Tracking the Dynamic Histone Methylation of H3K27 in Live Cancer Cells.

Histone methylations play a crucial role in chromatin remodeling and genome regulations. However, there is a lack of tools to visualize these histone modifications with high spatiotemporal resolutions in live cells. We have developed a biosensor based on fluorescence resonance energy transfer (FRET) and incorporated it into nucleosomes, capable of monitoring the trimethylation of H3K27 (H3K27me3) in live cells. We also revealed that the performance of the FRET biosensor can be significantly improved by adjusting the linkers within the biosensor. An improved biosensor enables the live-cell imaging of different histone methylation status, induced by the suppressive H3.3K27M or existing in breast cancer cells with varying genetic backgrounds. We have further applied the biosensor to reveal the dynamic coupling between H3K27me3 changes and caspase activity representing the initiation of apoptosis in cancer cells by imaging both H3K27me3 and caspase activity simultaneously in the same live cells. Thus, this new FRET biosensor can provide a powerful tool to visualize the epigenetic regulation in live cells with high spatial temporal resolutions.

Circulating Levels of IL-13, TGF-ß1, and Periostin as Potential Biomarker for Coronary Artery Disease with Acute Heart Failure.

OBJECTIVE: Coronary artery disease (CAD) and associated comorbidities such as heart failure (HF) remain the leading cause of morbidity and mortality worldwide, attributed to, at least partially, the lack of biomarkers for efficient disease diagnosis. The study intended to explore potential biomarkers for predicting the presence of HF in CAD patients. METHODS: According to the presence of HF, 83 CAD patients with HF were assigned to the AHF group and 52 CAD patients without HF to the CAD group. Additionally, healthy controls (n = 52) were those who had received physical examinations at the same period. The serum levels of IL-13, TGF-ß1, and periostin were detected by the enzyme-linked immunosorbent assay (ELISA). Left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricle-end diastolic volume (LVEDV), and left ventricular mass index (LVMI) were detected 3 times by color Doppler ultrasound. The predictive values of IL-13, TGF-ß1, and periostin methods were compared by receiver-operating characteristic (ROC) analysis and the area under the curve (AUC). RESULTS: Increased levels of IL-13, TGF-ß1, and periostin were noted in the AHF group than in the control and CAD groups (p < 0.001); the CAD group showed higher levels of IL-13, TGF-ß1, and periostin than the control group (p < 0.001). Based on the NYHA classification, there were 33 cases with grade II, 28 cases with grade III, and 22 cases with grade IV among 83 CAD patients with HF. It was found that the serum levels of IL-13, TGF-ß1, and periostin were higher in the AHF-IV group than in the AHF-III and AHF-II groups (p < 0.001); these levels were also higher in the AHF-III group than in the AHF-II group (p < 0.001). The periostin level was positively correlated with the levels of IL-13 (r = 0.458) and TGF-ß1 (r = 0.569) in CAD patients with AHF. Besides, the serum levels of periostin (r = -0.425), IL-13 (r = -0.341), and TGF-ß1 (r = -0.435) were negatively correlated with the LVEF of CAD patients with AHF, respectively. When IL-13, TGF-ß1, and periostin levels were used to predict the presence of AHF in CAD patients in combination, the sensitivity and specificity were 75.9% and 90.38%, respectively, with the AUC of 0.906 (95% CI: 0.912-0.996). CONCLUSION: These data reveal that IL-13, TGF-ß1, and periostin levels might be associated with the occurrence of AHF in CAD patients and their combination shows the predictive value for the presence of AHF in CAD patients.