Doklady Biochemistry and Biophysics最新文献

The genotypic variability of the SARS-CoV-2 virus is extremely high, and the emergence of new strains raises concerns about their possible high virulence and ability to bypass responses of the body's immune system induced by previous infection or vaccination. Therefore, one of the main tasks is to study the pathogenesis of various variants of the virus using experimental animal biomodels of SARS-CoV-2 to quickly find methods and approaches to fighting new viruses. The study was performed on humanized mice of the C57BL/6-Tgtn line. Mice were infected intranasally at different doses with three variants of the SARS-CoV-2 virus. We showed that humanized hACE2 mice, when infected with all three variants of the SARS-CoV-2 virus, showed typical pathological changes in lung consistency comparable to those found in COVID-19 in humans. At a dose of 4 log plaque-forming unit (PFU), all variants showed 100% mortality. In a comparative assessment of different variants of the SARS-CoV-2 virus in hACE2 humanized mouse model, it was found that the Delta variant leads to more severe damage compared to Wuhan or Omicron.

Aging is a key challenge for modern society. In particular, brain aging is accompanied by chronic inflammation, depletion of energy potential, and an increased level of oxidative stress, with changes in blood composition playing a special role in this process. Recent studies also show that aging progresses non-linearly throughout life. Primates are genetically and anthropometrically the closest laboratory animals to humans, thus representing the most accurate model for research. This study establishes baseline values for biochemical parameters (including the state of the body's antioxidant system), cellular-hematological, and genomic indicators in aging primates of various species, sexes, and ages from the Kurchatov Complex of Medical Primatology. In aging males, the concentration of lipid peroxidation products was lower than in females of the same age and species. Analysis of antioxidant defense parameters indicates a more stable redox balance in old cynomolgus macaques of both sexes, which may be associated with their lower aggressiveness and high adaptability. The biochemical profile analysis in aging rhesus macaques revealed that females exhibit elevated levels of all measured parameters. In aging cynomolgus macaques, there are fewer sex-related differences in blood composition characteristics compared to rhesus macaques. It can be noted that under the housing conditions of the primates at the nursery of the Kurchatov Complex of Medical Primatology, several types of aging based on blood parameters can be observed within the same age category across different species and sexes.

Ferroptosis is considered a promising strategy for inducing the death of tumor cells. However, the effectiveness of known ferroptosis inducers, such as erastin, is in some cases limited, which stimulates the search for new combined application strategies. In this study, the combined effect of erastin and docosahexaenoic acid (DHA) on prostate cancer cells was examined over time. It was shown that the combination of these agents is more toxic compared to their separate use for all tumor cells considered. At the same time, known ferroptosis inhibitors, ferrostatin-1 and deferoxamine, effectively prevented cell death, indicating the specificity of the mechanism of action. Transcriptomic analysis of cell lines differing in sensitivity to the combination revealed activation of antioxidant systems in more resistant cells (in particular, pronounced expression of the NQO1 and GCLM genes responsible for the reduction of quinones to hydroquinones and the synthesis of glutathione, respectively). The obtained results indicate the high synergistic potential of the erastin-DHA combination for ferroptosis induction and open new possibilities for the development of combined approaches to the therapy of resistant tumors.

This study investigated the printability and textural properties of 3D-printed pectin–κ-carrageenan hydrogels with varying polysaccharide ratios. Inks with 50 and 60% κ-carrageenan exhibited optimal printability, producing structures consistent with digital designs. Rheological temperature sweep tests showed increased viscosity and moduli with higher κ-carrageenan content, affecting extrusion behavior. Hydrogels printed with high-methoxyl (HM) pectin were softer, less cohesive, and more adhesive than those with low-methoxyl (LM) pectin, attributable to lower network strength confirmed by rheological tests. Sensory evaluations favored HM hydrogels for ease of swallowing and taste, supported by reduced chewing effort and enhanced saliva absorption. These findings demonstrate that κ-carrageenan improves pectin ink printability and enables fabrication of edible gels with tunable texture for personalized nutrition.

Lectins of the Legume family have been identified as carbohydrate-binding proteins for a long time. However, despite long-standing and intensive research, there is insufficient information on the role of lectins of this family in the processes of normal plant cell physiology. Analysis of transcriptomic data of flax stem tissues [1] previously revealed the differential expression pattern of lectin genes of different families. Among lectins with increased gene expression levels in tissues with a primary cell wall, three representatives of the Legume family were identified. For one of them, Lus10021117, was optimized a method for producing the recombinant protein in plant expression system Nicotiana benthamiana. We report the identification of several glycoforms of the recombinant protein. One of this glycoform was found to form dimers stabilized by weak, non-covalent interactions. Furthermore, phosphorylation was first experimentally demonstrated for this protein.

Malectin and malectin-like proteins (M/MLPs) form one of the largest plant lectin families, yet the carbohydrate specificity of most members remains largely unexplored. FERONIA, a receptor-like kinase and key regulator of cell expansion, is the best-known member experimentally confirmed to bind pectins. Using transcriptomic data from plant species with contrasting cell wall pectin contents—Arabidopsis thaliana, maize (Zea mays), celery (Apium graveolens), and flax (Linum usitatissimum)—we revised all M/MLP genes and analyzed their expression profiles, alongside genes encoding glycosyltransferases (GTs) involved in cell wall polysaccharide biosynthesis. Distinct sets of M/MLPs were upregulated during cell expansion, in pectin-rich tissues, and during wall thickening, with only partial overlap between orthologs of monocots and dicots. A strong coexpression of M/MLP genes with those encoding GTs associated with pectin biosynthesis was found in celery, whereas M/MLPs expressed in flax fibers with tertiary walls exhibited little correlation. In contrast, almost all M/MLP genes in all analyzed samples showed no or negative expression correlation with genes encoding GTs for xyloglucan and cellulose biosynthesis. These results indicate functional specialization within the M/MLP family and highlight candidate genes for future studies on pectin recognition and cell wall sensing.

This study is aimed to evaluate the prebiotic potential of plant polysaccharides of various structural types and origins, including acacia gum arabinogalactan, beech wood xylan, apple pectin enriched in homogalacturonan, flaxseed mucilage (containing arabinoxylan, and rhamnogalacturonan I), and chicory inulin. All carbohydrate samples varied in their monosaccharide composition and molecular weight distribution. The prebiotic activity of the polysaccharides was assessed using in vitro models under anaerobic conditions with the Bifidobacterium bifidum 791 and Lactobacillus acidophilus n.v. Ep 317/402. It was found that adding various polysaccharides to the nutrient media intensified lactic acid production, increased the biomass yield of bifidobacteria and lactobacilli, and influenced the rate and extent of substrate assimilation. The lower molecular weight inulin (4.2 kDa) and arabinogalactan (115 kDa) supported higher biomass yields in both strains. The viable cell count of Bifidobacterium bifidum 791 (colony-forming units per mL) increased by 3.5, 12.3, 110.5, 128.1, and 215.8% compared to the control upon the addition of beech wood xylan, flaxseed mucilage polysaccharides, apple pectin, inulin, and acacia arabinogalactan, respectively. For L. acidophilus n.v. Ep 317/402, the addition of the same polysaccharides increased the biomass yield by 1.5, 7.7, 64.6, 69.2, and 207.7%, respectively, versus the control. Flaxseed mucilage, composed of rhamnogalacturonan I (3400 kDa) and arabinoxylan (1330 kDa), supported a high biomass yield in both cultures. Based on this research, it can be concluded that flaxseed mucilage promoted probiotic growth in a manner similar to, and often more effectively than, the established prebiotic inulin. Due to the availability of flaxseeds, simple mucilage extraction process, and the limited existing research, flaxseed polysaccharide complex emerges as a promising candidate for further development as a prebiotic supplement.

All vital processes in plants are regulated by a complex network of transcription factors. The formation of the cell wall, one of the key structures of plant cells that determines plant development and function, is tightly controlled. In particular, the main target genes regulated by transcription factors encode enzymes involved in polysaccharide metabolism, specifically their biosynthesis and modification. The transcriptional network governing secondary cell wall formation comprises the bulk of vascular and mechanical tissues, which together constitute a general component of wood. Despite overlapping main components, secondary cell walls in fibers and vessels are controlled by distinct master regulators. Flax phloem fibers form a tertiary cell wall composed mainly of cellulose and a small portion of pectins, with an absence of xylan and lignin. Formation of the tertiary cell wall requires the deposition of even a thin layer of secondary cell wall. For the first time, a comprehensive revision of VNS genes, belonging to the NAC family of transcription factors, has been performed in flax. The NST group of NAC transcription factors, potentially involved in secondary cell wall formation in both phloem and xylem fibers, has been identified. These genes represent valuable targets for both fundamental studies on cell wall biogenesis and molecular-genetic manipulation aimed at improving plant quality.

Exopolysaccharide (EPS) production is one of the key mechanisms of bacterial survival in hypermineralized environments. Representatives of the Halomonadaceae family are recognized as basic organisms for next-generation industrial biotechnology; however, the range of Halomonas used and information on the structural diversity of their EPSs are rather limited. The results of metagenomic analysis of salt, peloid, and soil samples from the coastal zone of salt lakes in the Volgograd region with subsequent seeding on selective mineral media made it possible to isolate bacteria of the Halomonadaceae family. For taxonomically identified strains, cultivation conditions were optimized and EPSs were obtained, the structure of which was characterized based on chemical analysis data and NMR spectroscopy. The study of the physicochemical properties of EPSs (viscosity, hygroscopicity, emulsifying activity, and antioxidant properties) showed that these polymers are promising for biotechnological applications.

NK cells participate in the antimicrobial immune response. NK cell activation by bacterial polysaccharides (PSs) can occur indirectly through signals from other immune cells or through direct influence of PSs on NK cells via interaction with activating receptors. This study demonstrated that peripheral NK cells bind fluorescently labeled PSs from the Gram-negative bacteria Escherichia coli, Shigella flexneri, and Pseudomonas aeruginosa with varying efficiency depending on the PS origin and the NK cell donor. PSs from Escherichia coli strain O19ab induced an increased IFN-γ production by NK cells in the absence of high levels of PS binding to the cell surface. The obtained results provide new insights into the interactions of NK cells with polysaccharides and open new prospects for understanding the NK cell-mediated immune response to bacterial infections.