1.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.
2.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.
3.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.
4.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.
5.A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer
Chang Min KIM ; Kyong Hwa PARK ; Yun Suk YU ; Ju Won KIM ; Jin Young PARK ; Kyunghee PARK ; Jong-Han YU ; Jeong Eon LEE ; Sung Hoon SIM ; Bo Kyoung SEO ; Jin Kyeoung KIM ; Eun Sook LEE ; Yeon Hee PARK ; Sun-Young KONG
Cancer Research and Treatment 2024;56(4):1113-1125
Purpose:
Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies.
Materials and Methods:
In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing.
Results:
By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores.
Conclusion
Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.
6.Vibration-controlled transient elastography for significant fibrosis in treatment-naïve chronic hepatitis B patients: A systematic review and meta-analysis
Mi Na KIM ; Jihyun AN ; Eun Hwa KIM ; Hee Yeon KIM ; Han Ah LEE ; Jung Hwan YU ; Young-Joo JIN ; Young Eun CHON ; Seung Up KIM ; Dae Won JUN ; Ji Won HAN ; Miyoung CHOI
Clinical and Molecular Hepatology 2024;30(suppl):s106-s116
Background:
s/Aims: Accurate diagnosis of significant liver fibrosis in patients with chronic hepatitis B (CHB) is crucial when determining whether to initiate antiviral treatment (AVT). We conduct a meta-analysis to assess the diagnostic performance of vibration-controlled transient elastography (VCTE) for significant liver fibrosis in AVT-naïve CHB patients with serum alanine transaminase (ALT) levels within 5-fold the upper limit of normal (ULN).
Methods:
The Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases were searched to identify studies that compared the performance of VCTE and liver biopsy (reference standard) when diagnosing significant liver fibrosis (≥F2) in AVT-naïve CHB patients with ALT within 5-fold the ULN. A hierarchical summary receiver operating characteristic curve (HSROC) and bivariate model were performed to evaluate the diagnostic performance of VCTE in the meta-analysis.
Results:
Eight studies (2,003 patients) were included. The summary sensitivity and specificity for diagnosis of significant liver fibrosis were 0.78 (95% confidence interval [CI], 0.66–0.86) and 0.72 (95% CI, 0.60–0.82), respectively. The HSROC for the diagnosis of significant liver fibrosis was 0.81 (95% CI, 0.72–0.86). The optimal cutoff value of VCTE for diagnosis of significant liver fibrosis was 7.7 kPa with a sensitivity of 0.64 (95% CI, 0.50–0.76) and specificity of 0.83 (95% CI, 0.72–0.90).
Conclusions
Our study demonstrated that VCTE has an acceptable diagnostic performance for significant liver fibrosis in AVT-naïve CHB patients with ALT within 5-fold the ULN.
7.Contemporary Statistics of Acute Ischemic Stroke and Transient Ischemic Attack in 2021: Insights From the CRCS-K-NIH Registry
Do Yeon KIM ; Tai Hwan PARK ; Yong-Jin CHO ; Jong-Moo PARK ; Kyungbok LEE ; Minwoo LEE ; Juneyoung LEE ; Sang Yoon BAE ; Da Young HONG ; Hannah JUNG ; Eunvin KO ; Hyung Seok GUK ; Beom Joon KIM ; Jun Yup KIM ; Jihoon KANG ; Moon-Ku HAN ; Sang-Soon PARK ; Keun-Sik HONG ; Hong-Kyun PARK ; Jeong-Yoon LEE ; Byung-Chul LEE ; Kyung-Ho YU ; Mi Sun OH ; Dong-Eog KIM ; Dong-Seok GWAK ; Soo Joo LEE ; Jae Guk KIM ; Jun LEE ; Doo Hyuk KWON ; Jae-Kwan CHA ; Dae-Hyun KIM ; Joon-Tae KIM ; Kang-Ho CHOI ; Hyunsoo KIM ; Jay Chol CHOI ; Joong-Goo KIM ; Chul-Hoo KANG ; Sung-il SOHN ; Jeong-Ho HONG ; Hyungjong PARK ; Sang-Hwa LEE ; Chulho KIM ; Dong-Ick SHIN ; Kyu Sun YUM ; Kyusik KANG ; Kwang-Yeol PARK ; Hae-Bong JEONG ; Chan-Young PARK ; Keon-Joo LEE ; Jee Hyun KWON ; Wook-Joo KIM ; Ji Sung LEE ; Hee-Joon BAE ;
Journal of Korean Medical Science 2024;39(34):e278-
This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively.Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques.There has been a decrease in intravenous thrombolysis rates, from 12% in 2017–2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for noncardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.
8.Characteristics of COVID-19 outbreaks and risk factors for transmission at an army training center in South Korea from June to August 2021
U Jin CHO ; Seongjin WANG ; Seonju YI ; Yeon Hwa CHOI ; Eun-Young KIM ; Jin A KIM ; Sanghwan BAE ; Jungyeon YU ; Jangkyu CHOI ; Young-Joon PARK
Osong Public Health and Research Perspectives 2022;13(4):263-272
Objectives:
It is crucial to establish the characteristics of coronavirus disease 2019 (COVID-19) outbreaks at army training centers to develop preventive measures. Therefore, this study aimed to determine the COVID-19 transmission patterns and risk factors in a sequence of outbreaks at an army training center from June to August 2021.
Methods:
This study included 1,324 trainees at an army training center where outbreaks occurred from June to August 2021. The outbreak was qualitatively analyzed according to the period, attack rate, demographic characteristics, vaccination history, and living areas. An aerodynamic experiment was performed to evaluate aerosol transmission in living areas.
Results:
Three outbreaks occurred at the army training center from June to August 2021. The first, second, and third outbreaks lasted for 32, 17, and 24 days, and the attack rates were 12.8%, 18.1%, and 8.9%, respectively. Confirmed cases were distributed in all age groups. Recruits and the unvaccinated were at higher risk for COVID-19. The aerodynamic experiment verified the possibility of aerosol transmission within the same living area.
Conclusion
COVID-19 transmission at army training centers should be minimized through quarantine and post-admission testing during the latency period as part of integrated measures that include facility ventilation, vaccination, indoor mask-wearing, and social distancing.
9.Adverse Events in Healthcare Workers after the First Dose of ChAdOx1 nCoV-19 or BNT162b2 mRNA COVID-19 Vaccination: a Single Center Experience
Si-Ho KIM ; Yu Mi WI ; Su Yeon YUN ; Jeong Seon RYU ; Jung Min SHIN ; Eun Hui LEE ; Kyung Hwa SEO ; Sung Hee LEE ; Kyong Ran PECK
Journal of Korean Medical Science 2021;36(14):e107-
Coronavirus disease 2019 vaccinations for healthcare workers (HCWs) have begun in South Korea. To investigate adverse events (AEs) of the first dose of each vaccine, any symptom was collected daily for seven days after vaccination in a tertiary hospital. We found that 1,301 of 1,403 ChAdOx1 nCoV-19 recipients and 38 of 80 BNT162b2 recipients reported AEs respectively (90.9% vs. 52.5%): injection-site pain (77.7% vs. 51.2%), myalgia (60.5% vs.11.2%), fatigue (50.7% vs. 7.5%), headache (47.4% vs. 7.5%), and fever (36.1% vs. 5%; P < 0.001 for all). Young HCWs reported more AEs with ChAdOx1 nCoV-19 than with BNT162b2.No incidences of anaphylaxis were observed. Only one serious AE required hospitalization for serious vomiting, and completely recovered. In conclusion, reported AEs were more common in recipients with ChAdOx1 nCoV-19 than in those with BNT162b2. However, most of the reported AEs were mild to moderate in severity. Sufficient explanation and preparation for expected AEs required to promote widespread vaccination.
10.Adverse Events in Healthcare Workers after the First Dose of ChAdOx1 nCoV-19 or BNT162b2 mRNA COVID-19 Vaccination: a Single Center Experience
Si-Ho KIM ; Yu Mi WI ; Su Yeon YUN ; Jeong Seon RYU ; Jung Min SHIN ; Eun Hui LEE ; Kyung Hwa SEO ; Sung Hee LEE ; Kyong Ran PECK
Journal of Korean Medical Science 2021;36(14):e107-
Coronavirus disease 2019 vaccinations for healthcare workers (HCWs) have begun in South Korea. To investigate adverse events (AEs) of the first dose of each vaccine, any symptom was collected daily for seven days after vaccination in a tertiary hospital. We found that 1,301 of 1,403 ChAdOx1 nCoV-19 recipients and 38 of 80 BNT162b2 recipients reported AEs respectively (90.9% vs. 52.5%): injection-site pain (77.7% vs. 51.2%), myalgia (60.5% vs.11.2%), fatigue (50.7% vs. 7.5%), headache (47.4% vs. 7.5%), and fever (36.1% vs. 5%; P < 0.001 for all). Young HCWs reported more AEs with ChAdOx1 nCoV-19 than with BNT162b2.No incidences of anaphylaxis were observed. Only one serious AE required hospitalization for serious vomiting, and completely recovered. In conclusion, reported AEs were more common in recipients with ChAdOx1 nCoV-19 than in those with BNT162b2. However, most of the reported AEs were mild to moderate in severity. Sufficient explanation and preparation for expected AEs required to promote widespread vaccination.

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