scholarly journals Metformin: A Possible Option in Cancer Chemotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Chidiebere V. Ugwueze ◽  
Odunze J. Ogamba ◽  
Ekenechukwu E. Young ◽  
Belonwu M. Onyenekwe ◽  
Basil C. Ezeokpo
Keyword(s):  
Cancer Chemotherapy ◽  
Metabolic Diseases ◽  
Adenosine Monophosphate ◽  
Antitumor Action ◽  
Cancer Management ◽  
The United Kingdom ◽  
Long Time ◽  
A1 Receptor ◽  
Experimental Trials

Metformin has been used for a long time as an antidiabetic medication for type 2 diabetes. It is used either as a monotherapy or in combination with other antidiabetic medications. The drug came into prominence in diabetes and other conditions with cardiovascular risk after the landmark study of 1995 by the United Kingdom Prospective Diabetes Study which emphasized its importance. However, the drug has been used in experimental trials in various aspects of medicine and pharmacology such as in reproductive medicine, cancer chemotherapy, metabolic diseases, and neurodegenerative diseases. It has been in use in the treatment of polycystic ovarian disease and obesity and is being considered in type 1 diabetes. This study seeks to evaluate the relevance of metformin in cancer management. Different mechanisms have been proposed for its antitumor action which involves the following: (a) the activation of adenosine monophosphate kinase, (b) modulation of adenosine A1 receptor (ADORA), (c) reduction in insulin/insulin growth factors, and (d) the role of metformin in the inhibition of endogenous reactive oxygen species (ROS); and its resultant damage to deoxyribonucleic acid (DNA) molecule is another paramount antitumor mechanism.

scholarly journals Role of small leucine zipper protein in hepatic gluconeogenesis and metabolic disorder

2020 ◽  
Author(s):  
Minsoo Kang ◽  
Sun Kyoung Han ◽  
Suhyun Kim ◽  
Sungyeon Park ◽  
Yerin Jo ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glucose Metabolism ◽  
Metabolic Disorder ◽  
Leucine Zipper ◽  
Metabolic Diseases ◽  
Adenosine Monophosphate ◽  
The Body ◽  
Hepatic Gluconeogenesis ◽  
Leucine Zipper Protein

Abstract Hepatic gluconeogenesis is the central pathway for glucose generation in the body. The imbalance between glucose synthesis and uptake leads to metabolic diseases such as obesity, diabetes, and cardiovascular diseases. Small leucine zipper protein (sLZIP) is an isoform of LZIP and it mainly functions as a transcription factor. Although sLZIP is known to regulate the transcription of genes involved in various cellular processes, the role of sLZIP in hepatic glucose metabolism is not known. In this study, we investigated the regulatory role of sLZIP in hepatic gluconeogenesis and its involvement in metabolic disorder. We found that sLZIP expression was elevated during glucose starvation, leading to the promotion of phosphoenolpyruvate carboxylase and glucose-6-phosphatase expression in hepatocytes. However, sLZIP knockdown suppressed the expression of the gluconeogenic enzymes under low glucose conditions. sLZIP also enhanced glucose production in the human liver cells and mouse primary hepatic cells. Fasting-induced cyclic adenosine monophosphate impeded sLZIP degradation. Results of glucose and pyruvate tolerance tests showed that sLZIP transgenic mice exhibited abnormal blood glucose metabolism. These findings suggest that sLZIP is a novel regulator of gluconeogenic enzyme expression and plays a role in blood glucose homeostasis during starvation.

scholarly journals The Role of Reunified Germany in Poland’s Accession to NATO and the European Union

Politeja ◽  
2021 ◽  
Vol 18 (6(75)) ◽  
pp. 51-74
Author(s):  
Józef Fiszer
Keyword(s):  
United States ◽  
European Union ◽  
Soviet Union ◽  
The United States ◽  
The European Union ◽  
The United Kingdom ◽  
The Soviet Union ◽  
Long Time ◽  
The Eu

The study is devoted to Poland’s accession to NATO and the European Union (EU) and describes Germany’s stance on Poland’s Euro-Atlantic aspirations after 1989, which, despite various assessments, was not explicit and enthusiastic. However, it evolved gradually and was determined by a difficult internal situation after the reunification of Germany and its new geopolitics and geoeconomics. For Germany that reunified on 3 October 1990, an issue of greater importance than Polish accession to NATO and the EU was the presence of Soviet troops on the territory of the former GDR and normalization of relations with neighbors, particularly with France, Poland, the Soviet Union, and the United States. Both France and the United Kingdom, as well as the Soviet Union, and to a lesser extent, the United States initially were afraid of a reunified Germany and opposed Polish membership in Euro-Atlantic structures. At the time, hopes and fears were rife about the future of Europe. A common question was being asked in Paris, London, Moscow, Washington, and Warsaw – would reunified Germany remain a European state, or would Europe become German? Should Germany stay in NATO or leave after the reunification? There were questions also about Moscow’s policy towards reunified Germany and its position on Poland’s accession to Euro-Atlantic structures. Unfortunately, for a long time, it was negative. Today, thirty years after the fall of the Berlin Wall and the reunification of Germany, we can see that the black scenarios that were outlined in 1989-1990 did not actually come true. Despite the fears, those events opened the way for Poland to “return to Europe” and to gain membership in Euro-Atlantic structures, i.e., NATO and the European Union (EU). The path was not at all simple and it was not easy for Poland to make it through. In the study the author analyses subjective and objective difficulties related to Poland's accession to NATO and the EU and describes the evolution and role of Germany in this process.

scholarly journals Diaspora Identity and a New Generation: Armenian Diaspora Youth on the Genocide and the Karabakh War

2019 ◽  
Vol 48 (5) ◽  
pp. 915-930
Author(s):  
Dmitry Chernobrov ◽  
Leila Wilmers
Keyword(s):  
Digital Communication ◽  
Early 20Th Century ◽  
Collective Memories ◽  
The Past ◽  
The United Kingdom ◽  
Armenian Diaspora ◽  
Long Time ◽  
New Generation ◽  
Shed Light

AbstractIn this article, we explore the role of the early 20th-century Armenian genocide and the unresolved Karabakh conflict of the 1990s in identity shaping among the new generation of Armenian diaspora—those who grew up after the establishment of the independent Armenian state in 1991. We draw on original interviews with diasporic youth in France, the United Kingdom, and Russia—diasporas that were largely built in the aftermath of the genocide and the Karabakh war. Diaspora youth relate to these events through transmitted collective memories, but also reconnect with the distant homeland’s past and present in new ways as they engage with new possibilities of transnational digital communication and mobility. Their experiences of identity shed light on how the new generation of diasporic Armenians defines itself in relation to the past; how this past is (re)made present in their interpretations of the Karabakh conflict and in everyday behaviors; and how diasporic youth experience the dilemmas of “moving on” from traumatic narratives that for a long time have been seen as foundational to their identity.

The Problem of Identifying and Modeling the Relationship between Monetary Factor and Inflation in the Russian Economy

2008 ◽  
pp. 61-76
Author(s):  
A. Porshakov ◽  
A. Ponomarenko
Keyword(s):  
Money Supply ◽  
Money Demand ◽  
Russian Economy ◽  
Long Run ◽  
Complex Approach ◽  
Wide Range ◽  
Long Time ◽  
The Relationship ◽  
Supply Side Factors

The role of monetary factor in generating inflationary processes in Russia has stimulated various debates in social and scientific circles for a relatively long time. The authors show that identification of the specificity of relationship between money and inflation requires a complex approach based on statistical modeling and involving a wide range of indicators relevant for the price changes in the economy. As a result a model of inflation for Russia implying the decomposition of inflation dynamics into demand-side and supply-side factors is suggested. The main conclusion drawn is that during the recent years the volume of inflationary pressures in the Russian economy has been determined by the deviation of money supply from money demand, rather than by money supply alone. At the same time, monetary factor has a long-run spread over time impact on inflation.

The role of demographic variables as the moderator between organizational variables and job stress among teachers in Sabah

2009 ◽  
Vol 6 (1) ◽  
pp. 1
Author(s):  
Najihah Hanisah Marmaya ◽  
Syed Azizi Wafa
Keyword(s):  
United Kingdom ◽  
Sample Size ◽  
Job Stress ◽  
Demographic Variables ◽  
Personal Factors ◽  
Occupational Groups ◽  
Organizational Variables ◽  
Population Norms ◽  
The United Kingdom

A nationwide investigation into stress among teachers in the United Kingdom, found teachers to be reporting stress-related problems which were far higher than those of the population norms and other comparable occupational groups. Job stress can be influenced by personal factors (Matteson & Ivancevich, 1999). The present study examined the role of demographic variables as the moderator between organizational variables and job stress. A sample size of 177 teachers participated in this study revealed that teachers in Tawau and Lahad Datu experienced low stress levels. This study found that demographic variables do not serve as the moderator between organizational variables and job stress.

Euratom and Brexit: Could the United Kingdom Maintain One Foot in the European Union? Current Scenarios and Future Prospects of British withdrawal from the EAEC

2018 ◽  
Vol 18 (2) ◽  
pp. 134-151
Author(s):  
Andrea Circolo ◽  
Ondrej Hamuľák
Keyword(s):  
European Union ◽  
United Kingdom ◽  
Independent Solution ◽  
Legal Regulation ◽  
The European Union ◽  
The United Kingdom ◽  
The Status ◽  
Long Time ◽  
Energy Community ◽  
The Impact

Abstract The paper focuses on the very topical issue of conclusion of the membership of the State, namely the United Kingdom, in European integration structures. The ques­tion of termination of membership in European Communities and European Union has not been tackled for a long time in the sources of European law. With the adop­tion of the Treaty of Lisbon (2009), the institute of 'unilateral' withdrawal was intro­duced. It´s worth to say that exit clause was intended as symbolic in its nature, in fact underlining the status of Member States as sovereign entities. That is why this institute is very general and the legal regulation of the exercise of withdrawal contains many gaps. One of them is a question of absolute or relative nature of exiting from integration structures. Today’s “exit clause” (Art. 50 of Treaty on European Union) regulates only the termination of membership in the European Union and is silent on the impact of such a step on membership in the European Atomic Energy Community. The presented paper offers an analysis of different variations of the interpretation and solution of the problem. It´s based on the independent solution thesis and therefore rejects an automa­tism approach. The paper and topic is important and original especially because in the multitude of scholarly writings devoted to Brexit questions, vast majority of them deals with institutional questions, the interpretation of Art. 50 of Treaty on European Union; the constitutional matters at national UK level; future relation between EU and UK and political bargaining behind such as all that. The question of impact on withdrawal on Euratom membership is somehow underrepresented. Present paper attempts to fill this gap and accelerate the scholarly debate on this matter globally, because all consequences of Brexit already have and will definitely give rise to more world-wide effects.

Mechanisms of ATP to cAMP Conversion Catalyzed by the Mammalian Adenylyl Cyclase: A Role of Magnesium Coordination Shells and Proton Wires

2019 ◽  
Author(s):  
Bella Grigorenko ◽  
Igor Polyakov ◽  
Alexander Nemukhin
Keyword(s):  
Adenylyl Cyclase ◽  
Bond Cleavage ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Md Simulations ◽  
Coordination Shell ◽  
Energy Profile ◽  
One Step ◽  
Type V

<p>We report a mechanism of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) conversion by the mammalian type V adenylyl cyclase revealed in molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) simulations. We characterize a set of computationally derived enzyme-substrate (ES) structures showing an important role of coordination shells of magnesium ions in the solvent accessible active site. Several stable six-fold coordination shells of Mg<sub>A</sub><sup>2+ </sup>are observed in MD simulations of ES complexes. In the lowest energy ES conformation, the coordination shell of Mg<sub>A</sub><sup>2+ </sup>does not include the O<sub>δ1</sub> atom of the conserved Asp440 residue. Starting from this conformation, a one-step reaction mechanism is characterized which includes proton transfer from the ribose O<sup>3'</sup>H<sup>3' </sup>group in ATP to Asp440 via a shuttling water molecule and P<sup>A</sup>-O<sup>3A</sup> bond cleavage and O<sup>3'</sup>-P<sup>A</sup> bond formation. The energy profile of this route is consistent with the observed reaction kinetics. In a higher energy ES conformation, Mg<sub>A</sub><sup>2+</sup> is bound to the O<sub>δ1</sub>(Asp440) atom as suggested in the relevant crystal structure of the protein with a substrate analog. The computed energy profile initiated by this ES is characterized by higher energy expenses to complete the reaction. Consistently with experimental data, we show that the Asp440Ala mutant of the enzyme should exhibit a reduced but retained activity. All considered reaction pathways include proton wires from the O<sup>3'</sup>H<sup>3' </sup>group via shuttling water molecules. </p>

Charles de Gaulle and European Community

2020 ◽  
Vol 2020 (10-3) ◽  
pp. 70-81
Author(s):  
David Ramiro Troitino ◽  
Tanel Kerikmae ◽  
Olga Shumilo
Keyword(s):  
World War Ii ◽  
European Community ◽  
World War ◽  
Charles De Gaulle ◽  
The United Kingdom ◽  
History Of ◽  
The Common ◽  
Post War ◽  
De Gaulle

This article highlights the role of Charles de Gaulle in the history of united post-war Europe, his approaches to the internal and foreign French policies, also vetoing the membership of the United Kingdom in the European Community. The authors describe the emergence of De Gaulle as a politician, his uneasy relationship with Roosevelt and Churchill during World War II, also the roots of developing a “nationalistic” approach to regional policy after the end of the war. The article also considers the emergence of the Common Agricultural Policy (hereinafter - CAP), one of Charles de Gaulle’s biggest achievements in foreign policy, and the reasons for the Fouchet Plan defeat.

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