Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

The diagnosis of acute ischemic stroke (AIS) can be challenging when neuroimaging findings are normal or equivo‑ cal. Neutrophil extracellular traps (NETs), particularly histone H3.1, have potential as biomarkers for AIS. This study evaluated NETs, specifically histone H3.1, as diagnostic biomarkers for AIS. This prospective study included 89 patients with AIS and 20 healthy controls. Plasma histone H3.1 levels were measured using the Nu.Q® H3.1 enzyme-linked immunosorbent assay (ELISA). Seven cytokines were analyzed using a bead-based immunoassay. Statistical analy‑ ses were used to compare histone H3.1 levels between groups and evaluate correlations with clinical parameters and cytokines. Histone H3.1 levels were significantly higher in patients with AIS (271.05 ± 33.40 ng/mL) versus controls (95.33 ± 12.86 ng/mL, p < 0.001). Multivariable logistic regression identified H3.1 as an independent risk factor for AIS (p = 0.006), with an area under the curve of 0.907. Significant correlations were found between H3.1, interleukin-6 (0.290, p = 0.013) and vascular cell adhesion molecule 1 (0.297, p = 0.011). In conclusion, the NETs H3.1 ELISA test is a reliable new diagnostic option that supports the diagnosis of AIS.

Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

The diagnosis of acute ischemic stroke (AIS) can be challenging when neuroimaging findings are normal or equivo‑ cal. Neutrophil extracellular traps (NETs), particularly histone H3.1, have potential as biomarkers for AIS. This study evaluated NETs, specifically histone H3.1, as diagnostic biomarkers for AIS. This prospective study included 89 patients with AIS and 20 healthy controls. Plasma histone H3.1 levels were measured using the Nu.Q® H3.1 enzyme-linked immunosorbent assay (ELISA). Seven cytokines were analyzed using a bead-based immunoassay. Statistical analy‑ ses were used to compare histone H3.1 levels between groups and evaluate correlations with clinical parameters and cytokines. Histone H3.1 levels were significantly higher in patients with AIS (271.05 ± 33.40 ng/mL) versus controls (95.33 ± 12.86 ng/mL, p < 0.001). Multivariable logistic regression identified H3.1 as an independent risk factor for AIS (p = 0.006), with an area under the curve of 0.907. Significant correlations were found between H3.1, interleukin-6 (0.290, p = 0.013) and vascular cell adhesion molecule 1 (0.297, p = 0.011). In conclusion, the NETs H3.1 ELISA test is a reliable new diagnostic option that supports the diagnosis of AIS.

Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

The diagnosis of acute ischemic stroke (AIS) can be challenging when neuroimaging findings are normal or equivo‑ cal. Neutrophil extracellular traps (NETs), particularly histone H3.1, have potential as biomarkers for AIS. This study evaluated NETs, specifically histone H3.1, as diagnostic biomarkers for AIS. This prospective study included 89 patients with AIS and 20 healthy controls. Plasma histone H3.1 levels were measured using the Nu.Q® H3.1 enzyme-linked immunosorbent assay (ELISA). Seven cytokines were analyzed using a bead-based immunoassay. Statistical analy‑ ses were used to compare histone H3.1 levels between groups and evaluate correlations with clinical parameters and cytokines. Histone H3.1 levels were significantly higher in patients with AIS (271.05 ± 33.40 ng/mL) versus controls (95.33 ± 12.86 ng/mL, p < 0.001). Multivariable logistic regression identified H3.1 as an independent risk factor for AIS (p = 0.006), with an area under the curve of 0.907. Significant correlations were found between H3.1, interleukin-6 (0.290, p = 0.013) and vascular cell adhesion molecule 1 (0.297, p = 0.011). In conclusion, the NETs H3.1 ELISA test is a reliable new diagnostic option that supports the diagnosis of AIS.

Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

Background: Kidney transplantation (KT) improves physical and psychological prognoses for patients with end-stage kidney disease (ESKD). However, few comparative studies have examined depression and suicide rates among patients with ESKD treated with dialysis versus KT. Methods: Data on 21,809 patients with ESKD were extracted from the Korean National Health Insurance Service database, extending from January 2002 to December 2018.These patients exhibited no history of depression or insomnia before starting renal replacement therapy. Outcomes were compared between dialysis and KT recipients using 1:2 propensity score matching (PSM). Results: Of the patients, 17,649 received dialysis (hemodialysis, 15,537; peritoneal dialysis, 2,112), while 4,160 underwent KT. Of those on dialysis, 45.04% (7,949) experienced insomnia, compared to 25.72% (1,070) of KT recipients (P<0.001). Depression was more frequent among dialysis recipients (22.77%, 4,019) than KT recipients (8.61%, 358;P<0.001). Additionally, those on dialysis had a higher incidence of suicide (0.19%, 33) than recipients of KT (0.12%, 5; P=0.047). After PSM, the hazard ratio (HR) for depression in patients on dialysis compared to KT recipients was 1.76 (95% confidence interval [CI], 1.56–1.99). In subgroup analysis, the relative likelihood of depression among dialysis recipients was particularly high for residents of urban areas (HR, 2.10; 95% CI, 1.80–2.44) and patients under 65 years old (HR, 1.82; 95% CI, 1.62–2.09). Conclusions KT recipients exhibit a lower suicide rate than patients on dialysis. Furthermore, KT is associated with a lower prevalence of depression among Korean patients with ESKD, particularly urban residents and individuals under 65 years old.