The investigation of alkylresorcinols has drawn an increasing interest recently. Alkylresorcinols (ARs) are natural chemical compounds synthesized by bacteria, fungi, sponges, and higher plants, possessing a lipophilic polyphenol structures and a myriad of biological properties. Human takes ARs as a component of a whole grain diet (from whole grain rye, wheat, and barley products), and thus, alkylresorcinols are frequently used as whole grain intake markers. Besides, ARs are considered as promising bioregulators of metabolic and immune processes, as well as adjuvant therapeutic agents for antimicrobial and anticancer treatment. In this review, we attempted to systematize the accumulated information concerning ARs origin, metabolism, biological properties, and their effect on human health.

The role of lactic acid (lactate) in cell metabolism has been significantly revised in recent decades. Initially, lactic acid was attributed to the role of a toxic end-product of metabolism, with its accumulation in the cell and extracellular space leading to acidosis, muscle pain, and other adverse effects. However, it has now become obvious that lactate is not only a universal fuel molecule and the main substrate for gluconeogenesis but also one of the most ancient metabolites, with a signaling function that has a wide range of regulatory activity. The Warburg effect, described 100 years ago (the intensification of glycolysis associated with high lactate production), which is characteristic of many malignant tumors, confirms the key role of lactate not only in physiological conditions but also in pathologies. The study of lactate’s role in the malignant transformation becomes more relevant in the light of the “atavistic theory of carcinogenesis,” which suggests that tumor cells return to a more primitive hereditary phenotype during microevolution. In this review, we attempt to summarize the accumulated knowledge about the functions of lactate in cell metabolism and its role in the process of carcinogenesis and to consider the possible evolutionary significance of the Warburg effect.

Alkylresorcinols (ARs) are polyphenolic compounds with a wide spectrum of biological activities and are potentially involved in the regulation of host metabolism. The present study aims to establish whether ARs can be produced by the human gut microbiota and to evaluate alterations in content in stool samples as well as metabolic activity of the gut microbiota of C57BL, db/db, and LDLR (−/−) mice according to diet specifications and olivetol (5-n-pentylresorcinol) supplementation to estimate the regulatory potential of ARs. Gas chromatography with mass spectrometric detection was used to quantitatively analyse AR levels in mouse stool samples; faecal microbiota transplantation (FMT) from human donors to germ-free mice was performed to determine whether the intestinal microbiota could produce AR molecules; metagenome sequencing analysis of the mouse gut microbiota followed by reconstruction of its metabolic activity was performed to investigate olivetol’s regulatory potential. A significant increase in the amounts of individual members of AR homologues in stool samples was revealed 14 days after FMT. Supplementation of 5-n-Pentylresorcinol to a regular diet influences the amounts of several ARs in the stool of C57BL/6 and LDLR (−/−) but not db/db mice, and caused a significant change in the predicted metabolic activity of the intestinal microbiota of C57BL/6 and LDLR (−/−) but not db/db mice. For the first time, we have shown that several ARs can be produced by the intestinal microbiota. Taking into account the dependence of AR levels in the gut on olivetol supplementation and microbiota metabolic activity, AR can be assumed to be potential quorum-sensing molecules, which also influence gut microbiota composition and host metabolism.

Currently, obesity is a critical global public health burden. Numerous studies have demonstrated the regulation of the pathogenesis of obesity and metabolic abnormalities by the gut microbiota and microbial factors; however, their involvement in the various degrees of obesity is not yet well understood. Previously, obesity has been shown to be associated with decreased levels of vitamin B12. Considering exclusive microbial production of vitamin B12, we hypothesized that a decrease in cobalamin levels in obese individuals may be at least partially caused by its depleted production in the intestinal tract by the commensal microbiota. In the present study, our aim was to estimate the abundance of enzymes and metabolic pathways for vitamin B12 synthesis in the gut microbiota of mouse models of alimentary and genetically determined obesity, to evaluate the contribution of the obesogenic microbiome to vitamin B12 synthesis in the gut. We have defined a significantly lower predicted abundance of enzymes and metabolic pathways for vitamin B12 biosynthesis in obese mice compared to non-obese mice, wherein enzyme depletion was more pronounced in lepr(−/−) (db/db) mice, which developed severe obesity. The predicted abundance of enzymes involved in cobalamin synthesis is strongly correlated with the representation of several microbes in high-fat diet-fed mice, while there were almost no correlations in db/db mice. Therefore, the degree of obesity and the composition of the correspondent microbiota are the main contributors to the representation of genes and pathways for cobalamin biosynthesis in the mouse gut.

Background: The discovery of RNA interference phenomenon (RNAi) and understanding of its mechanisms has revolutionized our views on many molecular processes in the living cell. Among the other, RNAi is involved in silencing of transposable elements and in inhibition of virus infection in various eukaryotic organisms. Recent experimental studies demonstrate few cases of viral replication suppression via complementary interactions between the mammalian small RNAs and viral transcripts. Presentation of the hypothesis: It was found that >50% of the human genome is transcribed in different cell types and that these transcripts are mainly not associated with known protein coding genes, but represent non-coding RNAs of unknown functions. We propose a hypothesis that mammalian DNAs encode thousands RNA motifs that may serve for antiviral protection. We also presume that the evolutional success of some groups of genomic repeats and, in particular, of transposable elements (TEs) may be due to their ability to provide antiviral RNA motifs to the host organism. Intense genomic repeat propagation into the genome would inevitably cause bidirectional transcription of these sequences, and the resulting double-stranded RNAs may be recognized and processed by the RNA interference enzymatic machinery. Provided that these processed target motifs may be complementary to viral transcripts, fixation of the repeats into the host genome may be of a considerable benefit to the host. It fits with our bioinformatical data revealing thousands of 21-28 bp long motifs identical between human DNA and human-pathogenic adenoviral and herpesviral genomes. Many of these motifs are transcribed in human cells, and the transcribed part grows proportionally to their lengths. Many such motifs are included in human TEs. For example, one 23 nt-long motif that is a part of human abundant Alu retrotransposon, shares sequence identity with eight human adenoviral genomes. Testing the hypothesis: This hypothesis could be tested on various mammalian species and viruses infecting mammalian cells. Implications of the hypothesis: This hypothesis proposes that mammalian organisms may use their own genomes as sources of thousands of putative interfering RNA motifs that can be recruited to repress intracellular pathogens like proliferating viruses. Reviewers: This article was reviewed by Eugene V. Koonin, Valerian V. Dolja and Yuri V. Shpakovski.

Advances in cancer molecular profiling have enabled the development of more effective approaches to the diagnosis and personalized treatment of tumors. However, treatment planning has become more labor intensive, requiring hours or even days of clinician effort to optimize an individual patient case in a trial-and-error manner. Lessons learned from the world cancer programs provide insights into ways to develop approaches for the treatment strategy definition which can be introduced into clinical practice. This article highlights the variety of breakthroughs in patients cancer treatment and some challenges that this field faces now in Russia. In this report, we consider the key characteristics for planning an optimal clinical treatment regimen and which should be included in the algorithm of clinical decision support systems. We discuss the perspectives of implementing artificial intelligence-based systems in cancer treatment planning in Russia.