| 1. |
- Bianco, Cristiana, et al.
(författare)
-
Predictors of controlled attenuation parameter in metabolic dysfunction
- 2024
-
Ingår i: United European Gastroenterology Journal. - 2050-6406 .- 2050-6414. ; 12:3, s. 364-373
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Hepatic fat content can be non-invasively estimated by controlled attenuation parameter (CAP) during transient elastography. The aim of this study was to examine the determinants and predictors of CAP values in individuals with metabolic dysfunction. Methods: We enrolled 1230 consecutive apparently healthy individuals (Liver-Bible-2022 cohort) with ≥3 metabolic dysfunction features. CAP was measured by Fibroscan. CAP determinants and predictors were identified using backward stepwise analysis and introduced in generalized linear models. Results: Participants were predominantly males (82.9%), mean age was 53.8±6.4years, 600 (48.8%) had steatosis (CAP≥275dB/m), and 27 had liver stiffness measurement (LSM)≥8kPa. CAP values correlated with LSM (p<10−22). In multivariable analysis, fasting insulin and abdominal circumference (AC) were the main determinants of CAP (p<10−6), together with body mass index (BMI; p<10−4), age, diabetes, triglycerides, ferritin, and lower HDL and thyroid stimulating hormone (TSH; p<0.05 for all). In a subset of 592 participants with thyroid hormone measurement, we found an association between higher free triiodothyronine levels, correlating with lower TSH, and CAP values, independent of TSH and of levothyroxine treatment (p=0.0025). A clinical CAP score based on age, BMI, AC, HbA1c, ALT, and HDL predicted CAP≥275dB/m with moderate accuracy (AUROC=0.73), which was better than that of the Fatty Liver Index and of ALT (AUROC=0.70/0.61, respectively) and validated it in multiple cohorts. Conclusion: Abdominal adiposity and insulin resistance severity were the main determinants of CAP in individuals with metabolic dysfunction and may improve steatotic liver disease risk stratification. CAP values were modulated by the hypophysis-thyroid axis.
|
|
| 2. |
- Cantù, Claudio, et al.
(författare)
-
A highly conserved SOX6 double binding site mediates SOX6 gene downregulation in erythroid cells
- 2011
-
Ingår i: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 39:2, s. 486-501
-
Tidskriftsartikel (refereegranskat)abstract
- The Sox6 transcription factor plays critical roles in various cell types, including erythroid cells. Sox6-deficient mice are anemic due to impaired red cell maturation and show inappropriate globin gene expression in definitive erythrocytes. To identify new Sox6 target genes in erythroid cells, we used the known repressive double Sox6 consensus within the εy-globin promoter to perform a bioinformatic genome-wide search for similar, evolutionarily conserved motifs located within genes whose expression changes during erythropoiesis. We found a highly conserved Sox6 consensus within the Sox6 human gene promoter itself. This sequence is bound by Sox6 in vitro and in vivo, and mediates transcriptional repression in transient transfections in human erythroleukemic K562 cells and in primary erythroblasts. The binding of a lentiviral transduced Sox6FLAG protein to the endogenous Sox6 promoter is accompanied, in erythroid cells, by strong downregulation of the endogenous Sox6 transcript and by decreased in vivo chromatin accessibility of this region to the PstI restriction enzyme. These observations suggest that the negative Sox6 autoregulation, mediated by the double Sox6 binding site within its own promoter, may be relevant to control the Sox6 transcriptional downregulation that we observe in human erythroid cultures and in mouse bone marrow cells in late erythroid maturation.
|
|
