1.CKD-581 Downregulates Wnt/β-Catenin Pathway by DACT3 Induction in Hematologic Malignancy
Soo Jin KIM ; Suntae KIM ; Yong June CHOI ; U Ji KIM ; Keon Wook KANG
Biomolecules & Therapeutics 2022;30(5):435-446
The present study evaluated the anti-cancer activity of histone deacetylase (HDAC)-inhibiting CKD-581 in multiple myeloma (MM) and its pharmacological mechanisms. CKD-581 potently inhibited a broad spectrum of HDAC isozymes. It concentration-dependently inhibited proliferation of hematologic cancer cells including MM (MM.1S and RPMI8226) and T cell lymphoma (HH and MJ). It increased the expression of the dishevelled binding antagonist of β-catenin 3 (DACT3) in T cell lymphoma and MM cells, and decreased the expression of c-Myc and β-catenin in MM cells. Additionally, it enhanced phosphorylated p53, p21, cleaved caspase-3 and the subG1 population, and reversely, downregulated cyclin D1, CDK4 and the anti-apoptotic BCL-2 family. Finally, administration of CKD-581 exerted a significant anti-cancer activity in MM.1S-implanted xenografts. Overall, CKD-581 shows anticancer activity via inhibition of the Wnt/β-catenin signaling pathway in hematologic malignancies. This finding is evidence of the therapeutic potential and rationale of CKD-581 for treatment of MM.
2.Aucubin Promotes Neurite Outgrowth in Neural Stem Cells and Axonal Regeneration in Sciatic Nerves.
Yong Min KIM ; U Cheol SIM ; Yongsung SHIN ; Yunhee Kim KWON
Experimental Neurobiology 2014;23(3):238-245
Aucubin is an iridoid glycoside with a wide range of biological activities, including anti-inflammatory, anti-microbial, anti-algesic as well as anti-tumor activities. Recently, it has been shown that aucubin prevents neuronal death in the hippocampal CA1 region in rats with diabetic encephalopathy. In addition, it has protective effects on H2O2-induced apoptosis in PC12 cells. We have shown here that aucubin promotes neuronal differentiation and neurite outgrowth in neural stem cells cultured primarily from the rat embryonic hippocampus. We also investigated whether aucubin facilitates axonal elongation in the injured peripheral nervous system. Aucubin promoted lengthening and thickness of axons and re-myelination at 3 weeks after sciatic nerve injury. These results indicate that administration of aucubin improved nerve regeneration in the rat model of sciatic nerve injury, suggesting that aucubin may be a useful therapeutic compound for the human peripheral nervous system after various nerve injuries.
Animals
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Apoptosis
;
Axons*
;
CA1 Region, Hippocampal
;
Hippocampus
;
Humans
;
Models, Animal
;
Nerve Regeneration
;
Neural Stem Cells*
;
Neurites*
;
Neurons
;
PC12 Cells
;
Peripheral Nervous System
;
Rats
;
Regeneration*
;
Sciatic Nerve*
3.Expression and Neuroprotection of Vascular Endothelial Growth Factor in an in vitro Ischemia.
Moon Ku HAN ; Man Ho KIM ; Jong Ho RHA ; Yong Seok LEE ; Seung U KIM ; Jae Kyu ROH
Journal of the Korean Neurological Association 2002;20(6):634-640
BACKGROUND: Vascular endothelial growth factor (VEGF) is an angiogenic peptide that enhances microvascular perfusion. Recently, VEGF is known to have neurotrophic effect and rescues neurons from cell death induced by serum deprivation. To investigate the serial changes in VEGF expression and neuroprotective properties of VEGF during acute ischemia. METHODS: Human cortical-neuroblastoma hybrid cell line (A1G11), human neuroglioma cell line (H4), and human vascular endothelial cell line (ECV304) were placed in the glucose/serum free media and incubated in the hypoxic chamber (94% N2/5% CO2/1% room air) at 37 degrees C. Cell viability was determined by MTT assay. Western blot analysis was performed to detect VEGF and its receptor (VEGFR) expression. To test the protective effect of VEGF, human recombinant VEGF165 was used. RESULTS: Morphological changes and the decrease of cell viability were observed following 6 hr ischemia. In A1G11 cells, VEGF expression was not noted until 3 hr ischemia, but was induced after 6hr and continued to 12 hr and then diminished. In H4 and ECV304, the change of VEGF expression was not observed. VEGFR-2/Flk-1 expression was induced from 6 hr (peak level) to 12 hr in A1G11, and induced after 3 hr and continued to 12hr in ECV304. Administration of VEGF increased cell viability in A1G11 cells at 6 hr, 12 hr and 18 hr ischemia (p=0.009, p=0.01 p=0.013), but not in H4 or ECV304 cells ( p>0.05). CONCLUSION: Ischemia induces VEGF production in neurons and VEGF may exert a direct neuron-specific protective effect through VEGFR-2/Flk receptors during the acute phase of ischemic neuronal injury.
Blotting, Western
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Cell Death
;
Cell Line
;
Cell Survival
;
Endothelial Cells
;
Humans
;
Hybrid Cells
;
Ischemia*
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Neurons
;
Perfusion
;
Vascular Endothelial Growth Factor A*
4.Activation of nicotinic acetylcholine receptor prevents the production of reactive oxygen species in fibrillar beta amyloid peptide (1-42)-stimulated microglia.
Ju Hyun MOON ; Soo Yoon KIM ; Hwan Goo LEE ; Seung U KIM ; Yong Beom LEE
Experimental & Molecular Medicine 2008;40(1):11-18
Recent studies have reported that the "cholinergic anti-inflammatory pathway" regulates peripheral inflammatory responses via alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) and that acetylcholine and nicotine regulate the expression of proinflammatory mediators such as TNF-alpha and prostaglandin E2 in microglial cultures. In a previous study we showed that ATP released by beta-amyloid-stimulated microglia induced reactive oxygen species (ROS) production, in a process involving the P2X7 receptor (P2X7R), in an autocrine fashion. These observations led us to investigate whether stimulation by nicotine could regulate fibrillar beta amyloid peptide (1-42) (fA beta(1-42))-induced ROS production by modulating ATP efflux-mediated Ca2+ influx through P2X7R. Nicotine inhibited ROS generation in fA beta(1-42)-stimulated microglial cells, and this inhibition was blocked by mecamylamine, a non-selective nAChR antagonist, and a-bungarotoxin, a selective alpha7 nAChR antagonist. Nicotine inhibited NADPH oxidase activation and completely blocked Ca2+ influx in fA beta(1-42)-stimulated microglia. Moreover, ATP release from fA beta(1-42)-stimulated microglia was significantly suppressed by nicotine treatment. In contrast, nicotine did not inhibit 2',3'-O-(4-benzoyl)-benzoyl ATP (BzATP)-induced Ca2+ influx, but inhibited ROS generation in BzATP-stimulated microglia, indicating an inhibitory effect of nicotine on a signaling process downstream of P2X7R. Taken together, these results suggest that the inhibitory effect of nicotine on ROS production in fA beta(1-42)-stimulated microglia is mediated by indirect blockage of ATP release and by directly altering the signaling process downstream from P2X7R.
Adenosine Triphosphate/analogs & derivatives/metabolism/pharmacology
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Amyloid/*metabolism
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Amyloid beta-Protein/*pharmacology
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Animals
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Calcium/metabolism
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Enzyme Activation/drug effects
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Microglia/cytology/*drug effects/enzymology/*metabolism
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NADPH Oxidase/metabolism
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Nicotine/pharmacology
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Nicotinic Antagonists/pharmacology
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Peptide Fragments/*pharmacology
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Rats
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Rats, Sprague-Dawley
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Reactive Oxygen Species/*metabolism
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Receptors, Nicotinic/*metabolism
;
Receptors, Purinergic P2/metabolism
5.Erratum: Intrathoracic kidney with left-sided Bochdalek hernia in a woman with bacteremic acute pyelonephritis due to Escherichia coli.
Yong Sun NOH ; Yeonguk KIM ; Yun SEO ; Seong Heon WIE ; U Im CHANG
The Korean Journal of Internal Medicine 2015;30(3):421-421
In the article cited above, upper part page in title page has an error. Ending page of the article should be 268, not 269.
6.A comparison of the clinical characteristics of elderly and non-elderly women with community-onset, non-obstructive acute pyelonephritis.
U Im CHANG ; Hyung Wook KIM ; Yong Sun NOH ; Seong Heon WIE
The Korean Journal of Internal Medicine 2015;30(3):372-383
BACKGROUND/AIMS: Acute pyelonephritis (APN) is the most common cause of community-onset bacteremia in hospitalized elderly patients. The objectives of this study were to investigate the differences in the clinical and microbiological data of hospitalized elderly and non-elderly women with community-onset APN. METHODS: Women with community-onset APN as a discharge diagnosis were identified from January 2004 to December 2013 using an electronic medical records system. We compared the clinical and microbiologic data in elderly and non-elderly women with community-onset APN due to Enterobacteriaceae. RESULTS: Of the 1,134 women with community-onset APN caused by Enterobacteriaceae, 443 were elderly and 691 were non-elderly women. The elderly group had a lower frequency of upper and lower urinary tract symptoms/signs than the non-elderly. The incidence of bacteremia, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, patients with a C-reactive protein (CRP) level > or = 15 mg/dL, and patients with a leukocyte count > or = 15,000/mm3 in the blood, were significantly higher in the elderly group than in the non-elderly group. The proportion of patients requiring hospitalization for 10 days or more was significantly higher in the elderly group compared to the non-elderly group (51.5% vs. 26.2%, p < 0.001). The clinical cure rates at 4 to 14 days after the end of therapy were 98.3% (338/344) and 97.4% (519/533) in the elderly and non-elderly groups, respectively (p = 0.393). CONCLUSIONS: Elderly women with APN exhibit higher serum CRP levels, a higher frequency of bacteremia, a higher proportion of ESBL-producing uropathogens, and require a longer hospitalization than non-elderly women, although these patients may not complain of typical urinary symptoms.
Acute Disease
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Adult
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Age Factors
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Aged
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Anti-Bacterial Agents/therapeutic use
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Community-Acquired Infections/*diagnosis/drug therapy/microbiology
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Electronic Health Records
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Enterobacteriaceae Infections/*diagnosis/drug therapy/microbiology
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Female
;
Hospitalization
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Hospitals, University
;
Humans
;
Middle Aged
;
Pyelonephritis/*diagnosis/drug therapy/microbiology
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Remission Induction
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Republic of Korea
;
Retrospective Studies
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Risk Factors
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Sex Factors
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Time Factors
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Treatment Outcome
;
Urinary Tract Infections/*diagnosis/drug therapy/microbiology
7.Intrathoracic kidney with left-sided Bochdalek hernia in a woman with bacteremic acute pyelonephritis due to Escherichia coli.
Yong Sun NOH ; Yeonguk KIM ; Yun SEO ; Seong Heon WIE ; U Im CHANG
The Korean Journal of Internal Medicine 2015;30(2):267-268
No abstract available.
Acute Disease
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Adult
;
Anti-Bacterial Agents/therapeutic use
;
Choristoma/*complications/radiography
;
Escherichia coli Infections/diagnosis/drug therapy/*microbiology
;
Female
;
Hernias, Diaphragmatic, Congenital/*complications/radiography
;
Humans
;
*Kidney
;
Predictive Value of Tests
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Pyelonephritis/diagnosis/drug therapy/*microbiology
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Thoracic Diseases/*complications/radiography
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Tomography, X-Ray Computed
;
Treatment Outcome
8.Effectiveness of Posterolateral Lumbar Fusion Varies with the Physical Properties of Demineralized Bone Matrix Strip.
Yong Soo CHOI ; Dae Hee KIM ; Ji Hun PARK ; Brian JOHNSTONE ; Jung U YOO
Asian Spine Journal 2015;9(3):433-439
STUDY DESIGN: A randomized, controlled animal study. PURPOSE: To investigate the effectiveness of fusion and new bone formation induced by demineralized bone matrix (DBM) strips with jelly strengths. OVERVIEW OF LITERATURE: The form of the DBM can make a difference to the outcome. The effect of different jelly strengths on the ability of DBM to form new bone is not known. METHODS: Forty-eight rabbits were randomized into a control group and two experimental groups. In the control group (group 1), 1.4 g of autologous iliac crest bone was placed bilaterally. In the experimental groups, a high jelly strength DBM-hyaluronic acid (HA)-gelatin strip (group 2) and a low jelly strength DBM-HA-gelatin strip (group 3) were used. The fusion was assessed with manual manipulation and radiographs. The volume of the fusion mass was determined from computed tomographic images. RESULTS: The fusion rates as determined by manual palpation were 37.5%, 93.8% and 50.0% in group 1, group 2, and group 3, respectively (p<0.05). By radiography, the fusion rate of High jelly strength DBM strip was statistically significantly greater than that of the other alternatives (p<0.05). The mean bone volume of the fusion mass as determined by computed tomography was 2,142.2+/-318.5 mm3, 3,132.9+/-632.1 mm3, and 2,741.5+/-380.4 mm3 in group 1, group 2, and group 3, respectively (p<0.05). CONCLUSIONS: These results indicate that differences in the structural and mechanical properties of gelatin that are associated with jelly strength influenced cellular responses such as cell viability and bony tissue ingrowth, facilitating greater bone fusion around high jelly strength implants.
Animals
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Bone Matrix*
;
Cell Survival
;
Gelatin
;
Osteogenesis
;
Palpation
;
Rabbits
;
Radiography
;
Spinal Fusion
9.Facial Reconstruction of Father Dae -Gun (Andrea) Kim.
Seung Ho HAN ; Dae Kyoon PARK ; U Young LEE ; Ki Seok KOH ; Hee Jin KIM ; Kyung Seok HU ; Yong Seok NAM
Korean Journal of Physical Anthropology 2001;14(3):187-194
This study was designed for the facial reconstruction of Father Dae -Gun (Andrea) Kim, who is the first priest in Korea. The study was entrusted by Seoul great parish, Myeongdong Cathedral and was conducted during 15 months from September 1999. To reconstruct the face of Father Dae -Gun (Andrea) Kim, we used photographs and metric data of Father Dae -Gun (Andrea) Kim's skull, which was measured by Department of Anatomy, Catholic Medical College at 1971. Based on above data, we found a skull similar to Father Dae -Gun (Andrea) Kim, replicated it, and modified it to be consistent with that of Father Dae -Gun (Andrea) Kim measured at 1971. The face of Father Dae -Gun (Andrea) Kim was reconstructed on the modified replica of Father Dae -Gun (Andrea) Kim's skull using the forensic anthropological data about the average skin depth and the relationships of skull morphology to facial features of Korean. The average skin depth of Korean face was obtained from direct measurement of cadavers and indirect measurement of live Korean using ultrasonography. The result of facial reconstruction of Father Dae -Gun (Andrea) Kim was made as the bronze bust. The forensic anthropologic method such as facial reconstruction is one of the methods to identify unidentified -skull. This study is the first facial reconstruction on the base of Korean physical anthropological data and is thought to be helpful to the facial reconstruction for identification.
Cadaver
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Fathers*
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Forensic Anthropology
;
Humans
;
Korea
;
Seoul
;
Skin
;
Skull
;
Ultrasonography
10.The Incidence of Sore Throat and Hoarseness after Double-Lumen Endobronchial Tube Intubation.
Kwang Ho LEE ; Hyun Kyo LIM ; Kyoung Min LEE ; Soon Yul KIM ; Hae Yong U
Korean Journal of Anesthesiology 1998;35(3):484-487
INTRODUCTION: Sore throat and hoarseness often follow general anesthesia administered via a single-lumen endotracheal tube (SLT). Numerous studies have investigated the role of factors as contributing causes, but the influence of double-lumen endobronchial tube (DLT) has not been examined systemically. The goal of this study was to examine the incidence of sore throat and hoarseness after DLT insertion. METHODS: 70 patients who were intubated with SLT or DLT were studied. Sore throat and hoarseness were evaluated after 24~48 hr from extubation of each tubes. RESULTS: In SLT and DLT group, the incidence of sore throat and hoarseness was 14 patients (40%) vs 16 patients (45.7%) and 8 patients (22.8%) vs 10 patients (28.5%), respectively. CONCLUSIONS: There are no statistical differences in incidence of sore throat and hoarseness between SLT and DLT.
Anesthesia, General
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Hoarseness*
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Humans
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Incidence*
;
Intubation*
;
Pharyngitis*