NAD+metabolism:pathophysiologic mechanisms and therapeutic potential

Nicotinamide adenine dinucleotide(NAD^(+))and its metabolites function as critical regulators to maintain physiologic processes,enabling the plastic cells to adapt to environmental changes including nutrient perturbation,genotoxic factors,circadian disorder,infection,inflammation and xenobiotics.These effects are mainly achieved by the driving effect of NAD^(+)on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions.Besides,multiple NAD^(+)-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA,RNA and proteins,or releasing second messenger cyclic ADPribose(cADPR)and NAADP^(+).Prolonged disequilibrium of NAD^(+)metabolism disturbs the physiological functions,resulting in diseases including metabolic diseases,cancer,aging and neurodegeneration disorder.In this review,we summarize recent advances in our understanding of the molecular mechanisms of NAD^(+)-regulated physiological responses to stresses,the contribution of NAD^(+)deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.

Radiotherapy-induced heart disease:a review of the literature

Radiotherapy as one of the four pillars of cancer therapy plays a critical role in the multimodal treatment of thoracic cancers.Due to significant improvements in overall cancer survival,radiotherapy-induced heart disease(RIHD)has become an increasingly recognized adverse reaction which contributes to major radiationassociated toxicities including non-malignant death.This is especially relevant for patients suffering from diseases with excellent prognosis such as breast cancer or Hodgkin’s lymphoma,since RIHD may occur decades after radiotherapy.Preclinical studies have enriched our knowledge of many potential mechanisms by which thoracic radiotherapy induces heart injury.Epidemiological findings in humans reveal that irradiation might increase the risk of cardiac disease at even lower doses than previously assumed.Recent preclinical studies have identified non-invasive methods for evaluation of RIHD.Furthermore,potential options preventing or at least attenuating RIHD have been developed.Ongoing research may enrich our limited knowledge about biological mechanisms of RIHD,identify non-invasive early detection biomarkers and investigate potential treatment options that might attenuate or prevent these unwanted side effects.Here,we present a comprehensive review about the published literature regarding clinical manifestation and pathological alterations in RIHD.Biological mechanisms and treatment options are outlined,and challenges in RIHD treatment are summarized.