Toll like receptors and inflammatory factors in sepsis and differential expression related to age

In recent years, the incidence of systematic severe .infection in intensive care units （ICUs） has increased significantly. Sepsis is a＂ complex, multifactorial syndrome that can develop into conditions of different severity, described as severe sepsis or septic shock. The immunology of severe sepsis and septic shock is poorly defined, despite many studies investigating the pathogenesis of this syndrome. With mortality rates of up to 50%, greater understanding of the interactions between host and microbe is necessary to improve patient outcome. Given the rapid progression of sepsis and immediate recruitment of the inflammatory cytokine cascade, the early innate response of the immune system to the pathogen is likely to play a critical role.

Interrelationship between Toll-like receptors and infection after orthotopic liver transplantation

Early microbial recognition by the innate immune system is accomplished by Toll-like receptors(TLRs),with resultant initiation of a pro-inflammatory response against infecting organisms.In spite of presence of an abundance of Toll-like receptors on the surface of the liver,gut bacteria does not elicit an inflammatory reaction in healthy individuals due to tolerance to these TLRs,suggesting that the inflammatory responses seen in the liver are the result of breakdown of this tolerance.While orthotopic liver transplantation is often life saving in many instances,death following this procedure is most commonly due to infection that occurs in up to 80%of transplant recipients,most commonly due to microbial causes in up to 70%of cases and viral infections in 20%,while fungal infections affect only 8%of cases.The probability of acquiring infection following hepatic transplantation is heightened due to affection of the innate immune defense mechanisms of the host following this procedure.Single nucleotide polymorphisms of TLRs have been associated with increased likelihood of either development of post-transplant infection or eradication of infecting organism.However,conflicting reports from other studies reveal that prevalence of this single nucleotide polymorphism is not increased in infected patients.

Gut microbiome dysbiosis in the setting of solid organ transplantation:What we have gleaned from human and animal studies

The human gut microbiome refers to all of the microorganisms present throughout the length of the gastrointestinal tract.Gut flora influence host metabolic and immune processes in myriad ways.They also play an important role in maturation and modulation of the immune system.Dysbiosis or a pathologic alteration in gut flora has been implicated in a number of diseases ranging from metabolic,autoimmune and degenerative.Whether dysbiosis has similar implications in organ transplant has been the focus of a number of pre-clinical and clinical studies.Researchers have observed significant microbiome changes after solid organ transplantation in humans that have been associated with clinical outcomes such as post-transplant urinary tract infections and diarrhea.In this article,we will discuss the available data regarding pathologic alterations in gut microbiome(dysbiosis)in solid organ transplant recipients as well as some of challenges in this field.We will also discuss animal studies focusing on mouse models of transplantation that shed light on the underlying mechanisms that explain these findings.

General principles of developing novel radioprotective agents for nuclear emergency

With the rapid application of nuclear energy and radiological technology in national economy and military field,the risk of nuclear accidents increases as well.Exposure to irradiation causes severe damages to the human body,and radioprotective agents are required for medical protection.To find the safe and effective radioprotective agents is the key for nuclear emergency.Recently,Toll like receptors(TLRs)and PHD-HIF oxygen sensing signal pathway have been extensively studied for radioprotection.Great progress has been made in this field and a number of radioprotective agents have been found.In this review,we have summarized recent findings of radioprotective roles of TLRs signaling pathway and PHD-HIF signaling pathway and discussed the general principles of developing novel radioprotective agents.These findings will provide opportunities for developing new strategies to prevent IR-induced injuries in public health events.