Nowadays, the sorbates are the third largest group of antimicrobial preservatives in food and pharmaceutical industries, following the parabens and benzoates whose safety is questioned by recent publications. A disadvantage of sorbates is their pH dependence, as their antimicrobial effect is greatly reduced in alkaline environment. The main, widely used sorbate derivatives are sorbic acid and potassium sorbate, no sorbic acid esters are involved in current industrial application. We aimed to test whether the esters of sorbic acid are capable to extend the antimicrobial spectrum of the original molecule while maintaining its advantageous biocompatibility profile. A comparative biocompatibility study of different derivatives (sorbic acid, potassium sorbate, isopropyl sorbate and ethyl sorbate) was carried out. In vitro cell viability assays of MTT (2-(4,5-dimethyl-2-thiazolyl)-3,5-diphenyl-2H-tetrazolium bromide), Neutral Red (3-amino-7-dimethylamino-2-methylphenazine hydrochloride) and flow cytometry with propidium iodide and annexin were performed on Caco-2 cells. In case of in vivo toxicity study, G. mellonella larvae were injected with different concentrations of the test compounds. Time-kill tests were executed on reference strains of C. albicans, E. coli, and S. aureus. According to the MTT-assay, the IC50 values were the following: ethyl sorbate, sorbic acid 0.75% w/w, while Neutral Red values were >0.75% w/w for the esters and potassium sorbate and 0.66% w/w for sorbic acid. Flow cytometry results indicated the higher cell damage in case of isopropyl sorbate. However, the cytotoxic results of isopropyl sorbate, in vivo toxicity study on G. mellonella larvae did not show significant mortality. It was found, that the antimicrobial properties of isopropyl sorbate were outstanding compared to sorbic acid and potassium sorbate. These results indicate, that the use of sorbate esters can be advantageous, hence, further toxicity studies are needed to prove their safety.

In cancer therapy, immunogenic cell death eliminates tumor cells more efficiently than conventional apoptosis. During photodynamic therapy (PDT), some photosensitizer (PS) targeting lysosomes divert apoptosis to the immunologically more relevant necrosis-like cell death. Acridine orange (AO) is a PS targeting lysosome. We synthesized a new compound, 3-N,N-dimethylamino-6-isocyanoacridine (DM), a modified AO, aiming to target lysosomes better. To compare DM and AO, we studied optical properties, toxicity, cell internalization, and phototoxicity. In addition, light-mediated effects were monitored by the recently developed QUINESIn method on nuclei, and membrane stability, morphology, and function of lysosomes utilizing fluorescent probes by imaging cytometry in single cells. DM proved to be a better lysosomal marker at 405 nm excitation and lysed lysosomes more efficiently. AO injured DNA and histones more extensively than DM. Remarkably, DM’s optical properties helped visualize shockwaves of nuclear DNA released from cells during the PDT. The asymmetric polar modification of the AO leads to a new compound, DM, which has increased efficacy in targeting and disrupting lysosomes. Suitable AO modification may boost adaptive immune response making PDT more efficient.

Background/Objectives: Monoclonal antibody therapies for HER2-positive tumors frequently encounter resistance, requiring alternative treatment strategies. This study investigates the use of natural killer (NK) cells expressing HER2-specific chimeric antigen receptor (CAR) to address this issue. CAR NK cells have several benefits over CAR T cells: they are less likely to cause severe side effects such as cytokine release syndrome and neurotoxicity, can be sourced from various origins, and do not trigger Graft versus Host Disease, making them ideal for “off-the-shelf” applications. Methods: We have generated NK-92 cell lines expressing first, second and third-generation HER2-specific CARs with CD28 and/or 41BB costimulatory domains using a retroviral transduction system, followed by FACS sorting and expansion to obtain pure HER2-CAR NK-92 cell products for functional benchmarking. Results: In vitro tests showed that these CAR NK cells were effective against both trastuzumab-sensitive (CD44⁻) and -resistant (CD44⁺) tumors in monolayer cultures. However, in three-dimensional spheroid models and in vivo xenografts, they were less effective against CD44+ trastuzumab-resistant tumors. Conclusions: This reduced efficacy highlights the significant role of the tumor microenvironment, particularly the extracellular matrix, in hindering the therapeutic potential of CAR NK cells. Despite the promising in vitro performance of CAR NK cells, this study emphasizes the need for improved strategies to enhance their penetration and effectiveness in resistant tumors: optimizing CAR constructs and devising methods to overcome extracellular matrix barriers are crucial for advancing CAR NK cell therapies in oncology.

STAT3 is a transcription factor that regulates various cellular processes with oncogenic potential, thereby promoting tumorigenesis when activated uncontrolled. STAT3 activation is mediated by its tyrosine phosphorylation, triggering dimerization and nuclear translocation. STAT3 also contains a serine phosphorylation site, with a postulated regulatory role in STAT3 activation and G2/M transition. Interleukin-6, a major activator of STAT3, is present in elevated concentrations in uveal melanomas, suggesting contribution of dysregulated STAT3 activation to their pathogenesis. Here, we studied the impact of chelidonine on STAT3 signaling in human uveal melanoma cells. Chelidonine, an alkaloid isolated from Chelidonium majus, disrupts microtubules, causes mitotic arrest and provokes cell death in numerous tumor cells. According to our flow cytometry and confocal microscopy data, chelidonine abrogated IL-6-induced activation and nuclear translocation, but amplified constitutive serine phosphorylation of STAT3. Both effects were restricted to a fraction of cells only, in an all-or-none fashion. A partial overlap could be observed between the affected subpopulations; however, no direct connection could be proven. This study is the first proof on a cell-by-cell basis for the opposing effects of a microtubule-targeting agent on the two types of STAT3 phosphorylation.

Background and Objectives: Multiple myeloma (MM) remains an incurable plasma cell malignancy with heterogeneous clinical outcomes. Although current prognostic systems integrate biochemical and cytogenetic parameters, they do not fully capture disease complexity. Adipocytes within the bone marrow microenvironment secrete adipokines that regulate inflammation, metabolism, and immune interactions and may influence disease progression. This study aimed to assess circulating adipokines and related microenvironmental mediators as potential biomarkers of disease activity and treatment response in MM. Materials and Methods: In this case–control, cross-sectional study, the serum levels of eight adipokine-related molecules—adiponectin, leptin, resistin, chemerin, adipsin, thrombospondin-1 (TSP-1), paraoxonase-1 (PON-1), and myeloperoxidase (MPO)—were measured in 40 MM patients and 38 age- and sex-matched healthy controls. Enzyme-linked immunosorbent assays (ELISA) and bead-based multiplex immunoassays were used. Associations with prognostic markers (serum β₂-microglobulin (sB2M), LDH, albumin, hemoglobin, renal function) and treatment response were analyzed using correlation and non-parametric statistical methods. Results: Compared to the controls, MM patients exhibited significantly higher circulating levels of adiponectin, resistin, chemerin, adipsin, TSP-1, and MPO, while leptin was decreased. Among clinical correlations, chemerin and PON-1 correlated positively with sB2M, TSP-1 correlated with LDH, and MPO correlated with M-protein and albumin. Resistin was lower in patients with renal impairment and an advanced disease stage. Adiponectin and TSP-1 were significantly lower in progressive disease compared to complete remission, suggesting their potential association with treatment response. Conclusions: This study demonstrates that multiple adipokines are dysregulated in MM and exhibit distinct associations with disease burden, renal function, and therapeutic response. Novel associations identified for TSP-1, PON-1, and adipsin highlight previously unrecognized microenvironmental pathways in MM biology. Adipokine profiling may complement established prognostic markers and provide new insights into the tumour microenvironment in MM.