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61.
Down-regulation of the microRNAs miR-34a, miR-127, and miR-200b in rat liver during hepatocarcinogenesis induced by a methyl-deficient diet 总被引:1,自引:0,他引:1
Altered expression of microRNAs (miRNAs) has been reported in diverse human cancers; however, the down-regulation or up-regulation of any particular miRNAs in cancer is not sufficient to address the role of these changes in carcinogenesis. In this study, using the rat model of liver carcinogenesis induced by a methyl-deficient diet, which is relevant to the hepatocarcinogenesis in humans associated with viral hepatitis C and B infections, alcohol exposure and metabolic liver diseases, we showed that the development of hepatocellular carcinoma (HCC) is characterized by prominent early changes in expression of miRNA genes, specifically by inhibition of expression of microRNAs miR-34a, miR-127, miR-200b, and miR-16a involved in the regulation of apoptosis, cell proliferation, cell-to-cell connection, and epithelial-mesenchymal transition. The mechanistic link between these alterations in miRNAs expression and the development of HCC was confirmed by the corresponding changes in the levels of E2F3, NOTCH1, BCL6, ZFHX1B, and BCL2 proteins targeted by these miRNAs. The significance of miRNAs expression dysregulation in respect to hepatocarcinogenesis was confirmed by the persistence of these miRNAs alterations in the livers of methyl-deficient rats re-fed a methyl-adequate diet. Altogether, the early occurrence of alterations in miRNAs expression and their persistence during the entire process of hepatocarcinogenesis indicate that the dysregulation of microRNAs expression may be an important contributing factor in the development of HCC. 相似文献
62.
Bagnyukova TV Tryndyak VP Montgomery B Churchwell MI Karpf AR James SR Muskhelishvili L Beland FA Pogribny IP 《Carcinogenesis》2008,29(3):638-646
Genotoxic carcinogens, including 2-acetylaminofluorene (2-AAF), in addition to exerting their genotoxic effects, often cause a variety of non-genotoxic alterations in cells. It is believed that these non-genotoxic effects may be indispensable events in tumorigenesis; however, there is insufficient knowledge to clarify the role of carcinogens in both the genetic and epigenetic changes in premalignant tissues and a lack of conclusive information on the link between epigenetic alterations and carcinogenic exposure. In the current study, we investigated whether or not the mechanism of 2-AAF-induced hepatocarcinogenesis consists of both genotoxic (genetic) and non-genotoxic (epigenetic) alterations. Male and female Sprague-Dawley rats were fed NIH-31 diet containing 0.02% of 2-AAF for 6, 12, 18 or 24 weeks. The levels of DNA adducts obtained from 2-AAF in liver and kidney tissues were assessed by high-performance liquid chromatography combined with electrospray tandem mass spectrometry (HPLC-ES-MS/MS). N-(Deoxyguanosine-8-yl)-2-aminofluorene was the major adduct detected at all time points in both tissues. Global DNA methylation in the livers and kidneys, as determined by an HpaII-based cytosine extension assay and by HPLC-ES-MS/MS, did not change over the 24-week period. In the livers of male rats, there was a progressive decrease of global and long interspersed nucleotide element-1-associated histone H4 lysine 20 trimethylation, as well as hypermethylation of the p16(INK4A) gene. These epigenetic changes were not observed in the livers of female rats or the kidneys of both sexes. Importantly, morphological evidence of formation and progression of neoplastic process was observed in the liver of male rats only. In conclusion, we have demonstrated that exposure of rats to genotoxic hepatocarcinogen 2-AAF, in addition to formation of 2-AAF-specific DNA lesions, resulted in substantial alterations in cellular epigenetic status. 相似文献
63.
Khrystyna Bolibrukh Svyatoslav Polovkovych Omar Khoumeri Tetyana Halenova Irina Nikolaeva Olexiy Savchuk Thierry Terme Patrice Vanelle Vira Lubenets Volodymyr Novikov 《Scientia pharmaceutica》2015,83(2):221-231
Thiosulfonate derivatives based on quinones were synthesized for studying “structure-activity relationship” compounds with an acylated and a free amino-group. Anti-platelet activity of the synthesized compounds was determined and the influence of substituents on the activity of the derivatives was assessed. 相似文献
64.
Oberemok Volodymyr V. Laikova Kateryna V. Yurchenko Kseniya A. Fomochkina Irina I. Kubyshkin Anatolii V. 《Inflammation research》2020,69(7):635-640
Inflammation Research - At the population level, the virus-host relationship is not set up to end with the complete elimination of either or both. Pathogen-resistant individuals will always remain... 相似文献
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66.
Susanne S. Pedersen Andriy Yagensky Otto R. F. Smith Oksana Yagenska Volodymyr Shpak Johan Denollet 《International journal of behavioral medicine》2009,16(2):108-115
Background Type D personality is a risk indicator in cardiac patients. The validity and reliability of the Type D Scale (DS14) have been
confirmed in Western Europe but not outside this context.
Purpose We examined the structural, convergent, and divergent validity and the reliability of the DS14 in the Ukrainian setting.
Method Healthy Ukrainian respondents (n = 250) completed the DS14, the Eysenck Personality Questionnaire, the State Trait Anxiety Inventory, and the Beck Depression
Inventory. A subsample (n = 57) completed the DS14 again after 4 weeks.
Results The prevalence of Type D personality was 22.4%. The two-factor structure and the validity of the DS14 were confirmed. The
DS14 subscales were internally consistent (Cronbach’s α = 0.86/0.71; mean inter-item correlation = 0.48/0.27) and stable over a 4-week period (r = 0.85/0.63). Type D individuals had significantly higher mean scores on anxiety (p < 0.001), depressive symptoms (p < 0.001), and negative affect (p < 0.001), and lower scores on positive affect (p < 0.001) compared to non-Type D individuals.
Conclusion Preliminary evidence suggests that the Ukrainian DS14 is a valid and reliable measure. Future studies are warranted to test
the utility of the scale in cardiac patients in the Ukraine, including whether Type D also predicts adverse health outcomes
beyond the boundaries of Western Europe. 相似文献
67.
68.
Exogenous nitric oxide reduces glucose transporters translocation and lactate production in ischemic myocardium in vivo
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Lei B Matsuo K Labinskyy V Sharma N Chandler MP Ahn A Hintze TH Stanley WC Recchia FA 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(19):6966-6971
Nitric oxide (NO) inhibits myocardial glucose transport and metabolism, although the underlying mechanism(s) and functional consequences of this effect are not clearly understood. We tested the hypothesis that NO inhibits the activation of AMP-activated protein kinase (AMPK) and translocation of cardiac glucose transporters (GLUTs; GLUT-4) and reduces lactate production. Ischemia was induced in open-chest dogs by a 66% flow reduction in the left anterior descending coronary artery (LAD). During ischemia, dogs were untreated (control) or treated by direct LAD infusion of (i) nitroglycerin (NTG) (0.5 microg.kg(-1).min(-1)); (ii) 8-Br-cGMP (50 microg.kg(-1).min(-1)); or (iii) NO synthase inhibitor L-nitro-argininemethylester (40 microg.kg(-1).min(-1); n = 9 per group). Cardiac substrate oxidation was measured with isotopic tracers. There were no differences in myocardial blood flow or oxygen delivery among groups; however, at 45 min of ischemia, the activation of AMPK was significantly less in NTG (77 +/- 12% vs. nonischemic myocardium) and 8-Br-cGMP (104 +/- 13%), compared with control (167 +/- 17%). Similarly, GLUT-4 translocation was significantly reduced in NTG (74 +/- 7%) and 8-Br-cGMP (120 +/- 11%), compared with control (165 +/- 17%). Glucose uptake and lactate output were 30% and 60% lower in NTG compared with control. Inhibition of NO synthesis stimulated glucose oxidation (67% increase compared with control) but did not affect AMPK phosphorylation, GLUT-4 translocation and glucose uptake. Contractile function in the ischemic region was significantly improved by NTG and L-nitro-argininemethylester. In conclusion, in ischemic myocardium an NO donor inhibits glucose uptake and lactate production via a reduction in AMPK stimulation of GLUT-4 translocation, revealing a mechanism of metabolic modulation and myocardial protection activated by NO donors. 相似文献
69.
Igor Mokryk Vitaly Demyanchuk Volodymyr Vashkeba Ilya Nechay Borys Todurov 《Congenital heart disease》2022,17(6):641-646
Congenital heart disease (CHD) is one of the risk factors for developing infective endocarditis (IE). Right-sided IE occurs in 5%–10% of endocarditis cases, and pulmonary valve (PV) is involved in less than 2% of such patients. Literature data are few, and optimal treatment methods, indications for surgery, and types of operative techniques are still under debate. We present an adult patient with a rare combination of the ventricular septal defect (VSD) and PV IE who underwent surgical treatment. Neocuspidization with autologous pericardium was utilized for the reconstruction of his PV. We discuss details of this novel surgical technique. 相似文献
70.