1.The Role of De novo Serine Biosynthesis from Glucose in Papillary Thyroid Cancer
Seong Eun LEE ; Na Rae CHOI ; Jin-Man KIM ; Mi Ae LIM ; Bon Seok KOO ; Yea Eun KANG
International Journal of Thyroidology 2023;16(2):175-183
		                        		
		                        			 Background and Objectives:
		                        			The de novo serine biosynthetic pathway from glucose has emerged as one of cancer metabolism; however, it is not explored the interplay between papillary thyroid cancer and metabolic flux of de novo serine synthesis. In this study, we explored the interplay between glucose utilization via GLUT1 expression and phosphoglycerate dehydrogenase (PHGDH).  
		                        		
		                        			Materials and Methods:
		                        			The Cancer Genome Atlas (TCGA) database was used to determine the association between glucose importation and the serine metabolic pathway. The effects of glucose on serine biosynthesis and the role of PHGDH were investigated in papillary thyroid cancer cell lines. PHGDH and GLUT1 expression in 230 patients with papillary thyroid cancer (PTC) was explored using immunohistochemistry to explore the impact of the de novo serine biosynthetic pathway from glucose.  
		                        		
		                        			Results:
		                        			Glucose importation was significantly correlated with the serine biosynthetic and L-serine metabolic processes. Glucose uptake and serine synthesis were significantly increased and mitochondrial complex expression was upregulated in PTC cell lines grown in high-glucose media. Knockdown and inhibition of PHGDH decreased cell migration associated with glucose utilization. High PHGDH expression is significantly related with tumor aggressiveness and GLUT1 expression in patients with PTC.  
		                        		
		                        			Conclusion
		                        			In this study, we demonstrated that de novo serine biosynthesis from glucose is highly expressed in papillary thyroid cancer and associated with cancer cell metastasis through glucose utility. Our findings suggest the link between glucose utilization PHGDH to regulate tumor aggressiveness in PTC. 
		                        		
		                        		
		                        		
		                        	
2.Differential Gene Expression in the Hippocampi of Nonhuman Primates Chronically Exposed to Methamphetamine, Cocaine, or Heroin
Mi Ran CHOI ; Yeung-Bae JIN ; Han-Na KIM ; Heejin LEE ; Young Gyu CHAI ; Sang-Rae LEE ; Dai-Jin KIM
Psychiatry Investigation 2022;19(7):538-550
		                        		
		                        			 Objective:
		                        			Methamphetamine (MA), cocaine, and heroin cause severe public health problems as well as impairments in neural plasticity and cognitive function in the hippocampus. This study aimed to identify the genes differentially expressed in the hippocampi of cynomolgus monkeys in response to these drugs. 
		                        		
		                        			Methods:
		                        			After the monkeys were chronically exposed to MA, cocaine, and heroin, we performed large-scale gene expression profiling of the hippocampus using RNA-Seq technology and functional annotation of genes differentially expressed. Some genes selected from RNA-Seq analysis data were validated with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). And the expression changes of ADAM10 protein were assessed using immunohistochemistry. 
		                        		
		                        			Results:
		                        			The changes in genes related to axonal guidance (PTPRP and KAL1), the cell cycle (TLK2), and the regulation of potassium ions (DPP10) in the drug-treated groups compared to the control group were confirmed using RT-qPCR. Comparative analysis of all groups showed that among genes related to synaptic long-term potentiation, CREBBP and GRIN3A were downregulated in both the MA- and heroin-treated groups compared to the control group. In particular, the mRNA and protein expression levels of ADAM10 were decreased in the MA-treated group but increased in the cocaine-treated group compared to the control group. 
		                        		
		                        			Conclusion
		                        			These results provide insights into the genes that are upregulated and downregulated in the hippocampus by the chronic administration of MA, cocaine, or heroin and basic information for developing novel drugs for the treatment of hippocampal impairments caused by drug abuse. 
		                        		
		                        		
		                        		
		                        	
3.Evaluation of sleep quality and stress response in patients requiring dental prosthetic treatment
Hye-Mi JEON ; Kyoung-Hwa JUNG ; Na-Rae CHOI ; Jae-Min SONG ; So-Hyoun LEE ; So-Yeun KIM
The Journal of Korean Academy of Prosthodontics 2021;59(2):181-189
		                        		
		                        			Purpose:
		                        			The purpose of this study is to investigate the stress response and sleep state of the new patients who visit the hospital for prosthodontic treatment due to tooth loss to make reference to further treatment direction. 
		                        		
		                        			Materials and methods:
		                        			Examinations, consultations, and surveys were conducted on 236 patients (94 males, 142 females, and 24-86 years old), who newly registered at the department of prosthodontics at Pusan national university hospital, for 2 years from 2018. The number of remaining teeth, edentulous arch, possibility of mastication, and future prosthetic treatment directions were recorded. The visual analogue scale (VAS), stress response inventory (SRI) and Insomnia severity index (ISI) were used as tools to measure patient’s subjective discomfort, stress response, and sleep status. 
		                        		
		                        			Results:
		                        			Among the entire prosthodontic patient group, the average value of ‘fatigue’ was significantly higher among the 7 items of SRI, and the value of ‘aggression’ was significantly lower (P<.001). There are a significant difference between the edentulous and full dentition in the oral discomfort value measured by VAS (P=.004). In cases where less than 20 teeth remain, mastication is impossible, and patients who are planning treatment with removable prostheses, VAS value and ‘depression’ and ‘fatigue’ values in SRI were higher than those in the reverse case (P<.05).The patients showed severe level in VAS value have high value of ‘tension’, ‘somatization’, ‘depression’, ‘fatigue’and ‘frustration’in SRI than non-serious patients (P<.05). Clinical insomnia occurred in 11.4% of all patients, and women had significantly lower sleep quality than men (P=.044). Patients with insomnia showed significantly higher scores on the VAS value and all 7 SRI items than those of normal sleepers (P<.05). 
		                        		
		                        			Conclusion
		                        			The new prosthetics had high ‘fatigue’ value among the 7 items of SRI. The oral condition, number of residual teeth and mastication function and clinical insomnia affected oral discomfort and the stress response.
		                        		
		                        		
		                        		
		                        	
4.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.
		                        		
		                        		
		                        		
		                        	
5.Evaluation of sleep quality and stress response in patients requiring dental prosthetic treatment
Hye-Mi JEON ; Kyoung-Hwa JUNG ; Na-Rae CHOI ; Jae-Min SONG ; So-Hyoun LEE ; So-Yeun KIM
The Journal of Korean Academy of Prosthodontics 2021;59(2):181-189
		                        		
		                        			Purpose:
		                        			The purpose of this study is to investigate the stress response and sleep state of the new patients who visit the hospital for prosthodontic treatment due to tooth loss to make reference to further treatment direction. 
		                        		
		                        			Materials and methods:
		                        			Examinations, consultations, and surveys were conducted on 236 patients (94 males, 142 females, and 24-86 years old), who newly registered at the department of prosthodontics at Pusan national university hospital, for 2 years from 2018. The number of remaining teeth, edentulous arch, possibility of mastication, and future prosthetic treatment directions were recorded. The visual analogue scale (VAS), stress response inventory (SRI) and Insomnia severity index (ISI) were used as tools to measure patient’s subjective discomfort, stress response, and sleep status. 
		                        		
		                        			Results:
		                        			Among the entire prosthodontic patient group, the average value of ‘fatigue’ was significantly higher among the 7 items of SRI, and the value of ‘aggression’ was significantly lower (P<.001). There are a significant difference between the edentulous and full dentition in the oral discomfort value measured by VAS (P=.004). In cases where less than 20 teeth remain, mastication is impossible, and patients who are planning treatment with removable prostheses, VAS value and ‘depression’ and ‘fatigue’ values in SRI were higher than those in the reverse case (P<.05).The patients showed severe level in VAS value have high value of ‘tension’, ‘somatization’, ‘depression’, ‘fatigue’and ‘frustration’in SRI than non-serious patients (P<.05). Clinical insomnia occurred in 11.4% of all patients, and women had significantly lower sleep quality than men (P=.044). Patients with insomnia showed significantly higher scores on the VAS value and all 7 SRI items than those of normal sleepers (P<.05). 
		                        		
		                        			Conclusion
		                        			The new prosthetics had high ‘fatigue’ value among the 7 items of SRI. The oral condition, number of residual teeth and mastication function and clinical insomnia affected oral discomfort and the stress response.
		                        		
		                        		
		                        		
		                        	
6.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.
		                        		
		                        		
		                        		
		                        	
7.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. 
		                        		
		                        		
		                        		
		                        	
8.Age-related Effects of Heroin on Gene Expression in the Hippocampus and Striatum of Cynomolgus Monkeys
Mi Ran CHOI ; Yeung-Bae JIN ; Sol Hee BANG ; Chang-Nim IM ; Youngjeon LEE ; Han-Na KIM ; Kyu-Tae CHANG ; Sang-Rae LEE ; Dai-Jin KIM
Clinical Psychopharmacology and Neuroscience 2020;18(1):93-108
		                        		
		                        			 Objective:
		                        			The aim of this study was to investigate differentially expressed genes and their functions in the hippocampus and striatum after heroin administration in cynomolgus macaques of different ages. 
		                        		
		                        			Methods:
		                        			Cynomolgus monkeys were divided by age as follows: 1 year (A1, n = 2); 3 to 4 years (A2, n = 2); 6 to 8 years (A3, n = 2); and older than 11 years (A4, n = 2). After heroin was injected intramuscularly into the monkeys (0.6 mg/kg), we performed large-scale transcriptome profiling in the hippocampus (H) and striatum (S) using RNA sequencing technology. Some genes were validated with real-time quantitative PCR. 
		                        		
		                        			Results:
		                        			In the hippocampus, the gene expression of A1H was similar to that of A4H, while the gene expression of A2H was similar to that of A3H. Genes associated with the mitogen-activated protein kinase signaling pathway (STMN1, FGF14, and MAPT) and -aminobutyric acid-ergic synapses (GABBR2 and GAD1) were differentially expressed among control and heroin-treated animals. Differential gene expression between A1S and A4S was the least significant, while differential gene expression between A3S and A2S was the most significant. Genes associated with the neurotrophin signaling pathway (NTRK1 and NGFR), autophagy (ATG5), and dopaminergic synapses (AKT1) in the striatum were differentially expressed among control and heroin-treated animals. 
		                        		
		                        			Conclusion
		                        			These results suggest that even a single heroin exposure can cause differential gene expression in the hippocampus and striatum of nonhuman primates at different ages. 
		                        		
		                        		
		                        		
		                        	
9.Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Ji Eun JUN ; In Kyung JEONG ; Jae Myung YU ; Sung Rae KIM ; In Kye LEE ; Kyung Ah HAN ; Sung Hee CHOI ; Soo Kyung KIM ; Hyeong Kyu PARK ; Ji Oh MOK ; Yong ho LEE ; Hyuk Sang KWON ; So Hun KIM ; Ho Cheol KANG ; Sang Ah LEE ; Chang Beom LEE ; Kyung Mook CHOI ; Sung Ho HER ; Won Yong SHIN ; Mi Seung SHIN ; Hyo Suk AHN ; Seung Ho KANG ; Jin Man CHO ; Sang Ho JO ; Tae Joon CHA ; Seok Yeon KIM ; Kyung Heon WON ; Dong Bin KIM ; Jae Hyuk LEE ; Moon Kyu LEE
Diabetes & Metabolism Journal 2020;44(1):78-90
		                        		
		                        			 BACKGROUND:
		                        			Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia.
		                        		
		                        			METHODS:
		                        			This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment.
		                        		
		                        			RESULTS:
		                        			After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups.
		                        		
		                        			CONCLUSION
		                        			The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia. 
		                        		
		                        		
		                        		
		                        	
10.Effectiveness of Autologous Fat Graft in Treating Fecal Incontinence
Hyeonseok JEONG ; Sung Hwan HWANG ; Hyoung Rae KIM ; Kil O RYU ; Jiyong LIM ; Hye Mi YU ; Jihoon YOON ; Chee Young KIM ; Kwang Yong JEONG ; Young Jae JUNG ; In Seob JEONG ; Young Gil CHOI
Annals of Coloproctology 2019;35(3):144-151
		                        		
		                        			
		                        			PURPOSE: The most common risk factor for fecal incontinence (FI) is obstetric injury. FI affects 1.4%–18% of adults. Most patients are unaware when they are young, when symptoms appear suddenly and worsen with aging. Autologous fat graft is widely used in cosmetic surgical field and may substitute for injectable bulky agents in treating FI. Authors have done fat graft for past several years. This article reports the effectiveness of the fat graft in treating FI and discusses satisfaction with the procedure. METHODS: Fat was harvested from both lateral thighs using 10-mL Luer-loc syringe. Pure fat was extracted from harvests and mixed with fat, oil, and tumescent through refinement. Fats were injected into upper border of posterior ano-rectal ring, submucosa of anal canal and intersphincteric space. Thirty-five patients with FI were treated with this method from July 2016 to February 2017 in Busan Hangun Hospital. They were 13 male (mean age, 60.8 years) and 22 female patients (mean age, 63.3 years). The Wexner score was checked before procedure. We evaluated outcome in outpatients by asking the patients. For 19 patients we checked the Wexner score after procedure. RESULTS: Symptom improved in 29 (82.9%), and not improved in 6 (17.1%). In 2 of 6 patients, they felt better than before procedure, although not satisfied. No improvement in 4. Mean Wexner score was 9.7 before procedure. There were no serious complications such as inflammation or fat embolism. CONCLUSION: Autologous fat graft can be an effective alternative treatment for FI. It is safe and easy to perform, and cost effective.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aging
		                        			;
		                        		
		                        			Anal Canal
		                        			;
		                        		
		                        			Busan
		                        			;
		                        		
		                        			Embolism, Fat
		                        			;
		                        		
		                        			Fats
		                        			;
		                        		
		                        			Fecal Incontinence
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Inflammation
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Methods
		                        			;
		                        		
		                        			Outpatients
		                        			;
		                        		
		                        			Risk Factors
		                        			;
		                        		
		                        			Syringes
		                        			;
		                        		
		                        			Thigh
		                        			;
		                        		
		                        			Transplants
		                        			
		                        		
		                        	
            
Result Analysis
Print
Save
E-mail