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.Annular Pancreas: A Rare Cause of Upper Gastrointestinal Bleeding in Adults
Joung Ah KWEUN ; Hyung Mook KANG ; Jang Eon KIM ; Sung Jae PARK
The Korean Journal of Gastroenterology 2022;79(4):182-186
Annular pancreas is a rare congenital anomaly in which a thin band of pancreatic tissue partially or completely surrounds the duodenum.It is challenging to diagnose due to its variable clinical presentation. Approximately two-thirds of patients have no symptoms in their lifetime, and most symptomatic cases are seen in neonates and infants. Symptomatic adult patients present with upper gastrointestinal symptoms, such as epigastric pain, vomiting, and postprandial fullness associated with gastric outlet obstruction. Complications associated with annular pancreas include peptic ulcer disease, pancreatitis, pancreatic head carcinoma, and biliary obstruction. Annular pancreas is also a rare cause of upper gastrointestinal bleeding in adults, but it should be considered as one of the differential diagnoses in patients presenting with a peptic ulcer and duodenal stricture. Here, we report the case of a 60-year-old man who presented with melena and was subsequently diagnosed with an annular pancreas.
3.Identification of microRNAs and their target genes in the placenta as biomarkers of inflammation
Hee Yeon JANG ; Seung Mook LIM ; Hyun Jung LEE ; Joon-Seok HONG ; Gi Jin KIM
Clinical and Experimental Reproductive Medicine 2020;47(1):42-53
Objective:
Recently, microRNA (miRNA) has been identified both as a powerful regulator involved in various biological processes through the regulation of numerous genes and as an effective biomarker for the prediction and diagnosis of various disease states. The objective of this study was to identify and validate miRNAs and their target genes involved in inflammation in placental tissue.
Methods:
Microarrays were utilized to obtain miRNA and gene expression profiles from placentas with or without inflammation obtained from nine normal pregnant women and 10 preterm labor patients. Quantitative real-time polymerase chain reaction and Western blots were performed to validate the miRNAs and differentially-expressed genes in the placentas with inflammation. Correlations between miRNA and target gene expression were confirmed by luciferase assays in HTR-8/SVneo cells.
Results:
We identified and validated miRNAs and their target genes that were differentially expressed in placentas with inflammation. We also demonstrated that several miRNAs (miR-371a-5p, miR-3065-3p, miR-519b-3p, and miR-373-3p) directly targeted their target genes (LEF1, LOX, ITGB4, and CD44). However, some miRNAs and their direct target genes showed no correlation in tissue samples. Interestingly, miR-373-3p and miR-3065-3p were markedly regulated by lipopolysaccharide (LPS) treatment, although the expression of their direct targets CD44 and LOX was not altered by LPS treatment.
Conclusion
These results provide candidate miRNAs and their target genes that could be used as placental biomarkers of inflammation. These candidates may be useful for further miRNA-based biomarker development.
4.The Association of Hospital Volume of Percutaneous Coronary Intervention with Cardiac Mortality
Jae Hyun KIM ; Jang Mook KIM ; Eun Cheol PARK
Health Policy and Management 2018;28(2):168-177
BACKGROUND: This study investigates the potential volume and outcome association of coronary heart disease (CHD) patients who have undergone percutaneous coronary intervention (PCI) using a large and representative sample. METHODS: We used a National Health Insurance Service-Cohort Sample Database from 2002 to 2013 released by the Korean National Health Insurance Service. A total of 8,908 subjects were analyzed. The primary analysis was based on Cox proportional hazards models to examine our hypothesis. RESULTS: After adjusting for confounders, the hazard ratio of thirty-day and 1-year mortality in hospitals with a low volume of CHD patients with PCI was 2.8 and 2.2 times higher (p=0.00) compared to hospitals with a high volume of CHD patients with PCI, respectively. Thirty-day and 1-year mortality of CHD patients with PCI in low-volume hospitals admitted through the emergency room were 3.101 (p=0.00) and 2.8 times higher (p=0.01) than those in high-volume hospitals, respectively. Only 30-day mortality in low-volume hospitals of angina pectoris and myocardial infarction patients with PCI was 5.3 and 2.4 times those in high-volume hospitals with PCI, respectively. CONCLUSION: Mortality was significantly lower when PCI was performed in a high-volume hospital than in a low-volume hospital. Among patients admitted through the emergency room and diagnosed with angina pectoris, total PCI volume (low vs. high) was associated with significantly greater cardiac mortality risk of CHD patients. Thus, There is a need for better strategic approaches from both clinical and health policy standpoints for treatment of CHD patients.
Angina Pectoris
;
Coronary Disease
;
Emergency Service, Hospital
;
Health Policy
;
Hospitals, High-Volume
;
Hospitals, Low-Volume
;
Humans
;
Mortality
;
Myocardial Infarction
;
National Health Programs
;
Percutaneous Coronary Intervention
;
Proportional Hazards Models
5.Acute toxicity and cytotoxicity evaluation of Dendrobium moniliforme aqueous extract in vivo and in vitro.
Mu Jin LEE ; Ho Kyung JUNG ; Min Suk KIM ; Ji Hun JANG ; Mi Ok SIM ; Tea Mook KIM ; Ho PARK ; Byung Kwan AHN ; Hyun Woo CHO ; Jung Hee CHO ; Won Seok JUNG ; Jong Choon KIM
Laboratory Animal Research 2016;32(3):144-150
Dendrobium moniliforme (L.) Sw., an herb of the Orchidaceae family, has long been used in traditional medicine to strengthen bones, nourish the stomach, and promote the production of bodily fluid. Recently, polysaccharides isolated from Dendrobium have been used in functional foods and nutraceutical products. A traditional method to process Dendrobium is to soak fresh stems in an ethanol solution, which is the most important factor to ensure high yields of aqueous-extractable polysaccharides. The present study was carried out to investigate the potential acute toxicity of D. moniliforme aqueous extract (DMAE), by a single oral dose in Sprague-Dawley rats. The test article was orally administered once by gavage to male and female rats at doses of 0, 2,500, and 5,000 mg/kg body weight (n=5 male and female rats for each dose). Throughout the study period, no treatment-related deaths were observed and no adverse effects were noted in clinical signs, body weight, food consumption, serum biochemistry, organ weight, or gross findings at any dose tested. The results show that a single oral administration of DMAE did not induce any toxic effects at a dose below 5,000 mg/kg in rats, and the minimal lethal dose was considered to be over 5,000 mg/kg body weight for both sexes. With respect to cytotoxicity, the cell viability of human embryonic kidney (HEK293) cells was less than 50% when the cells were treated with 10 mg/mL aqueous extract for 24 h.
Administration, Oral
;
Animals
;
Biochemistry
;
Body Weight
;
Cell Survival
;
Dendrobium*
;
Dietary Supplements
;
Ethanol
;
Female
;
Functional Food
;
Humans
;
In Vitro Techniques*
;
Kidney
;
Male
;
Medicine, Traditional
;
Methods
;
Orchidaceae
;
Organ Size
;
Polysaccharides
;
Rats
;
Rats, Sprague-Dawley
;
Stomach
6.Autologous Bone Marrow Mesenchymal Cell Induced Chondrogenesis for the Treatment of Osteoarthritis of Knee.
Sung Woo HUH ; Asode Ananthram SHETTY ; Jang Mook KIM ; Mi La CHO ; Seon Ae KIM ; Siyoung YANG ; Young Ju KIM ; Palaksha Kanive JAVAREGOWDA ; Nam Yong CHOI ; Jin KANG ; Seok Jung KIM
Tissue Engineering and Regenerative Medicine 2016;13(2):200-209
Healthy and high quality of life has become the main issue with increasing human life span. Many biological treatments for osteoarthritis of the knee have been tried with limited success. We compared data from 7 patients who underwent total knee arthroplasty and 46 patients who underwent autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) for osteoarthritis of grade IV of the Kellgren-Lawrence classification and grade IV of modified Outerbridge classification from 50 to 65 years of age. Clinical evaluation of the 2 groups showed significant improvement in the mean telephone Knee Society Scoring system (tKSS)-A (pain) and tKSS-B (function) scores throughout the postoperative follow-up period. There was no difference in the patients' satisfaction between the 2 groups. MCIC is a treatment option at least for delaying disease progression of osteoarthritis of the knee.
Arthroplasty, Replacement, Knee
;
Bone Marrow*
;
Chondrogenesis*
;
Classification
;
Disease Progression
;
Follow-Up Studies
;
Humans
;
Knee
;
Osteoarthritis*
;
Osteoarthritis, Knee*
;
Quality of Life
;
Telephone
7.A Case of Hepatocellular Carcinoma in a Patient with Crohn's Disease.
Seung Hyeon JANG ; Jee Hyun KIM ; Jae Woo LEE ; June Young LEE ; Young Youn CHO ; Won Mook CHOI ; Hyun Chae JUNG
Korean Journal of Medicine 2015;88(4):424-429
Hepatocellular carcinomas (HCCs) in patients with Crohn's disease (CD) without underlying chronic hepatitis or liver cirrhosis are extremely rare. Previously reported cases occurred in patients who had developed CD at a young age and had been treated with immunosuppressive agents long-term. We herein report the first case of HCC in a 34-year-old patient with CD in Korea. The patient was treated with azathioprine for 14 years and had undergone repeated surgeries for CD. During the follow-up period, the patient was hospitalized for colon perforation and pericolic abscess formation. Computed tomography showed a liver mass, and HCC was diagnosed based on liver biopsy. The patient underwent right hemicolectomy for colon perforation and transcatheter arterial chemoembolization followed by radiofrequency ablation for the HCC. The present case is similar to previously reported cases with the exception of the liver pathology findings, which exhibited neither primary sclerosing cholangitis nor focal hepatic glycogenolysis.
Abscess
;
Adult
;
Azathioprine
;
Biopsy
;
Carcinoma, Hepatocellular*
;
Catheter Ablation
;
Cholangitis, Sclerosing
;
Colon
;
Crohn Disease*
;
Follow-Up Studies
;
Glycogenolysis
;
Hepatitis, Chronic
;
Humans
;
Immunosuppressive Agents
;
Korea
;
Liver
;
Liver Cirrhosis
;
Pathology
;
Infliximab
8.Sarcopenia in Korea: Prevalence and Clinical Aspects.
Kyoung Min KIM ; Soo LIM ; Kyung Mook CHOI ; Jung Hee KIM ; Sung Hoon YU ; Tae Nyun KIM ; Wook SONG ; Jae Young LIM ; Chang Won WON ; Hyung Joon YOO ; Hak Chul JANG
Journal of the Korean Geriatrics Society 2015;19(1):1-8
Sarcopenia has been defined as the considerable loss of skeletal muscle mass and strength that results in frailty in the elderly. Because muscle tissue plays diverse important roles in human, sarcopenia presents many negative health-related consequences including impaired energy homeostasis, falls and cardiovascular disease, and subsequently higher mortality. It is becoming evident that sarcopenia has a negative impact on the healthy life of the elderly. The European Working Group on Sarcopenia, the International Working Group on Sarcopenia and the Asian Working Group on Sarcopenia have released position statement regarding sarcopenia, and more recently the Foundation for the National Institutes of Health Sarcopenia Project has provided a new guideline for assessment of sarcopenia. At this time, there have been several data delineating the status of sarcopenia in Korea. This review focuses on largescale cohorts that assessed sarcopenia and highlights the controversies surrounding the clinical definition and prevalence of sarcopenia in Korea.
Aged
;
Asian Continental Ancestry Group
;
Cardiovascular Diseases
;
Cohort Studies
;
Homeostasis
;
Humans
;
Korea
;
Mortality
;
Muscle, Skeletal
;
National Institutes of Health (U.S.)
;
Prevalence*
;
Sarcopenia*
9.A novel prognostic factor for hepatocellular carcinoma: protein disulfide isomerase.
Su Jong YU ; Jae Kyung WON ; Han Suk RYU ; Won Mook CHOI ; Hyeki CHO ; Eun Ju CHO ; Jeong Hoon LEE ; Yoon Jun KIM ; Kyung Suk SUH ; Ja June JANG ; Chung Yong KIM ; Hyo Suk LEE ; Jung Hwan YOON ; Kwang Hyun CHO
The Korean Journal of Internal Medicine 2014;29(5):580-587
BACKGROUND/AIMS: Protein disulfide isomerase (PDI) has been implicated in the survival and progression of some cancer cells, by compensating for endoplasmic reticulum stress by upregulating the protein-folding capacity. However, its prognostic role in patients with hepatocellular carcinoma (HCC) has not been investigated. METHODS: We collected HCC tissues from 83 HCC patients who underwent surgical resection for an immunohistochemical study of PDI. Overall survival (OS) was measured from the date of surgical resection until the date of death from any cause. Radiological progression was evaluated using the modified Response Evaluation Criteria in Solid Tumors in an independent radiological assessment. RESULTS: PDI expression was found to be increased in human HCC compared to adjacent nontumor tissues. Increased immunopositivity for PDI was associated with a high Edmondson-Steiner grade (p = 0.028). Univariate analysis of patients who had undergone surgical resection for HCC showed that tumor PDI upregulation is a significant risk factor for poor OS (p = 0.016; hazard ratio [HR], 1.980) and time to progression (TTP; p = 0.007; HR, 1.971). Multivariate analyses revealed that high PDI expression was an independent predictor of a shorter TTP (p = 0.015; HR, 1.865) and poor OS (p = 0.012; HR, 2.069). CONCLUSIONS: Upregulated PDI expression is associated with aggressive clinicopathological features of HCC; thus, PDI might serve as an independent prognostic factor and a potential therapeutic target for HCC patients.
Carcinoma, Hepatocellular/*enzymology/pathology
;
Female
;
Humans
;
Kaplan-Meier Estimate
;
Liver Neoplasms/*enzymology/pathology
;
Male
;
Middle Aged
;
Prognosis
;
Protein Disulfide-Isomerases/*metabolism
;
Retrospective Studies
;
Tumor Markers, Biological/metabolism
10.Scalp Reconstruction after Resection of a Large Recurred Proliferating Trichilemmal Tumor Using an Anterolateral Thigh Free Flap.
Matthew Seung Suk CHOI ; Eui Jong KIM ; Jang Hyun LEE ; Ju Yeon PYO ; Yong Wook PARK ; Kyung Mook LEE
Archives of Plastic Surgery 2013;40(4):458-460
No abstract available.
Free Tissue Flaps
;
Scalp
;
Thigh

Result Analysis
Print
Save
E-mail