AI-Assisted Identification of Primary and Secondary Metabolomic Markers for Postoperative Delirium.

Despite considerable investigative efforts, the molecular mechanisms of postoperative delirium (POD) remain unresolved. The present investigation employs innovative methodologies for identifying potential primary and secondary metabolic markers of POD by analyzing serum metabolomic profiles utilizing the genetic algorithm and artificial neural networks. The primary metabolomic markers constitute a combination of metabolites that optimally distinguish between POD and non-POD groups of patients.

Reconstruction and analysis of the gene regulatory network for cell wall function in Arabidopsis thaliana L. leaves in response to water deficit.

The plant cell wall represents the outer compartment of the plant cell, which provides a physical barrier and triggers signaling cascades under the influence of biotic and abiotic stressors. Drought is a factor that negatively affects both plant growth and development. Cell wall proteins (CWP) play an important role in the plant response to water deficit.

Molecular-genetic pathways of hepatitis C virus regulation of the expression of cellular factors PREB and PLA2G4C, which play an important role in virus replication.

The participants of Hepatitis C virus (HCV) replication are both viral and host proteins. Therapeutic approaches based on activity inhibition of viral non-structural proteins NS3, NS5A, and NS5B are undergoing clinical trials. However, rapid mutation processes in the viral genome and acquisition of drug resistance to the existing drugs remain the main obstacles to fighting HCV.

Prioritization of potential pharmacological targets for the development of anti-hepatocarcinoma drugs modulating the extrinsic apoptosis pathway: the reconstruction and analysis of associative gene networks help.

Hepatocellular carcinoma (HCC) is a common severe type of liver cancer characterized by an extremely aggressive course and low survival rates. It is known that disruptions in the regulation of apoptosis activation are some of the key features inherent in most cancer cells, which determines the pharmacological induction of apoptosis as an important strategy for cancer therapy. The computer design of chemical compounds capable of specifically regulating the external signaling pathway of apoptosis induction represents a promising approach for creating new effective ways of therapy for liver cancer and other oncological diseases.

Reconstruction of the regulatory hypermethylation network controlling hepatocellular carcinoma development during hepatitis C viral infection.

Hepatocellular carcinoma (HCC) has been associated with hepatitis C viral (HCV) infection as a potential risk factor. Nonetheless, the precise genetic regulatory mechanisms triggered by the virus, leading to virus-induced hepatocarcinogenesis, remain unclear. We hypothesized that HCV proteins might modulate the activity of aberrantly methylated HCC genes through regulatory pathways.

Primary and Secondary micro-RNA Modulation the Extrinsic Pathway of Apoptosis in Hepatocellular Carcinoma.

-One of the most common malignant liver diseases is hepatocellular carcinoma, which has a high recurrence rate and a low five-year survival rate. It is very heterogeneous both in structure and between patients, which complicates the diagnosis, prognosis and response to treatment. In this regard, an individualized, patient-centered approach becomes important, in which the use of mimetics and hsa-miRNA inhibitors involved in the pathogenesis of the disease may be determinative.

[Primary and Secondary micro-RNA Modulation the Extrinsic Pathway of Apoptosis in Hepatocellular Carcinoma].

One of the most common malignant liver diseases is hepatocellular carcinoma, which has a high recurrence rate and a low five-year survival rate. It is very heterogeneous both in structure and between patients, which complicates the diagnosis, prognosis and response to treatment. In this regard, an individualized, patient-centered approach becomes important, in which the use of mimetics and hsa-miRNA inhibitors involved in the pathogenesis of the disease may be determinative.

The impact of short-term confinement on human innate immunity.

During space missions cosmonauts are exposed to a myriad of distinct stressors such as radiation, overloads, weightlessness, radiation, isolation in artificial environmental conditions, which causes changes in immune system. During space flights it is very difficult to determine the particular factor associated with the observed immunological responses. This makes ground-based experiments examining the effect of each space flight associated factor along of particular value.

[Non-delusional hypochondriac disorders in old age].

This review aims to present main concepts of hypochondria and 'hypochondriac mood' in old age. Attention is paid to historical and modern positions of old age hypochondria as a meta-syndromic pathology and as an independent mental disorder. Relationships of hypochondriac manifestations with affective variations and anxiety disorders, as well as somatic diseases, organic degenerative brain diseases and vascular disorders are discussed.

Analysis of femurs from mice embarked on board BION-M1 biosatellite reveals a decrease in immune cell development, including B cells, after 1 wk of recovery on Earth.

Bone loss and immune dysregulation are among the main adverse outcomes of spaceflight challenging astronauts' health and safety. However, consequences on B-cell development and responses are still under-investigated. To fill this gap, we used advanced proteomics analysis of femur bone and marrow to compare mice flown for 1 mo on board the BION-M1 biosatellite, followed or not by 1 wk of recovery on Earth, to control mice kept on Earth.

[TOLL-LIKE RECEPTORS IN COSMONAUT'S PERIPHERAL BLOOD CELLS AFTER LONG-DURATION MISSIONS TO THE INTERNATIONAL SPACE STATION].

Studies of Toll-like receptors (TLR) in 20 cosmonauts-members of long-duration (124-199-day) missions to the International space station evidenced changes in relative and absolute counts of peripheral blood monocytes with TLR2, TLR4 and TLR6 on the surface, expression of TLR2 and TLR6 genes, and genes of molecules involved in the TLR signaling pathway and TLR-related NF-KB-, JNK/p38- and IRF pathways on the day of return to Earth. The observed changes displayed individual variability.

[Status of the osteoclast-activating system in cosmonauts after long-duration missions to the International Space Station].

The results of studying the system of osteoprotegerin/ receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) in 22 cosmonauts after long-duration (124 to 199 days) ISS missions are presented. Immediately on return to 1 g, changes were observed in OPG and RANKL serum levels and the ability to produce unstimulated and stimulated PGA of peripheral blood mononuclear cells in vitro. Individual variability of these changes was noticed.

[Immunological aspects of a piloted mission to Mars].

The paper deals with the results of the effects of 520-day isolation and confinement modeling some elements of a mission to Mars on the immune system. Longitudinal analyses revealed that the mechanisms of adaptive response of the human immune system to the conditions of extremely long isolation led to a change of the parameters, characterizing innate and adaptive immunity. Among them the most important are: changes in the signaling PRRs--TLR, manifested in the reduction of the percentage of circulating monocytes and granulocytes expressed on its own surfaces TLR2, TLR4 and TLR6, decreases early NK cell activation potential, increases in the percentage T- and B-lymphocytes, that expressed early activation marker CD69 after adequate stimulation, and in production of cytokines in response to PHA stimulation.

[Analysis of the relationships between the psychophysiological status and system of adaptive immunity in the conditions of 5-day dry immersion].

Relationships of the T- and B-components of adaptive immunity and the psychophysiological status were studied in 14 volunteers for the experiment with 5-d dry immersion (DI) w/o countermeasures. Comparison of frequency of deviations in immunity parameters of psychologically different subjects demonstrated the highest frequency in non-anxious and extravert individuals on day-5 in DI. These differences in immune reactions as a function of psychological type and temperament point to existence of a neuroimmune typology and, therefore, the necessity of concurrent immunologic and psychological investigations in order to develop separate measures of rehabilitation from and prevention of stress in people with polar psychological status.

[Congenital human immunity during 5-day dry immersion].

The system of congenital immunity was studied in 12 essentially healthy males 18 to 26 years of age subjected to 5-day dry immersion without use of countermeasures. Peripheral blood was analyzed for monocytes, granulocytes and lymphocytes expressing the TLR2+, TLR4+, TLR6+, CD11b+, CD14+, CD16+, CD18+, CD24+, CD36+, CD54+, CD56+ and CD206+ receptors. Expression of early activation marker CD69 on lymphocytes-natural killers was studied in unstimulated and interleukin-2 activated mononuclear cell cultures.

[Indicators of innate and adaptive immunity of cosmonauts after long-term space flight to international space station].

Results of innate and adaptive immunity indicators research at 12 cosmonauts who took part in long (128-215 days) expeditions to the International space station (ISS) are presented. It is shown that a space flight can lead to deflection of deviations in human immune system. These shifts occurred in decrease of phagocytes, NK, T-lymphocytes functional activity and also in abilities of immunocompetent cells to synthesize cytokines.

[Human immunity system status during 7-day dry immersion].

Subpopulations of lymphocytes, activation potential of T-, B- and NK-cells as well as cytokines production by immunocompetent cells in peripheral blood were studied in five volunteers for 7-day dry immersion without use of countermeasures. Results of the investigation revealed several negative shifts in the immunity and cytokines systems instigated by the experimental conditions. The considerable variability of the immune reactions to immersion suggests individual predisposition to immunological breaks in a changed gravity environment.

[Immune system parameters of healthy humans in a chamber experiment with hyperbaric oxygen-nitrogen-argon air].

The investigation into the immune effects of 9-d exposure to elevated pressures of normoxic and hypoxic O2-N-Ar atmosphere showed changes in a number of indices of genetic and adaptive immunity in normal humans. Dynamics and depth of the functional shifts under the influence of the experimental factors appear to be connected with genetically coded mechanisms of immunoreactivity. Monitoring of immune homeostasis is basic to the prevention of immune adaptation failure.

[The activation processes of the immune system during low intensity exercise without relaxation].

The activation processes of T-, B- and NK-cells were studied during 8-week low intensity strength training without relaxation. After the long-term training, no changes occurred in the peripheral blood contents of the main subpopulations of immunocompetent cells (CD3+, CD4+, CD8+, CD19+ and CD16+/CD56+ lymphocytes) and serum levels of immunoglobulin A, M, and G. At the same time, training was accompanied by positive activation of the immunocompetent cells which was evident from increased percentage of CD3+, CD19+ and /CD56+ cells expressing CD69 after activation (PHA, PW and II.

[Immunoglobulin e and allergen-specific IgE antibodies in cosmonauts before and after long-duration missions on the International Space Station].

Immunoglobulins (IgG, IgA, IgM, IgE), specific IgE-antibodies, and interleukin-4 (IL-4) were investigated in blood serum of nine cosmonauts before and after 128- to 195-day ISS missions. It was shown that long-duration space flight does not change significantly the content of serum immunoglobulins, allergen-specific IgE-antibodies or IL-4. Analysis for probable ratios of the total IgE and IL-4 contents in the pre- and post-flight periods did not reveal any linear correlation of these parameters.

Cell interactions in microgravity: cytotoxic effects of natural killer cells in vitro.

To study cell-to-cell interactions in microgravity we examined the functional activity of natural killer cells on board of the ISS. NK cells are the effector cells with direct cytotoxic activity to oncogenic, virus-infected cells and cells with modified differentiation. Ground-based experiments have shown that the examination of target cell lysis after incubation with NK cells is a simple and informative model for studying the influence of microgravity.

[Modification of a method for determining the cytotoxic activity of lymphocytes--natural killers in space experiments].

A space modification of a method for determining the cytotoxic activity of natural killers (NK) uses cultures of human lymphocytes and re-inoculated suspension of tumorous myeloblasts K-562. The 3H-uridine labeled target-cells fixated in 0.1 % formalin solution proved to be best suited to the conditions prohibiting regular recharge of cultural medium and utilization of radioactive agents.