Selected aspects of the biological activity of a series of six nitrate silver(I) complexes with pyridine and (benz)imidazole derivatives were investigated. The present study evaluated the antibacterial activities of the complexes against three Gram-negative strains: Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922 and Proteus hauseri ATCC 13315. The results were compared with those of silver nitrate, a silver sulfadiazine drug and appropriate ligands. The most significant antibacterial properties were exerted by silver(I) complexes containing benzimidazole derivatives. The cytotoxic activity of the complexes was examined against B16 (murine melanoma) and 10T1/2 (murine fibroblasts) cells. All of the tested silver(I) compounds were not toxic to fibroblast cells in concentration inhibited cancer cell (B16) viability by 50%, which ranged between 2.44–28.65 µM. The molecular and crystal structure of silver(I) complex of 2,6-di(hydroxymethyl)pyridine was determined by single-crystal X-ray diffraction analysis. The most important features of the crystal packing and intermolecular non-covalent interactions in the Ag(I) complex were quantified via Hirshfeld surface analysis.

The Central Nervous System (CNS) is vulnerable to a range of diseases, including neurodegenerative and oncological conditions, which present significant treatment challenges. The blood–brain barrier (BBB) restricts molecule penetration, complicating the achievement of therapeutic concentrations in the CNS following systemic administration. Gene therapy using recombinant adeno-associated virus (rAAV) vectors emerges as a promising strategy for treating CNS diseases, demonstrated by the registration of six gene therapy products in the past six years and 87 ongoing clinical trials. This review explores the implementation of rAAV vectors in CNS disease treatment, emphasizing AAV biology and vector engineering. Various administration methods—such as intravenous, intrathecal, and intraparenchymal routes—and experimental approaches like intranasal and intramuscular administration are evaluated, discussing their advantages and limitations in different CNS contexts. Additionally, the review underscores the importance of optimizing therapeutic efficacy through the pharmacokinetics (PK) and pharmacodynamics (PD) of rAAV vectors. A comprehensive analysis of clinical trials reveals successes and challenges, including barriers to commercialization. This review provides insights into therapeutic strategies using rAAV vectors in neurological diseases and identifies areas requiring further research, particularly in optimizing rAAV PK/PD.

Post-radiation inflammatory reaction leads to an irreversible pulmonary fibrosis which may cause lethal respiratory insufficiency. Pathological inflammatory and fibrotic changes might be attenuated by inhibiting tumour necrosis factor (TNF)-α activity using TNF-α soluble receptors. Thus, an experimental antifibrotic gene therapy with the plasmid vector encoding a mouse soluble receptor I for TNF-α (psTNFR-I) was assessed. Soluble TNFR-I encoding gene was cloned into pcDNA3.1 plasmid. The ability of psTNFR-I expressing vector to transfect cells, and its biological activity in vitro and in vivo were examined by PCR, RT-PCR, MTT assay and ELISA. The C57Bl/6J mice received single intramuscular injection of psTNFR-I, conjugated with polyetylenimine (PEI) 25 kDa, equally divided to both hind legs, 3 days before irradiation (20 Gy, Co60), and either a single injection or ten injections once a week after irradiation. The data proved the effectiveness of psTNFR-I product to neutralise TNF-α activity in vitro. The in vivo plasmid incorporation and maintenance was confirmed. Measurements of plasma soluble TNFR-I levels showed that the in vivo gene transfer was effective. PEI was found to enhance transfection efficiency in vivo. The psTNFR-I/PEI complexes caused no toxicity in the transfected mice. C57Bl/6J mice that received prolonged psTNFR-I/PEI injections developed lethal fibrotic syndrome and died 8 weeks later than the mice treated with a double plasmid injection and the control mice treated with a control plasmid. Sequential administration of soluble TNFR-I by a nonviral, intramuscular gene transduction in the early and late post-radiation inflammatory phase prolonged survival of irradiated mice and attenuated the symptoms of lung fibrosis. The psTNFR-I gene transduction may provide a safe and simple method to partially neutralise TNF-α activity and prevent radiation-induced lung injury.

Currently, a major challenge in material engineering is to develop a cell-safe biomaterial with significant utility in processing technology such as 3D bioprinting. The main goal of this work was to optimize the composition of a new graphene oxide (GO)-based bioink containing additional extracellular matrix (ECM) with unique properties that may find application in 3D bioprinting of biomimetic scaffolds. The experimental work evaluated functional properties such as viscosity and complex modulus, printability, mechanical strength, elasticity, degradation and absorbability, as well as biological properties such as cytotoxicity and cell response after exposure to a biomaterial. The findings demonstrated that the inclusion of GO had no substantial impact on the rheological properties and printability, but it did enhance the mechanical properties. This enhancement is crucial for the advancement of 3D scaffolds that are resilient to deformation and promote their utilization in tissue engineering investigations. Furthermore, GO-based hydrogels exhibited much greater swelling, absorbability and degradation compared to non-GO-based bioink. Additionally, these biomaterials showed lower cytotoxicity. Due to its properties, it is recommended to use bioink containing GO for bioprinting functional tissue models with the vascular system, e.g., for testing drugs or hard tissue models.

Objectives: Cisplatin is a classical anticancer drug used in the treatment of ovarian cancer. Unfortunately, the treatment is associated with numerous adverse effects. Studies concerning new platinum derivatives with less organ toxicity are conducted. The aim of this study was to analyse the effect of a new trans-platinum(II) complex of 3-aminoflavone on the viability and mortality of the cells from OVCAR 3 and CAOV 3 ovarian cancer cell lines and on the expression of the selected genes involved in the process of apoptosis. Material and methods: The viability of ovarian cancer cells and the cytotoxicity of a trans-platinum(II) complex of 3-amino­flavone: [trans-Pt(3-af )₂Cl₂), trans-bis-(3-aminoflavone) dichloridoplatinum(II)] and cisplatin were analysed using a spectrophotometric method with the use of MTT assay and LDH assay. BAX, BCL2, BIRC5 gene expression analysis on mRNA level was conducted with the use of Real-Time PCR method. Results: It was observed that parallel to an increase in the concentration of the new complex compound and cisplatin there is a decrease in viability and an increase in mortality of ovarian cancer cells. As a result of exposure to the studied compound and cisplatin, an increased BAX gene expression and decreased BCL2 and BIRC5 gene expression were observed in the studied ovarian cancer cell lines. Conclusion: Trans-Pt(3-af )₂Cl₂ exhibits anticancer activity towards OVCAR 3 and CAOV 3 ovarian cancer cell lines. The studied complex compound can be considered as a potential anticancer drug. Objectives: Cisplatin is a classical anticancer drug used in the treatment of ovarian cancer. Unfortunately, the treatment is associated with numerous adverse effects. Studies concerning new platinum derivatives with less organ toxicity are conducted. The aim of this study was to analyse the effect of a new trans-platinum(II) complex of 3-aminoflavone on the viability and mortality of the cells from OVCAR 3 and CAOV 3 ovarian cancer cell lines and on the expression of the selected genes involved in the process of apoptosis. Material and methods: The viability of ovarian cancer cells and the cytotoxicity of a trans-platinum(II) complex of 3-amino­flavone: [trans-Pt(3-af )₂Cl₂), trans-bis-(3-aminoflavone) dichloridoplatinum(II)] and cisplatin were analysed using a spectrophotometric method with the use of MTT assay and LDH assay. BAX, BCL2, BIRC5 gene expression analysis on mRNA level was conducted with the use of Real-Time PCR method. Results: It was observed that parallel to an increase in the concentration of the new complex compound and cisplatin there is a decrease in viability and an increase in mortality of ovarian cancer cells. As a result of exposure to the studied compound and cisplatin, an increased BAX gene expression and decreased BCL2 and BIRC5 gene expression were observed in the studied ovarian cancer cell lines. Conclusion: Trans-Pt(3-af )₂Cl₂ exhibits anticancer activity towards OVCAR 3 and CAOV 3 ovarian cancer cell lines. The studied complex compound can be considered as a potential anticancer drug.

Eosinophilic esophagitis (EoE) is a chronic disease, characterized clinically by esophageal disfunction. Topical corticosteroids (tCS), predominantly fluticasone and budesonide, are considered the effective first line treatment, as well as an option of maintenance therapy in EoE. The way that tCS are administered significantly affects their effectiveness. There is still no ready-to-use steroid drug to be applied topically to the esophagus in children—a few experimental viscous slurries (mainly of budesonide) have been shown in trials to be more effective than steroids administered via metered dose inhalers (MDIs) and swallowed. The best examined steroid solvent of all is sucralose, a high-intensity artificial sweetener. Although it has been shown in a critical review that it is non-toxic and safe for all consumers, there are still some concerns among patients about its potential adverse effect on humans. Due to that fact, we developed a new viscous formulation and evaluated its effectiveness in the treatment of children with EoE. In an open, prospective, single-center study, we administered our new formulation of viscous budesonide twice daily for 8 weeks in patients with an active EoE. After treatment, we performed a control gastroscopy with the collection and evaluation of histopathological samples. We have proven our formulation effectiveness at 64%, as far as histological remission is concerned. We have also shown a reduction in the mean endoscopic reference score (EREFS) from 3.1 points at the beginning of the study to 1.6 points at the end of the study. Bearing in mind how important the acceptance of the solvent is for long-time compliance, especially among children, we also decided to assess the taste of the formulation. Therefore, we asked 46 adults and 10 children to swallow a sample of the solvent and fill in a short anonymous questionnaire about its taste, smell, consistency and easiness of swallowing. General acceptance for the proprietary solvent was high, reaching 7.5/10 among adults and 6.5/10 in children. To be able to compare the results of our preliminary experience, we reviewed the studies which evaluated substances that have been used so far as steroid solvents for the treatment of EoE. The overall effectiveness of the oral viscous budesonide (OVB) ranged from 65% to 90%, which is consistent with the results obtained in our study. Unfortunately, the high heterogeneity of the studies did not allow us to draw reliable conclusions.