BACKGROUND: Alcohol is one of the main economic commodities, which represents a significant amount of government tax revenues and consumer spending. Alcohol is associated with health, economic and social impacts on people ́s lives. The task of national governments is not only to address the effects of alcohol but also to address the causes that help eliminate alcohol dependence. Tools that governments can use include price policy through alcohol taxation rates (excise duties, VAT), reduce accessibility to purchase alcohol beverages, raising awareness of the harmful effects of drinking for driving or among teenagers, etc. AIM: The main goal of the research was to examine dependencies between the amount of alcohol consumption and VAT rate for alcohol in EU Member States from 2010–2018. Selected data for the years 2010, 2012, 2014, 2016 and 2018 correspond to the published reports of the European Commission and the OECD. DESIGN AND MEASUREMENTS (METHODS): Secondary data for the research were obtained from available international statistics, which include databases from European Commission, the OECD, the WHO and Eurostat. Statistical methods as Kruskall-Wallis test were used for data analysis. SAMPLE: The sample consisted of complete data of 23 European Union Member States. RESULTS: The results of the research did not show a significant difference in the median alcohol consumption in the period 2010–2018 in the measured 23 EU countries. While the study of the dependence of VAT and alcohol consumption has shown a significant dependence. The highest base of alcohol consumption was recorded in Lithuania, Austria and Estonia, while the lowest base was recorded in Italy and Sweden. The VAT rate has been shown to have the highest impact on reducing alcohol consumption in Lithuania, Greece and Estonia. CONCLUSIONS: Among other things, it is possible to formulate a clear and concrete conclusion that increasing VAT on alcohol beverages will reduce the amount of alcohol consumption. This research finding would undoubtedly support the field of population health and prevention of alcoholism, but would have a negative effect on the economic functioning of individual EU Member States.
Viruses have developed numerous strategies to counteract the host cell defense. Kaposi's sarcoma-associated herpesvirus (KSHV) is a DNA tumor virus linked to the development of Kaposi's sarcoma, Castleman's disease, and primary effusion lymphoma (PEL). The virus-encoded viral interferon regulatory factor 3 (vIRF-3) gene is a latent gene which is involved in the regulation of apoptosis, cell cycle, antiviral immunity, and tumorigenesis. vIRF-3 was shown to interact with p53 and inhibit p53-mediated apoptosis. However, the molecular mechanism underlying this phenomenon has not been established. Here, we show that vIRF-3 associates with the DNA-binding domain of p53, inhibits p53 phosphorylation on serine residues S15 and S20, and antagonizes p53 oligomerization and the DNA-binding affinity. Furthermore, vIRF-3 destabilizes p53 protein by increasing the levels of p53 polyubiquitination and targeting p53 for proteasome-mediated degradation. Consequently, vIRF-3 attenuates p53-mediated transcription of the growth-regulatory p21 gene. These effects of vIRF-3 are of biological relevance since the knockdown of vIRF-3 expression in KSHV-positive BC-3 cells, derived from PEL, leads to an increase in p53 phosphorylation, enhancement of p53 stability, and activation of p21 gene transcription. Collectively, these data suggest that KSHV evolved an efficient mechanism to downregulate p53 function and thus facilitate uncontrolled cell proliferation and tumor growth.
- MeSH
- apoptóza genetika MeSH
- fosforylace MeSH
- HCT116 buňky MeSH
- HEK293 buňky MeSH
- inhibitor p21 cyklin-dependentní kinasy genetika metabolismus MeSH
- interferonové regulační faktory genetika metabolismus MeSH
- lidé MeSH
- lidský herpesvirus 8 genetika metabolismus MeSH
- multimerizace proteinu MeSH
- mutace MeSH
- nádorové buněčné linie MeSH
- nádorový supresorový protein p53 chemie genetika metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- promotorové oblasti (genetika) genetika MeSH
- protein X asociovaný s bcl-2 genetika metabolismus MeSH
- regulace genové exprese u nádorů MeSH
- RNA interference MeSH
- serin genetika metabolismus MeSH
- stabilita proteinů MeSH
- transfekce MeSH
- ubikvitinace MeSH
- vazba proteinů MeSH
- virové proteiny genetika metabolismus MeSH
- western blotting MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent associated with Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). Similar to other herpesviruses, KSHV has two life cycles, latency and lytic replication. In latency, the KSHV genome persists as a circular episome in the nucleus of the host cell and only a few viral genes are expressed. In this review, we focus on oncogenic, antiapoptotic, and immunomodulating properties of KSHV-encoded homologues of cellular interferon regulatory factors (IRFs)--viral IRF1 (vIRF1) to vIRF4--and their possible role in the KSHV-mediated antiviral response, apoptosis, and oncogenicity.
- MeSH
- apoptóza MeSH
- biologické modely MeSH
- interferonové regulační faktory genetika imunologie MeSH
- interferony metabolismus MeSH
- karcinogeneze MeSH
- lidé MeSH
- lidský herpesvirus 8 genetika imunologie patogenita MeSH
- multigenová rodina MeSH
- signální transdukce MeSH
- virové geny MeSH
- virové proteiny genetika imunologie MeSH
- zánět etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The Kaposi sarcoma-associated herpesvirus (KSHV) has been linked to Kaposi sarcoma, body cavity-based lymphoma, and Castleman disease. vIRF-3 is a KSHV latent gene that is critical for proliferation of KSHV-positive lymphoid cells. Furthermore, vIRF-3 contributes to KSHV-associated pathogenesis by stimulating c-Myc transcription activity. Here we show that vIRF-3 can associate with Skp2, a key component of the SCF(skp2) ubiquitin ligase complex. Skp2 is a transcriptional co-factor for c-Myc that was shown to regulate the stability of c-Myc protein as well as c-Myc-dependent transcription. In this study, we show that vIRF-3 binds to the F-box of Skp2 and recruits it to c-Myc-regulated promoters to activate c-Myc-dependent transcription. Additionally, cells overexpressing vIRF-3 exhibit higher levels of c-Myc ubiquitylation, suggesting that ubiquitylation is necessary for c-Myc-mediated transcription. Moreover, vIRF-3 can stabilize the c-Myc protein by increasing its half-life. Collectively, these results indicate that vIRF-3 can effectively manipulate c-Myc stability and function and thus contribute to c-Myc-induced KSHV-associated lymphomagenesis.
- MeSH
- genetická transkripce genetika MeSH
- HEK293 buňky MeSH
- HeLa buňky MeSH
- hyperplazie velkých lymfatických uzlin genetika metabolismus virologie MeSH
- interferonové regulační faktory genetika metabolismus MeSH
- lidé MeSH
- lidský herpesvirus 8 genetika metabolismus MeSH
- lymfocyty metabolismus virologie MeSH
- proteiny asociované s kinázou S-fáze genetika metabolismus MeSH
- protoonkogenní proteiny c-myc genetika metabolismus MeSH
- stabilita proteinů MeSH
- ubikvitinace genetika MeSH
- vazba proteinů MeSH
- virové proteiny genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- herpetické infekce * MeSH
- interferonový regulační faktor 3 MeSH
- Kaposiho sarkom * virologie MeSH
- komplexy ubikvitinligas MeSH
- lidé MeSH
- proteinligasy komplexu SCF MeSH
- protoonkogenní proteiny c-myc * metabolismus MeSH
- stabilita proteinů MeSH
- ubikvitinace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Klíčová slova
- KSHV,
- Publikační typ
- abstrakt z konference MeSH
- Klíčová slova
- KSHV, p53, HAUSP/USP7,
- Publikační typ
- abstrakty MeSH
