Synergistic Renoprotective Effect of Melatonin and Zileuton by Inhibition of Ferroptosis via the AKT/mTOR/NRF2 Signaling in Kidney Injury and Fibrosis

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis.Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.

Relationship between Clock-Drawing Performance and Neuropsychological Functions in Patients with Chronic Schizophrenia / 대한정신분열병학회지

Objectives@#This study investigated the relationship between clock-drawing test (CDT) performance and neuropsychological functions in patients with chronic schizophrenia. @*Methods@#Thirty-one patients with schizophrenia and 30 healthy controls participated in this study. The CDT was administered in three conditions and analyzed using both quantitative and qualitative scoring systems. Comprehensive neuropsychological tests were administered. @*Results@#The results of the quantitative analysis showed that the schizophrenia group performed significantly worse in all three conditions of the CDT compared with the control group. However, no significant differences were observed between the two groups, when the IQ and educational level were controlled. The qualitative analysis showed that the schizophrenia group exhibited significantly more errors in “graphic difficulty” compared with the control group. In addition, CDT quantitative scores were significantly correlated with visuospatial function, memory, attention and executive functions in patients with schizophrenia. Conversely, each qualitative error type was correlated with specific cognitive domains. Furthermore, “graphic difficulty” and “spatial/ planning deficit” were identified as predictors of depression symptoms in patients with schizophrenia. @*Conclusion@#The present study demonstrated that the CDT is useful for assessing cognitive dysfunctions in patients with schizophrenia, while qualitative analyses provide more specific information about cognitive deficits compared with quantitative analyses.

Prevalence of Diplopia and Extraocular Movement Limitation according to the Location of Isolated Pure Blowout Fractures

BACKGROUND: Isolated pure blowout fractures are clinically important because they are the main cause of serious complications such as diplopia and limitation of extraocular movement. Many reports have described the incidence of blowout fractures associated with diplopia and limitation of extraocular movement; however, no studies have statistically analyzed this relationship. The purpose of this study was to demonstrate the correlation between the location of isolated pure blowout fractures and orbital symptoms such as diplopia and limitation of extraocular movement. METHODS: We enrolled a total of 354 patients who had been diagnosed with isolated pure blowout fractures, based on computed tomography, from June 2008 to November 2011. Medical records were reviewed, and the prevalence of extraocular movement limitations and diplopia were determined. RESULTS: There were 14 patients with extraocular movement limitation and 58 patients complained of diplopia. Extraocular movement limitation was associated with the following findings, in decreasing order of frequency: floor fracture (7.1%), extended fracture (3.6%), and medial wall (1.7%). However, there was no significant difference among the types of fractures (P=0.60). Diplopia was more commonly associated with floor fractures (21.4%) and extended type fractures (23.6%) than medial wall fractures (10.4%). The difference was statistically significant (Bonferroni-corrected chi-squared test P<0.016). CONCLUSIONS: Data indicate that extended type fractures and orbital floor fractures tend to cause diplopia more commonly than medial wall fractures. However, extraocular movement limitation was not found to be dependent on the location of the orbital wall fracture.

Buerger's Disease Associated with IgA Nephropathy: A Case Report / 대한신장학회잡지

No abstract available.

Development of Multiplex PCR Detection of Blood-borne Viruses by Nucleic Acid Hybridization

Polymerase chain reaction (PCR) has been used as a substitute for conventional serological methods in order to provide blood or blood products free from contaminating viruses and recently attempts have focused to detect 2 or 3 viruses by a single multiplex PCR (M-PCR) reaction. We were able to detect human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), hepatitis B virus (HBV) and human cytomegalovirus (HCMV) simultaneously by a single M-PCR. However detection by gel electrophoresis of the products from M-PCR suffers from drawbacks such as low sensitivity and product sizes. Here we report enhanced detection systems of M-PCR based on nucleic acid hybridization with arrays built on membrane. Membrane array was manufactured by spotting appropriate probe DNAs on nylon membrane. Single or multiplex PCR was performed and the PCR products were labeled with DIG and allowed to hybridize with the membrane array. Results indicate that nonspecific hybridization was not observed for membrane DNA array. Additionally, membrane array method could detect small amount of viruses that were not detectable by conventional gel electrophoresis. At least 25-fold, and in some cases more than 125-fold increases in sensitivity was obtained with DNA array method. Thus, the nucleic acid hybridization with membrane array could be applied for the detection of M-PCR of viruses in blood or blood products.