1.Coronary Artery Calcium Score as a Sensitive Indicator of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus: A Long-Term Cohort Study
Dae-Jeong KOO ; Mi Yeon LEE ; Sun Joon MOON ; Hyemi KWON ; Sang Min LEE ; Se Eun PARK ; Cheol-Young PARK ; Won-Young LEE ; Ki Won OH ; Sung Rae CHO ; Young-Hoon JEONG ; Eun-Jung RHEE
Endocrinology and Metabolism 2023;38(5):568-577
		                        		
		                        			 Background:
		                        			Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden. 
		                        		
		                        			Methods:
		                        			We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease. 
		                        		
		                        			Results:
		                        			The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100. 
		                        		
		                        			Conclusion
		                        			CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM. 
		                        		
		                        		
		                        		
		                        	
2.The Effect of Vanishing Twin on Firstand Second-Trimester Maternal Serum Markers and Nuchal Translucency: A Multicenter Prospective Cohort Study
Se Jin LEE ; You Jung HAN ; Minhyoung KIM ; Jae-Yoon SHIM ; Mi-Young LEE ; Soo-young OH ; JoonHo LEE ; Soo Hyun KIM ; Dong Hyun CHA ; Geum Joon CHO ; Han-Sung KWON ; Byoung Jae KIM ; Mi Hye PARK ; Hee Young CHO ; Hyun Sun KO ; Ji Hye BAE ; Chan-Wook PARK ; Joong Shin PARK ; Jong Kwan JUN ; Sohee OH ; Da Rae LEE ; Hyun Mee RYU ; Seung Mi LEE
Journal of Korean Medical Science 2023;38(38):e300-
		                        		
		                        			 Background:
		                        			The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). 
		                        		
		                        			Methods:
		                        			This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. 
		                        		
		                        			Results:
		                        			Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment,AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. 
		                        		
		                        			Conclusion
		                        			VT can be considered as an adjustment factor for risk assessment in the secondtrimester serum screening test. 
		                        		
		                        		
		                        		
		                        	
3.Organized Hematoma of the Maxillary Sinus: Surgical Excision by Midfacial Degloving Approach
Seul Ki LEE ; Mi Ri MOON ; Sang Rae PARK ; Hye Hyeon JO ; Yong Bin LEE
Journal of Korean Dental Science 2022;15(1):68-74
		                        		
		                        			
		                        			 Organized hematoma of maxillary sinus is a rare pathologically benign mass in which pressure in the hematoma increases as it undergoes a process of organization, causing the deformation of the surrounding tissue, mimicking malignancies. The midfacial degloving approach can be used when extensive exposure is required in the treatment of lesions or traumas in the midfacial area with intranasal and intraoral incisions. We report a surgical excision case of organized hematoma of maxillary sinus using midfacial degloving approach without major complications and recurrence after one-year follow up. 
		                        		
		                        		
		                        		
		                        	
5.Deletion of adipose triglyceride lipase abolishes blood flow increase after β3-adrenergic stimulation in visceral adipose tissue of mice
Hye-Jin LEE ; Bo-Yeong JIN ; Mi-Rae PARK ; Kwan Sik SEO ; Yong Taek JEONG ; Sang-Hyun CHOI ; Dong-Hoon KIM
The Korean Journal of Physiology and Pharmacology 2021;25(4):355-363
		                        		
		                        			
		                        			Dynamic changes in adipose tissue blood flow (ATBF) with nutritional status play a role in the regulation of metabolic and endocrine functions. Activation of the sympathetic nervous system via β-adrenergic receptors (β-AR) contributes to the control of postprandial enhancement of ATBF. Herein, we sought to identify the role of each β-AR subtype in the regulation of ATBF in mice. We monitored the changes in visceral epididymal ATBF (VAT BF), induced by local infusion of dobutamine, salbutamol, and CL316,243 (a selective β1-, β2-, and β3-AR agonist, respectively) into VAT of lean CD-1 mice and global adipose triglyceride lipase (ATGL) knockout (KO) mice, using laser Doppler flowmetry. Administration of CL316,243, known to promote lipolysis in adipocytes, significantly increased VAT BF of CD-1 mice to a greater extent compared to that of the vehicle, whereas administration of dobutamine or salbutamol did not produce significant differences in VAT BF. The increase in VAT BF induced by β3-AR stimulation disappeared in ATGL KO mice as opposed to their wild-type (WT) littermates, implying a role of ATGL-mediated lipolysis in the regulation of VAT BF. Different vascular reactivities occurred despite no significant differences in vessel density and adiposity between the groups. Additionally, the expression levels of the angiogenesis-related genes were significantly higher in VAT of ATGL KO mice than in that of WT, implicating an association of ATBF responsiveness with angiogenic activity in VAT. Our findings suggest a potential role of β3-AR signaling in the regulation of VAT BF via ATGL-mediated lipolysis in mice.
		                        		
		                        		
		                        		
		                        	
6.Protective effect of Artemisiae Capillaris Herba water extract on liver injury induced by thioacetamide
Min Ju KIM ; Jin A LEE ; Mi-Rae SHIN ; Hae-Jin PARK ; Seong-Soo ROH
Journal of Nutrition and Health 2021;54(4):412-421
		                        		
		                        			Purpose:
		                        			Thioacetamide (TAA) produces reactive oxygen species (ROS) in the liver, and the generated ROS induces liver injury through inflammatory reactions. The current study was undertaken to investigate the hepatoprotective effect of Artemisiae Capillaris Herba water extract (AC), imparted via its antioxidant activity, in an animal model of TAA-induced liver injury. 
		                        		
		                        			Methods:
		                        			Animal experiments were conducted in 5 groups: normal, control (TAA 200 mg/kg), SM (TAA 200 mg/kg + silymarin 100 mg/kg), ACL (TAA 200 mg/kg + AC 100 mg/kg), ACH (TAA 200 mg/kg + AC 200mg/kg). TAA (intraperitoneal) and treatment compounds (per oral) were administered for 3 days. Serum levels of ammonia concentration and myeloperoxidase (MPO) activity were subsequently measured. Liver tissues were subjected to western blot analysis for measuring the oxidative stress (NADPH oxidase), anti-oxidative activity (Nrf2, heme oxygenase-1 [HO-1], superoxide dismutase [SOD], catalase, and GPx-1/2), tissue inhibitors of metalloproteinase (TIMP)-1, and matrix metalloproteinases (MMPs) protein expressions. 
		                        		
		                        			Results:
		                        			Serum ammonia levels and MPO activity were significantly increased in the TAAinduced control group, whereas groups administered AC treatment showed markedly reduced levels. Western blot analysis revealed significantly increased NOX2 and p22phox expressions, (oxidative stress-related factors) in the TAA-induced control group. These levels were determined to be significantly decreased after AC exposure. Moreover, antioxidantrelated factors including Nrf2, HO-1, SOD, catalase, and GPx-1/2 were significantly decreased in the control group and increased in the AC treated groups. In addition, MMP expressions were significantly suppressed in the AC treatment group due to increased levels of TIMP-1. 
		                        		
		                        			Conclusion
		                        			Taken together, these data indicate that exposure to AC reduces the oxidative stress by inhibiting the expression of NADPH oxidase (NOX2 and p22phox ) through the Nrf2 signaling pathway. We therefore propose the potential of AC for the prevention and treatment of TAA-induced liver injury.
		                        		
		                        		
		                        		
		                        	
7.Effects of a mixture of Citri Pericarpium and Scutellariae Radix on acute reflux esophagitis in rats
Jin A LEE ; Mi-Rae SHIN ; Seong-Soo ROH ; Hae-Jin PARK
Journal of Nutrition and Health 2021;54(3):321-333
		                        		
		                        			Purpose:
		                        			Reflux esophagitis is a disease caused by the reflux of stomach contents and stomach acid etc. into the esophagus due to defect in the lower esophageal sphincter and is currently increasing worldwide. This study was conducted to evaluate the effect of a mixture of Citrus Reticulata and Scutellariae Radix (CS) extract on acute reflux esophagitis in rats. 
		                        		
		                        			Methods:
		                        			Rats were divided into five groups for examination: normal group (Normal, n = 8), water-treated acute reflux esophagitis rats (Control, n = 8), tocopherol 30 mg/kg body weight-treated acute reflux esophagitis rats (Toco, n = 8), CS 100 mg/kg body weight-treated acute reflux esophagitis rats (CS100, n = 8), CS 200 mg/kg body weight-treated acute reflux esophagitis rats (CS200, n = 8). The experimental groups were administrated of each treatment compounds and after 90 min, acute reflux esophagitis was induced through surgery. Rats were sacrificed 5 h after surgery. We measured the level of reactive oxygen species (ROS) in serum and analyzed the expression of nicotinamide adenine dinucleotide phosphate, inflammatory, and tight junction-related proteins by western blot in the esophageal tissues. 
		                        		
		                        			Results:
		                        			CS administration significantly protected the esophageal mucosal damage due to reflux esophagitis, and the level of ROS in the serum was significantly reduced with CS administration as compared to Control. In addition, CS administration significantly suppressed mitogen-activated protein kinase (MAPK or MAP kinase) and nuclear factorkappa B (NF-κB) pathways and increased protein expressions of tight junction protein. 
		                        		
		                        			Conclusion
		                        			These results suggest that the CS not only regulates the expression of inflammatory proteins by inhibiting oxidative stress, but also reduces damage to the esophageal mucosa by inhibiting the expression of tight junction proteins.
		                        		
		                        		
		                        		
		                        	
8.Deletion of adipose triglyceride lipase abolishes blood flow increase after β3-adrenergic stimulation in visceral adipose tissue of mice
Hye-Jin LEE ; Bo-Yeong JIN ; Mi-Rae PARK ; Kwan Sik SEO ; Yong Taek JEONG ; Sang-Hyun CHOI ; Dong-Hoon KIM
The Korean Journal of Physiology and Pharmacology 2021;25(4):355-363
		                        		
		                        			
		                        			Dynamic changes in adipose tissue blood flow (ATBF) with nutritional status play a role in the regulation of metabolic and endocrine functions. Activation of the sympathetic nervous system via β-adrenergic receptors (β-AR) contributes to the control of postprandial enhancement of ATBF. Herein, we sought to identify the role of each β-AR subtype in the regulation of ATBF in mice. We monitored the changes in visceral epididymal ATBF (VAT BF), induced by local infusion of dobutamine, salbutamol, and CL316,243 (a selective β1-, β2-, and β3-AR agonist, respectively) into VAT of lean CD-1 mice and global adipose triglyceride lipase (ATGL) knockout (KO) mice, using laser Doppler flowmetry. Administration of CL316,243, known to promote lipolysis in adipocytes, significantly increased VAT BF of CD-1 mice to a greater extent compared to that of the vehicle, whereas administration of dobutamine or salbutamol did not produce significant differences in VAT BF. The increase in VAT BF induced by β3-AR stimulation disappeared in ATGL KO mice as opposed to their wild-type (WT) littermates, implying a role of ATGL-mediated lipolysis in the regulation of VAT BF. Different vascular reactivities occurred despite no significant differences in vessel density and adiposity between the groups. Additionally, the expression levels of the angiogenesis-related genes were significantly higher in VAT of ATGL KO mice than in that of WT, implicating an association of ATBF responsiveness with angiogenic activity in VAT. Our findings suggest a potential role of β3-AR signaling in the regulation of VAT BF via ATGL-mediated lipolysis in mice.
		                        		
		                        		
		                        		
		                        	
9.Validation of a Strict Obesity Definition Proposed for Asians to Predict Adverse Pregnancy Outcomes in Korean Pregnant Women
Seo-Yeon KIM ; Soo-young OH ; Ji-Hee SUNG ; Suk-Joo CHOI ; Cheong-Rae ROH ; Seung Mi LEE ; Jong Kwan JUN ; Mi-Young LEE ; JoonHo LEE ; Soo Hyun KIM ; Dong Hyun CHA ; You Jung HAN ; Min Hyoung KIM ; Geum Joon CHO ; Han-Sung KWON ; Byoung Jae KIM ; Mi Hye PARK ; Hee Young CHO ; Hyun Sun KO ; Jae-Yoon SHIM ; Hyun Mee RYU
Journal of Korean Medical Science 2021;36(44):e281-
		                        		
		                        			 Background:
		                        			People are generally considered overweight and obese if their body mass index (BMI) is above 25 kg/m 2 and 30.0 kg/m 2 , respectively. The World Health Organization proposed stricter criteria for Asians (≥ 23 kg/m2 : overweight, ≥ 25 kg/m2 : obese). We aimed to verify whether this criteria could predict adverse pregnancy outcomes in Korean women. 
		                        		
		                        			Methods:
		                        			We included 7,547 Korean women from 12 institutions enrolled between June 2016 and October 2018. Women with no pre-pregnancy BMI data, not Korean, or lost to followup were excluded, leaving 6,331. The subjects were categorized into underweight, normal, overweight, class I obesity, and class II/III obesity based on a pre-pregnancy BMI of < 18.5, 18.5–22.9, 23.0–24.9, 25.0–29.9, and ≥ 30.0 kg/m2 , respectively. 
		                        		
		                        			Results:
		                        			Overall, 13.4%, 63.0%, 11.8%, 9.1%, and 2.6% of women were underweight, normal, and overweight and had class I obesity and class II/III obesity, respectively. In the multivariable analysis adjusted for maternal age, a higher BMI significantly increased the risk of preeclampsia, gestational diabetes, preterm delivery caused by maternal-fetal indications, cesarean section, large for gestational age, and neonatal intensive care unit admission. 
		                        		
		                        			Conclusion
		                        			Adverse pregnancy outcomes started to increase in those with a pre-pregnancy BMI ≥ 23.0 kg/m2 after adjusting for maternal age. The modified obesity criteria could help predict adverse pregnancy outcomes in Koreans. 
		                        		
		                        		
		                        		
		                        	
10.Protective effect of Artemisiae Capillaris Herba water extract on liver injury induced by thioacetamide
Min Ju KIM ; Jin A LEE ; Mi-Rae SHIN ; Hae-Jin PARK ; Seong-Soo ROH
Journal of Nutrition and Health 2021;54(4):412-421
		                        		
		                        			Purpose:
		                        			Thioacetamide (TAA) produces reactive oxygen species (ROS) in the liver, and the generated ROS induces liver injury through inflammatory reactions. The current study was undertaken to investigate the hepatoprotective effect of Artemisiae Capillaris Herba water extract (AC), imparted via its antioxidant activity, in an animal model of TAA-induced liver injury. 
		                        		
		                        			Methods:
		                        			Animal experiments were conducted in 5 groups: normal, control (TAA 200 mg/kg), SM (TAA 200 mg/kg + silymarin 100 mg/kg), ACL (TAA 200 mg/kg + AC 100 mg/kg), ACH (TAA 200 mg/kg + AC 200mg/kg). TAA (intraperitoneal) and treatment compounds (per oral) were administered for 3 days. Serum levels of ammonia concentration and myeloperoxidase (MPO) activity were subsequently measured. Liver tissues were subjected to western blot analysis for measuring the oxidative stress (NADPH oxidase), anti-oxidative activity (Nrf2, heme oxygenase-1 [HO-1], superoxide dismutase [SOD], catalase, and GPx-1/2), tissue inhibitors of metalloproteinase (TIMP)-1, and matrix metalloproteinases (MMPs) protein expressions. 
		                        		
		                        			Results:
		                        			Serum ammonia levels and MPO activity were significantly increased in the TAAinduced control group, whereas groups administered AC treatment showed markedly reduced levels. Western blot analysis revealed significantly increased NOX2 and p22phox expressions, (oxidative stress-related factors) in the TAA-induced control group. These levels were determined to be significantly decreased after AC exposure. Moreover, antioxidantrelated factors including Nrf2, HO-1, SOD, catalase, and GPx-1/2 were significantly decreased in the control group and increased in the AC treated groups. In addition, MMP expressions were significantly suppressed in the AC treatment group due to increased levels of TIMP-1. 
		                        		
		                        			Conclusion
		                        			Taken together, these data indicate that exposure to AC reduces the oxidative stress by inhibiting the expression of NADPH oxidase (NOX2 and p22phox ) through the Nrf2 signaling pathway. We therefore propose the potential of AC for the prevention and treatment of TAA-induced liver injury.
		                        		
		                        		
		                        		
		                        	
            
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