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Minchenko D.M.,Ukrainian Academy of Sciences | Minchenko D.M.,National Oo Bohomolets Medical University | Lypova N.M.,Ukrainian Academy of Sciences | Harmash Y.A.,Ukrainian Academy of Sciences | And 4 more authors.
Research Journal of Pharmaceutical, Biological and Chemical Sciences | Year: 2013

The endoplasmic reticulum-nuclei-1 (ERN1) sensing and signaling enzyme mediates a set of complex intracellular signaling events known as the unfolded protein response. We have studied the effect of hypoxia on the expression of genes encoded different 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB1, PFKFB2, PFKFB3 and PFKFB4) and 6-phosphofructo-1-kinase (PFKL, PFKM and PFKP) as well as lactate dehydrogenase (LDHA) in glioma U87 cells and its subline with suppressed function of ERN1 signaling enzyme. It was shown that blockade a function of ERN1 enzyme, the key endoplasmic reticulum stress sensor, leads to an increase in the expression levels of PFKFB1, PFKFB2, PFKFB3 and PFKFB4 mRNA, being more significant for PFKFB4 and PFKFB2. Moreover, the expression level of PFKL and PFKP as well as LDHA mRNA also increases in cells with ERN1 loss of function, being more significant for PFKL. At the same time, the expression level of PFKM mRNA significantly decreases at this experimental condition. Exposure cells under hypoxic conditions leads to an increase of the expression level of PFKFB3 and PFKFB4 mRNA both in control glioma cells and cells with ERN1 loss of function, being more significant for PFKFB4. Moreover, the blockade of ERN1 signaling enzyme function decreases the effect of hypoxia on the expression level of both PFKFB3 and PFKFB4 mRNA. At the same time, the expression level of PFKFB1 and PFKFB2 mRNA does not change significantly in control glioma cells; however, in cells with ERN1 loss of function decreases PFKFB2 mRNA only. It was also shown that increased expression of PFKFB3 and PFKFB4 under hypoxic conditions correlates with strong induction of PFKL expression in control glioma cells only. The expression level of PFKP as well as LDHA mRNA increases in both cell types. Thus, results of this study clearly demonstrate that blockade of ERN1 signaling enzyme function leads to glycolysis activation mainly via increased expression of PFKFB4 and PFKL and eliminates effect of hypoxia on PFKL expression as well as suppresses its effect on the expression of PFKFB3 and PFKFB4 and decreases PFKFB2 mRNA level. It is possible that expression level of some PFKFB and PFK1 genes in normoxic and hypoxic conditions in glioma cells is mediated by ERN1 signaling system of endoplasmic reticulum stress.

Kyslychenko V.,University of Kharkiv | Karpiuk U.,National Oo Bohomolets Medical University | Diakonova I.,University of Kharkiv | Abu-Darwish M.S.,Al - Balqa Applied University
Advances in Environmental Biology | Year: 2010

A study was conducted to determine the phenolic compounds and terpenes in the chloroform and water extracts of the green parts of Glycine hispida collected during the flowering stage. The organoleptic and physico-chemical parameters were defined. The phenolic and terpenoied component of chloroform and water extracts was studied using gas-chromatograph/mass spectrometer (Hewlett Packard HP-6890) with a mass-selective detector (HP-5972). The results showed that, chloroform and water extracts from the green parts of the Glycine hispida were 2.69 and 32.12% of the mass, respectively. The Gc/Mass analysis of the samples revealed that, the chloroform extract had components that are belong to terpenes, including megastigmatrienone I, phytol, isophytol and alpha-pinene. Megastigmatrienone I, is the one of the main components of the terpenes that has been found. The quantitative content of Megastigmatrienone I is 84.19 mg/kg. Megastigmatrienone I, has a specific tobacco-like odor and is the one of the main odor components of the chloroform extract. Pyrogallol and phenolic acids were found in the water extract of the green parts of Glycine hispida,.The phenolic acids in this water extract were; isovanillic and salicylic acids (benzoic acid derivatives), and ferulic and m-coumaric acid (cinnamic acid derivatives). Salicylic acid has the greatest quantitative content in the water extract (71.43) mg/kg. The greatest quantitative content of the cinnamic acid derivatives is ferulic acid (77.9) mg/kg.

Minchenko D.O.,Ukrainian Academy of Sciences | Minchenko D.O.,National Oo Bohomolets Medical University | Prylutska S.V.,Taras Shevchenko National University | Moenner M.,University of Bordeaux 1 | And 4 more authors.
Materialwissenschaft und Werkstofftechnik | Year: 2013

The effect of C60 fullerene on the expression levels of genes, related to endoplasmic reticulum stress and cell proliferation, in human astrocytes was investigated. The exposure of human astrocytes to C60 fullerene during 24 or 72 h increases the expression levels of transcription factor E2F8, insulin-like growth factor binding protein-2, and tumor suppressor SMAD mRNAs in human astrocytes. At the same time, the expression levels of HSD17B2, PBEF1, HSPB8 mRNA decrease in cells treated with C60 fullerene, being more intense for HSD17B2. Moreover, C60 fullerene increases the proliferation rate of astrocytes. Thus, C60 fullerene affects the expression of genes which control proliferation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gruzieva O.,Karolinska Institutet | Gruzieva O.,National Oo Bohomolets Medical University | Bellander T.,Karolinska Institutet | Eneroth K.,Environment and Health Administration | And 9 more authors.
Journal of Allergy and Clinical Immunology | Year: 2012

Background: The role of exposure to air pollution in the development of allergic sensitization remains unclear. Objective: We sought to assess the development of sensitization until school age related to longitudinal exposure to air pollution from road traffic. Methods: More than 2500 children in the birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) from Stockholm, Sweden, were followed with repeated questionnaires and blood sampling until 8 years of age. Outdoor concentrations of nitrogen oxides, as a marker of exhaust particles, and particles with an aerodynamic diameter of less than 10 μm (PM 10), mainly representing road dust, were assigned to residential, day care, and school addresses by using dispersion models. Time-weighted average exposures were linked to levels of IgE against common inhalant and food allergens at 4 and 8 years of age. Results: Air pollution exposure during the first year of life was associated with an increased risk of pollen sensitization at 4 years of age (odds ratio, 1.83; 95% confidence interval, 1.02-3.28) for a 5th to 95th difference in exposure to nitrogen oxides. At 8 years, there was no general increase in the risk of sensitization; however, the risk of food sensitization was increased, particularly among children free of sensitization at 4 years of age (odds ratio, 2.30; 95% confidence interval, 1.10-4.82). Results were similar by using PM 10. No associations between air pollution exposure after the first year of life and sensitization were seen. Conclusion: Traffic-related air pollution exposure does not seem to increase the overall risk of sensitization to common inhalant and food allergens up to school age, but sensitization to certain allergens might be related to exposure during infancy. © 2011 American Academy of Allergy, Asthma & Immunology.

Unukovych D.,Karolinska Institutet | Unukovych D.,National Oo Bohomolets Medical University | Khrapach V.,National Oo Bohomolets Medical University | Wickman M.,Karolinska Institutet | And 7 more authors.
World Journal of Surgery | Year: 2012

Background: Polyacrylamide gel (PAAG) was first manufactured in Ukraine in the late 1980s and introduced as a biomaterial for "breast augmentation without surgery." Since it is prohibited in most countries, PAAG injections are rare nowadays, but their consequences and long-term complications can be crucial. Methods: We identified 106 patients consecutively operated on for PAAG complications at three teaching Ukrainian hospitals between 1998 and 2009. All relevant sociodemographic, clinical, and treatment characteristics were collected. Forty-five (42%) patients were available for clinical follow-up. Results: The majority (88%) had had bilateral PAAG injections. The mean volume of injected PAAG was 230 ml/breast (range = 50-400). Mean age at injection was 29 years (range = 17-49) and the mean time from the injection to complications was 6.1 years (SD = 4.1). Symptoms preceding debridement were pain in 85 patients (80%), breast hardening in 79 (74%), breast deformity in 77 (73%), lumps in 57 (54%), gel migration in 39 (37%), fistulas in 17 (16%), and gel leakage in 12 (11%). The surgical interventions in 199 breasts included gel evacuation alone in 107 (54%) or in combination with partial mastectomy in 65 (33%), partial mastectomy and partial pectoralis muscle resection in 12 (6%), or subcutaneous mastectomy in 15 (7%). Of the 199 operated breasts, 86 (43%) immediate and 58 (29%) delayed implant-based breast reconstructions were performed. Conclusion: Injections of PAAG can cause irreversible damage to the breast necessitating complex debridement procedures, even mastectomy and breast reconstruction. Despite numerous surgical interventions, gel remnants are still found on subsequent breast imaging. Although PAAG is prohibited in many countries, different types of injections with unknown long-term effects are currently being used. Making the public aware of the problems of injectables for breast augmentation is warranted. © Société Internationale de Chirurgie 2011.

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