Search

Goal. To analyze gene expression in patients with cerebral insufficiency during the critical period and during late convalescence after severe neuroinfection. Materials and methods. The study involved patients with infectious diseases aged from 3 to 17 years, admitted for treatment to the department of resuscitation and intensive care of the Federal State Budgetary Institution DNACIB FMBA of Russia. Whole blood samples were collected before the start of therapy — «Acute period» and during the period of late convalescence after the disease (9, 12, 13 months). RNA sequencing was performed to analyze differential gene expression. Results. Statistically significant differences in expression in the comparison group «Acute period» and «Late convalescence» were detected in 14 genes. Thus, in the «Acute period» group, 12 genes with decreased expression and 2 genes with increased expression were identified: ANGPTL2, encoding angiopoietin-like protein 2 and PCK1 of the phosphoenolpyruvate carboxykinase enzyme. Of the 14 genes, 5 had unknown functions and unidentified orthologues. Conclusion. The authors suggest that increased expression of the ANGPTL2 gene may be the cause of the consequences of hypoxia, which leads to acute cerebral failure during a severe infectious process. Increased expression of PCK1 may indicate increased brain glucose demand during recovery.

Objective: to look for differences in the transcriptome profiles in mononuclear blood cells of a group of patients with radiologically isolated syndrome (RIS) who developed symptoms of multiple sclerosis (MS) in the following three years of observation and a group of patients with RIS who did not develop MS during this period.Material and methods. The study included 19 patients with RIS (9 men and 10 women), six of whom developed symptoms of MS during the three-year follow-up period. The transcription profiles of blood mononuclear cells were compared between the groups of patients with RIS who developed or did not develop MS symptoms during this period. The work was conducted in the format of a prospective study; the time of blood collection was taken as the reference point. Full transcriptome profiling was performed using RNA sequencing on an MGISEQ-200 platform. Differential gene expression analysis was performed using the DESeq2 package for the R programming language. Subsequent analysis involved constructing a network of interactions between the protein products of the detected differentially expressed genes based on data from the STRING database, identifying a cluster of interacting proteins, and analyzing the enrichment of this cluster by participants in pathways annotated in the KEGG database.Results. The expression of 146 genes differed significantly (p1) in the studied groups of patients with RIS: in patients with subsequent manifestation of MS symptoms, the expression of 67 genes was lower and expression of 79 genes was higher than in patients without MS symptoms. The decrease in expression of two of the 67 genes (ADGRG7 and LGALS9C) remained significant even after correction for multiple comparisons (padj=2.17⋅10-11 and padj=6.19⋅10-6, respectively). Analyzing the network of interactions between the protein products of the differentially expressed genes allowed the identification of a cluster of 12 genes: APBB2, CCL4, CCL4L2, CDH2, DAZL, FOSB, H2BC17, JUN, KLF4, KLF5, MAPK8IP1, SYCE1; it is over-represented by components of the Toll-like receptor signaling pathway.Conclusion. The transcriptome profiles of blood mononuclear cells differ in groups of patients with RIS who did or did not develop MS symptoms during the three-year follow-up period. The decrease in the expression level of ADGRG7 and LGALS9C genes detected in this study as a sign of rapid conversion of RIS to MS needs to be confirmed in independent samples.

Abiotic stressors like salt and drought are two examples that may harm crop production. Therefore, increasing production and creating stress-tolerant cultivars requires crop innovation in response to these stresses. Whole genome sequence (WGS) data releases are used for crop trait development. Tolerance to abiotic stress cannot be induced through single-gene engineering transformation. Plants like finger millet can be mined for undiscovered genes because they already have the gene in their genomes, but it is dormant. Therefore, abiotic stress-tolerant genes can be expressed in the same plant by RNA sequencing and transcriptomics by creating abiotic stress for agricultural development. New genes can have their profiles refined with the aid of this transcriptome research.

The purpose of the study was to identify functional features of circulation monocytes in patients with nonmetastatic breast cancer.Material and Methods. The study cohort consisted of 10 breast cancer patients treated at Tomsk Cancer Research Institute. 7 healthy female volunteers were enrolled as a control group. CD14+16-, CD14+16+ and CD14-16+ monocytes subsets were obtained from blood by sorting. Whole transcriptome profling was provided in monocytes from patients and healthy females. Macrophages were differentiated from the obtained monocytes under in vitro conditions. The ability of conditioned media obtained from macrophages to infuence apoptosis and proliferation of MDA-MB 231 cell line was evaluated.Results. Transcriptomic profling revealed signifcant changes in monocytes of breast cancer patients. CD14+16- subset showed higher expression of transporters ABCA1 and ABCG1; chemokines CCR1, CRRL2, CXCR4; maturation and differentiation factors Mafb and Jun; endocytosis mediating factors CD163 and Siglec1; proteases and tetrasponins ADAM9, CD151, CD82, and growth factor HBEGF in patient group. Macrophages derived from monocytes of breast cancer patients produced factors that supported proliferation of the MDA-MB 231 cell line, which was not observed for monocytes from healthy volunteers.Conclusion. Thus, breast carcinoma has a systemic effect on peripheral blood monocytes, programming them to differentiate into macrophages with tumor supporting capacity.

Aim. Heart failure (HF) is accompanied by skeletal muscle atrophy and exercise intolerance. The aim was to study the molecular mechanisms underlying the therapeutic effect of personalized exercise in patients with HF.Material and methods. RNA sequencing obtained from skeletal muscle biopsies before and after a 12-week exercise course was used to identify changes in gene expression and signaling pathways induced by the physical rehabilitation program for patients with HF.Results. We have shown that personalized exercise program in patients with HF stimulates the activation of molecular pathways regulating the differentiation and functioning of skeletal muscles: commitment of muscle progenitor cells; mechanisms regulating the calcium release and sensitivity of myofibrillar contraction, electrical excitability of the muscle membrane, synaptic vesicle proton gradient creation, maintenance of electrochemical gradients of Na+ /K+ . Also, the analysis of differentially expressed genes revealed an increase in the expression of transcription factors MyoD and MEF2, which are responsible for the differentiation of muscle stem cells, and sarcomeric genes MYOM1, MYOM2, MYH7. Along with this, we observed activation of the CYR61 expression — a potential prognostic biomarker for HF patients.Conclusion. Our data show that the beneficial effect of personalized aerobic exercise in patients with HF depends, at least in part, on an improvement in the physiological and biochemical parameters of skeletal muscle.

Modern techniques of next-generation sequencing (NGS) allow obtaining expression profile of all genes and provide an essential basis for characterizing metabolism in the organism of interest on a broad scale. An important condition for obtaining a demonstrative physiological picture using high throughput sequencing data is the availability of the genome sequence and its sufficient annotation for the target organism. However, a list of species with properly annotated genomes is limited. Transcriptome profiling is often performed in the so-called non-model organisms, which are those with unknown or poorly assembled and/or annotated genome sequences. The transcriptomes of non-model organisms are possible to investigate using algorithms of de novo assembly of the transcripts from sequences obtained as the result of RNA sequencing. A physiological interpretation of the data is difficult in this case because of the absence of annotation of the assembled transcripts and their classification by metabolic pathway and functional category. An algorithm for transcriptome profiling in non-model organisms was developed, and a transcriptome analysis was performed for the basidiomycete Lentinus edodes. The algorithm includes open access software and custom scripts and encompasses a complete analysis pipeline from the selection of cDNA reads to the functional classification of differentially expressed genes and the visualization of the results. Based on this algorithm, a comparative transcriptome analysis of the nonpigmented mycelium and brown mycelial mat was performed in L. edodes. The comparison revealed physiological differences between the two morphogenetic stages, including an induction of cell wall biogenesis, intercellular communication, ion transport, and melanization in the brown mycelial mat.