Publications by authors named "Hyun Young Kim"

375 Publications

Aberrant Loss of Surface CD3 and TCRγδ Expression in Relapsed Hepatosplenic T-cell Lymphoma.

Ann Lab Med 2021 Nov;41(6):598-600

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3343/alm.2021.41.6.598DOI Listing
November 2021

A Case of Burkitt-Like Lymphoma With 11q Aberration With HIV Infection in East Asia and Literature Review.

Ann Lab Med 2021 Nov;41(6):593-597

Department of Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3343/alm.2021.41.6.593DOI Listing
November 2021

Cecal intubation time in screening colonoscopy.

Authors:
Hyun Young Kim

Medicine (Baltimore) 2021 May;100(19):e25927

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea.

Abstract: The time required to intubate the cecum varies. The aim of this study was to determine whether demographic and anthropometric factors, such as body mass index (BMI), percent body fat, muscle mass, and fat mass, affect the cecal intubation time (CIT) during complete colonoscopy.A retrospective chart review of 1229 patients (aged 40-80 years) was performed. These patients underwent average-risk screening colonoscopies performed by expert gastroenterologists at Health Check-up Center, Seoul National University Bundang Hospital, during a health check-up. We collected data on age, sex, BMI, percent body fat, muscle mass, fat mass, history of prior abdominal or pelvic surgery, CIT, and bowel preparation quality (Boston Bowel Preparation Scale [BBPS] score).Of the 1229 patients, 62% were men. The mean age was 55 years, and the mean BMI was 24 kg/m2. The median CIT was 5 min. The patients were categorized into two groups according to CIT: easy colonoscopy (CIT ≤ 10 min) and difficult colonoscopy (CIT > 10 min). In univariate analysis, CIT was prolonged by the following factors: older age, poor bowel preparation, lower BMI, lower percent body fat, and less fat mass. Multivariate analysis showed that anthropometric indices including BMI, percent body fat, muscle mass, and fat mass were not significant factors for CIT. Older age (≥ 70 years) (odds ratio [OR]: 2.272, 95% confidence interval [CI]: 1.056-4.890, P = .036) and poor bowel preparation (BBPS score ≤ 5) (OR: 3.817, 95% CI: 1.866-7.808, P = .000) were found to be correlated with difficult colonoscopy.Our study suggests that anthropometric indices including BMI, percent body fat, muscle mass, and fat mass are not associated with significantly different CIT. Furthermore, sex and prior abdominal or pelvic surgery are not useful factors for a prolonged CIT. Older age (≥ 70 years) and poor bowel preparation (BBPS score ≤ 5) are significant variables predicting the CIT of expert gastroenterologists.
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http://dx.doi.org/10.1097/MD.0000000000025927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133265PMC
May 2021

Clinical Outcomes of Pediatric Chronic Intestinal Pseudo-Obstruction.

J Clin Med 2021 May 28;10(11). Epub 2021 May 28.

Department of Pediatric Surgery, Seoul National University Children's Hospital, Seoul 03080, Korea.

Chronic intestinal pseudo-obstruction (CIPO) is an extremely rare condition with symptoms of recurrent intestinal obstruction without any lesions. The outcomes of pediatric CIPO and predictors for the outcomes have not yet been well established. We analyzed the clinical outcomes and associated factors for the outcomes of pediatric CIPO. We retrospectively reviewed 66 primary CIPO patients diagnosed between January 1985 and December 2017. We evaluated parenteral nutrition (PN) factors such as PN duration, PN use over 6 months, home PN, and mortality as outcomes. We selected onset age, presence of urologic symptoms, pathologic type, and involvement extent as predictors. The early-onset CIPO was found in 63.6%, and 21.2% of the patients presenting with urologic symptoms. Of the 66 patients, 47 and 11 had neuropathy and myopathy, respectively. The generalized involvement type accounted for 83.3% of the cases. At the last follow-up, 24.2% of the patients required home PN management. The mean duration of PN was 11.8 ± 21.0 months. The overall mortality rate of primary CIPO was 18.2%. PN factors were predicted by the urologic symptoms and extent of involvement. However, mortality was predicted by pathologic type. The onset age was not significantly associated with the outcomes. CIPO with urologic symptoms and generalized CIPO had poor PN outcomes. Myopathy is suggested as a predictor of mortality in children with primary CIPO.
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http://dx.doi.org/10.3390/jcm10112376DOI Listing
May 2021

Disease-specific eQTL screening reveals an anti-fibrotic effect of AGXT2 in non-alcoholic fatty liver disease.

J Hepatol 2021 Apr 20. Epub 2021 Apr 20.

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) poses an impending clinical burden. Genome-wide association studies have revealed a limited contribution of genomic variants to the disease, requiring alternative but robust approaches to identify disease-associated variants and genes. We carried out a disease-specific expression quantitative trait loci (eQTL) screen to identify novel genetic factors that specifically act on NAFLD progression on the basis of genotype.

Methods: We recruited 125 Korean biopsy-proven NAFLD patients and healthy individuals and performed eQTL analyses using 21,272 transcripts and 3,234,941 genotyped and imputed SNPs. We then selected eQTLs that were detected only in the NAFLD group, but not in the control group (i.e., NAFLD-eQTLs). An additional cohort of 162 Korean NAFLD individuals was used for replication. The function of the selected eQTL toward NAFLD development was validated using HepG2, primary hepatocytes and NAFLD mouse models.

Results: The NAFLD-specific eQTL screening yielded 242 loci. Among them, AGXT2, encoding alanine-glyoxylate aminotransferase 2, displayed decreased expression in NAFLD patients homozygous for the non-reference allele of rs2291702, compared to no-NAFLD subjects with the same genotype (P = 4.79 × 10). This change was replicated in an additional 162 individuals, yielding a combined P-value of 8.05 × 10 from a total of 245 NAFLD patients and 48 controls. Knockdown of AGXT2 induced palmitate-overloaded hepatocyte death by increasing ER stress, and exacerbated NAFLD diet-induced liver fibrosis in mice. However, overexpression of AGXT2 reversely attenuated liver fibrosis and steatosis as well.

Conclusions: We implicate a new molecular role of AGXT2 in NAFLD. Our overall approach will serve as an efficient tool for uncovering novel genetic factors that contribute to liver steatosis and fibrosis in patients with NAFLD.

Lay Summary: Elucidating causal genes for NAFLD has been challenging due to limited tissue availability and the polygenic nature of the disease. Using liver and blood samples from 125 biopsy-proven NAFLD and no-NAFLD Korean individuals and an additional 162 individuals for replication, we devised a new analytic method to identify causal genes. Among the candidates, we found that AGXT2-rs2291702 protects against liver fibrosis in a genotype-dependent manner with the potential for therapeutic interventions. Our approach enables the discovery of NAFLD causal genes that act on the basis of genotype.
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http://dx.doi.org/10.1016/j.jhep.2021.04.011DOI Listing
April 2021

Incidence of necrotizing enterocolitis in South Korea from 2007 to 2017.

J Perinatol 2021 May 16;41(5):1092-1099. Epub 2021 Apr 16.

Department of Pediatric Surgery, College of Medicine, Seoul National University, Seoul, Korea.

Objectives: The aim of this study was to investigate the trends of the incidence of and mortality from necrotizing enterocolitis (NEC) in South Korea.

Methods: Claim data were extracted with diagnosis code, including all stage of NEC. Kaplan-Meier curves for cumulative mortality rates are presented by birth weight (Bwt) and gestational age (GA).

Result: The total number of NEC cases was 5840. The ratio of males to females was 1.2:1. There were 11.9 cases per 10,000 births. There were approximately 10 cases per 1000 preterm births and 50 per 1000 very preterm births. The mortality of patients born under 37 weeks decreased from 38.7% in 2007 to 20.9% in 2017. Male sex, lower GA, and lower Bwt were risk factors for mortality.

Conclusions: NEC incidence and mortality have been decreasing over time in South Korea. Male sex, lower GA, and Bwt were risk factors for mortality.
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http://dx.doi.org/10.1038/s41372-021-01053-2DOI Listing
May 2021

Effects of the fermented in the amyloid β-induced Alzheimer's disease mouse model.

Nutr Res Pract 2021 Apr 25;15(2):173-186. Epub 2020 Sep 25.

Department of Food Science, Gyeongnam National University of Science and Technology, Jinju 52725, Korea.

Backgroud/objectives: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Due to the increased incidence of dementia, there is a corresponding increase concerning the importance of AD. In this study, we investigated the protective effects conferred by (Zj) and fermented by yeast (Zj-Y), on cognitive impairment in an AD mouse model.

Materials/methods: AD was induced by injecting amyloid beta (Aβ) in ICR mice, and subsequently 200 mg/kg Zj or Zj-Y was administered daily for 14 days. The cognitive ability of AD mice was observed through behavioral experiments in T-maze, novel object recognition, and Morris water maze tests. We subsequently measured the levels of malondialdehyde (MDA), nitric oxide (NO), aspartate aminotransferase, and alanine aminotransferase in either tissues or serum.

Results: In behavioral tests, deterioration was revealed in the short- and long-term learning and memory functions in the Aβ-injected control group compared to the normal group, indicating that Aβ injection impairs cognitive functions. However, administration of Zj and Zj-Y improved cognitive function in mice, as compared to the Aβ-injected control mice. In addition, the Aβ induced elevations of MDA and NO in the brain, kidney, and liver were suppressed after exposure to Zj and Zj-Y. Especially, Zj-Y showed stronger scavenging effect against MDA and NO, as compared to Zj.

Conclusions: Results of the present study indicate that Zj-Y exerts a protective effect on cognitive impairment and memory dysfunction, which is exerted by attenuating the oxidative stress induced by Aβ.
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http://dx.doi.org/10.4162/nrp.2021.15.2.173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007403PMC
April 2021

Lutonarin from Barley Seedlings Inhibits the Lipopolysacchride-Stimulated Inflammatory Response of RAW 264.7 Macrophages by Suppressing Nuclear Factor-κB Signaling.

Molecules 2021 Mar 12;26(6). Epub 2021 Mar 12.

Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju 55365, Korea.

Extracts from barley seedlings (BS) have known antioxidant and anti-inflammatory activities. The flavonoid lutonarin (LN) is a component of BS extract and has several known bioactivities. Here, we evaluated LN anti-inflammatory efficacy against lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Lutonarin was isolated from BS by methanol extraction and characterized by ultra-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Lutonarin did not reduce the viability or enhance the apoptosis rate of RAW 264.7 macrophages at concentrations up to 150 µM. Concentrations within 20-60 µM dose-dependently suppressed the LPS-induced expression, phosphorylation, and nuclear translocation of the inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Furthermore, LN suppressed the LPS-induced upregulation of proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α and of the inflammatory enzyme cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Lutonarin may be a safe and effective therapeutic agent for alleviation of pathological inflammation.
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http://dx.doi.org/10.3390/molecules26061571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999162PMC
March 2021

Quantitative Analysis of UV-B Radiation Interception in 3D Plant Structures and Intraindividual Distribution of Phenolic Contents.

Int J Mol Sci 2021 Mar 7;22(5). Epub 2021 Mar 7.

Department of Agriculture, Forestry and Bioresources (Horticultural Science and Biotechnology), Seoul National University, Seoul 08826, Korea.

Ultraviolet-B (UV-B) acts as a regulatory stimulus, inducing the dose-dependent biosynthesis of phenolic compounds such as flavonoids at the leaf level. However, the heterogeneity of biosynthesis activation generated within a whole plant is not fully understood until now and cannot be interpreted without quantification of UV-B radiation interception. In this study, we analyzed the spatial UV-B radiation interception of kales ( L. var. ) grown under supplemental UV-B LED using ray-tracing simulation with 3-dimension-scanned models and leaf optical properties. The UV-B-induced phenolic compounds and flavonoids accumulated more, with higher UV-B interception and younger leaves. To distinguish the effects of UV-B energy and leaf developmental age, the contents were regressed separately and simultaneously. The effect of intercepted UV-B on flavonoid content was 4.9-fold that of leaf age, but the effects on phenolic compound biosynthesis were similar. This study confirmed the feasibility and relevance of UV-B radiation interception analysis and paves the way to explore the physical and physiological base determining the intraindividual distribution of phenolic compound in controlled environments.
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http://dx.doi.org/10.3390/ijms22052701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962183PMC
March 2021

Azathioprine antagonizes aberrantly elevated lipid metabolism and induces apoptosis in glioblastoma.

iScience 2021 Mar 26;24(3):102238. Epub 2021 Feb 26.

Drug Discovery Platform Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with poor survival rate. Temozolomide (TMZ) is used as standard chemotherapy to treat GBM, but a large number of patients either respond poorly and/or develop resistance after long-term use, emphasizing the need to develop potent drugs with novel mechanisms of action. Here, using high-throughput compound screening (HTS), we found that azathioprine, an immunosuppressant, is a promising therapeutic agent to treat TMZ-resistant GBM. Through integrative genome-wide analysis and global proteomic analysis, we found that elevated lipid metabolism likely due to hyperactive EGFR/AKT/SREBP-1 signaling was inhibited by azathioprine. Azathioprine also promoted ER stress-induced apoptosis. Analysis of orthotopic xenograft models injected with patient-derived GBM cells revealed reduced tumor volume and increased apoptosis after azathioprine and TMZ co-treatment. These data indicate that azathioprine could be a powerful therapeutic option for TMZ-resistant GBM patients.
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http://dx.doi.org/10.1016/j.isci.2021.102238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957120PMC
March 2021

Comparison of long-term biliary complications between open and laparoscopic choledochal cyst excision in children.

Ann Surg Treat Res 2021 Mar 26;100(3):186-192. Epub 2021 Feb 26.

Department of Pediatric Surgery, Seoul National University College of Medicine, Seoul, Korea.

Purpose: Cyst excision with hepaticojejunostomy has been the classic procedure for treating choledochal cysts, and the use of laparoscopic treatment has been favored recently. The purpose of this study was to compare the long-term biliary complication of laparoscopic operation with open surgery for choledochal cyst presenting in children.

Methods: A retrospective study comparing the laparoscopic and open procedures was performed in 185 patients with choledochal cyst in a single children's hospital. There were 109 patients who were operated with open surgery, and 76 patients operated with laparoscopic surgery. The primary outcome was long-term biliary complications and the secondary outcome included operative time, intraoperative transfusion, length of hospital stay, and other late postoperative complications.

Results: In the patient's demographics, there was no significant difference between the 2 groups. Notably, it was shown that the operative time was longer in the laparoscopic group. The number of patients requiring blood transfusion intraoperatively was lower in the laparoscopic group. It was noted that the hospital stay was not statistically different. The duration to resumption of diet and duration of drainage were longer in the laparoscopic group. Biliary complications were shown to be significantly higher in the open group. The risk factor for long-term biliary complications was noted with the intraoperative transfusion.

Conclusion: The use of a laparoscopic choledochal cyst excision with hepaticojejunostomy is a safe and feasible technique in a young patient. The long-term biliary complication was lower compared to open surgery, rendering this a good option for pediatric patients.
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http://dx.doi.org/10.4174/astr.2021.100.3.186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943283PMC
March 2021

Methyl Caffeate Isolated from the Flowers of (L.) Batsch Enhances Glucose-Stimulated Insulin Secretion.

Biomolecules 2021 02 14;11(2). Epub 2021 Feb 14.

College of Korean Medicine, Gachon University, Seongnam 13120, Korea.

Phenolic compounds from natural products are considered effective enhancers of insulin secretion to prevent and treat type 2 diabetes (T2DM). The flowers of (L.) Batsch also contain many phenolic compounds. In this study, the extract of flowers of (PRPE) exhibited an insulin secretion effect in a glucose-stimulated insulin secretion (GSIS) assay, which led us to isolate and identify the bioactive compound(s) responsible for these effects. Compounds isolated from PRPE were screened for their efficacy in INS-1 rat pancreatic β-cells. Among them, caffeic acid (5), methyl caffeate (6), ferulic acid (7), chlorogenic acid (8), naringenin (11), nicotiflorin (12), and astragalin (13) isolated from PRPE increased GSIS without inducing cytotoxicity. Interestingly, the GSIS effect of methyl caffeate (6) as a phenolic compound was similar to gliclazide, an antidiabetic sulfonylurea drug. Western blot assay showed that methyl caffeate (6) enhanced the related signaling proteins of the activated pancreatic and duodenal homeobox-1 (PDX-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ), but also the phosphorylation of the total insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), and Akt, which influence β-cell function and insulin secretion. This study provides evidence that methyl caffeate (6) isolated from PRPE may aid in the management of T2DM.
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http://dx.doi.org/10.3390/biom11020279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917615PMC
February 2021

Clinical outcomes and risk factors of hepatopulmonary syndrome in children.

Sci Rep 2021 Feb 18;11(1):4134. Epub 2021 Feb 18.

Department of Pediatrics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-Gu, Seoul, 110-769, Korea.

Hepatopulmonary syndrome (HPS) is defined as three distinct features: liver disease, hypoxemia, and intrapulmonary vasodilation. The purpose of this study was to investigate the clinical outcomes of pediatric HPS and to identify the risk factors for HPS in children with biliary atresia (BA). We performed a retrospective cohort study of all children who were diagnosed with HPS between 2000 and 2018 at Seoul National University Hospital. The clinical features and outcomes of the 10 patients diagnosed with HPS were reviewed. To clarify the risk factors of HPS in patients with BA, we reviewed 120 patients diagnosed with BA. Underlying liver disease was BA in 8 patients, portal vein agenesis in 1 patient, and portal vein thrombosis in 1 patient. A total of 7 patients underwent liver transplantation (LT). Currently, all seven patients, including 3 patients with severe HPS, survived after LT. The prevalence of HPS in children with BA was 7%. Polysplenia/interrupted inferior vena was the only risk factor for HPS in BA patients in multivariate analysis. The Pediatric End-Stage Liver Disease score was not associated with the development of HPS. Children with severe HPS undergoing LT had excellent outcomes. Screening for HPS in children with BA is required regardless of the severity of liver diseases.
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http://dx.doi.org/10.1038/s41598-021-83785-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892858PMC
February 2021

Low CtBP2 expression is associated with a stem cell-like signature and adverse clinical outcome in childhood B-cell lymphoblastic leukemia.

Leukemia 2021 Feb 12. Epub 2021 Feb 12.

Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.

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http://dx.doi.org/10.1038/s41375-021-01151-2DOI Listing
February 2021

Bacteriophage-Delivering Hydrogels: Current Progress in Combating Antibiotic Resistant Bacterial Infection.

Antibiotics (Basel) 2021 Jan 29;10(2). Epub 2021 Jan 29.

Advanced Drug Delivery Group, Faculty of Medicine and Health, School of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia.

Antibiotic resistance remains as an unresolved global challenge in the health care system, posing serious threats to global health. As an alternative to antibiotics, bacteriophage (phage) therapy is rising as a key to combating antibiotic-resistant bacterial infections. In order to deliver a phage to the site of infection, hydrogels have been formulated to incorporate phages, owing to its favorable characteristics in delivering biological molecules. This paper reviews the formulation of phage-delivering hydrogels for orthopedic implant-associated bone infection, catheter-associated urinary tract infection and trauma-associated wound infection, with a focus on the preparation methods, stability, efficacy and safety of hydrogels as phage carriers.
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http://dx.doi.org/10.3390/antibiotics10020130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911734PMC
January 2021

Comparison of patients with transient and sustained increments of antiphospholipid antibodies after acute ischemic stroke.

J Neurol 2021 Feb 6. Epub 2021 Feb 6.

Department of Neurology, College of Medicine, Kyung-Hee University, Seoul, Republic of Korea.

Background And Purpose: Antiphospholipid syndrome (APS) is one of the uncommon causes of ischemic stroke, and is associated with young and female patients. However, the significance of antiphospholipid antibody (aPL) in older ischemic stroke patients is uncertain. We aimed to examine the significance of aPLs in ischemic stroke in these older patients.

Materials And Methods: A total of 739 patients with acute ischemic stroke within 7 days of initial symptoms were collected consecutively. Clinical and laboratory data were obtained from medical records. aPLs (lupus anticoagulant, anti-cardiolipin antibody, anti-β2glycoprotein-I antibody) were measured the day after admission and the presence of at least one antibody was regarded as positive aPL. Patients with positive aPL were rechecked after at least 12 weeks for confirmation of APS.

Result: Of the 739 patients, 103 (13.9%) had at least one aPL initially. These patients were older, had more atrial fibrillation and higher levels of inflammatory markers. Among the 103 aPL positive patients, 41 remained positive at 3 months, 23 showed negative conversion, and 39 were not available for follow-up. Patients diagnosed with APS had higher numbers of aPL and had specifically anti-β2glycoprotein-I IgG antibody. The patients with aPLs did not differ significantly from the others in terms of stroke subtype.

Conclusion: aPL was rather common in ischemic stroke patients regardless of age. Although the influence of transient positive aPL on ischemic stroke remains uncertain, two or more aPLs and the presence of anti-β2glycoprotein-I IgG may predict a diagnosis of APS.
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http://dx.doi.org/10.1007/s00415-021-10432-wDOI Listing
February 2021

Protective Effect of γ-mangostin Isolated from the Peel of against Glutamate-Induced Cytotoxicity in HT22 Hippocampal Neuronal Cells.

Biomolecules 2021 01 27;11(2). Epub 2021 Jan 27.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-lo, Gwanak-gu, Seoul 08826, Korea.

The aim of the present study was to examine the protective effect of γ-mangostin, a component of the mangosteen shell, against oxidative damage to nerve cells induced by excessive glutamate, a known excitatory neurotransmitter. To investigate the effect of γ-mangostin on apoptosis, 5 mM of glutamate was used to induce apoptotic cell death in mouse hippocampal HT22 cells. In this study, γ-mangostin was found to exert a stronger protection than N-acetyl cysteine against glutamate-induced cell damage. γ-Mangostin showed prevented glutamate-induced apoptosis in HT22 cells by reducing the production of reactive oxygen species and stimulating the expression of heme oxygenase-1 protein. In addition, glutamate significantly induced the accumulation of intracellular calcium ions, whereas treatment with γ-mangostin markedly reduced it. Hoechst 33342 staining showed an improvement in glutamate-induced nuclear condensation following γ-mangostin treatment. Furthermore, the number of annexin V-positive cells was significantly reduced following treatment with γ-mangostin. Western blot analysis showed the inhibition of glutamate-induced mitogen-activated protein kinase phosphorylation by γ-mangostin. γ-mangostin also inhibited the regulation of the intrinsic mitochondrial apoptotic pathway. Thus, the results of this study suggest that γ-mangostin is an active ingredient of mangosteen and exerts neuroprotective activities in HT22 cells.
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http://dx.doi.org/10.3390/biom11020170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910862PMC
January 2021

Discovery and Structure-Activity Relationships of Novel Template, Truncated 1'-Homologated Adenosine Derivatives as Pure Dual PPARγ/δ Modulators.

J Med Chem 2020 12 16;63(24):16012-16027. Epub 2020 Dec 16.

Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea.

Following our report that A adenosine receptor (AR) antagonist exhibited a polypharmacological profile as a dual modulator of peroxisome proliferator-activated receptor (PPAR)γ/δ, we discovered a new template, 1'-homologated adenosine analogues , as dual PPARγ/δ modulators without AR binding. Removal of binding affinity to AAR was achieved by 1'-homologation, and PPARγ/δ dual modulation was derived from the structural similarity between the target nucleosides and PPAR modulator drug, rosiglitazone. All the final nucleosides were devoid of AR-binding affinity and exhibited high binding affinities to PPARγ/δ but lacked PPARα binding. 2-Cl derivatives exhibited dual receptor-binding affinity to PPARγ/δ, which was absent for the corresponding 2-H derivatives. 2-Propynyl substitution prevented PPARδ-binding affinity but preserved PPARγ affinity, indicating that the C2 position defines a pharmacophore for selective PPARγ ligand designs. PPARγ/δ dual modulators functioning as both PPARγ partial agonists and PPARδ antagonists promoted adiponectin production, suggesting their therapeutic potential against hypoadiponectinemia-associated cancer and metabolic diseases.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01874DOI Listing
December 2020

Rearrangement in Acute Myeloid Leukemia With a Jumping Translocation Involving 3q13.31.

Ann Lab Med 2021 May;41(3):342-345

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3343/alm.2021.41.3.342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748089PMC
May 2021

Paeoniflorin ameliorates Aβ-stimulated neuroinflammation via regulation of NF-κB signaling pathway and Aβ degradation in C6 glial cells.

Nutr Res Pract 2020 Dec 30;14(6):593-605. Epub 2020 Jul 30.

Department of Food Science, Gyeongnam National University of Science and Technology, Jinju 52725, Korea.

Background/objectives: Alzheimer's disease is common age-related neurodegenerative condition characterized by amyloid beta (Aβ) accumulation that leads cognitive impairment. In the present study, we investigated the protective effect of paeoniflorin (PF) against Aβ-induced neuroinflammation and the underlying mechanism in C6 glial cells.

Materials/methods: C6 glial cells were treated with PF and Aβ and cell viability, nitric oxide (NO) production, and pro-inflammatory cytokine release were measured. Furthermore, the mechanism underlying the effect of PF on inflammatory responses and Aβ degradation was determined by Western blot.

Results: Aβ significantly reduced cell viability, but this reduction was prevented by the pretreatment with PF. In addition, PF significantly inhibited Aβ-induced NO production in C6 glial cells. The secretion of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha was also significantly reduced by PF. Further mechanistic studies indicated that PF suppressed the production of these pro-inflammatory cytokines by regulating the nuclear factor-kappa B (NF-κB) pathway. The protein levels of inducible NO synthase and cyclooxygenase-2 were downregulated and phosphorylation of NF-κB was blocked by PF. However, PF elevated the protein expression of inhibitor kappa B-alpha and those of Aβ degrading enzymes, insulin degrading enzyme and neprilysin.

Conclusions: These findings indicate that PF exerts protective effects against Aβ-mediated neuroinflammation by inhibiting NF-κB signaling, and these effects were associated with the enhanced activity of Aβ degradation enzymes.
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http://dx.doi.org/10.4162/nrp.2020.14.6.593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683209PMC
December 2020

Performance evaluation of platelet counting of Abbott Alinity hq and Sysmex XN-9000 automated hematology analyzer compared with international reference method.

Int J Lab Hematol 2021 Jun 20;43(3):387-394. Epub 2020 Nov 20.

Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Introduction: Accurate platelet counting is essential for risk assessment of bleeding and thrombosis. Abbott Alinity hq hematology analyzer was recently introduced, and its performance in platelet counting has yet to be evaluated comprehensively. In this study, we evaluated the performance of the optical platelet counting of Abbott Alinity hq (Alinity-PLT) and the impedance and fluorescent platelet counting of Sysmex XN-9000 (XN-PLT-I and XN-PLT-F) compared with the international reference method.

Methods: Blood samples were analyzed via Alinity hq and XN-9000 with PLT-F channel. Immuno-platelet (ImmnoPLT) reference method was performed with CD41/CD61 antibodies using FACSLyric flow cytometer (BD). Precision was determined using 10 replicates in a single run, and the platelet counts of Alinity-PLT, XN-PLT-I, XN-PLT-F, and ImmnoPLT were compared.

Results: At a platelet count of 13 × 10 /L, the CVs of Alinity-PLT, XN-PLT-I, and XN-PLT-F were 4.2%, 6.7%, and 4.3%, respectively, and at a platelet count of 44 × 10 /L, all showed a CV of less than 3%. For the total 210 samples, all three methods showed a very strong correlation with ImmunoPLT (r > 0.99). For platelet levels below 20 × 10 /L, XN-PLT-F showed the strongest correlation with ImmunoPLT (r = 0.975), and for platelet levels of 20-100 × 10 /L, Alinity-PLT and XN-PLT-I were comparable to ImmunoPLT. For platelet levels of 100-450 × 10 /L, XN-PLT-I was the most comparable to ImmunoPLT, and for platelet levels above 450 × 10 /L, Alinity-PLT was comparable to ImmunoPLT.

Conclusions: All three methods were highly correlated with ImmunoPLT, and each method had different performance advantages according to the platelet levels.
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http://dx.doi.org/10.1111/ijlh.13396DOI Listing
June 2021

Influence of Thermal Processing on Free and Bound Forms of Phenolics and Antioxidant Capacity of Rice Hull ( L.).

Prev Nutr Food Sci 2020 Sep;25(3):310-318

Department of Food Science and Biotechnology, Chungbuk National University, Chungbuk 28644, Korea.

The objective of this study was to evaluate the effects of heat treatment on the phenolics and antioxidant activity of rice hull. Heat treatment was performed at temperatures 80∼140°C for 1∼5 h, and the heated rice hull was extracted with 80% (v/v) methanol in an ultrasonic bath. The highest total polyphenol and flavonoid content (10.68 mg gallic acid equivalents/g and 1.83 mg catechin equivalents/g, respectively) occurred in rice hull heated at 130°C for 5 h. During heat treatment, the content of free phenolic acids increased compared with that of the bound phenolic acids. The highest 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity and reducing power was observed in rice hull heated at 140°C for 3 h. The highest OH radical scavenging activity was 75.30% in rice hull heated at 140°C for 5 h. These results suggested that heat treatment was an efficient method to enhance the antioxidant characteristics of rice hull.
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http://dx.doi.org/10.3746/pnf.2020.25.3.310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541924PMC
September 2020

Filifactor alocis-derived extracellular vesicles inhibit osteogenesis through TLR2 signaling.

Mol Oral Microbiol 2020 10 14;35(5):202-210. Epub 2020 Aug 14.

Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University, Seoul, Korea.

Filifactor alocis, an asaccharolytic anaerobic Gram-positive rod (AAGPR), is an emerging marker of periodontitis. Severe periodontitis causes destruction of the alveolar bone that supports teeth and can even lead to tooth loss. Based on our previous report that F. alocis-derived extracellular vesicles (FA EVs) contain various effector molecules and have immunostimulatory activity, we investigated the effect of FA EVs on osteogenesis using mouse bone-derived mesenchymal stromal cells (BMSCs). FA EVs dramatically inhibited bone mineralization similar to whole bacteria and reduced the expression levels of osteogenic marker genes. The osteogenic differentiation of TLR2-deficient BMSCs was not inhibited by FA EVs, suggesting that their inhibitory effect on osteogenesis is dependent on TLR2 signaling. FA EVs effectively activated TLR2 downstream signaling of the MAPK and NF-κB pathways. In addition, FA EVs regulated RANKL and OPG gene expression, increasing the RANKL/OPG ratio in BMSCs in a TLR2-dependent manner. Our study suggests that F. alocis-derived EVs interfere with bone metabolism via TLR2 activation, providing insight into the pathogenesis of bone loss associated with periodontitis.
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http://dx.doi.org/10.1111/omi.12307DOI Listing
October 2020

Causes, Risk Factors, and Clinical Outcomes of Stroke in Korean Young Adults: Systemic Lupus Erythematosus is Associated with Unfavorable Outcomes.

J Clin Neurol 2020 Oct;16(4):605-611

Department of Neurology, Kyung Hee University College of Medicine, Seoul, Korea.

Background And Purpose: The incidence of ischemic stroke (IS) in young adults is increasing, and the associated large socioeconomic impact makes understanding IS in young adults important. We investigated the causes of and risk factors for IS in young adults, and their impact on outcomes.

Methods: The Stroke in Korean Young Adults (SKY) study is a standardized multicenter prospective study involving eight medical centers of the Republic of Korea. First-ever IS patients aged 18 years to 44 years were prospectively included in this study within 7 days of stroke onset. Their outcomes at 3 months were analyzed.

Results: This study enrolled 270 patients from April 2014 to December 2018, most (67.8%) of whom were male. About 41.5% of the patients had one or more vascular risk factors from among hypertension, diabetes mellitus, and dyslipidemia. However, only half of them had received regular treatment. Arterial dissection was more common in males, and systemic lupus erythematosus (SLE) and Moyamoya disease were more common in females. The outcome was favorable (modified Rankin Scale score of 0 or 1) in 81.9% of the patients at 3 months after stroke onset. More severe initial symptoms, higher initial glucose level, and SLE as a comorbidity were associated with unfavorable outcomes.

Conclusions: Young adult IS patients in Korea exhibit low awareness and poor management of their risk factors. Although the short-term outcome was relatively favorable in those patients, having SLE was associated with unfavorable outcomes. More attention needs to be paid for improving awareness and controlling risk factors in this population.
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http://dx.doi.org/10.3988/jcn.2020.16.4.605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541989PMC
October 2020

Coexistence of Growth Hormone Deficiency and Pituitary Microadenoma in a Child with Unique Mosaic Turner Syndrome: A Case Report and Literature Review.

Diagnostics (Basel) 2020 Oct 4;10(10). Epub 2020 Oct 4.

Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Korea.

Turner syndrome (TS) is a genetic disorder with phenotypic heterogeneity caused by the monosomy or structural abnormalities of the X chromosome, and it has a prevalence of about 1/2500 females live birth. The variable clinical features of TS include short stature, gonadal failure, and skeletal dysplasia. The association with growth hormone (GH) deficiency or other hypopituitarism in TS is extremely rare, with only a few case reports published in the literature. Here, we report the first case of a patient with mosaic TS with complete GH deficiency and pituitary microadenoma, and we include the literature review. During the work-up of the patient for severe short stature, three GH provocation tests revealed peak GH levels of less than 5 ng/mL, which was compatible with complete GH deficiency. Sella magnetic resonance imaging showed an 8 mm non-enhancing pituitary adenoma with mild superior displacement of the optic chiasm. Karyotyping revealed the presence of ring chromosome X and monosomy X (46,X,r(X)/45,X/46,X,psu dic r(X;X)), which indicated a mosaic TS. It is important to consider not only chromosome analyses in females with short stature, but also the possibility of the coexistence of complete GH deficiency accompanying pituitary lesions in TS. In conclusion, the present study reports the first case of GH deficiency and pituitary adenoma in a patient with rare mosaic TS, which extends the genotype-phenotype spectrum for TS.
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http://dx.doi.org/10.3390/diagnostics10100783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600578PMC
October 2020

Homocysteinemia is Associated with the Presence of Microbleeds in Cognitively Impaired Patients.

J Stroke Cerebrovasc Dis 2020 Dec 18;29(12):105302. Epub 2020 Sep 18.

Department of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea.

Background & Objective: Homocysteine is possibly associated with cerebral small vessel diseases such as leukoaraiosis, silent brain infarction and cerebral microbleeds, which are in turn associated with cognitive dysfunction. We aimed to examine the relationships between cerebral microbleeds (CMBs) and plasma total homocysteine (tHcy) level, methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and cognitive function.

Methods: A total of 819 patients with memory disturbance who visited a dementia clinic consecutively were included in this study. We retrospectively collected demographic, clinical and laboratory data including tHcy level, MTHFR C677T polymorphism and Mini-Mental State Examination (MMSE). All patients underwent brain MRI including fluid attenuated inversion recovery (FLAIR) image and T2*-weighed gradient-echo (GRE) image. Logistic regression analysis was performed to test the association between risk factors and the presence of microbleeds.

Results: One hundred and sixty-one (19.7%) patients had CMBs, of whom 88 (54.7%) had CMBs in the lobar region. CMBs were more common in older hypertensive male patients with hyperhomocysteinemia. In multivariable analysis, plasma tHcy remained an independent predictor of the presence of CMBs after adjusting other confounders (OR: 1.035, 95% CI: 1.009-1.062, p = 0.009). Higher plasma tHcy level was also associated with number of CMBs, TT MTHFR genotype, and lower MMSE scores.

Conclusions: Elevated plasma tHcy level is related to high prevalence of CMBs and cognitive dysfunction. Lowering plasma tHcy could be helpful in cognitively impaired patients who have CMBs or the MTHFR TT genotype.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105302DOI Listing
December 2020

Inflammatory response of uric acid produced by Porphyromonas gingivalis gingipains.

Mol Oral Microbiol 2020 10 4;35(5):222-230. Epub 2020 Sep 4.

Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.

Uric acid is a potential metabolite that serves as a danger-associated molecular pattern (DAMP) and induces inflammatory responses in sterile environments. Porphyromonas gingivalis is a keystone periodontopathogen, and its gingipain proteases play a critical role in the pathogenesis of periodontitis. In this study, we demonstrate that P. gingivalis gingipains play a role in THP-1 macrophage uric acid production by increasing the expression and activity of xanthine oxidoreductase (XOR). Uric acid sodium salt induces caspase-1 activation, cell death, and the expression of proinflammatory cytokines, including IL-1α, IL-6, and IL-8, in the human keratinocyte HOK-16B cell line. Our results suggest that gingipain-induced uric acid can mediate inflammation in periodontal tissue cells.
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http://dx.doi.org/10.1111/omi.12309DOI Listing
October 2020

Variation in Knowledge of Stroke Warning Signs by Age and Presence of Conventional Risk Factors: A Community Health Survey in Korea.

J Cardiovasc Nurs 2020 Jul 29. Epub 2020 Jul 29.

Juyeon Oh, RN, PhD Assistant Professor, College of Nursing, Dankook University, Cheonan, South Korea. Hyun Young Kim, MD, PhD Professor, Department of Neurology, College of Medicine, Hanyang University, Seoul, South Korea. Young Seo Kim, MD, PhD Assistant Professor, Department of Neurology, College of Medicine, Hanyang University, Seoul, South Korea. Sun Hwa Kim, RN, PhD Registered Nurse, Stroke Unit, Department of Nursing, Hanyang University Medical Center, Seoul, South Korea.

Background: It is important to recognize stroke in the general public.

Objectives: The purpose of this study was to investigate factors affecting knowledge of stroke warning signs (SWSs) according to age group in the Korean population.

Methods: This study is a cross-sectional study. Using data from the Korean Community Health Survey conducted in Korea in 2017, 198 403 subjects were analyzed. Knowledge about SWSs was assessed by face-to-face interviews using structured close-ended questionnaires with 5 items about stroke symptoms (sudden unilateral weakness of face, arm or leg; sudden difficulty in speaking, or trouble understanding speech; sudden visual impairment in 1 eye, or double vision; sudden dizziness or loss of balance; and sudden severe headache).

Results: The overall percentage of subjects with good knowledge of SWSs (>4 correct answers to the SWS questionnaire) was 66.5%. It was highest in the middle-aged subjects (72.6%), followed by the young subjects (63.5%) and the older subjects (61.5%). The youngest of the young subjects and the oldest of the older subjects had the least knowledge. Subjects with conventional risk factors generally had more knowledge about SWSs, except for those with diabetes mellitus. However, in the young subjects, knowledge about SWSs was not increased by the presence of conventional risk factors such as hypertension and dyslipidemia.

Conclusion: Stoke risk factors are increasing among young people; they still have poor knowledge about SWSs. More education is needed to increase appropriate treatment, especially in young people with stroke-related risk factors.
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http://dx.doi.org/10.1097/JCN.0000000000000736DOI Listing
July 2020

Metabolite Profiling and Chemometric Study for the Discrimination Analyses of Geographic Origin of Perilla () and Sesame () Seeds.

Foods 2020 Jul 24;9(8). Epub 2020 Jul 24.

Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea.

Perilla and sesame are traditional sources of edible oils in Asian and African countries. In addition, perilla and sesame seeds are rich sources of health-promoting compounds, such as fatty acids, tocopherols, phytosterols and policosanols. Thus, developing a method to determine the geographic origin of these seeds is important for ensuring authenticity, safety and traceability and to prevent cheating. We aimed to develop a discriminatory predictive model for determining the geographic origin of perilla and sesame seeds using comprehensive metabolite profiling coupled with chemometrics. The orthogonal partial least squares-discriminant analysis models were well established with good validation values ( = 0.761 to 0.799). Perilla and sesame seed samples used in this study showed a clear separation between Korea and China as geographic origins in our predictive models. We found that glycolic acid could be a potential biomarker for perilla seeds and proline and glycine for sesame seeds. Our findings provide a comprehensive quality assessment of perilla and sesame seeds. We believe that our models can be used for regional authentication of perilla and sesame seeds cultivated in diverse geographic regions.
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http://dx.doi.org/10.3390/foods9080989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466206PMC
July 2020

Computed tomography-negative symptomatic intracerebral hemorrhage in a patient with cerebral small vessel disease: A case report.

Medicine (Baltimore) 2020 Jul;99(29):e21382

Department of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea.

Rationale: Computed tomography plays a key role in the initial evaluation of suspected acute stroke by ruling out the possibility of hemorrhage before thrombolysis. Recently, many reports have described cases of symptomatic microbleeds, and there may also have been a case of computed tomography- negative intracerebral hemorrhage.

Patient Concerns: A 70-year-old female patient who had a history of lacunar infarction and severe small vessel disease developed dysarthria. On brain non-contrast computed tomography there was no evidence of intracerebral hemorrhage. However, brain magnetic resonance imaging performed at 3 hours after the initial computed tomography showed cerebral hemorrhage.

Diagnoses: The diagnosis was computed tomography-negative intracerebral hemorrhage.

Interventions: The patient was treated with cilostazole 100 mg twice a day with blood pressure management.

Outcomes: The dysarthria was fully recovered within 5 days and the patient did not suffer recurrent stroke symptoms over the following 2 years.

Lessons: In patients with underlying severe small vessel disease and microbleeds, there could be computed tomography-negative hemorrhage and susceptibility weighted magnetic resonance image could be needed. More attention is required before applying thrombolysis therapy because there is a possibility of cerebral hemorrhage in those patients.
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http://dx.doi.org/10.1097/MD.0000000000021382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373521PMC
July 2020