| 1. |
- Choi, Sungchul, et al.
(author)
-
Global burden of primary liver cancer and its asso- ciation with underlying aetiologies, sociodemo- graphic status, and sex differences from 1990-2019: A DALY-based analysis of the Global Burden of Disease 2019 study
- 2023
-
In: Clinical and Molecular Hepatology. - : KOREAN ASSOC STUDY LIVER. - 2287-2728 .- 2287-285X. ; 29:2, s. 433-452
-
Journal article (peer-reviewed)abstract
- Background/Aims: Global distribution of dominant liver cancer aetiologies has significantly changed over the past decades. This study analyzed the updated temporal trends of liver cancer aetiologies and sociodemographic status in 204 countries and territories from 1990 to 2019.Methods: The Global Burden of Disease 2019 report was used for statistical analysis. In addition, we performed stratification analysis to five quintiles using sociodemographic index and 21 geographic regions.Results: The crude numbers of liver cancer disease-adjusted life years (DALYs) and deaths significantly increased during the study period (DALYs; 11,278,630 in 1990 and 12,528,422 in 2019, deaths; 365,215 in 1990 and 484,577 in 2019). However, the Age-standardized DALY and mortality rates decreased. Hepatitis B virus (HBV) remains the leading cause of liver cancer DALYs and mortality, followed by hepatitis C virus (HCV), alcohol consumption, and non-alcoholic steatohepatitis/non-alcoholic fatty liver disease (NASH/NAFLD). Although Age-standardized DALY and mortality rates of liver cancer due to HBV and HCV have decreased, the rates due to alcohol consumption and NASH/NAFLD have increased. In 2019, the population of the East Asia region had the highest Age-standardized DALY and mortality rates, followed by high-income Asia-Pacific and Central Asia populations. Although East Asia and high-income Asia-Pacific regions showed a decrease during the study period, Age-standardized DALY rates increased in Central Asia. High-income North American and Australasian populations also showed a significant increase in Age-standardized DALY.Conclusions: Liver cancer remains an ongoing global threat. The burden of liver cancer associated with alcohol consumption and NASH/NAFLD is markedly increasing and projected to continuously increase. (Clin Mol Hepatol 2023;29:433-452)
|
|
| 2. |
- Jang, Seongmin, et al.
(author)
-
Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase
- 2019
-
In: Genes & Development. - : NLM (Medline). - 0890-9369 .- 1549-5477. ; 33:11-12, s. 620-625
-
Journal article (peer-reviewed)abstract
- DOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B ubiquitination. Here, we present cryo-EM structures of DOT1L complexes with unmodified or H2B ubiquitinated nucleosomes, showing that DOT1L recognizes H2B ubiquitin and the H2A/H2B acidic patch through a C-terminal hydrophobic helix and an arginine anchor in DOT1L, respectively. Furthermore, the structures combined with single-molecule FRET experiments show that H2B ubiquitination enhances a noncatalytic function of the DOT1L-destabilizing nucleosome. These results establish the molecular basis of the cross-talk between H2B ubiquitination and H3 Lys79 methylation as well as nucleosome destabilization by DOT1L.
|
|
