Our study demonstrates that high-protein/cholesterol pattern scores are associated with higher prevalence of AFLD in males. We also show high-carbohydrate/sweet pattern scores are associated with higher prevalence of NAFLD in females; but, interestingly, this pattern shows a favorable effect on AFLD in males.

UTX is implicated in embryonic development and lineage specification. However, how this X-linked histone demethylase contributes to the occurrence and progression of breast cancer remains to be clarified. Here we report that UTX is physically associated with estrogen receptor (ER) and functions in ER-regulated transcription. We showed that UTX coordinates with JHDM1D and CBP to direct H3K27 methylation-acetylation transition and to create a permissive chromatin state on ER targets. Genome-wide analysis of the transcriptional targets of UTX by ChIP-seq identified a set of genes such as chemokine receptor CXCR4 that are intimately involved in breast cancer tumorigenesis and metastasis. We demonstrated that UTX promotes the proliferation and migration of ER breast cancer cells. Interestingly, UTX itself is transactivated by ER, forming a feed-forward loop in the regulation of hormone response. Indeed, UTX is upregulated during ER breast cancer progression, and the expression level of UTX is positively correlated with that of CXCR4 and negatively correlated with the overall survival of ER breast cancer patients. Our study identified a feed-forward loop between UTX and ER in the regulation of hormonally responsive breast carcinogenesis, supporting the pursuit of UTX as an emerging therapeutic target for the intervention of certain ER breast cancer with specific epigenetic vulnerability.

As an AEG-1/MTDH/LYRIC-binding protein, Staphylococcal nuclease domain-containing 1 (SND1) is upregulated in numerous human cancers where it has been assigned multiple functional roles. In this study, we discovered that SND1 was upregulated in breast cancer tissues, particularly the tissues from patients with distant metastases. The underlying molecular mechanisms demonstrated a novel role of SND1 in regulating the activity of transforming growth factor β1 (TGFβ1) signaling pathway, which promotes metastasis in breast cancer. We illustrated that SND1 physically associated with and recruited the histone acetylase GCN5 to the promoter regions of Smad2/3/4, and consequently enhanced the gene transcriptional activation of Smad2/3/4, which are essential downstream regulators in the TGFβ1 pathway. An electrophoretic mobility shift assay experiment further verified that SND1 could recognize the conserved domains (motifs 1 and 2) in the promoter regions of the Smad genes. Glutathione S-transferase (GST) pulldown assays indicated that the tudor domain of SND1 was responsible for the recruitment of GCN5, which increased histone H3K9 acetylation. Consistent with these results, a loss-of-function of SND1 reduced the protein level of Smads and the phosphorylation of R-Smads, thereby attenuating the R-Smad/Co-Smad depended transcription and, as a result, inhibited TGFβ signaling activation.

No abstract

Although the prevalence of prehypertension is rapidly increasing in China, the medical community has paid little attention to its prevention. Prior studies have demonstrated that uric acid directly contributes to vascular remodelling and endothelial dysfunction. However, few prospective studies have assessed the relationship between serum uric acid and prehypertension. We therefore designed a larger-scale cohort study to examine whether uric acid level is a predictive factor for developing prehypertension in adults. Participants were recruited from Tianjin Medical University General Hospital-Health Management Centre. A prospective assessment (n=15 143) was performed. Participants without a history of hypertension or prehypertension were followed up for 2 to 6 years with a median follow-up duration of 2.8 years. Serum uric acid levels and blood pressure were assessed yearly during the follow-up. Adjusted Cox proportional hazards regression models were used to assess relationships between the quintiles of uric acid levels and the incidence of prehypertension. The incidence of prehypertension was 191 per 1000 person-years. In the final multivariate models, the hazard ratios (95% confidence interval) for prehypertension across uric acid quintiles were 1.00 (reference), 0.98 (0.90-1.07), 1.01 (0.93-1.10), 1.09 (1.001-1.20) and 1.17 (1.06-1.29) (P for trend <0.001), respectively. This population-based prospective cohort study has demonstrated that uric acid level is an independent predictor for developing prehypertension.