Micheliolide Attenuates Lipopolysaccharide-Induced Inflammation by Modulating the mROS/NF-κB/NLRP3 Axis in Renal Tubular Epithelial Cells.

Chronic kidney disease is a common disease closely related to renal tubular inflammation and oxidative stress, and no effective treatment is available. Activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is an important factor in renal inflammation, but the mechanism remains unclear. Micheliolide (MCL), which is derived from parthenolide, is a new compound with antioxidative and anti-inflammatory effects and has multiple roles in tumors and inflammatory diseases. In this study, we investigated the effect of MCL on lipopolysaccharide- (LPS-) induced inflammation in renal tubular cells and the related mechanism. We found that MCL significantly suppressed the LPS-induced NF-κB signaling and inflammatory expression of cytokines, such as tumor necrosis factor-α and monocyte chemoattractant protein-1 in a rat renal proximal tubular cell line (NRK-52E). MCL also prevented LPS- and adenosine triphosphate-induced NLRP3 inflammasome activation in vitro, as evidenced by the inhibition of NLRP3 expression, caspase-1 cleavage, and interleukin-1ß and interleukin-18 maturation and secretion. Additionally, MCL inhibited the reduction of mitochondrial membrane potential and decreases the release of reactive oxygen species (ROS). Moreover, MCL can prevent NLRP3 inflammasome activation induced by rotenone, a well-known mitochondrial ROS (mROS) agonist, indicating that the mechanism of MCL's anti-inflammatory effect may be closely related to the mROS. In conclusion, our study indicates that MCL can inhibit LPS-induced renal inflammation through suppressing the mROS/NF-κB/NLRP3 axis in tubular epithelial cells.

Micheliolide ameliorates lipopolysaccharide-induced acute kidney injury through suppression of NLRP3 activation by promoting mitophagy via Nrf2/PINK1/Parkin axis.

BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) represents a frequent complication of in critically ill patients. The objective of this study is to illuminate the potential protective activity of Micheliolide (MCL) and its behind mechanism against SA-AKI. METHODS: The protective potential of MCL on SA-AKI was investigated in lipopolysaccharide (LPS) treated HK2 cells and SA-AKI mice model. The mitochondrial damage was determined by detection of reactive oxygen species and membrane potential. The Nrf2 silencing was achieved by transfection of Nrf2-shRNA in HK2 cells, and Nrf2 inhibitor, ML385 was employed in SA-AKI mice. The mechanism of MCL against SA-AKI was evaluated through detecting hallmarks related to inflammation, mitophagy and Nrf2 pathway via western blotting, immunohistochemistry, and enzyme linked immunosorbent assay. RESULTS: MCL enhanced viability, suppressed apoptosis, decreased inflammatory cytokine levels and improved mitochondrial damage in LPS-treated HK2 cells, and ameliorated renal injury in SA-AKI mice. Moreover, MCL could reduce the activation of NLRP3 inflammasome via enhancing mitophagy. Additionally, Nrf2 deficiency reduced the suppression effect of MCL on NLRP3 inflammasome activation and blocked the facilitation effect of MCL on mitophagy in LPS-treated HK2 cells, the consistent is true for ML385 treatment in SA-AKI mice. CONCLUSIONS: MCL might target Nrf2 and further reduce the NLRP3 inflammasome activation via enhancing mitophagy, which alleviated SA-AKI.

Treatment Efficacy of Continuous Renal Replacement on Symptoms, Inflammatory Mediators, and Coagulation Function in Patients with Sepsis-Associated Acute Kidney Injury.

INTRODUCTION: The aim of this study is to compare the treatment efficacy between continuous renal replacement therapy (CRRT) and conventional intermittent hemodialysis (IHD) in patients with sepsis (SIRS) combined with acute kidney injury (AKI) and its impact on inflammatory mediators and coagulation function. METHOD: 122 patients (25-60 years) with SIRS combined with AKI were enrolled in the sudy. The study group (SG) comprised 62 patients who received CRRT (8-10 h/day) + routine treatment, whereas the control group (CG) comprised 60 patients who received conventional IHD (4 h/day, 3 times per week) + routine treatment. inflammatory mediators and coagulation function measures were assessed and compared in each group. RESULTS: C-reactive protein, blood creatinine, blood urea nitrogen, blood lactic acid, oxygenation index, central venous oxygen saturation, SOFA (Sequential Organ Failure Assessment) score, interleukin 6, interleukin 8, hypersensitive C-reactive protein, tumor necrosis factor-α, prothrombin time, activated partial thromboplastin time, FIB, and platelet count were better in the SG than in the CG (p < 0.05). The 12- and 24-month survival rates were significantly higher in the SG than in the CG (p < 0.05). CONCLUSIONS: CRRT can effectively improve clinical symptoms, remove inflammatory factors, and maintain blood coagulation function in patients with SIRS combined with AKI. It is more efficient than IHD treatment and is worthy of clinical promotion.

Effect of continuous renal replacement therapy adjuvant to broad-spectrum enzyme inhibitors on the efficacy and inflammatory cytokines in patients with severe acute pancreatitis.

OBJECTIVE: To investigate the effect of continuous renal replacement therapy (CRRT) combined with ulinastatin, a broad-spectrum enzyme inhibitor, on the treatment effect and inflammatory mediator levels in patients with severe acute pancreatitis (SAP). METHODS: A total of 80 patients with SAP admitted to our hospital were divided into two groups according to a random number table, with 40 cases in the control group and 40 cases in the experimental group. The control group was treated with the broad-spectrum enzyme inhibitor ulinastatin, and the experimental group was treated with continuous renal replacement therapy (CRRT) in addition to the control group's treatment method. The clinical efficacy was evaluated. Serum inflammation indicators, critical illness-related scores, pancreatic microcirculation and coagulation indicators were also detected before and after treatment. RESULTS: After 14 days of continuous intervention, the total effective rate of the experimental group was 92.50%, and that of the control group was 75.00%, with statistical significance between the two groups (P<0.05). The expression of APN in the two groups' serum increased, and the other inflammatory indexes decreased. The experimental group's serum APN was higher than that of the control group, and the other inflammatory indexes were lower than those of the control group (all P<0.001). The two groups' critical illness-related scores were improved, and there was a difference between the two groups (P<0.05). The levels of BF and BV increased, while TTP levels decreased, and there was a difference between the experimental and control groups (all P<0.01). The coagulation indexes of the two groups of patients were all improved. Compared with the control group, the coagulation indexes of the experimental group were lower. There was a difference between the two groups (P<0.01). CONCLUSION: CRRT adjuvant to broad-spectrum enzyme inhibitor ulinastatin can significantly improve the inflammatory response, microcirculation, hypercoagulability and clinical treatment efficacy in patients with severe acute pancreatitis.

Efficacy of continuous ambulatory peritoneal dialysis combined with hemodialysis versus single hemodialysis in patients with end-stage renal disease.

OBJECTIVE: This study aimed to compare the efficacy of single hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) combined with HD in the treatment of end-stage renal disease. METHODS: Seventy patients with end-stage renal disease in our hospital from January 2019 to December 2020 were included and divided into 35 patients in the single group (SG) and 35 patients in the combination group (CG) according to a random number table. The SG received HD treatment and the CG received CAPD combined with HD treatment. RESULTS: Hemoglobin and serum albumin levels were higher, blood urea nitrogen (BUN) and serum creatinine (Scr) levels were lower, and interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) levels were lower in the CG than in SG at the end of treatment (P < 0.05). Ca2+ levels were higher and P3+ levels were decreased at the end of treatment in both groups compared with those before treatment (P < 0.05), and Ca2+ and P3+ levels at the end of treatment in the CG were not different from those in the SG (P > 0.05). The complication rate in the CG was 5.71%, which was lower than 25.71% in the SG (P < 0.05). Quality of life scores were higher in the CG than in the SG at the end of treatment (P < 0.05). CONCLUSION: CAPD combined with HD can improve renal function and nutritional levels more significantly, control inflammatory responses more effectively, and reduce complications compared to single HD treatment in patients with end-stage renal disease.