Many photosensitive substances suitable for photodynamic therapy (PDT) have limited applications due to their insufficient solubility in polar solvents. Our research overcomes this challenge by means of nanotechnology in order to transform hydrophobic compounds into stable aqueous solutions, enabling them to use their full potential and unique properties in cancer therapy. In this study, the novel nano-composite cGQDs-PEG-curcumin was developed to overcome the insolubility of curcumin in water and its extraordinary efficacy in PDT was evaluated. Complex characterization was performed using high-resolution transmission electron microscopy (HR-TEM), FTIR, and UV-Vis spectroscopy. Further analysis involved fluorescence lifetime imaging (FLIM), and its cellular localization was mapped with confocal microscopy. In order to evaluate PDT effectiveness, cells treated with cGQDs-PEG-curcumin were irradiated with 5 J/cm2 of 414 nm light. After irradiation, cell viability assay, scanning electron microscopy (SEM), reactive oxygen species (ROS) detection, comet assay, and γH2AX-based DNA double-strand breaks (DSBs) detection were assessed and revealed a remarkable ability of the nano-composite to induce DNA damage after irradiation without ROS production. Our findings highlight the potential of cGQDs-PEG-curcumin as a cutting-edge PDT agent, capable of disrupting cell membrane and nucleolar integrity and impairing ribosomal synthesis, which is crucial for proliferating tumour cells.
- MeSH
- Cell Nucleolus * drug effects metabolism MeSH
- DNA Breaks, Double-Stranded drug effects MeSH
- Photochemotherapy * methods MeSH
- Photosensitizing Agents * pharmacology MeSH
- Graphite * chemistry pharmacology MeSH
- Curcumin * pharmacology chemistry MeSH
- Quantum Dots * chemistry MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Neoplasms * drug therapy MeSH
- Polyethylene Glycols * chemistry pharmacology MeSH
- DNA Damage * drug effects MeSH
- Reactive Oxygen Species metabolism MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The potentials of electrochemical processes in ideal aqueous media are related to the potential of a normal hydrogen electrode (NHE). However, in non-ideal media, the potentials of a metallocene redox couple are used as a reference. Such measurements with free metallocene in solution are complicated by adsorption and mass transport phenomena and solvation effects. Herein, a platinum electrode with an anchored ferrocene moiety (Pt,Fc) was used for cyclic voltammetric measurements of the potential of ferrocene/ferrocenium (Fc/Fc+) redox transformation in not only non-aqueous but, for the first time, aqueous solutions as well. This enabled us to eliminate the aforementioned problems associated with the application of free metallocene molecules in solution and, thus, to relate the midpoint potential (Epm) of the Fc/Fc+ redox couple to a NHE. After elimination of the liquid junction potential in an aqueous 0.1 M KCl solution at 25 °C, the average intraday Epm value obtained with freshly prepared Pt,Fc electrodes was found to be 0.312 ± 0.008 V versus the secondary Ag|AgCl electrode. The Pt,Fc electrode can be applied for the standardization of electrochemical measurements and investigation of solvation phenomena at interfaces in non-ideal media.
- Publication type
- Journal Article MeSH
This study investigates the interaction of two approved and one newly developed latanoprost formulation with in vitro and in silico models of the tear film and tear film lipid layer (TFLL). Latanoprost, a prostaglandin analogue used for intraocular elevated pressure treatment, is topically delivered by nanocarriers within aqueous solutions or emulsions. The study focuses on the impact of these carriers on drug interactions with the tear film and their effect on the TFLL. Three different types of latanoprost carriers, micellar, nanoemulsion, and polymer-based, were compared, and each revealed distinct interaction patterns with the TFLL. Surface pressure kinetics demonstrated a rapid increase for the benzalkonium chloride formulation and a slow rise for the preservative-free variants. Visualization of the acellular in vitro TFLL model revealed different patterns of incorporation for each formulation, indicating unique interaction mechanisms. Molecular dynamics simulations further revealed different mechanisms of drug release in the TFLL between micellar and nanoemulsion formulations. In-depth examination highlighted the role of triglyceride molecules in replenishing the nonpolar layer of the TFLL, which suggests potential improvements in ocular surface compatibility by adjusting the quality and concentration of the oily phase. These findings suggest the potential for optimizing latanoprost formulations by tuning the oily phase-to-surfactant ratio and selecting suitable surfactants.
- MeSH
- Antihypertensive Agents therapeutic use MeSH
- Glaucoma * drug therapy MeSH
- Latanoprost therapeutic use MeSH
- Drug Delivery Systems MeSH
- Humans MeSH
- Intraocular Pressure MeSH
- Eye * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Nanocrystalline cerium dioxide is able to protect living cells from oxidative stress under the influence of various stress factors, in particular under the one of low temperatures. This study investigates the phase-structural transformations in aqueous solutions containing CeO2 nanoparticles (NPs) and their impact on the cryopreservation process. Differential scanning calorimetry and thermomechanical analysis were used to analyse the phase transitions in aqueous suspensions of CeO2 NPs and aqueous solutions of the cryoprotectant dimethyl sulfoxide (Me2SO) with CeO2 NPs. Various concentrations of CeO2 NPs were tested to observe their effects on the crystallization and melting behaviours. The addition of CeO2 NPs significantly altered the temperatures and enthalpies of melting and crystallization in water. Low concentrations of CeO2 NPs promoted crystallization, while higher concentrations inhibited it, reducing supercooling and recrystallization during thawing. In Me2SO solutions, CeO2 NPs raised the glass transition temperature and affected the recrystallization process, with higher concentrations leading to more pronounced vitrification and reduced recrystallization. We also investigated the regularities of the effect of CeO2 NPs on phase transitions in combined cryoprotective media with Ham's F12, fetal bovine serum and Me2SO, which can be used in future to design the cryopreservation protocols. In the complex media, CeO2 NPs decreased the metastability and altered eutectic crystallization patterns, indicating potential cryoprotective effects. In conclusion, CeO2 NPs modulate the thermophysical properties of cryoprotective solutions, enhancing vitrification and reducing recrystallization, which could improve cryopreservation efficiency. Optimizing NP concentrations is crucial for practical applications in cryopreservation.
- MeSH
- Cerium * chemistry pharmacology MeSH
- Calorimetry, Differential Scanning * MeSH
- Dimethyl Sulfoxide * chemistry MeSH
- Cryopreservation * methods MeSH
- Cryoprotective Agents * chemistry pharmacology MeSH
- Crystallization * MeSH
- Nanoparticles * chemistry MeSH
- Transition Temperature MeSH
- Vitrification * drug effects MeSH
- Phase Transition * MeSH
- Publication type
- Journal Article MeSH
Formalin, an aqueous solution of formaldehyde, has been the gold standard for fixation of histological samples for over a century. Despite its considerable advantages, growing evidence points to objective toxicity, particularly highlighting its carcinogenicity and mutagenic effects. In 2016, the European Union proposed a ban, but a temporary permission was granted in consideration of its fundamental role in the medical-diagnostic field. In the present study, we tested an innovative fixative, glyoxal acid-free (GAF) (a glyoxal solution deprived of acids), which allows optimal tissue fixation at structural and molecular level combined with the absence of toxicity and carcinogenic activity. An open-label, non-inferiority, multicentric trial was performed comparing fixation of histological specimens with GAF fixative vs standard phosphate-buffered formalin (PBF), evaluating the morphological preservation and the diagnostic value with four binary score questions answered by both the central pathology reviewer and local center reviewers. The mean of total score in the GAF vs PBF fixative groups was 3.7 ± 0.5 vs 3.9 ± 0.3 for the central reviewer and 3.8 ± 0.5 vs 4.0 ± 0.1 for the local pathologist reviewers, respectively. In terms of median value, similar results were observed between the two fixative groups, with a median value of 4.0. Data collected indicate the non-inferiority of GAF as compared to PBF for all organs tested. The present clinical performance study, performed following the international standard for performance evaluation of in vitro diagnostic medical devices, highlights the capability of GAF to ensure both structural preservation and diagnostic value of the preparations.
- MeSH
- Tissue Fixation * methods MeSH
- Fixatives * chemistry MeSH
- Formaldehyde * chemistry MeSH
- Glyoxal * MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Equivalence Trial MeSH
- Multicenter Study MeSH
- Comparative Study MeSH
Levandule jako rostlina a levandulová silice mají široké spektrum biologických účinků, levandule se v kosmetice a léčivých přípravcích využívá již od dob starého Řecka a Říma. V dnešní době se na trhu vyskytuje nepřeberná škála produktů obsahujících levanduli, ať už jako takovou (levandulový čaj nebo sušenky či jiné pochutiny s květy levandule), případně obsahující levandulovou silici či vodné extrakty levandule (kosmetika, drogerie, potraviny či farmaceutické přípravky). Tato práce se zaměřuje na zjištění obsahu silice, zastoupení těkavých látek a stanovení celkových fenolů a flavonoidů u vzorků levandule lékařské z Levandulového údolí a porovnání výsledků se složením levandulových květů prodávaných jako bylinné čaje v tržní síti České republiky.
Lavender as a herb and the lavender essential oil have a wide range of biological effects. They have been used in cosmetics and medicinal products since the times of ancient Greece and Rome. Nowadays, there is a wide range of products containing lavender on the market, either as such (lavender tea or biscuits or other snacks with lavender flowers) or containing lavender essential oil or aqueous solutions of lavender (cosmetics, drugstore goods, food or pharmaceutical preparations). This work focuses on the determination of the essential oil content, the representation of volatile substances and the determination of total phenols and flavonoids in samples of medicinal lavender from the Levandulové údolí and bought in the Czech shops.
A benzodiazepine, diazepam, has been the leading antidote for seizures caused by nerve agents, the most toxic chemical weapons of mass destruction, since the 1960s. However, its limitations have often brought questions about its usefulness. Extensive effort has been devoted into exploring alternatives, such as other benzodiazepines, anticholinergics, or glutamate antagonists. However, only few showed clear clinical benefit. The only two options to ultimately reach clinical milestones are Avizafone, a water-soluble prodrug of diazepam adopted by the French and UK armed forces, and intramuscular midazolam, adopted by the US Army. The recently FDA-approved new intramuscular application of midazolam brought several advantages, such as rapid onset of action, short duration with predictable pharmacokinetics, increased water solubility for aqueous injectable solutions, and prolonged storage stability. Herein, we discuss the pitfalls and prospects of using midazolam as a substitute in anticonvulsant therapy with a particular focus on military purposes in combat casualty care. We have also considered and discussed several other alternatives that are currently at the experimental level. Recent studies have shown the superiority of midazolam over other benzodiazepines in the medical management of poisoned casualties. While its use in emergency care is straightforward, the proper dose for soldiers under battlefield conditions is questionable due to its sedative effects.
- MeSH
- Anticonvulsants * administration & dosage therapeutic use MeSH
- Diazepam * administration & dosage MeSH
- Humans MeSH
- Midazolam * administration & dosage MeSH
- Nerve Agents * MeSH
- Seizures * drug therapy chemically induced MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
This study investigates the factors modulating the reactivity of 5'-deoxyadenosyl (5'dAdo ̇) radical, a potent hydrogen atom abstractor that forms in the active sites of radical SAM enzymes and that otherwise undergoes a rapid self-decay in aqueous solution. Here, we compare hydrogen atom abstraction (HAA) reactions between native substrates of radical SAM enzymes and 5'dAdo ̇ in aqueous solution and in two enzymatic microenvironments. With that we reveal that HAA efficiency of 5'dAdo ̇ is due to (i) the in situ formation of 5'dAdo ̇ in a pre-ordered complex with a substrate, which attenuates the unfavorable effect of substrate:5'dAdo ̇ complex formation, and (ii) the prevention of the conformational changes associated with self-decay by a tight active-site cavity. The enzymatic cavity, however, does not have a strong effect on the HAA activity of 5'dAdo ̇. Thus, we performed an analysis of in-water HAA performed by 5'dAdo ̇ based on a three-component thermodynamic model incorporating the diagonal effect of the free energy of reaction, and the off-diagonal effect of asynchronicity and frustration. To this aim, we took advantage of the straightforward relationship between the off-diagonal thermodynamic effects and the electronic-structure descriptor - the redistribution of charge between the reactants during the reaction. It allows to access HAA-competent redox and acidobasic properties of 5'dAdo ̇ that are otherwise unavailable due to its instability upon one-electron reduction and protonation. The results show that all reactions feature a favourable thermodynamic driving force and tunneling, the latter of which lowers systematically barriers by ∼2 kcal mol-1. In addition, most of the reactions experience a favourable off-diagonal thermodynamic contribution. In HAA reactions, 5'dAdo ̇ acts as a weak oxidant as well as a base, also 5'dAdo ̇-promoted HAA reactions proceed with a quite low degree of asynchronicity of proton and electron transfer. Finally, the study elucidates the crucial and dual role of asynchronicity. It directly lowers the barrier as a part of the off-diagonal thermodynamic contribution, but also indirectly increases the non-thermodynamic part of the barrier by presumably controlling the adiabatic coupling between proton and electron transfer. The latter signals that the reaction proceeds as a hydrogen atom transfer rather than a proton-coupled electron transfer.
Background: Ivacaftor is a modern drug used in the treatment of cystic fibrosis. It is highly lipophilic and exhibits a strong positive food effect. These characteristics can be potentially connected to a pronounced lymphatic transport after oral administration. Methods: A series of studies was conducted to describe the basic pharmacokinetic parameters of ivacaftor in jugular vein cannulated rats when dosed in two distinct formulations: an aqueous suspension and an oil solution. Additionally, an anesthetized mesenteric lymph duct cannulated rat model was studied to precisely assess the extent of lymphatic transport. Results: Mean ± SD ivacaftor oral bioavailability was 18.4 ± 3.2% and 16.2 ± 7.8%, respectively, when administered as an aqueous suspension and an oil solution. The relative contribution of the lymphatic transport to the overall bioavailability was 5.91 ± 1.61% and 4.35 ± 1.84%, respectively. Conclusion: Lymphatic transport plays only a minor role in the process of ivacaftor intestinal absorption, and other factors are, therefore, responsible for its pronounced positive food effect.
- Publication type
- Journal Article MeSH
The colonisation of the surface of removable acrylic dentures by various types of microorganisms can lead to the development of various diseases. Therefore, the creation of a bioactive material is highly desirable. This study aimed to develop a denture base material designed to release bioactive ions into the oral environment during use. Four types of bioactive glasses (BAG)-S53P4, Biomin F, 45S5, and Biomin C-were incorporated into the PMMA acrylic resin, with each type constituting 20 wt.% (10 wt.% non-silanised and 10% silanised) of the mixture, while PMMA acrylic resin served as the control group. The specimens were subsequently immersed in distilled water, and pH measurements of the aqueous solutions were taken every seven days for a total of 38 days. Additionally, surface roughness and translucency measurements were recorded both after preparation and following seven days of immersion in distilled water. The cytotoxicity of these materials on human fibroblast cells was evaluated after 24 and 48 h using Direct Contact and MTT assays. Ultimately, the elemental composition of the specimens was determined through energy-dispersive X-ray (EDX) spectroscopy. In general, the pH levels of water solutions containing BAG-containing acrylics gradually increased over the storage period, reaching peak values after 10 days. Notably, S53P4 glass exhibited the most significant increase, with pH levels rising from 5.5 to 7.54. Surface roughness exhibited minimal changes upon immersion in distilled water, while a slight decrease in material translucency was observed, except for Biomin C. However, significant differences in surface roughness and translucency were observed among some of the BAG-embedded specimens under both dry and wet conditions. The composition of elements declared by the glass manufacturer was confirmed by EDX analysis. Importantly, cytotoxicity analysis revealed that specimens containing BAGs, when released into the environment, did not adversely affect the growth of human gingival fibroblast cells after 48 h of exposure. This suggests that PMMA acrylics fabricated with BAGs have the potential to release ions into the environment and can be considered biocompatible materials. Further clinical trials are warranted to explore the practical applications of these materials as denture base materials.
- Publication type
- Journal Article MeSH
