Hao Tian

Postoperative cognitive dysfunction (POCD) is a prevalent complication affecting the central nervous system after surgery, manifesting as a decline in cognitive abilities, particularly common among elderly patients. Surgical stress and anesthesia can activate systemic inflammation, prompting immune cells, including neutrophils, to infiltrate the brain, thereby triggering neuroinflammation and resulting in cognitive impairment. Neutrophils, as crucial effector cells in innate immunity, have been increasingly recognized in recent years for their significant role in the pathogenesis of POCD due to their vital function in inflammatory responses. They are not only rapidly activated in peripheral blood, secreting a range of cytokines, chemokines, and neutrophil extracellular traps (NETs), but also possess the capacity to alter the permeability of the blood-brain barrier (BBB), further facilitating the development of neuroinflammation. This paper systematically reviews the recent findings on the diverse functions of neutrophils and their role in POCD, aiming to provide novel theoretical foundations and cutting-edge perspectives for advancing foundational research and optimizing clinical intervention strategies for POCD.

Background: The cause of aggravation of diabetic myocardial damage is yet to be elucidated; damage to mitochondrial function has been a longstanding focus of research. During diabetic myocardial ischaemia–reperfusion (MI/R), it remains unclear whether reduced mitochondrial fusion exacerbates myocardial injury by generating free damaged mitochondrial DNA (mitoDNA) and activating the cGAS-STING pathway.Methods: In this study, a mouse model of diabetes was established (by feeding mice a high-fat diet (HFD) plus a low dose of streptozotocin (STZ)), a MI/R model was established by cardiac ischaemia for 2 h and reperfusion for 30 min, and a cellular model of glycolipid toxicity induced by high glucose (HG) and palmitic acid (PA) was established in H9C2 cells.Results: We observed that altered mitochondrial dynamics during diabetic MI/R led to increased mitoDNA in the cytosol, activation of the cGAS-STING pathway, and phosphorylation of the downstream targets TBK1 and IRF3. In the cellular model we found that cytosolic mitoDNA was the result of reduced mitochondrial fusion induced by HG and PA, which also resulted in cGAS-STING signalling and activation of downstream targets. Moreover, inhibition of STING by H-151 significantly ameliorated myocardial injury induced by MFN2 knockdown in both the cell and mouse models. The use of a fat-soluble antioxidant CoQ10 improved cardiac function in the mouse models.Conclusions: Our study elucidated the critical role of cGAS-STING activation, triggered by increased cytosolic mitoDNA due to decreased mitochondrial fusion, in the pathogenesis of diabetic MI/R injury. This provides preclinical insights for the treatment of diabetic MI/R injury.Graphical

Myocardial ischemia-reperfusion (I/R) injury is a major cause of poor hemodynamic reconstitution outcomes after myocardial infarction or circulatory arrest. Currently, the search for effective therapeutic agents and tools is a focus of research in the field of myocardial I/R injury. Resveratrol (Res) has been extensively studied in recent years because of its good cardiovascular therapeutic effects, but its specific mechanism of action has not been fully elucidated. Therefore, the aim of this study was to investigate the mechanism of interaction between myocardial I/R injury and Res in vitro and in vivo. In our in vivo study, we used PI/TUNEL staining and western blotting to detect relevant necroptotic key molecules such as RIP1, RIP3 and p-MLKL/MLKL to observe myocardial necroptosis. The extent of myocardial injury was determined using hematoxylin and eosin (HE) staining and 2,3,5-triphenyltetrazolium chloride (TTC) staining as well as serum levels of CK-MB and LDH and echocardiography. In the in vitro study, cellular injury was assessed by CCK-8 and cell supernatant LDH levels. In addition, we used small interfering RNA (siRNA) transfection to knock down YAP, a key effector molecule of the Hippo pathway, to validate the molecular mechanism of action by which Res exerts myocardial protection. The localization of YAP in H9c2 cardiomyocytes was examined using immunofluorescence. Our data demonstrated that Res could ameliorate myocardial I/R-induced necroptosis by modulating the Hippo pathway, and that the beneficial effect of Res might be associated with nuclear translocation of the transcriptional regulator YAP.