Lipoxin A4 Restores Septic Renal Function via Blocking Crosstalk Between Inflammation and Premature Senescence.

Acute kidney injury (AKI) occurs in half of patients with septic shock, resulting in unacceptably high mortality. However, effective preventive treatments are still lacking. We hypothesized that pretreatment with lipoxin A4 (LXA4), known to promote inflammation resolution, may attenuate septic AKI via blocking crosstalk between inflammation and cellular senescence. In this study, rats developed AKI following cecal ligation and puncture (CLP), as evidenced by a dynamic increase in serum creatinine, blood urea nitrogen, urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and pathological injury, accompanied by increased levels of inflammation (IL-6, TNF-α, and HMGB1) and tubular cell senescence. While, on the one hand, inhibition of senescence with rapamycin restored renal function and attenuated septic inflammatory response, on the other hand, LXA4 administration inhibited renal inflammation and tubular epithelial cell senescence after CLP. Ultimately, pretreatment with LXA4 significantly restored renal function and increased the survival rate of rats after CLP. Furthermore, LXA4 inhibited NF-κB-mediated inflammatory response and the p53/p21 senescence pathway in vivo and in vitro. However, the effect was reversed by PPAR-γ siRNA and antagonist. These results indicated that LXA4 exerted its renoprotective effects by blocking the crosstalk between inflammation and premature senescence in a PPAR-γ-dependent manner. Our findings also suggested that premature senescence plays a critical role in septic AKI and that inhibition of the crosstalk between inflammation and premature senescence may represent a new and major mechanism through which LXA4 attenuates septic AKI.

Laryngoscopic techniques modulate anaesthesiologists' perception of halitosis in patients: A randomised controlled trial.

BACKGROUND: Perception of halitosis in patients during intubation is a common and additional stressor for anaesthesiologists and may lead to potential health risks. OBJECTIVES: We hypothesised that intubation with videolaryngoscopy could help reduce the anaesthesiologists' perception of patients' oral malodor during intubation. DESIGN: A single-blinded, randomised controlled trial. SETTING: Single centre general hospital, Guangdong Province, China. PARTICIPANTS: A total of 440 patients who underwent intubation under general anaesthesia for elective surgery, aged 18 to 60 years old, American Society of Anaesthesiologists class I to III, without upper airway abnormality or airway infection were enrolled. INTERVENTION: Patients were randomly assigned to receive either UE videolaryngoscopy (UE) or Macintosh's direct laryngoscopy (Macintosh) group. All intubations were performed by one of six very experienced anaesthesiologists. MAIN OUTCOME MEASURES: The patient's oral odour score was measured prior to induction of anaesthesia. The anaesthesiologists' perception of the patient's oral malodor during intubation was recorded. The shortest distance from patient's mouth to the anaesthesiologist's nose (MN distance), the exertion rating and discomfort were also measured. RESULTS: The oral malodor score did not differ in the UE and Macintosh groups prior to the induction of anaesthesia. However, the incidence of the anaesthesiologists' perception of halitosis during intubation was significantly lower in the UE group compared with the Macintosh group (P < 0.001). Similarly, the MN distance was significantly greater in the UE group compared with the Macintosh group (P < 0.001). The first-attempt success rate was higher in the UE group compared to the Macintosh group (P < 0.001). However, the exertion scores were considerably higher in the Macintosh group. After intubation, anaesthesiologists experienced more waist and shoulder discomfort with the Macintosh than the UE technique of intubation. CONCLUSION: Compared with direct laryngoscopy, videolaryngoscopy might reduce the anaesthesiologists' perception of the patients' oral malodor, help improve first-attempt success rate, as well as alleviate the anaesthesiologists' waist and shoulder discomfort. TRIAL REGISTRATION: Clinicaltrials.gov (ChiCTR-IOR-15007038).

Propofol attenuates monocyte-endothelial adhesion via modulating connexin43 expression in monocytes.

AIMS: Monocyte-endothelial adhesion is considered to be the primary initiator of inflammatory vascular diseases, such as atherosclerosis. Connexin 43 (Cx43) has been reported to play an important part in this process, however, the underlying mechanisms are not fully understood. Intravenous anesthetics, propofol is commonly used in the perioperative period and in the intensive care unit, and considered to have good anti-inflammatory and antioxidant effects. Thus, we speculate that propofol could influence monocyte-endothelial adhesion, and explore whether its possible mechanism is relative with Cx43 expression in U937 monocytes influencing cell adhesion of U937 monocytes to human umbilical vein endothelial cells (HUVEC). MAIN METHODS: Cx43-siRNAs or pc-DNA-Cx43 were used to alter Cx43 expression in U937 monocytes. Propofol was given as pretreatments to U937 monocytes. Then, cell adhesion, ZO-1, LFA-1, VLA-4, COX and MCP-1 were determined. PI3K/AKT/NF-κB signaling pathway was explored to clarify the possible mechanism. KEY FINDINGS: Alternation of Cx43 expression affects cell adhesion and adhesion molecules significantly, such as ZO-1, LFA-1, VLA-4, COX-2 and MCP-1, the mechanism of which is relative with Cx43 influencing the activation of PI3K/AKT/NF-κB signaling pathway. Preconditioning with propofol at its clinically relevant anesthesia concentration attenuates cell adhesion. Propofol not only decreases Cx43 expression in U937 monocytes, but also depresses the activation of PI3K/AKT/NF-κB signaling pathway. SIGNIFICANCE: Modulation Cx43 expression in U937 monocytes could affect cell adhesion via regulating the activation of PI3K/AKT/NF-κB signaling pathway. Propofol attenuates cell adhesion via inhibiting Cx43 and its downstream signaling pathway of PI3K/AKT/NF-κB.