180 results on '"Byung Hak Kim"'
Search Results
2. Study on Twisted Product Almost Gradient Yamabe Solitons
- Author
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Byung Hak Kim, Jin Hyuk Choi, and Sang Deok Lee
- Subjects
Mathematics ,QA1-939 - Abstract
In this paper, we first study gradient Yamabe solitons on the twisted product spaces. Then, we classify and characterize the warped product and twisted product spaces with almost gradient Yamabe solitons. We also study the construction of almost gradient Yamabe solitons in the Riemannian product spaces.
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- 2021
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3. Reducing Contextual Bias in Cardiac Magnetic Resonance Imaging Deep Learning Using Contrastive Self-Supervision.
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Makiya Nakashima, Donna Salem, HW Wilson Tang, Christopher Nguyen, Tae-Hyun Hwang, Ding Zhao, Byung-Hak Kim, Deborah Kwon, and David Chen 0006
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- 2023
4. Can Current Explainability Help Provide References in Clinical Notes to Support Humans Annotate Medical Codes?
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Byung-Hak Kim, Zhongfen Deng, Philip S. Yu, and Varun Ganapathi
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- 2022
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5. Multimodal Representation Learning of Cardiovascular Magnetic Resonance Imaging.
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Jielin Qiu, Peide Huang, Makiya Nakashima, Jaehyun Lee, Jiacheng Zhu, W. H. Wilson Tang, Pohao Chen, Christopher Nguyen, Byung-Hak Kim, Debbie Kwon, Douglas Weber, Ding Zhao, and David Chen 0006
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- 2023
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6. Read, Attend, and Code: Pushing the Limits of Medical Codes Prediction from Clinical Notes by Machines.
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Byung-Hak Kim and Varun Ganapathi
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- 2021
7. RegCLR: A Self-Supervised Framework for Tabular Representation Learning in the Wild.
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Weiyao Wang 0002, Byung-Hak Kim, and Varun Ganapathi
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- 2022
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8. Medical Codes Prediction from Clinical Notes: From Human Coders to Machines.
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Byung-Hak Kim
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- 2022
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9. Deep Learning-Based Telephony Speech Recognition in the Wild.
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Kyu Jeong Han, Seongjun Hahm, Byung-Hak Kim, Jungsuk Kim, and Ian R. Lane
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- 2017
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10. Deep Claim: Payer Response Prediction from Claims Data with Deep Learning.
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Byung-Hak Kim, Seshadri Sridharan, Andy Atwal, and Varun Ganapathi
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- 2020
11. GritNet: Student Performance Prediction with Deep Learning.
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Byung-Hak Kim, Ethan Vizitei, and Varun Ganapathi
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- 2018
12. Deep Learning to Predict Student Outcomes.
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Byung-Hak Kim
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- 2019
13. LumièreNet: Lecture Video Synthesis from Audio.
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Byung-Hak Kim and Varun Ganapathi
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- 2019
14. Recent Advances, Applications and Open Challenges in Machine Learning for Health: Reflections from Research Roundtables at ML4H 2022 Symposium
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Hegselmann, Stefan, Zhou, Helen, Yuyin Zhou, Chien, Jennifer, Sujay Nagaraj, Hulkund, Neha, Shreyas Bhave, Oberst, Michael, Amruta Pai, Ellington, Caleb, Wisdom Ikezogwo, Dou, Jason Xiaotian, Agrawal, Monica, Changye Li, Peniel Argaw, Biswas, Arpita, Mehak Gupta, Xinhui Li, Lemanczyk, Marta, Yuhui Zhang, Garbin, Christian, Healey, Elizabeth, Heejong Kim, Boone, Claire, Daneshjou, Roxana, Siyu Shi, Pezzotti, Nicola, Pfohl, Stephen R., Fong, Edwin, Aakanksha Naik, Lengerich, Ben, Xu, Ying, Bidwell, Jonathan, Sendak, Mark, Byung-Hak Kim, Hendrix, Nathaniel, Spathis, Dimitris, Seita, Jun, Quast, Bastiaan, Coffee, Megan, Stultz, Collin, Chen, Irene Y., Shalmali Joshi, and Girmaw Abebe Tadesse
- Subjects
machine learning ,medicine ,healthcare - Abstract
The second Machine Learning for Health (ML4H) symposium was held both virtually and in-person on November 28, 2022, in New Orleans, Louisiana, USA (Parziale et al.,2022). The symposium included research roundtable sessions to foster discussions between participants and senior researchers on timely and relevant topics for the ML4H community. Encouraged by the successful virtual roundtables in the previous year (Roy et al.,2021), we organized nine in-person and four virtual roundtables at ML4H 2022 (Parziale et al.,2022). A roundtable session included invited senior chairs (with substantial experience in the field), junior chairs (responsible for facilitating the discussion), and attendees from di- verse backgrounds with interest in the session’s topic. This document explains the organization process we used and compiles the takeaways from the roundtable discussions, including recent advances, applications, and open challenges for each topic. We conclude with a summary and lessons learned across all roundtables.
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- 2023
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15. Supplementary Fig. S1 from A small-molecule compound identified through a cell-based screening inhibits JAK/STAT pathway signaling in human cancer cells
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Gyeong-Hun Baeg, Dennis G. Hall, Agnieszka Ulaczyk-Lesanko, Somasundaram Jayabose, Claudio Sandoval, Haeryun Lee, Erika A. Bach, Qianxu Guo, Chang-Hong Yin, and Byung Hak Kim
- Abstract
Supplementary Fig. S1 from A small-molecule compound identified through a cell-based screening inhibits JAK/STAT pathway signaling in human cancer cells
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- 2023
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16. Data from A small-molecule compound identified through a cell-based screening inhibits JAK/STAT pathway signaling in human cancer cells
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Gyeong-Hun Baeg, Dennis G. Hall, Agnieszka Ulaczyk-Lesanko, Somasundaram Jayabose, Claudio Sandoval, Haeryun Lee, Erika A. Bach, Qianxu Guo, Chang-Hong Yin, and Byung Hak Kim
- Abstract
Inappropriate activation of JAK/STAT signaling occurs with high frequency in human cancers and is associated with cancer cell survival and proliferation. Therefore, the development of pharmacologic STAT signaling inhibitors has therapeutic potential in the treatment of human cancers. Here, we report 2-[(3,5-bis-trifluoromethyl-phenyl)-hydroxy-methyl]-1-(4-nitro-phenylamino)-6-phenyl-1,2,4a,7a-tetrahydro-pyrrolo[3,4-b]-pyridine-5,7-dione (AUH-6-96) as a novel small-molecule inhibitor of JAK/STAT signaling that we initially identified through a cell-based high-throughput screening using cultured Drosophila cells. Treatment of Drosophila cells with AUH-6-96 resulted in a reduction of Unpaired-induced transcriptional activity and tyrosine phosphorylation of STAT92E, the sole Drosophila STAT homologue. In human cancer cell lines, AUH-6-96 inhibited both constitutive and interleukin-6-induced STAT3 phosphorylation. Specifically, in Hodgkin lymphoma L540 cells, treatment with AUH-6-96 resulted in reduced levels of tyrosine phosphorylated STAT3 and of the STAT3 downstream target gene SOCS3 in a dose- and time-dependent manner. In addition, AUH-6-96-treated L540 cells showed decreased expression of persistently activated JAK3, suggesting that AUH-6-96 inhibits the JAK/STAT pathway signaling in L540 cells by affecting JAK3 activity and subsequently blocking STAT3 signaling. Importantly, AUH-6-96 selectively affected cell viability only of cancer cells harboring aberrant JAK/STAT signaling. In support of the specificity of AUH-6-96 for inhibition of JAK/STAT signaling, treatment with AUH-6-96 decreased cancer cell survival by inducing programmed cell death by down-regulating the expression of STAT3 downstream target antiapoptotic genes, such as Bcl-xL. In summary, this study shows that AUH-6-96 is a novel small-molecule inhibitor of JAK/STAT signaling and may have therapeutic potential in the treatment of human cancers harboring aberrant JAK/STAT signaling. [Mol Cancer Ther 2008;7(9):2672–80]
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- 2023
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17. Purple Corn Extract Improves Benign Prostatic Hyperplasia by Regulating Prostate Cell Proliferation and Apoptosis
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Hyo-Jung Kim, Byung-Hak Kim, Bo-Ram Jin, Sang Jae Park, and Hyo-Jin An
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Male ,Plant Extracts ,Prostate ,Prostatic Hyperplasia ,Apoptosis ,Dihydrotestosterone ,General Chemistry ,Zea mays ,Rats ,Testosterone Propionate ,Anthocyanins ,Rats, Sprague-Dawley ,Phosphatidylinositol 3-Kinases ,Animals ,Humans ,Testosterone ,General Agricultural and Biological Sciences ,Cell Proliferation - Abstract
Purple corn (
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- 2022
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18. GritNet 2: Real-Time Student Performance Prediction with Domain Adaptation.
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Byung-Hak Kim, Ethan Vizitei, and Varun Ganapathi
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- 2018
19. Heukharang Lettuce (Lactuca Sativa L.) Extract Displays Sleep-Promoting Effects Through GABA A Receptor
- Author
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Yejin Ahn, Hee Hwan Lee, Byung-Hak Kim, Sang Jae Park, Young Suk Kim, Hyung Joo Suh, and Kyungae Jo
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- 2023
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20. An Iterative Joint Linear-Programming Decoding of LDPC Codes and Finite-State Channels.
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Byung-Hak Kim and Henry D. Pfister
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- 2011
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21. On the joint decoding of LDPC codes and finite-state channels via linear programming.
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Byung-Hak Kim and Henry D. Pfister
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- 2010
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22. Joint Decoding of LDPC Codes and Finite-State Channels Via Linear-Programming.
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Byung-Hak Kim and Henry D. Pfister
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- 2011
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23. Anticancer Activity of Tubulosine through Suppression of Interleukin-6-Induced Janus Kinase 2/Signal Transducer and Activation of Transcription 3 Signaling
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Sang Kyu Ye, In Chul Park, Yu Chen Li, Byung Hak Kim, Jung Youl Park, and Eun Hee Yi
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0301 basic medicine ,STAT3 Transcription Factor ,Cancer Research ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine ,IL-6 ,Janus kinase 2 ,biology ,business.industry ,Tubulosine ,Tyrosine phosphorylation ,Janus Kinase 2 ,Glycoprotein 130 ,030104 developmental biology ,Oncology ,Terminal deoxynucleotidyl transferase ,chemistry ,Cell culture ,030220 oncology & carcinogenesis ,Cancer cell ,biology.protein ,Cancer research ,STAT protein ,Original Article ,Breast neoplasms ,business - Abstract
Purpose The chemical structure of tubulosine has been known since the mid-1960s. However, little is known about its biological and pharmacological functions. The aim of this study was to investigate the novel functions of tubulosine in cancer treatment, specifically in breast cancer. Methods An Unpaired (Upd)-induced Drosophila cell line and interleukin (IL)-6-stimulated human breast cancer cell lines were used to investigate the biological and pharmacological activities of tubulosine in vitro. To investigate the activities of tubulosine, we performed molecular and cellular experiments such as Western blot and reverse transcription polymerase chain reaction analyses, immunoprecipitation and terminal deoxynucleotidyl transferase dUTP nick end labeling assays, and immunofluorescence staining using breast cancer cell lines. Results Tubulosine exhibited anticancer activity in IL-6-stimulated human breast cancer cells. Moreover, tubulosine reduced the tyrosine phosphorylation level and transcriptional activity of signal transducer and activator of transcription (STAT) protein at 92E in Upd-induced Drosophila cells. Additionally, tubulosine suppressed IL-6-induced Janus kinase 2 (JAK2)/STAT3 signaling, resulting in decreased viability and induction of apoptotic cell death in breast cancer cells. Interestingly, inhibition of IL-6-induced JAK2/STAT3 signaling by tubulosine was associated with the blocking of IL-6 receptor (IL-6R) and glycoprotein 130 (gp130) binding. Conclusion Tubulosine exhibits anticancer activity through functional inhibition of IL-6-induced JAK2/STAT3 signaling by targeting IL-6Rα/gp130 binding in breast cancer cells. These findings suggest that tubulosine may hold promise for the treatment of inflammation-associated cancers, including breast cancer.
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- 2019
24. CHARACTERIZATIONS OF BERGER SPHERES FROM THE VIEWPOINT OF SUBMANIFOLD THEORY
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In-Bae Kim, Sadahiro Maeda, and Byung Hak Kim
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Pure mathematics ,Geodesic ,General Mathematics ,Complex projective space ,010102 general mathematics ,0103 physical sciences ,SPHERES ,Mathematics::Differential Geometry ,010307 mathematical physics ,0101 mathematics ,Submanifold ,01 natural sciences ,Mathematics - Abstract
In this paper, Berger spheres are regarded as geodesic spheres with sufficiently big radii in a complex projective space. We characterize such real hypersurfaces by investigating their geodesics and contact structures from the viewpoint of submanifold theory.
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- 2019
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25. Sophoricoside from Sophora japonica ameliorates allergic asthma by preventing mast cell activation and CD4+ T cell differentiation in ovalbumin-induced mice
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Byung-Hak Kim and Sanghyun Lee
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0301 basic medicine ,Sophoricoside ,Ovalbumin ,Allergic asthma ,RM1-950 ,Mast cell ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Immune system ,medicine ,CD4+T cell ,Asthma ,Pharmacology ,medicine.diagnostic_test ,biology ,General Medicine ,respiratory system ,medicine.disease ,respiratory tract diseases ,030104 developmental biology ,medicine.anatomical_structure ,Bronchoalveolar lavage ,chemistry ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Arachidonic acid ,Therapeutics. Pharmacology ,Histamine ,Airway inflammation - Abstract
Asthma is a chronic inflammatory lung disorder with continuously increasing prevalence worldwide. Novel strategies are needed to prevent or improve asthma. The aim of this study was to investigate the effects of sophoricoside from Sophora japonica on allergic asthma. The mature seeds of S. japonica contain a large amount of sophoricoside. Sophoricoside reduced allergic and asthmatic symptoms by suppressing airway inflammation and antibody-antigen reaction in mouse models. In particular, sophoricoside suppressed immune cell recruitment into the airway lumens of the lungs and production of pro-inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of ovalbumin (OVA)-induced mice. It also decreased the amounts of histamine and arachidonic acid metabolites released in OVA-induced mice and antibody-antigen stimulated mast cells. In addition, sophoricoside decreased differentiation of naive CD4+ T cells into T helper type 1 (Th1), Th2, and Th17 cells. Overall, we demonstrated that sophoricoside improved allergic asthma by suppressing mast cell activation and CD4+ T cell differentiation.
- Published
- 2021
26. Study on Twisted Product Almost Gradient Yamabe Solitons
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Jin Hyuk Choi, Sang Deok Lee, and Byung Hak Kim
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Pure mathematics ,Article Subject ,010308 nuclear & particles physics ,General Mathematics ,010102 general mathematics ,01 natural sciences ,Nonlinear Sciences::Exactly Solvable and Integrable Systems ,Product (mathematics) ,0103 physical sciences ,QA1-939 ,Mathematics::Differential Geometry ,0101 mathematics ,Nonlinear Sciences::Pattern Formation and Solitons ,Mathematics - Abstract
In this paper, we first study gradient Yamabe solitons on the twisted product spaces. Then, we classify and characterize the warped product and twisted product spaces with almost gradient Yamabe solitons. We also study the construction of almost gradient Yamabe solitons in the Riemannian product spaces.
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- 2021
27. An Iterative Joint Linear-Programming Decoding of LDPC Codes and Finite-State Channels
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Byung-Hak Kim and Henry D. Pfister
- Published
- 2010
28. Message-Passing Inference on a Factor Graph for Collaborative Filtering
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Byung-Hak Kim, Arvind Yedla, and Henry D. Pfister
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- 2010
29. IMP: A Message-Passing Algorithmfor Matrix Completion
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Byung-Hak Kim, Arvind Yedla, and Henry D. Pfister
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- 2010
30. Sophoricoside from Styphnolobium japonicum improves experimental atopic dermatitis in mice
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Byung-Hak Kim and Sanghyun Lee
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Sophoricoside ,Ovalbumin ,medicine.medical_treatment ,Population ,Pharmaceutical Science ,Inflammation ,Picryl Chloride ,Dermatitis, Atopic ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Immune system ,Th2 Cells ,Drug Discovery ,medicine ,Animals ,Benzopyrans ,Viability assay ,Mast Cells ,education ,030304 developmental biology ,Skin ,Pharmacology ,0303 health sciences ,education.field_of_study ,Mice, Inbred BALB C ,biology ,Chemistry ,Fabaceae ,T-Lymphocytes, Helper-Inducer ,Immunoglobulin E ,Mast cell ,Disease Models, Animal ,Cytokine ,medicine.anatomical_structure ,Complementary and alternative medicine ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Molecular Medicine ,Cytokines ,Female ,Antibody ,medicine.symptom - Abstract
Background: Abnormal immune responses, specifically excessive differentiation of Th2 cells, are associated with the development of atopic dermatitis (AD). Sophoricoside, the genistein-4′-β-D-glucoside isolated from Styphnolobium japonicum, has previously demonstrated anti-inflammatory and immunosuppressive effects along with IL-3 and IL-5 inhibitory activities. Therefore, we speculated that sophoricoside could regulate AD by regulating abnormal immune responses. Purpose: To investigate the role of sophoricoside on AD-like allergic skin inflammation induced by ovalbumin (OVA) or 2,4,6-trinitrochlorobenzene (TNCB) in mouse models. Methods: Sophoricoside was isolated from the 70% ethanol extract of S. japonicum dried mature seeds. After being submitted to a purification process, its purity was assessed by high-performance liquid chromatography (HPLC). The effects of sophoricoside were determined in vivo by OVA- and TNCB-induced AD-like allergic skin inflammation in mice. Skin tissues were subjected with hematoxylin-eosin (H&E), Giemsa and toluidine blue staining. In vitro CD4+ T cell differentiation was performed and the levels of serum immunoglobulins, cytokines, and genes related to CD4+ T cell differentiation were determined by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR. Cytokine bioassay, mixed lymphocytes reaction and cell viability assay were performed. Results: Topical application of sophoricoside decreased the symptoms of AD-like allergic skin inflammation, including elevated hypertrophic scars with spongiotic epidermis, epidermal hyperplasia, hyperkeratosis, infiltration of immune, and mast cells, dermal thickness, amounts of immunoglobulins, and pro-inflammatory cytokines, and the mast cell population in the skin. Sophoricoside also decreased T cell antigen receptor (TCR)-mediated immune responses. In particular, sophoricoside suppressed the differentiation of naive CD4+ T cells into Th cell subsets, including Th1, Th2, and Th17, by inhibiting the expression of their subset-specific master transcription factors, leading to suppression of the expression and production of these cell subset-specific cytokines. Conclusion: Sophoricoside can improve AD-like allergic skin diseases mainly by inhibiting pathogenic CD4+ T cell differentiation and immune responses.
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- 2020
31. Sophoricoside from Sophora japonica ameliorates allergic asthma by preventing mast cell activation and CD4
- Author
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Byung-Hak, Kim and Sanghyun, Lee
- Subjects
CD4-Positive T-Lymphocytes ,Mice, Inbred BALB C ,Ovalbumin ,Plant Extracts ,Immunoglobulins ,Cell Differentiation ,Histamine Release ,Asthma ,Cell Degranulation ,Disease Models, Animal ,Anti-Allergic Agents ,Animals ,Cytokines ,Benzopyrans ,Anti-Asthmatic Agents ,Mast Cells ,Inflammation Mediators ,Lung ,Sophora ,Cells, Cultured - Abstract
Asthma is a chronic inflammatory lung disorder with continuously increasing prevalence worldwide. Novel strategies are needed to prevent or improve asthma. The aim of this study was to investigate the effects of sophoricoside from Sophora japonica on allergic asthma. The mature seeds of S. japonica contain a large amount of sophoricoside. Sophoricoside reduced allergic and asthmatic symptoms by suppressing airway inflammation and antibody-antigen reaction in mouse models. In particular, sophoricoside suppressed immune cell recruitment into the airway lumens of the lungs and production of pro-inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of ovalbumin (OVA)-induced mice. It also decreased the amounts of histamine and arachidonic acid metabolites released in OVA-induced mice and antibody-antigen stimulated mast cells. In addition, sophoricoside decreased differentiation of naïve CD4
- Published
- 2020
32. Effects of Astragalus Extract Mixture HT042 on Circulating IGF-1 Level and Growth Hormone Axis in Rats
- Author
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Young-Sik Kim, Sung-Hyun Lee, Won-Young Cho, Byung-Hak Kim, Donghun Lee, and Hocheol Kim
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medicine.medical_specialty ,Pituitary gland ,Chemistry ,Growth hormone secretagogue receptor ,Growth hormone receptor ,Pediatrics ,RJ1-570 ,Article ,Growth hormone secretion ,HT042 ,Endocrinology ,medicine.anatomical_structure ,Somatostatin ,circulating insulin-like growth factor-1 ,Hormone receptor ,Hypothalamus ,growth plate ,Internal medicine ,growth hormone ,immunohistochemistry ,Pediatrics, Perinatology and Child Health ,medicine ,Autocrine signalling ,hormones, hormone substitutes, and hormone antagonists - Abstract
Astragalus extract mixture HT042 is a standardized functional food granted by the Korean FDA for promoting “Children’s Height Growth”. In this study, we determined whether HT042 affects circulatory Insulin-like growth factor-1 (IGF-1) after administration and investigated whether Growth hormone (GH), Growth hormone-releasing hormone receptor (GHRH-R), and Growth hormone secretagogue receptor (GHS-R) mRNAs are expressed in the pituitary, and whether Growth hormone-releasing hormone (GHRH) and Somatostatin (SST) are expressed in the hypothalamus. We also evaluated the growth effect of HT042 on endochondral bone formation. Male Sprague-Dawley rats in the control and HT042 groups were orally administered a single dose of the control and HT042, respectively, and those in the recombinant human GH (rhGH) group were subcutaneously injected with rhGH. Tetracycline was injected intraperitoneally 72 h prior to sacrifice to decide endochondral bone formation. To determine the endocrine or paracrine/autocrine mechanism, we evaluated the expression of local BMP-2 and IGF-1, an immunohistochemical study after HT042 administration. It was confirmed that the growth-promoting effect of HT042 can be contributed to the increase in serum IGF-1, which can be stimulated by GH secretion. Administration of HT042 modulated the activity of GHRH-R and GHR-S in the pituitary gland and promoted GH secretion, thereby changing longitudinal growth through GH/IGF-1 mediation. Results for GHRH and SST expression demonstrated that the hypothalamus can be influenced and mediated by HT042 through a complex neuroendocrine regulatory system. In addition, it was confirmed by oral administration for 10 days that HT042 increased bone formation in cartilage, which is important for height growth. The effect of HT042 could be owing to upregulation of local Bone morphogenetic protein-2 (BMP-2) and IGF-1 expression in the growth plate, which could be regarded as a GH-dependent autocrine/paracrine pathway, as well as circulatory IGF-1.
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- 2021
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33. Dysfunction of Microglial STAT3 Alleviates Depressive Behavior via Neuron–Microglia Interactions
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Byung Hak Kim, Sun Ho Kwon, Jeong Kyu Han, Sang Jeong Kim, Moonseok Choi, Ik Hyun Cho, Sung Joon Kim, Eun Hee Yi, Sang Kyu Ye, Jae Cheon Shin, and Yong Jin Kwon
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Male ,STAT3 Transcription Factor ,0301 basic medicine ,Glutamic Acid ,Mice, Transgenic ,Stimulation ,Synaptic Transmission ,Tissue Culture Techniques ,03 medical and health sciences ,0302 clinical medicine ,Neurotrophic factors ,Neuroimmune system ,medicine ,Animals ,STAT3 ,Cells, Cultured ,Neurons ,Pharmacology ,Depressive Disorder ,Microglia ,biology ,Chemistry ,Brain-Derived Neurotrophic Factor ,Macrophage Colony-Stimulating Factor ,Brain ,Coculture Techniques ,Disease Models, Animal ,Psychiatry and Mental health ,030104 developmental biology ,medicine.anatomical_structure ,STAT protein ,Excitatory postsynaptic potential ,biology.protein ,Original Article ,Neuron ,Neuroscience ,030217 neurology & neurosurgery ,Synaptosomes - Abstract
Neuron–microglia interactions have a crucial role in maintaining the neuroimmune system. The balance of neuroimmune system has emerged as an important process in the pathophysiology of depression. However, how neuron–microglia interactions contribute to major depressive disorders has been poorly understood. Herein, we demonstrated that microglia-derived synaptic changes induced antidepressive-like behavior by using microglia-specific signal transducer and activator of transcription 3 (STAT3) knockout (KO) (STAT3fl/fl;LysM-Cre+/−) mice. We found that microglia-specific STAT3 KO mice showed antidepressive-like behavior in the forced swim, tail suspension, sucrose preference, and open-field tests. Surprisingly, the secretion of macrophage colony-stimulating factor (M-CSF) was increased from neuronal cells in the brains of STAT3fl/fl;LysM-Cre+/− mice. Moreover, the phosphorylation of antidepressant-targeting mediators and brain-derived neurotrophic factor expression were increased in the brains of STAT3fl/fl;LysM-Cre+/− mice as well as in neuronal cells in response to M-CSF stimulation. Importantly, the miniature excitatory postsynaptic current frequency in the medial prefrontal cortex was increased in STAT3fl/fl;LysM-Cre+/− mice and in the M-CSF treatment group. Collectively, microglial STAT3 regulates depression-related behaviors via neuronal M-CSF-mediated synaptic activity, suggesting that inhibition of microglial STAT3 might be a new therapeutic strategy for depression.
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- 2017
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34. A~characterization of a~certain real hypersurface of type $({\rm A}_2)$ in a~complex projective space
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Sadahiro Maeda, In-Bae Kim, and Byung Hak Kim
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Pure mathematics ,Hopf manifold ,Mathematics::Complex Variables ,Hyperbolic space ,Complex projective space ,010102 general mathematics ,Mathematical analysis ,Holomorphic function ,Type (model theory) ,01 natural sciences ,Hypersurface ,Complex space ,0103 physical sciences ,Mathematics::Differential Geometry ,010307 mathematical physics ,Sectional curvature ,0101 mathematics ,Mathematics - Abstract
In the class of real hypersurfaces M 2n−1 isometrically immersed into a nonflat complex space form $$\widetilde {{M_n}}\left( c \right)$$ of constant holomorphic sectional curvature c (≠ 0) which is either a complex projective space ℂP n (c) or a complex hyperbolic space ℂH n (c) according as c > 0 or c < 0, there are two typical examples. One is the class of all real hypersurfaces of type (A) and the other is the class of all ruled real hypersurfaces. Note that the former example are Hopf manifolds and the latter are non-Hopf manifolds. In this paper, inspired by a simple characterization of all ruled real hypersurfaces in $$\widetilde {{M_n}}\left( c \right)$$ , we consider a certain real hypersurface of type (A2) in ℂP n (c) and give a geometric characterization of this Hopf manifold.
- Published
- 2017
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35. On freshmen's academic achievements of college mathematics and the efficient methods of education
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Byung Hak Kim, Jae Woong Kim, and Jiyun Kim
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General Medicine - Published
- 2017
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36. ON A CLASSIFICATION OF WARPED PRODUCT SPACES WITH GRADIENT RICCI SOLITONS
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Jin Hyuk Choi, Sang Deok Lee, and Byung Hak Kim
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Pure mathematics ,010102 general mathematics ,Mathematical analysis ,Ricci flow ,Function (mathematics) ,01 natural sciences ,Ricci soliton ,Nonlinear Sciences::Exactly Solvable and Integrable Systems ,Product (mathematics) ,0103 physical sciences ,Mathematics::Metric Geometry ,Product topology ,Mathematics::Differential Geometry ,010307 mathematical physics ,0101 mathematics ,Nonlinear Sciences::Pattern Formation and Solitons ,Ricci curvature ,Mathematics - Abstract
In this paper, we study Ricci solitons, gradient Ricci solitons in the warped product spaces and gradient Yamabe solitons in the Riemannian product spaces. We obtain the necessary and sufficient conditions for the Riemannian product spaces to be Ricci solitons. Moreover we classify the warped product space which admit gradient Ricci solitons under some conditions of the potential function.
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- 2016
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37. Development of Oxadiazole-Based ODZ10117 as a Small-Molecule Inhibitor of STAT3 for Targeted Cancer Therapy
- Author
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Changdev G. Gadhe, Haeri Lee, Sang Kyu Ye, Joon Suk Park, Jiwon Choi, Ae Nim Pae, Sanghee Kim, Chung Gi Lee, Yeonghun Song, and Byung Hak Kim
- Subjects
medicine.medical_treatment ,lcsh:Medicine ,Tumor initiation ,Article ,stat3 ,Targeted therapy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,structure-based computational database screening ,In vivo ,Cancer stem cell ,Medicine ,STAT3 ,030304 developmental biology ,0303 health sciences ,biology ,business.industry ,lcsh:R ,Tyrosine phosphorylation ,General Medicine ,medicine.disease ,sh2 domain ,targeted therapy ,3-(2,4-dichloro-phenoxymethyl)-5-trichloromethyl-[1,2,4]oxadiazole (odz10117) ,cell-based high-throughput screening ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,business - Abstract
Persistently activated STAT3 is a promising target for a new class of anticancer drug development and cancer therapy, as it is associated with tumor initiation, progression, malignancy, drug resistance, cancer stem cell properties, and recurrence. Here, we discovered 3-(2,4-dichloro-phenoxymethyl)-5-trichloromethyl-[1,2,4]oxadiazole (ODZ10117) as a small-molecule inhibitor of STAT3 to be used in STAT3-targeted cancer therapy. ODZ10117 targeted the SH2 domain of STAT3 regardless of other STAT family proteins and upstream regulators of STAT3, leading to inhibition of the tyrosine phosphorylation, dimerization, nuclear translocation, and transcriptional activity of STAT3. The inhibitory effect of ODZ10117 on STAT3 was stronger than the known STAT3 inhibitors such as S3I-201, STA-21, and nifuroxazide. ODZ10117 suppressed the migration and invasion, induced apoptosis, reduced tumor growth and lung metastasis, and extended the survival rate in both in vitro and in vivo models of breast cancer. Overall, we demonstrated that ODZ10117 is a novel STAT3 inhibitor and may be a promising agent for the development of anticancer drugs.
- Published
- 2019
38. Evaluation and Optimization of the Anti-Melanogenic Activity of 1-(2-Cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone Derivatives
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Byung Hak Kim, Jung Youl Park, Soo Nam Hong, and Sang Kyu Ye
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Chalcone ,Stereochemistry ,Cell Survival ,Tyrosinase ,Pharmaceutical Science ,Down-Regulation ,chalcone ,tyrosinase ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,03 medical and health sciences ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Mice ,0302 clinical medicine ,Chalcones ,lcsh:Organic chemistry ,Cell Line, Tumor ,melanin biosynthesis ,Drug Discovery ,Animals ,Hydroxymethyl ,Physical and Theoretical Chemistry ,Melanoma ,030304 developmental biology ,Melanins ,0303 health sciences ,Monophenol Monooxygenase ,Organic Chemistry ,Arbutin ,Biological activity ,(E)-N-(4-(3-(2-(cyclohexylmethoxy)phenyl)-3-oxoprop-1-en-1-yl)phenyl)acetamide (chalcone 21-21) ,alpha-melanocyte stimulating hormone (α-MSH) ,alpha-melanocyte stimulating hormone (-MSH) ,Gene Expression Regulation, Neoplastic ,chemistry ,Chemistry (miscellaneous) ,030220 oncology & carcinogenesis ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Kojic acid ,Lead compound ,Acetamide ,Signal Transduction - Abstract
The chemical modification and optimization of biologically active compounds are essential steps in the identification of promising lead compounds for drug development. We previously reported the anti-melanogenic activity of 1-(2-cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone (chalcone 21). In this study, we synthesized 21 derivatives of chalcone 21 and evaluated their anti-melanogenic activity in α-MSH-induced B16F10 cells. (E)-N-(4-(3-(2-(Cyclohexylmethoxy)phenyl)-3-oxoprop-1-en-1-yl)phenyl)acetamide (chalcone 21-21) exhibited the strongest inhibition of cellular melanin production, with an IC50 value of 0.54 μM. It was more potent than chalcone 21 and the known anti-melanogenic agents kojic acid and arbutin, whose IC50 values were 4.9, 38.5, and 148.4 μM, respectively. Chalcone 21-21 decreased the expression and activity of tyrosinase. It also decreased the expression of TRP1, TRP2 and MITF, the phosphorylation of CREB and ERK1/2, and the transcriptional activity of MITF and CRE. Our results demonstrate that chalcone-21-21 is an effective lead compound with anti-melanogenic activity.
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- 2019
39. Effects of Astragalus Extract Mixture HT042 on Circulating IGF-1 Level and Growth Hormone Axis in Rats.
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Donghun Lee, Byung-Hak Kim, Sung-Hyun Lee, Won-Young Cho, Young-Sik Kim, and Hocheol Kim
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ASTRAGALUS (Plants) ,PLANT extracts ,SOMATOMEDIN C ,FUNCTIONAL foods ,IMMUNOHISTOCHEMISTRY ,MESSENGER RNA - Abstract
Astragalus extract mixture HT042 is a standardized functional food granted by the Korean FDA for promoting “Children’s Height Growth”. In this study, we determined whether HT042 affects circulatory Insulin-like growth factor-1 (IGF-1) after administration and investigated whether Growth hormone (GH), Growth hormone-releasing hormone receptor (GHRH-R), and Growth hormone secretagogue receptor (GHS-R) mRNAs are expressed in the pituitary, and whether Growth hormonereleasing hormone (GHRH) and Somatostatin (SST) are expressed in the hypothalamus. We also evaluated the growth effect of HT042 on endochondral bone formation. Male Sprague-Dawley rats in the control and HT042 groups were orally administered a single dose of the control and HT042, respectively, and those in the recombinant human GH (rhGH) group were subcutaneously injected with rhGH. Tetracycline was injected intraperitoneally 72 h prior to sacrifice to decide endochondral bone formation. To determine the endocrine or paracrine/autocrine mechanism, we evaluated the expression of local BMP-2 and IGF-1, an immunohistochemical study after HT042 administration. It was confirmed that the growth-promoting effect of HT042 can be contributed to the increase in serum IGF-1, which can be stimulated by GH secretion. Administration of HT042 modulated the activity of GHRH-R and GHR-S in the pituitary gland and promoted GH secretion, thereby changing longitudinal growth through GH/IGF-1 mediation. Results for GHRH and SST expression demonstrated that the hypothalamus can be influenced and mediated by HT042 through a complex neuroendocrine regulatory system. In addition, it was confirmed by oral administration for 10 days that HT042 increased bone formation in cartilage, which is important for height growth. The effect of HT042 could be owing to upregulation of local Bone morphogenetic protein-2 (BMP-2) and IGF-1 expression in the growth plate, which could be regarded as a GH-dependent autocrine/paracrine pathway, as well as circulatory IGF-1. [ABSTRACT FROM AUTHOR]
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- 2021
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40. STAT3 Potentiates SIAH-1 Mediated Proteasomal Degradation of β-Catenin in Human Embryonic Kidney Cells
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Kang Yell Choi, Byung Hak Kim, Sang Kyu Ye, Jae Cheon Shin, Jung Youl Park, Chung-Hyun Cho, Jong Wan Park, Min Kyung Shin, and Eun Hee Yi
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STAT3 Transcription Factor ,0301 basic medicine ,proteasomal degradation ,Proteasome Endopeptidase Complex ,Beta-catenin ,Transcription, Genetic ,Ubiquitin-Protein Ligases ,Kidney ,Transfection ,Article ,STAT3 ,03 medical and health sciences ,Transcription Factor 4 ,0302 clinical medicine ,Humans ,Phosphorylation ,Nuclear protein ,Molecular Biology ,Transcription factor ,beta Catenin ,biology ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,HEK 293 cells ,Wnt signaling pathway ,Nuclear Proteins ,Cell Biology ,General Medicine ,β-catenin ,Ubiquitin ligase ,Cell biology ,HEK293 Cells ,030104 developmental biology ,030220 oncology & carcinogenesis ,Catenin ,SIAH-1 ,biology.protein ,Transcription Factors - Abstract
The β-catenin functions as an adhesion molecule and a component of the Wnt signaling pathway. In the absence of the Wnt ligand, β-catenin is constantly phosphorylated, which designates it for degradation by the APC complex. This process is one of the key regulatory mechanisms of β-catenin. The level of β-catenin is also controlled by the E3 ubiquitin protein ligase SIAH-1 via a phosphorylation-independent degradation pathway. Similar to β-catenin, STAT3 is responsible for various cellular processes, such as survival, proliferation, and differentiation. However, little is known about how these molecules work together to regulate diverse cellular processes. In this study, we investigated the regulatory relationship between STAT3 and β-catenin in HEK293T cells. To our knowledge, this is the first study to report that β-catenin-TCF-4 transcriptional activity was suppressed by phosphorylated STAT3; furthermore, STAT3 inactivation abolished this effect and elevated activated β-catenin levels. STAT3 also showed a strong interaction with SIAH-1, a regulator of active β-catenin via degradation, which stabilized SIAH-1 and increased its interaction with β-catenin. These results suggest that activated STAT3 regulates active β-catenin protein levels via stabilization of SIAH-1 and the subsequent ubiquitin-dependent proteasomal degradation of β-catenin in HEK293T cells.
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- 2016
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41. Inhibition of tyrosinase activity and melanin production by the chalcone derivative 1-(2-cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone
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Jeong Ho Park, Chung Gi Lee, Kyoung Chan Park, Sang Kyu Ye, Byung Hak Kim, and Jung Youl Park
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0301 basic medicine ,Chalcone ,Tyrosinase ,Biophysics ,Down-Regulation ,Biochemistry ,Melanin ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Chalcones ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Enzyme Inhibitors ,Melanoma ,Molecular Biology ,Melanins ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,integumentary system ,Protoporphyrin IX ,Monophenol Monooxygenase ,Pigmentation ,Cell Biology ,medicine.disease ,Microphthalmia-associated transcription factor ,Hyperpigmentation ,Enzyme Activation ,030104 developmental biology ,Enzyme ,chemistry ,030220 oncology & carcinogenesis ,medicine.symptom - Abstract
Abnormal accumulation of melanin pigments in the skin can be lead to hyperpigmentation disorders and melanoma. Melanin biosynthesis is ultimately regulated by the rate-limiting enzyme tyrosinase. In the present study, we synthesized chalcone derivatives and identified 1-(2-cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone (chalcone-21) as an anti-melanogenic substance in B16F10 melanoma cells. Chalcone-21 strongly inhibited cellular melanin production and tyrosinase activity in B16F10 melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH) or protoporphyrin IX. In addition, the compound suppressed not only the expression of tyrosinase, tyrosinase-related protein-1 (TRP-1), TRP-2, and microphthalmia-associated transcription factor (MITF), but also the transcriptional activity of tyrosinase and MITF. Our results demonstrated chalcone-21 to be an effective depigmenting agent.
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- 2016
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42. Signal transducer and activator of transcription 3 as a therapeutic target for cancer and the tumor microenvironment
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Byung Hak Kim, Sang Kyu Ye, and Eun Hee Yi
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STAT3 Transcription Factor ,0301 basic medicine ,Angiogenesis ,Antineoplastic Agents ,Metastasis ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,Immune system ,Neoplasms ,Drug Discovery ,Tumor Microenvironment ,medicine ,Animals ,Humans ,STAT3 ,Transcription factor ,Tumor microenvironment ,biology ,Cell growth ,Organic Chemistry ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,STAT protein ,Cancer research ,Molecular Medicine - Abstract
Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that modulates the transcription of a variety of genes to regulate important biological functions, including cell proliferation, differentiation, survival, angiogenesis, and immune response. Constitutive activation of STAT3 is important in oncogenic signaling and occurs at high frequency in human cancers, including diverse solid tumors and hematologic malignancies. Moreover, it is associated with a poor prognosis. The tumor microenvironment has recently been recognized as a key condition for cancer progression, invasion, angiogenesis, metastasis, and drug resistance by activation of STAT3 signaling. Therefore, understanding the biology associated with STAT3-mediated signaling cascades in the tumor microenvironment may offer the therapeutic potential to treat human cancers. This review presents an overview of the critical roles of STAT3 in the tumor microenvironment related to cancer biology and discusses recent advancements in the development of anticancer drugs that therapeutically inhibit STAT3 signaling cascades.
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- 2016
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43. Alleviation of collagen-induced arthritis by the benzoxathiole derivative BOT-4-one in mice: Implication of the Th1- and Th17-cell-mediated immune responses
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Sang Kyu Ye, Won Woo Lee, Seong Wook Kang, Eun Kyoung Kim, Sun Ho Kwon, Eun Hee Yi, Kum Hee Noh, Bo Ruem Yoon, Hyun Gyu Lee, Jung Sook Choi, In Chul Park, and Byung Hak Kim
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0301 basic medicine ,Interleukin-1beta ,Anti-Inflammatory Agents ,Arthritis ,Inflammation ,Biochemistry ,Cell Line ,Proinflammatory cytokine ,Mice ,03 medical and health sciences ,Immune system ,medicine ,Animals ,Humans ,Cyclic AMP Response Element-Binding Protein ,Interleukin 6 ,Pharmacology ,biology ,Interleukin-6 ,business.industry ,Macrophages ,NF-kappa B ,Cell Differentiation ,Th1 Cells ,Bridged Bicyclo Compounds, Heterocyclic ,NFKB1 ,medicine.disease ,Arthritis, Experimental ,Immunity, Innate ,Mice, Inbred C57BL ,Transcription Factor AP-1 ,030104 developmental biology ,Gene Expression Regulation ,Rheumatoid arthritis ,Immunology ,STAT protein ,biology.protein ,Th17 Cells ,Joints ,Mitogen-Activated Protein Kinases ,medicine.symptom ,business ,Spleen ,Signal Transduction - Abstract
Autoimmune rheumatoid arthritis is characterized by chronic inflammation and hyperplasia in the synovial joints. Although the cause of rheumatoid arthritis is largely unknown, substantial evidence has supported the importance of immune cells and inflammatory cytokines in the initiation and progression of this disease. Herein, we demonstrated that the benzoxathiole derivative 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one) alleviated type II collagen-induced arthritis in a mouse model. The levels of pro-inflammatory cytokines are elevated in both human patients with rheumatoid arthritis and mice with collagen-induced arthritis. BOT-4-one treatment reduced the levels of pro-inflammatory cytokines in mice and endotoxin-stimulated macrophages. BOT-4-one treatment suppressed the polarization of Th1- and Th17-cell subsets by inhibiting the expression and production of their lineage-specific master transcription factors and cytokines, as well as activation of signal transducer and activator of transcription proteins. In addition, BOT-4-one inhibited mitogen-activated protein kinase and NF-kappaB signaling as well as the transcriptional activities and DNA-binding of transcription factors, including activator protein-1, cAMP response element-binding protein and NF-kappaB. Our results suggest that BOT-4-one may have therapeutic potential for the treatment of chronic inflammation associated with autoimmune rheumatoid arthritis.
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- 2016
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44. Potential role of 8-oxoguanine DNA glycosylase 1 as a STAT1 coactivator in endotoxin-induced inflammatory response
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Sang Kyu Ye, Joo Eun Jung, Myung Hee Chung, Jung Weon Lee, Hong Sook Kim, Kun Ho Lee, Ho Jin You, Hyun Gyu Lee, Byung Hak Kim, and Chang Seok Lee
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Transcriptional Activation ,0301 basic medicine ,Guanine ,DNA Repair ,DNA damage ,DNA repair ,Biology ,Biochemistry ,Chromatin remodeling ,DNA Glycosylases ,Myelin oligodendrocyte glycoprotein ,Interferon-gamma ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Coactivator ,Animals ,Humans ,Promoter Regions, Genetic ,Inflammation ,Regulation of gene expression ,Promoter ,Chromatin Assembly and Disassembly ,Molecular biology ,Endotoxins ,Oxidative Stress ,STAT1 Transcription Factor ,030104 developmental biology ,Gene Expression Regulation ,DNA glycosylase ,030220 oncology & carcinogenesis ,biology.protein ,Myelin-Oligodendrocyte Glycoprotein ,DNA Damage - Abstract
Human 8-oxoguanine DNA glycosylase 1 (OGG1) is the major DNA repair enzyme that plays a key role in excision of oxidative damaged DNA bases such as 8-oxoguainine (8-oxoG). Recent studies suggest another function of OGG1, namely that it may be involved in the endotoxin- or oxidative stress-induced inflammatory response. In this study, we investigated the role of OGG1 in the inflammatory response. OGG1 expression is increased in the organs of endotoxin-induced or myelin oligodendrocyte glycoprotein (MOG)-immunized mice and immune cells, resulting in induction of the expression of pro-inflammatory mediators at the transcriptional levels. Biochemical studies showed that signal transducer and activator of transcription 1 (STAT1) plays a key role in endotoxin-induced OGG1 expression and inflammatory response. STAT1 regulates the transcriptional activity of OGG1 through recruiting and binding to the gamma-interferon activation site (GAS) motif of the OGG1 promoter region, and chromatin remodeling by acetylation and dimethylation of lysine-14 and -4 residues of histone H3. In addition, OGG1 acts as a STAT1 coactivator and has transcriptional activity in the presence of endotoxin. The data presented here identifies a novel mechanism, and may provide new therapeutic strategies for the treatment of endotoxin-mediated inflammatory diseases.
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- 2016
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45. Immunomodulatory Activities of the Benzoxathiole Derivative BOT-4-One Ameliorate Pathogenic Skin Inflammation in Mice
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Yong Nyun Kim, Ae Nim Pae, Byung Hak Kim, Sang Kyu Ye, Youngsoo Kim, Ae Jin Jeong, Yu Chen Li, Kwang-Ho Lee, Sung Ja Rhie, Jung Sook Choi, Myoung Hwan Kim, Hyun Gyu Lee, and Nam-Chul Cho
- Subjects
0301 basic medicine ,Lipopolysaccharide ,Regulatory T cell ,Inflammation ,Dermatology ,IκB kinase ,Biology ,Lymphocyte Activation ,Sensitivity and Specificity ,Biochemistry ,Dermatitis, Atopic ,Immunomodulation ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Immune system ,T-Lymphocyte Subsets ,RAR-related orphan receptor gamma ,medicine ,Animals ,Molecular Biology ,Cells, Cultured ,Biopsy, Needle ,FOXP3 ,Cell Differentiation ,Cell Biology ,Bridged Bicyclo Compounds, Heterocyclic ,Immunohistochemistry ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Dermatitis, Allergic Contact ,Immunology ,STAT protein ,medicine.symptom - Abstract
T-cell-mediated immune responses play an important role in body protection. However, aberrantly activated immune responses are responsible for inflammatory and autoimmune diseases. The regulation of pathologic immune responses may be a potential therapeutic strategy for the treatment of these diseases. Despite that multiple pharmacologic properties of benzoxathiole derivatives have been defined, the molecular mechanisms underlying these properties remain to be clarified. Here, we demonstrated the benzoxathiole derivative 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one) regulated immune responses and ameliorated experimentally induced inflammatory skin diseases both in vitro and in vivo. BOT-4-one inhibited the differentiation of CD4(+) T-cell subsets by regulating the expression and production of T-cell lineage-specific master transcription factors and cytokines and activating the signal transducer and activator of transcription proteins. In addition, BOT-4-one inhibited TCR-mediated Akt and NF-κB signaling. Topical application of BOT-4-one ameliorated experimentally induced inflammatory skin diseases in mice models such as 2,4,6-trinitrochlorobenzene-induced contact and atopic dermatitis and IL-23-induced psoriasis-like skin inflammation. Our study demonstrated that BOT-4-one ameliorates inflammatory skin diseases by suppressing the pathogenic CD4(+) T cell differentiation and overall immune responses.
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- 2016
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46. Anti-osteoporotic effects of Salvia miltiorrhiza Bunge EtOH extract both in ovariectomized and naturally menopausal mouse models
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Se Chan Kang, Byung Hak Kim, Min-Kyu Yun, Sung Ryul Lee, Ye Ji Lim, Jeong Eun Kwon, Hyelin Jeon, and Heeju Suh
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medicine.medical_specialty ,Ovariectomy ,Osteoporosis ,Osteoclasts ,Salvia miltiorrhiza ,Bone resorption ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Bone Density ,Osteoclast ,Internal medicine ,Drug Discovery ,medicine ,Animals ,Humans ,Osteoporosis, Postmenopausal ,030304 developmental biology ,Pharmacology ,Bone mineral ,Mice, Inbred ICR ,0303 health sciences ,Dose-Response Relationship, Drug ,Ethanol ,biology ,Plant Extracts ,business.industry ,medicine.disease ,Disease Models, Animal ,Endocrinology ,medicine.anatomical_structure ,RANKL ,030220 oncology & carcinogenesis ,Ovariectomized rat ,Osteocalcin ,biology.protein ,Female ,Menopause ,business - Abstract
Ethnopharmacological relevance Salvia miltiorrhiza is a traditional oriental medicine widely used for preventing and treating disorders of the liver, menstrual, and blood circulation systems. Osteoporosis, loss of bone with age and/or estrogen deficiency, is an important causal factor of fracture. S. miltiorrhiza extract has been used to alleviate dysmenorrhea and painful osteoarthritis. Aim of the study This study was performed to investigate the anti-osteoporosis activity of the Salvia miltiorrhiza ethanol extract (SME) in osteoporosis-prone conditions: ovariectomized (OVX) and naturally menopaused (NM) ICR mice. Materials and methods Anti-osteoporotic potentials of SME (50–200 mg/kg) were evaluated based on bone mineral density using microCT analysis, biochemical parameters, and changes in the gene expressions involved in bone resorption. Results SME ameliorated the loss of trabecular bone both in OVX and NM mice. SME was effective in correcting aberrant levels of RANKL, osteocalcin, and BALP, which are critically involved in bone resorption. In addition, SME suppressed the expression of TRAF6 and NFATc1, which play a role in osteoclast differentiation. Conclusions SME suppressed the loss of trabecular bone via suppressing bone resorption and osteoclast differentiation both in OVX and NM mice. SME is likely to be developed as a therapeutic agent for osteoporosis.
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- 2020
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47. STAT3 Inhibitor ODZ10117 Suppresses Glioblastoma Malignancy and Prolongs Survival in a Glioblastoma Xenograft Model
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Cheol Gyu Park, Sang Kyu Ye, Byung Hak Kim, Kum Hee Noh, Sun Ha Paek, Song Hee Lee, Chung Gi Lee, Jong Bae Park, Hyunggee Kim, Haeri Lee, and Ae Jin Jeong
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STAT3 Transcription Factor ,medicine.medical_treatment ,Drug resistance ,Malignancy ,Article ,glioma stem cell (GSC) ,Targeted therapy ,STAT3 ,Mice ,Cell Line, Tumor ,Glioma ,medicine ,Animals ,Humans ,lcsh:QH301-705.5 ,neoplasms ,biology ,business.industry ,glioblastoma ,Cancer ,General Medicine ,targeted therapy ,medicine.disease ,Survival Analysis ,Xenograft Model Antitumor Assays ,ODZ10117 ,nervous system diseases ,Disease Models, Animal ,lcsh:Biology (General) ,Cancer research ,biology.protein ,Stem cell ,business ,Glioblastoma - Abstract
Constitutively activated STAT3 plays an essential role in the initiation, progression, maintenance, malignancy, and drug resistance of cancer, including glioblastoma, suggesting that STAT3 is a potential therapeutic target for cancer therapy. We recently identified ODZ10117 as a small molecule inhibitor of STAT3 and suggested that it may have an effective therapeutic utility for the STAT3-targeted cancer therapy. Here, we demonstrated the therapeutic efficacy of ODZ10117 in glioblastoma by targeting STAT3. ODZ10117 inhibited migration and invasion and induced apoptotic cell death by targeting STAT3 in glioblastoma cells and patient-derived primary glioblastoma cells. In addition, ODZ10117 suppressed stem cell properties in glioma stem cells (GSCs). Finally, the administration of ODZ10117 showed significant therapeutic efficacy in mouse xenograft models of GSCs and glioblastoma cells. Collectively, ODZ10117 is a promising therapeutic candidate for glioblastoma by targeting STAT3.
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- 2020
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48. Microgravity induces autophagy via mitochondrial dysfunction in human Hodgkin’s lymphoma cells
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Sungwan Kim, Jin Woong Chung, Yoon Jae Kim, Haeri Lee, Min Hyuk Lim, Sang Kyu Ye, Byung Hak Kim, Ae Jin Jeong, Chung-Hyun Cho, and Kumhee Noh
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0301 basic medicine ,MAPK/ERK pathway ,lcsh:Medicine ,Article ,03 medical and health sciences ,Stress, Physiological ,Cell Line, Tumor ,Autophagy ,Humans ,lcsh:Science ,Protein kinase B ,Weightlessness Simulation ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,chemistry.chemical_classification ,Reactive oxygen species ,Multidisciplinary ,NADPH oxidase ,biology ,Chemistry ,lcsh:R ,AMPK ,Hodgkin Disease ,Acetylcysteine ,Mitochondria ,Cell biology ,Gene Expression Regulation, Neoplastic ,Oxidative Stress ,030104 developmental biology ,Cell culture ,biology.protein ,lcsh:Q ,Reactive Oxygen Species - Abstract
Gravitational forces can impose physical stresses on the human body as it functions to maintain homeostasis. It has been reported that astronauts exposed to microgravity experience altered biological functions and many subsequent studies on the effects of microgravity have therefore been conducted. However, the anticancer mechanisms of simulated microgravity remain unclear. We previously showed that the proliferation of human Hodgkin’s lymphoma (HL) cells was inhibited when these cells were cultured in time-averaged simulated microgravity (taSMG). In the present study, we investigated whether taSMG produced an anticancer effect. Exposure of human HL cells to taSMG for 2 days increased their reactive oxygen species (ROS) production and NADPH oxidase family gene expression, while mitochondrial mass, ATPase, ATP synthase, and intracellular ATP levels were decreased. Furthermore, human HL cells exposed to taSMG underwent autophagy via AMPK/Akt/mTOR and MAPK pathway modulation; such autophagy was inhibited by the ROS scavenger N-acetylcysteine (NAC). These results suggest an innovative therapeutic approach to HL that is markedly different from conventional chemotherapy and radiotherapy.
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- 2018
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49. Warped product spaces with Ricci conditions
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Sang Deok Lee, Jin Hyuk Choi, and Byung Hak Kim
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Pure mathematics ,010308 nuclear & particles physics ,General Mathematics ,Product (mathematics) ,010102 general mathematics ,0103 physical sciences ,Mathematics::Differential Geometry ,Ricci curvature,warped product space,Ricci soliton ,0101 mathematics ,01 natural sciences ,Mathematics - Abstract
In this paper, we study the Ricci soliton in the Riemannian products$M=R^n \times B$ and warped products $M=R \times _f B$ of theEuclidean space and Riemannian manifolds, and the gradient Riccisoliton in the warped products $M=S^1 \times _f B$ of 1-dimensionalcircle and Riemannian manifolds. Moreover, we introduce the concept ofthe generalized Ricci soliton and we suggest the method of constructionof the Riemannian manifold $(M, g)$ with a Ricci soliton $g$.Finally, we also study the Lorentzian warped products with the Riccisoliton.
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- 2017
50. Signal transducer and activator of transcription 3‐mediated CD133 up‐regulation contributes to promotion of hepatocellular carcinoma
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Sang Kyu Ye, Byung Hak Kim, Kyung Ju Choi, Stephanie Ma, Cheolhee Won, Ja June Jang, Eun Hee Yi, Snorri S. Thorgeirsson, Jae Ho Lee, In Chul Park, Jong Min Jeong, Tae Woo Kim, Jung Hwan Yoon, Eun Kyung Kim, Valentina M. Factor, Won-Il Jeong, Sun Sik Bae, and Yun-Han Lee
- Subjects
STAT3 Transcription Factor ,Sorafenib ,Carcinoma, Hepatocellular ,Mice ,Antigens, CD ,RNA interference ,Cancer stem cell ,medicine ,Hepatobiliary Malignancies ,Animals ,Humans ,Gene silencing ,AC133 Antigen ,STAT3 ,neoplasms ,Glycoproteins ,Hepatology ,biology ,Interleukin-6 ,Liver Neoplasms ,Cell Hypoxia ,Up-Regulation ,Mice, Inbred C57BL ,Tumor progression ,Cancer cell ,biology.protein ,Cancer research ,STAT protein ,Peptides ,medicine.drug - Abstract
Enhanced expression of the cancer stem cell (CSC) marker, CD133, is closely associated with a higher rate of tumor formation and poor prognosis in hepatocellular carcinoma (HCC) patients. Despite its clinical significance, the molecular mechanism underlying the deregulation of CD133 during tumor progression remains to be clarified. Here, we report on a novel mechanism by which interleukin‐6/signal transducer and activator of transcription 3 (IL‐6/STAT3) signaling up‐regulates expression of CD133 and promotes HCC progression. STAT3 activated by IL‐6 rapidly bound to CD133 promoter and increased protein levels of CD133 in HCC cells. Reversely, in hypoxic conditions, RNA interference silencing of STAT3 resulted in decrease of CD133 levels, even in the presence of IL‐6, with a concomitant decrease of hypoxia‐inducible factor 1 alpha (HIF‐1α) expression. Active STAT3 interacted with nuclear factor kappa B (NF‐κB) p65 subunit to positively regulate the transcription of HIF‐1α providing a mechanistic explanation on how those three oncogenes work together to increase the activity of CD133 in a hypoxic liver microenvironment. Activation of STAT3 and its consequent induction of HIF‐1α and CD133 expression were not observed in Toll‐like receptor 4/IL‐6 double‐knockout mice. Long‐term silencing of CD133 by a lentiviral‐based approach inhibited cancer cell‐cycle progression and suppressed in vivo tumorigenicity by down‐regulating expression of cytokinesis‐related genes, such as TACC1, ACF7, and CKAP5. We also found that sorafenib and STAT3 inhibitor nifuroxazide inhibit HCC xenograft formation by blocking activation of STAT3 and expression of CD133 and HIF‐1α proteins. Conclusion: IL‐6/STAT3 signaling induces expression of CD133 through functional cooperation with NF‐κB and HIF‐1α during liver carcinogenesis. Targeting STAT3‐mediated CD133 up‐regulation may represent a novel, effective treatment by eradicating the liver tumor microenvironment. (Hepatology 2015;62:1160‐1173)
- Published
- 2015
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