Inflammatory processes underlie many diseases associated with injury of the heart muscle, including conditions without an obvious inflammatory pathogenic component such as hypertensive and diabetic cardiomyopathy. Persistence of cardiac inflammation can cause irreversible structural and functional deficits. Some are induced by direct damage of the heart muscle by cellular and soluble mediators but also by metabolic adaptations sustained by the inflammatory microenvironment. It is well established that both cardiomyocytes and immune cells undergo metabolic reprogramming in the site of inflammation, which allow them to deal with decreased availability of nutrients and oxygen. However, like in cancer, competition for nutrients and increased production of signalling metabolites such as lactate initiate a metabolic cross-talk between immune cells and cardiomyocytes which, we propose, might tip the balance between resolution of the inflammation versus adverse cardiac remodeling. Here we review our current understanding of the metabolic reprogramming of both heart tissue and immune cells during inflammation, and we discuss potential key mechanisms by which these metabolic responses intersect and influence each other and ultimately define the prognosis of the inflammatory process in the heart.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid cancers with dismal prognosis. Several mechanisms that are mainly responsible for aggressiveness and therapy resistance of PDAC cells include epithelial to mesenchymal transition (EMT), stemness and Mitogen Activated Protein Kinase (MAPK) signaling. Strategies that inhibit these mechanisms are critically important to improve therapeutic outcome in PDAC. In the current study, we wanted to investigate whether gold nanoparticles (AuNPs) could sensitize pancreatic cancer cells to the chemotherapeutic agent gemcitabine. We demonstrated that treatment with AuNPs of 20 nm diameter inhibited migration and colony forming ability of pancreatic cancer cells. Pre-treatment with AuNPs sensitized pancreatic cancer cells to gemcitabine in both viability and colony forming assays. Mechanistically, pre-treatment of pancreatic cancer cells with AuNPs decreased gemcitabine induced EMT, stemness and MAPK activation. Taken together, these findings suggest that AuNPs could be considered as a potential agent to sensitize pancreatic cancer cells to gemcitabine.

Ceramides are central intermediates of sphingolipid metabolism that can activate a variety of tumor suppressive cellular programs, including cell cycle arrest, senescence and apoptosis. Indeed, perturbations in ceramide generation and turnover are frequently linked to cancer cell survival and resistance to chemotherapy. Consequently, the potential of ceramide-based therapeutics in the treatment of cancer has become a major focus of interest. A growing body of evidence indicates that ceramides can act directly on mitochondria to trigger apoptotic cell death. However, molecular details of the underlying mechanism are scarce. In our recent study (Dadsena S et al., 2019, Nat Commun 10:1832), we used a photoactivatable ceramide probe combined with computer simulations and functional studies to identify the voltage-dependent anion channel VDAC2 as a critical effector of ceramide-induced mitochondrial apoptosis. Collectively, our findings provide a novel molecular framework for how ceramides execute their widely acclaimed anti-neoplastic activities.