Cholesterol is a unique lipid for all mammalian cells, with important functions in membrane biogenesis and maintenance of proper membrane integrity and fluidity. Therefore, it plays an important role in cellular homeostasis. Dysregulation of cholesterol homeostasis is associated with various diseases in humans, including cardiovascular diseases, inflammatory diseases, neurodegenerative disorders, and cancers. In the tumor microenvironment, intrinsic and extrinsic cellular factors reprogram cholesterol metabolism and consequently promote tumorigenesis. Here, we summarize the current knowledge on molecular mechanisms and functional roles of cholesterol homeostasis and its dysregulation in regard to cancer pathogenesis. We also discuss the interplay of cholesterol metabolism and the ATP-binding cassette (ABC) proteins, highly conserved cellular transmembrane lipid transporters. An emerging role of lipid ABC transporters as potential prognostic tools for cancer progression and invasiveness is emphasized. Targeting both cholesterol metabolism and proteins associated with membrane cholesterol holds promise as a novel therapeutic strategy for cancer treatment.

Head and neck cancers (HNCs), particularly head and neck squamous cell carcinoma (HNSCC), are among the most aggressive and prevalent malignancies of the upper aerodigestive tract. As the incidence of HNCs continues to rise, this cancer type presents a significant public health challenge. Despite conventional treatment options, such as surgery, chemotherapy, and radiotherapy, the five-year survival rates remain relatively low due to resistance to these therapies, local recurrence, local lymph node metastasis, and in some advanced cases also distant metastasis. Consequently, patients with HNCs face a high mortality risk and have reduced quality of life due to the side effects of chemo- and radiotherapy. Furthermore, targeted therapies and immunotherapies have also shown limited effectiveness in many cases, with issues related to resistance and the accessibility of these treatments. Therefore, new strategies, such as those based on combination therapies and nanotechnology, are being explored to improve the treatment of HNC patients. The proteolysis-targeting chimeras (PROTACs) also emerged as a promising therapeutic approach, though research is still ongoing to bring this technology into clinical practice. Here, we aim to highlight the current knowledge of HNC therapies, with a focus on recent advancements, including nanomedicine and PROTAC-based strategies. The development and advancement of novel emerging therapies hold promise for the improvement of patients’ survival and quality of life.

Red clover (Trifolium pratense L.) is a forage legume cultivated worldwide. This plant is capable of establishing a nitrogen-fixing symbiosis with Rhizobium leguminosarum symbiovar trifolii strains. To date, no comparative analysis of the symbiotic properties and heterogeneity of T. pratense microsymbionts derived from two distinct geographic regions has been performed. In this study, the symbiotic properties of strains originating from the subpolar and temperate climate zones in a wide range of temperatures (10–25 °C) have been characterized. Our results indicate that all the studied T. pratense microsymbionts from two geographic regions were highly efficient in host plant nodulation and nitrogen fixation in a wide range of temperatures. However, some differences between the populations and between the strains within the individual population examined were observed. Based on the nodC and nifH sequences, the symbiotic diversity of the strains was estimated. In general, 13 alleles for nodC and for nifH were identified. Moreover, 21 and 61 polymorphic sites in the nodC and nifH sequences were found, respectively, indicating that the latter gene shows higher heterogeneity than the former one. Among the nodC and nifH alleles, three genotypes (I–III) were the most frequent, whereas the other alleles (IV–XIII) proved to be unique for the individual strains. Based on the nodC and nifH allele types, 20 nodC-nifH genotypes were identified. Among them, the most frequent were three genotypes marked as A (6 strains), B (5 strains), and C (3 strains). Type A was exclusively found in the temperate strains, whereas types B and C were identified in the subpolar strains. The remaining 17 genotypes were found in single strains. In conclusion, our data indicate that R. leguminosarum sv. trifolii strains derived from two climatic zones show a high diversity with respect to the symbiotic efficiency and heterogeneity. However, some of the R. leguminosarum sv. trifolii strains exhibit very good symbiotic potential in the wide range of the temperatures tested; hence, they may be used in the future for improvement of legume crop production.

Prosthetic infections are associated with high morbidity, mortality, and relapse rates, making them still a serious problem for implantology. Staphylococcus aureus is one of the most common bacterial pathogens causing prosthetic infections. In response to the increasing rate of bacterial resistance to commonly used antibiotics, this work proposes a method for combating pathogenic microorganisms by modifying the surfaces of synthetic polymeric biomaterials using proteolytic enzyme inhibitors (serine protease inhibitors—4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride and puromycin). While using techniques based on the immobilization of biologically active molecules, it is important to monitor the changes occurring on the surface of the modified biomaterial, where spectroscopic techniques (e.g., FTIR) are ideal. ATR-FTIR measurements demonstrated that the immobilization of both inhibitors caused large structural changes on the surface of the tested vascular prostheses (polyester or polytetrafluoroethylene) and showed that they were covalently bonded to the surfaces of the biomaterials. Next, the bactericidal and antibiofilm activities of the tested serine protease inhibitors were determined using the CLSM microscopic technique with fluorescent staining. During LIVE/DEAD analyses, a significant decrease in the formation of Staphylococcus aureus biofilm after exposure to selected concentrations of native inhibitors (0.02–0.06 mg/mL for puromycin and 0.2–1 mg/mL for 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride) was demonstrated.

Prosthetic infections are associated with high morbidity, mortality, and relapse rates making them still a serious problem for implantology. Staphylococcus aureus is one of the most common bacterial pathogens causing prosthetic infections. In response to the increasing rate of bacterial resistance to commonly used antibiotics, the work proposed a method of combating pathogenic microorganisms by modifying the surface of synthetic polymeric biomaterials using proteolytic enzyme inhibitors (serine protease inhibitors - 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride and puromycin). While using techniques based on immobilization of biologically active molecules, it is important to monitor changes occurring on the surface of the modified biomaterial, where spectroscopic techniques (e.g. FTIR) are ideal. The ATR-FTIR measurements demonstrated that the immobilization of both inhibitors caused large structural changes on the surface of the tested vascular prostheses (polyester or polytetrafluoroethylene) and showed that they were covalently bonded to the surface of the biomaterials. Next, the bactericidal and antibiofilm activities of the tested serine protease inhibitors were determined using the CLSM microscopic technique with fluorescent staining. During LIVE/DEAD analyses, a significant decrease in the formation of Staphylococcus aureus biofilm after exposure to selected concentrations of native inhibitors (0.02-0.06 mg/mL for puromycin and 0.2-1 mg/mL for 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride was demonstrated.