PERK-STING-RIPK3 pathway facilitates cognitive impairment by inducing neuronal necroptosis in sepsis-associated encephalopathy.

AIMS: Sepsis-associated encephalopathy (SAE) is a common but serious complication in septic survivors and often causes long-term cognitive impairments. The role of RIPK3-participated necroptosis in SAE remains obscured. STING is a key molecule in regulating necroptosis and apoptosis. However, there is uncertainty as to the mechanisms of STING in CLP-induced SAE. The aim of this study was to investigate whether STING is involved in the underlying mechanism of SAE. METHODS: The contextual fear conditioning test (CFCT) assesses cognitive impairment. A transmission electron microscope (TEM) was used to notice the necroptosis. Western blotting and immunofluorescence labeling were applied for the observation of related proteins. RESULTS: The phosphorylated STING in the hippocampal neuron of SAE mice was significantly elevated. Knocking down STING inhibited necroptosis and attenuated cognitive impairment in SAE mice. Moreover, RIPK3-/- mice had less cognitive deficit in the SAE model. However, STING overexpression did not deteriorate cognitive impairment in RIPK3-/- mice with SAE, indicating that STING is upstream involved in necroptosis. Furthermore, PERK inhibition ameliorated cognitive deficits through a STING-dependent pathway in SAE mice. CONCLUSION: PERK-STING-RIPK3 pathway facilitates cognitive impairment by inducing neuronal necroptosis in the pathology of SAE, which provided a new therapeutic target in SAE treatment.

Recent progress of antimicrobial peptides in sepsis treatment / 中华危重病急救医学

Sepsis is a life-threatening organ dysfunction due to the dysregulation of host responses during infection. Severe systemic inflammatory response syndrome (SIRS) is the primary pathophysiological feature. Despite the classical antibiotic therapies play an important role in sepsis, the emergence of multi-resistant bacteria makes a greater challenge in clinical. Antimicrobial peptides (AMP) which consist of small cationic peptides, can be found in most organisms. As a result of their board-spectrum antibacterial activities and immunoregulatory functions, AMPs may have an excellent effect on the treatment of sepsis. In this review, we will discuss the basic role of AMPs in sepsis treatment and their application prospect and the challenges which need to be resolved in order to provide ideas for clinical application of AMPs.

How to improve the teaching ability of young teachers of critical care medicine? / 中华危重病急救医学

Intensive care unit (ICU) in teaching hospital plays important roles in teaching work. The young teachers of critical care medicine are gradually becoming the backbone of teaching work. Improving the teaching ability of young teachers is essential to increase learning motivation of the students and to promote the overall teaching quality of critical care medicine. Therefore, pay attention to help the young teachers of critical care medicine to improve their teaching skill is good for enhancing the faculty developing of critical care medicine, as well as essential for the prosperity and sustainable development of critical care medicine. Based on the problems existing during the teaching process of young teachers of critical care medicine and aimed to train excellent teachers, this article discussed the teaching methods and experience of young teachers of critical care medicine which focuses on teaching program design, class affinity improvement and humanistic education in order to improve the teaching level of young teachers of critical care medicine.

Neuroprotective Autophagic Flux Induced by Hyperbaric Oxygen Preconditioning is Mediated by Cystatin C / 神经科学通报·英文版

We have previously reported that Cystatin C (CysC) is a pivotal mediator in the neuroprotection induced by hyperbaric oxygen (HBO) preconditioning; however, the underlying mechanism and how CysC changes after stroke are not clear. In the present study, we demonstrated that CysC expression was elevated as early as 3 h after reperfusion, and this was further enhanced by HBO preconditioning. Concurrently, LC3-II and Beclin-1, two positive-markers for autophagy induction, exhibited increases similar to CysC, while knockdown of CysC blocked these elevations. As a marker of autophagy inhibition, p62 was downregulated by HBO preconditioning and this was blocked by CysC knockdown. Besides, the beneficial effects of preserving lysosomal membrane integrity and enhancing autolysosome formation induced by HBO preconditioning were abolished in CysC rats. Furthermore, we demonstrated that exogenous CysC reduced the neurological deficits and infarct volume after brain ischemic injury, while 3-methyladenine partially reversed this neuroprotection. In the present study, we showed that CysC is biochemically and morphologically essential for promoting autophagic flux, and highlighted the translational potential of HBO preconditioning and CysC for stroke treatment.