Davit Sargsyan

DNA methylome and transcriptome alterations and cancer prevention by curcumin in colitis-accelerated colon cancer in mice

Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms could play an important role in the initiation and progression of colon cancer. Curcumin, a dietary phytochemical, shows promising effects in suppressing colitis-associated colon cancer in azoxymethane-dextran sulfate sodium (AOM-DSS) mice. However, the potential epigenetic mechanisms of curcumin in colon cancer remain unknown. In this study, the anticancer effect of curcumin in suppressing colon cancer in an 18-week AOM-DSS colon cancer mouse model was confirmed. We identified lists of differentially expressed and differentially methylated genes in pairwise comparisons and several pathways involved in the potential anticancer effect of curcumin. These pathways include LPS/IL-1-mediated inhibition of RXR function, Nrf2-mediated oxidative stress response, production of NO and ROS in macrophages and IL-6 signaling. Among these genes, Tnf stood out with decreased DNA CpG methylation of Tnf in the AOM-DSS group and reversal of the AOM-DSS induced Tnf demethylation by curcumin. These observations in Tnf methylation correlated with increased and decreased Tnf expression in RNA-seq. The functional role of DNA methylation of Tnf was further confirmed by in vitro luciferase transcriptional activity assay. In addition, the DNA methylation level in a group of inflammatory genes was decreased in the AOM+DSS group but restored by curcumin and was validated by pyrosequencing. This study shows for the first time epigenomic changes in DNA CpG methylation in the inflammatory response from colitis-associated colon cancer and the reversal of their CpG methylation changes by curcumin. Future clinical epigenetic studies with curcumin in inflammation-associated colon cancer would be warranted.

ASSOCIATION BETWEEN MYOCARDIAL INFARCTION HOSPITAL PROCESS OF CARE SCORES WITH CLINICAL OUTCOMES IN A STATEWIDE STUDY

Background: Public reporting of hospital quality of care scores is freely available online and frequently accessed. Studies on the relationship of process improvement reports to clinical outcomes are contradictory. We examined the association between process of care scores for myocardial infarction

Risk Factors and Trends in Incidence of Heart Failure Following Acute Myocardial Infarction

Patients who develop heart failure (HF) after an acute myocardial infarction (AMI) are at higher risk of adverse fatal and nonfatal outcomes. Published studies on the incidence and associations of HF after infarction have been contradictory, with some reporting increasing and others decreasing incidence. Between 2000 and 2015, 109,717 patients admitted for a first AMI in New Jersey were discharged alive. In the 15 years from 2000 to 2015, the rates of admission for HF in AMI patients who were discharged alive decreased by 60%, from 3.48% to 1.4%, at 1-year follow-up. At 5 years of follow-up, the decline was more pronounced, from 7.21% to 1.4%, an 80% decline. All-cause death, and the combined end point of admission for HF or death, showed decreasing trends. Cox regression indicated a decrease in the risk of admission for HF over time (hazard ratio [HR] 0.955, 95% confidence interval [CI] 0.949 to 0.961). Younger age, male gender, and commercial insurance were associated with lower HRs for HF (p <0.001), whereas history of hypertension, diabetes, kidney, or lung disease were associated with higher HRs (p <0.001). There was no significant difference in the rate of HF between subendocardial and transmural AMI (adjusted OR was 0.96, CI 0.90 to 1.03, p = 0.241). Revascularization was associated with a marked decrease in HF admissions (adjusted OR 0.22, 95% CI 0.19 to 0.25, p <0.001 for percutaneous coronary intervention and OR 0.44, 95% CI 0.38 to 0.51, p <0.001 for CABG). In conclusion, the rate of admission for HF after discharge for a first myocardial infarction as well as all-cause death decreased markedly from 2000 to 2015.

ASSOCIATION OF ORTHOSTATIC HYPERTENSION WITH MORTALITY IN THE SYSTOLIC HYPERTENSION IN THE ELDERLY PROGRAM

History and physical, target organ damage, and biomarkers are used to estimate risk in patients with hypertension. Orthostatic hypertension is a marker of elevated risk that can be identified during physical examination but is not usually appreciated by clinicians. Vital status and cause of death