1.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.
2.Advancing Natural Killer Cell Therapy: Genetic Engineering Strategies for Enhanced Cancer Immunotherapy
Joo Dong PARK ; Ha Eun SHIN ; Yeon Su AN ; Hye Jung JANG ; Juwon PARK ; Se-Na KIM ; Chun Gwon PARK ; Wooram PARK
Annals of Laboratory Medicine 2025;45(2):146-159
Natural killer (NK) cells are pivotal innate immune system components that exhibit spontaneous cytolytic activity against abnormal cells, such as infected and tumor cells. NK cells have shown significant promise in adoptive cell therapy because of their favorable safety profiles and minimal toxicity in clinical settings. Despite their advantages, the therapeutic application of unmodified NK cells faces challenges, including limited in vivo persistence, particularly in the immunosuppressive tumor microenvironment. Recent advances in genetic engineering have enhanced the therapeutic potential of NK cells by addressing these limitations and improving their therapeutic efficacy. In this review, we have described various methodologies for the genetic modification of NK cells, including viral vectors, electroporation, and nanoparticle-based approaches. The ongoing research on nanomaterialbased approaches highlights their potential to overcome current limitations in NK cell therapy, paving the way for advanced cancer therapy and improved clinical outcomes. In this review, we also emphasize the potential of engineered NK cells in cancer immunotherapy and other clinical applications, highlighting the expanding scope of NK cell-based treatments and the critical role of innovative genetic engineering techniques.
3.Long-term outcomes and associated prognostic risk factors of childhood-onset lupus nephritis
Eujin PARK ; Jiwon JUNG ; Jeesu MIN ; Hyeonju LEE ; Min Ji PARK ; Ji Yeon SONG ; Ji Hyun KIM ; Kyung Mi JANG ; Eun Mi YANG ; Yo Han AHN ; Min Hyun CHO ; Joo Hoon LEE ; Young Seo PARK ; Soon Chul KIM ; Se Jin PARK ; Jung Won LEE ; Kee Hyuck KIM ; Ki Soo PAI ; Hee Gyung KANG ; Seong Heon KIM
Kidney Research and Clinical Practice 2025;44(2):389-395
This study investigated the clinical characteristics and kidney outcomes of childhood-onset lupus nephritis (LN), and risk factors associated with prognosis. Methods: We enrolled 216 patients with histologically diagnosed LN during childhood. The Korean Society of Pediatric Nephrology organized a retrospective cohort study of childhood-onset LN in 13 major pediatric nephrology centers in South Korea. Results: The mean age at kidney biopsy was 13.2 ± 3.22 years. The main forms of presentation were nephrotic syndrome and/or hematuria in 152 patients (70.4%), and the most common histological finding was World Health Organization (WHO) class IV in 138 patients (63.9%), followed by WHO class III in 34 patients (15.7%). In the outcome analysis, the mean follow-up period of the patients was 7.8 ± 5.11 years. At last follow-up, 32 patients (14.8%) developed advanced chronic kidney disease (CKD). Male sex and failure to achieve remission at 12 months of treatment were significant risk factors for developing advanced CKD (hazard ratio of 2.57 and 2.29, respectively). Conclusion: Our study demonstrated the clinical characteristics and long-term outcomes of patients with childhood-onset LN. Male sex and failure to achieve remission in the first year of treatment were predictive of advanced CKD. Therefore, prompt awareness and close monitoring of these high-risk patients are needed, which may further improve the prognosis of children with LN.
4.Associations of Alcohol Consumption with All-Cause and Cancer Mortalities in Patients with Type 2 Diabetes Mellitus: A Nationwide Population Cohort Study
Da Yeon LEE ; Sun-Joon MOON ; Kyung-Do HAN ; Ji-Hee KO ; Han-na JANG ; Hye-Mi KWON ; Se-Eun PARK ; Eun-Jung RHEE ; Won-Young LEE
Endocrinology and Metabolism 2025;40(6):893-903
Background:
To investigate the impact of alcohol consumption on all-cause and cancer mortalities in patients with type 2 diabetes (T2D).
Methods:
This nationwide cohort study included Korean patients with T2D aged >20 years from a national health exams cohort (2009 to 2012). Participants were categorized based on alcohol consumption: non, mild (<30 g/day), and heavy drinkers (≥30 g/day). Primary outcomes were all-cause and cancer mortality rates. Cox proportional hazard regression analyses were used to calculate adjusted hazard ratios (aHRs) with a 95% confidence interval (CI) with adjustments for age, sex, body mass index, smoking, exercise, comorbidities, diabetes duration, and medications.
Results:
Among 2,642,359 participants (median follow-up, 7.8 years), 57.2%, 32.7%, and 10.1% were non, mild, and heavy drinkers, respectively. Compared to non-drinkers, mild alcohol consumption was associated with reduced all-cause mortality (aHR, 0.81; 95% CI, 0.80 to 0.82) and cancer mortality (aHR, 0.88; 95% CI, 0.86 to 0.89), while heavy drinking increased both all-cause (aHR, 1.06; 95% CI, 1.04 to 1.07) and cancer mortalities (aHR, 1.09; 95% CI, 1.06 to 1.11). Subgroup analyses revealed variations: in chronic kidney disease and older age groups, heavy drinkers showed lower risk of all-cause mortality compared to non-drinkers. Regarding cancer mortality, younger and middle-aged groups showed protective effects of alcohol even for heavy drinkers, while females showed linear association between alcohol consumption and cancer mortality.
Conclusion
This study indicates a J-shaped relationship between alcohol consumption and all-cause and cancer mortality risk in patients with T2D, with variations across subgroups. These findings suggest the need for personalized recommendations considering individual risk factors.
5.Observation of neutrophil extracellular traps in the development of diabetic nephropathy using diabetic murine models
You Hyun JEON ; Se-Hyun OH ; Soo-Jung JUNG ; Eun-Joo OH ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Chang-Won HONG ; Jang-Hee CHO
Laboratory Animal Research 2024;40(4):424-434
Background:
Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.
Results:
Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.
Conclusions
NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.
6.Major clinical research advances in gynecologic cancer in 2023:a tumultuous year for endometrial cancer
Seung-Hyuk SHIM ; Jung-Yun LEE ; Yoo-Young LEE ; Jeong-Yeol PARK ; Yong Jae LEE ; Se Ik KIM ; Gwan Hee HAN ; Eun Jung YANG ; Joseph J NOH ; Ga Won YIM ; Joo-Hyuk SON ; Nam Kyeong KIM ; Tae-Hyun KIM ; Tae-Wook KONG ; Youn Jin CHOI ; Angela CHO ; Hyunji LIM ; Eun Bi JANG ; Hyun Woong CHO ; Dong Hoon SUH
Journal of Gynecologic Oncology 2024;35(2):e66-
In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.
7.Observation of neutrophil extracellular traps in the development of diabetic nephropathy using diabetic murine models
You Hyun JEON ; Se-Hyun OH ; Soo-Jung JUNG ; Eun-Joo OH ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Chang-Won HONG ; Jang-Hee CHO
Laboratory Animal Research 2024;40(4):424-434
Background:
Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.
Results:
Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.
Conclusions
NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.
8.Observation of neutrophil extracellular traps in the development of diabetic nephropathy using diabetic murine models
You Hyun JEON ; Se-Hyun OH ; Soo-Jung JUNG ; Eun-Joo OH ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Chang-Won HONG ; Jang-Hee CHO
Laboratory Animal Research 2024;40(4):424-434
Background:
Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.
Results:
Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.
Conclusions
NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.
9.Observation of neutrophil extracellular traps in the development of diabetic nephropathy using diabetic murine models
You Hyun JEON ; Se-Hyun OH ; Soo-Jung JUNG ; Eun-Joo OH ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Chang-Won HONG ; Jang-Hee CHO
Laboratory Animal Research 2024;40(4):424-434
Background:
Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.
Results:
Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.
Conclusions
NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.
10.Major clinical research advances in gynecologic cancer in 2023:a tumultuous year for endometrial cancer
Seung-Hyuk SHIM ; Jung-Yun LEE ; Yoo-Young LEE ; Jeong-Yeol PARK ; Yong Jae LEE ; Se Ik KIM ; Gwan Hee HAN ; Eun Jung YANG ; Joseph J NOH ; Ga Won YIM ; Joo-Hyuk SON ; Nam Kyeong KIM ; Tae-Hyun KIM ; Tae-Wook KONG ; Youn Jin CHOI ; Angela CHO ; Hyunji LIM ; Eun Bi JANG ; Hyun Woong CHO ; Dong Hoon SUH
Journal of Gynecologic Oncology 2024;35(2):e66-
In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.

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