Anticancer Effects of Spiperone in C57BL/6 Mice with Emphysema and Lung Carcinoma.

The antitumor and antimetastatic activity of dopamine D2 receptor antagonists spiperone was studied in C57BL/6 mice in a model of combined pathology (emphysema and lung cancer). Emphysema was induced by administration of LPS and cigarette smoke extract. Lung cancer was induced by injection of Lewis lung carcinoma cells into the lung. It has been shown that under conditions of combined lung pathology, spiperone prevents inflammatory infiltration and emphysematous expansion of the lungs and reduces the size of the primary tumor node, the number of metastases, and the area of the lungs affected by metastases. Spiperone reduces the number of cancer stem cells (CSCs) in the lungs and blood of mice with combined pathology. CSCs isolated from the lungs and blood of mice with combined pathology treated with spiperone had a significantly lower potential to form a tumorosphere in vitro than CSCs from untreated mice with emphysema and lung carcinoma. Thus, blockade of dopamine D2 receptors is a promising approach for correcting combined lung pathology and can be used in the development of a method for treating lung cancer in patients with emphysema.

The Role of Cancer and Somatic Stem Cells in the Anti-Inflammatory and Antitumor Effects of Aconitum baicalense Extract on Experimental Breast Cancer.

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.

Effects of Age and Suntan on the Expression of Second Messenger Signaling Pathways of Necroptosis in Skin Cells during Facelifting Surgery.

We studied the effects of age and suntan on the expression of necroptosis signaling molecules (RIPK1, RIPK3, and MLKL kinases) and first TNF receptor (TNFR1) in isolated skin cells from women undergoing facelift surgery. In women above 50 years, the expression of the TNFR1, kinases RIPK1, RIPK3, and MLKL, the phosphorylated forms of these kinases was significantly (p<0.05) increased in comparison with the corresponding parameters in women under 30 years. The expression of all necroptosis proteins and TNFR1 in women with suntan was significantly (p<0.05) higher than in those without tan. Cells from the surgical material were incubated with TNFα to determine the level of induced necroptosis. In women aged >50 years and women with suntan, the expression of phosphorylated forms of kinases was significantly increased, which attested to necroptosis activation. This study allowed identifying the targets on skin cells for prevention of necrosis and inflammation after facelift surgery.

Effects of Release-Active Antibodies to CD4 Receptor on the Level of lck-Kinase in Cultured Mononuclear Cells from Human Peripheral Blood.

For evaluation of effects of release-active antibodies to CD4 on cultured lymphocytes from human peripheral blood, we measured intracellular content of lck-kinase cell-based ELISA. In cells treated with release-active antibodies to CD4, the content of intracellular lck-kinase significantly (p<0.01) decreased in comparison with the control (purified water processed in a similar way). Phytohemagglutinin had no effect on the concentration of lck-kinase in cells. The decrease in the content of CD4-associated lck protein suggests that the preparation enhanced intracellular coupling of lck-kinase with T-cell receptor and potentiated T-cell immune response.

[Cellular Model Based on Laser Microsurgery of Cell Spheroids to Study the Repair Process].

In this study, modern techniques of laser microsurgery of cell spheroids have been used to develop a new simple, reproducible model for studying the mechanisms of repair and regeneration in vitro. Nanosecond laser pulses were applied to perform a microdissection of the outer and the inner zones of the spheroids from dermal fibroblasts. To achieve effective dissection and preservation of spheroid viability, the optimal parameters were chosen: 355 nm wavelength, 100 Hz frequency, 2 ns pulse duration, laser pulses in the range of 7­9 µ J. After microdissection, we observed injury of the spheroids : the edges of the wound surface opened and the angular opening reached a value of more than 180°. As early as during the first hour after spheroid microdissection with laser radiation, the surviving cells changed their shape: cells on the spheroid surface and directly in the damaged area became rounded. One day after microdissection, the structure of the spheroids began to partially recover, the cells in the surface layers began to take the original flattened shape; debris of dead damaged cells and their fragments was gradually cleared from the spheroid composition. In the proposed model, the first data on stimulation of structure recovery of injured spheroids from dermal fibroblasts with a P199 synthetic polypeptide, which is used in cosmetology for the initiation of antiaging and regenerative effects in the skin, were received. After microdissection, recovery of the spheroids structure with a few surface layers of flattened imbricated arranged cells and polygonal cells of the inner zone in the presence of P199 peptide was faster than in the control group, and was completed within 7 days, presumably due to the remodeling of the survived cells.

[The role of innate immunity system in the course of adenomyosis].

The investigation of leukocytic elastase (LE) and alpha1-proteinase inhibitor (alpha1-PI) from patients with different stage adenomyosis and in control group was found activation innate immunity system in all the patients with adenomyosis. The degree of LE activity is a prevalence rate of adenomyosis. The degree of alpha1-PI activity is correlated with antiproteolytic potential that blocks the effects shown by LE. It can lead the prognose of disease and timely treatment.

[Level of interferon-gamma, tumor necrosis factor alpha, and antibodies to them in blood serum from Parkinson disease patients]. / Soderzhanie interferona-gamma, faktora nekroza opukholi al'fa i autoantiteal k nim v syvorotke krovi pri bolezni Parkinsona.

Serum levels of interferon-gamma (IF gamma), tumor necrosis factor alpha (TNF alpha) and autoantibodies (a-AT) to these cytokines were investigated in patients with Parkinson's disease (PD). The increased levels of TNF alpha (50%) and IF gamma (35%) were found in PD patients. There was close correlation between the serum level of TNF alpha and the manifestation of neurological symptoms (r = 0.434; p < 0.05), and between levels of IF gamma and the duration of this disease (r = 0.4511, p < 0.05) and patients age as well (r = 0.4358; p < 0.05). There was increased level of a-AT to TNF alpha in PD patients versus healthy controls (130.3 +/- 11.92 and 105.3 +/- 4.62, respectively, p < 0.05). The combined increase of levels of a-AT to TNF alpha and IF gamma (r = 0.91, p < 0.01) close reverse correlation between duration of PD and levels of a-AT to TNF alpha and IF gamma (r = 0.4644 and r = 0.606, respectively, p < 0.01) were also recognised. The data obtained suggest the involvement of TNF alpha and IF gamma into the pathological process during PD, which requires further investigation in this direction.

[Autoantibodies against nerve tissue proteins long after cranio-cerebral injury]. / Autoantitela k belkam nervnoi tkani v otdalennom periode cherepno-mozgovoi travmy.

20 samples of serum of patients with remote consequences of brain trauma were tested to detect autoantibodies (a-AB) against brain proteins S-100 and NKP. Essential pathology was not found out by standard solid-phase immunoassay. The original method was used to detect a-AB to the whole complex of antigen determinants. Using this method the elevation of a-AB against S-100 and NKP was shown at 16 cases. The disturbance of idiotype-antiidiotype regulation was revealed at this group of patients. It is suggested that insufficient level of corresponding antiidiotypes creates the conditions for autoimmune aggressor of a-AB against brain tissue.

[Autoantibodies to brain tissue antigens in epilepsy patients]. / Autoantitela k antigenam tkani mozga u bol'nykh épilepsiei.

The observation of 38 patients with different forms of epilepsy was carried out in terms of autoantibodies (aAB) to nervous tissue proteins: p16, p30 and S-100. The pathological increase or decrease of aAB titers to at least one of the antigens (AG) mentioned above was found in 31 cases. The qualitatively new approach was further used for the revelation of aAB to S-100. Not the very protein was adsorbed on the plates for immunoenzyme assay but antiidiotypic Abs which were the "mirror reflection" of corresponding protein molecules' determinants. The authors suggested that the method permitted to estimate the level of aAB to the whole complex of AG determinants. Thus, the percent of positive tests was approximately twice higher. The index of aAB binding by corresponding anti-idiotypes was decreased in 29 patients. It's quite possible that it formed some conditions for brain tissue damages by aAB.

[Immunoenzyme analysis of ferritin in diagnosing brain tumors]. / Immunofermentnyi analiz ferritina v diagnostike opukholei golovnogo mozga.

A procedure was developed to purify ferritin from the human brain tissue. The preparation is a heavy chain of ferritin. The level of ferritin in biological fluids was evaluated using the sandwich solid-phase immunoassay. This fraction of ferritin was found in the cerebrospinal fluid of patients with brain tumors. Content of the ferritin heavy chain in cerebrospinal fluid correlated with the rate of brain tissue malignancy.

[The immunoenzyme analysis of the specific alpha2-glycoprotein in the brain in patients with neuropsychic diseases]. / Immunofermentnyi analiz spetsificheskogo al'fa2-glikoproteida mozga u bol'nykh nervno-psikhicheskimi zabolevaniiami.

The authors have developed an enzyme immunoassay test system for measurements of the specific cerebral alpha 2-glycoprotein (alpha 2-GP), whose sensitivity limit is 0.8 ng/ml. Blood serum alpha 2-GP level is 7 ng/ml, cerebrospinal fluid level is 12.8 ng/ml in health; detection of alpha 2-GP in these biological fluids in concentrations surpassing such values indicates impairment of the hematoencephalic barrier permeability and active release of the cerebral proteins into the blood. The hematoencephalic barrier is most frequently disrupted in the brain-blood direction in purulent meningitis, encephalitis, open craniocerebral injuries; such impairments may be detected with the use of alpha 2-GP measurements. A direct correlation between the blood serum alpha 2-GP level and the severity of the disease clinical course has been revealed.