1.Pan-Nox inhibitor treatment improves renal function in aging murine diabetic kidneys
Jeong Hoon PARK ; Sung Gi YOON ; Jung Yeon GHEE ; Ji Ae YOO ; Jin Joo CHA ; Young Sun KANG ; Sang Youb HAN ; Yun Jae SEOL ; Jee Young HAN ; Dae Ryong CHA
Kidney Research and Clinical Practice 2024;43(6):763-773
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.
2.Pan-Nox inhibitor treatment improves renal function in aging murine diabetic kidneys
Jeong Hoon PARK ; Sung Gi YOON ; Jung Yeon GHEE ; Ji Ae YOO ; Jin Joo CHA ; Young Sun KANG ; Sang Youb HAN ; Yun Jae SEOL ; Jee Young HAN ; Dae Ryong CHA
Kidney Research and Clinical Practice 2024;43(6):763-773
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.
3.Pan-Nox inhibitor treatment improves renal function in aging murine diabetic kidneys
Jeong Hoon PARK ; Sung Gi YOON ; Jung Yeon GHEE ; Ji Ae YOO ; Jin Joo CHA ; Young Sun KANG ; Sang Youb HAN ; Yun Jae SEOL ; Jee Young HAN ; Dae Ryong CHA
Kidney Research and Clinical Practice 2024;43(6):763-773
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.
4.Pan-Nox inhibitor treatment improves renal function in aging murine diabetic kidneys
Jeong Hoon PARK ; Sung Gi YOON ; Jung Yeon GHEE ; Ji Ae YOO ; Jin Joo CHA ; Young Sun KANG ; Sang Youb HAN ; Yun Jae SEOL ; Jee Young HAN ; Dae Ryong CHA
Kidney Research and Clinical Practice 2024;43(6):763-773
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.
5.Motor Weakness of Contralateral Upper and Lower Limbs in a Patient with Septic Arthritis of the Knee Combined with Infective Endocarditis: Embolic Infarction Due to Infective Endocarditis
Jae-Ryong CHA ; Ki-Bong PARK ; Seong-Min JANG
The Journal of the Korean Orthopaedic Association 2022;57(2):150-154
An 82-year-old man visited with fever and severe pain in the right knee. Septic arthritis was confirmed by magnetic resonance imaging (MRI) and joint fluid analysis, and the patient underwent arthroscopic synovectomy and received empirical antibiotic therapy. One day later, motor weakness of contralateral upper and lower limbs developed. Brain MRI confirmed embolic infarction and transthoracic echocardiography confirmed mitral valve infective endocarditis. This paper reports a case of motor weakness after arthroscopic synovectomy for septic arthritis of the knee and provides a review of relevant literature regarding infective endocarditis.
6.Primary Synovial Chondromatosis Presented as Non-Calcified Loose Bodies in the Popliteal Cyst
Jae-Ryong CHA ; Jae-Hee SUH ; Sung-Who CHANG ; Ki-Bong PARK
The Journal of the Korean Orthopaedic Association 2021;56(4):346-350
A magnetic resonance imaging test was performed on a 56-year-old male patient, who visited with a one-month history of painless swelling at the popliteal area of the left knee. A popliteal cyst and non-calcified loose body in the cyst were identified. Synovial chondromatosis was diagnosed from a histology examination by excision and biopsy. This paper reports this case of extra-articular synovial chondromatosis of the knee with a review of the relevant literature.
7.Practice Patterns for Eosinophilic Esophagitis Patients in Busan and Gyeongnam: A Korean Multicenter Database Study
Su Jin KIM ; Moo In PARK ; Gwang Ha KIM ; Moon Won LEE ; Kyoungwon JUNG ; Jin LEE ; Sang Young SEOL ; Sam Ryong JEE ; Hong Sub LEE ; Jin Seok JANG ; Jae Hwang CHA ;
Journal of Neurogastroenterology and Motility 2021;27(1):71-77
Background/Aims:
The prevalence of eosinophilic esophagitis is increasing in Korea and there are few single-center studies regarding eosinophilic esophagitis in Korea. In particular, data about management for eosinophilic esophagitis are lacking. We aim to evaluate the practice patterns, including initial treatment and response, in the Busan city and Gyeongnam province area.
Methods:
We retrospectively reviewed medical records to gain data on patient characteristics, medication, endoscopic images, and esophageal biopsy results. From January 2009 to December 2019, a total of 42 patients were diagnosed with eosinophilic esophagitis.
Results:
The mean age was 50.7 (from 22 to 81) years and the cohort was predominantly male (78.6%, 33/42). The proton pump inhibitor was the preferred treatment as an initial trial for 64.3% (27/42) of patients, followed by swallowed topical steroids (16.7%, 7/42).Clinical improvement after proton pump inhibitor therapy was achieved in 88.9% (24/27) of patients. Two patients who did not achieve improvement showed a clinical and endoscopic response after swallowed topical steroids treatment. No patient received diet elimination or balloon dilatation therapy.
Conclusions
The treatment response of eosinophilic esophagitis was good in Busan city and Gyeongnam province area in Korea. Proton pump inhibitor therapy was the preferred and most effective treatment for eosinophilic esophagitis as the initial therapy.
8.Open-Door Laminoplasty Using Lateral Mass Anchoring Screws and Nonabsorbable Sutures in Patients with Multilevel Cervical Myelopathy
Jae-Ryong CHA ; Han Wook KIM ; Doo Guen YANG ; Hee-Yoon CHUNG ; Il-Yeong HWANG
Clinics in Orthopedic Surgery 2020;12(4):477-484
Background:
The purpose of this study was to evaluate the clinical usefulness of open-door laminoplasty using lateral mass anchoring screws and nonabsorbable sutures (ODLLM) for multilevel cervical myelopathy.
Methods:
We retrospectively studied 30 patients who underwent ODLLM. Clinical evaluations were performed using a visual analog scale (VAS), Japanese Orthopaedic Association (JOA) score, and Neck Disability Index (NDI) preoperatively, at 1 year postoperatively, and at the last follow-up. Radiographic evaluation was done using cervical spine radiographs to measure changes in the lordotic angle and range of motion (ROM) preoperatively, at 1 year postoperatively, and at the last follow-up and computed tomography at 1 year postoperatively to measure the opening angle and anteroposterior diameter of the spinal canal.
Results:
Significant improvement in VAS, JOA, and NDI was seen overall at 1 year after operation. However, there was no significant difference between 1 year after operation and the last follow-up. There were no significant changes in the lordotic angle and neck ROM. The mean opening angle of the opened lamina was measured as 39.04°. The mean anteroposterior diameter was significantly increased from 7.51 ± 1.79 mm before surgery to 13.98 ± 1.80 mm at 1 year of operation. Complications such as laminar reclosure and screw loosening were not observed in all cases.
Conclusions
The ODLLM was technically easy to perform and showed good results comparable to those of conventional techniques. It can be suggested that ODLLM is an appropriate treatment option for multilevel cervical myelopathy.
9.Autogenous Bone Grafts versue Metal Cage with Allogenic Bone Grafts for Post-Corpectomy Anterior Column Reconstruction in Patients with Infectious Spondylitis
Jae-Ryong CHA ; Il-Yeong HWANG ; Sun-Hwan KWON ; Hee-Yoon CHUNG
Journal of Korean Neurosurgical Society 2020;63(2):218-227
Objective:
: To evaluate and compare the clinical and radiographic features of 25 patients with infectious spondylitis treated with anterior debridement and reconstruction using autogenous bone grafts vs. a metal cage with allogenic bone grafts.
Methods:
: The study analyzed 25 patients diagnosed with infectious thoracolumbar spondylitis who underwent anterior radical debridement and reconstruction. Autogenous bone grafts were used in 13 patients (group 1), and a metal cage with allogenic bone grafts was used in 12 patients (group 2). Clinical outcomes were assessed by the visual analogue scale (VAS) scores and neurological status. Additionally, the serological results and the radiographic results using the sagittal Cobb angle were compared. Fusion was evaluated by computed tomography (CT) imaging at 24 months postoperatively.
Results:
: Both groups showed a significant decrease in the postoperative mean VAS scores; however, only, group 1 patients showed a significantly higher VAS score than group 2 patients, 1 month postoperatively (p=0.002). The postoperative neurological status significantly improved. Elevated C-reactive protein levels and erythrocyte sedimentation rate values returned to normal limits at the 2-year follow-up without recurrent infection. No significant intergroup difference was observed in Cobb angle. Bony fusion was confirmed in all patients at CT 24 months postoperatively.
Conclusion
: Although the use of a metal cage with allogenic bone grafts for anterior column reconstruction remains controversial, our results suggest that it can be considered as an effective treatment of option for anterior column reconstruction in patients with infectious spondylitis.
10.Circulating renalase predicts all-cause mortality and renal outcomes in patients with advanced chronic kidney disease
Seon Ha BAEK ; Ran hui CHA ; Shin Wook KANG ; Cheol Whee PARK ; Dae Ryong CHA ; Sung Gyun KIM ; Sun Ae YOON ; Sejoong KIM ; Sang Youb HAN ; Jung Hwan PARK ; Jae Hyun CHANG ; Chun Soo LIM ; Yon Su KIM ; Ki Young NA
The Korean Journal of Internal Medicine 2019;34(4):858-866
BACKGROUND/AIMS:
Patients with chronic kidney disease (CKD) have been found to show markedly increased rates of end-stage renal disease, major adverse cardiovascular and cerebrovascular events (MACCEs), and mortality. Therefore, new biomarkers are required for the early detection of such clinical outcomes in patients with CKD. We aimed to determine whether the level of circulating renalase was associated with CKD progression, MACCEs, and all-cause mortality, using data from a prospective randomized controlled study, Kremezin STudy Against Renal disease progression in Korea (K-STAR; NCT 00860431).
METHODS:
A retrospective analysis of the K-STAR data was performed including 383 patients with CKD (mean age, 56.4 years; male/female, 252/131). We measured circulating renalase levels and examined the effects of these levels on clinical outcomes.
RESULTS:
The mean level of serum renalase was 75.8 ± 34.8 μg/mL. In the multivariable analysis, lower hemoglobin levels, higher serum creatinine levels, and diabetes mellitus were significantly associated with a higher renalase levels. Over the course of a mean follow-up period of 56 months, 25 deaths and 61 MACCEs occurred. Among 322 patients in whom these outcomes were assessed, 137 adverse renal outcomes occurred after a mean follow-up period of 27.8 months. Each 10-μg/mL increase in serum renalase was associated with significantly greater hazards of all-cause mortality and adverse renal outcomes (hazard ratio [HR] = 1.112, p = 0.049; HR = 1.052, p = 0.045). However, serum renalase level was not associated with the rate of MACCEs in patients with CKD.
CONCLUSIONS
Our results indicated that circulating renalase might be a predictor of mortality and adverse renal outcomes in patients with CKD.

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