Aptamers are short single-stranded nucleic acid molecules with a unique ability to bind with high specificity andaffinity to a wide range of biomolecules, including proteins, viruses, and small molecules, due to the formation of tertiary structures, making them a powerful alternative to antibodies in biosensing, diagnostics, and therapy. Their advantages, such as high stability, the possibility of targeted chemical modification, and reproducible solid-phase synthesis without the use of cell-based systems or bioreactors, have driven the active development of methods for their design and optimization. This review systematizes the key stages in the evolution of aptamer development technologies, starting with the classic SELEX technology, and considers its modifications, including CE-SELEX, M-SELEX, Cell-SELEX, HT-SELEX, and others, aimed at improving the efficiency, specificity, and automation of the process. Special attention is paid to the integration of computational methods such as secondary and tertiary structure prediction (RNAfold, MXfold2, RNAComposer), molecular docking (AutoDock Vina, HADDOCK, ZDOCK), molecular dynamics (GROMACS, AMBER, NAMD), and SELEX data analysis (AptaSUITE, FASTAptamer). The implementation of machine learning and deep learning algorithms (AptaDiff, RaptGen, Apta-MCTS, Xelari) is also described, opening up new opportunities for the rational design of de novo aptamers, optimization of their affinity, and minimization of experimental costs. The review discusses the limitations of the current methods, such as limited amount of structural data, the complexity of predicting noncanonical pairs and pseudoknots, and the insufficient generalizability of ML models to new sequence families. This review highlights the transformative potential of aptamers in biomedicine but emphasizes the need for rigorous experimental validation of computational predictions to overcome current limitations.
A set of genes activated by the hormone ecdysone has previously been identified in the salivary glands of wandering Drosophila larvae, along with a group of regulatory elements involved in transcriptional induction by ecdysone. New evidence was obtained to implicate the DNA-binding protein Crol in the transcriptional regulation of ecdysone-dependent genes in larval salivary glands. Crol was shown to bind to the promoters and enhancers of ecdysone-depending genes, demonstrating an increased binding in the salivary glands, where the genes are active, compared to brain tissue, where the genes are silent. Crol was found to prime the recruitment of the ecdysone receptor (EcR) at least on some ecdysone-dependent enhancers. Disruption of Crol binding at these sites in crol knockout larvae reduced the EcR binding level and decreased the transcriptional level of genes possessing the respective regulatory elements. Based on the findings, Crol was assumed to function as one of the many proteins that render regulatory regions susceptible to EcR binding, thereby enabling the specific effect of ecdysone on D. melanogaster tissues.
Brain malignancies, such as glioblastoma, remain one of the most aggressive and difficult-to-treat cancers because of their heterogeneity, invasive growth, and resistance to conventional therapy. Significant recent progress in the treatment of these diseases has been associated with the development of gene and cell technologies, which open up new possibilities for targeted therapy, immunotherapy, and personalized approaches. The review systematically summarizes the data on current treatment strategies, including gene therapy, cell therapy, and combined approaches. Particular attention is paid to preclinical and clinical studies, as well as the prospects for overcoming major limitations, such as the blood-brain barrier, the immunosuppressive tumor microenvironment, and toxicity. Analysis of the literature demonstrates that integration of gene and cell technologies could provide a basis for developing effective treatments aimed at improving the survival of patients with central nervous system tumors.
RecQ helicases are a conserved family of DNA-unwinding enzymes that play a key role in maintaining genomic stability by participating in DNA damage repair, recombination, replication, and telomere homeostasis. Five RecQ helicases are known in humans: BLM (the Bloom syndrome protein), WRN (Werner syndrome helicase), RECQL4, RECQL1, and RECQL5. All members of the RecQ family possess 3' → 5' helicase activity and are capable of unwinding DNA, including its complex secondary structures, in the 3'-to-5' direction by using the energy of ATP hydrolysis. WRN is unique among RecQ helicases in possessing additional 3' → 5' exonuclease activity, which expands its functionality in maintaining genomic stability. Mutations of the RecQ helicase genes lead to Werner, Bloom, and Rothmund–Thomson syndromes and are associated with a predisposition to cancer and premature aging. The enzymes consequently attract significant interest of the scientific community. Many viruses rely on host cell replication and repair mechanisms for their reproduction, and RecQ helicases may therefore influence the development of viral infections. The review discusses the role of RecQ helicases in replication of various viruses, including socially significant ones, such as the human immunodeficiency virus, herpes simplex virus, Epstein–Barr virus, hepatitis C virus, and others.
The history of research on lactate is quite interesting. At first, it was considered an unnecessary product of glycolysis, which humans use only by converting it back into glucose (gluconeogenesis, Cori cycle). Then it turned out that it is a ready-made source of food for cells and, moreover, that some cells (neurons) may prefer it to glucose. Lactate receptors were discovered, and it became a regulator. Finally, in 2019 (after more than 200 years of study), the lactylation of histones and other proteins ( hundreds of targets) was discovered. Lactate became an epigenetic regulator. A single, very small molecule combines many functions. One of the main functions of interest to oncologists is that lactate, together with hypoxia, is a sign of supply dysfunction in the body and causes reactions aimed at normalization (angiogenesis, etc.). As a result, tumors, with the immune system silent, undergo “normalization,” with blood vessels growing in them to reduce hypoxia and the lactate concentration. In addition, in the tumor microenvironment, where the concentration of lactate is dozens of times higher than normal, lactate acts as an immunosuppressant. In recent years, antitumor therapy has been reoriented from targeting tumor cells themselves to targeting immune cells (using “checkpoints”). Lactate has become one of the targets of such therapy. Various aspects of the molecular biology of lactate are covered in this review. Particular attention is paid to the role of lactate in antitumor therapy.
