Rhabdomyolysis is a severe condition that commonly leads to acute kidney injury (AKI), with limited targeted treatments for rhabdomyolysis-induced AKI (RIAKI) adding to the challenge. Emerging evidence implicates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) in the pathological processes of various kidney diseases, but its role in RIAKI remains unclear. We applied renal tubular epithelial cell (RTEC)-specific NOX4 knockout and the NOX4 inhibitor GKT137831 to treat RIAKI in vivo and in vitro. We found that genetic and pharmacological inhibition of NOX4 protected against glycerol-induced renal dysfunction, mitigated inflammatory responses and attenuated apoptotic rates. Additionally, NOX4 blockade suppressed the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), and enhanced the activities of antioxidant enzymes. Furthermore, NOX4 inhibition reduced the expression of endoplasmic reticulum stress (ERS)-associated proteins at both the RNA and protein levels. Collectively, these findings demonstrate that genetic and pharmacological suppression of NOX4 protects against RIAKI by reducing ROS generation, boosting antioxidant defense and inhibiting ERS activation. NOX4 inhibition may offer a potential approach for developing new treatment options for RIAKI.
Kidney diseases are major global health problems, with high prevalence and mortality. However, current treatment strategies for kidney diseases fail to achieve satisfactory efficacy. Mesenchymal stem cell (MSC)-based therapy has been a promising strategy for treating kidney diseases. Preclinical studies have proven its safety and effectiveness in treating acute kidney injury and chronic kidney disease, but the outcomes of clinical trials have shown very limited clinical efficacy. A variety of innovative approaches have been proposed to enhance the therapeutic potential of MSCs, and hydrogels are attractive candidates. Hydrogels are three-dimensional networks formed by hydrophilic polymers of natural or synthetic origin with diverse physical and chemical properties. They have been widely applied in the field of drug delivery and regenerative medicine, including MSC-based therapy. Many studies have proven that hydrogels can improve the therapeutic efficacy of MSCs for kidney diseases, but there are still challenges limiting the widespread application of this method. In this review, we introduce the application of MSCs in kidney diseases and factors that influence therapeutic efficiency and focus on the beneficial effects of hydrogels in MSC-based therapy for AKI and CKD.
The recreational use of nitrous oxide (N2O) is sharply increasing among young adults. N2O abuse can cause serious complications. However, the association between acute pancreatitis and N2O is rarely reported. Here we report a case of a young and previously healthy female with widespread cutaneous lesions, neurologic symptoms, and abdominal pain. Acute pancreatitis was the patient's primary diagnosis when she was admitted to the gastroenterology unit. We added the diagnosis of N2O intoxication after an additional inquiry into the patient's personal history revealed that she had abused N2O for 1 month. With the application of mecobalamin and other symptomatic treatments, the symptoms and laboratory indexes improved gradually. In this case, we highlight that acute pancreatitis may be a rare complication induced by N2O.