1.Primed Mesenchymal Stem Cells by IFN-γγ and IL-1β Ameliorate Acute Respiratory Distress Syndrome through Enhancing Homing Effect and Immunomodulation
Taeho KONG ; Su Kyoung SEO ; Yong-Seok HAN ; Woo Min SEO ; Bokyong KIM ; Jieun KIM ; Young-Jae CHO ; Seunghee LEE ; Kyung-Sun KANG
Biomolecules & Therapeutics 2025;33(2):311-324
Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.
2.Primed Mesenchymal Stem Cells by IFN-γγ and IL-1β Ameliorate Acute Respiratory Distress Syndrome through Enhancing Homing Effect and Immunomodulation
Taeho KONG ; Su Kyoung SEO ; Yong-Seok HAN ; Woo Min SEO ; Bokyong KIM ; Jieun KIM ; Young-Jae CHO ; Seunghee LEE ; Kyung-Sun KANG
Biomolecules & Therapeutics 2025;33(2):311-324
Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.
3.Primed Mesenchymal Stem Cells by IFN-γγ and IL-1β Ameliorate Acute Respiratory Distress Syndrome through Enhancing Homing Effect and Immunomodulation
Taeho KONG ; Su Kyoung SEO ; Yong-Seok HAN ; Woo Min SEO ; Bokyong KIM ; Jieun KIM ; Young-Jae CHO ; Seunghee LEE ; Kyung-Sun KANG
Biomolecules & Therapeutics 2025;33(2):311-324
Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.
4.Diagnostic accuracy of preoperative ultrasound in predicting diffuse sclerosing variant papillary thyroid carcinoma: a retrospective diagnostic accuracy study
Buseon KANG ; Hyeong Won YU ; Yoon KONG ; Ja Kyung LEE ; June Young CHOI ; Hee Young NA ; So Yeon PARK ; Min Joo KIM ; Jae Hoon MOON ; Wonjae CHA ; Woo-Jin JEONG ; Won Woo LEE ; Hunjong LIM ; Sang Il CHOI
Annals of Surgical Treatment and Research 2025;109(1):35-43
Purpose:
Diffuse sclerosing variant papillary thyroid carcinoma (DSV-PTC) is a rare and aggressive subtype of PTC.Preoperative diagnosis is challenging owing to the overlapping of imaging characteristics with those of other thyroid conditions. This study aimed to evaluate the accuracy of preoperative ultrasound (US) in predicting DSV-PTC and to identify significant diagnostic factors.
Methods:
This retrospective study analyzed 34 patients who were preoperatively suspected of having DSV-PTC based on US findings and later underwent thyroidectomy. Patients were divided into 2 groups based on the final histopathological diagnosis: DSV-PTC and non-DSV-PTC. Demographic, radiological, and pathological characteristics were also compared.
Results:
Only 32.4% of patients initially suspected of having DSV-PTC were confirmed postoperatively. Among the US features, the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) score 5 was significantly associated with DSV-PTC (P = 0.038), whereas other radiological factors, including echogenicity and microcalcifications, were not. The histopathological features, such as tumor size, BRAF and TERT mutations, vascular invasion, and lymph node metastasis, showed no significant differences between the groups.
Conclusion
Preoperative US has limited accuracy (32.4%) in diagnosing DSV-PTC. Because of the aggressive treatment recommendations based on preoperative suspicion, clinicians should carefully consider the limitations of imaging. Further studies incorporating fine-needle aspiration or core needle biopsy are required to improve diagnostic accuracy.
5.The pathologic and clinical outcomes of risk-reducing salpingo-oophorectomy in asymptomatic carriers of homologous recombination repair gene mutation
Yeon Jee LEE ; Ji Hyu KIM ; Youn Jee KIM ; Yoon Jung CHANG ; Sun-Young KONG ; Chong Woo YOO ; Dong Ock LEE ; Sang-Soo SEO ; Sokbom KANG ; Sang-Yoon PARK ; Myong Cheol CHEOL
Journal of Gynecologic Oncology 2025;36(2):e15-
Objective:
To investigate the prevalence of pathological findings and clinical outcomes of riskreducing salpingo-oophorectomy (RRSO) in asymptomatic carriers with germline homologous recombination repair (HRR) gene pathogenic/likely pathogenic variants (PV/LPV).
Methods:
This retrospective study enrolled asymptomatic carriers with germline HR gene PV/ LPV who underwent RRSO between 2006 and 2022 at the National Cancer Center in Korea.Clinical characteristics, including history of breast cancer, family history of ovarian/breast cancer, parity, and oral contraceptive use, were analyzed.
Results:
Of the 255 women who underwent RRSO, 129 (50.6%) had PV/LPV in BRCA1, 121 (47.5%) in BRCA2, and 2 (0.7%) had both BRCA1 and BRCA2 PV/LPV. In addition, 1 carried PV/ LPV in RAD51D, and 2 in BRIP1. Among the BRCA1/2 PV/LPV carriers, occult neoplasms were identified in 3.5% of patients: serous tubal intraepithelial carcinoma (1.1%, n=3), fallopian tubal cancers (0.8%, n=2), ovarian cancer (1.2%, n=3), and breast cancer (0.4%, n=1). Of the 9 patients with occult neoplasms, 5 (2.0%) were identified from the 178 breast cancer patients, and 4 (1.6%) were detected in 65 healthy mutation carriers. During the median follow-up period of 36.7 months (interquartile range, 25.9–71.4), 1 (0.4%) BRCA1 PV carrier with no precursor lesions at RRSO developed primary peritoneal carcinomatosis after 30.1 months.
Conclusion
Women with HRR gene mutations PV/LPV who undergo RRSO are at a risk of detecting occult neoplasms, with a of 3.5%. Even in the absence of precursor lesions during RRSO, there was a cumulative risk of peritoneal carcinomatosis development, emphasizing the need for continued surveillance.
6.Concomitant Pulmonary and Cranial Abscesses Caused by Streptococcus Gordonii
Jeong-Woo HA ; Kwan-Young SONG ; Min-Ho KONG ; Se-Youn JANG ; Jung-Hee KIM ; Sung-Hoon KIM ; Soon-O HONG
Journal of Neurointensive Care 2025;8(2):57-61
Streptococcus gordonii is an oral commensal viridans streptococcus that rarely causes invasive infections such as lung abscess or intracranial empyema. The sequential presentation of concomitant pulmonary and cranial abscesses by this organism is extremely uncommon. A 70-year-old man presented with progressive dyspnea and fever. Chest CT demonstrated a 14.4 × 6.8cm mass like lung lesion consistent with a lung abscess. Percutaneous drainage yielded Streptococcus gordoniii. On hospital day 5 following drainage, patient presented with scalp swelling and headache. Brain MRI revealed a subgaleal abscess with an epidural empyema. Emergent craniectomy and debridement were performed, and cultures again grew Streptococcus gordonii. This case is a rare but clinically significant pattern of sequential presentation of concomitant pulmonary and cranial abscesses caused by Streptococcus gordonii, emphasizing the need for dental evaluation, meticulous inpatient monitoring, and early neuroimaging when viridans streptococci are revealed from deep infections.
7.Multivariable analysis to identify predictors of dental implant failure after alveolar ridge preservation:a non-interventional observational study
Dae-Young KANG ; Hyeon-Seong AHN ; Jun-Hyeong KONG ; Sangmin KIM ; Sung-Jo LEE ; In-Woo CHO ; Hyun-Seung SHIN ; Leonardo TROMBELLI ; Jung-Chul PARK ; Hyun-Chang LIM
Journal of Periodontal & Implant Science 2025;55(6):447-461
Purpose:
The aim of this study was to determine predictors of implant treatment failure after alveolar ridge preservation (ARP).
Methods:
The study included patients who received implant treatment after ARP between 2014 and 2020. The demographic, clinical, and radiographic data of these patients were collected. Implant success was defined as the absence of pain or tenderness, no mobility, a change of <2 mm in marginal bone level, and no exudation. A Cox proportional hazards model with shared frailty was used to estimate hazard ratios (HRs) for the demographic, clinical, and radiographic factors contributing to implant failure.
Results:
The study included 528 implants from 412 patients. The cumulative success rate over 3.5±1.8 years (mean ± standard deviation) was 89.0% (95% confidence interval [CI], 85.4%–92.8%), with 43 failed implants. The multiple Cox proportional hazards model with shared frailty indicated that a pristine bone engagement (PBE) of <1.1 mm was significantly associated with implant failure (HR, 2.50; 95% CI, 1.34–4.67; P=0.004).
Conclusions
PBE of at least 1.1 mm appears to decrease the probability of implant failure after ARP.
8.Medication-related osteonecrosis of the jaw: an evidence-based 2025position statement from a Korean multidisciplinary task force
Jin-Woo KIM ; Sung-Hye KONG ; Jae-Young KIM ; Mi Kyung KWAK ; Jun-Young KIM ; Ji-Hyeon OH ; Hyung-Youl PARK ; BeomTaek KIM ; Young-Kyun LEE ; Jeong Joon HAN ; Moon-Young KIM ; Yong Jun CHOI ; Yong-Dae KWON ; Kwang-Sup SONG ; Beom-Jun KIM ; Sun-Jong KIM ; Seung-Hoon BAEK ; Dong Ock LEE ; Han Seok CHOI ; Ha Young KIM ; Tae-Geon KWON ;
Journal of the Korean Association of Oral and Maxillofacial Surgeons 2025;51(6):333-353
With a rapidly aging population and increasing use of antiresorptive agents, medication-related osteonecrosis of the jaw (MRONJ) represents a growing clinical challenge worldwide. To address the need for tailored clinical guidance, a multidisciplinary task force was convened. Five Korean academic societies—the Korean Society for Bone and Mineral Research, the Korean Association of Oral and Maxillofacial Surgeons, the Korean Association of Maxillofacial Plastic and Reconstructive Surgeons, the Korean Society of Osteoporosis, and the Korean Endocrine Society—collaborated to develop this position statement. The consensus was formulated through comprehensive reviews of literature, combined with three rounds of formal surveys to consolidate expert opinion on controversial topics. This position paper provides evidence-based clinical guidelines for the prevention, diagnosis, and management of MRONJ tailored to the Korean healthcare environment. The diagnostic criteria affirm the standard definition but add a provision for diagnosis based on clinical or radiographic evidence of necrotic bone, even if the traditional 8-week timeframe has not been met. The committee advocates for retaining Stage 0 in the staging system to emphasize early detection and preventive intervention. Key recommendations include prescriptive, drug-specific guidelines for prophylactic drug holidays (e.g., a 2-month pause for oral bisphosphonates; timing surgery 3-4 months after the last denosumab injection) to minimize MRONJ risk from dental procedures. This statement also provides a clear framework for therapeutic drug holidays in established MRONJ, carefully balancing the need for jaw healing against systemic fracture risk. For treatment, this statement advocates for early and active surgical intervention across all MRONJ stages, supported by evidence of superior long-term outcomes compared to conservative management.This position statement offers a unique, evidence-based Korean clinical practice guideline for managing MRONJ. It is intended to standardize care, reduce clinical confusion, and ultimately improve patient outcomes by providing a clear framework for decision-making.
9.Medication-Related Osteonecrosis of the Jaw: An Evidence-Based 2025 Position Statement from a Korean Multidisciplinary Task Force
Jin-Woo KIM ; Sung-Hye KONG ; Jae-Young KIM ; Mi Kyung KWAK ; Jun-Young KIM ; Ji-Hyeon OH ; Hyung-Youl PARK ; BeomTaek KIM ; Young-Kyun LEE ; Jeong Joon HAN ; Moon-Young KIM ; Yong Jun CHOI ; Yong-Dae KWON ; Kwang-Sup SONG ; Beom-Jun KIM ; Sun-Jong KIM ; Seung-Hoon BAEK ; Dong Ock LEE ; Han Seok CHOI ; Ha Young KIM ; Tae-Geon KWON
Endocrinology and Metabolism 2025;40(6):787-810
With a rapidly aging population and increasing use of antiresorptive agents, medication-related osteonecrosis of the jaw (MRONJ) represents a growing clinical challenge worldwide. To address the need for tailored clinical guidance, a multidisciplinary task force was convened. Five Korean academic societies—the Korean Society for Bone and Mineral Research, the Korean Association of Oral and Maxillofacial Surgeons, the Korean Society of Maxillofacial Plastic and Reconstructive Surgeons, the Korean Osteoporosis Society, and the Korean Endocrine Society—collaborated to develop this position statement. The consensus was formulated through comprehensive reviews of literature, combined with three rounds of formal surveys to consolidate expert opinion on controversial topics. This position paper provides evidence-based clinical guidelines for the prevention, diagnosis, and management of MRONJ tailored to the Korean healthcare environment. The diagnostic criteria affirm the standard definition but add a provision for diagnosis based on clinical or radiographic evidence of necrotic bone, even if the traditional 8-week timeframe has not been met. The committee advocates for retaining stage 0 in the staging system to emphasize early detection and preventive intervention. Key recommendations include prescriptive, drug-specific guidelines for prophylactic drug holidays (e.g., a 2-month pause for oral bisphosphonates; timing surgery 3 to 4 months after the last denosumab injection) to minimize MRONJ risk from dental procedures. This statement also provides a clear framework for therapeutic drug holidays in established MRONJ, carefully balancing the need for jaw healing against systemic fracture risk. For treatment, this statement advocates for early and active surgical intervention across all MRONJ stages, supported by evidence of superior long-term outcomes compared to conservative management. This position statement offers a unique, evidence-based Korean clinical practice guideline for managing MRONJ. It is intended to standardize care, reduce clinical confusion, and ultimately improve patient outcomes by providing a clear framework for decision-making.
10.Clinical Features of Li-Fraumeni Syndrome in Korea
Ran SONG ; Sun-Young KONG ; Wonyoung CHOI ; Eun-Gyeong LEE ; Jaeyeon WOO ; Jai Hong HAN ; Seeyoun LEE ; Han-Sung KANG ; So-Youn JUNG
Cancer Research and Treatment 2024;56(1):334-341
Purpose:
Li-Fraumeni syndrome (LFS) is a hereditary disorder caused by germline mutation in TP53. Owing to the rarity of LFS, data on its clinical features are limited. This study aimed to evaluate the clinical characteristics and prognosis of Korean patients with LFS.
Materials and Methods:
Patients who underwent genetic counseling and confirmed with germline TP53 mutation in the National Cancer Center in Korea between 2011 and 2022 were retrospectively reviewed. Data on family history with pedigree, types of mutation, clinical features, and prognosis were collected.
Results:
Fourteen patients with LFS were included in this study. The median age at diagnosis of the first tumor was 32 years. Missense and nonsense mutations were observed in 13 and one patients, respectively. The repeated mutations were p.Arg273His, p.Ala138Val, and pPro190Leu. The sister with breast cancer harbored the same mutation of p.Ala138Val. Seven patients had multiple primary cancers. Breast cancer was most frequently observed, and other types of tumor included sarcoma, thyroid cancer, pancreatic cancer, brain tumor, adrenocortical carcinoma, ovarian cancer, endometrial cancer, colon cancer, vaginal cancer, skin cancer, and leukemia. The median follow-up period was 51.5 months. Two and four patients showed local recurrence and distant metastasis, respectively. Two patients died of leukemia and pancreatic cancer 3 and 23 months after diagnosis, respectively.
Conclusion
This study provides information on different characteristics of patients with LFS, including types of mutation, types of cancer, and prognostic outcomes. For more appropriate management of these patients, proper genetic screening and multidisciplinary discussion are required.

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