1.Melatonin Protects Chronic Kidney Disease Mesenchymal Stem/Stromal Cells against Accumulation of Methylglyoxal via Modulation of Hexokinase-2 Expression
Gyeongyun GO ; Yeo Min YOON ; Sungtae YOON ; Gaeun LEE ; Ji Ho LIM ; Su-Yeon HAN ; Sang Hun LEE
Biomolecules & Therapeutics 2022;30(1):28-37
Treatment options for patients with chronic kidney disease (CKD) are currently limited; therefore, there has been significant interest in applying mesenchymal stem/stromal cell (MSC)-based therapy to treat CKD. However, MSCs harvested from CKD patients tend to show diminished viability and proliferation due to sustained exposure to uremic toxins in the CKD environment, which limits their utility for cell therapy. The application of melatonin has been demonstrated to improve the therapeutic efficacy of MSCs derived from and engrafted to tissues in patients suffering from CKD, although the underlying biological mechanism has not been elucidated. In this study, we observed overexpression of hexokinase-2 (HK2) in serum samples of CKD patients and MSCs harvested from an adenine-fed CKD mouse model (CKD-mMSCs). HK2 upregulation led to increased production levels of methylglyoxal (MG), a toxic metabolic intermediate of abnormal glycolytic processes. The overabundance of HK2 and MG was associated with impaired mitochondrial function and low cell proliferation in CKD-mMSCs. Melatonin treatment inhibited the increases in HK2 and MG levels, and further improved mitochondrial function, glycolytic metabolism, and cell proliferation. Our findings suggest that identifying and characterizing metabolic regulators such as HK2 in CKD may improve the efficacy of MSCs for treating CKD and other kidney disorders.
4.Two Korean siblings with autosomal recessive spinocerebellar ataxia 20 caused by homozygous variants in SNX14
Ae Ryoung KIM ; Jong-Mok LEE ; Go Hun SEO ; Sang In LEE ; Hyunwoo BAE ; Yun Jeong LEE
Journal of Genetic Medicine 2021;18(2):127-131
Autosomal recessive spinocerebellar ataxia 20 (SCAR20; OMIM #616354) is a recently described disorder that is characterized by ataxia, intellectual disability, cerebellar atrophy, macrocephaly, coarse face, and absent speech. It is caused by lossof-function mutations in SNX14. To date, all cases with homozygous pathogenic variants have been identified in consanguineous families. This report describes the first Korean cases of SCAR20 family caused by homozygous variants in SNX14. Two siblings were referred to our clinic because of severe global developmental delay. They presented similar facial features, including a high forehead, long philtrum, thick lips, telecanthus, depressed nasal bridge, and broad base of the nose. Because the older sibling was unable to walk and newly developed ataxia, repeated brain magnetic resonance imaging (MRI) was performed at the age of 4 years, revealing progressive cerebellar atrophy compared with MRI performed at the age of 2 years.The younger sibling’s MRI revealed a normal cerebellum at the age of 2 years. Whole-exome sequencing was performed, and homozygous variants, such as c.2746-2A>G, were identified in SNX14 from the older sibling. Sanger sequencing confirmed homozygous SNX14 variants in the two siblings as well as a heterozygous variant in both parents. This report extends our knowledge of the phenotypic and mutational spectrum of SCAR20. We also highlight the importance of deep phenotyping for the diagnosis of SCAR20 in individuals with developmental delay, ataxia, cerebellar atrophy, and distinct facial features.
5.A single-arm phase II study of olaparib maintenance with pembrolizumab and bevacizumab in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer (OPEB-01)
Yong Jae LEE ; Myong Cheol LIM ; Byoung-Gie KIM ; Natalie YL NGOI ; Chel Hun CHOI ; Sang-Yoon PARK ; David SP TAN ; Yunjung GO ; Jung-Yun LEE
Journal of Gynecologic Oncology 2021;32(2):e31-
Background:
The optimal treatment of BRCA wild-type patients with platinum-sensitive recurrent ovarian cancer remains unknown. Recently, there is an increase in the evidence to support the role of the combination of a poly(adenosine diphosphate-ribose) polymerase inhibitor, anti-angiogenic agents, and immunotherapy as maintenance therapy in BRCA wild-type patients with platinum-sensitive recurrence. We hypothesized that adding pembrolizumab and bevacizumab to olaparib maintenance can increase progression-free survival (PFS) in BRCA wild-type patients with platinum-sensitive recurrent ovarian cancer.
Methods
BRCA wild-type patients who received two previous courses of platinum-containing therapy, achieved complete or partial response to last treatment, and the treatment-free interval is >6 months after the penultimate platinum-based chemotherapy offered olaparib maintenance with pembrolizumab and bevacizumab. Forty-four patients will be included from 4 sites across Singapore and Korea. The primary endpoint of the study is 6-month PFS rate.
6.Distribution of Pathogenic Vibrio Species in the Coastal Seawater of South Korea (2017–2018)
Seung Hun LEE ; Hee Jung LEE ; Go Eun MYUNG ; Eun Jin CHOI ; In A KIM ; Young Il JEONG ; Gi Jun PARK ; Sang Moon SOH
Osong Public Health and Research Perspectives 2019;10(6):337-342
OBJECTIVES: Pathogenic Vibrio species are widely distributed in warm estuarine and coastal environments, and can infect humans through the consumption of raw or mishandled contaminated seafood and seawater. For this reason, the distribution of these bacteria in South Korea was investigated.METHODS: Seawater samples were collected from 145 coastal area points in the aquatic environment in which Vibrio species live. Environmental data (i.e., water temperature, salinity, turbidity, and atmospheric temperature) was collected which may help predict the distribution of the species (data not shown). Seawater samples were filtered, and incubated overnight in alkaline peptone water, at 37°C. Using species-specific polymerase chain reaction methods, screening tests were performed for the hlyA, ctxA, vvhA, and tlh genes. Clones of pathogenic Vibrio species were isolated using 3 selective plating media.RESULTS: In 2017, total seawater isolation rates for Vibrio vulnificus, Vibrio cholerae (non-pathogenic, non-O1, non-O139 serogroups), and Vibrio parahaemolyticus were 15.82%, 13.18%, 65.80%, respectively. However, in 2018 isolation rates for each were 21.81%, 19.40%, and 70.05%, respectively.CONCLUSION: The isolation rates of pathogenic Vibrio species positively correlated with the temperature of seawater and atmosphere, but negatively correlated with salinity and turbidity. From 2017 to 2018, the most frequent seawater-isolated Vibrio species were V. parahaemolyticus (68.10 %), V. vulnificus (16.54%), and non-toxigenic V. cholerae (19.58%). Comprehensive monitoring, prevention, and control efforts are needed to protect the public from pathogenic Vibrio species.
Atmosphere
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Bacteria
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Cholera
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Clone Cells
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Humans
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Korea
;
Mass Screening
;
Peptones
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Polymerase Chain Reaction
;
Salinity
;
Seafood
;
Seawater
;
Vibrio cholerae
;
Vibrio parahaemolyticus
;
Vibrio vulnificus
;
Vibrio
;
Water
7.Development of Korean Teaching Model for Surgical Procedures in Trauma -Essential Surgical Procedures in Trauma Course-
Hohyun KIM ; Chan Yong PARK ; Hyun Min CHO ; Kwang Hee YEO ; Jae Hun KIM ; Byungchul YU ; Seung Je GO ; Oh Sang KWON
Journal of the Korean Society of Traumatology 2019;32(1):8-16
PURPOSE:
The Essential Surgical Procedures in Trauma (ESPIT) course was developed as a model to teach necessary surgical procedures to trauma physicians. Its goals are to improve knowledge, self-confidence, and technical competence.
METHODS:
The ESPIT course consisted of five lectures and a porcine lab operative experience. The ESPIT course has been run seven times between February 2014 and April 2016. ESPIT participants completed a questionnaire to assess self-efficacy regarding essential surgical procedures in trauma before and immediately after taking the ESPIT course. Sixty-three participants who completed both pre- and post-course questionnaires on self-efficacy were enrolled in this study.
RESULTS:
The overall post-ESPIT mean self-efficacy score was higher than the pre-ESPIT mean self-efficacy score (8.3±1.30 and 4.5±2.13, respectively) (p<0.001). Self-efficacy was significantly improved after the ESPIT course in general surgeons (p<0.001), thoracic and cardiovascular surgeons (p<0.001), emergency medicine doctors, and others (neurosurgeons, orthopedic surgeons) (p<0.001). The differences in self-efficacy score according to career stage (<1 year, 1–3 years, 3–5 years, and >5 years) were also statistically significant (p<0.001).
CONCLUSIONS
The data of the ESPIT participants indicated that they felt that the ESPIT course improved their self-efficacy with regard to essential surgical procedures in trauma. The ESPIT course may be an effective strategy for teaching surgical procedures, thus promoting better management of traumatic injuries.
8.Effect of Resveratrol on Cell Differentiation and Mineralization in Cultured Odontoblasts
Sang Hun SHIN ; Jae Sung KIM ; Su Gwan KIM ; Dae San GO ; Sun Kyoung YU ; Chun Sung KIM ; Joo Cheol PARK ; Do Kyung KIM
International Journal of Oral Biology 2018;43(3):133-140
Resveratrol (3,4′,5,-trihydroxystilbene), a phytoalexin present in grapes, exerts a variety of actions to reduce superoxides, prevents diabetes mellitus, and inhibits inflammation. Resveratrol acts as a chemo-preventive agent and induces apoptotic cell death in various cancer cells. However, the role of resveratrol in odontoblastic cell differentiation is unclear. In this study, the effect of resveratrol on regulating odontoblast differentiation was examined in MDPC-23 mouse odontoblastic cells derived from mouse dental papilla cells. Resveratrol significantly accelerated mineralization as compared with the control culture in differentiation of MDPC-23 cells. Resveratrol significantly increased expression of ALP mRNA as compared with the control in differentiation of MDPC-23 cells. Resveratrol significantly accelerated expression of ColImRNA as compared with the control in differentiation of MDPC-23 cells. Resveratrol significantly increased expressions of DSPP and DMP-1 mRNAs as compared with the control in differentiation of MDPC-23 cells. Treatment of resveratrol did not significantly affect cell proliferation in MDPC-23 cells. Results suggest resveratrol facilitates odontoblast differentiation and mineralization in differentiation of MDPC-23 cells, and may have potential properties for development and clinical application of dentin regeneration materials.
Animals
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Cell Death
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Cell Differentiation
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Cell Proliferation
;
Dental Papilla
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Dentin
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Diabetes Mellitus
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Inflammation
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Mice
;
Miners
;
Odontoblasts
;
Regeneration
;
RNA, Messenger
;
Superoxides
;
Vitis
9.Patient's Factors at Entering Hospice Affecting Length of Survival in a Hospice Center.
Guk Jin LEE ; Hye Shin AHN ; Se Eun GO ; Ji Hyun KIM ; Min Wu SEO ; Seung Hun KANG ; Yeo Ree YANG ; Mi Yeong LEE ; Ku Ock LEE ; Sang Hoon CHUN ; Jong Youl JIN
Cancer Research and Treatment 2015;47(1):1-8
PURPOSE: In order to provide effective hospice care, adequate length of survival (LOS) in hospice is necessary. However the reported average LOS is much shorter. Analysis of LOS in hospice has not been reported from Korea. We evaluated the duration of LOS and the factors associated with LOS at our hospice center. MATERIALS AND METHODS: We retrospectively examined 446 patients who were admitted to our hospice unit between January 2010 and December 2012. We performed univariate and multivariate analysis for analysis of factors associated with LOS. RESULTS: The median LOS was 9.5 days (range, 1 to 186 days). The LOS of 389 patients (86.8%) was< 1 month. At the time of admission to hospice, 112 patients (25.2%) were completely bedridden, 110 patients (24.8%) had mouth care only without intake, and 134 patients (30.1%) had decreased consciousness, from confusion to coma. The median time interval between the day of the last anticancer treatment and the day of hospice admission was 75 days. By analysis of the results of multivariate analysis, decreased intake and laboratory results showing increased total white blood cell (WBC), decreased platelet count, increased serum creatinine, increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) level were poor prognostic factors for survival in hospice. CONCLUSION: Before hospice admission, careful evaluation of the patient's performance, particularly the oral intake, and total WBC, platelet, creatinine, AST, ALT, and LDH level is essential, because these were strong predictors of shorter LOS. In the future, conduct of prospective controlled studies is warranted in order to confirm the relationship between potential prognostic factors and LOS in hospice.
Alanine Transaminase
;
Aspartate Aminotransferases
;
Blood Platelets
;
Coma
;
Consciousness
;
Creatinine
;
Hospice Care
;
Hospices*
;
Humans
;
Korea
;
L-Lactate Dehydrogenase
;
Leukocytes
;
Mouth
;
Multivariate Analysis
;
Platelet Count
;
Prognosis
;
Retrospective Studies
;
Survival Analysis
10.Clinical feature of Fitz-Hugh-Curtis syndrome: Analysis of 25 cases.
Hyeon Woong YANG ; Sung Hee JUNG ; Hyun Young HAN ; Anna KIM ; Yun Jung LEE ; Sang Woo CHA ; Hun GO ; Gi Young CHOI ; Soung Hoon CHO ; Sin Hyung LIM
The Korean Journal of Hepatology 2008;14(2):178-184
BACKGROUND/AIMS: Fitz-Hugh-Curtis syndrome is defined as perihepatitis associated with pelvic inflammatory disease (PID). We retrospectively analyzed clinical and laboratory manifestations as well as the therapeutic response in patients with clinically diagnosed Fitz-Hugh-Curtis syndrome. METHODS: A cohort of 25 patients with PID and perihepatitis (as diagnosed by dynamic abdominal computed tomography (CT)) was enrolled. The prognosis, clinical manifestations, and physical examination, laboratory, and CT findings were analyzed. RESULTS: The mean (+/-SD) age of the patients was 32(+/-8) years, and all of them were sexually active, premenopausal women, and presented with abdominal pain. Of these, 52% complained of vaginal discharge. On physical examination, right upper-quadrant tenderness was the most common finding (84%), with lower-abdominal tenderness being present in 20% of patients. On laboratory examination, erythrocyte sedimentation rate and C-reactive protein were increased in 76% and 92% of the patients, respectively. The white blood cell count was increased in 60% of them. Most patients had a normal liver function test. Using a specimen of the cervical discharge, the polymerase chain reaction to test for Chlamydia trachomatis were positive in 87% (13/15) of the patients, and Chlamydia antigen was found in 75% (9/12) of them. Dynamic abdominal CT revealed subcapsular enhancement of the liver in the arterial phase. All of the patients improved with antibiotic therapy. CONCLUSIONS: Symptoms and physical findings suggestive of PID are not present in many patients with Fitz-Hugh-Curtis syndrome. When a premenopausal woman complains of upper abdominal pain and shows CT findings compatible with perihepatitis, examination of cervical discharge would be recommended to assess the possibility of Fitz-Hugh-Curtis syndrome.
Adult
;
Anti-Bacterial Agents/therapeutic use
;
Chlamydia Infections/diagnosis/microbiology
;
Chlamydia trachomatis/isolation & purification
;
Cohort Studies
;
Diagnosis, Differential
;
Drug Therapy, Combination
;
Female
;
Gonorrhea/complications/*diagnosis/radiography
;
Hepatitis/complications/*diagnosis/radiography
;
Humans
;
Pelvic Inflammatory Disease/complications/*diagnosis/radiography
;
Retrospective Studies
;
Syndrome
;
Tomography, X-Ray Computed

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