1.Role of APE1/Ref-1 in hydrogen peroxide-induced apoptosis in human renal HK-2 cells
Ha Yeon KIM ; Jung Sun PARK ; Byeong Hwa JEON ; Hong Sang CHOI ; Chang Seong KIM ; Seong Kwon MA ; Soo Wan KIM ; Eun Hui BAE
Kidney Research and Clinical Practice 2024;43(2):186-201
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multipotent protein that plays essential roles in cellular responses to oxidative stress. Methods: To examine the role of APE1/Ref-1 in ischemia-reperfusion (I/R) injuries and hydrogen peroxide (H2O2)-induced renal tubular apoptosis, we studied male C57BL6 mice and human proximal tubular epithelial (HK-2) cells treated with H2O2 at different concentrations. The colocalization of APE1/Ref-1 in the proximal tubule, distal tubule, thick ascending limb, and collecting duct was observed with confocal microscopy. The overexpression of APE1/Ref-1 with knockdown cell lines using an APE1/Ref-1–specific DNA or small interfering RNA (siRNA) was used for the apoptosis assay. The promotor activity of nuclear factor kappa B (NF-κB) was assessed and electrophoretic mobility shift assay was conducted. Results: APE1/Ref-1 was predominantly localized to the renal tubule nucleus. In renal I/R injuries, the levels of APE1/Ref-1 protein were increased compared with those in kidneys subjected to sham operations. The overexpression of APE1/Ref-1 in HK-2 cells enhanced the Bax/Bcl-2 ratio as a marker of apoptosis. Conversely, the suppression of APE1/Ref-1 expression by siRNA in 1-mM H2O2-treated HK-2 cells decreased the Bax/Bcl-2 ratio, the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and NF-κB. In HK-2 cells, the promoter activity of NF-κB increased following H2O2 exposure, and this effect was further enhanced by APE1/Ref-1 transfection. Conclusion: The inhibition of APE1/Ref-1 with siRNA attenuated H2O2-induced apoptosis through the modulation of mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 and the nuclear activation of NF-κB and proapoptotic factors.
2.Efficacy and safety of radioiodine therapy for 10 hyperthyroid cats: a retrospective case series study in South Korea
Yeon CHAE ; Jae-Cheong LIM ; Taesik YUN ; Yoonhoi KOO ; Dohee LEE ; Mhan-Pyo YANG ; Hakhyun KIM ; Byeong-Teck KANG
Korean Journal of Veterinary Research 2024;64(2):e10-
Hyperthyroidism, characterized by elevated thyroid hormone levels and thyroid gland hyperplasia or adenoma, is a prevalent endocrinopathy in older cats. Treatment options include antithyroid drugs, surgical thyroidectomy, and radioiodine therapy (RAIT), which is non-invasive treatment option that can achieve complete remission. However, efficacy and safety of RAIT in hyperthyroid cats have not been investigated in South Korea. This study includes 10 hyperthyroid cats with RAIT. Initial assessments comprised history, physical examination, blood analysis, and serum total T4 (tT4) concentration. Thyroid scintigraphy revealed hyperactivity and enlargement of thyroid gland at 24 hours before the RAIT. Radioiodine (RAI) was injected subcutaneously with 2 to 6 mCi, determined by the fixed dose or the scoring system based on severity of clinical signs, tT4 concentration, and thyroid size individually. After RAIT, the concentration of serum tT4 and liver enzymes were significantly decreased at discharge. However, no significant differences were noted in blood urea nitrogen, creatinine, symmetric dimethylarginine, hematocrits, and white blood cell counts pre- and post-treatment. Although 4 cats received RAI twice, clinical signs disappeared and tT4 levels decreased following the RAIT. All 10 cats achieved complete remission after 6 months without critical adverse effect. The safety and the effectiveness of RAIT was confirmed based on protocols reported other countries. Therefore, RAIT could be considered the treatment option and prevent adverse effects from medication or surgery. This preliminary study presents the first evaluation of RAIT for hyperthyroid cats using locally produced RAI in South Korea and provide valuable insight for clinicians and further studies.
3.Muscle Pathology Associated With Cardiac Function in Duchenne Muscular Dystrophy
Jin A YOON ; Heirim LEE ; In Sook LEE ; You Seon SONG ; Byeong-Ju LEE ; Soo-Yeon KIM ; Yong Beom SHIN
Annals of Rehabilitation Medicine 2024;48(6):405-412
Objective:
To compare the progression of muscle fibrosis of various site and its relation between cardiac deterioration in Duchenne muscular dystrophy (DMD). In this study aimed to examine the associations between echocardiogram-based cardiac function indices and fibrosis of the abdominal and lower extremity muscles in patients with DMD to facilitate early detection of cardiac dysfunction and identify its predictors.
Methods:
Twenty-one patients with DMD patients were enrolled in the study. The association between cardiac dysfunction and fibrosis of the abdominal and lower extremity muscles was determined by analyzing the echocardiography and elastography. Non-parametric Spearman rank correlation coefficients were used to examine the pairwise relationships between cardiac function and muscle elasticity.
Results:
All patients were male and non-ambulant. Their mean age was 18.45±4.28 years. The strain ratios of the abdominal muscle and quadriceps muscles were significantly higher than those of the medial gastrocnemius. The strain ratio of the rectus abdominis muscle has a significant negative correlation with left ventricular ejection fraction. Cardiac function and valvular insufficiency were not significantly correlated with muscle strain ratio. According to the result of our study, the only skeletal muscle which showed significant correlation with cardiac dysfunction was degree abdominal muscle fibrosis.
Conclusion
The degree of fibrosis of respiratory muscles was also significantly associated with cardiac dysfunction; therefore, it can be used as a predictor of cardiac dysfunction in patients with DMD in clinical practice.
4.Grain-free diet-induced dilated cardiomyopathy with atrial fibrillation in a Labrador Retriever: a case report
Minju BAEK ; Minseok CHOI ; Yeon CHAE ; Taesik YUN ; Byeong-Teck KANG ; Hakhyun KIM
Korean Journal of Veterinary Research 2024;64(3):e20-
We describe the first reported case of grain-free diet-induced dilated cardiomyopathy (DCM) in a dog in Korea. An 11-year-old female dog was referred with abdominal distention, anorexia, and vomiting, having been fed a grain-free diet for > 5 years. Thoracic radiography revealed cardiomegaly and pulmonary edema. Atrial fibrillation was detected using electrocardiography. The dog was tentatively diagnosed with congestive heart failure (CHF) secondary to grain-free diet-induced DCM, and its diet changed to contain grain. Digoxin and diltiazem were prescribed for the atrial fibrillation, and pimobendan, enalapril, and furosemide for CHF. Significant improvements in echocardiographic indices were confirmed after 3 months.
5.Muscle Pathology Associated With Cardiac Function in Duchenne Muscular Dystrophy
Jin A YOON ; Heirim LEE ; In Sook LEE ; You Seon SONG ; Byeong-Ju LEE ; Soo-Yeon KIM ; Yong Beom SHIN
Annals of Rehabilitation Medicine 2024;48(6):405-412
Objective:
To compare the progression of muscle fibrosis of various site and its relation between cardiac deterioration in Duchenne muscular dystrophy (DMD). In this study aimed to examine the associations between echocardiogram-based cardiac function indices and fibrosis of the abdominal and lower extremity muscles in patients with DMD to facilitate early detection of cardiac dysfunction and identify its predictors.
Methods:
Twenty-one patients with DMD patients were enrolled in the study. The association between cardiac dysfunction and fibrosis of the abdominal and lower extremity muscles was determined by analyzing the echocardiography and elastography. Non-parametric Spearman rank correlation coefficients were used to examine the pairwise relationships between cardiac function and muscle elasticity.
Results:
All patients were male and non-ambulant. Their mean age was 18.45±4.28 years. The strain ratios of the abdominal muscle and quadriceps muscles were significantly higher than those of the medial gastrocnemius. The strain ratio of the rectus abdominis muscle has a significant negative correlation with left ventricular ejection fraction. Cardiac function and valvular insufficiency were not significantly correlated with muscle strain ratio. According to the result of our study, the only skeletal muscle which showed significant correlation with cardiac dysfunction was degree abdominal muscle fibrosis.
Conclusion
The degree of fibrosis of respiratory muscles was also significantly associated with cardiac dysfunction; therefore, it can be used as a predictor of cardiac dysfunction in patients with DMD in clinical practice.
6.Grain-free diet-induced dilated cardiomyopathy with atrial fibrillation in a Labrador Retriever: a case report
Minju BAEK ; Minseok CHOI ; Yeon CHAE ; Taesik YUN ; Byeong-Teck KANG ; Hakhyun KIM
Korean Journal of Veterinary Research 2024;64(3):e20-
We describe the first reported case of grain-free diet-induced dilated cardiomyopathy (DCM) in a dog in Korea. An 11-year-old female dog was referred with abdominal distention, anorexia, and vomiting, having been fed a grain-free diet for > 5 years. Thoracic radiography revealed cardiomegaly and pulmonary edema. Atrial fibrillation was detected using electrocardiography. The dog was tentatively diagnosed with congestive heart failure (CHF) secondary to grain-free diet-induced DCM, and its diet changed to contain grain. Digoxin and diltiazem were prescribed for the atrial fibrillation, and pimobendan, enalapril, and furosemide for CHF. Significant improvements in echocardiographic indices were confirmed after 3 months.
7.Grain-free diet-induced dilated cardiomyopathy with atrial fibrillation in a Labrador Retriever: a case report
Minju BAEK ; Minseok CHOI ; Yeon CHAE ; Taesik YUN ; Byeong-Teck KANG ; Hakhyun KIM
Korean Journal of Veterinary Research 2024;64(3):e20-
We describe the first reported case of grain-free diet-induced dilated cardiomyopathy (DCM) in a dog in Korea. An 11-year-old female dog was referred with abdominal distention, anorexia, and vomiting, having been fed a grain-free diet for > 5 years. Thoracic radiography revealed cardiomegaly and pulmonary edema. Atrial fibrillation was detected using electrocardiography. The dog was tentatively diagnosed with congestive heart failure (CHF) secondary to grain-free diet-induced DCM, and its diet changed to contain grain. Digoxin and diltiazem were prescribed for the atrial fibrillation, and pimobendan, enalapril, and furosemide for CHF. Significant improvements in echocardiographic indices were confirmed after 3 months.
8.Grain-free diet-induced dilated cardiomyopathy with atrial fibrillation in a Labrador Retriever: a case report
Minju BAEK ; Minseok CHOI ; Yeon CHAE ; Taesik YUN ; Byeong-Teck KANG ; Hakhyun KIM
Korean Journal of Veterinary Research 2024;64(3):e20-
We describe the first reported case of grain-free diet-induced dilated cardiomyopathy (DCM) in a dog in Korea. An 11-year-old female dog was referred with abdominal distention, anorexia, and vomiting, having been fed a grain-free diet for > 5 years. Thoracic radiography revealed cardiomegaly and pulmonary edema. Atrial fibrillation was detected using electrocardiography. The dog was tentatively diagnosed with congestive heart failure (CHF) secondary to grain-free diet-induced DCM, and its diet changed to contain grain. Digoxin and diltiazem were prescribed for the atrial fibrillation, and pimobendan, enalapril, and furosemide for CHF. Significant improvements in echocardiographic indices were confirmed after 3 months.
9.Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient Mice
Eun-Ok LEE ; Hao JIN ; Sungmin KIM ; Hee Kyoung JOO ; Yu Ran LEE ; Soo Yeon AN ; Shuyu PIAO ; Kwon Ho LEE ; Byeong Hwa JEON
Endocrinology and Metabolism 2024;39(6):932-945
Background:
The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution.
Methods:
APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes.
Results:
APE1/Ref-1+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1+/- mice.
Conclusion
APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.
10.Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient Mice
Eun-Ok LEE ; Hao JIN ; Sungmin KIM ; Hee Kyoung JOO ; Yu Ran LEE ; Soo Yeon AN ; Shuyu PIAO ; Kwon Ho LEE ; Byeong Hwa JEON
Endocrinology and Metabolism 2024;39(6):932-945
Background:
The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution.
Methods:
APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes.
Results:
APE1/Ref-1+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1+/- mice.
Conclusion
APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.

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