Experimental evidence suggests an immense variety of processes associated with and aimed at producing reactive oxygen and/or nitrogen species. Clinical studies implicate an enormous range of pathologies associated with reactive oxygen/nitrogen species metabolism deregulation, particularly oxidative stress. Recent advances in biochemistry, proteomics and molecular biology/biophysics of cells suggest oxidative stress to be an endpoint of complex dysregulation events of conjugated pathways consolidated under the term, proposed here, "oxidative status". The oxidative status concept, in order to allow for novel diagnostic and therapeutic approaches, requires elaboration of a new logic system comprehending all the features, versatility and complexity of cellular pro- and antioxidative components of different nature. We have developed a curated and regularly updated interactive interactome map of human cellular-level oxidative status allowing for systematization of the related most up-to-date experimental data. A total of more than 600 papers were selected for the initial creation of the map. The map comprises more than 300 individual factors with respective interactions, all subdivided hierarchically for logical analysis purposes. The pilot application of the interactome map suggested several points for further development of oxidative status-based technologies.

Although further testing of the approach is required, the interactomic pathway activation assaying concept was preliminarily experimentally proven to be a highly promising clinical diagnostic tool that may easily be adapted for current tasks.

Uterine cervical incompetence (UCI) is a pregnancy complication affecting about 10% of the pregnancies in the western world. Studying the etiology of the UCI requires a specific approach adequate for this highly heterogenous syndrome. Oxidative status disorders are associated with various pathologies, including pregnancy complications. As such, general oxidative status profiling is a promising methodology to treat UCI. We aimed at assaying the closely interrelated oxidative status markers in the uterine cervical incompetence patients by means of the systems biology-oriented approach. Chemiluminescent assay, circulating thioredoxin 1 protein, uric acid, and homocysteine level measurements were used to assess the character of the oxidative status regulation in the UCI patients. We found UCI to be associated with the atypical plasma oxidative status deregulation; UCI plasma samples demonstrated lowered proneness to the pro-oxidative processes, and this was not due to the excessive antioxidant activity. There were neither signs of oxidative stress nor destructive pro-oxidant feedforward circuit locking in the UCI group. We also report increased circulating levels of uric acid in the UCI patients.

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Pathway activity assessment-based approaches are becoming highly influential in various fields of biology and medicine. However, these approaches mostly rely on analysis of mRNA expression, and total mRNA from a given locus is measured in the majority of cases. Notably, a significant portion of protein-coding genes produces more than one transcript. This biological fact is responsible for significant noise when changes in total mRNA transcription of a single gene are analyzed. The NFE2L2/AP-1 pathway is an attractive target for biomedical applications. To date, there is a lack of data regarding the agreement in expression of even classical target genes of this pathway. In the present paper we analyzed whether transcript variants of GPX2, NQO1 and SQSTM1 were characterized by individual features of expression when HeLa cells were exposed to pro-oxidative stimulation with hydrogen peroxide. We found that all the transcripts (10 in total) appeared to be significantly individually regulated under the conditions tested. We conclude that individual transcripts, rather than total mRNA, are best markers of pathway activation. We also discuss here some biological roles of individual transcript regulation.