http://hdl.handle.net/11089/1 2026-04-10T02:09:43Z http://hdl.handle.net/11089/57929 Wstępna ocena potencjału terapeutycznego miechunki pomidorowej (Physalis philadelphica) w kontekście przebudowy tkanek i gojenia ran (dataset) Liudvytska, Oleksandra Chronic wounds represent a growing problem in lifestyle diseases (e.g., atherosclerosis, diabetes). They are characterized, among other things, by disturbances in the mechanisms controlling the course of inflammatory processes, degeneration of the tissue surrounding the wound, scarring, and susceptibility to infections. Hard‑to‑heal wounds constitute a serious and burdensome issue for patients, as they significantly reduce their quality of life and require long-term, specialized therapy. The search for natural bioactive substances is one of the important directions in contemporary wound‑healing research. Natural compounds can serve as the basis for therapies that support all stages of healing, including modulation of the inflammatory response, fibroblast proliferation, and epithelial regeneration. They are often characterized by high biocompatibility and low cytotoxicity, making them very promising candidates for applications in wound‑healing support. The project focused on key aspects relevant to the potential use of extracts from the tomatillo (Physalis philadelphica) in wound‑healing support: anti‑inflammatory properties, effects on tissue remodeling, assessment of cytotoxicity risk, and metabolism by the skin microbiome. Four extracts were tested: from fruits (green – unripe, and yellow), leaves, and roots. The study employed dermal (fibroblast) and epithelial (keratinocyte) cell lines. Additionally, the effects of the extracts on proteins of the fibrinolytic system were evaluated, as this system plays an important regulatory role in tissue remodeling within the wound area. Spis plików: 1. Generowanie plazminy 2. IL- 6 3. IL- 8 4. Mikrobiota skóry 5. MMP3 6. MMP9 7. MTT 8. PLUA 9. PLUAR soluble 10. PLUAR 11. Test rany 2026-03-31T00:00:00Z http://hdl.handle.net/11089/57731 Opracowanie modelu badawczego in vitro do analiz wpływu stanu ketozy na angiogenezę nowotworową; Miniatura 8 (2024/08/X/NZ3/00599) (dataset) Soboska, Kamila As part of the Miniatura 8 research project, the effect of the ketosis state on tumour-associated angiogenesis was investigated. An in vitro model reflecting the conditions during ketogenic diet was developed, and the effects of glucose deprivation and ketone bodies were compared in tumour (TECs) and normal (NECs) endothelial cells. The studies were performed using the HMEC-1 cell line, in which a tumour endothelial cell model was generated under hypoxic conditions and in the presence of cancer cell-secreted pro-angiogenic factors. The expression of ketone body transporters and ketolytic enzymes was analysed at both the mRNA and protein levels in NECs and TECs, and their ability to metabolise ketone bodies was compared. In further experiments, the effect of ketone bodies on endothelial cell viability and the secretion of pro-angiogenic factors by colorectal cancer cell lines were evaluated. The dataset contains the results of the following tests: sqPCR from the analysis of the expression of markers confirming tumor endothelial cell model (TECs markers_sqPCR_RawData) and from the analysis of the expression of genes encoding ketolytic enzymes and the ketone body transporter (ketolysis_sqPCR_RawData), images of the results of the Western immunoblot analysis (WB scan), acetyl-CoA concentration in cells treated with ketone bodies (Acetyl-CoA conc_RawData), results of endothelial cell proliferation tests under conditions of variable glucose concentration (ECs prolif_glucose conc_RawData) and in conditions of simulated ketosis (ECs prolif_KBs conc_RawData) and results of the analysis of cytokine profiling secreted by tumor cells under simulated ketosis conditions (ProteomeProfiler) 2024-09-01T00:00:00Z http://hdl.handle.net/11089/57702 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. 2025-01-01T00:00:00Z http://hdl.handle.net/11089/57701 Właściwości biologiczne nanocząstek złota modyfikowanych polietylenoglikolem i ich zastosowanie jako potencjalnych nośników leczniczego siRNA w badaniach in vitro Okła, Elżbieta Drug carriers are systems designed to enhance the delivery of bioactive compounds to specific target sites in the body, including transport across biological barriers. Among the various nanomaterials investigated as potential carriers, gold nanoparticles (AuNPs) have gained considerable attention due to their favorable biophysical properties. They are characterized by high biocompatibility, low cytotoxicity, and the possibility of straightforward surface functionalization. One of the promising modification strategies is PEGylation, i.e., conjugation with polyethylene glycol (PEG), which improves the potential of AuNPs as carriers of drugs and nucleic acids, particularly for the delivery of therapeutic siRNA to tissues and cells protected by the blood–brain barrier. The aim of this study was to evaluate whether PEG-coated gold nanoparticles, AuNP14a and AuNP14b, differing in the ratio of carbosilane dendrons to PEG chains, can form complexes with siRNA and be internalized by cells in a blood–brain barrier model. The investigated siRNA targeted the apoE gene, whose ε4 allele is associated with an increased risk of Alzheimer’s disease. The results confirmed that AuNPs can successfully form complexes with siRNA (siApoE), with AuNP14a forming stable complexes at lower concentrations than AuNP14b. The nanoparticles interacted with plasma proteins without significantly altering their secondary structure and showed interactions with lipid membranes. Efficient uptake of AuNP/siRNA complexes by endothelial cells and their accumulation mainly in the cytoplasm were observed. The nanoparticles demonstrated low cytotoxicity toward endothelial cells, astrocytes, and pericytes, which was further reduced in the presence of siRNA. Both AuNPs and their siRNA complexes exhibited relatively low genotoxicity, while alterations in reactive oxygen species levels and mitochondrial membrane potential returned to baseline within 24 hours. Overall, the findings indicate that PEGylated AuNP14a and AuNP14b meet essential criteria for therapeutic siRNA carriers, with AuNP14a showing greater potential.; Nośniki leków są związkami umożliwiającymi transport substancji bioaktywnych do miejsca ich działania, w tym przez bariery biologiczne. Wśród potencjalnych systemów dostarczania leków szczególne zainteresowanie budzą nanocząstki złota (AuNP), które dzięki swoim właściwościom biofizycznym znajdują szerokie zastosowanie w biomedycynie. Cechują się one wysoką biokompatybilnością, niską cytotoksycznością oraz możliwością łatwej modyfikacji powierzchni. Jedną z obiecujących metod ich funkcjonalizacji jest pegylacja, czyli sprzęganie z glikolem polietylenowym (PEG), co zwiększa ich potencjał jako nośników leków i kwasów nukleinowych, w tym terapeutycznych siRNA, zwłaszcza w kontekście transportu przez barierę krew–mózg. Celem pracy było sprawdzenie, czy pegylowane nanocząstki złota AuNP14a i AuNP14b, różniące się stosunkiem dendronów karbokrzemowych do PEG, mogą tworzyć kompleksy z siRNA oraz przenikać do komórek modelu bariery krew–mózg. Badany siRNA był skierowany przeciwko genowi apoE, którego allel ε4 wiąże się ze zwiększonym ryzykiem rozwoju choroby Alzheimera. Wyniki potwierdziły zdolność AuNP do kompleksowania z siRNA (siApoE), przy czym AuNP14a tworzyły kompleksy przy niższych stężeniach niż AuNP14b. Wykazano także oddziaływania nanocząstek z białkami osocza bez istotnych zmian w ich strukturze drugorzędowej oraz interakcje z błonami lipidowymi. Kompleksy AuNP/siRNA efektywnie wnikały do komórek śródbłonka i akumulowały się głównie w cytoplazmie. Badane nanocząstki wykazywały niską cytotoksyczność wobec komórek śródbłonka, astrocytów i perycytów, która dodatkowo zmniejszała się w obecności siRNA. Zaobserwowana genotoksyczność była niewielka, a zmiany poziomu reaktywnych form tlenu i potencjału mitochondrialnego ulegały normalizacji w ciągu 24 godzin. Uzyskane wyniki wskazują, że pegylowane nanocząstki AuNP14a i AuNP14b spełniają podstawowe kryteria nośników terapeutycznego siRNA, przy czym bardziej obiecującą formulacją wydaje się AuNP14a. 2025-01-01T00:00:00Z