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.

Mitochondrial dysfunction and oxidative stress in aging and cancer

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.) and inductors of AS bulking and flocculation (Comamonadaceae, Flavobacteriaceae, etc.), which are abundantly represented in incoming sewage, were significantly decreased in AS of all WWTPs, except for the slaughterhouse wastewater, which was rich in organic matter. 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 flocculation and bulking (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.

Introduction: Enhancement of glucose metabolism and repression of oxidative phosphorylation followed by the Warburg effect is the common hallmark of cancer cells. Hexokinase II (HKII) plays a dual ...

Important molecular genetic markers of colorectal cancer

CHL1 gene (also known as CALL) on 3p26.3 encodes a one-pass trans-membrane cell adhesion molecule (CAM). Previously CAMs of this type, including L1, were shown to be involved in cancer growth and metastasis. We used Clontech Cancer Profiling Arrays (19 different types of cancers, 395 samples) to analyze expression of the CHL1 gene. The results were further validated by RT-qPCR for breast, renal and lung cancer. Cancer Profiling Arrays revealed differential expression of the gene: down-regulation/silencing in a majority of primary tumors and up-regulation associated with invasive/metastatic growth. Frequent down-regulation (>40% of cases) was detected in 11 types of cancer (breast, kidney, rectum, colon, thyroid, stomach, skin, small intestine, bladder, vulva and pancreatic cancer) and frequent up-regulation (>40% of cases) – in 5 types (lung, ovary, uterus, liver and trachea) of cancer. Using real-time quantitative PCR (RT-qPCR) we found that CHL1 expression was decreased in 61% of breast, 60% of lung, 87% of clear cell and 89% papillary renal cancer specimens (P<0.03 for all the cases). There was a higher frequency of CHL1 mRNA decrease in lung squamous cell carcinoma compared to adenocarcinoma (81% vs. 38%, P = 0.02) without association with tumor progression. Our results suggested that CHL1 is involved in the development of different human cancers. Initially, during the primary tumor growth CHL1 could act as a putative tumor suppressor and is silenced to facilitate in situ tumor growth for 11 cancer types. We also suggested that re-expression of the gene on the edge of tumor mass might promote local invasive growth and enable further metastatic spread in ovary, colon and breast cancer. Our data also supported the role of CHL1 as a potentially novel specific biomarker in the early pathogenesis of two major histological types of renal cancer.