1.AM1638, a GPR40-Full Agonist, Inhibited Palmitate- Induced ROS Production and Endoplasmic Reticulum Stress, Enhancing HUVEC Viability in an NRF2-Dependent Manner
Hwan-Jin HWANG ; Joo Won KIM ; SukHwan YUN ; Min Jeong PARK ; Eyun SONG ; Sooyeon JANG ; Ahreum JANG ; Kyung Mook CHOI ; Sei Hyun BAIK ; Hye Jin YOO
Endocrinology and Metabolism 2023;38(6):760-769
Background:
G protein-coupled receptor 40 (GPR40) is a key molecule in diabetes and fatty liver, but its role in endothelial dysfunction remains unclear. Our objective in this study was to determine whether GPR40 agonists protect endothelial cells against palmitatemediated oxidative stress.
Methods:
Human umbilical vein endothelial cells (HUVECs) were used to investigate effects of various GPR40 agonists on vascular endothelium.
Results:
In HUVECs, AM1638, a GPR40-full agonist, enhanced nuclear factor erythroid 2–related factor 2 (NRF2) translocation to the nucleus and heme oxygenase-1 (HO-1) expression, which blocked palmitate-induced superoxide production. Those antioxidant effects were not detected after treatment with LY2922470 or TAK875, GPR40-partial agonists, suggesting that GPR40 regulates reactive oxygen species (ROS) removal in a ligand-dependent manner. We also found that palmitate-induced CCAAT/enhancer‐binding protein homologous protein expression; X-box binding protein-1 splicing, nuclear condensation, and fragmentation; and caspase-3 cleavage were all blocked in an NRF2-dependent manner after AM1638 treatment. Both LY2922470 and TAK875 also improved cell viability independent of the NRF2/ROS pathway by reducing palmitate-mediated endoplasmic reticulum stress and nuclear damage. GPR40 agonists thus have beneficial effects against palmitate in HUVECs. In particular, AM1638 reduced palmitate-induced superoxide production and cytotoxicity in an NRF2/HO-1 dependent manner.
Conclusion
GPR40 could be developed as a good therapeutic target to prevent or treat cardiovascular diseases such as atherosclerosis.
2.Differences in the heritability of craniofacial skeletal and dental characteristics between twin pairs with skeletal Class I and II malocclusions
Heon-Mook PARK ; Pil-Jong KIM ; Joohon SUNG ; Yun-Mi SONG ; Hong-Gee KIM ; Young Ho KIM ; Seung-Hak BAEK
The Korean Journal of Orthodontics 2021;51(6):407-418
Objective:
To investigate differences in the heritability of skeletodental characteristics between twin pairs with skeletal Class I and Class II malocclusions.
Methods:
Forty Korean adult twin pairs were divided into Class I (C-I) group (0° ≤ angle between point A, nasion, and point B [ANB]) ≤ 4°; mean age, 40.7 years) and Class II (C-II) group (ANB > 4°; mean age, 43.0 years). Each group comprised 14 monozygotic and 6 dizygotic twin pairs. Thirty-three cephalometric variables were measured using lateral cephalograms and were categorized as the anteroposterior, vertical, dental, mandible, and cranial base characteristics. The ACE model was used to calculate heritability (A > 0.7, high heritability). Thereafter, principal component analysis (PCA) was performed.
Results:
Twin pairs in C-I group exhibited high heritability values in the facial anteroposterior characteristics, inclination of the maxillary and mandibular incisors, mandibular body length, and cranial base angles. Twin pairs in C-II group showed high heritability values in vertical facial height, ramus height, effective mandibular length, and cranial base length. PCA extracted eight components with 88.3% in the C-I group and seven components with 91.0% cumulative explanation in the C-II group.
Conclusions
Differences in the heritability of skeletodental characteristics between twin pairs with skeletal Class I and II malocclusions might provide valuable information for growth prediction and treatment planning.
3.The association between quality of direct supervisor's behavior and depressive mood in Korean wage workers: the 4th Korean Working Conditions Survey
Cham Jin PARK ; Ji Hoo YOOK ; Min Seok KIM ; Dongwook LEE ; Hyun Mook LIM ; Yun Chul HONG
Annals of Occupational and Environmental Medicine 2019;31(1):e16-
BACKGROUND: Workers spend most of their social lives at work and have relationships of varying nature with people in the workplace. Direct supervisors, in particular, have a direct and lasting impact on workers, which may influence workers' mental health. Depression is very prevalent worldwide, and social concern about the disease is on the rise. The aim of this study is to investigate the effect of direct supervisors' behavior on the depressive mood of Korean wage workers. METHODS: We used data from the 4th Korean Working Conditions Survey held in 2014; 22,212 participants were included in the analysis. The quality of a direct supervisor's behavior was categorized from 0 (= lowest) to 5 (= highest) points. The degree of depressive mood was measured on a scale from “normal mood” to “likely depression” based on the 5-item World Health Organization Well-Being Index (WHO-5) questionnaire. Multiple logistic regression was used to analyze the association between the quality of the direct supervisor's behavior and the depressive mood of wage workers. RESULTS: After multivariable adjustment, significantly increased odds ratio (OR) for likely depression was found in the 4, 3, 2, 1, and 0 points of the quality of the direct supervisor's behavior compared to 5 points. After stratification for the level of satisfaction with working conditions, the OR of the unsatisfied groups was higher than that of the satisfied groups. CONCLUSIONS: Likely depression was found to be significantly associated with a low quality of direct supervisor's behavior. This association was stronger in workers who were not satisfied with their working conditions. This study suggests that proper management of the direct supervisor's behavior is needed to reduce the risk of depression among Korean wage workers.
Depression
;
Logistic Models
;
Mental Health
;
Odds Ratio
;
Salaries and Fringe Benefits
;
World Health Organization
4.Acute Pancreatitis Associated with Intraductal Tubulopapillary Neoplasm of the Pancreas.
Eun Young KIM ; Jae Uk SHIN ; Yeon Ho JOO ; Jue Yong LEE ; Ji Hun KIM ; Yun Jung PARK ; Myeng Nam BAE ; Sang Mook BAE
The Ewha Medical Journal 2013;36(Suppl):S9-S13
Intraductal tubulopapillary neoplasm (ITPN) of the pancreas has been recently reported. It is very rare, therefore clinical behavior and prognosis has not yet been characterized. We experienced a case of ITPN of the pancreas which presented with acute pancreatitis and treated with Whipple's operation. Histopathologic finding showed papillary hyperplasia with carcinomatous change. The tumor recurred after 47 month of operation, and she underwent total pancreatectomy. Pathologic finding revealed tubulopapillary growth with high grade dysplasia. Immunohistochemial staining was not performed, however gross and microscopic findings were compatible with ITPN of the pancreas. We report a case of ITPN of the pancreas.
Hyperplasia
;
Pancreas*
;
Pancreatectomy
;
Pancreatitis*
;
Prognosis
5.Acute Pancreatitis Associated with Intraductal Tubulopapillary Neoplasm of the Pancreas.
Eun Young KIM ; Jae Uk SHIN ; Yeon Ho JOO ; Jue Yong LEE ; Ji Hun KIM ; Yun Jung PARK ; Myeng Nam BAE ; Sang Mook BAE
The Ewha Medical Journal 2013;36(Suppl):S9-S13
Intraductal tubulopapillary neoplasm (ITPN) of the pancreas has been recently reported. It is very rare, therefore clinical behavior and prognosis has not yet been characterized. We experienced a case of ITPN of the pancreas which presented with acute pancreatitis and treated with Whipple's operation. Histopathologic finding showed papillary hyperplasia with carcinomatous change. The tumor recurred after 47 month of operation, and she underwent total pancreatectomy. Pathologic finding revealed tubulopapillary growth with high grade dysplasia. Immunohistochemial staining was not performed, however gross and microscopic findings were compatible with ITPN of the pancreas. We report a case of ITPN of the pancreas.
Hyperplasia
;
Pancreas*
;
Pancreatectomy
;
Pancreatitis*
;
Prognosis
6.Mechanism of Relaxation Via TASK-2 Channels in Uterine Circular Muscle of Mouse.
Seung Hwa HONG ; Rohyun SUNG ; Young Chul KIM ; Hikaru SUZUKI ; Woong CHOI ; Yeon Jin PARK ; Ill Woon JI ; Chan Hyung KIM ; Sun Chul MYUNG ; Moo Yeol LEE ; Tong Mook KANG ; Ra Young YOU ; Kwang Ju LEE ; Seung Woon LIM ; Hyo Yung YUN ; Young Jin SONG ; Wen Xie XU ; Hak Soon KIM ; Sang Jin LEE
The Korean Journal of Physiology and Pharmacology 2013;17(4):359-365
Plasma pH can be altered during pregnancy and at labor. Membrane excitability of smooth muscle including uterine muscle is suppressed by the activation of K+ channels. Because contractility of uterine muscle is regulated by extracellular pH and humoral factors, K+ conductance could be connected to factors regulating uterine contractility during pregnancy. Here, we showed that TASK-2 inhibitors such as quinidine, lidocaine, and extracellular acidosis produced contraction in uterine circular muscle of mouse. Furthermore, contractility was significantly increased in pregnant uterine circular muscle than that of non-pregnant muscle. These patterns were not changed even in the presence of tetraetylammonium (TEA) and 4-aminopyridine (4-AP). Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretchactivated channels in myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed increased immunohistochemical expression of TASK-2. Therefore, TASK-2, seems to play a key role during regulation of myometrial contractility in the pregnancy and provides new insight into preventing preterm delivery.
4-Aminopyridine
;
Acidosis
;
Animals
;
Contracts
;
Female
;
Hydrogen-Ion Concentration
;
Lidocaine
;
Membranes
;
Methionine
;
Mice
;
Muscle, Smooth
;
Muscles
;
Myometrium
;
Plasma
;
Pregnancy
;
Quinidine
;
Relaxation
;
Uterine Contraction
;
Uterus
7.Methanolic Extract Isolated from Root of Lycoris aurea Inhibits Cancer Cell Growth and Endothelial Cell Tube Formation In Vitro.
Moo Rim KANG ; Chang Woo LEE ; Jieun YUN ; Soo Jin OH ; Song Kyu PARK ; Kiho LEE ; Hwan Mook KIM ; Sang Bae HAN ; Hyoung Chin KIM ; Jong Soon KANG
Toxicological Research 2012;28(1):33-38
In this study, we investigated the effect of methanolic extract isolated from the root of Lycoris aurea (LA) on the growth of cancer cells and the tube formation activity of endothelial cells. Various cancer cells were treated with LA at doses of 0.3, 1, 3, 10 or 30 microg/ml and LA significantly suppressed the growth of several cancer cell lines, including ACHN, HCT-15, K-562, MCF-7, PC-3 and SK-OV-3, in a dose-dependent manner. We also found that LA induced cell cycle arrest at G2/M phase in ACHN renal cell adenocarcinoma cells. Further study demonstrated that LA concentration-dependently inhibited the tube formation, which is a widely used in vitro model of reorganization stage of angiogenesis, in human umbilical vein endothelial cells. Collectively, these results show that LA inhibits the growth of cancer cells and tube formation of endothelial cells and the growth-inhibitory effect of LA might be mediated, at least in part, by blocking cell cycle progression.
Carcinoma, Renal Cell
;
Cell Cycle
;
Cell Cycle Checkpoints
;
Cell Line
;
Endothelial Cells
;
Human Umbilical Vein Endothelial Cells
;
Lycoris
;
Methanol
8.Partial gastric outlet obstruction caused by a huge submucosal tumor originating in the heterotopic pancreas.
Gum O JUNG ; Dong Eun PARK ; Ki Jung YUN ; Kwon Mook CHAE
Korean Journal of Hepato-Biliary-Pancreatic Surgery 2011;15(3):194-197
A 21-year-old woman presented gastrointestinal manifestation showing intermittent abdominal pain, nausea, and vomiting. An upper endoscopic examination showed round, elevated mucosa at the antrum of the stomach anterior wall. After CT scanning, a huge degenerated gastrointestinal stromal tumor was suspected. Subtotal gastrectomy with Billroth II anastomosis was performed. Histologically, pseudocystic degeneration of the heterotopic pancreas was confirmed. The patient showed eventful postoperative course except temporary dilated gastric emptying. The patient is doing well without any abnormal symptom at 8-month follow-up. This report is a rare case of gastric outlet obstruction caused by a pseudocyst originating from a heterotopic pancreas in the gastric antrum.
Abdominal Pain
;
Female
;
Follow-Up Studies
;
Gastrectomy
;
Gastric Emptying
;
Gastric Outlet Obstruction
;
Gastroenterostomy
;
Gastrointestinal Stromal Tumors
;
Humans
;
Mucous Membrane
;
Nausea
;
Pancreas
;
Pyloric Antrum
;
Stomach
;
Vomiting
;
Young Adult
9.A Case of Liver Metastasis of Gastrointestinal Stromal Tumor That Was Resected after Treatment with Imatinib Mesylate and Sunitinib.
Gum O JUNG ; Kwon Mook CHAE ; Dong Eun PARK ; Hyeok SHIM ; Sang Hyun PARK ; Ki Jung YUN
Korean Journal of Hepato-Biliary-Pancreatic Surgery 2010;14(4):262-266
A 65-year old man underwent wedge resection for a gastrointestinal stromal tumor (GIST) of the gastric fundus in 1997. In 2003, the abdominal CT and sono-guided biopsy revealed he had a large GIST liver metastasis. He underwent treatment with 400 mg/day of imatinib mesylate. As a result, the liver metastasis markedly decreased in size. However, focal progression of the liver metastasis was observed on the follow up CT, so we increased the imatinib from 400 mg/day to 800 mg/day. We then performed extended left hepatectomy. We report here on a patient who presented with an isolated metastatic GIST to the liver, and the patient was successfully treated with imatinib therapy and hemihepatectomy.
Benzamides
;
Biopsy
;
Follow-Up Studies
;
Gastric Fundus
;
Gastrointestinal Stromal Tumors
;
Hepatectomy
;
Humans
;
Indoles
;
Liver
;
Mesylates
;
Neoplasm Metastasis
;
Piperazines
;
Pyrimidines
;
Pyrroles
;
Imatinib Mesylate
10.Clinical Outcome of Cranial Neuropathy in Patients with Pituitary Apoplexy.
Hyun Jin WOO ; Jeong Hyun HWANG ; Sung Kyoo HWANG ; Yun Mook PARK
Journal of Korean Neurosurgical Society 2010;48(3):213-218
OBJECTIVE: Pituitary apoplexy (PA) is described as a clinical syndrome characterized by sudden headache, vomiting, visual impairment, and meningismus caused by rapid enlargement of a pituitary adenoma. We retrospectively analyzed the clinical presentation and surgical outcome in PA presenting with cranial neuropathy. METHODS: Twelve cases (3.3%) of PA were retrospectively reviewed among 359 patients diagnosed with pituitary adenoma. The study included 6 males and 6 females. Mean age of patients was 49.0 years, with a range of 16 to 74 years. Follow-up duration ranged from 3 to 20 months, with an average of 12 months. All patients were submitted to surgery, using the transsphenoidal approach (TSA). RESULTS: Symptoms included abrupt headache (11/12), decreased visual acuity (12/12), visual field defect (11/12), and cranial nerve palsy of the third (5/12) and sixth (2/12). Mean height of the mass was 29.0 mm (range 15-46). Duration between the ictus and operation ranged from 1 to 15 days (mean 7.0). The symptom duration before operation and the recovery period of cranial neuropathy correlated significantly (p = 0.0286). TSA resulted in improvement of decreased visual acuity in 91.6%, visual field defect in 54.5%, and cranial neuropathy in 100% at 3 months after surgery. CONCLUSION: PA is a rare event, complicating 3.3% in our series. Even in blindness following pituitary apoplexy cases, improvement of cranial neuropathy is possible if adequate management is initiated in time. Surgical decompression must be considered as soon as possible in cases with severe visual impairment or cranial neuropathy.
Blindness
;
Cranial Nerve Diseases
;
Decompression, Surgical
;
Female
;
Follow-Up Studies
;
Headache
;
Humans
;
Male
;
Meningism
;
Pituitary Apoplexy
;
Pituitary Neoplasms
;
Retrospective Studies
;
Vision Disorders
;
Visual Acuity
;
Visual Fields
;
Vomiting

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