Bulletin of Experimental Biology and Medicine最新文献

Hematological parameters were evaluated, proinflammatory immune response indices lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) were calculated, and iron was detected in tumor tissues by Perls' staining of histological sections in high (HR) and low resistant (LR) to hypoxia male C57BL/6 mice with colitis-associated colorectal cancer (CAC) induced by intraperitoneal injection of azoxymethane and three cycles of consumption of dextran sulfate sodium. The animals were euthanized on day 141 after azoxymethane administration. The relative number of monocytes in the blood increased in HR mice of the experimental group in comparison with the control group, and was higher than in LR animals. In LR mice with CAC, the relative number of lymphocytes and monocytes, absolute number of monocytes in the blood decreased and the NLR increased in comparison with the control; the LMR was higher than in HR animals. Regardless of hypoxia resistance, the mice developed normocytic hypochromic anemia; iron accumulation in the tumor was observed only in LR animals. The obtained data on more pronounced changes in hematological parameters in LR animals should be taken into account in the development of new approaches to the inflammatory and tumor diseases therapy, including CAC.

Transdermal drug delivery is an effective method of drug administration, and for certain substances, it may be the only viable option. The most efficient and advanced approach to implementation of this method is the use of microneedles made from biodegradable materials. The method for producing transdermal patches with microneedles has been proposed, including techniques for their biodegradation and implantation in vivo. This method involves creating a 3D model of the patch master form, printing it with a 3D printer, creating a mold from polydimethylsiloxane, and then casting the patch from a biopolymer such as PLGA, PLA, DL-PLA, or PDLLA. Among these biopolymers, PLGA has demonstrated better biodegradation properties in comparison with the others. The implantation of patches with a universal animal harness has been found to be the most effective method.

We performed a comparative study of the effect of a new acetylcholinesterase inhibitor 1,3-bis[5-(o-nitrobenzylethylamino)pentyl]-6-methyluracil (C-35) and a commercial drug donepezil on the density and morphology of dendritic spines in the entorhinal cortex of transgenic APP/PS1 mice with a model of Alzheimer's disease. Administration of donepezil to transgenic mice did not significantly change spine density or morphology. In contrast, treatment with C-35 increased dendritic spine density by 56 and 34% in comparison with donepezil and the control group (untreated transgenic mice), respectively. This effect of C-35 was associated with an increase in the number of thin spines and a decrease number of stubby spines.

The parameters of DNA-containing extracellular structures formed by immortalized fibroblasts and HCT116 adenocarcinoma cells during cultivation were studied. Fluorescence microscopy with SYBR Green dye was used to visualize DNA-containing extracellular structures. In contrast to intact neutrophils, immortalized fibroblasts and adenocarcinoma cells spontaneously formed DNA-containing extracellular structures during incubation. The process begins with the release of a single DNA-containing strand from the cell immediately after the cells are fixed to the substrate (1 h) and ends after 3 h with the formation of DNA-containing extracellular structures in the form of bundles of parallel fibers. These findings indicate active nature of the secretion of DNA-containing structures by immortalized fibroblasts and HCT116 adenocarcinoma cells.

We studied the efficiency of a conditioned medium containing the secretome of bone marrow mesenchymal stem cells in preventing corneal damage in rabbits using an experimental model of dry eye syndrome caused by impaired blinking reflex. The conditioned medium produced a pronounced protective effect on the epithelial layer of the cornea of rabbits and suppressed the activation of MMP-9 in the tear film. As is known, an increase in MMP-9 activity leads to degradation of extracellular matrix components and disruption of the corneal epithelial barrier function. Our results indicate the possibility of using the bone marrow mesenchymal stem cell secretome in the treatment of dry eye syndrome.

Data on the distribution of insulin biosynthesis enzymes in the developing human pancreas are limited and do not provide comprehensive understanding of mechanisms of β-cell maturation. In this study, the distribution of prohormone convertase 1/3 (PC1/3) in β and α cells of the pancreas of 15 fetuses (gestational age 8-20 weeks) was analyzed using double immunofluorescence staining. It has been demonstrated that numerous cells positively stained for PC1/3 but not containing insulin are present in the pancreatic islets during prenatal development. These cells probably represent maturing β cells that accumulate the enzyme prior to the insulin biosynthesis. In some of these cells, co-localization of PC1/3 and glucagon was revealed, which indicates a possible temporary expression of glucagon in differentiating and maturing β cells.

Deviations in neuropsychological development in the adolescence are considered in a pediatric clinic as the first peak of deviations with possible suicidal acts, and in the early adulthood - as a second peak their manifestations. The influence of the serotonin reuptake inhibitor fluoxetine in the infantile period (P25-P39) was studied in rats subjected to inflammatory pain in the neonatal period, on cognitive function and the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis in juvenile period (P54-P63), which correspond to the listed age periods in humans. Fluoxetine did not affect the spatial memory of control rats of both sexes and normalized the memory of the first day impaired by inflammatory pain in females; combination of pain and fluoxetine worsened long-term memory in females in comparison with males and in comparison with memory of the first day; shorter retention of spatial memory in females compared to males was associated with lower HPA axis reactivity. Our findings suggest that the effect of fluoxetine on the integrative function of the brain and reactivity of the HPA axis in the juvenile period depends on rat sex and neonatal pain.

Axial spondyloarthritis is characterized by activation of innate immune cells, which manifested in elevation of classical monocytes and predominance of the proinflammatory phenotype. However, the immunosuppressive potential of monocyte/macrophages remains practically unexplored. We evaluated the expression of Mer tyrosine kinase (MerTK) and arginase-1 (Arg1) in monocyte subsets in patients with axial spondyloarthritis, considering different clinical features. The expression of MerTK and Arg1 in intermediate and non-classical monocytes from patients with axial spondyloarthritis was reduced in comparison with the normal. The most pronounced decrease in monocyte expression of MerTK and Arg1 was associated with a more aggressive course of the disease (presence of coxitis, high disease activity, HLA-B27 positivity) and lack of response to conventional therapy. These data demonstrate an important role of MerTK and Arg1 in limiting myeloid-driven inflammation.

5-Androstenediol esters, dibutanoate and dipropionate, were synthesized as prototypes of effective cytoprotectors with prolonged action. The cytoprotective effect of the new 5-androstenediol derivatives was assessed in human lung and skin fibroblasts and human blood mononuclear cells exposed to UV radiation. 5-Androstenediol esters showed a regenerating, cytoprotective effect on different types of fibroblasts, but not on human peripheral blood mononuclear cells. The DNA comet assay revealed no genotoxic effect of the new steroids on the mononuclear fraction of human blood, which indicates their safety. The cytoprotective activity of 5-androstenediol dibutanoate and dipropionate in human fibroblasts attests to their possible use for creating ointments and liniments for the treatment of skin injuries requiring regeneration (including irradiation damage).

We studied the effect of fractionated gamma irradiation at cumulative doses of 0.1, 1, and 5 Gy during the first month of life on the indices of anxious behavior in C57BL/6 mice in the early and delayed terms after the exposure. Anxiety was evaluated using the marble burying test. Persistent dose-dependent behavioral changes were revealed: irradiation at a dose of 0.1 Gy led to an increase in the anxiety level at the age of 1 and 6 months, whereas exposure at a dose of 5 Gy suppressed animal activity in the marble burying test until the age of 12 months. Irradiation at a dose of 1 Gy decreased anxiety parameters only in the delayed period after the irradiation.