Usp9x contributes to the development of sepsis-induced acute kidney injury by promoting inflammation and apoptosis in renal tubular epithelial cells via activation of the TLR4/nf-κb pathway.

As a pattern recognition receptor, Toll-like receptor 4 (TLR4) is crucial for the development and progression of acute kidney injury (AKI). This study aims to explore whether the deubiquitinase Usp9x influences the TLR4/NF-B pathway to cause sepsis-induced acute kidney injury (S-AKI). The model of AKI was established in Sprague-Dawley rats using the cecal ligation and puncture (CLP) method, while renal tubular epithelial cell NRK-52E was stimulated with lipopolysaccharide (LPS) in vitro. All plasmids were transfected into NRK-52E cells according to the indicated group. The deubiquitinase of TLR4 was predicted by the online prediction software Ubibrowser. Subsequently, Western blot and Pearson correlation analysis identified Usp9x protein as a potential candidate. Co-IP analysis verified the interaction between TLR4 and Usp9x. Further research revealed that overexpression of Usp9x inhibited degradation of TLR4 protein by downregulating its ubiquitination modification levels. Both in vivo and in vitro experiments observed that interference with Usp9x effectively alleviated the inflammatory response and apoptosis of renal tubular epithelial cells (RTECs) induced by CLP or LPS, whereas overexpression of TLR4 reversed this situation. Transfection with sh-Usp9x in NRK-52E cells suppressed the expression of proteins associated with the TLR4/NF-κB pathway induced by LPS. Moreover, the overexpression of TLR4 reversed the effect of sh-Usp9x transfection. Therefore, the deubiquitinase Usp9x interacts with TLR4, leading to the upregulation of its expression through deubiquitination modification, and the activation of the TLR4/NF-κB signaling pathway, thereby promoting inflammation and apoptosis in renal tubular epithelial cells and contributing to sepsis-induced acute kidney injury.

Extracorporeal membrane oxygenation combined with sequential blood purification in the treatment of myocardial damage and cardiac arrest caused by mushroom poisoning.

Mushroom poisoning is a common clinical problem. Severe mushroom poisoning often causes liver and kidney failure. Although severe myocardial damage is rare, the fatality rate is extremely high. This case report describes a 56-year-old male suffered severe myocardial damage, multiple organ dysfunction, circulatory failure, recurrent malignant arrhythmia, and cardiac arrest after the ingestion of wild mushrooms. He was administered venoarterial extracorporeal membrane oxygenation (VA-ECMO) combined with hemoperfusion, plasma exchange and continuous renal replacement therapy. The heart rhythm gradually stabilized 3 hours after ECMO surgery. On the 6th day after ECMO, heart function recovered. The patient was then weaned from ECMO, and he ultimately recovered and was discharged. In patients with fatal mushroom poisoning leading to refractory arrhythmia and cardiac arrest, early implementation of VA-ECMO combined with sequential blood purification treatment can improve the prognosis and increase the survival rate.

"Awake" Extracorporeal Membrane Oxygenation Combined With Continuous Renal Replacement Therapy For the Treatment of Severe Chemical Gas Inhalation Lung Injury.

Lung injury caused by chemical gas inhalation is a common clinically severe disease that very easily progresses to acute respiratory distress syndrome (ARDS). Traditional respiratory support consists mainly of mechanical ventilation, but the prognosis of this condition is still poor. "Awake" extracorporeal membrane oxygenation (ECMO) maintains oxygenation, improves ventilation, adequately allows the injured lungs to rest, and avoids complications associated with sedation, intubation, and mechanical ventilation. Continuous renal replacement therapy (CRRT) can provide better fluid management and reduce pulmonary edema. Herein, we describe the case of a patient with severe chemical gas inhalation lung injury who failed to respond to traditional mechanical ventilation and was subsequently treated with awake ECMO combined with CRRT.

[Effect of angiotensin II on the expression of aquaporin 1 in lung of rats following acute lung injury].

OBJECTIVE: To investigate the effect of angiotensin II (Ang II) on the expression of aquaporin 1 (AQP1) in lung of rats with acute lung injury (ALI) and the role of Ang II in the formation of lung edema. METHODS: Forty healthy Sprague-Dawley (SD) rats were randomly divided into sham-operated group, model group, Ang II receptor blocker pretreatment group, and Ang II receptor blocker treatment group according to random digits table, with 10 rats in each group. ALI model of rats was reproduced with administration of endotoxin after hemorrhagic shock. In rats of pretreatment group Ang II receptor blocker 30 microg/kg was given 30 minutes before lipopolysaccharide (LPS) injection; rats in treatment group Ang II receptor blocker 30 microg/kg was given 30 minutes after LPS injection; rats in model group received 30 microg/kg normal saline 30 minutes before and after LPS injection. Rats were sacrificed 6 hours after model establishment, samples of venous blood and lung tissue were collected, radioimmunoassay was used to measure the level of tumor necrosis factor-alpha (TNF-alpha) in serum and the expression of Ang II in lung tissue, ratio of wet to dry (W/D) weight of lung tissue was calculated, reverse transcription-polymerase chain reaction was used to measure the expression of AQP1 mRNA in lung tissue. RESULTS: Compared with rats of sham-operated group, the level of TNF-alpha in venous blood, W/D ratio and the expression of Ang II in lung tissue increased significantly, the expression of AQP1 mRNA in lung tissue decreased significantly in rats of ALI. Compared with rats of model group, the level of TNF-alpha in venous blood (microg/L) decreased significantly (4.79+/-0.24, 5.55+/-0.36 vs. 6.34+/-0.31, both P<0.05), W/D ratio decreased significantly (4.34+/-0.23, 4.85+/-0.20 vs. 5.41+/-0.26, both P<0.05), the expression of AQP1 mRNA in lung tissue increased significantly (0.854+/-0.067, 0.727+/-0.081 vs. 0.358+/-0.071, both P<0.05), and the expression of Ang II in lung tissue (ng/g) decreased to some extent (172.19+/-15.82, 202.82+/-20.47 vs. 245.88+/-26.31), but without statistical significance (both P>0.05) in rats of pretreatment group and treatment group. The expression of AQP1 mRNA was negatively correlated with both the level of Ang II and W/D ratio (r1=-0.782, r2=-0.726, both P<0.05). CONCLUSION: During ALI, Ang II may downregulate the expression of AQP1 mRNA in lung tissue directly or through inflammatory mediators, Ang II may play a role in the formation of lung edema.