Reactive oxygen species (ROS) are by-products of normal cell activity. They are produced in many cellular compartments and play a major role in signaling pathways. Overproduction of ROS is associated with the development of various human diseases (including cancer, cardiovascular, neurodegenerative, and metabolic disorders), inflammation, and aging. Tumors continuously generate ROS at increased levels that have a dual role in their development. Oxidative stress can promote tumor initiation, progression, and resistance to therapy through DNA damage, leading to the accumulation of mutations and genome instability, as well as reprogramming cell metabolism and signaling. On the contrary, elevated ROS levels can induce tumor cell death. This review covers the current data on the mechanisms of ROS generation and existing antioxidant systems balancing the redox state in mammalian cells that can also be related to tumors.

Aging and cancer are the most important issues to research. The population in the world is growing older, and the incidence of cancer increases with age. There is no doubt about the linkage between aging and cancer. However, the molecular mechanisms underlying this association are still unknown. Several lines of evidence suggest that the oxidative stress as a cause and/or consequence of the mitochondrial dysfunction is one of the main drivers of these processes. Increasing ROS levels and products of the oxidative stress, which occur in aging and age-related disorders, were also found in cancer. This review focuses on the similarities between ageing-associated and cancer-associated oxidative stress and mitochondrial dysfunction as their common phenotype.

DNA double-strand breaks (DSBs) are involved in many cellular mechanisms, including replication, transcription, and genome rearrangements. The recent observation that hot spots of DSBs in human chromosomes delimit DNA domains that possess coordinately expressed genes suggests a strong relationship between the organization of transcription patterns and hot spots of DSBs. In this study, we performed mapping of hot spots of DSBs in a human 43-kb ribosomal DNA (rDNA) repeated unit. We observed that rDNA units corresponded to the most fragile sites in human chromosomes and that these units possessed at least nine specific regions containing clusters of extremely frequently occurring DSBs, which were located exclusively in non-coding intergenic spacer (IGS) regions. The hot spots of DSBs corresponded to only a specific subset of DNase-hypersensitive sites, and coincided with CTCF, PARP1, and HNRNPA2B1 binding sites, and H3K4me3 marks. Our rDNA-4C data indicate that the regions of IGS containing the hot spots of DSBs often form contacts with specific regions in different chromosomes, including the pericentromeric regions, as well as regions that are characterized by H3K27ac and H3K4me3 marks, CTCF binding sites, ChIA-PET and RIP signals, and high levels of DSBs. The data suggest a strong link between chromosome breakage and several different mechanisms of epigenetic regulation of gene expression.

Activated sludge (AS) plays a crucial role in the treatment of domestic and industrial wastewater. AS is a biocenosis of microorganisms capable of degrading various pollutants, including organic compounds, toxicants, and xenobiotics. We performed 16S rRNA gene sequencing of AS and incoming sewage in three wastewater treatment plants (WWTPs) responsible for processing sewage with different origins: municipal wastewater, slaughterhouse wastewater, and refinery sewage. In contrast to incoming wastewater, the taxonomic structure of AS biocenosis was found to become stable in time, and each WWTP demonstrated a unique taxonomic pattern. Most pathogenic microorganisms (Streptococcus, Trichococcus, etc.), which are abundantly represented in incoming sewage, were significantly decreased in AS of all WWTPs, except for the slaughterhouse wastewater. Additional load of bioreactors with influent rich in petroleum products and organic matter was associated with the increase of bacteria responsible for AS bulking and foaming. Here, we present a novel approach enabling the prediction of the metabolic potential of bacterial communities based on their taxonomic structures and MetaCyc database data. We developed a software application, XeDetect, to implement this approach. Using XeDetect, we found that the metabolic potential of the three bacterial communities clearly reflected the substrate composition. We revealed that the microorganisms responsible for AS bulking and foaming (most abundant in AS of slaughterhouse wastewater) played a leading role in the degradation of substrates such as fatty acids, amino acids, and other bioorganic compounds. Moreover, we discovered that the chemical, rather than the bacterial composition of the incoming wastewater was the main factor in AS structure formation. XeDetect (freely available: https://sourceforge.net/projects/xedetect) represents a novel powerful tool for the analysis of the metabolic capacity of bacterial communities. The tool will help to optimize bioreactor performance and avoid some most common technical problems.

Colorectal cancer is one of the most common cancers in the world. It is well known that the chronic inflammation can promote the progression of colorectal cancer (CRC). Recently, a number of studies revealed a potential association between colorectal inflammation, cancer progression, and infection caused by enterotoxigenic Bacteroides fragilis (ETBF). Bacterial enterotoxin activates spermine oxidase (SMO), which produces spermidine and H2O2 as byproducts of polyamine catabolism, which, in turn, enhances inflammation and tissue injury. Using qPCR analysis, we estimated the expression of SMOX gene and ETBF colonization in CRC patients. We found no statistically significant associations between them. Then we selected genes involved in polyamine metabolism, metabolic reprogramming, and inflammation regulation and estimated their expression in CRC. We observed overexpression of SMOX, ODC1, SRM, SMS, MTAP, c-Myc, C/EBPβ (CREBP), and other genes. We found that two mediators of metabolic reprogramming, inflammation, and cell proliferation c-Myc and C/EBPβ may serve as regulators of polyamine metabolism genes (SMOX, AZIN1, MTAP, SRM, ODC1, AMD1, and AGMAT) as they are overexpressed in tumors, have binding site according to ENCODE ChIP-Seq data, and demonstrate strong coexpression with their targets. Thus, increased polyamine metabolism in CRC could be driven by c-Myc and C/EBPβ rather than ETBF infection.