmitters in the central nervous system, has a positive effect on the functioning of the liver and determines the production of glutathione, which is why it is classified as an indirect antioxidant [5]. Future research would include, inter alia, the effect of S-adenosylmethionine supplementation on the above-mentioned hepatotoxicity biomarkers. However, the first step is to investigate advanced markers of hepatotoxicity in a group of HCV uninfected mephedrone patients. Conducting these studies would allow to determine whether taking mephedrone with heroin or alcohol is actually hepatotoxic, or whether future studies should focus more on HCV infection in this group of patients. The obtained results would be related to the quality of life measured with appropriate questionnaires. Reducing the number of concomitant psychotropic drugs in patients taking mephedrone by introducing additional supplementation with a preparation regenerating the liver, could also contribute to reducing the number of hospitalizations, and thus lowering the costs incurred by the state generated by the use of polypharmacy.

Despite numerous solutions in dentistry, there is still the problem of tightness of the applied coatings and fillings, which favors the recurrence of caries. The use of polymers is an innovative solution printed with ion-imprinted polymer (IIP) ions that have not yet been studied for use in dentistry. The designed IIP could be used as a dental bonding system that stimulates mineralization at the material-dentin interface (prolonged release of Ca2 + and OH- ions) and connects with the tissue by interacting with biological apatite and / or collagen (using appropriate monomers). The aim of the scientific activity is the synthesis and characterization of polymers printed with Ca2 + and OH ions and investigation of the basics of the Ca2 + and OH- ion mapping process in relation to the proposed new monomers and cross-linking agents. IIP synthesis will be carried out in a thin layer by photopolymerization in the monomer-template-cross-linker system. I chose monomers and cross-linking agents for polymerization from compounds already used in dentistry, among others, 2-hydroxyethyl methacrylate, ethylene glycol dimethacrylate and methacrylic compounds showing adhesion to human pulp stem cells, such as tetrahydrofurfuryl methacrylate, 2- (methacryloyloxy) ethyl acetoacetate, N- (4-hydroxyphenyl) methacrylamide, 1,6-hexanediol diacrylate, ethoxylated trimethylolpropane triacrylate, whereas the latter having not yet been investigated by ion printing. The polymerization pattern will be Ca (OH) 2.

The presented project is a pilot study, before a larger research project planned to be submitted in the future competition of the National Science Center. Its aim will be to assess the differences in the miRNA expression profile of clinically benign and aggressive forms of vestibular nerve sheaths, and the possibility of using these differences as a diagnostic and prognostic tool. The presented project will allow to verify the hypothesis that the miRNA expression profile found in tumor tissues corresponds to the miRNA profile determined in the cerebrospinal fluid obtained from the same patient. In the next stage, in a larger project, this hypothesis will be confirmed in a wider group of patients, the study will also be extended to other study groups: patients diagnosed with type 2 neurofibromatosis, which is characterized by bilateral presence of atrial sheaths, and patients with tumor regrowth after prior radiotherapy treatment (gamma knife). Understanding the miRNA expression profile characteristic of atrial sheaths of various types of growth will allow for the selection of specific types of miRNAs, the expression of which is increased or decreased, for further studies on their function in the development and progression of this type of cancer. This will allow a better understanding of the biology of atrial shielding in the context of new nonsurgical treatments for these tumors. In addition, the identification of specific miRNA profiles in the cerebrospinal fluid collected from patients diagnosed with atrial bronchiectasis may contribute to the development of a diagnostic method to assess the risk of rapid tumor progression, without the need for a surgical biopsy.

Aurora A kinase is one of the serine-threonine kinases that control mitotic and meiosis processes in cells. In the literature, its overexpression is often associated with the occurrence of various neoplastic diseases [1]. The search for compounds that can inhibit the overexpression of this protein is one of the strategies that is a field of research in the field of pharmaceutical and medical sciences [2-3]. Most reports, however, focus on synthetic compounds. As part of the project, a significant group will be compounds of natural origin, primarily capsaicin and its derivatives capsaicinoids. Capsaicin as a compound with a potential to inhibit Aurora A kinase was selected because capsaicin supplementation had previously been shown to abolish resistance to cisplatin treatment induced by overexpression of Aurora A kinase [4]. Preliminary analyzes using molecular docking indicate that capsaicin may show just such a potential [5]. In the first stage of the project, using molecular docking to find potential Aurora A kinase inhibitors, a group of compounds (mainly of natural origin), showing structural similarities with capsaicin, will be tested. Among the compounds planned to be tested are natural and synthetic capsaicinoids (dihydrocapsaicin, homocapsaicin, nonivamide, arvanil, olvanil, capsiat), curcumin, piperine, allicin and zingerone. Molecular docking will be performed with the use of two packages - Surflex and AutoDock [6]. It will also include compounds known to be active on Aurora kinases, e.g. barasertib, alisertib, danusertib [7-8].
Molecular docking is currently one of the widely used methods in pharmaceutical sciences to describe the modeling, simulation and visualization of biological and medical processes using computers. Due to the relatively low financial and time costs, they are used as the first step before undertaking appropriate in vitro and in vivo experiments. Based on the results obtained from docking, it is planned to perform verifying in vitro tests. A test kit to evaluate the inhibition of Aurora A kinase (CycLex Aurora Family Kinase Assay / Inhibitor Screening Kit) will be performed. Such tests are commonly used in the evaluation of Aurora A inhibitors [9]. Although Aurora A kinase is a known protein and numerous experiments have been carried out on it for years, so far no combination of numerical and experimental methods has been used in the study of its inhibitors. The use of compounds of different structures will also allow to assess the influence of the structure of the molecule on the potential biological effect.This project is a continuation of the doctoral dissertation "Structural and physicochemical analysis of selected ligands of the TRPV1 receptor". As part of this dissertation, the structural analysis of capsaicin and its derivatives was carried out. The information on the crystal structure obtained during these studies will be the starting point for in silico analyzes. The arrangement and the interaction network formed by the inhibitor molecule bound by Aurora A kinase will serve as a benchmark for the results obtained with the test compounds. The research on biological activity will therefore be the next stage of research on capsaicin and its derivatives.