The pathogenesis and diagnosis of sepsis post burn injury

Burn is an under-appreciated trauma that is associated with unacceptably high morbidity and mortality.Although the survival rate after devastating burn injuries has continued to increase in previous decades due to medical advances in burn wound care,nutritional and fluid resuscitation and improved infection control practices,there are still large numbers of patients at a high risk of death.One of the most common complications of burn is sepsis,which is defined as“severe organ dysfunction attributed to host’s disordered response to infection”and is the primary cause of death in burn patients.Indeed,burn injuries are accompanied by a series of events that lead to sepsis and multiple organ dysfunction syndrome,such as a hypovolaemic state,immune and inflammatory responses and metabolic changes.Therefore,clear diagnostic criteria and predictive biomarkers are especially important in the prevention and treatment of sepsis and septic shock.In this review,we focus on the pathogenesis of burn wound infection and the post-burn events leading to sepsis.Moreover,the clinical and promising biomarkers of burn sepsis will also be summarized.

Polydopamine-coated i-motif DNA/Gold nanoplatforms for synergistic photothermal-chemotherapy

The combination of photothermal therapywith chemotherapy has gradually developed into promising cancer therapy.Here,a synergistic photothermal-chemotherapy nanoplatform based on polydopamine(PDA)-coated gold nanoparticles(AuNPs)were facilely achieved via the in situ polymerization of dopamine(DA)on the surface of AuNPs.This nanoplatform exhibited augmented photothermal conversion efficiency and enhanced colloidal stability in comparison with uncoated PDA shell AuNPs.The i-motif DNA nanostructure was assembled on PDA-coated AuNPs,which could be transformed into a C-quadruplex structure under an acidic environment,showing a characteristic pH response.The PDA shell served as a linker between the AuNPs and the i-motif DNA nanostructure.To enhance the specific cellular uptake,the AS1411 aptamer was introduced to the DNA nanostructure employed as a targeting ligand.In addition,Dox-loaded NPs(DAu@PDA-AS141)showed the pH/photothermal-responsive release of Dox.The photothermal effect of DAu@PDA-AS141 elicited excellent photothermal performance and efficient cancer cell inhibition under 808 nm near-infrared(NIR)irradiation.Overall,these results demonstrate that the DAu@PDA-AS141 nanoplatform shows great potential in synergistic photothermal-chemotherapy.

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.