1.Assessment of the Therapeutic Effectiveness of Glutathione-Enhanced Mesenchymal Stem Cells in Rat Models of Chronic Bladder Ischemia-Induced Overactive Bladder and Detrusor Underactivity
Jung Hyun SHIN ; Hwan Yeul YU ; Hyungu KWON ; Hong Duck YUN ; Chae-Min RYU ; Dong-Myung SHIN ; Myung-Soo CHOO
International Journal of Stem Cells 2025;18(1):72-86
Overactive bladder (OAB) and detrusor underactivity (DUA) are representative voiding dysfunctions with a chronic nature and limited treatment modalities, and are ideal targets for stem cell therapy. In the present study, we investigated the therapeutic efficacy of human mesenchymal stem cells (MSCs) with a high antioxidant capacity generated by the Primed Fresh OCT4 (PFO) procedure in chronic bladder ischemia (CBI)-induced OAB and DUA rat models. Sixteen-week-old male Sprague-Dawley rats were divided into three groups (sham, OAB or DUA, and stem cell groups; n=10, respectively).CBI was induced by bilateral iliac arterial injury (OAB, 10 times; DUA, 30 times) followed by a 1.25% cholesterol diet for 8 weeks. Seven weeks after injury, rats in the stem cell and other groups were injected with 1×10 6 PFO-MSCs and phosphate buffer, respectively. One week later, bladder function was analyzed by awake cystometry and bladders were harvested for histological analysis. CBI with a high-fat diet resulted in atrophy of smooth muscle and increased collagen deposits correlating with reduced detrusor contractility in both rat models. Arterial injury 10 and 30 times induced OAB (increased number of non-voiding contractions and shortened micturition interval) and DUA (prolonged micturition interval and increased residual volume), respectively. Injection of PFO-MSCs with the enhanced glutathione dynamics reversed both functional and histological changes; it restored the contractility, micturition interval, residual volume, and muscle layer, with reduced fibrosis. CBI followed by a high-fat diet with varying degrees of arterial injury induced OAB and DUA in rats. In addition, PFO-MSCs alleviated functional and histological changes in both rat models.
2.Assessment of the Therapeutic Effectiveness of Glutathione-Enhanced Mesenchymal Stem Cells in Rat Models of Chronic Bladder Ischemia-Induced Overactive Bladder and Detrusor Underactivity
Jung Hyun SHIN ; Hwan Yeul YU ; Hyungu KWON ; Hong Duck YUN ; Chae-Min RYU ; Dong-Myung SHIN ; Myung-Soo CHOO
International Journal of Stem Cells 2025;18(1):72-86
Overactive bladder (OAB) and detrusor underactivity (DUA) are representative voiding dysfunctions with a chronic nature and limited treatment modalities, and are ideal targets for stem cell therapy. In the present study, we investigated the therapeutic efficacy of human mesenchymal stem cells (MSCs) with a high antioxidant capacity generated by the Primed Fresh OCT4 (PFO) procedure in chronic bladder ischemia (CBI)-induced OAB and DUA rat models. Sixteen-week-old male Sprague-Dawley rats were divided into three groups (sham, OAB or DUA, and stem cell groups; n=10, respectively).CBI was induced by bilateral iliac arterial injury (OAB, 10 times; DUA, 30 times) followed by a 1.25% cholesterol diet for 8 weeks. Seven weeks after injury, rats in the stem cell and other groups were injected with 1×10 6 PFO-MSCs and phosphate buffer, respectively. One week later, bladder function was analyzed by awake cystometry and bladders were harvested for histological analysis. CBI with a high-fat diet resulted in atrophy of smooth muscle and increased collagen deposits correlating with reduced detrusor contractility in both rat models. Arterial injury 10 and 30 times induced OAB (increased number of non-voiding contractions and shortened micturition interval) and DUA (prolonged micturition interval and increased residual volume), respectively. Injection of PFO-MSCs with the enhanced glutathione dynamics reversed both functional and histological changes; it restored the contractility, micturition interval, residual volume, and muscle layer, with reduced fibrosis. CBI followed by a high-fat diet with varying degrees of arterial injury induced OAB and DUA in rats. In addition, PFO-MSCs alleviated functional and histological changes in both rat models.
3.Assessment of the Therapeutic Effectiveness of Glutathione-Enhanced Mesenchymal Stem Cells in Rat Models of Chronic Bladder Ischemia-Induced Overactive Bladder and Detrusor Underactivity
Jung Hyun SHIN ; Hwan Yeul YU ; Hyungu KWON ; Hong Duck YUN ; Chae-Min RYU ; Dong-Myung SHIN ; Myung-Soo CHOO
International Journal of Stem Cells 2025;18(1):72-86
Overactive bladder (OAB) and detrusor underactivity (DUA) are representative voiding dysfunctions with a chronic nature and limited treatment modalities, and are ideal targets for stem cell therapy. In the present study, we investigated the therapeutic efficacy of human mesenchymal stem cells (MSCs) with a high antioxidant capacity generated by the Primed Fresh OCT4 (PFO) procedure in chronic bladder ischemia (CBI)-induced OAB and DUA rat models. Sixteen-week-old male Sprague-Dawley rats were divided into three groups (sham, OAB or DUA, and stem cell groups; n=10, respectively).CBI was induced by bilateral iliac arterial injury (OAB, 10 times; DUA, 30 times) followed by a 1.25% cholesterol diet for 8 weeks. Seven weeks after injury, rats in the stem cell and other groups were injected with 1×10 6 PFO-MSCs and phosphate buffer, respectively. One week later, bladder function was analyzed by awake cystometry and bladders were harvested for histological analysis. CBI with a high-fat diet resulted in atrophy of smooth muscle and increased collagen deposits correlating with reduced detrusor contractility in both rat models. Arterial injury 10 and 30 times induced OAB (increased number of non-voiding contractions and shortened micturition interval) and DUA (prolonged micturition interval and increased residual volume), respectively. Injection of PFO-MSCs with the enhanced glutathione dynamics reversed both functional and histological changes; it restored the contractility, micturition interval, residual volume, and muscle layer, with reduced fibrosis. CBI followed by a high-fat diet with varying degrees of arterial injury induced OAB and DUA in rats. In addition, PFO-MSCs alleviated functional and histological changes in both rat models.
4.Circulating Tumor DNA–Based Genotyping and Monitoring for Predicting Disease Relapses of Patients with Peripheral T-Cell Lymphomas
Seok Jin KIM ; Yeon Jeong KIM ; Sang Eun YOON ; Kyung Ju RYU ; Bon PARK ; Donghyun PARK ; Duck CHO ; Hyun-Young KIM ; Junhun CHO ; Young Hyeh KO ; Woong-Yang PARK ; Won Seog KIM
Cancer Research and Treatment 2023;55(1):291-303
Purpose:
Plasma circulating tumor DNA (ctDNA) could reflect the genetic alterations present in tumor tissues. However, there is little information about the clinical relevance of cell-free DNA genotyping in peripheral T-cell lymphoma (PTCL).
Materials and Methods:
After targeted sequencing plasma cell-free DNA of patients with various subtypes of PTCL (n=94), we analyzed the mutation profiles of plasma ctDNA samples and their predictive value of dynamic ctDNA monitoring for treatment outcomes.
Results:
Plasma ctDNA mutations were detected in 53 patients (56%, 53/94), and the detection rate of somatic mutations was highest in angioimmunoblastic T-cell lymphoma (24/31, 77%) and PTCL, not otherwise specified (18/29, 62.1%). Somatic mutations were detected in 51 of 66 genes that were sequenced, including the following top 10 ranked genes: RHOA, CREBBP, KMT2D, TP53, IDH2, ALK, MEF2B, SOCS1, CARD11, and KRAS. In the longitudinal assessment of ctDNA mutation, the difference in ctDNA mutation volume after treatment showed a significant correlation with disease relapse or progression. Thus, a ≥ 1.5-log decrease in genome equivalent (GE) between baseline and the end of treatment showed a significant association with better survival outcomes than a < 1.5-log decrease in GE.
Conclusion
Our results suggest the clinical relevance of plasma ctDNA analysis in patients with PTCL. However, our findings should be validated by a subsequent study with a larger study population and using a broader gene panel.
5.Diagnostic index for acute eosinophilic pneumonia without bronchoscopy in military smokers
Sunmin PARK ; Deokjae HAN ; Ji Eun LEE ; Duck Hyun RYU ; Hyung-Jun KIM
The Korean Journal of Internal Medicine 2022;37(2):377-386
Background/Aims:
Acute eosinophilic pneumonia (AEP) is common among military smokers; however, bronchoscopy is required for the diagnosis. We aimed to derive and validate a scoring system to diagnose AEP without bronchoscopy.
Methods:
We conducted a retrospective study including patients diagnosed with AEP or any other pneumonia among military smokers hospitalized in the Armed Forces Capital Hospital from 15 November 2016 through 25 December 2019. The patients were divided into derivation and validation groups according to their admission day. Patient symptoms, laboratory findings, and computed tomography findings were candidate variables. Least absolute shrinkage and selection operator (LASSO) regression was used to calculate the scores for each variable.
Results:
Among 414 patients, AEP was confirmed in 54 of 279 patients (19.4%) in the derivation group and in 18 of 135 patients (13.3%) in the validation group. Ten variables were selected using LASSO regression: new-onset or a recently increased smoking (≤ 4 weeks) (8 points), interlobular septal thickening (5 points), absence of sputum (3 points), ground glass opacity (3 points), acute onset (≤ 3 days) (2 points), dyspnea (2 points), chest pain (2 points), leukocytosis (2 points), bronchovascular bundle thickening (2 points), and bilateral involvement (2 points). The area under the receiver-operating characteristic curve of the score to diagnose AEP was 0.997 (95% confidence interval, 0.992 to 1.000) in the derivation group and 0.985 (95% confidence interval, 0.965 to 1.000) in the validation group.
Conclusions
We introduce a scoring system that can distinguish AEP from other types of pneumonia in military smokers without the need for bronchoscopy.
6.Defining the Relationship between Daily Exposure to Particulate Matter and Hospital Visits by Psoriasis Patients
Eun Hye LEE ; Daesick RYU ; Nam-Soo HONG ; Jun Young KIM ; Kyung Duck PARK ; Weon Ju LEE ; Seok-Jong LEE ; Sang-Hyun KIM ; Younghae DO ; Yong Hyun JANG
Annals of Dermatology 2022;34(1):40-45
Background:
Although particulate matter likely provokes inflammatory reactions in those with chronic skin disorders like atopic dermatitis, no study has examined the relationship between particulate matter and psoriasis exacerbation.
Objective:
This study evaluated possible associations between particulate matter and hospital visits for psoriasis patients in 7 major cities in South Korea.
Methods:
We investigated the relationship between psoriasis and particulate matter. To do this, we used psoriasis patient data from the Korean National Health Insurance Service database. In addition, PM 10 and PM 2.5 concentration data spanning a 3-year time frame were obtained from the Korea Environment Corporation.
Results:
A pattern analysis generated by the sample cross-correlation function and time series regression showed a correlation between particulate matter concentration and the number of hospital visits by psoriasis patients. However, the prewhitening method, which minimizes the effects of other variables besides particulate matter, revealed no correlation between the two.
Conclusion
This study suggests that particulate matter has no impact on hospital visit frequency among psoriasis patients in South Korean urban areas.
7.Chairside computer-aided design/computer-aided manufacturing (CAD/ CAM)-based restoration of anterior teeth with customized shade and surface characterization: a report of 2 cases
Hyun-Jung KIM ; Ji-Hyun JANG ; Gil-Joo RYU ; Kyoung-Kyu CHOI ; Duck-Su KIM
Journal of Dental Rehabilitation and Applied Science 2020;36(2):128-137
Over the last 30 years, the use of chairside computer-aided design (CAD) and computer-aided manufacturing (CAM) systems has evolved and has become increasingly popular in dentistry. Although CAD/CAM restorations have been used in the anterior dentition, satisfying the esthetic requirements of clinicians and patients, where the restorations are limited to the chairside, remains a challenge. To reproduce multi-shades of CAD/CAM restorations in the clinic, a preliminary experiment to express several shades on A2 lithium disilicate (LS2) blocks using a staining kit was performed. After measurement of the CIE L*a*b* value of specimens, it was compared with that of the commercial shade guide. This report presents two cases with individual customization of shade and surface characterization of the CAD/CAM restorations using predictable methods based on the preliminary experimental data. The anatomical shape of restoration was obtained from ‘copy and paste technique’ and ‘mirror image acquisition technique’. All treatment procedures and fabrication of restorations performed in this report were executed in the clinic itself.
8.NAMPT enzyme activity regulates catabolic gene expression in gingival fibroblasts during periodontitis.
Ka Hyon PARK ; Duck Kyu KIM ; Yun Hyun HUH ; Gyuseok LEE ; Su Hyeon LEE ; Yunkyung HONG ; Sun Hun KIM ; Min Suk KOOK ; Jeong Tae KOH ; Jang Soo CHUN ; Shee Eun LEE ; Je Hwang RYU
Experimental & Molecular Medicine 2017;49(8):e368-
Periodontal disease is one of the most prevalent chronic disorders worldwide. It is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss. Here, we focused on the role of adipokines, which are locally expressed by periodontal tissues, in the regulation of catabolic gene expression leading to periodontal inflammation. The expression of the nicotinamide phosphoribosyltransferase (NAMPT) adipokine was dramatically increased in inflamed human and mouse gingival tissues. NAMPT expression was also increased in lipopolysaccharide- and proinflammatory cytokine-stimulated primary cultured human gingival fibroblasts (GF). Adenovirus-mediated NAMPT (Ad-Nampt) overexpression upregulated the expression and activity of COX-2, MMP1 and MMP3 in human GF. The upregulation of IL-1β- or Ad-Nampt-induced catabolic factors was significantly abrogated by the intracellular NAMPT (iNAMPT) inhibitor, FK866 or by the sirtuin (SIRT) inhibitor, nicotinamide (NIC). Recombinant NAMPT protein or extracellular NAMPT (eNAMPT) inhibition using a blocking antibody did not alter NAMPT target gene expression levels. Moreover, intragingival Ad-Nampt injection mediated periodontitis-like phenotypes including alveolar bone loss in mice. SIRT2, a part of the SIRT family, was positively associated with NAMPT actions in human GF. Furthermore, in vivo inhibition of the NAMPT-NAD⁺-SIRT axis by NIC injection in mice ameliorated the periodontal inflammation and alveolar bone erosion caused by intragingival injection of Ad-Nampt. Our findings indicate that NAMPT is highly upregulated in human GF, while its enzymatic activity acts as a crucial mediator of periodontal inflammation and alveolar bone destruction via regulation of COX-2, MMP1, and MMP3 levels.
Adipokines
;
Alveolar Bone Loss
;
Animals
;
Fibroblasts*
;
Gene Expression*
;
Gingiva
;
Humans
;
Inflammation
;
Mice
;
Niacinamide
;
Nicotinamide Phosphoribosyltransferase
;
Periodontal Diseases
;
Periodontitis*
;
Phenotype
;
Up-Regulation
9.A Case of Mycobacterium abscessus Lung Disease in a Patient with Cystic Fibrosis.
Ho Jung JEONG ; Jung Hoon KIM ; Duck Hyun RYU ; Ji Eun LEE ; Ji Eun JUN ; Suk Hyeon JEONG ; Won Jung KOH
Korean Journal of Medicine 2015;88(1):74-77
Although cystic fibrosis (CF) is one of the most common hereditary disorders among Caucasians, it is very rare in the Korean population. Patients with CF are at particularly high risk for developing lung disease caused by nontuberculous mycobacteria such as the Mycobacterium avium-intracellulare complex or Mycobacterium abscessus. Here, we report a successfully treated case of M. abscessus lung disease in a Korean patient with CF.
Cystic Fibrosis*
;
Humans
;
Korea
;
Lung Diseases*
;
Mycobacterium avium Complex
;
Mycobacterium*
;
Nontuberculous Mycobacteria
10.Efficacy of Magnesium Trihydrate of Ursodeoxycholic Acid and Chenodeoxycholic Acid for Gallstone Dissolution: A Prospective Multicenter Trial.
Jong Jin HYUN ; Hong Sik LEE ; Chang Duck KIM ; Seok Ho DONG ; Seung Ok LEE ; Ji Kon RYU ; Don Haeng LEE ; Seok JEONG ; Tae Nyeun KIM ; Jin LEE ; Dong Hee KOH ; Eun Taek PARK ; Inseok LEE ; Byung Moo YOO ; Jin Hong KIM
Gut and Liver 2015;9(4):547-555
BACKGROUND/AIMS: Cholecystectomy is necessary for the treatment of symptomatic or complicated gallbladder (GB) stones, but oral litholysis with bile acids is an attractive alternative therapeutic option for asymptomatic or mildly symptomatic patients. This study was conducted to evaluate the efficacy of magnesium trihydrate of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on gallstone dissolution and to investigate improvements in gallstone-related symptoms. METHODS: A prospective, multicenter, phase 4 clinical study to determine the efficacy of orally administered magnesium trihydrate of UDCA and CDCA was performed from January 2011 to June 2013. The inclusion criteria were GB stone diameter < or =15 mm, GB ejection fraction > or =50%, radiolucency on plain X-ray, and asymptomatic/mildly symptomatic patients. The patients were prescribed one capsule of magnesium trihydrate of UDCA and CDCA at breakfast and two capsules at bedtime for 6 months. The dissolution rate, response rate, and change in symptom score were evaluated. RESULTS: A total of 237 subjects were enrolled, and 195 subjects completed the treatment. The dissolution rate was 45.1% and the response rate was 47.2% (92/195) after 6 months of administration of magnesium trihydrate of UDCA and CDCA. Only the stone diameter was significantly associated with the response rate. Both the symptom score and the number of patients with symptoms significantly decreased regardless of stone dissolution. Adverse events necessitating discontinuation of the drug, surgery, or endoscopic management occurred in 2.5% (6/237) of patients. CONCLUSIONS: Magnesium trihydrate of UDCA and CDCA is a well-tolerated bile acid that showed similar efficacy for gallstone dissolution and improvement of gallstone-related symptoms as that shown in previous studies.
Adult
;
Aged
;
Antacids/*administration & dosage
;
Chenodeoxycholic Acid/*administration & dosage
;
Cholagogues and Choleretics/*administration & dosage
;
Drug Administration Schedule
;
Drug Combinations
;
Female
;
Gallstones/*drug therapy
;
Humans
;
Magnesium Hydroxide/*administration & dosage
;
Male
;
Middle Aged
;
Prospective Studies
;
Severity of Illness Index
;
Solubility/drug effects
;
Ursodeoxycholic Acid/*administration & dosage

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