ABSTRACT
The responses of tumor stem cells and various populations of CD4 and CD8 T cells of young and aged C57BL/6 mice were studied in a lung cancer model. Using Lewis lung carcinoma cell line, an orthotopic model of lung cancer was modeled. Cancer stem cells, circulating tumor cells, and various populations of CD4 and CD8 T cells in the blood and lung tissue were studied by cytometry. We revealed age-related differences in the content of various populations of CD4 and CD8 T cells in the blood and lungs of intact young and aged mice. Age-related features of the reaction of various populations of cancer stem cells and CD4 and CD8 T cells in the blood and lungs of animals in the Lewis lung carcinoma were shown.
Subject(s)
Carcinoma, Lewis Lung , Lung Neoplasms , Animals , Mice , Carcinoma, Lewis Lung/pathology , Mice, Inbred C57BL , Lung Neoplasms/pathology , CD8-Positive T-Lymphocytes/metabolism , Neoplastic Stem Cells/metabolismABSTRACT
We studied the effects of the extract of the terrestrial part of Aconitum baicalense in BALB/c female mice at the early stages after the injection of N-methyl-N-nitrosourea (MNU). The extract reduced inflammatory activity and tumor growth in the mammary gland. The antitumor and anti-inflammatory effects of the extract are based on the inhibition of cancer stem cells, hematopoietic stem cells, and hematopoietic progenitor cells that promote inflammation. The extract of A. baicalense disrupted the recruitment of epithelial progenitor cells and angiogenesis precursors to the mammary gland preventing neovascularization and transformation of epithelial cells into tumor cells.
Subject(s)
Aconitum , Adult Stem Cells , Mammary Neoplasms, Experimental , Female , Mice , Animals , Methylnitrosourea , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Adult Stem Cells/pathology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Mammary Neoplasms, Experimental/chemically induced , Mammary Neoplasms, Experimental/drug therapy , Mammary Neoplasms, Experimental/pathologyABSTRACT
Regenerative processes in the liver were studied in 3-month-old (young) and 9-month-old (aged) male Wistar rats on day 1 after 30 and 70% hepatectomy. Regardless of the resected liver volume, shifts in the biochemical parameters of the serum in aged rats were more pronounced than in young animals. After 30% hepatectomy, no age differences in the rate of hepatic regeneration were found, while after 70% liver resection this parameter was higher in young rats. Hepatectomy in young rats led to recruitment of MSC, hepatocyte precursors, endothelial and epithelial progenitor cells into the liver parenchyma and increased fluidity of the plasma and mitochondrial membranes of hepatocytes. In aged rats, the recruitment of MSC, hepatocyte precursors, and endothelial progenitor cells into the injured liver was impaired and the rigidity of the mitochondrial membranes of hepatocytes increased.
Subject(s)
Hepatectomy , Liver Regeneration , Rats , Male , Animals , Rats, Wistar , Liver/surgery , HepatocytesABSTRACT
Various stem cells were studied in female BALB/c mice at the early terms after administration of N-methyl-N-nitrosourea to search early diagnostic markers and therapeutic targets. At these terms, damage to the epithelium and endothelium, inflammation, and fibrosis were observed in the mammary gland, but the tumor was not detected. Cancer stem cells, hematopoietic stem cells (HSC), hematopoietic progenitor cells, angiogenic precursors, and epithelial progenitor cells were found in the blood and mammary gland. Cancer stem cells (CD44+CD24-) are proposed as the early diagnostic marker of breast cancer, and short-living HSC, hematopoietic progenitor cells, and angiogenic precursors (CD45-CD117+FLK-1+) as predictors of the formation of tumor microenvironment.
Subject(s)
Breast Neoplasms , CD24 Antigen , Animals , Biomarkers, Tumor , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Line, Tumor , Epithelium/pathology , Female , Hematopoietic Stem Cells/pathology , Humans , Hyaluronan Receptors , Mice , Neoplastic Stem Cells/pathology , Tumor MicroenvironmentABSTRACT
The viscosity of plasma and mitochondrial membranes of hepatocytes was studied in young (3-month-old) and old (9-month-old) male Wistar rats. It was shown that viscosity of hepatocyte plasma and mitochondrial membranes in young rats under optimal vital functions in the area of protein-lipid membrane contacts was significantly lower than in old rats. No age-related differences in the viscosity of lipid-lipid membrane contacts and in the polarity of protein-lipid contacts and lipid layers were found. Liver cirrhosis induced by carbon tetrachloride and ethanol administration was associated with increased fluidity of the plasma and mitochondrial membranes of hepatocytes in rats of both age groups. The decrease in membrane viscosity in young rats occurred due to a decrease of the viscosity in the area of protein-lipid and lipid-lipid contacts, while in old rats in the area of protein-lipid contacts. Carbon tetrachloride and ethanol did not affect the polarity of lipid contacts and lipid layers.
Subject(s)
Carbon Tetrachloride/toxicity , Ethanol/toxicity , Hepatocytes/drug effects , Liver Cirrhosis, Experimental/metabolism , Liver/drug effects , Age Factors , Animals , Cell Membrane/chemistry , Cell Membrane/drug effects , Hepatocytes/metabolism , Hepatocytes/pathology , Liver/metabolism , Liver/pathology , Liver Cirrhosis, Experimental/chemically induced , Liver Cirrhosis, Experimental/pathology , Male , Mitochondria/chemistry , Mitochondria/drug effects , Mitochondrial Membranes/chemistry , Mitochondrial Membranes/drug effects , Rats , Rats, Wistar , Viscosity/drug effectsABSTRACT
We studied the age-related characteristics of the response of stem cells and liver in male Wistar rats to administration of carbon tetrachloride (CCl4) and ethanol. It was shown that modeling of liver cirrhosis caused inflammation, fibrosis, damage to sinusoidal capillaries, necrosis, and disturbances in the functional activity of hepatocytes in young rats. These processes were accompanied by mobilization of profibrotic mesenchymal stem cells (MSC), proinflammatory hematopoietic stem cells (HSC) and lymphocytes (CD45hiCD133+) from the bone marrow into the blood and migration to the liver. On the other hand, the number of hepatocyte precursors expressing Sox9 (cells of Hering's canal), immature cholangiocytes, Ito cells, oval cells, and endothelial cells of the liver sinusoids) sharply increased in the liver. In young rats, mobilization and migration of MSC, HSC, and hepatocyte precursors against the background of liver cirrhosis were more intensive than in old animals. The higher resistance of old rats to exposure is associated with age-related changes in the niches as well as in mobilization and migration of cells.
Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Animals , Carbon Tetrachloride/toxicity , Endothelial Cells , Hepatocytes/pathology , Liver/metabolism , Liver Cirrhosis/metabolism , Male , Rats , Rats, WistarABSTRACT
We studied the formation of injuries in lung endothelium and the response of angiogenesis cells during modeling of pulmonary emphysema in male and female C57BL/6 mice with metabolic disorders. Hemodynamic disturbances and reduction in the area of the microvasculature caused by combined pathology in male mice were more pronounced than in females. Mobilization and migration of angiogenic precursors were impaired in both male and female mice. In males, activity of recruiting endothelial progenitor cells, vascular smooth muscle cells, luminal cells of nascent vessels and pericytes into the lungs was additionally reduced. In females, accumulation of endothelial progenitor cells (CD45-CD31+CD34+), vascular smooth muscle cells, and pericytes in the lungs was observed, which indicated activation of endothelial regeneration. Sex differences in the reaction of the lung endothelium and angiogenesis cells can be explained by genetic factors of lipid and glucose metabolism.
Subject(s)
Endothelium/metabolism , Endothelium/pathology , Lung/metabolism , Lung/pathology , Pulmonary Emphysema/metabolism , Pulmonary Emphysema/pathology , Animals , Antigens, CD34/metabolism , Dyslipidemias/metabolism , Dyslipidemias/pathology , Female , Hyperglycemia/metabolism , Hyperglycemia/pathology , Leukocyte Common Antigens/metabolism , Male , Mice , Mice, Inbred C57BL , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Sex CharacteristicsABSTRACT
We studied the effects of spiperone, a selective blocker of dopamine D2 receptors, on the model of pulmonary emphysema provoked by administration of elastase and D-galactosamine hydrochloride to female C57BL/6 mice and characterized by activation of proteases in the lungs and systemic deficiency of its inhibitor α1-antitrypsin. In this model, spiperone prevented the development of inflammatory reaction and reduced the area of emphysematous expanded alveolar tissue. The expression of angiogenic marker CD31 in the lungs increased under these conditions. Regeneration of the damaged microvascular bed under the action of spiperone resulted from recruiting of Notch1+ endothelial progenitor cells (CD45-CD31+CD34+) into the lungs and blockade of the inhibitory effect of dopamine on phosphorylation of VEGF-2 receptors in endothelial cells of different maturity. In addition, spiperone produced a protective effect on hepatocytes and restored the production and secretion of α1-antitrypsin by these cells.
Subject(s)
Dopamine Antagonists/pharmacology , Endothelial Progenitor Cells/drug effects , Pulmonary Emphysema/drug therapy , Receptor, Notch1/genetics , Receptors, Dopamine D2/genetics , Spiperone/pharmacology , alpha 1-Antitrypsin Deficiency/drug therapy , Animals , Endothelial Progenitor Cells/metabolism , Endothelial Progenitor Cells/pathology , Female , Galactosamine/administration & dosage , Gene Expression Regulation , Hepatocytes/drug effects , Hepatocytes/metabolism , Hepatocytes/pathology , Liver/drug effects , Liver/metabolism , Liver/pathology , Lung/drug effects , Lung/metabolism , Lung/pathology , Mice , Mice, Inbred C57BL , Neovascularization, Physiologic/drug effects , Pancreatic Elastase/administration & dosage , Phosphorylation/drug effects , Platelet Endothelial Cell Adhesion Molecule-1/genetics , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Pulmonary Emphysema/chemically induced , Pulmonary Emphysema/genetics , Pulmonary Emphysema/metabolism , Receptor, Notch1/agonists , Receptor, Notch1/metabolism , Receptors, Dopamine D2/metabolism , Regeneration/drug effects , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-2/metabolism , alpha 1-Antitrypsin/genetics , alpha 1-Antitrypsin/metabolism , alpha 1-Antitrypsin Deficiency/enzymology , alpha 1-Antitrypsin Deficiency/genetics , alpha 1-Antitrypsin Deficiency/pathologyABSTRACT
To study collagen metabolism in reparative regeneration of duodenal ulcer in response to peat mud electrophoresis of Uva sanatorium using sinusoidal modulated currents (SMC) as monotherapy in a day hospital, 82 duodenal ulcer patients in exacerbation or attenuation were examined. They received SMC-electrophoresis of peat mud diluted by sulfate sodium-calcium mineral water Uvinskaya of moderate mineralization. The dynamics of clinico-endoscopic and morphological picture of the disease was controlled with fibrogastroduodenoscopy with target biopsy of the periulcer zone and antral stomach, investigation of secretory and acid-producing function of the stomach, hormone profile and collagen metabolism. Positive changes were found attributed to favourable shifts in the hormone status and normalization of collagen metabolism in duodenal mucosa.
