Curcumin has been modified in various ways to broaden its application in medicine and address its limitations. In this study, we present a series of curcumin-based derivatives obtained by replacing the hydroxy groups in the feruloyl moiety with polyethylene glycol (PEG) chains and the addition of the BF2 moiety to the carbonyl groups. Tested compounds were screened for their cytotoxic activity toward two bladder cancer cell lines, 5637 and SCaBER, and a noncancerous cell line derived from lung fibroblasts (MRC-5). Cell viability was analyzed under normoxic and hypoxic conditions (1% oxygen). Structure–activity relationships (SARs) are discussed, and curcumin derivatives equipped within feruloyl moieties with 3-methoxy and 4-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy} substituents (5) were selected for further analysis. Compound 5 did not affect the viability of MRC-5 cells and exerted a stronger cytotoxic effect under hypoxic conditions. However, the flow cytometry studies showed that PEGylation did not improve cellular uptake. Another observation was that the lack of serum proteins limits the intracellular uptake of curcumin derivative 5. The preliminary mechanism of action studies indicated that compound 5 under hypoxic conditions induced G2/M arrest in a dose-dependent manner and increased the expression of stress-related proteins such as p21/CIP1, phosphorylated HSP27, ADAMTS-1, and phosphorylated JNK. In summary, the results of the studies indicated that PEGylated curcumin is a more potent compound against bladder cancer cell lines than the parent compound, and derivative 5 is worthy of further investigation to clarify its mechanism of anticancer action under hypoxic conditions.
This work presents the synthesis and characterization of metal-free, zinc (II), and cobalt (II) porphyrins substituted with short PEG chains. The synthesized compounds were characterized by UV-Vis, 1H and 13C NMR spectroscopy, and MALDI-TOF mass spectrometry. The origin of the absorption bands for tested compounds in the UV-Vis range was determined using a computational model based on the electron density functional theory (DFT) and its time-dependent variant (TD-DFT). The photosensitizing activity was evaluated by measuring the ability to generate singlet oxygen (ΦΔ), which reached values up to 0.54. The photodynamic activity was tested using bladder (5637), prostate (LNCaP), and melanoma (A375) cancer cell lines. In vitro experiments clearly showed the structure–activity relationship regarding types of substituents, their positions in the phenyl ring, and the variety of central metal ions on the porphyrin core. Notably, the metal-free derivative 3 and its zinc derivative 6 exerted strong cytotoxic activity toward 5637 cells, with IC50 values of 8 and 15 nM, respectively. None of the tested compounds induced a cytotoxic effect without irradiation. In conclusion, these results highlight the potential value of the tested compounds for PDT application.
In recent years, the administration of fentanyl (FNTL) implicitly in transdermal drug delivery systems (TDDS) has vastly increased in chronic pain treatment. Non-medical and uncontrolled use of FNTL in TFDS (transdermal fentanyl delivery systems) may reveal toxic effects by the route of exposure, dermal or alternative, by ingestion of patches, and drug release in the stomach. The purpose of this study was to present three different cases of FNTL poisonings, two of which resulted in death due to TFDS abuse. The first case is a 66-year-old woman treated for accidental FTNL poisoning resulting in acute respiratory distress syndrome. Two remaining cases are a 31-year-old woman and a 25-year-old man who died as a result of FNTL overdose after on-skin and ingestion application of the drug patches. During the hospitalization of the 66-year-old patient, in blood samples, FNTL was confirmed at a concentration of 10.0 ng/mL. Tests run on blood taken from the corpses of 25- and 31-year-old patients exhibited FNTL presence in concentrations of 29.1 ng/mL and 38.7 ng/mL, respectively. The various routes of administration and ultimately toxic effects are important to present because, in TDDS, fentanyl can be a reason for severe to fatal poisoning, as shown by the three cases above.
Introduction: This study aimed to assess the analgesic efficacy of oxycodone at doses of 10 mg and 20 mg in dressings after surgery of burn wounds. Material and Methods: Twenty adult patients who underwent surgical treatment of third-degree burn wounds under general anaesthesia were included. Burn wounds were treated with dressings, to which oxycodone was added at 20 mg in Group 1 and 10 mg in Group 2. After the surgery, plasma oxycodone and noroxycodone concentrations were assayed, and pain intensity was assessed with Numerical Rating Scale (NRS). Results: In Group 1, no patient reported pain; in Group 2, four patients reported pain. The pain intensity, according to NRS, was 1–8. Plasma concentration of oxycodone in the blood serum was in the range of 1.24–3.15 ng/mL and 1.09–1.28 ng/mL in Group 1 and Group 2, respectively. Noroxycodone was not detected in the plasma. Adverse effects were not observed in any of the treated patients. Conclusions: Oxycodone in dressings provides patients with adequate and safe analgesia.
In recent years, an increasing amount of research has investigated the impact of chronic inflammation on the development and progression of both neurological and psychiatric disorders, including epilepsy, depression, schizophrenia, and bipolar disorder. Moreover, growing attention is being paid to how inflammatory processes contribute to disease mechanisms, influence symptom severity, and interact with pharmacological treatments in these conditions. Changes in the levels of inflammatory biomarkers, such as cytokines and C-reactive protein, may signal the early stages of neurological disorder development. Furthermore, specific biomarker profiles have been identified for individual diseases, and chronic treatment may affect their blood levels. Over the last two decades, significant progress in the study of inflammatory biomarkers in psychiatric disorders and epilepsy has been achieved, demonstrating an association between biomarkers with symptoms, a potential prognostic role, and possible use in personalising therapy. Furthermore, widely used methods for biomarker evaluation, such as immunoenzymatic assays and flow cytometry, remain essential tools for current research. Despite numerous indications of the importance of inflammation in psychiatry and neurology, the available studies are characterised by considerable heterogeneity in terms of both population selection and methodology. Based on the available data, inflammatory biomarkers represent a promising diagnostic and therapeutic tool for epilepsy and psychiatric disorders. Although existing studies suggest a correlation between inflammation and the symptoms of various disorders, inconsistent results highlight the need for further research to enable wider implementation of these findings in psychiatric and epilepsy practice. Advancing knowledge of inflammatory biomarkers is essential for improving treatment outcomes and promoting the development of targeted interventions.