National Science Centre

According to the European Chemicals Agency, microplastics are very small particles composed of mixtures of polymers, functional additives and post-process residues. Surface water contamination with microplastics includes: primary microplastics from resins used in industry and secondary microplastics produced during fragmentation of larger pieces of polymers. Despite the increasing amount of scientific research into plastics in the environment, research into the aging of microplastics remains limited. The consumption of micro- and nanoplastics has been observed in many invertebrate species, especially in filtering organisms, e.g. shellfish and clams. Changes caused by the aging process of microplastics may affect their biological activity and sorption processes. There are scientific reports indicating the possibility of transferring into living organisms, hydrophobic, toxic organic compounds adsorbed on the surface of microparticles of plastics. It is also possible to release harmful functional additives. Many articles have been published on sorption on plastics: polycyclic aromatic hydrocarbons, selected pharmaceuticals and personal care products. However, no studies have been conducted to date on the interaction of microplastics with antidepressants. Antidepressants are one of the most important classes of drugs that are released into surface waters. They affect aquatic organisms already at low concentrations, in the range of several μg / l. Moreover, the use of antidepressants has skyrocketed worldwide due to the global "epidemic of depression". Protozoa play an important role in the aquatic environment as first order consumers. Ciliates - filter feeders feed on bacteria, suspended organic matter and phytoplankton. They are an important link in the food chain from bacteria to higher organisms. Therefore, they can be important vectors carrying adsorbed and absorbed toxic substances, including microplastics, in food network.
The first aim of the project is to assess the acute and chronic toxicity of different types of microplastics (polystyrene, PET and polyvinyl chloride; both colorless and colored) for ciliates: Spirostomum ambiguum and Tetrahymena thermophila. Both raw and aged plastics will be assessed. The microplastics will be aged in the Atlas SUNTEST CPS + accelerated aging apparatus, as well as by incubation for 6 and 12 months in a climatic chamber. We believe that inert particles will be eaten by protozoa and can affect their vital functions: eating behavior and growth rate. We expect that aging and weathering of plastics will have an impact on toxicity by changing the composition, shape and physicochemical properties of particles. In the food intake / excretion test, the protozoa will be immobilized and observed under the KEYENCE VHZ 700 microscope. The second aim of the project is to evaluate the effect of microplastics on the toxicity and bioaccumulation of antidepressants (fluoxetine, sertraline, paroxetine and duloxetine) in protozoa. Our previous research indicates that S. ambiguum is highly sensitive to sertraline and other antidepressants. We believe that microplastics can serve as vectors for the transport of toxic substances into cells, and the process depends on the type of plastic and environmental conditions, especially pH and salinity. Parallel to the bioaccumulation assessment, the sorption and desorption of antidepressants on microplastics (at different pH values) will be analyzed. We believe that drugs adsorbed from the aquatic environment can be desorbed in the acidic environment of food protozoa. Trace analysis of antidepressants in water and protozoan cells will be performed by mass spectrometric detection chromatography. An important novelty of the project is the use of two protozoa: a very large S. ambiguum and a small T. thermophila differing in the metabolic rate and growth rate. In addition, the research will use microplastic particles with natural, irregular shapes, obtained from products available on the market, both raw and aged. Finally, interactions between chemically inert particles and antidepressants will be assessed. These studies will expand our understanding of the fate of these pollutant classes in the aquatic environment.

The aim of the project is the assessment of the role of apelinergic system in the development of cardiotoxic effects of doxorubicin.

The aim of the project is to mark the expression of PD-L1 (Programmed Death Ligand 1) antygen in tissue preparations of 100 patients undergoing surgical treatment (liver resection/transplantation) in the years 2010-2020 in the Department of General, Transplant and Liver Surgery of the MUW University Clinical Centre and their correlation with the available clinical and pathomorphological data along with the preparation of introduction to research into tumour microenvironment characteristics.

The objectives of the project

Objective 1. To study whether voluntary cough and/or CPAP facilitate the recruitment of atelectatic

lung regions and elevation of Ppl in patients undergoing TT.

Objective 2. To assess the percentage of patients in whom TT is associated with a decline in blood

oxygenation and whether this decline is caused by increased V/Q mismatch and pulmonary shunt.

Objective 3. To evaluate whether mediastinum and diaphragm compliance and the anatomical shift of these structures have a significant impact on the pattern of Ppl fall

Objective 4. To study PPP and its changes in terms of the relationship with systolic and diastolic heart

volume and the changes in stroke volume.

Objective 5. To evaluate whether large volume PE impairs function of the respiratory muscles and

whether impaired function of inspiratory muscles is associated with the sensation of the breathlessness.

The main aim of this proposal is to identify the causative genetic variants responsible for the LLDD and to broaden our knowledge of LLDDs. The LLDDs are underdiagnosed due to a limited access to diagnostic tools.
The overarching hypothesis is that LLDDs result from abnormal genomic and transcriptomic profiles, including changes involving FOXF1, TBX4, FGF10, or other not yet determined genes. The identification is necessary for precise LLDD diagnosis and for better understanding its etiology.

The aim of the project is to identify the deregulated miRNA at early stages of larynx carcinogenesis. Determination of the processes accompanying the transformation of larynx hypertrophic changes into dysplastic changes and invasive larynx cancer is necessary to obtain knowledge about factors determining individual stages of carcinogenesis in larynx cancer. Identification of molecular mechanisms responsible for larynx cancer progression at early stages of dysplasia and malignant transformation may in the future constitute a basis for developing different methods of personalised therapy to prevent and/or suppress the laryngeal cancer progression. The proposed study is an introduction to the planned project, encompassing a wide assessment of the miRNA expression profile in dysplastic changes and in early phase of laryngeal cancer in order to identify the important markers related to the histopathological stadium of carcinogenesis, financed from the funds obtained under OPUS or Sonata BIS programmes.

The principal goal of this project is to assess the importance of atherosclerotic protective pathways inhibition during atherosclerotic plaque progression. We hypothesize, that relative expression levels of microRNA particles inhibiting transcription of proteins involved in protection from atherosclerotic plaque progression are correlated positively with atherosclerotic plaque severity.

Two purposes will be fulfilled in this project. The first aim is development of bioengineering techniques that will allow to produce substantial amounts of newly identified plant metabolite belonging to the group of naphthoquinone derivatives named rinderol (2-methoxy-5O, 6-(isohex-1-ene-1,2-diyl)-5,8-dihydroxynaphthalene-1,4-dione). This compound was for the first time described by member of our research team in cultivated in vitro roots of Cynoglossum columnae (Boraginaceae), followed by its isolation and identification in roots of Rindera graeca (Boraginaceae). R. graeca in vitro root cultures are going to be used for production of this compound. The second aim of current project is the elucidation of the molecular mechanism underlaying anticancer properties of rinderol and comparison of its cytotoxicity with doxorubicin as a reference, clinically established anticancer drug. This compound was selected for the investigation among metabolites found in phytochemical profile of R. graeca roots, on the basis of distinguishing, high cytotoxicity against cancer cell lines. According to results of our preliminary research, rinderol occurred to be an extraordinarily fast-acting compound in induction of apoptotic cell death, which was confirmed in series of experiments.

The aim of this project is to elucidate the mechanisms regulating the functions of cytotoxic cells in oxidative tumor microenvironment (TME) and to identify strategies potentiating the efficacy of chimeric antigen receptor (CAR)-based adoptive cell therapy in preclinical models. TME is characterized by an increased inflammation that is associated with the enhanced production of reactive oxygen species (ROS) which in turn generate oxidative stress that impairs antitumor response. Our preliminary results indicate that individual subsets of lymphocytes have different redox capacity. Moreover, we discovered that the construction of CARs used to modify effector cells influence their viability and ability to exert cytotoxic functions in prescence of oxidative stress. Thus, within this project, we will specifically determine the antioxidant potential and ability of various populations of cytotoxic cells to kill target tumor cells in the presence of elevated ROS levels. Next, we will explore the influence of various co-stimulating domains on antioxidant potential of CAR-modified effector cells. To further improve the cytotoxic functions of CAR-modified cells in highly oxidative milieu we will modulate the expression of selected antioxidant enzymes by genetic modifications. Finally, we will evaluate the efficacy of oxidant-resistant CAR-bearing cytotoxic cells both in vitro and in vivo.

The aim of the project is to discover genetic factors underlying neurodevelopmental disorders (ND) within non-coding genomic regions. The hypothesis of the project is based on the fact that the RNA-seq results will indicate the impaired biological pathway leading to the onset of the disease. This can shed a new light on previously obtained whole-genome sequencing (WGS) data and give a clue for the area of search for the causative variants. The results will provide more information on the mechanism underlying pathogenesis of the neurodevelopmental diseases, and will also contribute to create an algorithm for increasing the efficiency of new causative genes and pathogenic variants detection.