1.Langerhans Cell Histiocytosis with Frontal Bone Indentation by an Adjoining Primary Soft Tissue Lesion in a 17-Month-Old Asian Male Child.
Seungchan KIM ; Jiye KIM ; Sug Won KIM
Archives of Plastic Surgery 2015;42(5):665-668
No abstract available.
Asian Continental Ancestry Group*
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Child*
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Frontal Bone*
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Histiocytosis, Langerhans-Cell*
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Humans
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Infant*
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Male*
2.Calcium-influx increases SOD1 aggregates via nitric oxide in cultured motor neurons.
Hyun Jung KIM ; Wooseok IM ; Seungchan KIM ; Sung Hun KIM ; Jung Jun SUNG ; Manho KIM ; Kwang Woo LEE
Experimental & Molecular Medicine 2007;39(5):574-582
Familial amyotrophic lateral sclerosis (fALS) is caused by mutations in Cu/Zn-superoxide dismutase (SOD1), and SOD1 aggregation and calcium toxicity are involved in neuronal death. However, the effect of altered calcium homeostasis on the SOD1 aggregation is unknown. To investigate whether calcium triggers mutant SOD1 aggregation in vitro, human mutant SOD1 (G93A) was transfected into motor neuronal cell line (VSC 4.1 cells). These cells were then treated with calcium ionophore A23187 or agents that induce intracellular calcium release like cyclic ADP ribose, ryanodine or thapsigargin. A23187 was found to increase mutant SOD1 aggregation and neuronal nitric oxide synthase (nNOS) expression. Moreover, the NOS inhibitor (L-NAME) and a NO-dependent cyclic GMP cascade inhibitor (ODQ) reduced SOD1 aggregation, whereas an exogenous NO donor (GSNO) increased mutant SOD1 aggregation, which was also prevented by NOS or cGMP cascade inhibitor. Our data demonstrate that calcium-influx increases SOD1 aggregation by upregulating NO in cultured motor neuronal cells.
Amyotrophic Lateral Sclerosis/genetics/metabolism
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Animals
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Calcimycin/pharmacology
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Calcium/*metabolism
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Calpain/metabolism
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Caspase 3/metabolism
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Cell Line
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Humans
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Ionophores/pharmacology
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Motor Neurons/*metabolism
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Multiprotein Complexes
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Mutation
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Nitric Oxide/*metabolism
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Rats
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Recombinant Proteins/chemistry/genetics/metabolism
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Superoxide Dismutase/chemistry/genetics/*metabolism
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Transfection
3.Abiraterone Acetate Attenuates SARS-CoV-2 Replication by Interfering with the Structural Nucleocapsid Protein
Jinsoo KIM ; Seok Young HWANG ; Dongbum KIM ; Minyoung KIM ; Kyeongbin BAEK ; Mijeong KANG ; Seungchan AN ; Junpyo GONG ; Sangkyu PARK ; Mahmoud KANDEEL ; Younghee LEE ; Minsoo NOH ; Hyung-Joo KWON
Biomolecules & Therapeutics 2022;30(5):427-434
The drug repurposing strategy has been applied to the development of emergency COVID-19 therapeutic medicines. Current drug repurposing approaches have been directed against RNA polymerases and viral proteases. Recently, we found that the inhibition of the interaction between the SARS-CoV-2 structural nucleocapsid (N) and spike (S) proteins decreased viral replication. In this study, drug repurposing candidates were screened by in silico molecular docking simulation with the SARS-CoV-2 structural N protein. In the ChEMBL database, 1994 FDA-approved drugs were selected for the in silico virtual screening against the N terminal domain (NTD) of the SARS-CoV-2 N protein. The tyrosine 109 residue in the NTD of the N protein was used as the center of the ligand binding grid for the docking simulation. In plaque forming assays performed with SARS-CoV-2 infected Vero E6 cells, atovaquone, abiraterone acetate, and digoxin exhibited a tendency to reduce the size of the viral plagues without affecting the plaque numbers. Abiraterone acetate significantly decreased the accumulation of viral particles in the cell culture supernatants in a concentration-dependent manner. In addition, abiraterone acetate significantly decreased the production of N protein and S protein in the SARS-CoV-2-infected Vero E6 cells. In conclusion, abiraterone acetate has therapeutic potential to inhibit the viral replication of SARS-CoV-2.
4.Comparison of Pharmacodynamics between Tegoprazan and Dexlansoprazole Regarding Nocturnal Acid Breakthrough: A Randomized Crossover Study
Sungpil HAN ; Hee Youn CHOI ; Yo Han KIM ; SeungChan CHOI ; Seokuee KIM ; Ji Yeon NAM ; Bongtae KIM ; Geun Seog SONG ; Hyeong-Seok LIM ; Kyun-Seop BAE
Gut and Liver 2023;17(1):92-99
Background/Aims:
Tegoprazan, a novel potassium-competitive acid blocker, is expected to overcome the limitations of proton pump inhibitors and effectively control nocturnal acid breakthrough. To evaluate the pharmacodynamics of tegoprazan versus dexlansoprazole regarding nocturnal acid breakthrough in healthy subjects.
Methods:
In a randomized, open-label, single-dose, balanced incomplete block crossover study, 24 healthy male volunteers were enrolled and randomized to receive oral tegoprazan (50, 100, or 200 mg) or dexlansoprazole (60 mg) during each of two administration periods, separated by a 7- to 10-day washout period. Blood samples were collected for pharmacokinetic parameter analysis; gastric monitoring was performed for pharmacodynamic parameter evaluation.
Results:
All 24 subjects completed the study. Average maximum plasma concentration, area under the plasma concentration–time curve, and mean time with gastric pH >4 and pH >6 for tegoprazan demonstrated dose-dependent incremental increases. All the tegoprazan groups reached mean pH ≥4 within 2 hours, whereas the dexlansoprazole group required 7 hours after drug administration. Based on pharmacodynamic parameters up to 12 hours after evening dosing, 50, 100, and 200 mg of tegoprazan presented a stronger acid-suppressive effect than 60 mg of dexlansoprazole. Moreover, the dexlansoprazole group presented a comparable acid-suppressive effect with the tegoprazan groups 12 hours after dosing.
Conclusions
All the tegoprazan groups demonstrated a significantly faster onset of gastric pH increase and longer holding times above pH >4 and pH >6 up to 12 hours after evening dosing than the dexlansoprazole group.
5.Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator
Hyejin KO ; Seungchan AN ; Hongjun JANG ; Sungjin AHN ; In Guk PARK ; Seok Young HWANG ; Junpyo GONG ; Soyeon OH ; Soo Yeon KWAK ; Won Jun CHOI ; Hyoungsu KIM ; Minsoo NOH
Biomolecules & Therapeutics 2023;31(3):312-318
The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activated receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesisinducing activity by macakurzin C derivatives (2–7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadiponectinemia-related metabolic diseases.
6.Diallyl Biphenyl-Type Neolignans Have a Pharmacophore of PPARα/γ Dual Modulators
Yujia HAN ; Jingjing LIU ; Sungjin AHN ; Seungchan AN ; Hyejin KO ; Jeayoung C. SHIN ; Sun Hee JIN ; Min Won KI ; So Hun LEE ; Kang Hyuk LEE ; Song Seok SHIN ; Won Jun CHOI ; Minsoo NOH
Biomolecules & Therapeutics 2020;28(5):397-404
Adiponectin secretion-promoting compounds have therapeutic potentials in human metabolic diseases. Diallyl biphenyl-type neolignan compounds, magnolol, honokiol, and 4-O-methylhonokiol, from a Magnolia officinalis extract were screened as adiponectin-secretion promoting compounds in the adipogenic differentiation model of human bone marrow mesenchymal stem cells (hBM-MSCs). In a target identification study, magnolol, honokiol, and 4-O-methylhonokiol were elucidated as PPARα and PPARγ dual modulators. Diallyl biphenyl-type neolignans affected the transcription of lipid metabolism-associated genes in a different way compared to those of specific PPAR ligands. The diallyl biphenyl-type neolignan structure provides a novel pharmacophore of PPARα/γ dual modulators, which may have unique therapeutic potentials in diverse metabolic diseases.