1.The Effect of Nerve Growth Factor on Cartilage Fibrosis and Hypertrophy during In Vitro Chondrogenesis Using Induced Pluripotent Stem Cells
Se In JUNG ; Si Hwa CHOI ; Jang-Woon KIM ; Jooyoung LIM ; Yeri Alice RIM ; Ji Hyeon JU
International Journal of Stem Cells 2025;18(1):59-71
Nerve growth factor (NGF) is a neurotrophic factor usually involved in the survival, differentiation, and growth of sensory neurons and nociceptive function. Yet, it has been suggested to play a role in the pathogenesis of osteoarthritis (OA). Previous studies suggested a possible relationship between NGF and OA; however, the underlying mechanisms remain unknown. Therefore, we investigated the impact of NGF in chondrogenesis using human induced pluripotent stem cells (hiPSCs)-derived chondrogenic pellets. To investigate how NGF affects the cartilage tissue, hiPSC-derived chondrogenic pellets were treated with NGF on day 3 of differentiation, expression of chondrogenic, hypertrophic, and fibrotic markers was confirmed. Also, inflammatory cytokine arrays were performed using the culture medium of the NGF treated chondrogenic pellets. As a result, NGF treatment decreased the expression of pro-chondrogenic markers by approximately 2∼4 times, and hypertrophic (pro-osteogenic) markers and fibrotic markers were increased by approximately 3-fold or more in the NGF-treated cartilaginous pellets. In addition, angiogenesis was upregulated by approximately 4-fold or more, bone formation by more than 2-fold, and matrix metalloproteinase induction by more than 2-fold. These inflammatory cytokine array were using the NGF-treated chondrogenic pellet cultured medium.Furthermore, it was confirmed by Western blot to be related to the induction of the glycogen synthase kinase-3 beta (GSK3β) pathway by NGF. In Conclusions, these findings provide valuable insights into the multifaceted role of NGF in cartilage hypertrophy and fibrosis, which might play a critical role in OA progression.
2.The Effect of Nerve Growth Factor on Cartilage Fibrosis and Hypertrophy during In Vitro Chondrogenesis Using Induced Pluripotent Stem Cells
Se In JUNG ; Si Hwa CHOI ; Jang-Woon KIM ; Jooyoung LIM ; Yeri Alice RIM ; Ji Hyeon JU
International Journal of Stem Cells 2025;18(1):59-71
Nerve growth factor (NGF) is a neurotrophic factor usually involved in the survival, differentiation, and growth of sensory neurons and nociceptive function. Yet, it has been suggested to play a role in the pathogenesis of osteoarthritis (OA). Previous studies suggested a possible relationship between NGF and OA; however, the underlying mechanisms remain unknown. Therefore, we investigated the impact of NGF in chondrogenesis using human induced pluripotent stem cells (hiPSCs)-derived chondrogenic pellets. To investigate how NGF affects the cartilage tissue, hiPSC-derived chondrogenic pellets were treated with NGF on day 3 of differentiation, expression of chondrogenic, hypertrophic, and fibrotic markers was confirmed. Also, inflammatory cytokine arrays were performed using the culture medium of the NGF treated chondrogenic pellets. As a result, NGF treatment decreased the expression of pro-chondrogenic markers by approximately 2∼4 times, and hypertrophic (pro-osteogenic) markers and fibrotic markers were increased by approximately 3-fold or more in the NGF-treated cartilaginous pellets. In addition, angiogenesis was upregulated by approximately 4-fold or more, bone formation by more than 2-fold, and matrix metalloproteinase induction by more than 2-fold. These inflammatory cytokine array were using the NGF-treated chondrogenic pellet cultured medium.Furthermore, it was confirmed by Western blot to be related to the induction of the glycogen synthase kinase-3 beta (GSK3β) pathway by NGF. In Conclusions, these findings provide valuable insights into the multifaceted role of NGF in cartilage hypertrophy and fibrosis, which might play a critical role in OA progression.
3.The Effect of Nerve Growth Factor on Cartilage Fibrosis and Hypertrophy during In Vitro Chondrogenesis Using Induced Pluripotent Stem Cells
Se In JUNG ; Si Hwa CHOI ; Jang-Woon KIM ; Jooyoung LIM ; Yeri Alice RIM ; Ji Hyeon JU
International Journal of Stem Cells 2025;18(1):59-71
Nerve growth factor (NGF) is a neurotrophic factor usually involved in the survival, differentiation, and growth of sensory neurons and nociceptive function. Yet, it has been suggested to play a role in the pathogenesis of osteoarthritis (OA). Previous studies suggested a possible relationship between NGF and OA; however, the underlying mechanisms remain unknown. Therefore, we investigated the impact of NGF in chondrogenesis using human induced pluripotent stem cells (hiPSCs)-derived chondrogenic pellets. To investigate how NGF affects the cartilage tissue, hiPSC-derived chondrogenic pellets were treated with NGF on day 3 of differentiation, expression of chondrogenic, hypertrophic, and fibrotic markers was confirmed. Also, inflammatory cytokine arrays were performed using the culture medium of the NGF treated chondrogenic pellets. As a result, NGF treatment decreased the expression of pro-chondrogenic markers by approximately 2∼4 times, and hypertrophic (pro-osteogenic) markers and fibrotic markers were increased by approximately 3-fold or more in the NGF-treated cartilaginous pellets. In addition, angiogenesis was upregulated by approximately 4-fold or more, bone formation by more than 2-fold, and matrix metalloproteinase induction by more than 2-fold. These inflammatory cytokine array were using the NGF-treated chondrogenic pellet cultured medium.Furthermore, it was confirmed by Western blot to be related to the induction of the glycogen synthase kinase-3 beta (GSK3β) pathway by NGF. In Conclusions, these findings provide valuable insights into the multifaceted role of NGF in cartilage hypertrophy and fibrosis, which might play a critical role in OA progression.
4.Newly Developed Sex-Specific Z Score Model for Coronary Artery Diameter in a Pediatric Population
Jeong Jin YU ; Hee Joung CHOI ; Hwa Jin CHO ; Sung Hye KIM ; Eun Jung CHEON ; Gi Beom KIM ; Lucy Youngmin EUN ; Se Yong JUNG ; Hyun Ok JUN ; Hyang-Ok WOO ; Sin-Ae PARK ; Soyoung YOON ; Hoon KO ; Ji-Eun BAN ; Jong-Woon CHOI ; Min Seob SONG ; Ji Whan HAN
Journal of Korean Medical Science 2024;39(16):e144-
Background:
This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice.
Methods:
This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit.
Results:
Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula.
Conclusion
A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.
5.Lower Atrial Fibrillation Risk With Sodium-Glucose Cotransporter 2Inhibitors Than With Dipeptidyl Peptidase-4 Inhibitors in Individuals With Type 2 Diabetes: A Nationwide Cohort Study
Min KIM ; Kyoung Hwa HA ; Junyoung LEE ; Sangshin PARK ; Kyeong Seok OH ; Dae-Hwan BAE ; Ju Hee LEE ; Sang Min KIM ; Woong Gil CHOI ; Kyung-Kuk HWANG ; Dong-Woon KIM ; Myeong-Chan CHO ; Dae Jung KIM ; Jang-Whan BAE
Korean Circulation Journal 2024;54(5):256-267
Background and Objectives:
Accumulating evidence shows that sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce adverse cardiovascular outcomes. However, whether SGLT2i, compared with other antidiabetic drugs, reduce the new development of atrial fibrillation (AF) is unclear. In this study, we compared SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4is) in terms of reduction in the risk of AF in individuals with type 2 diabetes.
Methods:
We included 42,786 propensity score-matched pairs of SGLT2i and DPP-4i users without previous AF diagnosis using the Korean National Health Insurance Service database between May 1, 2016, and December 31, 2018.
Results:
During a median follow-up of 1.3 years, SGLT2i users had a lower incidence of AF than DPP-4i users (1.95 vs. 2.65 per 1,000 person-years; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55–0.97; p=0.028]). In individuals without heart failure, SGLT2i users was associated with a decreased risk of AF incidence (HR, 0.70; 95% CI, 0.52–0.94; p=0.019) compared to DPP-4i users. However, individuals with heart failure, SGLT2i users was not significantly associated with a change in risk (HR, 1.04; 95% CI, 0.44–2.44; p=0.936).
Conclusions
In this nationwide cohort study of individuals with type 2 diabetes, treatment with SGLT2i was associated with a lower risk of AF compared with treatment with DPP-4i.
6.Efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for hepatitis C in Korea: a Phase 3b study
Jeong HEO ; Yoon Jun KIM ; Sung Wook LEE ; Youn-Jae LEE ; Ki Tae YOON ; Kwan Soo BYUN ; Yong Jin JUNG ; Won Young TAK ; Sook-Hyang JEONG ; Kyung Min KWON ; Vithika SURI ; Peiwen WU ; Byoung Kuk JANG ; Byung Seok LEE ; Ju-Yeon CHO ; Jeong Won JANG ; Soo Hyun YANG ; Seung Woon PAIK ; Hyung Joon KIM ; Jung Hyun KWON ; Neung Hwa PARK ; Ju Hyun KIM ; In Hee KIM ; Sang Hoon AHN ; Young-Suk LIM
The Korean Journal of Internal Medicine 2023;38(4):504-513
Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.
7.Change in Severity and Clinical Manifestation of MIS-C Over SARSCoV-2 Variant Outbreaks in Korea
Young June CHOE ; Eun Hwa CHOI ; Jong Woon CHOI ; Byung Wook EUN ; Lucy Youngmin EUN ; Yae-Jean KIM ; Yeo Hyang KIM ; Young A KIM ; Yun-Kyung KIM ; Ji Hee KWAK ; Hyukmin LEE ; June Dong PARK ; Yeon Haw JUNG ; Jin GWACK ; Sangwon LEE ;
Journal of Korean Medical Science 2023;38(30):e225-
Background:
There is difference in the incidence of multi-system inflammatory syndrome in children (MIS-C) in patients with different variants of severe acute respiratory syndrome coronavirus 2, however, little is known about the epidemiology in Asian countries. We investigated and compared the epidemiology of the MIS-C during omicron-dominant period with that of previous periods in South Korea.
Methods:
We obtained clinical, epidemiological and laboratory data on MIS-C cases from national MIS-C surveillance in South Korea. We defined pre-delta period as January 2020–May 2021; delta period as June 2021–December 2021; and omicron period as January 2022–April 2022. We describe the clinical characteristics and outcomes of MIS-C patients by period.
Results:
A total of 91 cases were assessed to be MIS-C cases. Number of MIS-C cases have increased from six cases during pre-delta period to 66 cases during omicron period, while the incidence rate (the number of MIS-C cases per 100,000 cases of reported coronavirus disease 2019) has decreased from 38.5 cases per 100,000 (95% confidence interval [CI], 14.1–83.9) during pre-delta period to 1.6 cases per 100,000 (95% CI, 1.2–2.0) during omicron periods. During pre-delta period, 66.7% and 100% had hypotension and gastrointestinal involvement, respectively; while during omicron period, 12.1% and 6.1% had such clinical manifestations. Fifty percent of pre-delta MIS-C patients were taken intensive care unit (ICU) cares, while 10.6% of patients during omicron periods were in ICUs.
Conclusion
Omicron period were associated with less severe clinical manifestation compared to pre-delta and delta periods. Although incidence rate of MIS-C was lower for the omicron period than pre-delta and delta periods, number of patients reported with MIS-C may pose a substantial clinical burden.
8.Expert opinion: The clinical usefulness of skin tests prior to the administration of beta-lactam antibiotics
Sung-Ryeol KIM ; Sujeong KIM ; Sae-Hoon KIM ; Jong-Sook PARK ; Hye Jung PARK ; Dong In SUH ; Da Woon SIM ; Min Suk YANG ; Jae-Hyun LEE ; Hwa Young LEE ; Jae-Woo JUNG ; Mira CHOI ; Hye-Ryun KANG ;
Allergy, Asthma & Respiratory Disease 2022;10(1):3-8
An allergy skin test is used to diagnose certain allergies by identifying sensitized allergens. In other words, it is a test for patients who are already sensitized to certain allergens. Because of the prevailing perception that beta-lactam allergy can be dangerous and potentially lethal, the intradermal test has long been routinely performed before use to screen beta-lactam allergy in Korea. The prevalence of penicillin allergy is estimated to be 1% to 2%. However, only 14% of the subjects with perceived penicillin allergy is considered to have true penicillin allergy. Moreover, it is difficult to justify performing a skin test on subjects who are very unlikely to be sensitized to beta-lactam, such as those who never used beta-lactam or never experienced allergy after previous use of beta-lactam.Therefore, allergists recommend beta-lactam skin testing in those who have allergy after the use of beta-lactam. Nevertheless, many hospitals in Korea are conducting routine skin tests on patients regardless of a history of beta-lactam allergy, which are not clinically validated but consume considerable human and material resources. False-positive results can consequently result in inappropriate labeling of beta-lactam allergy, leading to the unnecessary restriction of medication prescriptions and the increase in medical expenses. Herein, the drug allergy working group affiliated with the Korean Academy of Asthma, Allergy, and Clinical Immunology announces an expert opinion on the preuse beta-lactam skin test for subjects without a history of beta-lactam allergy based on the objective evidence from the literature and clinical relevance.
9.Fat Graft with Allograft Adipose Matrix and Magnesium Hydroxide-Incorporated PLGA Microspheres for Effective Soft Tissue Reconstruction
Dae-Hee KIM ; Da-Seul KIM ; Hyun-Jeong HA ; Ji-Won JUNG ; Seung-Woon BAEK ; Seung Hwa BAEK ; Tae-Hyung KIM ; Jung Chan LEE ; Euna HWANG ; Dong Keun HAN
Tissue Engineering and Regenerative Medicine 2022;19(3):553-563
BACKGROUND:
Autologous fat grafting is one of the most common procedures used in plastic surgery to correct soft tissue deficiency or depression deformity. However, its clinical outcomes are often suboptimal, and lack of metabolic and architectural support at recipient sites affect fat survival leading to complications such as cyst formation, calcification.Extracellular matrix-based scaffolds, such as allograft adipose matrix (AAM) and poly(lactic-co-glycolic) acid (PLGA), have shown exceptional clinical promise as regenerative scaffolds. Magnesium hydroxide (MH), an alkaline ceramic, has attracted attention as a potential additive to improve biocompatibility. We attempted to combine fat graft with regenerative scaffolds and analyzed the changes and viability of injected fat graft in relation to the effects of injectable natural, and synthetic (PLGA/MH microsphere) biomaterials.
METHODS:
In vitro cell cytotoxicity, angiogenesis of the scaffolds, and wound healing were evaluated using human dermal fibroblast cells. Subcutaneous soft-tissue integration of harvested fat tissue was investigated in vivo in nude mouse with random fat transfer protocol Fat integrity and angiogenesis were identified by qRT-PCR and immunohistochemistry.
RESULTS:
In vitro cell cytotoxicity was not observed both in AAM and PLGA/MH with human dermal fibroblast.PLGA/MH and AAM showed excellent wound healing effect. in vivo, the AAM and PLGA/MH retained volume compared to that in the only fat group. And the PLGA/MH showed the highest angiogenesis and anti-inflammation.
CONCLUSION
In this study, a comparison of the volume retention effect and angiogenic ability between autologous fat grafting, injectable natural, and synthetic biomaterials will provide a reasonable basis for fat grafting.
10.Neurologic Prognostication by QEEG in Post Cardiac Arrest Patients with Therapeutic Hypothermia
Sue Hyun LEE ; Hyung Seok AHN ; Yong Hwan KIM ; Hyang Woon LEE ; Jung Hwa LEE
Journal of the Korean Neurological Association 2020;38(4):260-271
Background:
Post-cardiac arrest syndrome (PCAS) is one of the critical conditions which can result in a more serious brain injury. Early and accurate prognostication is crucial for deciding the patient’s therapeutic plan and setting the treatment goal. This study aimed to establish the prognostication values of quantitative electroencephalography (QEEG) in PCAS patients.
Methods:
We recruited 183 PCAS patients treated with therapeutic hypothermia. Electroencephalography (EEG) data within 72 hours after cardiac arrest (CA) and clinical data were collected. QEEG analysis including power spectral density (PSD) and connectivity analysis of default mode network (DMN) with imaginary coherence were performed.
Results:
There were significantly different patterns of PSD between neurologic good and poor outcome groups; absolute and relative power of the alpha 2 and beta 1 frequency (10-15 Hz) bands were increased in all brain regions of good outcome group. However, the relative power of the delta band and higher frequency bands over fast alpha (beta 3 and gamma bands over 20 Hz) were poor outcome markers. We found out that connectivity of DMN were significantly decreased in the poor outcome group compared with the good outcome group.
Conclusions
These findings suggest that QEEG analysis could quantify and automate the interpretation of EEG. Furthermore, they can improve the prognostic values for neurologic outcomes relatively accurately and objectively in PCAS patients treated with hypothermia compared with traditional visual grading.

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