To assess functional characteristics of cells of the neurovascular unit in Alzheimer's disease (AD), we performed differentiation of induced pluripotent stem cells from an AD patient (Alz9L cell line) into neuronal, glial, and endothelial cells with the formation of a three-cell model of the blood-brain barrier (BBB). Increased BBB permeability combined with changes in synaptic plasticity of neurons and changes in the metabolism of endothelial cells was detected in AD. The obtained results confirm the presence of vascular dysfunction during AD development and indicate the possibility of using personalized BBB models to assess the features of barrier formation.

Diabetic cardiomyopathy (DCM) represents a significant complication of diabetes, with a considerable number of deaths attributed to DCM on an annual global basis. We investigated the role and mechanism of action of imperatorin in the prevention and treatment of DCM using a diabetic rat model. The results of animal experiments showed that diabetic rats treated with imperatorin had lower levels of lactate dehydrogenase, aspartate aminotransferase, and creatine kinase MB isoenzyme, lower heart/body weight ratio, less pronounced histopathological changes in the myocardium, reduced expression of Caspase-3 and Bax, and increased expression of Bcl-2. Thus, imperatorin could attenuate pathological damage in diabetic myocardial tissue, which may be attributed to its regulatory effects on apoptosis.

We studied ex vivo effect of α2A/D-adrenoreceptor (α2A/D-AR) antagonist RX821002 at concentrations of 10-9-10-6 M on inotropy, chronotropy, and coronary flow in Langendorff-isolated rat heart. The minimum concentration of the antagonist did not affect the studied cardiac parameters. The α2A/D-AR antagonist at the concentrations of 10-8-10-6 M increased contraction pressure of the left ventricular myocardium and coronary flow. RX821002 exerted a positive and negative chronotropic effect depending on the concentration. Application of RX821002 at a concentration of 10-7 M caused dual-effect: both an increase and a decrease in heart rate were observed. The most pronounced changes in chronotropy and inotropy were revealed after application of α2A/D-AR blocker at a concentration of 10-7 M.

To study corneal homeostasis, corneal fibroblasts were cultured for 24 and 72 h on a corneal lens in the presence of conditioned media from cells of healthy cornea (keratocytes and limbal MSCs) or fibrous cornea (myofibroblasts). Conditioned media from keratocytes and limbal MSCs induced changes in fibroblast morphology, increased cell necrosis throughout the observation period (72 h), reduced proliferative activity and the number of CXCR4+ corneal fibroblasts, and induced opposite shifts in the level of SDF-1 secretion. The conditioned medium of myofibroblasts increased the number of Ki-67+ and CXCR4+ fibroblasts after 24 h and cell apoptosis after 72 observations; it also decreased SDF-1 production by fibroblasts. Our data demonstrate that regulation of CXCR4 receptor expression on corneal fibroblasts by the total soluble secretome plays an important role in maintaining corneal homeostasis.

The article investigates the influence of extracellular vesicles (EVs) isolated from donor seminal plasma (SP) on the expression of key reproductive genes AURKA and KLHL10 in human spermatozoa before and after cryopreservation. This study arises from the necessity to improve the effectiveness of assisted reproductive technologies (ART) and to advance the comprehension of how cryopreservation affects male gamete quality. A total of 17 sperm samples were examined. EVs were isolated from SP by asymmetric depth filtration and used for co-culturing with sperm samples prior to cryopreservation. Gene expression was analyzed by real-time PCR. The results demonstrated that sperm co-culturing with donor SP-EVs helped maintain or upregulate the expression of AURKA and KLHL10 genes that play critical roles in cell division and acrosome formation, respectively. These findings indicate a protective effect of EVs on spermatozoa during cryopreservation. The study highlights the potential utility of SP-EVs for augmenting sperm cryotolerance and boosting the efficacy of ART programs. Further research is warranted to investigate protein-level changes and functional implications of the observed gene expression patterns.

Endogenous immunotropic factors that promote the development of non-infectious inflammation can act as pathogenetic targets in the development of new agents for the treatment and prevention of type 2 diabetes mellitus (T2DM). Nucleotide motifs circulating in the blood can activate the immune system, thus playing an important role in the pathogenesis of T2DM and its vascular complications. We studied the effect of isoflavones extracted from red clover flowers (Trifolium pratense) on the plasma levels of extracellular nucleic acids and histone proteins in rats with a model of T2DM. It was shown that oral administration of isoflavones for 1 month to animals with diabetes reduced the plasma content of extracellular DNA and histones, which was accompanied by restoration of the number of granulocytes and alleviation of glycemia.

Neutrophil extracellular traps (NETs) are considered as a potential mechanism contributing to inflammation in pregnancy complications. To date, no "gold standard" for NET quantification has been established. The content of NETs varies depending on the detection method. The level of NETs and their components in pregnant women with preeclampsia was assessed using cytological and immunofluorescence methods, ELISA, and flow cytometry. All applied methods showed significantly elevated levels of both NETs and their individual components in women with preeclampsia.

Exhaustion of cytotoxic T cells was investigated in C57Bl/6 mice with modeled lung cancer. Differences in the formation of T cell exhaustion in orthotopic and metastatic lung cancer were identified. Regardless of the model, cancer stem cells (CSCs) contributed to the formation of hyporeactive T-cell phenotypes with low antitumor activity and survival in the context of tumor progression. A pilot study confirmed the role of CSCs and T cell exhaustion in tumor progression and metastatic disease in patients with small-cell lung carcinoma (SCLC). It is proposed to consider CSCs and exhausted T cells are proposed as predictors of progression and poor prognosis of SCLC. A novel approach to combat effector T cell exhaustion based on the regulation of PD-1/PD-L1 and MAPK/ERK signaling pathways was developed and tested in preclinical studies. The reprogramming efficiency has been demonstrated for both mouse and human T cells. A dedicated section of this work addresses the influence of aging on the effector T cell exhaustion and the choice of therapy for lung cancer under these conditions. Understanding and implementing these achievements will improve the treatment outcome and the quality of life for lung cancer patients from different age groups.

Using high-cancer CBA mice we showed that regulation of the expression of β2 leukocyte integrins LFA-1 and Mac-1 on peripheral blood cells, serum levels of IL-6 and IL-10, and number of dopaminergic neurons in combination with CD8+ lymphocyte infiltration of the tumor and destruction of tumor nodes after preventive administration of a multiphytoadaptogen during the early ontogeny substantially affects the incidence and size of spontaneous hepatocarcinomas and increases the duration and quality of life.

We studied cardiac relaxation disorders on a rat model of DOX-induced cardiomyopathy (DOX, 2 mg/kg/week for 2 weeks). Left ventricular pressure and volume were synchronously recorded in vivo at baseline and under increased doses of dobutamine (DBA, 1-32 μg/kg/min). Left ventricular diastolic stiffness constants were calculated; the dose dependence of HR and isovolumic relaxation time (tau) was evaluated. In rats with cardiomyopathy, the diastolic stiffness constants increased with increasing the DBA doses, which was absent in the control; HR and tau showed opposite changes. The mean angular coefficient of linear trends in the dose dependence of stiffness constants on infusion was 2.98 × 10-4 in rats with cardiomyopathy and -0.014 × 10-4 in control animals. Thus, DOX cardiomyopathy led to an increase in the diastolic stiffness constants against the background of DBA treatment.