The concept of epigenetic reprogramming predicts long-term functional health effects. This reprogramming can be activated by exogenous or endogenous insults, leading to altered healthy and different disease states. The exogenous or endogenous changes that involve developing a roadmap of epigenetic networking, such as drug components on epigenetic imprinting and restoring epigenome patterns laid down during embryonic development, are paramount to establishing youthful cell type and health. This epigenetic landscape is considered one of the hallmarks of cancer. The initiation and progression of cancer are considered to involve epigenetic abnormalities and genetic alterations. Cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer development, including DNA methylation, histone modifications, nucleosome positioning, non-coding RNAs, and microRNA expression. Endocannabinoids are natural lipid molecules whose levels are regulated by specific biosynthetic and degradative enzymes. They bind to and activate two primary cannabinoid receptors, type 1 (CB1) and type 2 (CB2), and together with their metabolizing enzymes, form the endocannabinoid system. This review focuses on the role of cannabinoid receptors CB1 and CB2 signaling in activating numerous receptor tyrosine kinases and Toll-like receptors in the induction of epigenetic landscape alterations in cancer cells, which might transmogrify cancer metabolism and epigenetic reprogramming to a metastatic phenotype. Strategies applied from conception could represent an innovative epigenetic target for preventing and treating human cancer. Here, we describe novel cannabinoid-biased G protein-coupled receptor signaling platforms (GPCR), highlighting putative future perspectives in this field.

Background: Non-platelet thromboxane generation, stimulated largely by oxidative stress, is a novel mortality risk factor in individuals with coronary artery disease. Though inversely associated with left ventricular ejection fraction (LVEF), a potential role in the pathobiology of heart failure (HF) remains poorly defined. Methods: Non-platelet thromboxane generation and oxidative stress were assessed by measuring urine thromboxane B2 metabolites (TXB2-M) and 8-isoPGF2α by ELISA in 105 subjects taking aspirin undergoing right heart catheterization for evaluation of HF, valve disease or after transplantation. Multivariable logistic regression and survival analyses were used to define associations of TXB2-M to invasive measures of cardiovascular performance and 4-year clinical outcome. Results: TXB2-M was elevated (>1500 pg/mg creatinine) in 46% of subjects and correlated with HF severity by NYHA functional class and brain natriuretic peptide level, modestly with LVEF, but not with HF etiology. There was no association of oxidative stress to HF type or etiology but a trend with NYHA functional class. Multiple invasive hemodynamic parameters independently associated with TXB2-M after adjustment for oxidative stress, age, sex and race with pulmonary effective arterial elastance (Ea (pulmonary)), reflective of right ventricular afterload, being the most robust on hierarchical analysis. Similar to Ea (pulmonary), elevated urinary TXB2-M associated with increased risk of death (adjusted HR 2.15, P=0.037) and combination of death, transplant, or mechanical support initiation (adjusted HR 2.0, P=0.042). Conclusions: Non-platelet TXA2 thromboxane generation independently associated with HF severity reflected by invasive measures of cardiovascular performance, particularly right ventricular afterload, and independently predicted long-term mortal

Since the discovery of insulin over 100 years ago, our understanding of the insulin signaling pathway has greatly expanded [...]