Znf202 Affects High Density Lipoprotein Cholesterol Levels and Promotes Hepatosteatosis in Hyperlipidemic Mice

Background: The zinc finger protein Znf202 is a transcriptional suppressor of lipid related genes and has been linked to hypoalphalipoproteinemia. A functional role of Znf202 in lipid metabolism in vivo still remains to be established. Methodology and Principal Findings: We generated mouse Znf202 expression vectors, the functionality of which was established in several in vitro systems. Next, effects of adenoviral znf202 overexpression in vivo were determined in normo- as well as hyperlipidemic mouse models. Znf202 overexpression in mouse hepatoma cells mhAT3F2 resulted in downregulation of members of the Apoe/c1/c2 and Apoa1/c3/a4 gene cluster. The repressive activity of Znf202 was firmly confirmed in an apoE reporter assay and Znf202 responsive elements within the ApoE promoter were identified. Adenoviral Znf202 transfer to Ldlr-/- mice resulted in downregulation of apoe, apoc1, apoa1, and apoc3 within 24 h after gene transfer. Interestingly, key genes in bile flux (abcg5/8 and bsep) and in bile acid synthesis (cyp7a1) were also downregulated. At 5 days post-infection, the expression of the aforementioned genes was normalized, but mice had developed severe hepatosteatosis accompanied by hypercholesterolemia and hypoalphalipoproteinemia. A much milder phenotype was observed in wildtype mice after 5 days of hepatic Znf202 overexpression. Interestingly and similar to Ldl-/- mice, HDL-cholesterol levels in wildtype mice were lowered after hepatic Znf202 overexpression. Conclusion/Significance: Znf202 overexpression in vivo reveals an important role of this transcriptional regulator in liver lipid homeostasis, while firmly establishing the proposed key role in the control of HDL levels

Contemporary migration patterns in the prevalence of Helicobacter pylori infection: a systematic review

Background: A rapid growth in the number of international migrants over the past years has occurred with most traveling to more affluent settings. As Helicobacter pylori infects over half of the adult population and its prevalence is higher in developing countries, understanding the prevalence of infection in migrants can provide insight into future trends in the burden and management of infection. We aimed to describe the prevalence of H. pylori among migrants through a systematic literature review. Methods: We searched PubMed® from inception to September 2015 to identify studies reporting the prevalence of H. pylori in international migrants according to country of birth for first‐generation, and country of birth and parents' nationality for successive generations. Comparable data from origin and destination populations were obtained from the same studies or, when not present, from a previous systematic review on H. pylori worldwide. Results: A total of 28 eligible studies were identified with data for 29 origin and 12 destination countries. Two studies that evaluated refugees presented prevalences of infection higher than both the origin and destination countries. Otherwise, the prevalences among migrants were generally similar or below that of the origin and higher than the destination. Second‐ or more generation had lower prevalences compared to first‐generation migrants. Conclusions: Our study findings are consistent with what would be expected based on the prevalence of H. pylori worldwide. The results of this review show that migrants are particularly at risk of infection and help to identify gaps in the knowledge of migrants' prevalence of infection globally.This work was supported by “Fundo Europeu de Desenvolvimento Regional” (FEDER) funds through the “Programa Operacional Factores de Competitividade” (POFC) – COMPETE (FCOMP‐01‐0124‐FEDER‐021181) and by national funds through the “Fundação para a Ciência e a Tecnologia” (PTDC/SAU‐EPI/122460/2010) and the Epidemiology Research Unit – Institute of Public Health, University of Porto supported by the “Fundação para a Ciência e a Tecnologia” (UID/DTP/047507/2013). Individual grants attributed to SM (SFRH/BD/102585/2014), ARC (SFRH/BD/102181/2014), AF (PD/BD/105823/2014), and BP (SFRH/BPD/75918/2011 and SFRH/BPD/108751/2015) were supported by “Fundação para a Ciência e a Tecnologia.” The funders had no role in study design, data collection, decision to publish, or preparation of the manuscript