Recent cancer immunotherapy breakthroughs have fundamentally changed oncology and revived the fading hope for a cancer cure. The immune checkpoint inhibitors (ICI) became an indispensable tool for the treatment of many malignant tumors. Alongside ICI, the application of oncolytic viruses in clinical trials is demonstrating encouraging outcomes. Dozens of combinations of oncolytic viruses with conventional radiotherapy and chemotherapy are widely used or studied, but it seems quite complicated to highlight the most effective combinations. Our review summarizes the results of clinical trials evaluating oncolytic viruses with or without genetic alterations in combination with immune checkpoint blockade, cytokines, antigens and other oncolytic viruses as well. This review is focused on the efficacy and safety of virotherapy and the most promising combinations based on the published clinical data, rather than presenting all oncolytic virus variations, which are discussed in comprehensive literature reviews. We briefly revise the research landscape of oncolytic viruses and discuss future perspectives in virus immunotherapy, in order to provide an insight for novel strategies of cancer treatment.

The hereditary aspect of obesity is a major focus of modern medical genetics. The genetic background is known to determine a higher-than-average prevalence of obesity in certain regions, like Oceania. There is evidence that dysfunction of brown adipose tissue (BAT) may be a risk factor for obesity and type 2 diabetes (T2D). A significant number of studies in the field focus on the UCP family. The Ucp genes code for electron transport carriers. UCP1 (thermogenin) is the most abundant protein of the UCP superfamily and is expressed in BAT, contributing to its capability of generating heat. Single nucleotide polymorphisms (SNPs) of Ucp1–Ucp3 were recently associated with risk of cardiometabolic diseases. This review covers the main Ucp SNPs A–3826G, A–1766G, A–112C, Met229Leu, Ala64Thr (Ucp1), Ala55Val, G–866A (Ucp2), and C–55 T (Ucp3), which may be associated with the development of obesity, disturbance in lipid metabolism, T2D, and cardiovascular diseases.

Transcriptional regulators are crucial in adipocyte differentiation. We now show that the homeodomain-containing transcription factor Prep1 is a repressor of adipogenic differentiation since its down-regulation (DR) in both ex vivo bone marrow-derived mesenchymal stromal cells (MSC) and in vitro 3T3-L1 preadipocytes significantly increases their adipogenic differentiation ability. Prep1 acts at a stage preceding the activation of the differentiation machinery because its DR makes cells more prone to adipogenic differentiation even in the absence of the adipogenic inducers. Prep1 DR expands the DNA binding landscape of C/EBPβ (CCAAT enhancer binding protein β) without affecting its expression or activation. The data indicate that Prep1 normally acts by restricting DNA binding of transcription factors to adipogenic enhancers, in particular C/EBPβ.

Insulin stimulates carbohydrate uptake by cells and induces their conversion into lipids as a more efficient form of energy storage. Insulin resistance is associated with a decrease in glucose uptake by muscle and adipose cells and also with a decrease in glycogen synthesis on retention of glucose synthesis by liver cells. Disorders in the insulin signaling cascade on development of insulin resistance can be caused by both changes in functioning of transcriptional factors and in the secretion profile of hormone-like substances. Diacylglycerols and ceramides responsible for activation of some kinases and phosphatases can directly trigger these changes in muscle and liver cells. In adipose tissue, insulin mainly stimulates adipogenesis (adipocyte differentiation) and lipogenesis (lipid accumulation in the cells). Thus, studies on the action mechanisms of factors influencing adipogenesis can be of help for understanding the molecular mechanisms of insulin resistance.

роблема метаболического синдрома, харак-теризующегося развитием висцерального ожирения в сочетании с инсулинорезистент-ностью и артериальной гипертензией, является крайне актуальной в настоящее время. Особую роль в разви-тии метаболического синдрома играет жировая ткань. Она чувствительна к действию инсулина, и, в то же время, является одним из основных регуляторов метаболизма. Ее избыточное развитие, возникающее за счет гипер-плазии и/или гипертрофии составляющих ее клеток, сначала приводит к развитию ожирения, а затем и ин-сулинорезистентности. Транскрипционный каскад, обуславливающий развитие клеток жировой ткани, относительно хорошо изучен, и известно множество факторов, регулирующих транскрипцию генов в адипо-цитах. Однако для более полного понимания адипоген-ной дифференцировки необходим комплексный взгляд на процесс. Молекулярные и клеточные механизмы адипогенеза