http://hdl.handle.net/11089/1309 2026-04-24T00:24:06Z 2026-04-24T00:24:06Z Strzelczyk, Joanna http://hdl.handle.net/11089/58174 2026-04-23T10:38:58Z 2025-01-01T00:00:00Z

Characteristics of Aeromonas salmonicida, a rainbow trout pathogen, and early signatures of host immune response Strzelczyk, Joanna Rainbow trout is a key aquaculture species valued for its high nutritional content and adaptable immune system. However, intensive farming increases susceptibility to infectious diseases such as furunculosis, caused by Aeromonas salmonicida, a highly adaptable pathogen with significant genomic variability driven in part by plasmids. This variability complicates the study of its virulence and infection strategies. This study aimed to elucidate early infection mechanisms of A. salmonicida in rainbow trout using a systems biology approach, treating host and pathogen as a dynamic, interdependent system. Bacterial strains with similar genotypes but differing virulence were compared. Genomic analyses revealed that even minor sequence differences can significantly impact virulence, particularly among genes associated with infection processes. Transcriptomic analyses demonstrated that infection is governed by a complex network of interacting pathways on both the bacterial and host sides. Pathways, including arginine metabolism, iron acquisition, and flagellar regulation, contribute to infection. Both known and novel genes were implicated in early infection stages, with virulence-associated molecular patterns (VAMPs) playing a key role in immune recognition. Cellular analyses showed cytotoxic effects on erythrocytes and highlighted the importance of head kidney leukocytes in early defense. Myeloid cells were primarily responsible for pathogen recognition, while some lymphoid cells also contributed. Based on the conducted analyses, this study provides a comprehensive characterization of Aeromonas salmonicida virulence mechanisms and their dynamic interactions with the immune system of rainbow trout, highlighting the complexity of infection and adaptation processes that ultimately shape disease progression.

2025-01-01T00:00:00Z Wasilewska, Karina http://hdl.handle.net/11089/58146 2026-04-23T02:44:03Z 2025-01-01T00:00:00Z

Charakterystyka kompleksów płytkowo-leukocytarnych i analiza ekspresji miRNA jako wskaźników stanu zapalnego i neurodegeneracji w rzutowo-remisyjnej i wtórnie postępującej postaci stwardnienia rozsianego Wasilewska, Karina Multiple sclerosis (MS) is a chronic neurodegenerative disease with an autoimmune background primarily affecting the central nervous system (CNS). The most common form of the condition is inflammatory relapsing-remitting MS (RRMS), whereas secondary progressive MS (SPMS), which typically develops after RRMS, is characterized by progressive neurodegeneration. However, recent reports indicate coexistence of inflammatory and neurodegenerative features in both phenotypes, complicating early differentiation, therapeutic decisions, and prognosis. The primary objective of the research was to identify markers enabling differentiation of disease phenotypes in patients with RRMS in remission and SPMS. In the first stage, platelet-leukocyte hetero-aggregates (PLAs) were characterized as elements linking vascular injury with inflammation. Increased leukocyte chemotaxis toward platelets and PLAs formation, predominantly involving B-cells, were demonstrated in MS. Next, screening of miRNA expression from extracellular vesicles (EVs) was conducted, followed by measurement of inflammatory cytokines and markers of neuronal/glial damage in plasma. A model combining miRNA expression with basic fibroblast growth factor achieved an AUC of 0.97, confirming its high ability to discriminate RRMS and SPMS. In the third stage, EVs presenting L1CAM, a protein used to enrich the neuronal fraction of EVs, were characterized in serum and cerebrospinal fluid to assess their usefulness as biomarkers for monitoring response to rituximab treatment, an anti-CD20 monoclonal antibody, in RRMS patients. In summary, the research expands understanding of MS pathophysiology, linking immune response with vascular injury, and identifies opportunities for non-invasive biomarkers to differentiate RRMS and SPMS as well as to monitor CNS immunopathology and treatment response.

2025-01-01T00:00:00Z Tończyk, Aleksandra http://hdl.handle.net/11089/58145 2026-04-23T02:43:00Z 2025-01-01T00:00:00Z

Aktywność biologiczna i toksyczność nanocząstek srebra pozyskanych na drodze mikrobiologicznej przy udziale grzyba strzępkowego Gloeophyllum striatum Tończyk, Aleksandra Silver nanoparticles (AgNPs) are among the most widely commercialized nanomaterials due to their versatile properties and strong antimicrobial activity, making them valuable in electronics, textiles, cosmetics, and biomedicine. The increasing demand for AgNPs highlights the need for synthesis methods that are cost-effective, rapid, and environmentally sustainable. Biological synthesis, particularly using filamentous fungi, offers an attractive alternative to conventional methods due to their ease of cultivation, high biomass production, and ability to produce metabolites influencing nanoparticle properties. This doctoral dissertation focused on the microbiological synthesis of silver nanoparticles using the brown-rot wood fungus Gloeophyllum striatum DSM 9592 under various process conditions, followed by evaluation of their antimicrobial, cytotoxic, ecotoxic, and synergistic activity with antibiotics. The results confirmed that G. striatum can efficiently synthesize silver nanoparticles, and that synthesis conditions, such as temperature and shaking, significantly affect their physicochemical and biological properties. The synthesized nanoparticles demonstrated antimicrobial activity against tested microorganisms, with fungi showing greater sensitivity than bacteria. The most sensitive organisms included the yeast Malassezia furfur and the bacterium Pseudomonas aeruginosa. Toxicity assessments revealed variable cytotoxic and ecotoxic effects depending on synthesis conditions. Nanoparticles synthesized at 4°C exhibited the lowest cytotoxicity while maintaining antimicrobial effectiveness. Ecotoxicity studies showed the highest sensitivity in the freshwater crustacean Daphnia magna and the lowest in tested crop plants. Overall, nanoparticles synthesized at 4°C without shaking showed the most favorable balance between antimicrobial activity and low toxicity. Additionally, these nanoparticles exhibited synergistic effects with antibiotics, enabling dose reduction. The findings demonstrate that optimization of fungal biosynthesis conditions enables the production of effective antimicrobial nanomaterials with reduced toxic potential.

2025-01-01T00:00:00Z Gronkowska, Karolina http://hdl.handle.net/11089/57702 2026-04-13T09:45:59Z 2025-01-01T00:00:00Z

Rola kompleksu SWI/SNF-EP300 w powstawaniu oporności komórek nowotworowych na chemioterapię Gronkowska, Karolina Cancer remains a major global health problem and many tumours develop resistance to available therapies. Because drug resistance is often associated with genetic and epigenetic changes, targeting epigenetic regulators such as the histone acetyltransferase p300 and the SWI/SNF chromatin-remodelling complex may represent an effective therapeutic strategy.The aim of this thesis was to investigate the role of the SWI/SNF–p300 complex in the development of cancer drug resistance related to two mechanisms: overexpression of ABC transporters and activation of the DNA damage response pathway. In the first part of the study, I demonstrated that the chromatin remodelling ATPase BRG1 and the acetyltransferase p300 regulate the transcription of ABCC transporter genes (ABCC3, ABCC5 and ABCC10) in paclitaxel-resistant cancer cells. These lysosomal transporters were shown to sequester chemotherapeutic drugs such as doxorubicin and paclitaxel, reducing their cytotoxicity. Active promoters of these genes were enriched in BRG1, p300, HIF1A and activating histone marks. Pharmacological inhibition of SWI/SNF (PFI3), inhibition of p300 (C646), degradation of SWI/SNF ATPases, or silencing of HIF1A significantly increased drug toxicity by simultaneously reducing the expression of multiple ABC transporters. Bioinformatic analysis of clinical data further indicated that high expression of EP300, SMARCA4 and HIF1A may serve as prognostic markers of response to taxane-based chemotherapy in breast cancer. In the second part, I showed that cisplatin-induced activation of the ATM/ATR-Chk1/Chk2-p53 pathway enhances the association of p300 with chromatin and activates transcription of genes involved in DNA damage response. Inhibition of p300 or SWI/SNF reduced the expression of these genes and sensitised cancer cells to cisplatin. Overall, the results indicate that targeting SWI/SNF and p300 may reverse drug resistance and improve chemotherapy effectiveness.

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