Objective: Autophagy is highly active in ovariectomized mice experiencing hormone deprivation, especially in the uterine mesenchyme. Autophagy is responsible for the turnover of vasoactive factors in the uterus, which was demonstrated in anti-Müllerian hormone receptor type 2 receptor (Amhr2)-Cre-driven autophagy-related gene 7 (Atg7) knockout (Amhr-Cre/Atg7f/f mice). In that study, we uncovered a striking difference in the amount of sequestosome 1 (SQSTM1) accumulation between virgin mice and breeder mice with the same genotype. Herein, we aimed to determine whether repeated breeding changed the composition of mesenchymal cell populations in the uterine stroma. Methods: All female mice used in this study were of the same genotype. Atg7 was deleted by Amhr2 promoter-driven Cre recombinase in the uterine stroma and myometrium, except for a triangular stromal region on the mesometrial side. Amhr-Cre/Atg7f/f female mice were divided into two groups: virgin mice with no mating history and aged between 11 and 12 months, and breeder mice with at least 6-month breeding cycles with multiple pregnancies and aged around 12 months. The uteri were used for Western blotting and immunofluorescence staining. Results: SQSTM1 accumulation, representing Atg7 deletion and halted autophagy, was much higher in virgin mice than in breeders. Breeders showed reduced accumulation of several vasoconstrictive factors, which are potential autophagy targets, in the uterus, suggesting that the uterine stroma was repopulated with autophagy-intact cells during repeated pregnancies. Conclusion Multiple pregnancies seem to have improved the uterine environment by replacing autophagy-deficient cells with autophagy-intact cells, providing evidence of cell mixing.

Purpose: This study evaluated the nutrition and food intake status among adults in Jeju, Republic of Korea, based on their sociodemographic characteristics and obesity. Methods: Nine hundred and forty-nine adults aged 19 years or older were included based on the 2022 Jeju Nutrition and Physical Activity Survey data. A dietary assessment was conducted using a one-day, 24-hour recall method, and the nutrition status was evaluated using the 2020 Dietary Reference Intakes for Koreans. The sociodemographic status included sex, age, education, and household income, and obesity was defined as a body mass index (BMI) of ≥ 25 kg/m 2 . Results: The mean age of the subjects was 49.8 years, and the overall prevalence of obesity was 48.4% (59.5% for males and 37.2% for females). The top three insufficient nutrients consumed at less than the estimated average requirement were calcium (77.7%), vitamin A (77.3%), and vitamin C (61.3%), while 40.9% of the subjects consumed fat as more than 30% of their total energy intake. The sodium intake was approximately 1.5 times higher than the chronic disease risk reduction intake level. In terms of food groups, the participants consumed more meat (148.2 g/day), seafood (69.0 g/day), potatoes, and starches (41.6 g/day) but consumed fewer vegetables (214.3 g/day) and less dairy (62.0 g/day) than Korean adults. The nutritional status and food intake patterns differed by the sociodemographic status. In addition, the obese group consumed more poultry and beverages than the non-obese group (p < 0.05 for all). Conclusion Adults in Jeju under-consume essential nutrients while over-consuming certain nutrients, such as fat and sodium. The nutritional status also varied according to the sociodemographic characteristics. These findings suggest that sociodemographic factors should be considered carefully when developing nutritional policies and programs to improve the nutritional status and address obesity among adults in Jeju.

Purpose: This study evaluated the nutrition and food intake status among adults in Jeju, Republic of Korea, based on their sociodemographic characteristics and obesity. Methods: Nine hundred and forty-nine adults aged 19 years or older were included based on the 2022 Jeju Nutrition and Physical Activity Survey data. A dietary assessment was conducted using a one-day, 24-hour recall method, and the nutrition status was evaluated using the 2020 Dietary Reference Intakes for Koreans. The sociodemographic status included sex, age, education, and household income, and obesity was defined as a body mass index (BMI) of ≥ 25 kg/m 2 . Results: The mean age of the subjects was 49.8 years, and the overall prevalence of obesity was 48.4% (59.5% for males and 37.2% for females). The top three insufficient nutrients consumed at less than the estimated average requirement were calcium (77.7%), vitamin A (77.3%), and vitamin C (61.3%), while 40.9% of the subjects consumed fat as more than 30% of their total energy intake. The sodium intake was approximately 1.5 times higher than the chronic disease risk reduction intake level. In terms of food groups, the participants consumed more meat (148.2 g/day), seafood (69.0 g/day), potatoes, and starches (41.6 g/day) but consumed fewer vegetables (214.3 g/day) and less dairy (62.0 g/day) than Korean adults. The nutritional status and food intake patterns differed by the sociodemographic status. In addition, the obese group consumed more poultry and beverages than the non-obese group (p < 0.05 for all). Conclusion Adults in Jeju under-consume essential nutrients while over-consuming certain nutrients, such as fat and sodium. The nutritional status also varied according to the sociodemographic characteristics. These findings suggest that sociodemographic factors should be considered carefully when developing nutritional policies and programs to improve the nutritional status and address obesity among adults in Jeju.

Purpose: This study evaluated the nutrition and food intake status among adults in Jeju, Republic of Korea, based on their sociodemographic characteristics and obesity. Methods: Nine hundred and forty-nine adults aged 19 years or older were included based on the 2022 Jeju Nutrition and Physical Activity Survey data. A dietary assessment was conducted using a one-day, 24-hour recall method, and the nutrition status was evaluated using the 2020 Dietary Reference Intakes for Koreans. The sociodemographic status included sex, age, education, and household income, and obesity was defined as a body mass index (BMI) of ≥ 25 kg/m 2 . Results: The mean age of the subjects was 49.8 years, and the overall prevalence of obesity was 48.4% (59.5% for males and 37.2% for females). The top three insufficient nutrients consumed at less than the estimated average requirement were calcium (77.7%), vitamin A (77.3%), and vitamin C (61.3%), while 40.9% of the subjects consumed fat as more than 30% of their total energy intake. The sodium intake was approximately 1.5 times higher than the chronic disease risk reduction intake level. In terms of food groups, the participants consumed more meat (148.2 g/day), seafood (69.0 g/day), potatoes, and starches (41.6 g/day) but consumed fewer vegetables (214.3 g/day) and less dairy (62.0 g/day) than Korean adults. The nutritional status and food intake patterns differed by the sociodemographic status. In addition, the obese group consumed more poultry and beverages than the non-obese group (p < 0.05 for all). Conclusion Adults in Jeju under-consume essential nutrients while over-consuming certain nutrients, such as fat and sodium. The nutritional status also varied according to the sociodemographic characteristics. These findings suggest that sociodemographic factors should be considered carefully when developing nutritional policies and programs to improve the nutritional status and address obesity among adults in Jeju.

Previous studies have demonstrated that rottlerin, a specific PKCdelta inhibitor, potentiates death receptor- mediated apoptosis through a cytochrome c-dependent or -independent pathway. However, its ability to regulate necrotic cell death, as well as the underlying mechanism, remains unknown. We found that in murine fibrosarcoma L929 cells, treatment with rottlerin protected the cells against TNF-induced necrosis, whereas it sensitized the cells to apoptosis induced by co-treatment with Hsp90 inhibitor geldanamycin and TNF, in a manner independent of its ability to inhibit PKC-delta. TNF treatment induced rapid accumulation of mitochondrial superoxide (O2") through the Nox1 NADPH oxidase when cells undergo necrosis. Moreover, pretreatment with rottlerin failed to induce the GTP-bound form of small GTPase Rac1 by TNF treatment, and subsequently suppressed mitochondrial O2(-) production and poly(ADP-ribose) polymerase activation, thus inhibiting necrotic cell death. Therefore, our study suggests that Nox1 NADPH oxidase is a new molecular target for anti-necrotic activity of rottlerin upon death-receptor ligation.
Acetophenones/*pharmacology ; Animals ; Benzopyrans/*pharmacology ; Cell Death/*drug effects ; Cell Line, Tumor ; Mice ; Protein Kinase Inhibitors/*pharmacology ; Superoxides/metabolism ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors/pharmacology

Activation of c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase family, is an important cellular response that modulates the outcome of the cells which are exposed to the tumor necrosis factor (TNF) or the genotoxic stress including DNA damaging agents. Although it is known that JNK is activated in response to genotoxic stress, neither the pathways to transduce signals to activate JNK nor the primary sensors of the cells that trigger the stress response have been identified. Here, we report that the receptor interacting protein (RIP), a key adaptor protein of TNF signaling, was required to activate JNK in the cells treated with certain DNA damaging agents such as adriamycin (Adr) and 1-beta-D-arabinofuranosylcytosine (Ara-C) that cause slow and sustained activation, but it was not required when treated with N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and short wavelength UV, which causes quick and transient activation. Our findings revealed that this sustained JNK activation was not mediated by the TNF (tumor necrosis factor) receptor signaling, but it required a functional ATM (ataxia telangiectasia) activity. In addition, JNK inhibitor SP-600125 significantly blocked the Adr-induced cell death, but it did not affect the cell death induced by MNNG. These findings suggest that the sustained activation of JNK mediated by RIP plays an important role in the DNA damage-induced cell death, and that the duration of JNK activation relays a different stress response to determine the cell fate.
Cell Death ; DNA ; DNA Damage ; Doxorubicin ; Humans ; JNK Mitogen-Activated Protein Kinases ; Methylnitronitrosoguanidine ; Necrosis ; Protein Kinases ; Tumor Necrosis Factor-alpha