ABSTRACT
AIM: The purpose of the study was to compare the morbidity from cancer (expressed as incidence) to the average levels of blood serum inflammatory markers in the population of the Sachkhere region (Georgia). METHODS: healthy residents of the Sachkhere district were examined. In the blood serum samples of patients, the cytokines (IL-1α, IL-10, TGF-ß, IL-12, IL-17, TNF-α, IL-6) and NOx content, as well as the total antioxidant activity of the non-enzymatic system (TAA) were determined; using light microscopy, buccal micronuclei (MnB) of epithelial cells of the oral mucosa, as indicators of chromosomal disorders, were studied. RESULTS: Study results show, that cancer incidence in Sareki was statistically significantly higher as in Chorvila and Sairkhe (p=0.002; p=0.004); in Sareki inhabitant's blood serum levels of the IL-6, NO are increased (p=0.004, p=0.05), and IL-17, TGFß, and IL-10 levels are decreased (p=0.010, p=0.001, p=0.033) in comparison to data in Chorvila; in Chorvila inhabitants' indicators of TAA of blood serum and MnB of epithelium cell levels were lower (p=0.001,p=0.045) then in Sairkhe and Sareki. CONCLUSION: The existence of statistically reliable associations between the levels of cancer incidence in the populations of the surveyed villages and the indicators of immune and oxidative status in their virtually healthy subpopulations, with a high degree of persuasiveness, allows us to assume a close causal link between them. Clarifying the reasons for the identified patterns and their significance requires more detailed studies.
Subject(s)
Neoplasms , Serum , Biomarkers , Georgia , Humans , Interleukin-10 , Interleukin-17 , Interleukin-6 , Morbidity , Neoplasms/epidemiology , Rural Population , Transforming Growth Factor betaABSTRACT
BACKGROUND: Galectins-galactose-specific lectins are involved in various types of cell activities, including apoptosis, cell cycle regulation, inflammation and cell transformation. Galectins are implicated in prostate malignat transformation. It is not known yet if prostate glands with different grade of pathologies are expressing different galectins and if these galectins express different effects on the cell viability. METHODS: Cytosolic galactose-spesific lectin fractions from prostate tissue with different diagnosis were purified by affinity chromatography and analyzed by electrophoresis in polyacrylamide gel electrophoresis with sodium dodecyl sulphate. The lectin effects in a source-dependent maner were studied on cell viability on peripheral lymphocytes by MTT reduction method and on apoptosis by flow cytometry method. RESULTS: Affinity purified galactose-specific lectins fractions from normal and pathological tissue samples are characterized with different protein composition and they express different effects on cell viability and apoptosis. CONCLUSION: The effects of cytosolic galactose-specific lectins depend on the source of lectin fraction (glandular tissue disease). We suppose that the released cytosolic galectins from prostatic high grade intraepithelial neoplasia and adenocarcinoma tissue could suppress the immune status of the host patients.
Subject(s)
Galectins/metabolism , Prostate/metabolism , Apoptosis , Biomarkers , Cell Fractionation , Disease Susceptibility , Galectins/genetics , Galectins/isolation & purification , Gene Expression Regulation , Hemagglutination , Humans , MaleABSTRACT
Background: Due to the possible biomedical potential of nanoparticles, titanium dioxide nanoparticles (TiO2 NPs) have received great attention in cancer research. Although selectivity of cytotoxicity with TiO2 NPs in various cells is clinically significant comparisons of cancer and non-cancer cells have been limited. Therefore, we here studied exposure to TiO2 NPs in colorectal cancer cells (CRCs) and human umbilical vein endothelial cells (HUVECs). Methods: After characterization of TiO2 NPs, culture and treatment of cells (HCT116, HT29 and HUVEC), viability was assessed by MTT assay and in terms of morphological features. Acridine orange (AO) and propidium iodide (PI) assays were carried out to estimate the incidence of apoptosis. The RT-PCR method was also employed to evaluate the expression of P53, Bax, Bcl-2 and Caspase 3. Results: Exposure to increasing concentrations of TiO2 NPs enhanced overall cell survival of HCT116 cells and reduced the Bcl-2 and Caspase 3 expression while the ratio of Bax/Bcl-2 was down-regulated. TiO2 NPs at 400 and 50 µg/ml concentrations suppressed cell proliferation and induced apoptosis of HT29 cells and also up-regulated P53 and Bax at the mRNA level, enhanced the Bax/Bcl-2 ratio and eventually up-regulated Caspase 3 mRNA. Although, inhibition of cell proliferation in HUVECs was seen at 200 and 400 µg/ml TiO2 NPs, it was not marked. Conclusion: TiO2 NPs have selective bio-effects on exposed cells with dose- and cell-dependent influence on viability. Cell proliferation in HCT116 as a metastatic colorectal cancer cell line appeared to be stimulated via multiple signaling pathways, with promotion of apoptosis in less metastatic cells at 50 and 400 µg/ml concentrations. This was associated with elevated P53, Bax and Caspase 3 mRNA and reduced Bcl-2 expression. However, TiO2 NPs did not exert any apparent significant effects on HUVECs as hyperproliferative angiogenic cells.
Subject(s)
Colorectal Neoplasms/drug therapy , Endothelial Cells/drug effects , Metal Nanoparticles/administration & dosage , Titanium/pharmacology , Umbilical Veins/drug effects , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Colorectal Neoplasms/metabolism , Endothelial Cells/metabolism , HCT116 Cells , HT29 Cells , Human Umbilical Vein Endothelial Cells , Humans , RNA, Messenger/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Tumor Suppressor Protein p53/metabolism , Umbilical Veins/metabolism , Up-Regulation/drug effects , bcl-2-Associated X Protein/metabolismABSTRACT
We have studied biochemical changes occurring in brain cell mitochondria of white rats on the background of stress induced by 30-day isolation and disruption of circadian rhythms. It was ascertained that due to long-lasting stress, there occurs activation of oxidative processes in mitochondria as well as inhibition of anti-oxidant system activity, causing development of energy deficiency in brain cells. The above-mentioned biochemical processes become the reason for activation and opening of the mitochondrial permeability transition pore (MPTP), which, in its turn, signals the start of neuroapoptosis and various neurodegenerative processes.
Subject(s)
Brain/metabolism , Mitochondria/metabolism , Mitochondrial Membrane Transport Proteins/metabolism , Nitric Oxide/metabolism , Stress, Physiological/physiology , Animals , Brain/drug effects , Calcium/pharmacology , Circadian Rhythm/physiology , Male , Mitochondria/drug effects , Mitochondrial Permeability Transition Pore , Nitric Oxide/biosynthesis , Rats , Rats, Wistar , Signal TransductionABSTRACT
We studied the functionality of the antioxidant system in laboratory rat cardiomyocytes and blood under psycho-emotional stress. It was found that 40-day isolation and violation of diurnal cycle among the animals were accompanied by the intensification of lipid peroxidation process and marked with a reduced activity of antioxidant system enzymes, such as catalase and superoxide dismutase activity. The results suggested that psycho-emotional stress was accompanied by oxidative stress, causing a reduction in the intensity of energy metabolism in cardiomyocytes, which was further strengthened by the fact that the activity of the enzymes involved in ATP synthesis in mitochondria was reduced. Based on the results, we proposed that psychological stress is one of the factors contributing to the development of various cardiac diseases.
