Excessive production of proinflammatory mediators is observed in patients undergoing hemorrhagic and septic shock. Here, we report the detection of cold-inducible RNA-binding protein (CIRP) in the blood of surgical ICU individuals. In animal models of hemorrhage and sepsis, CIRP is up-regulated in several organs and released into the circulation. Under hypoxic stresses, CIRP in macrophages is translocated from the nucleus to the cytosol and actively released. Recombinant CIRP stimulates TNF-α and HMGB1 release in macrophages as well as induces inflammatory responses and causes tissue injury in animals. Antisera to CIRP attenuate shock-induced inflammation, tissue injury, and lethality. Extracellular CIRP's activity is mediated through the TLR4/MD2 complex. Surface plasmon resonance analysis indicates that CIRP binds to the TLR4/MD2 complex as well as to individual TLR4 and MD2. The human CIRP amino-acid segment 106-125 binds to MD2 with high affinity. Collectively, CIRP is a new proinflammatory mediator of shock.

To examine the potential roles of melatonin in drought tolerance, we tested the effects of its long-term exogenous application on 'Hanfu' apple (Malus domestica Borkh.). When 100 μm melatonin was added to soils under drought conditions, the resultant oxidative stress was eased and leaf senescence was delayed. This molecule significantly reduced chlorophyll degradation and suppressed the up-regulation of senescence-associated gene 12 (SAG12) and pheophorbide a oxygenase (PAO). Such treatment also alleviated the inhibition of photosynthesis brought on by drought stress. We also investigated quenching and the efficiency of Photosystem II (PSII) photochemistry under dark and light conditions and found that melatonin helped to maintain better function of PSII under drought. The addition of melatonin also controlled the burst of hydrogen peroxide, possibly through direct scavenging and by enhancing the activities of antioxidative enzymes and the capacity of the ascorbate-glutathione cycle. Thus, understanding this effect of melatonin on drought tolerance introduces new possibilities to use this compound for agricultural purposes.

Sepsis is a deadly inflammatory syndrome caused by an exaggerated immune response to infection. Much has been focused on host response to pathogens mediated through the interaction of pathogen-associated molecular patterns (PAMPs) and pattern recognition receptors (PRRs). PRRs are also activated by host nuclear, mitochondrial, and cytosolic proteins, known as damage-associated molecular patterns (DAMPs) that are released from cells during sepsis. Some well described members of the DAMP family are extracellular cold-inducible RNA-binding protein (eCIRP), high mobility group box 1 (HMGB1), histones, and adenosine triphosphate (ATP). DAMPs are released from the cell through inflammasome activation or passively following cell death. Similarly, neutrophil extracellular traps (NETs) are released from neutrophils during inflammation. NETs are webs of extracellular DNA decorated with histones, myeloperoxidase, and elastase. Although NETs contribute to pathogen clearance, excessive NET formation promotes inflammation and tissue damage in sepsis. Here, we review DAMPs and NETs and their crosstalk in sepsis with respect to their sources, activation, release, and function. A clear grasp of DAMPs, NETs and their interaction is crucial for the understanding of the pathophysiology of sepsis and for the development of novel sepsis therapeutics.