1.Muscle Loss Driven by Extracellular Signal-Regulated Kinase Suppression via β-Adrenergic Activation in High-Normal Catecholamine Status
Jieun LEE ; Ju Yeon KWAK ; Ho Yeop LEE ; Ji Sun MOON ; Hyo Ju JANG ; Ha Thi NGA ; Thi Linh NGUYEN ; Alfin Mohammad ABDILLAH ; Junglyun KIM ; Sihwan KIM ; Yong Ryoul YANG ; Jeong Eun LEE ; Hyon-Seung YI
Endocrinology and Metabolism 2026;41(2):319-332
Background:
Catecholamines play a crucial role in muscle biogenesis, but their persistent elevation is linked to muscle wasting, which is poorly understood. This study aimed to investigate the association between catecholamine levels and age-related muscle loss.
Methods:
This retrospective study evaluated the plasma levels of two catecholamines, metanephrine and normetanephrine, and the clinical characteristics of 830 patients with adrenal incidentaloma on computed tomography (CT). Cross-sectional CT data at the L3 lumbar vertebrae were used to measure muscle areas. In vitro studies on C2C12 myotubes were conducted to examine β-adrenergic receptor signaling pathways and their role in myogenesis.
Results:
Men had significantly higher mean metanephrine levels of 0.17 nmol/L and normetanephrine levels of 0.63 nmol/L than women (P<0.05). Total abdominal muscle area was negatively correlated with catecholamine levels in both men and women, with the strongest negative correlation between normetanephrine levels and total abdominal muscle area in men (r=–0.31, P<0.001). Similarly, the strongest negative correlation between visceral fat area and metanephrine was observed in men (r=–0.25, P=0.004). Clenbuterol, a β-adrenergic receptor agonist, inhibited myogenesis, including myotube formation by extracellular signal-regulated kinase (ERK) suppression in C2C12 myoblasts. Conversely, β-blockers increased myogenesis via increasing ERK phosphorylation in C2C12 cells. These findings suggest that β-adrenergic modulation influences skeletal muscle differentiation, with ERK phosphorylation.
Conclusion
Catecholamine levels are associated with age, sex, muscle mass, and fat mass. Monitoring catecholamine levels, particularly in older men and in individuals with reduced muscle mass, may help manage age-related muscle loss and lead to individualized treatment strategies.
2.The Effect of Alcohol Consumption Behavior Changes on Gastric Cancer Risks Stratified by Sex in South Korea
Yonghoon CHOI ; Jieun JANG ; Hyeong Ho JO ; Nayoung KIM
Cancer Research and Treatment 2026;58(1):232-241
Purpose:
The effect of behavior changes in alcohol drinking on gastric cancer (GC) development, and the sex differences in those effects have not yet been fully elucidated. This study investigated the effect of behavior changes in alcohol drinking on the GC risk by sex.
Materials and Methods:
The cohort consisted of 310,192 Koreans (≥ 40 years) from the National Health Insurance Service–Health Screening Cohort with a median follow-up period of 12 years. Subjects were classified according to alcohol consumption behavior changes (non-drinker, quitter, reducer, sustainer, and increaser). The independent effect of changes in alcohol drinking patterns or concurrent effect of alcohol on GC risk were evaluated using the Cox proportional hazard regression.
Results:
In males, non-drinkers showed a lower risk of developing GC (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.84 to 0.98), whereas increasers showed a higher risk of GC than sustainers (HR, 1.11; 95% CI, 1.02 to 1.20). Starting to drink alcohol, even at a mild level, was associated with an increased GC risk, while a decreased GC risk was induced when alcohol consumption dose decreases to a mild from a moderate level among males. However, in females, only substantial change of alcohol consumption dose from non- to heavy-drinking was associated with increased GC risk (HR, 1.97; 95% CI, 0.98 to 3.96).
Conclusion
These results suggest that alcohol abstinence can reduce the risk of developing GC, particularly among males.
3.Establishment of an Organoid Culture Model Derived from Small Intestinal Epithelium of C57BL/6 Mice and Its Benefits over Tissues
Jae Young JANG ; Nayoung KIM ; Ryoung Hee NAM ; Eun Hye KIM ; Chin-Hee SONG ; Sungchan HA ; Jieun LEE
Journal of Cancer Prevention 2025;30(1):12-23
This study aimed to establish an organoid culture model using small intestine tissues from male and female C57BL/6 mice and to compare it with rat organoid cultures derived from frozen tissues. Crypts were isolated from the small intestines of eight-week-old male and female mice and cultured in 3D extracellular matrix with Wnt, R-spondin, and Noggin. In addition, small intestine tissues from sixteen-week-old F344 rats were preserved in a storage solution immediately post-sacrifice and stored at –80°C before being transferred to a nitrogen tank. Upon thawing, crypts from frozen rat tissues failed to develop into organoids due to structural damage, suggesting the need for fresh tissues or optimized preservation methods. In contrast, mouse-derived organoids showed viability for 7 days, with distinct morphological changes and clear differentiation by Day 7. Quantitative real-time PCR analysis revealed that Lgr5, a stem cell marker, showed significantly higher expression in organoids than in tissues, confirming the successful establishment of the organoid culture. Among epithelial markers, the antimicrobial enzyme Lyz1 was more highly expressed in organoids, while Muc2, a key goblet cell marker, was more highly expressed in male tissues. The enterocyte marker Alp exhibited higher expression in male organoids compared to females, with no sex differences in tissues. These findings highlight sex-specific differences in gene expression related to small intestine differentiation and demonstrate the challenges in organoid culture from frozen rat tissues. The results suggest the importance of immediate tissue processing or improved preservation methods for successful organoid cultures.
4.Differences in the Effect of Physical Activity on the Prevention of Gastric Cancer According to Sex
Hyeong Ho JO ; Nayoung KIM ; Jieun JANG ; Yonghoon CHOI ; Jung Won LEE
Journal of Gastric Cancer 2025;25(2):343-355
Purpose:
Physical activity (PA) is considered a potentially effective factor in the primary prevention of gastric cancer (GC). As body mass index (BMI) and waist circumference (WC) differ by sex, particularly with age, this study aimed to investigate the impact of PA on GC development, considering BMI and WC variations by sex.
Materials and Methods:
We analyzed the impact of PA on GC development using Cox proportional hazard regression in a cohort of 314,525 Korean individuals from the National Health Insurance Service–Health Screening database, using data from 2009–2019.Additionally, subgroup analyses were conducted based on BMI and WC. The models were adjusted for age, sex, smoking status, alcohol consumption, BMI, and comorbidities.
Results:
The effect of PA on the prevention of GC development was relatively evident in males. The high PA group (metabolic equivalents of task, METs/week of 500–999) showed a lower risk of GC compared to the group with METs/week of 0 (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79–0.98). Especially in males with WC <90 cm and BMI <23 kg/m2 , a lower risk of GC was observed in the group with METs/week of 1–499 compared to the group with METs/week of 0 (HR, 0.80; 95% CI, 0.67–0.96). In contrast, no consistent association was observed between PA levels and risk of GC in females.
Conclusions
Moderate PA had a preventive effect on GC development in males, particularly in those with low BMI and WC. However, this effect was not observed in females.
5.Establishment of an Organoid Culture Model Derived from Small Intestinal Epithelium of C57BL/6 Mice and Its Benefits over Tissues
Jae Young JANG ; Nayoung KIM ; Ryoung Hee NAM ; Eun Hye KIM ; Chin-Hee SONG ; Sungchan HA ; Jieun LEE
Journal of Cancer Prevention 2025;30(1):12-23
This study aimed to establish an organoid culture model using small intestine tissues from male and female C57BL/6 mice and to compare it with rat organoid cultures derived from frozen tissues. Crypts were isolated from the small intestines of eight-week-old male and female mice and cultured in 3D extracellular matrix with Wnt, R-spondin, and Noggin. In addition, small intestine tissues from sixteen-week-old F344 rats were preserved in a storage solution immediately post-sacrifice and stored at –80°C before being transferred to a nitrogen tank. Upon thawing, crypts from frozen rat tissues failed to develop into organoids due to structural damage, suggesting the need for fresh tissues or optimized preservation methods. In contrast, mouse-derived organoids showed viability for 7 days, with distinct morphological changes and clear differentiation by Day 7. Quantitative real-time PCR analysis revealed that Lgr5, a stem cell marker, showed significantly higher expression in organoids than in tissues, confirming the successful establishment of the organoid culture. Among epithelial markers, the antimicrobial enzyme Lyz1 was more highly expressed in organoids, while Muc2, a key goblet cell marker, was more highly expressed in male tissues. The enterocyte marker Alp exhibited higher expression in male organoids compared to females, with no sex differences in tissues. These findings highlight sex-specific differences in gene expression related to small intestine differentiation and demonstrate the challenges in organoid culture from frozen rat tissues. The results suggest the importance of immediate tissue processing or improved preservation methods for successful organoid cultures.
6.Differences in the Effect of Physical Activity on the Prevention of Gastric Cancer According to Sex
Hyeong Ho JO ; Nayoung KIM ; Jieun JANG ; Yonghoon CHOI ; Jung Won LEE
Journal of Gastric Cancer 2025;25(2):343-355
Purpose:
Physical activity (PA) is considered a potentially effective factor in the primary prevention of gastric cancer (GC). As body mass index (BMI) and waist circumference (WC) differ by sex, particularly with age, this study aimed to investigate the impact of PA on GC development, considering BMI and WC variations by sex.
Materials and Methods:
We analyzed the impact of PA on GC development using Cox proportional hazard regression in a cohort of 314,525 Korean individuals from the National Health Insurance Service–Health Screening database, using data from 2009–2019.Additionally, subgroup analyses were conducted based on BMI and WC. The models were adjusted for age, sex, smoking status, alcohol consumption, BMI, and comorbidities.
Results:
The effect of PA on the prevention of GC development was relatively evident in males. The high PA group (metabolic equivalents of task, METs/week of 500–999) showed a lower risk of GC compared to the group with METs/week of 0 (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79–0.98). Especially in males with WC <90 cm and BMI <23 kg/m2 , a lower risk of GC was observed in the group with METs/week of 1–499 compared to the group with METs/week of 0 (HR, 0.80; 95% CI, 0.67–0.96). In contrast, no consistent association was observed between PA levels and risk of GC in females.
Conclusions
Moderate PA had a preventive effect on GC development in males, particularly in those with low BMI and WC. However, this effect was not observed in females.
7.Establishment of an Organoid Culture Model Derived from Small Intestinal Epithelium of C57BL/6 Mice and Its Benefits over Tissues
Jae Young JANG ; Nayoung KIM ; Ryoung Hee NAM ; Eun Hye KIM ; Chin-Hee SONG ; Sungchan HA ; Jieun LEE
Journal of Cancer Prevention 2025;30(1):12-23
This study aimed to establish an organoid culture model using small intestine tissues from male and female C57BL/6 mice and to compare it with rat organoid cultures derived from frozen tissues. Crypts were isolated from the small intestines of eight-week-old male and female mice and cultured in 3D extracellular matrix with Wnt, R-spondin, and Noggin. In addition, small intestine tissues from sixteen-week-old F344 rats were preserved in a storage solution immediately post-sacrifice and stored at –80°C before being transferred to a nitrogen tank. Upon thawing, crypts from frozen rat tissues failed to develop into organoids due to structural damage, suggesting the need for fresh tissues or optimized preservation methods. In contrast, mouse-derived organoids showed viability for 7 days, with distinct morphological changes and clear differentiation by Day 7. Quantitative real-time PCR analysis revealed that Lgr5, a stem cell marker, showed significantly higher expression in organoids than in tissues, confirming the successful establishment of the organoid culture. Among epithelial markers, the antimicrobial enzyme Lyz1 was more highly expressed in organoids, while Muc2, a key goblet cell marker, was more highly expressed in male tissues. The enterocyte marker Alp exhibited higher expression in male organoids compared to females, with no sex differences in tissues. These findings highlight sex-specific differences in gene expression related to small intestine differentiation and demonstrate the challenges in organoid culture from frozen rat tissues. The results suggest the importance of immediate tissue processing or improved preservation methods for successful organoid cultures.
8.Differences in the Effect of Physical Activity on the Prevention of Gastric Cancer According to Sex
Hyeong Ho JO ; Nayoung KIM ; Jieun JANG ; Yonghoon CHOI ; Jung Won LEE
Journal of Gastric Cancer 2025;25(2):343-355
Purpose:
Physical activity (PA) is considered a potentially effective factor in the primary prevention of gastric cancer (GC). As body mass index (BMI) and waist circumference (WC) differ by sex, particularly with age, this study aimed to investigate the impact of PA on GC development, considering BMI and WC variations by sex.
Materials and Methods:
We analyzed the impact of PA on GC development using Cox proportional hazard regression in a cohort of 314,525 Korean individuals from the National Health Insurance Service–Health Screening database, using data from 2009–2019.Additionally, subgroup analyses were conducted based on BMI and WC. The models were adjusted for age, sex, smoking status, alcohol consumption, BMI, and comorbidities.
Results:
The effect of PA on the prevention of GC development was relatively evident in males. The high PA group (metabolic equivalents of task, METs/week of 500–999) showed a lower risk of GC compared to the group with METs/week of 0 (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79–0.98). Especially in males with WC <90 cm and BMI <23 kg/m2 , a lower risk of GC was observed in the group with METs/week of 1–499 compared to the group with METs/week of 0 (HR, 0.80; 95% CI, 0.67–0.96). In contrast, no consistent association was observed between PA levels and risk of GC in females.
Conclusions
Moderate PA had a preventive effect on GC development in males, particularly in those with low BMI and WC. However, this effect was not observed in females.
9.Gender and Menopause Impact on Recurrence and Cancer-Specific Mortality in Bladder Cancer After Radical Cystectomy: A Retrospective Cohort Study
Jee Soo PARK ; Won Sik JANG ; Jieun HEO ; Won Sik HAM ; Kyung Hwan KIM ; Jong Kil NAM ; Bum-Jin LIM ; Bum Sik HONG ; Wook NAM ; Sangchul LEE ; Jong Jin OH ; Seung Hwan JEONG ; Ja Hyeon KU ; Tae Il NOH ; Sung Gu KANG ; Seok Ho KANG ; Yun-Sok HA ; Tae Gyun KWON ; Tae‑Hwan KIM ; Jongchan KIM ; Geehyun SONG ; Ho Kyung SEO ; Wan SONG ; Hyun Hwan SUNG ; Byong Chang JEONG
Journal of Urologic Oncology 2025;23(1):88-93
Purpose:
Although bladder cancer occurs three to 4 times more frequently in men than in women, the relative number of deaths compared to incidence is higher in women, suggesting that women have a worse prognosis than men. Emerging evidence indicates that the activity of the sex steroid hormone pathway may play a role in bladder cancer development, with demonstrations that both androgens and estrogens have biological effects on bladder cancer in vitro and in vivo. This study investigates the influence of sex and menopausal status on recurrence and cancer-specific death (CSD) in bladder cancer patients undergoing radical cystectomy (RC).
Materials and Methods:
This retrospective analysis included 3,913 patients from the Korean Bladder Cancer Study Group Database who underwent RC between 2010 and 2019. Patients were categorized based on gender and menopausal status (≤50 years: premenopausal; >50 years: postmenopausal). Pathological factors, neoadjuvant chemotherapy, recurrence, and CSD rates were analyzed using chi-square and Fisher exact tests.
Results:
Among the 3,913 patients, 400 (10.2%) were female. Premenopausal females exhibited significantly lower recurrence rates (28.6%) compared to postmenopausal females (45.7%). CSD rates were similarly reduced in premenopausal females (12.0% vs. 22.2% in postmenopausal females). No significant sex differences in recurrence or CSD were observed among premenopausal patients. Pathological T stage, nodal status, and lymphovascular invasion were significantly associated with recurrence in males, while nodal status alone was significant in females. Neoadjuvant chemotherapy was significantly more frequently administered to male patients under the age of 50, while no difference was observed in the administration of neoadjuvant chemotherapy among female patients based on menopausal status.
Conclusion
Hormonal changes associated with menopause significantly influence bladder cancer outcomes in women. Premenopausal hormonal environments seem protective, underscoring the need for further research into hormone-driven mechanisms in bladder cancer.
10.Mitochondria Activity and CXCR4Collaboratively Promote the Differentiation of CD11c + B Cells Induced by TLR9 in Lupus
Sung Hoon JANG ; Joo Sung SHIM ; Jieun KIM ; Eun Gyeol SHIN ; Jong Hwi YOON ; Lucy Eunju LEE ; Ho-Keun KWON ; Jason Jungsik SONG
Immune Network 2024;24(4):e25-
Lupus is characterized by the autoantibodies against nuclear Ags, underscoring the importance of identifying the B cell subsets driving autoimmunity. Our research focused on the mitochondrial activity and CXCR4 expression in CD11c + B cells from lupus patients after ex vivo stimulation with a TLR9 agonist, CpG-oligodeoxyribonucleotide (ODN). We also evaluated the response of CD11c + B cells in ODN-injected mice. Post-ex vivo ODN stimulation, we observed an increase in the proportion of CD11chi cells, with elevated mitochondrial activity and CXCR4 expression in CD11c + B cells from lupus patients. In vivo experiments showed similar patterns, with TLR9 stimulation enhancing mitochondrial and CXCR4 activities in CD11chi B cells, leading to the generation of anti-dsDNA plasmablasts. The CXCR4 inhibitor AMD3100 and the mitochondrial complex I inhibitor IM156 significantly reduced the proportion of CD11c + B cells and autoreactive plasmablasts. These results underscore the pivotal roles of mitochondria and CXCR4 in the production of autoreactive plasmablasts.

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