The reaction of zinc(II) nitrate with 2-ferrocenyl-1,10-phenanthroline (L) produced the complex [ZnL(NO3)2] (I), which was analyzed by elemental analysis, powder X-ray diffraction, thermogravimetric analysis, cyclic voltammetry, and IR spectroscopy. According to the single-crystal X-ray diffraction analysis, the coordination environment of zinc(II) can be described as 5 + 1, and L acts as a chelating ligand that binds to the zinc(II) atom through the nitrogen atoms of the phenanthroline moiety. The cytotoxic properties of complex I were evaluated using the human two-dimensional cell lines Hep2 (laryngeal carcinoma cells), A549 (lung adenocarcinoma cells), and MRC5 (nontumor lung fibroblasts). Complex I exhibited cytotoxicity at concentrations between 50 and 100 μM. The activity of complex I in Hep2 spheroids (3D model) was found to be comparable to that in the two-dimensional model. The behavior of the complex in solution was studied using optical spectroscopy, conductometry, and cyclic voltammetry.
The copper(II) perchlorate complex [Cu2(phendione)2L4](ClO4)4·3H2O (I) is synthesized from 1,10-phenanthroline-5,6-dione (phendione) and 1-(1H-benzimidazol-1-ylmethyl)-1H-1,2,3-benzotriazole (L). Complex I is characterized by elemental and thermogravimetric analyses, optical and IR spectroscopy, and single-crystal and phase X-ray diffraction analyses (XRD). The crystal structure of the complex is determined by single-crystal XRD: the compound is binuclear due to the bridging function of L, and the coordination number of the copper atom is five. The cytotoxic properties of the complex toward tumor cell lines А549 and MCF7 and nontumor human fibroblasts MRC5 are studied. The complex has cytotoxic activity in the micromolar concentration range exceeding that for cisplatin served as the reference.
Background. Currently, gastropathy (band and punctate erosions) caused by the use of nonsteroidal anti-inflammatory drugs are the most common complications of drug therapy for acute respiratory viral infections and rheumatoid diseases. With prolonged use of nonsteroidal anti-inflammatory drugs and when treated in high doses, erosions of the gastric mucosa very often progress and transform into chronic gastric ulcers, which, in terms of pathophysiological mechanisms, are identical to gastric ulcer disease with the involvement of Helicobacter pylori. Currently, there are no effective means for the prevention of drug-induced gastropathy. Attempts to create nonsteroidal anti-inflammatory drugs that do not cause gastropathy have also been unsuccessful. The authors of the article propose the use of low molecular weight chitosan as a gastroprotective agent.Objective. To evaluate the effectiveness of low molecular weight chitosan (50 kDa) as a means of preventing damage to the gastric mucosa during the administration of nonsteroidal anti-inflammatory drugs in a model of indomethacin gastropathy in rats.Materials and Methods. The study was performed on 14 male Wistar rats, 3 months old with an average body weight of 240-250 g. Under light ether anesthesia, the animals were administered an intragastrically indomethacin suspension at a dose of 60 mg per 1 kg of body weight. One hour after the administration of the indomethacin suspension, the animals of the control group were administered intragastrically 2 ml of a 0.9% sodium chloride solution, and the animals of the experimental group were administered 2 ml of a 0.2% aqueous solution of low-molecular chitosan (50 kDa). Twenty-four hours after the administration of the test substances, all rats were euthanized by an overdose of ether anesthesia. The stomachs of the animals of the experimental and control groups were removed, cut along the lesser curvature, washed with saline, and the gastric mucosa was scanned at a resolution of 1200 dpi. The area of erosions in the gastric mucosa (ribbon and punctate) in mm2 and the area of the mucosa in mm2 were calculated in Corel Draw 13.Results. The studies showed that low-molecular chitosan (50 kDa) has a pronounced cytoprotective effect and significantly reduces the percentage of damage to the gastric mucosa in the indomethacin gastropathy model in rats. The most likely mechanism of the described therapeutic effect of low-molecular chitosan is the activation of gastric mucosal macrophages and the expression of the synthesis of antiinflammatory cytokines by them. Moreover, with intragastric administration of low-molecular chitosan, not only the total area of erosive damage to the stomach decreases, but also a significant (more than fivefold) decrease in the area of ribbon erosions.Conclusion. Low-molecular chitosan has a distinct gastroprotective effect when administered with indomethacin and can be considered as a promising drug for the prevention of non-steroidal gastropathy. At the same time, low-molecular chitosan may be a very promising additional component in the production of nonsteroidal anti-inflammatory drugs dosage forms with reduced side effects on the gastric mucosa.
Decision-making under risk lies at the core of strategic action in human activities. Nevertheless, the neural mechanisms underlying decision-making in trial-and-error-based learning in the absence of explicit risk ratios have not been thoroughly understood. This study investigates the neural correlates of long-term success during repeated risky decision-making. We combined a motion detection task with a higher-level risk task in a functional magnetic resonance imaging (fMRI) paradigm. Twenty-five healthy adults participated in an fMRI task that required stopping a ball covertly moving at a constant speed at a certain spot. Participants initially selected a task difficulty level progressively related to the magnitude of the monetary reward and then attempted the task of chosen difficulty. Positive versus negative feedback (a monetary gain versus no gain) contrast comprised clusters in the striatum, executive control regions, and the Default mode network (DMN). The activity in brain regions associated with metacognitive functions (DMN nodes) and not in those involved in reward evaluation and risk-taking (striatum) was positively related to the exploration index, which reflects the effectiveness of risk-taking. This study provides insights into the functional roles of the DMN (especially, its anterior node) in high-level decision-making in risky environments, highlighting its importance in metacognitive control during reward-related learning.
Background.Currently, there is a sharp increase in gynecological diseases with pathophysiological elements of connective tissue dysplasia and proliferative processes in the uterus. In this aspect, endometrial hyperplasia occupies a leading position and is observed not only during postmenopause, but also for this pathological process there is a very negative tendency towards rejuvenation. The clinical significance of endometrial hyperplasia lies in the associated risk of endometrial cancer progression, and "atypical" forms of endometrial hyperplasia are considered as precancerous lesions. The frequency and timing of malignancy of endometrial hyperplasia are quite variable. Some authors believe that the frequency of oncotransformation of the endometrium ranges from 25 to 50%, others – up to 80%.Objective. The purpose of the work was to evaluate the therapeutic and prophylactic effect of low molecular weight chitosan on a model of endometrial hyperplasia in mice induced by hyperestrogenemia.Materials and methods. 20 outbred nonlinear laboratory ICR (CD-1) mice (female) with an average body weight of 20-22 g, they were divided into 2 groups of 10 animals in each group. Endometrial hyperplasia was modeled by subcutaneous injection of 0.1 ml of 2% synestrol oil solution, 2 times a week for 2 weeks. The animals of the experimental group received a 0.05% aqueous solution of low molecular weight chitosan as a drink throughout the experiment, and the animals of the control group received drinking water. After removing the animals from the experiment under ether anesthesia, the liver and uterus were fixed in a 10% formalin solution and subjected to standard alcohol histological wiring. The sections were stained with hematoxylin and eosin according to the usual procedure. The height of the epithelium was measured in micrometers on a cross-section of the uterus. The number of cells in adipose dystrophy was calculated as a percentage per 1 mm2. The glass sections were scanned on a histopathological micropreparation scanner KF-PRO-005 (Konfoong Biotech International Co., Ltd). Statistical processing of the results was carried out using the Statistica10.0 program.Results. As can be seen from the results obtained, low molecular weight chitosan has a pronounced therapeutic and prophylactic effect in endometrial hyperplasia. It manifests itself not only at the level of a decrease in endometrial hyperplasia, but also at the level of liver damage in a decrease in the volume density of hepatocytes in a state of fatty degeneration.Conclusion. The results obtained objectively prove that oral administration of low molecular weight chitosan effectively affects all links in the etiopathogenesis of endometrial hyperplasia and can be recommended for the prevention of not only this disease, but also for the prevention of malignancy of endometrial hyperplasia and the prevention of uterine cancer.
