13 research outputs found
Exogenous nitric oxide inhibits GLUT-4 translocation to sarcolemma in ischemic myocardium.
No full textExogenous nitric oxide inhibits AMP-activated protein kinase (AMPK) phosphorylation and GLUT4 Translocation to Sarcolemma in ischemic myocardium
No full textChronic activation of PPAR-alpha prevents alterations in cardiac metabolic phenotype without changing the progression of pacing-induced heart failure.
No full textThe activation of glucose 6-phosphate dehydrogenase as a source of substrate for NADPH oxidase in the failing heart.
No full textChronic activation of PPARalpha prevents alterations in cardiac metabolic phenotype without changing the progression of pacing-induced heart failure
No full textEndothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice.
No full textRNA Sequencing Reveals Differential Expression of Mitochondrial and Oxidation Reduction Genes in the Long-Lived Naked Mole-Rat When Compared to Mice
No full textPubMed ID: 22073188This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease
No full textChronic obstructive pulmonary disease (COPD) is a global health problem. The current therapies for COPD are poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. An imbalance of oxidants/antioxidants caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g., NF-κB), autophagy and unfolded protein response leading to chronic lung inflammatory response. Cigarette smoke also activates canonical/alternative NF-κB pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervention in COPD
COGNITIVE AND METACOGNITIVE ASPECTS OF THE DEVELOPMENT OF LIFELONG LEARNING COMPETENCIES IN LAW STUDENTS
No full textLifelong learning is one of the main trends in educational and social policy in Europe, aimed at ensuring professional realization and social integrity of an individual. The article describes cognitive and metacognitive aspects of the formation of learning competence, as well as predisposition of law students to lifelong learning. A survey of 218 students and masters was conducted, data on the most popular and effective forms of knowledge acquisition (experience of formal, nonformal and informal learning over the past year), plans for further education and career development were collected. The dynamics of learning at different years of study is described. A group of students with pronounced learning and focus on lifelong learning (45% of the sample) was identified. A comparative analysis of two samples was carried out and qualities that could be considered markers of the LLL orientation were identified: a high level of metacognitive knowledge and metacognitive activity, reflective competence (at the cognitive, metacognitive and personal level), internal involvement in learning, focus on achieving professionalism and personal development, general self-efficacy, the prevalence of progressive and creative motives over consumer ones. Conclusions are drawn about the predominant role of metacognitions and personality determinants in the formation of lifelong learning competency among students. Reflection aimed at recognizing one’s own cognitive processes and understanding their contribution to personal development is the main mechanism for the formation of meta-cognitive abilities. The results obtained in the study determine the ways of pedagogical support and psychological intervention to ensure the development of lifelong learning competencies in different categories of students
Targeting of hepatocytes using vector-conjugated liposomes : evaluation of targeting strategies
No full textThe need for specific targeting strategies towards hepatocytes stems from the lack of
efficient therapeutic options to treat numerous serious liver diseases. Moreover, various
genetic disorders, such as α1-antitrypsin deficiency and hemophilia A and B, are depending
on an efficient gene delivery to defined cells, such as hepatocytes, preferentially avoiding
viral vectors. Since the asialoglycoprotein receptor is primarily expressed by liver
parenchymal cells, it offers a potential target for a cell specific delivery system.
First, the binding of various vectors was analyzed, using the human hepatocellular carcinoma
cell line HepG2 as an in vitro model. While the uptake of D-galactose as a monomer was
non-specific, the glycoprotein asialofetuin was analyzed as an alternative vector, which
represents the desialated derivative of fetuin, containing multi-antennary galactose-
terminating glycan residues. Next to a pronounced cellular accumulation, the uptake was
markedly inhibited in the presence of an excess of free asialofetuin, indicating specific
endocytosis through the asialoglycoprotein receptor. Therefore, asialofetuin was selected as
an ideal vector for the further development of a drug delivery system targeting liver
parenchymal cells.
Asialofetuin was covalently attached to pegylated liposomes, yielding a highly monodisperse
preparation with a particle size below 100 nm. A subsequently incubation with HepG2 cells
resulted in a specific endocytosis of the vesicles, providing an experimental proof of concept
for targeting hepatocytes in vitro. The delivery and intracellular accumulation in HepG2 cells
were investigated by incorporating various organic dyes and fluorescent semiconductor
nanocrystals, also known as quantum dots, into liposomes. The cellular uptake of
asialofetuin-conjugated liposomes, loaded with quantum dots, resulted in a bright fluorescent
signal, which was impaired by the need for a specific photoactivation prior to fluorescence
analysis. Despite their challenging optical properties, quantum dots are valuable
fluorochromes for further optimization of drug targeting strategies.
Finally, a proof of principle for a hepatocyte specific delivery was provided in vivo, by
intravenously injecting rats with asialofetuin-conjugated and pegylated liposomes, which
were taken up by the liver parenchymal cells. In contrast, accumulation in hepatocytes was
reduced by co-injecting free asialofetuin and conventional liposomes were uniquely engulfed
by Kupffer cells.
Summarized, asialofetuin-conjugated pegylated liposomes represent a novel approach,
combining desialated glycoproteins, which exhibit a high affinity towards the
asialoglycoprotein receptor, with long circulating vesicles, for a specific targeting of liver
parenchymal cells. This concept represents a most promising strategy for a hepatocyte
specific drug delivery system and gives the opportunity for further studies, such as the
isolated utilization of glycans only, to avoid immunogenic reactions.
These targeting strategies can be used to deliver drugs to diseased tissues or organs within
our body. This reflects our interests to modulate the pharmacokinetics of drugs using specific
formulation strategies. Two additional pharmacokinetic investigations of pharmaceutical
relevant substances were published in peer-reviewed journals. One study addresses the risk
of physical drug interactions of ceftriaxone with calcium in human plasma, and the second
one discusses the interaction potential of high doses of resveratrol with various cytochrome
P450 isoenzymes. These studies are presented in the section “Appendix”, to separate them
from the drug targeting approach of hepatocytes using liposomal formulations
