Ceramides (Cer) comprise the major constituent of sphingolipids in the epidermis and are known to play diverse roles in the outermost layers of the skin including water retention and provision of a physical barrier. In addition, they can be hydrolyzed into free sphingoid bases such as C18 sphingosine (SO) and C18 sphinganine (SA) or can be further metabolized to C18 So-1-phosphate (S1P) and C18 Sa-1-phosphate (Sa1P) in keratinocytes. The significance of ceramide metabolites emerged from studies reporting altered levels of SO and SA in skin disorders and the role of S1P and Sa1P as signaling lipids. However, the overall metabolism of sphingoid bases and their phosphates during keratinocyte differentiation remains not fully understood. Therefore, in this study, we analyzed these Cer metabolites in the process of keratinocyte differentiation. Three distinct keratinocyte differentiation stages were prepared using 0.07 mM calcium (Ca2+) (proliferation stage), 1.2 mM Ca2+ (early differentiation stage) in serum-free medium, or serum-containing medium with vitamin C (50 microL/mL) (late differentiation stage). Serum-containing medium was also used to determine whether vitamin C increases the concentrations of sphingoid bases and their phosphates. The production of sphingoid bases and their phosphates after hydrolysis by alkaline phosphatase was determined using high-performance liquid chromatography. Compared to cells treated with 0.07 mM Ca2+, levels of SO, SA, S1P, and SA1P were not altered after treatment with 1.2 mM Ca2+. However, in keratinocytes cultured in serum-containing medium with vitamin C, levels of SO, SA, S1P, and SA1P were dramatically higher than those in 0.07- and 1.2-mM Ca2+-treated cells; however, compared to serum-containing medium alone, vitamin C did not significantly enhance their production. Taken together, we demonstrate that late differentiation induced by vitamin C and serum was accompanied by dramatic increases in the concentration of sphingoid bases and their phosphates, although vitamin C alone had no effect on their production.
Alkaline Phosphatase ; Ascorbic Acid ; Calcium ; Ceramides ; Chromatography, Liquid ; Epidermis ; Hydrolysis ; Keratinocytes ; Phosphates ; Retention (Psychology) ; Skin ; Sphingolipids ; Sphingosine ; Vitamins ; Water

Trefoil factor 1 (TFF1, also known as pS2) is strongly expressed in the gastrointestinal mucosa and plays a critical role in the differentiation of gastric glands. Since approximately 50% of all human gastric cancers are associated with decreased TFF1 expression, it is considered a tumor suppressor gene. TFF1 deficiency in mice results in histological changes in the antral and pyloric gastric mucosa, with severe hyperplasia and dysplasia of epithelial cells, resulting in the development of antropyloric adenoma. Here, we generated TFF1-knockout (KO) mice, without a neomycin resistant (NeoR) cassette, using the clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRSIPR/Cas9) system. Though our TFF1-KO mice showed phenotypes very similar to the previous embryonic stem (ES)-cell-based KO mice, they differed from the previous reports in that a reduction in body weight was observed in males. These results demonstrate that these newly established TFF1-KO mice are useful tools for investigating genetic and environmental factors influencing gastric cancer, without the effects of artificial gene insertion. Furthermore, these findings suggest a novel hypothesis that TFF1 expression influences gender differences.
Adenoma ; Animals ; Body Weight* ; Carcinogenesis* ; Epithelial Cells ; Gastric Mucosa ; Genes, Synthetic ; Genes, Tumor Suppressor ; Humans ; Hyperplasia ; Lotus ; Male ; Mice* ; Mucous Membrane ; Neomycin ; Phenotype ; Stomach Neoplasms

Background: This study examined gender differences in occupational stress, depressive symptoms, and suicidal ideation by considering the potential moderating effect of grit on Korean employees. Methods: A total of 11,369 participants (7,735 men and 3,634 women) aged 19–65 years, employed across 18 private companies and local government organizations in Korea, completed questionnaires including the Short Grit Scale, Korean Occupational Stress Scale, and Center for Epidemiologic Studies Depression Scale between April 2020 and March 2022.Suicidal ideation was assessed based on its presence or absence. Mediation and moderation analyses were performed using the Statistical Package for the Social Sciences PROCESS macro. Results: Depressive symptoms partially mediated the relationship between occupational stress and suicidal ideation in male employees, whereas depressive symptoms fully mediated the relationship in female employees. Grit moderated the relationship between depressive symptoms and suicidal ideation in male employees but not in female employees.Furthermore, the moderated mediating effect of grit in male employees on the relationship between occupational stress and suicidal ideation provided less protection in cases of severe depression. The cross-sectional design does not allow for causal inferences. Conclusion These findings contribute to understanding of the gender differences in the impact of depressive symptoms on the relationship between occupational stress and suicidal ideation, as well as the protective effect of grit. These findings highlight the need for genderspecific approaches to prevent suicidal ideation among employees.

Background: This study examined gender differences in occupational stress, depressive symptoms, and suicidal ideation by considering the potential moderating effect of grit on Korean employees. Methods: A total of 11,369 participants (7,735 men and 3,634 women) aged 19–65 years, employed across 18 private companies and local government organizations in Korea, completed questionnaires including the Short Grit Scale, Korean Occupational Stress Scale, and Center for Epidemiologic Studies Depression Scale between April 2020 and March 2022.Suicidal ideation was assessed based on its presence or absence. Mediation and moderation analyses were performed using the Statistical Package for the Social Sciences PROCESS macro. Results: Depressive symptoms partially mediated the relationship between occupational stress and suicidal ideation in male employees, whereas depressive symptoms fully mediated the relationship in female employees. Grit moderated the relationship between depressive symptoms and suicidal ideation in male employees but not in female employees.Furthermore, the moderated mediating effect of grit in male employees on the relationship between occupational stress and suicidal ideation provided less protection in cases of severe depression. The cross-sectional design does not allow for causal inferences. Conclusion These findings contribute to understanding of the gender differences in the impact of depressive symptoms on the relationship between occupational stress and suicidal ideation, as well as the protective effect of grit. These findings highlight the need for genderspecific approaches to prevent suicidal ideation among employees.

Background: This study examined gender differences in occupational stress, depressive symptoms, and suicidal ideation by considering the potential moderating effect of grit on Korean employees. Methods: A total of 11,369 participants (7,735 men and 3,634 women) aged 19–65 years, employed across 18 private companies and local government organizations in Korea, completed questionnaires including the Short Grit Scale, Korean Occupational Stress Scale, and Center for Epidemiologic Studies Depression Scale between April 2020 and March 2022.Suicidal ideation was assessed based on its presence or absence. Mediation and moderation analyses were performed using the Statistical Package for the Social Sciences PROCESS macro. Results: Depressive symptoms partially mediated the relationship between occupational stress and suicidal ideation in male employees, whereas depressive symptoms fully mediated the relationship in female employees. Grit moderated the relationship between depressive symptoms and suicidal ideation in male employees but not in female employees.Furthermore, the moderated mediating effect of grit in male employees on the relationship between occupational stress and suicidal ideation provided less protection in cases of severe depression. The cross-sectional design does not allow for causal inferences. Conclusion These findings contribute to understanding of the gender differences in the impact of depressive symptoms on the relationship between occupational stress and suicidal ideation, as well as the protective effect of grit. These findings highlight the need for genderspecific approaches to prevent suicidal ideation among employees.

Background: This study examined gender differences in occupational stress, depressive symptoms, and suicidal ideation by considering the potential moderating effect of grit on Korean employees. Methods: A total of 11,369 participants (7,735 men and 3,634 women) aged 19–65 years, employed across 18 private companies and local government organizations in Korea, completed questionnaires including the Short Grit Scale, Korean Occupational Stress Scale, and Center for Epidemiologic Studies Depression Scale between April 2020 and March 2022.Suicidal ideation was assessed based on its presence or absence. Mediation and moderation analyses were performed using the Statistical Package for the Social Sciences PROCESS macro. Results: Depressive symptoms partially mediated the relationship between occupational stress and suicidal ideation in male employees, whereas depressive symptoms fully mediated the relationship in female employees. Grit moderated the relationship between depressive symptoms and suicidal ideation in male employees but not in female employees.Furthermore, the moderated mediating effect of grit in male employees on the relationship between occupational stress and suicidal ideation provided less protection in cases of severe depression. The cross-sectional design does not allow for causal inferences. Conclusion These findings contribute to understanding of the gender differences in the impact of depressive symptoms on the relationship between occupational stress and suicidal ideation, as well as the protective effect of grit. These findings highlight the need for genderspecific approaches to prevent suicidal ideation among employees.

Objective: To assess the influence of advanced maternal age on congenital malformations, short- and long-term outcomes in offspring of nulligravida. Methods: A retrospective study was conducted using the Korean National Health Insurance Service database spanning from January 2005 to December 2019. All live-born offspring of nulligravida (n=3,685,817) were included. The maternal age was subdivided into the following subgroups: <25 years (n=153,818), 25-29 years (n=845,355), 30-34 years (n=1,738,299), 35-39 years (n=787,530), 40-44 years (n=151,519), and >44 years (n=9,296). Outcomes were assessed based on International Classification of Diseases-10 codes. Adjusted odds ratios (aOR) were calculated with the group of 25-29 years as a reference.Result Most congenital malformations showed an age dependent increase, but cleft lip and abdominal wall defect exhibited a U-shape curve, indicating an increase even in those <25 years old. Similarly, various disorders included in the neonatal composite outcomes from short-term outcomes showed aged dependent escalation. However, the preterm birth from the short-term outcome and most of the long-term developmental outcomes, except for motor developmental delay and Tics, showed a U-shaped pattern. The aOR of autism and cerebral palsy, showing the most obvious U-shaped curved in the long-term outcomes, was 1.50 (95% confidence interval [CI], 1.24-1.82) and 1.54 (95% CI, 1.17-2.03), respectively in the group >44 years old and 1.18 (95% CI, 1.11-1.25) and 1.19 (95% CI, 1.09-1.30) in <25 years old group. Conclusion Overall, an advanced maternal age has an age-dependent correlation with most congenital malformations and shortand long-term outcomes of neonates.

Non-traumatic exertional rhabdomyolysis (exRML) occurs in individuals with normal muscles when the energy supplied to the muscle is insufficient. Here, we report 11 cases of spinning-induced rhabdomyolysis and review related literature. Spinning is a kind of indoor bicycle sport. The 11 patients who were diagnosed with exRML and admitted to CHA Bundang Medical Center were female and their ages ranged from 15 to 46 years. Two to three days prior to the presentation, the patients had attended a spinning class for the first time. All the patients had been otherwise healthy without any known medical illnesses. They were successfully treated without any complications, except mild non-symptomatic hypocalcemia. However, in the literature, severe complications such as compartment syndrome or acute kidney injury had been reported in relation to exRML including spinning-induced rhabdomyolysis. This spinning exercise needs prior guidelines and specific warnings to prevent exertional rhabdomyolysis.
Acute Kidney Injury ; Compartment Syndromes ; Creatine Kinase ; Female ; Humans ; Hypocalcemia ; Muscles ; Rhabdomyolysis* ; Sports

Oral administration of royal jelly (RJ) promotes wound healing in diabetic mice. Concerns have arisen regarding the efficacy of RJ on the wound healing process of normal skin cells. In this study, a wound was created by scratching normal human dermal fibroblasts, one of the major cells involved in the wound healing process. The area was promptly treated with RJ at varying concentrations of 0.1, 1.0, or 5 mg/ml for up to 48 hrs and migration was analyzed by evaluating closure of the wound margins. Furthermore, altered levels of lipids, which were recently reported to participate in the wound healing process, were analyzed by HPTLC and HPLC. Migration of fibroblasts peaked at 24 hrs after wounding. RJ treatment significantly accelerated the migration of fibroblasts in a dose-dependent manner at 8 hrs. Although RJ also accelerated the migration of fibroblasts at both 20 hrs and 24 hrs after wounding, the efficacy was less potent than at 8 hrs. Among various lipid classes within fibroblasts, the level of cholesterol was significantly decreased at 8 hrs following administration of both 0.1 ug/ml and 5 mg/ml RJ. Despite a dose-dependent increase in sphinganines, the levels of sphingosines, ceramides, and glucosylceramides were not altered with any concentration of RJ. We demonstrated that RJ enhances the migration of fibroblasts and alters the levels of various lipids involved in the wound healing process.
Administration, Oral ; Animals ; Ceramides ; Cholesterol ; Chromatography, High Pressure Liquid ; Fatty Acids ; Fibroblasts ; Glucosylceramides ; Humans ; Mice ; Skin ; Sphingosine ; Wound Healing

Background: s: Fimasartan is the most recently developed, potent, and long-acting angiotensin II receptor blocker (ARB). However, data are limited regarding treatment effects of fimasartan in patients with heart failure. Methods: Between 2010 and 2016, patients who underwent coronary revascularization for myocardial infarction (MI) with heart failure and prescription of ARB at hospital discharge were enrolled from the Korean nationwide medical insurance data. Clinical outcomes were compared between patients receiving fimasartan and those receiving other ARBs (candesartan, valsartan, losartan, telmisartan, olmesartan, and irbesartan). The primary outcome was a composite of all-cause death, recurrent MI, hospitalization for heart failure, and stroke. Results: Of 2,802 eligible patients, fimasartan was prescribed to 124 patients (4.4%). During a median follow-up of 2.2 years (interquartile range, 1.0–3.9), 613 events of the primary outcome occurred. There was no significant difference in the primary outcome between patients receiving fimasartan and those receiving other ARBs (adjusted hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.46–1.45). Compared with patients receiving other ARBs, those receiving fimasartan had comparable incidence of all-cause death (adjusted HR, 0.70; 95% CI, 0.30–1.63), recurrent MI (adjusted HR, 1.28; 95% CI, 0.49–3.34), hospitalization for heart failure (adjusted HR, 0.70; 95% CI, 0.27–1.84), and stroke (adjusted HR, 0.59; 95% CI, 0.18–1.96). Conclusion In this nationwide cohort, fimasartan, compared with other ARBs, had comparable treatment effects for a composite of all-cause death, recurrent MI, hospitalization for heart failure, and stroke in patients with heart failure after MI.