Doklady Biochemistry and Biophysics最新文献

This work finds suitable enzyme activity protectants to improve the recovery rate of enzyme activity in the preparation of human polymerized hemoglobin-superoxide dismutase-catalase-carbonic anhydrase (PolyHb-SOD-CAT-CA), including trehalose, sucrose, glucose, hydroxypropyl-β-cyclodextrin, and mannitol.Different types and concentrations of enzyme activity protective agents were added during polymerization to compare their protective ability to enzyme activity and the effect on the properties of hemoglobin. The study found that compared with trehalose, the protective effect of sucrose on CA enzyme activity is non-significant to that on hemoglobin, the recovery rate of SOD, and CAT enzyme activity has significant increased. Glucose, hydroxypropyl-β-cyclodextrin, and mannitol are unsuitable for the added enzyme activity protective agent of PolyHb-SOD-CAT-CA.The protective effect of sucrose on CA was non-significant with trehalose. The protective effect of sucrose on SOD and CAT enzyme activity was higher than trehalose, and the protective effect reached the maximum when the concentration reached 1.5%.

Analysis of the mechanisms underlying the occurrence and progression of cancer represents a key objective in contemporary clinical bioinformatics and molecular biology. Utilizing omics data, particularly transcriptomes, enables a detailed characterization of expression patterns and post-transcriptional regulation across various RNA types relative to the entire transcriptome. Here, we assembled a dataset comprising transcriptomic data from approximately 16 000 patients encompassing over 160 types of cancer. We employed state-of-the-art gradient boosting algorithms to discern intricate correlations in the expression levels of four clinically significant microRNAs, specifically, hsa-mir-21, hsa-let-7a-1, hsa-let-7b, and hsa-let-7i, with the expression levels of the remaining 60 660 unique RNAs. Our analysis revealed a dependence of the expression levels of the studied microRNAs on the concentrations of several small nucleolar RNAs and regulatory long noncoding RNAs. Notably, the roles of these RNAs in the development of specific cancer types had been previously established through experimental evidence. Subsequent evaluation of the created database will facilitate the identification of a broader spectrum of overarching dependencies related to changes in the expression levels of various RNA classes in diverse cancers. In future, it will make possible to discover unique alterations specific to certain types of malignant transformations.

Influenza A virus has a wide natural areal among birds, mammals, and humans. One of the main regulatory adaptors of the virus host range is the major NP protein of the viral nucleocapsid. Phylogenetic analysis of the NP protein of different viruses has revealed the existence of two phylogenetic cohorts in human influenza virus population. Cohort I includes classical human viruses that caused epidemics in 1957, 1968, 1977. Cohort II includes the H1N1/2009pdm virus, which had a mixed avian–swine origin but caused global human pandemic. Also, the highly virulent H5N1 avian influenza virus emerged in 2021 and caused outbreaks of lethal infections in mammals including humans, appeared to have the NP gene of the second phylogenetic cohort and, therefore, by the type of adaptation to human is similar to the H1N1/2009pdm virus and seems to possess a high epidemic potential for humans. The data obtained shed light on pathways and dynamics of adaptation of avian influenza viruses to humans and propose phylogenetic algorithm for systemic monitoring of dangerous virus strains to predict epidemic harbingers and take immediate preventive measures.

Lung cancer is one of the cancer types with the highest mortality worldwide. The most frequently mutated genes known to be clinically important in lung cancers are EGFR, BRAF, and KRAS genes. Therefore, the therapeutic agents developed are directed against variants that cause over-activation of the EGFR–KRAS–BRAF–BRAF–MEK/ERK signalling pathway. However, different responses of patients to Tyrosine Kinase Inhibitors (TKIs) suggest that new prognostic biomarkers should be defined and epigenetic mechanisms may be related to this situation. Methods: In this study, sequence analyses of AGO2, DICER, and DROSHA genes involved in miRNA biogenesis and EGFR, KRAS, and BRAF genes were performed in 35 patients with sporadic lung cancer. Results: We found variations in genes involved in miRNA biogenesis that have not been previously reported in the literature. In addition, we found 4 different variants in the EGFR gene that have been described in the literature. In addition, a statistically significant association was found between the presence of mutations in at least one of the genes involved in miRNA biogenesis and metastasis (p:0.02). Conclusions: In conclusion, genomic dysregulation of key miRNA biogenesis genes may be one of the possible reasons for the differential response of patients to therapeutic agents and the development of metastasis in EGFR wild type tumours.

The effect of carbon ions (¹²C) with the energy of 400 MeV/nucleon on the dynamics of induction and growth rate of solid tumors in mice under irradiation of Ehrlich ascites carcinoma cells (EAC) ex vivo at doses of 5–30 Gy relative to the action of equally effective doses of X-ray radiation was studied. The dynamics of tumor induction under the action of ¹²C and X-rays had a similar character and depended on the dose during 3 months of observation. The value of the latent period, both when irradiating cells with ¹²C and X-ray, increased with increasing dose, and the interval for tumor induction decreased. The rate of tumor growth after ex vivo irradiation of EAC cells was independent of either dose or type of radiation. The dose at which EAC tumors are not induced within 90 days was 30 Gy for carbon ions and 60 Gy for X-rays. The value of the relative biological effectiveness of carbon ions, calculated from an equally effective dose of 50% probability of tumors, was 2.59.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease leading to inevitable disability and primarily affecting the young and middle-aged population. Recent studies have shown a direct correlation between the risk of MS development and Epstein–Barr virus (EBV) infection. Analysis of the titer of EBV-specific antibodies among patients with MS and healthy donors among Russian population confirmed that MS is characterized by an increased level of serum IgG binding EBNA-1 (EBV nuclear antigen 1). The number of patients with elevated levels of EBNA-1-specific antibodies does not differ statistically significantly between two groups with diametrically opposite courses of MS: benign MS or highly active MS. It can be assumed that the primary link between EBV and the development of MS is restricted to the initiation of the disease and does not impact its severity.

In Drosophila, a large group of actively transcribed genes is located in pericentromeric heterochromatin. It is assumed that heterochromatic proteins recruit transcription factors to gene promoters. Two proteins, Ouib and Nom, were previously shown to bind to the promoters of the heterochromatic genes nvd and spok. Interestingly, Ouib and Nom are paralogs of the M1BP protein, which binds to the promoters of euchromatic genes. We have shown that, like M1BP, the Quib and Nom proteins bind to CP190, which is involved in the recruitment of transcription complexes to promoters. Unlike heterochromatic proteins, Ouib and Nom do not interact with the major heterochromatic protein HP1a and bind to euchromatic promoters on polytene chromosomes from the larval salivary glands. The results suggest a new mechanism for the recruitment of transcription factors into the heterochromatic compartment of the nucleus.

Study of swirling flows in channels corresponding to the static approximation of flow channels of the heart and major vessels with a longitudinal–radial profile zR² = const and a concave streamlined surface at the beginning of the longitudinal coordinate has been carried out. A comparative analysis of the flow structure in channel configurations zR^N = const, where N = –1, 1, 2, 3, in the absence and presence of a concave surface was carried out. The numerical modeling was compared with the results of hydrodynamic experiments on the flow characteristics and the shape of the flow lines. The numerical model was used to determine the velocity structure, viscous friction losses, and shear stresses. Numerical modeling of steady-state flows for channels without a concave surface showed that in the channel zR² = const there is a stable vortex flow structure with the lowest viscous friction losses. The presence of a concave surface of sufficient size significantly reduces viscous friction losses and shear stresses in both the steady state and pulsed modes.

High-throughput ribosome profiling demonstrates the translation of thousands of small open reading frames located in the 5′ untranslated regions of messenger RNAs (upstream ORFs). Upstream ORF can both perform a regulatory function by influencing the translation of the downstream main ORF and encode a small functional protein or microprotein. In this work, we showed that the 5′ untranslated region of the PRPF19 mRNA encodes an upstream ORF that is translated in human cells. Inactivation of this upstream ORF reduces the viability of human cells.

In the current study the effects of metformin and cyanidin on the immune system and intestinal flora in rats with type-2 diabetes was investigated. The findings showed that metformin or cyanidin treatment considerably reduced the rise in body weight and glucose levels induced by type-2 diabetes. The type-2 diabetic rats’ glucose tolerance was significantly increased by cyanidin administration comparable to that of metformin. Cyanidin administration resulted in a significant reduction in serum cholesterol and low-density lipoprotein (LDL) levels in rats with type-2 diabetes. Treatment with cyanidin significantly increased the ratio of high-density lipoprotein to low-density lipoprotein in type-2 diabetes rats. Cyanidin administration significantly raised the ratio of Firmicutes to Bacteroidetes in the fecal samples of type-2 diabetic rats compared to the model group. In comparison to the model group, it also significantly raised the levels of Lactobacillus intestinalis, Lactobacillus gasseri, and Lactobacillus reuteri in the type-2 diabetes rats. In type-2 diabetes rat fecal samples, the abundance of Christensenellaceae significantly increased while Enterobacteriaceae and Proteobacteria were found to decrease upon cyanidin administration. Furthermore, cyanidin administration to the rats with type-2 diabetes significantly improved the glucose homeostasis. In conclusion, the study demonstrates that cyanidin enhances glucose homeostasis in rats with type-2 diabetes, potentially through controlling intestinal flora. Thus, cyanidin may be looked into more as a possible therapeutic agent for type 2 diabetes.