1.Comparative Transcriptomic Profiling of Mesenchymal Stem Cells from Distinct Tissue Origins and Isolation Methods Highlights the Stability and Immunomodulatory Signature of Umbilical Cord-Derived Smumf Cells
Min Ji LEE ; Kyungtaek PARK ; Sungho WON ; Chris Hyunchul JO
Tissue Engineering and Regenerative Medicine 2026;23(1):157-173
BACKGROUND:
Mesenchymal stem cells (MSCs) derived from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) exhibit therapeutic potential in regenerative medicine. However, their properties, including transcriptomic profiles, vary based on tissue origin, passage stage, and isolation method, complicating their clinical standardization.Addressing these unresolved differences requires comprehensive approaches, such as RNA sequencing, to analyze transcriptomic profiles in detail.
METHODS:
In this study, RNA-seq was employed to analyze MSC transcriptomes from BM, AD, and UC tissues. UC MSCs were isolated using enzymatic digestion or the Minimal Cube Explant (MCE) method (smumf cells), and transcriptomes of early (P3–4) and late (P10) passages of smumf cells were compared. Differentially expressed genes (DEGs) were identified, followed by transcription factor (TF) and pathway analyses.
RESULTS:
Fetal MSCs (UC and smumf cells) exhibited distinct transcriptomic profiles compared to adult MSCs (BM and AD), with 2,208 upregulated and 2,594 downregulated DEGs. Key transcription factors, such as E2F1 and NF-jB1, and pathways, including glycolysis, cholesterol biosynthesis, and TNF-a signaling, were enriched in fetal MSCs. smumf cells demonstrated transcriptomic stability between early and late passages, with only 12 DEGs identified. Additionally, smumf cells showed enhanced innate immune responses and cholesterol metabolism compared to enzymatically isolated UC MSCs.
CONCLUSION
This study provides a comprehensive transcriptomic comparison of MSCs, highlighting the superior transcriptional stability, immunomodulatory capacity, and metabolic flexibility of fetal MSCs, particularly smumf cells. These findings underscore their potential as a reliable cell source for therapeutic applications and encourage further exploration of their clinical application.
2.A 3D Printed Poly(e-caprolactone)-Collagen Hybrid Mesh (TissueDerm) for Breast Reconstruction after Mastectomy in a Pig Model
Kyu-Sik SHIM ; Han-Saem JO ; Shin Hyun KIM ; Dohyun KIM ; Yong-Kyu PARK ; Da-Hye RYU ; Won-Jai LEE ; Tai-Suk ROH ; Wooyeol BAEK
Tissue Engineering and Regenerative Medicine 2026;23(1):107-123
BACKGROUND:
Implant supporting materials are currently used in breast reconstruction. However, when used in humans, they are associated with several problems. To address these issues, a new mesh called TissueDerm was created by combining a collagen sponge with a 3D printed polycaprolactone (PCL) mesh. It has shown promising results in pig experiments and could potentially replace the most commonly used acellular dermal matrix (ADM) for breast reconstruction.
METHODS:
Four 12-month-old minipigs were used in this experiment. Silicone implants were wrapped with ADM or TissueDerm, and the breast tissue was excised and implanted along with the wrapped implants. Three months later, the minipigs were sacrificed and the skin and mammary gland tissue surrounding the implants were harvested for further analysis. Histological analyses and immunostaining were performed.
RESULTS:
Although there was no significant difference in capsule thickness between the ADM and TissueDerm groups, collagen was more involved in TissueDerm, leading to better tissue regeneration. TissueDerm also induced lower levels of inflammatory markers TNF-a and IL-6 compared to ADM. However, capsules induced with ADM had significantly higher collagen fiber alignment and alpha-smooth muscle actin (a-SMA) positive immunoreactivity, suggesting that TissueDerm may be less likely to cause spherical contractures in the porcine model compared to ADM.
CONCLUSIONS
The study found that TissueDerm has advantages over ADM in terms of easier tissue invasion and reduced spheroidization in a porcine model. The results showed that TissueDerm is a promising new mesh for implantbased breast reconstruction (IBBR) and could potentially replace ADM.
3.Usefulness of DKK1 in Estimating Vasculitis Activity and End-Stage Kidney Disease in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Patients
Hyeok Chan KWON ; Yong-Beom PARK ; Sang-Won LEE
Yonsei Medical Journal 2026;67(1):9-16
Purpose:
To investigate whether serum levels of Dickkopf-related protein-1 (DKK1) are clinically useful in estimating cross-sectional vasculitis activity and predicting future prognosis in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).
Materials and Methods:
This study included 76 patients with AAV. Their clinical data were retrospectively reviewed and serum DKK1 levels were measured in blood samples collected and stored at diagnosis. At diagnosis, the Birmingham vasculitis activity score (BVAS) and the five-factor score (FFS) were assessed as AAV activity indices, and the erythrocyte sedimentation rate and Creactive protein (CRP) level were recorded as acute-phase reactants. All-cause mortality and end-stage kidney disease (ESKD) were investigated as poor outcomes during follow-up.
Results:
Among the 76 patients with AAV (31 males, and 45 females), the median age was 63.5 years. At diagnosis, serum DKK1 levels were significantly correlated with BVAS, FFS, CRP, serum albumin, and serum creatinine levels. Using receiver operating characteristic curve analysis, the cut-off serum DKK1 level for predicting ESKD was determined to be 3925.0 pg/mL. Patients with serum DKK1 levels ≥3925.0 pg/mL at diagnosis displayed a significantly higher risk of ESKD progression (relative risk 5.357) and exhibited a significantly lower cumulative ESKD-free survival rate during follow-up than those with lower levels.
Conclusion
The present study is the first to demonstrate that serum DKK1 levels at diagnosis are useful in assessing vasculitis activity at diagnosis and predicting future ESKD progression in patients with AAV.
4.Association of Aerobic Physical Activity and Resistance Exercise with Glycated Hemoglobin in Women with Diabetes
Susanna JUN ; Ji Won KANG ; Dong-Hyuk PARK ; Ki-Yong AN ; Dong Hoon LEE ; Minsuk OH ; Justin Y. JEON
Yonsei Medical Journal 2026;67(1):71-78
Purpose:
The American Diabetes Association recommends that patients with diabetes engage in at least 150 minutes of physical activity (PA) per week and perform resistance exercise (RE) at least twice weekly. However, their benefits in controlling glucose levels among women with diabetes are not completely understood. Therefore, we investigated whether meeting PA or RE guidelines is associated with lower odds of uncontrolled glycated hemoglobin (HbA1c) among women.
Materials and Methods:
We analyzed 1213 women with diabetes from the Korea National Health and Nutrition Examination Survey 2014–2018. Using PA questionnaires, participants were categorized according to whether they met aerobic PA guidelines (≥150 minutes of moderate-to-vigorous PA), RE guidelines (≥twice weekly), or both. Further, HbA1c levels >7.5% were classified as uncontrolled glycemic levels. Multivariate logistic regression models were employed to investigate whether meeting PA or RE guidelines is associated with uncontrolled HbA1c.
Results:
There was no association between meeting aerobic PA guidelines of >150 minutes per week and uncontrolled HbA1c.However, participating in RE > twice weekly was associated with a 49% lower odds of HbA1c >7.5% in fully adjusted models (odds ratio: 0.51; 95% confidence interval: 0.30–0.87; p<0.05). Moreover, the association between RE participation and lower odds of HbA1c >7.5% was observed regardless of age, body mass index, and prevalence of hypertension.
Conclusion
Participation in RE may be important for women with diabetes for glycemic control. Further research is needed to better understand the associations between HbA1c and different exercise modalities (i.e., resistance vs. aerobic exercise) in women with diabetes.
5.Korean Medication Algorithm Project for Depressive Disorder 2025:Comparisons with Other Treatment Guidelines
Won-Seok CHOI ; Young Sup WOO ; Won-Myong BAHK ; Nak-Young KIM ; Jeong Seok SEO ; Sheng-Min WANG ; Won KIM ; Sung-Yong PARK ; Jung Goo LEE ; Chan-Mo YANG ; Hyung Mo SUNG ; Young-Eun JUNG ; Moon-Doo KIM ; Jong-Hyun JEONG ; Bo-Hyun YOON ; Kyung Joon MIN
Clinical Psychopharmacology and Neuroscience 2026;24(1):2-14
The sixth edition of the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) was published in 2025. This review compared KMAP-DD 2025 with four major international clinical practice guidelines: Canadian Network for Mood and Anxiety Treatments Clinical Guidelines for the Management of Major Depressive Disorders, National Institute for Health and Care Excellence Depression Guideline, Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines for Mood Disorders, and British Association for Psychopharmacology Guideline. While KMAP-DD is based on expert consensus, and others on evidence-based methods, overall treatment strategies for depressive episodes were fairly consistent. Especially, KMAP-DD 2025 offers more structured recommendations in areas lacking strong evidence, such as premenstrual dysphoric disorder, perinatal depression, and depression with medical comorbidities. KMAP-DD 2025 also reflected Korean clinical practice patterns emphasizing rapid symptom relief and early use of combination strategies. Despite limitations as a consensus-based guideline, KMAP-DD 2025 complements evidence-based approaches and provides practical, situation-specific guidance for real-world clinical decision-making in Korea.
6.Donor-to-recipient sex match status has no prognostic effect on long-term survival following liver transplantation:a retrospective observational study
Woo-Hyoung KANG ; I-Ji JEONG ; Shin HWANG ; Chul-Soo AHN ; Deok-Bog MOON ; Tae-Yong HA ; Gi-Won SONG ; Dong-Hwan JUNG ; Gil-Chun PARK ; Young-In YOON ; Sung-Gyu LEE
Clinical Transplantation and Research 2026;40(1):76-86
Background:
Studies on whether donor-to-recipient sex match status affects long-term survival after liver transplantation (LT) have yielded contradictory results. This study evaluated whether donor-to-recipient sex match status influenced long-term survival after living donor liver transplantation (LDLT) or deceased donor liver transplantation (DDLT) at a high-volume center.
Methods:
The study included 6,664 patients who underwent primary LT between January 2000 and December 2022 at our institution. Patients were divided into four groups according to donor-to-recipient sex match status: male-to-male (n=3,427 [51.4%]), male-to-female (n=1,152 [17.3%]), female-to-male (n=1,385 [20.8%]), and female-to-female (n=700 [10.5%]).
Results:
Regarding clinical characteristics, the four groups differed significantly regarding background liver disease (P<0.001), model for end-stage liver disease score (P<0.001), serum protein induced by vitamin K absence or antagonist II level (P=0.003), presence of concurrent hepatocellular carcinoma (HCC; P<0.001), and type of LT (P=0.003). Overall survival (OS) of all LT recipients did not differ significantly among the groups (P=0.377). Donor-to-recipient sex match status did not affect long-term OS in either LDLT (P=0.176) or DDLT (P=0.220) groups. In addition, sex match status did not significantly influence posttransplant OS among patients who underwent LDLT without HCC (P=0.464), LDLT with HCC (P=0.236), DDLT without HCC (P=0.338), or DDLT with HCC (P=0.818).
Conclusions
Donor-to-recipient sex match status does not significantly affect posttransplant patient survival or HCC prognosis after LDLT or DDLT.
7.Early-Onset Dementia Risk Escalates with Diabetes Duration: Insights from a Nationwide Cohort Study
Ji-Hong PARK ; Sun-Joon MOON ; Da Yeon LEE ; Ji-Hee KO ; Han Na JANG ; Hye-Mi KWON ; Se-Eun PARK ; Kyung-Do HAN ; Eun-Jung RHEE ; Won-Young LEE
Endocrinology and Metabolism 2026;41(2):235-244
Background:
The prevalence of diabetes mellitus and early-onset dementia (EOD), defined as dementia diagnosed at an age <65 years, is increasing worldwide, with significant socioeconomic implications. We investigated the association between diabetes, prediabetes, and EOD, focusing on the influence of diabetes duration on EOD risk.
Methods:
Using the Korean National Health Insurance Service database, we analyzed data from 1,979,509 patients aged 40–60 years who underwent health checkups in 2009. Patients were categorized into five groups: normal, impaired fasting glucose (IFG), newly diagnosed diabetes, diabetes duration <5 years, and diabetes duration ≥5 years. Cox proportional hazard models were used to estimate the adjusted hazard ratios (aHRs) for EOD after adjusting for demographic and clinical covariates.
Results:
During the observation period (mean 7.75 years), 8,921 patients with EOD were identified. The diabetes group demonstrated a significantly higher incidence of EOD compared to the normal group (aHR, 1.334; 95% confidence interval [CI], 1.226 to 1.451). EOD risk increased with longer diabetes duration, with the highest risk observed in patients with diabetes ≥5 years (aHR, 1.543; 95% CI, 1.368 to 1.741). No significant difference was observed between the IFG and normal groups (aHR, 0.989; 95% CI, 0.938 to 1.043). Additionally, the hypertension group exhibited a significantly higher incidence of EOD compared to the non-hypertension group (aHR, 1.364; 95% CI, 1.291 to 1.442).
Conclusion
Diabetes is independently associated with increased risk of EOD, and this risk increases with longer diabetes duration. This association remained significant regardless of the presence and duration of hypertension.
8.Confounding and the healthy worker survivor effect in studies of medical radiation workers: a systematic review of methodological approaches
Eun Jung PARK ; Kyoungyeol YUK ; Jaeho JEONG ; Won Jin LEE
Epidemiology and Health 2026;48(1):e2026009-
Confounding and the healthy worker survivor effect (HWSE) represent major methodological challenges in epidemiology, particularly in studies of low-dose exposures, where effect sizes are small and risk estimates can be readily distorted by bias. This systematic review aimed to summarize the methods used to adjust for confounding and the HWSE in studies of medical radiation workers. We systematically searched PubMed and Embase for studies of medical radiation workers from inception through June 30, 2025. Studies reporting excess risk estimates for any health outcomes associated with occupational radiation exposure were included. Study selection followed the PECO (Population, Exposure, Comparator, Outcome) criteria, and data were synthesized descriptively. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in PROSPERO (CRD42024589851). Sixteen eligible studies from 3 countries were identified, all of which were rated as high quality. To control for confounding, regression was used in all studies, followed by stratification (62.5%) and restriction (18.8%). Age, sex, and birth year were adjusted for in all models, with smoking being the next most frequently controlled variable. To mitigate the HWSE, only a single approach, adjustment for employment characteristics, was identified, and it was applied in 3 studies (18.8%). No other approaches, including restriction or g-methods, were employed. Although confounding is generally addressed using conventional analytical approaches, the HWSE has rarely been considered in studies of medical radiation workers. More comprehensive strategies that explicitly account for the HWSE are needed to improve the validity of risk estimates, particularly in low-dose occupational studies.
9.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part II. Follow-up Surveillance after Initial Treatment 2026
Eun Kyung LEE ; Seung Heon KANG ; Bon Seok KOO ; Mijin KIM ; Min Joo KIM ; Bo Hyun KIM ; Ji Won KIM ; Dong Gyu NA ; Sohyun PARK ; Ji-In BANG ; Kyorim BACK ; Youngduk SEO ; Young-Ik SON ; Young Shin SONG ; Dong Yeob SHIN ; Jong-Hyuk AHN ; Hwa Young AHN ; So Won OH ; Ho-Ryun WON ; Won Sang YOO ; Min Kyoung LEE ; Sang-Woo LEE ; Jeongmin LEE ; Ji Ye LEE ; Dong-Jun LIM ; Ki-Wook CHUNG ; Ari CHONG ; Jin Hyang JUNG ; Sun Wook CHO ; Yoon Young CHO ; Chae Moon HONG ; Young Joo PARK ;
International Journal of Thyroidology 2026;19(1):1-40
In patients with differentiated thyroid cancer (DTC), initial recurrence risk stratification based on clinical, histopathological, and perioperative data remains the key determinant for guiding management strategies during the first 1-2 years post-treatment. However, the adoption of ongoing risk stratification (ORS), which dynamically reassesses risk by integrating longitudinal clinical data and treatment response, enables more precise long-term prognostic assessment and facilitates highly individualized management. Building upon recent guidelines, the 2026 KTA guideline has been further refined by incorporating robust evidence from large-scale national cohorts and comprehensive systematic reviews. These updated recommendations outline contemporary concepts of ORS, risk-adapted TSH suppression targets, optimized surveillance modalities for recurrence detection, and disease-specific long-term follow-up strategies. Reflecting the paradigm shift toward de-escalated treatment, this revision integrates evolved perspectives on TSH suppression intensity, the clinical interpretation of thyroglobulin levels, and tailored follow-up intervals. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the large proportion of patients with excellent prognosis after initial therapy, while ensuring that each patient receives appropriately tailored and effective long-term management.
10.A Practical Immunohistochemistry-Based Model for Predicting Pathologic Complete Response in Estrogen Receptor-Strong Positive and HER2-Negative Breast Cancer
Su Min LEE ; Jeong Eon LEE ; Seok Jin NAM ; Seok Won KIM ; Jonghan YU ; Byung Joo CHAE ; Se Kyung LEE ; Jai Min RYU ; Eun Yoon CHO ; Hyunwoo LEE ; Woong Ki PARK
Journal of Breast Cancer 2026;29(2):128-140
Purpose:
While the benefit of neoadjuvant chemotherapy (NAC) has been established in human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancers, its effectiveness in achieving pathological complete response (pCR) and optimal patient selection in estrogen receptor (ER)-positive, HER2-negative breast cancers remain less clearly defined. This study aimed to identify immunohistochemistry (IHC)-based predictors of pCR and to develop a scoring model for ER-strong positive/HER2-negative breast cancer.
Methods:
Data from a prospective cohort were retrospectively analyzed. We included 522 patients with ER-strong positive/HER2-negative tumors who received NAC and surgery between 2008 and 2021. IHC markers including progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), and p53 were evaluated to identify predictors of pCR. Independent predictors of pCR from multivariate logistic regression were used to develop a weighted 4-point model. Model performance was assessed using receiver operating characteristic analysis. The prognostic impact of pCR was evaluated using KaplanMeier and Cox regression analyses.
Results:
Independent predictors of pCR included PR-negative status, positivity for basallike markers (EGFR or CK5/6), and Ki-67 ≥ 50%. The scoring model demonstrated good discrimination for pCR (area under the curve = 0.754). pCR rates increased stepwise, with scores of 4.9% (low), 10.7% (intermediate), and 36.2% (high). In the high-score group, pCR was significantly associated with improved disease-free survival (hazard ratio [HR], 0.09; p = 0.023) and distant metastasis-free survival (HR, 0.11; p = 0.035), whereas no significant survival differences according to pCR status were observed in the low and intermediate score groups.
Conclusion
This IHC-based model predicts pCR and helps identify subgroups in which pCR is associated with meaningful survival benefit following NAC in ER-positive/HER2-negative breast cancers. High-scoring patients may benefit from NAC, while patients with low- or intermediatescores may be better managed with surgery and endocrine therapy. This model may support personalized treatment decisions regarding NAC.

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