Purpose: The aim of our research was to study sex differences and the severity of inflammatory changes in target organs and the peculiarities of immunological disorders when low and high doses of lipopolysaccharide (LPS) were administered to rats. Methods: Male and female 2- to 3-month-old Wistar rats (200–250 g) were injected intraperitoneally with Escherichia coli LPS in one of two doses: 1.5 or 15 mg/kg. In a day after the LPS injection, we studied endotoxin, corticosterone, sex steroids, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity levels in the serum; morphological disorders in the lung, liver, thymus, and spleen; ex vivo production of IL-2, IL-4, tumor necrosis factor (TNF), and interferon γ (IFNγ) by splenic cells activated by ConA; and relative amount of T- and B-lymphocytes in the peripheral blood. Results: After the injection of low-dose LPS, the serum endotoxin level increased only in males and was combined with a more pronounced inflammatory response in the lungs and thymus and an increase in ALT and AST activity levels without any changes in corticosterone level. After the injection of high-dose LPS, the inflammatory and pathological changes in the target organs manifested as severe endotoxemia and sex differences of pathological changes in the lungs and liver were not revealed. The level of production of IL-2, IL-4, IFNγ, and TNF by splenic cells and the number of T-lymphocytes, including cytotoxic cells, in the peripheral blood, decreased in males, which is an evidence of a pronounced suppression of the immune response. Conclusion: We have shown that the morphofunctional changes in the organs of the immune system in females and males, as well as the intensity of the sex differences of inflammation, depend on the severity of systemic inflammatory response, induced by different doses of LPS.

Background: In our studies, it was shown that the effectiveness of the conditioned medium obtained by cultivating mesenchymal stem cells depends on the microenvironment conditions used to cultivate the cells. It was demonstrated that the conditioned medium obtained by culturing cells with low oxygen content (10%) has a much more pronounced protective effect. Methods: Protein compositions obtained from MSCs cultured under hypoxic (10% O₂ hc-MSC) and normal (21% O₂ nc-MSC) conditions were used to treat acute liver failure (ALF) induced in mice by acetaminophen injection. Thus, we obtained fractions normalized by volume, which predominantly contained proteins with masses > 50, 50-30, 30-10, and 10-3 kDa. Results: The data from biochemical studies have shown that only fractions from 10 to 30 kDa (hcMSC and ncMSC) significantly reduced the level of liver enzymes in the beginning of the acute period after acetaminophen administration. Mass spectrometry analysis of the proteins contained in the isolated fractions showed a sharp increase in the protein levels in the 10-30 kDa hcMSC fraction as compared with that in 10-30 kDa ncMSCs. The composition obtained from MSCs cultured at lower O₂ level (fraction 10-30 kDa hcMSC) was shown to be more potent than the composition prepared from normoxic cells. Conclusion: The results have shown that a composition obtained by culturing the cells under a reduced content of O₂ (10%), significantly improves the biochemical parameters, and histological arrester reduces the degree of inflammation and stimulates regenerative processes in liver, compared to both the control group and group treated with the composition that was obtained by culturing the cells under normal oxygen content.

Chronic overuse of common pharmaceuticals, e.g. acetaminophen (paracetamol), often leads to the development of acute liver failure (ALF). This study aimed to elucidate the effect of cultured mesenchymal stem cells (MSCs) proteome on the onset of liver damage and regeneration dynamics in animals with ALF induced by acetaminophen, to test the liver protective efficacy of MSCs proteome depending on the oxygen tension in cell culture, and to blueprint protein components responsible for the effect. Protein compositions prepared from MSCs cultured in mild hypoxic (5% and 10% O₂₎ and normal (21% O₂) conditions were used to treat ALF induced in mice by injection of acetaminophen. To test the effect of reduced oxygen tension in cell culture on resulting MSCs proteome content we applied a combination of high performance liquid chromatography and mass-spectrometry (LC–MS/MS) for the identification of proteins in lysates of MSCs cultured at different O₂ levels. The treatment of acetaminophen-administered animals with proteins released from cultured MSCs resulted in the inhibition of inflammatory reactions in damaged liver; the area of hepatocyte necrosis being reduced in the first 24 h. Compositions obtained from MSCs cultured at lower O₂ level were shown to be more potent than a composition prepared from normoxic cells. A comparative characterization of protein pattern and identification of individual components done by a cytokine assay and proteomics analysis of protein compositions revealed that even moderate hypoxia produces discrete changes in the expression of various subsets of proteins responsible for intracellular respiration and cell signaling. The application of proteins prepared from MSCs grown in vitro at reduced oxygen tension significantly accelerates healing process in damaged liver tissue. The proteomics data obtained for different preparations offer new information about the potential candidates in the MSCs protein repertoire sensitive to oxygen tension in culture medium, which can be involved in the generalized mechanisms the cells use to respond to acute liver failure.

Objective: The molecular mechanisms of bladder cancer development and progression are not clear. Bladder cancer is an important focus for epidemiological studies and understanding clinical implications. Goal: The primary aim of prevention is achieved by limiting exposure to non-genetic risk factors such as smoking, diet, arsenic in drinking water, or aromatic amines at work or elsewhere. Current therapies for bladder cancer are affected by tumor morphology and associated acquired genetic mutations. Methods: A literature search was performed using PubMed, Scopus, ResearchGate, Google, MEDLINE, and ScienceDirect databases to find studies of bladder cancer published between 1984 and early 2020. The focus was articles that address epidemiological risk factors and underlying pathophysiological mechanism. Articles were selected that enabled our review of these factors as well as molecular and structural patterns. Results: There are multiple views of bladder cancer. The literature offers a number of novel insights regarding the development and progression of bladder cancer and possible biomarkers that may be useful in clinical and diagnostic practice. Conclusion: There are several molecular pathways associated with bladder cancer that are frequently updated. In addition, genetic subtypes of bladder tumors are not distinguished clearly that requires future more detailed analysis.