Immunotherapeutic methods, such as the use of checkpoint inhibitors, CAR T cells, dendritic cell vaccines, etc., offer promising approach to the treatment of glioblastomas. Dendritic cell (DC)-based vaccines used in glioma therapy have been well studied and are effective in some cases. However, the use of DC vaccines for the treatment of patients with gliomas, though shows promising results, is still limited by the suboptimal choice of tumor antigen and the method of its loading, as well as the immunosuppressive nature of the tumor cell microenvironment. In this work, we showed that glioma cell lines express a broad spectrum of immune checkpoints, suppress the maturation of allogeneic DCs during direct co-culturing, and do not stimulate the proliferation of allogeneic lymphocytes. Lymphocytes primed with dendritic cells loaded with the corresponding tumor lysates effectively lysed only two of three glioma cell lines, T98G and U373 MG, whereas 1321N1 cells completely suppressed the cytotoxic activity of lymphocytes primed by co-culturing with DCs loaded with the lysate of these cells. Thus, the efficacy of DC vaccines may be related to the individual characteristics of glioma cells.

We studied patterns of staining for early cell markers in the forming pancreatic islets during months 5 and 6 of human prenatal development. The study was performed on 10 autopsy specimens of the fetal pancreas (gestational age 16-23 weeks) using multiple immunohistochemical staining with antibodies to PDX1 and CK19. Two main types of cells have been identified: cells with the intense staining for PDX1 and weak or no staining for CK19 that were located in the central area of the mantle islets or at one the poles of bipolar islets and may be referred to a population of β cells and cells with staining for CK19 and weak or no staining for PDX1 that were located at the periphery of the mantle islets or at the other pole of bipolar islets and may be referred to a population of α cells. The islet cells had additional phenotypes based on the staining for CK19 and PDX1, which requires further studies to determine the fate of these cells.

The effects of constant illumination, melatonin deficiency, and melatonin administration on the lifespan and oncogenesis in rats were studied in a 55-month experiment. Constant illumination significantly reduced the mean lifespan and maximum age, increased the rate of aging, and increased mortality at the age of 3-12 months. Melatonin administration increased the mean lifespan, maximum age, slowed down aging, and decreased early mortality. Survival analysis (log-rank test, p ⩽ 0.001) and the Cox model confirmed that constant illumination increased the risk of mortality, while melatonin reduced it. Constant illumination was associated with increased incidence of tumor formation, while melatonin reduced the incidence of neoplasms. Tumor-free survival was maximum in the group of animals receiving melatonin and minimum in the group of constant illumination. Thus, constant illumination accelerates aging and increases oncogenic risk, while melatonin has a geroprotective and anti-carcinogenic effects.

Autoimmune myocarditis is a disease with pronounced sex-related differences. It is known that the incidence of myocarditis is higher in men; however, other autoimmune diseases are more commonly observed in women. The aim of this study was to assess molecular and biological changes in the myocardium of male and female BALB/c mice on days 14 and 60 of experimental autoimmune myocarditis. We examined the morphological properties of the myocardium, the expression of pro- and anti-inflammatory markers in the myocardium, and the concentrations of IL-1β and IL-10 in blood serum. Sex-specific differences in the molecular and biological changes in the myocardium were identified at both time points of autoimmune myocarditis. In males, a pronounced lymphoid-histiocytic infiltration was observed, along with alterations in the balance of pro- and anti-inflammatory cytokines. Males showed increased expression of Il1b, Il6, Hif1a, and Tgfb mRNA on day 14 and Il1b, Nfkb, Il10, and Tgfb mRNA on day 60. In females, changes were less pronounced: the expression of Il1b mRNA was elevated on day 14, but no significant changes were observed on day 60. The serum levels of IL-10 and IL-1β in males increased on days 14 and 60, respectively. These findings may explain the sex-specific differences in the course of autoimmune myocarditis.

We performed a comprehensive analysis of changes in the functional state of human multipotent mesenchymal stromal cells derived from the umbilical cord tissue (UC-MSCs) after a 30-day simulated microgravity exposure. It was found that simulated microgravity induced changes in the expression of stromal markers and cell cycle regulators in UC-MSCs but did not alter their viability and expression of the cytoskeletal genes. We also observed shifts in the expression of adhesion molecules and enhanced secretion of proinflammatory cytokines. These findings indicate that microgravity modulates functional properties of MSCs and confirm the possibility of using these cells as a model system for studies of the molecular and cellular mechanisms underlying adaptation to microgravity during long-term spaceflights.

mRNA vaccines have a number of advantages over traditional vaccines: high safety (no risk of infection, minimal possibility of integration into the genome), the ability to induce both cellular and humoral immune responses, as well as the possibility of repeated administration due to the absence of antiviral immunity. The effectiveness of Moderna and Pfizer/BioNTech products that use lipid nanoparticles for mRNA delivery have been proven, but they have disadvantages, including the need for ultra-low-temperature storage and side effects associated with lipid components of vaccines. Polymers, polypeptides, dendrimers, and other delivery systems are being investigated as alternative methods of mRNA delivery. This review analyzes the side effects of mRNA vaccines encapsulated in lipid nanoparticles and promising approaches to reducing their reactogenicity.

A model of chronic predatory stress was effectively reproduced in Danio rerio. It was found that during chronic stress, the fish used an active coping strategy. The results of the novel tank diving test indicate the presence of anxiety and phobic disorders in stressed fish. Behavioral disorders are associated with an increase in serotonin levels with a simultaneous decrease in Z-MAO activity and a decrease in the level of cortisol in stressed fish.

We measured the concentrations of phycobiliproteins (phycocyanin, allophycocyanin, and phycoerythrin) in the extract of the cyanobacterium Leptolyngbya cf. ectocarpi and studied their influence on the functional potential (NADPH-dependent activity of oxidoreductases) of immunocytes (peritoneal macrophages and splenocytes), hepatocytes, and enterocytes in male and female C57BL/6 mice in vitro. It was found that the intensity of light exposure affects the phycobiliprotein production spectrum in the cyanobacterium culture. No significant effects of phycobiliproteins on the intracellular activity of NADPH-dependent oxidoreductases in peritoneal macrophages, splenocytes, primary cultures of hepatocytes, and enterocytes from C57BL/6 mice were observed.

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.