1.A novel IRAK4/PIM1 inhibitor ameliorates rheumatoid arthritis and lymphoid malignancy by blocking the TLR/MYD88-mediated NF-κB pathway.
Sae-Bom YOON ; Hyowon HONG ; Hee-Jong LIM ; Ji Hye CHOI ; Yoon Pyo CHOI ; Seong Wook SEO ; Hyuk Woo LEE ; Chong Hak CHAE ; Woo-Kyu PARK ; Hyun Young KIM ; Daeyoung JEONG ; Tran Quang DE ; Chang-Seon MYUNG ; Heeyeong CHO
Acta Pharmaceutica Sinica B 2023;13(3):1093-1109
Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.
2.Acute Paraplegia After Lumbar Steroid Injection in Patients With Spinal Dural Arteriovenous Fistulas: Case Reports.
Sunwoong KIM ; Yuseong CHOI ; Jinyoung PARK ; Duk Hyun SUNG
Annals of Rehabilitation Medicine 2016;40(5):949-954
Spinal dural arteriovenous fistulas (SDAVFs) are the most common type of spinal vascular malformations. However, SDAVFs are still underdiagnosed entities because their clinical symptoms are usually non-specific, as they include low back pain or radiating pain to the limb. There have been several reports of acute paraplegia after lumbar epidural steroid injections in patients with SDAVFs. We present 4 patients with SDAVFs who received lumbar steroid injection. Among the 4 cases, acute paraplegia developed in 2 cases that received a larger volume of injectate than the other cases. Thus, we are suggesting that the volume of injectate may be a contributing factor for acute paraplegia after lumbar steroid injection in patients with SDAVFs.
Arteriovenous Fistula
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Central Nervous System Vascular Malformations*
;
Extremities
;
Humans
;
Low Back Pain
;
Paraplegia*
;
Spine
;
Steroids
;
Vascular Malformations
3.GSnet: An Integrated Tool for Gene Set Analysis and Visualization.
Yoon Jeong CHOI ; Hyun Goo WOO ; Ungsik YU
Genomics & Informatics 2007;5(3):133-136
The Gene Set network viewer (GSnet) visualizes the functional enrichment of a given gene set with a protein interaction network and is implemented as a plug-in for the Cytoscape platform. The functional enrichment of a given gene set is calculated using a hypergeometric test based on the Gene Ontology annotation. The protein interaction network is estimated using public data. Set operations allow a complex protein interaction network to be decomposed into a functionally-enriched module of interest. GSnet provides a new framework for gene set analysis by integrating a priori knowledge of a biological network with functional enrichment analysis.
Gene Ontology
;
Microarray Analysis
;
Protein Interaction Maps
4.Correlation between the Severity of Female Urinary Incontinence and Concomitant Morbidities: A Multi-Center Cross-Sectional Clinical Study.
Ji Seon KIM ; Suhn Yeop KIM ; Duck Won OH ; Jong Duk CHOI
International Neurourology Journal 2010;14(4):220-226
PURPOSE: The aim of this study was to identify the relationship between urinary incontinence (UI) and low back pain (LBP) discomfort and disability, static balance, and demographic factors. METHODS: A total of 348 women aged 20-80 years were included in this cross-sectional study. The general characteristics of the subjects and the main outcome (UI condition, LBP discomfort, LBP disability, and static balance ability) were assessed by using clinical questionnaires and assessment tools. RESULTS: Of all the subjects, 22.8% had experienced UI. Women with UI showed a significantly higher relationship of LBP and disability, and static balance ability (P<0.01). We found a significant correlation between UI, age, LBP and disability, and static balance ability (P<0.01). CONCLUSIONS: These findings suggest that UI correlates negatively with LBP discomfort, LBP disability, and static balance ability. Further studies should focus on the identification of the precise mechanisms underlying UI and its related physical symptoms and on the development of therapeutic strategies to manage this condition.
Aged
;
Cross-Sectional Studies
;
Female
;
Humans
;
Low Back Pain
;
Urinary Incontinence
5.Analysis of relationship between cracked tooth syndrome and occlusion using Q-ray and T-scan
Do-Gwan AHN ; Jin-Woo CHOI ; Yuseong KIM ; Se-Wook PYO ; Hee-Kyung KIM
The Journal of Korean Academy of Prosthodontics 2021;59(3):271-280
Purpose:
The aim of this study was to evaluate the relationship between the patient's occlusion and a cracked tooth by using T-scan occlusal analysis and a quantitative light-induced fluorescence (QLF) technology.
Materials and Methods:
This study was carried out on 51 patients having cracked teeth between January, 2019 and December, 2020. The tooth crack was determined with a Q-ray pen and QLF parameters (ΔFmax and ΔRmax) were obtained by a Q-ray software. T-scan tests were conducted to all subjects and then, the occlusal force and disclosing time were analyzed. Mann-Whitney U test was performed to compare the occlusal force and disclosing time between cracked teeth groups and contra-lateral normal teeth groups (α = .05). Mann-Whitney U test was performed to compare ΔFmax and ΔRmax according to the results of cold/bite tests (α = .05). A Spearman correlation analysis was run to determine the relationship between ΔFmax or ΔRmax and occlusal force or disclosing time (α=.05).
Results:
The mean occlusal force and disclosing time were significantly higher on cracked teeth than on normal teeth (P < .05). The ΔFmax or ΔRmax were not significantly different according to the results of cold/bite tests (P > .05). There was no correlation between ΔFmax or ΔRmax and occlusal force or disclosing time (P > .05).
Conclusion
There was a significant relationship between occlusion and cracked tooth syndrome. QLF has the potential to be a valuable tool for the diagnosis of tooth crack in clinical practice.
6.Analysis of relationship between cracked tooth syndrome and occlusion using Q-ray and T-scan
Do-Gwan AHN ; Jin-Woo CHOI ; Yuseong KIM ; Se-Wook PYO ; Hee-Kyung KIM
The Journal of Korean Academy of Prosthodontics 2021;59(3):271-280
Purpose:
The aim of this study was to evaluate the relationship between the patient's occlusion and a cracked tooth by using T-scan occlusal analysis and a quantitative light-induced fluorescence (QLF) technology.
Materials and Methods:
This study was carried out on 51 patients having cracked teeth between January, 2019 and December, 2020. The tooth crack was determined with a Q-ray pen and QLF parameters (ΔFmax and ΔRmax) were obtained by a Q-ray software. T-scan tests were conducted to all subjects and then, the occlusal force and disclosing time were analyzed. Mann-Whitney U test was performed to compare the occlusal force and disclosing time between cracked teeth groups and contra-lateral normal teeth groups (α = .05). Mann-Whitney U test was performed to compare ΔFmax and ΔRmax according to the results of cold/bite tests (α = .05). A Spearman correlation analysis was run to determine the relationship between ΔFmax or ΔRmax and occlusal force or disclosing time (α=.05).
Results:
The mean occlusal force and disclosing time were significantly higher on cracked teeth than on normal teeth (P < .05). The ΔFmax or ΔRmax were not significantly different according to the results of cold/bite tests (P > .05). There was no correlation between ΔFmax or ΔRmax and occlusal force or disclosing time (P > .05).
Conclusion
There was a significant relationship between occlusion and cracked tooth syndrome. QLF has the potential to be a valuable tool for the diagnosis of tooth crack in clinical practice.
7.Reliability, Validity, and Responsiveness of the Korean Version of the Shoulder Disability Questionnaire and Shoulder Rating Questionnaire.
Yuseong CHOI ; Jong Wook PARK ; Sujin NOH ; Min Su KIM ; Yun Hee PARK ; Duk Hyun SUNG
Annals of Rehabilitation Medicine 2015;39(5):705-717
OBJECTIVE: To translate, adapt, and test the reliability, validity, and responsiveness of the Korean version of the Shoulder Disability Questionnaire (SDQ) and the Shoulder Rating Questionnaire (SRQ). METHODS: The international guideline for the adaptation of questionnaires was referenced for the translation and adaptation of the original SDQ and SRQ. Correlations of the SDQ-K and SRQ-K with the Shoulder Pain and Disability Index (SPADI) and the Numeric Rating Scale (NRS) were assessed to determine the reliability and validity of the questionnaires. To evaluate reliability, surveys were performed at baseline and a mean of 6 days later in 29 subjects who did not undergo any treatment for shoulder problems. To evaluate responsiveness, assessments were performed at baseline with 4-week intervals in 23 subjects with adhesive capsulitis who were administered triamcinolone injection into the glenohumeral joint. RESULTS: Fifty-two subjects with shoulder-related problems were surveyed. Cronbach alpha for internal consistency was 0.82 for the summary SDQ-K and 0.75 for the summary SRQ-K. The test-retest reliability of the SDQ-K, SRQ-K, and domains of the SRQ-K ranged from 0.84 to 0.95. The SDQ-K and SRQ-K summary scores correlated well with the SPADI and NRS summary scores. Generally, the effect sizes and standardized response means of the summary scores of the SDQ-K, SRQ-K, and domains of the SRQ-K were large, reflecting their responsiveness to clinical changes after treatment. CONCLUSION: The reliability, validity, and responsiveness of the SDQ-K and SRQ-K were excellent. The SDQ-K and SRQ-K are feasible for Korean patients with shoulder pain or disability.
Bursitis
;
Disability Evaluation
;
Humans
;
Reproducibility of Results
;
Shoulder Joint
;
Shoulder Pain
;
Shoulder*
;
Translations
;
Triamcinolone
8.A Case of Primary Aortoenteric Fistula Mimicking Ulcer Bleeding.
Jae Su KIM ; Joung Ho HAN ; Min Ho KANG ; Young Rak CHOI ; Hee Bok CHAE ; Seon Mee PARK ; Sei Jin YOUN
The Korean Journal of Gastroenterology 2013;61(6):343-346
Primary aortoenteric fistula (PAEF) is a rare disease with a high mortality rate due to massive hemorrhaging and diagnostic difficulties. Although hemorrhagic regions can be identified by endoscopy, it is difficult to diagnose PAEF by this method. If PAEF is suspected, endoscopic procedure should be terminated and abdominal CT should be performed. Overlooking the herald bleeding of PAEF can lead to massive bleeding and death. An 85-year-old previously healthy male presented with a complaint of melena. Gastrointestinal endoscopy identified a hemorrhagic site in the third portion of the duodenum and endoscopic hemostasis was performed. However, during the procedure, it became apparent that the hemorrhage was probably not the result of a simple duodenal ulceration and abdominal CT was performed immediately. An aortic aneurysm connected to the duodenum was identified, confirming the diagnosis of PAEF. However, the patient died of massive hemorrhaging before an operation could be performed.
Aged, 80 and over
;
Aortic Aneurysm, Abdominal/*diagnosis/pathology
;
Diagnosis, Differential
;
Endoscopy, Gastrointestinal
;
Fibrin Tissue Adhesive/therapeutic use
;
Fistula/*diagnosis/pathology
;
Gastrointestinal Hemorrhage/diagnosis/therapy
;
Humans
;
Male
;
Tomography, X-Ray Computed
9.Prediction of itching diagnostic marker through RNA sequencing of contact hypersensitivity and skin scratching stimulation mice models.
Young Won KIM ; Tong ZHOU ; Eun A KO ; Seongtae KIM ; Donghee LEE ; Yelim SEO ; Nahee KWON ; Taeyeon CHOI ; Heejung LIM ; Sungvin CHO ; Gwanhui BAE ; Yuseong HWANG ; Dojin KIM ; Hyewon PARK ; Minjae LEE ; Eunkyung JANG ; Jeongyoon CHOI ; Hyemi BAE ; Inja LIM ; Hyoweon BANG ; Jae Hong KO
The Korean Journal of Physiology and Pharmacology 2019;23(2):151-159
Pruritus (itching) is classically defined as an unpleasant cutaneous sensation that leads to scratching behavior. Although the scientific criteria of classification for pruritic diseases are not clear, it can be divided as acute or chronic by duration of symptoms. In this study, we investigated whether skin injury caused by chemical (contact hypersensitivity, CHS) or physical (skin-scratching stimulation, SSS) stimuli causes initial pruritus and analyzed gene expression profiles systemically to determine how changes in skin gene expression in the affected area are related to itching. In both CHS and SSS, we ranked the Gene Ontology Biological Process terms that are generally associated with changes. The factors associated with upregulation were keratinization, inflammatory response and neutrophil chemotaxis. The Kyoto Encyclopedia of Genes and Genomes pathway shows the difference of immune system, cell growth and death, signaling molecules and interactions, and signal transduction pathways. Il1a , Il1b and Il22 were upregulated in the CHS, and Tnf, Tnfrsf1b, Il1b, Il1r1 and Il6 were upregulated in the SSS. Trpc1 channel genes were observed in representative itching-related candidate genes. By comparing and analyzing RNA-sequencing data obtained from the skin tissue of each animal model in these characteristic stages, it is possible to find useful diagnostic markers for the treatment of itching, to diagnose itching causes and to apply customized treatment.
Animals
;
Biological Processes
;
Chemotaxis
;
Classification
;
Cytokines
;
Dermatitis, Contact*
;
Gene Expression
;
Gene Ontology
;
Genome
;
Hypersensitivity
;
Immune System
;
Interleukin-6
;
Mice*
;
Models, Animal
;
Neutrophils
;
Pruritus*
;
RNA*
;
Sensation
;
Sequence Analysis, RNA*
;
Signal Transduction
;
Skin*
;
Transcriptome
;
Transient Receptor Potential Channels
;
Up-Regulation
;
Wound Healing