Proteins of the TRIM family are involved in both innate immunity and the nervous system processes and may play an important role in the development of neurodegenerative diseases. In this work, we analyzed the expression of 35 genes of the TRIM family in neural progenitors (NPs), terminally differentiated neurons (TDNs) and glial derivatives (NGs) obtained from induced pluripotent stem cells (iPSCs) of healthy donors (HD) and patients with Parkinson's disease (PD), in the absence of inflammatory stimuli and upon the induction of a nonspecific inflammatory response under the influence of TNFα. In NPs and TDNs of PD patients, compared with HD cells, differences in expression were observed for only a small number of TRIM genes. Under the influence of TNFα in TDNs, the expression of individual TRIM genes was activated, which was more significant in the cells of patients with PD compared to cells of HDs. In NGs of PD patients, the expression of many TRIM genes was initially reduced compared to HD cells and remained low or further decreased after exposure to TNFα. The data obtained demonstrate differences in the network of the TRIM family members in PD neurons and glia compared to control, and also show the multidirectional influence of the inflammatory stimulus on the expression of a number of TRIM genes in these types of cells. Considering the important role of many TRIM genes in the functioning of the innate immune system, it can be assumed that, in PD, more significant disturbances in the functioning of genes of this family occur in glia compared to neurons.

Multiple exogenous or endogenous factors alter gene expression patterns by different mechanisms that are poorly understood. We used RNA-Seq analysis in order to study changes in gene expression in melanoma cells that are capable of vasculogenic mimicry that is inhibited upon the action of an inhibitor of vasculogenic mimicry. Here, we show that the drug induces a strong upregulation of 50 genes that control the cell cycle and microtubule cytoskeleton coupled with a strong downregulation of 50 genes that control different cellular metabolic processes. We found that both groups of genes are simultaneously regulated by multiple sets of transcription factors. We conclude that one way for coordinated regulation of large groups of genes is regulation simultaneously by multiple transcription factors.

Uveal melanoma (UM) is a neuroectodermal tumor that results from malignant transformation of melanocytes in the eye uvea, including the iris, the ciliary body, and the choroid. UM accounts for 5% of all melanoma cases and is extremely aggressive with half of the UM patients developing metastases within the first 1-2 years after tumor development. Molecular mechanisms of UM carcinogenesis are poorly understood, but are known to differ from those of skin melanoma. Activating mutations of the GNAQ and GNA11 genes, which code for the large G protein subunits Gq and G11, respectively, are found in 90% of UM patients. The Gaq/PKC/MAPK signaling pathway is a main signaling cascade that leads to the transformation of melanocytes of the uveal tract, and major regulators of the cascade provide targets for the development of drugs. Metastatic UM (MUM) is most often associated with mutations of BAP1, EIF1AX, GNA11, GNAQ, and SF3B1. A combination of a commercial expression test panel of 15 genes and a mutation panel of 7 genes, supplemented with data on the size of the primary tumor, is highly efficient in predicting the risk of metastasis. The risk of metastasis determines the choice of therapy and the patient follow-up regimen. However, no systemic therapy for MUM has been developed to date. New drugs undergoing clinical trials are mostly targeted drugs designed to inhibit the protein products of mutant genes or immunotherapeutic agents designed to stimulate the immune response against specific antigens. In addition to these approaches, potential therapeutic targets of epigenetic regulation of UM development are considered in the review.

The main molecular mechanisms of the protective effect of minor bioactive compounds (BAC) of food, including rutin and hesperidin, along with antiradical and antioxidant activity, include their interaction with transcription factors modulating the functional state of the organism defense systems, one of which is the system of xenobiotic metabolizing enzymes. However, the data on their combined action are limited. The aim of the research was to study the effect of rutin and hesperidin on the activity and gene expression of cytochrome P450 isoforms 1A and 3A (CYP1A1, CYP1A2, CYP3A) in rat liver at their separate and combined intake. Material and methods. The study was carried out using 4 groups of 6 male Wistar rats with initial body weight 225±5 g. For 14 days the rats of the control group received a standard semi-synthetic diet. Rutin and hesperidin were administered separately or together at a calculated daily dose of 400 mg per 1 kg body weight. CYP1A1 and CYP1A2 activities were determined spectrofluorimetrically in liver microsomal fraction, CYP3A activity - by high-performance liquid chromatography. Gene expression was analyzed by real-time reverse transcription polymerase chain reaction. Results. Dietary intake of rutin and hesperidin did not significantly alter the activity of the studied enzymes of xenobiotic metabolism, but had an inducing effect on CYP1A1 and CYP1A2 genes, expression of which statistically significant increased both at separate and combined intake. The expression of CYP3A1 gene did not differ from control values at intake of rutin alone, but considerably and statistically significant decreased in the presence of hesperidin in the diet. An increase in transcription factor AhR gene expression was noted, moreover the expression in the group receiving rutin + hesperidin was significantly reduced in relation to the group receiving rutin alone. Conclusion. Combined intake of flavonoids (rutin and hesperidin) has a modulating effect on enzymes of xenobiotic metabolism at the level of their gene expression.

The Epstein-Barr virus (EBV), one of the most common in the human population, is capable of lifelong persistence in resting memory B-cells, in T-cells in case of type 2 EBV, and in some undifferentiated epithelial cells. In most people, EBV persistence is not accompanied by significant symptoms, but frequent virus activations are associated with the increased risks of severe diseases, such as chronic active Epstein-Barr virus infection, hemophagocytic lymphohistiocytosis, multiple sclerosis, systemic lupus erythematosus, gastric and nasopharyngeal carcinomas, and a variety of T- and B-cell lymphomas. Therefore, the molecular viral and host cell processes during asymptomatic or low-symptom EBV persistence are of great interest. This review describes the behavior of the viral DNA in an infected cell and the forms of its existence (linear, circular episome, chromosomally integrated forms), as well as methods of EBV genome copying. Two closely related cycles of viral reproduction are considered. Lytic activation is unfavorable for the survival of a particular viral genome in the cell, and may be a result of differentiation of a latently infected cell, or the arrival of stress signals due to adverse extracellular conditions. The EBV has a large number of adaptive mechanisms for limiting lytic reactivation and reducing hostility of host immune cells. Understanding the molecular aspects of EBV persistence will help in the future develop more effective targeted drugs for the treatment of both viral infection and associated diseases.

Medicines from the group of interferon inducers (IFNs) "swith on" the synthesis of type 1 interferons (IFN-I) and induce the expression of IFN-stimulated genes (ISGs) that regulate innate immunity reactions and protect the host from infectious agents and the tumour pathology.The purpose of the study was to determine the role of the drug celagrip (CA) in the activation of innate immunity genes and the effect on the production of reactive oxygen species (ROS) in patients with follicular lymphoma (FL).

In hepatocellular carcinoma (HCC), the presence of cancer stem cells (CSCs) have been linked to drug resistance, epithelial-mesenchymal transition (EMT), and cancer relapse. This study investigates the expression profile of ZEB1, ZEB2, ABCG2 in HCC-CSCs, and the role of EMT promoter ZEB2 in cells treated with resveratrol. The expression of ZEB1, ZEB2 and ABCG2 transcripts were analyzed in CD133^(+)/CD44^(+) cells isolated from the PLC/PRF/5 cell line. ZEB2-dependent ABCG2 gene expression and the effects of resveratrol on proliferation, cell cycle and apoptosis were explored in SNU398 cell clones. An inverse correlation between ZEB1/ZEB2 and ABCG2 levels were observed both in CSCs and in ZEB2-knock-down cells. The resveratrol treatment significantly decreased cell viability, while promoting cell cycle arrest in ZEB2-independent manner. Interestingly, resveratrol-treated cells with low levels of ZEB2 were resistant to apoptosis. The interplay of expression levels of ABCG2 and ZEB family EMT transcription factors may play a role in establishing CSC-like phenotype in HCC cells resistant to resveratrol.