Project description:Recent pre-clinical data provide strong evidence that short-term starvation before the administration of cytostatic drugs for the chemotherapy of solid tumors leads to significantly higher efficacy and lower toxicity levels. However, these findings have so far not been validated in patients. The aim of this trial is to provide first clinical evidence regarding the impact of pre-chemotherapeutic short-term starvation on response to therapy (primary endpoint). Additionally, progression-free survival, adverse events, and overall survival will be monitored (secondary endpoints). In perspective, short-term starvation before chemotherapy could represent a simple and secure way to improve both efficacy and tolerance of chemotherapies at low cost.
Project description:Increased beta-cell senescence contributes to the development of type 2 diabetes (T2D). Exercise is critical in the treatment of T2D and can attenuate aging-associated cellular changes, but its effects on beta-cell senescence are unknown. Using two mouse models of insulin resistance, we showed that exercise prevented and reversed beta-cell senescence. Mechanistic studies revealed that these effects were mediated by exercise-induced increases in serum glucagon leading to AMPK activation in beta-cells. Nuclear translocation of NRF2 in mouse islets after exercise and its inversely proportional regulation of p16Ink4a, suggested its role as a molecular mediator between AMPK activation and cellular senescence.
Project description:Molecular profiling of the hypothalamus in response to metabolic shifts is a critical cue to better understand the principle of the central control of whole-body energy metabolism. The transcriptional responses of the rodent hypothalamus to short-term calorie restriction have been documented. However, studies on the identification of hypothalamic secretory factors that potentially contribute to the control of appetite are lacking. In this study, we analyzed the differential expression of hypothalamic genes and compared the selected secretory factors from the fasted mice with those of fed control mice using bulk RNA-sequencing. We verified seven secretory genes that were significantly altered in the hypothalamus of fasted mice. In addition, we determined the response of secretory genes in cultured hypothalamic cells to treatment with ghrelin and leptin. The current study provides further insights into the neuronal response to food restriction at the molecular level and may be useful for understanding the hypothalamic control of appetite.