Objective: Fenbendazole (FZ) has potential anti-cancer effects, but its poor water solubility limits its use for cancer therapy. In this study, we investigated the anti-cancer effect of FZ with different drug delivery methods on epithelial ovarian cancer (EOC) in both in vitro and in vivo models. Methods: EOC cell lines were treated with FZ and cell proliferation was assessed. The effect of FZ on tumor growth in cell line xenograft mouse model of EOC was examined according to the delivery route, including oral and intraperitoneal administration. To improve the systemic delivery of FZ by converting fat-soluble drugs to hydrophilic, we prepared FZ-encapsulated poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (FZ-PLGA-NPs). We investigated the preclinical efficacy of FZ-PLGA-NPs by analyzing cell proliferation, apoptosis, and in vivo models including cell lines and patient-derived xenograft (PDX) of EOC. Results: FZ significantly decreased cell proliferation of both chemosensitive and chemoresistant EOC cells. However, in cell line xenograft mouse models, there was no effect of oral FZ treatment on tumor reduction. When administered intraperitoneally, FZ was not absorbed but aggregated in the intraperitoneal space. We synthesized FZ-PLGA-NPs to obtain water solubility and enhance drug absorption. FZ-PLGA-NPs significantly decreased cell proliferation in EOC cell lines. Intravenous injection of FZ-PLGA-NP in xenograft mouse models with HeyA8 and HeyA8-MDR significantly reduced tumor weight compared to the control group. FZ-PLGA-NPs showed anti-cancer effects in PDX model as well. Conclusion FZ-incorporated PLGA nanoparticles exerted significant anti-cancer effects in EOC cells and xenograft models including PDX. These results warrant further investigation in clinical trials.

Background: Human breast milk is essential and provides irreplaceable nutrients for early humans. However, breastfeeding is not easy for various reasons in medical institution environments. Therefore, in order to improve the breastfeeding environment, we investigated the difficult reality of breastfeeding through questionnaire responses from medical institution workers. Methods: A survey was conducted among 179 medical institution workers with experience in childbirth within the last five years. The survey results of 175 people were analyzed, with incoherent answers excluded. Results: Of the 175 people surveyed, a total of 108 people (61.7%) worked during the day, and 33 people (18.9%) worked in three shifts. Among 133 mothers who stayed with their babies in the same nursing room, 111 (93.3%) kept breastfeeding for more than a month, but among those who stayed apart, only 10 (71.4%) continued breastfeeding for more than a month (P = 0.024). Ninety-five (88.0%) of daytime workers, 32 (94.1%) two-shift workers, and 33 (100%) three-shift workers continued breastfeeding for more than a month (P = 0.026). Workers in general hospitals tended to breastfeed for significantly longer than those that worked in tertiary hospitals (P = 0.003). A difference was also noted between occupation categories (P = 0.019), but a more significant difference was found in the comparison between nurses and doctors (P = 0.012). Longer breastfeeding periods were noted when mothers worked three shifts (P = 0.037). Depending on the period planned for breastfeeding prior to childbirth, the actual breastfeeding maintenance period after birth showed a significant difference (P = 0.002). Of 112 mothers who responded to the question regarding difficulties in breastfeeding after returning to work, 87 (77.7%) mentioned a lack of time caused by being busy at work, 82 (73.2%) mentioned the need for places and appropriate circumstances. Conclusion In medical institutions, it is recommended that environmental improvements in medical institutions, the implementation of supporting policies, and the provision of specialized education on breastfeeding are necessary to promote breastfeeding.

Background/Aims: Favorable outcomes of potassium-competitive acid blocker (PCAB)-containing eradication therapy have been reported. In fact, tegoprazan, a recently developed PCAB, was presumed to show good eradication efficacy even for resistant Helicobacter pylori. We aimed to investigate the anti-H. pylori efficacy of tegoprazan compared with that of vonoprazan. Methods: A total of 220 resistant clinical H. pylori isolates were utilized. The anti-H. pylori efficacy of PCABs was determined by evaluating the minimum inhibitory concentrations (MICs) of clarithromycin, fluoroquinolone, metronidazole, and amoxicillin in combination with vonoprazan or tegoprazan by the agar dilution method. The impact of the mutations responsible for resistance development, such as 23S rRNA, gyrA, rdxA, frxA, and pbp1 mutations, was also analyzed. Results: H. pylori growth was significantly inhibited in a medium containing 1 μg/mL clarithromy-cin with tegoprazan (128 μg/mL). The MICs of clarithromycin (46.3%), fluoroquinolone (46.7%), metronidazole (55.6%), and amoxicillin (34.5%) against resistant H. pylori isolates improved after tegoprazan administration. Tegoprazan demonstrated more frequent susceptibility acquisitionwith metronidazole than with vonoprazan (20.6% vs 4.7%, p=0.014). However, there were nosignificant differences depending on the mutational status of each antimicrobial agent. Conclusions Tegoprazan administration may improve the susceptibility of antimicrobial-resistant H. pylori, independent of acid suppression.

Background/Aims: The gut microbiota regulates intestinal immune homeostasis through host-microbiota interactions. Multiple factors affect the gut microbiota, including age, sex, diet, and use of drugs. In addition, information on gut microbiota differs depending on the samples.The aim of this study is to investigate whether changes in cecal microbiota depend on aging. Methods: Gut microbiota in cecal contents of 6-, 31-, and 74-week-old and 2-year-old male Fischer-344 rats (corresponding to 5-, 30-, 60-, and 80-year-old humans in terms of age) were analyzed using 16S ribosomal RNA metagenome sequencing and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) based on the Kyoto Encyclopedia of Genes and Genomes orthology.Moreover, short-chain fatty acid (SCFA) level in cecum and inflammation related factors were measured using real-time quantitative polymerase chain reaction and enzyme linked immunosorbent assay. Results: Alpha and beta diversity did not change significantly with age. At the family level, Lachnospiraceae and Ruminococcaceae, which produce SCFAs, showed significant change in 31-week-old rats: Lachnospiraceae significantly increased at 31 weeks of age, compared to other age groups, while Ruminococcaceae decreased. Butyrate levels in cecum were significantly increased in 31-week-old rats, and the expression of inflammation related genes was increased followed aging. Especially, EU622775_s and EU622773_s, which were highly abundance species in 31-week-old rats, showed significant relationship with butyrate concentration. Enzymes required for producing butyrate—acetyl-CoA transferase, butyryl-CoA dehydrogenase, and butyrate kinase—were not predicted by PICRUSt. Conclusions Major bacterial taxa in the cecal lumen, such as Lachnospiraceae, well-known SCFAs-producing family, changed in 31-week-old rats.Moreover, unknown species EU622775_s and EU622773_s showed strong association with cecal butyrate level at 31 weeks of age.

PURPOSE: This study demonstrates that estradiol downregulates inflammation and inhibits colorectal cancer (CRC) development in azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model. MATERIALS AND METHODS: AOM/DSS-treated male and female mice were sacrificed at weeks 2, 10, and 16, to assess estrogen effects on colitis and carcinogenesis. Macroscopic and histologic severity of colitis and Western blot and quantitative real-time polymerase chain reaction were evaluated, to measure inflammatory mediators and cytokines. RESULTS: Compared with AOM/DSS-treated male mice (M-AOM/DSS group), AOM/DSS-treated male mice with estradiol administration (M-AOM/DSS+estr group) displayed at week 2 significantly decreased severity of colitis. At weeks 10 and 16, AOM/DSS-treated female mice (F-AOM/DSS group) and the M-AOM/DSS+estr group showed significantly lower tumor multiplicity compared with the M-AOM/DSS group. At week 2, F-AOM/DSS group had a lower level of nuclear factor-κB (NF-κB) expression and higher level of nuclear factor erythroid 2-related factor 2 (Nrf2) expression, compared to the M-AOM/DSS group. At week 2, expression levels of NF-κB and its related mediators decreased in the M-AOM/DSS+estr group, while levels of Nrf2 and Nrf2-related anti-oxidant enzymes increased. In addition, estradiol significantly increased Nod-like receptor protein 3 (NLRP3) inflammasome expressions in AOM/DSS-treated male mice. In contrast, at weeks 10 and 16, Nrf2 and its-related anti-oxidant enzymes and NLRP3 inflammasome were highly expressed in M-AOM/DSS group and in F-AOM/DSS group, who developed cancer. CONCLUSION: The data suggest that estradiol inhibits the initiation of CRC by regulating Nrf2-related pathways. Moreover, these imply the dual role of Nrf2 and NLRP3 inflammasome, including promotion of tumor progression upon tumor initiation.
Animals ; Blotting, Western ; Carcinogenesis ; Colitis ; Colorectal Neoplasms ; Cytokines ; Estradiol ; Estrogens ; Female ; Humans ; Inflammasomes ; Inflammation ; Male ; Mice ; NF-E2-Related Factor 2 ; NF-kappa B ; Real-Time Polymerase Chain Reaction ; Sex Characteristics ; Sodium

BACKGROUND: Gut microbiota is closely associated with development and exacerbation of inflammatory bowel diseases (IBD). The aim of this study was to investigate differences in gut microbiota depending on sex and changes of gut microbiota during IBD developments. METHODS: 16s rRNA metagenomic sequencing was performed for fecal materials from 8-week-old wild type (WT) and interleukin 10 (IL-10) knockout (KO) C57BL/6 mice of both sexes. Diversity indices, relative abundance of microbiota, and linear discriminant analysis effect size were examined to compare microbial communities between groups. Clustering of groups was performed by principal coordinates analysis (PCoA) and unweighted pair group method with arithmetic mean (UPGMA). Functional capabilities of microbiota were estimated using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) based on Kyoto Encyclopedia of Genes and Genomes database. RESULTS: PCoA and UPGMA tree analysis of beta-diversity demonstrated significant differences in gut microbiota between male and female groups of WT mice, but not of IL-10 KO mice. Firmicutes to Bacteroides ratio was higher in male group than that in female group in both WT mice and IL-10 KO mice. Phylum Proteobacteria significantly increased in female IL-10 KO mice than that in female WT mice. At species level, Lactobacillus murinus, Bacteroides acidifaciens, and Helicobacter hepaticus significantly increased in IL-10 KO mice than in WT mice. The relative abundance of beta-glucuronidase (K01195) was higher in female IL-10 KO mice than that in female WT mice by PICRUSt. CONCLUSIONS: Our results suggest that microbiota-host interactions might differ between sexes during development of IBD.
Animals ; Bacteroides ; Female ; Firmicutes ; Gastrointestinal Microbiome ; Genome ; Glucuronidase ; Helicobacter hepaticus ; Humans ; Inflammatory Bowel Diseases ; Interleukin-10 ; Lactobacillus ; Male ; Metagenomics ; Methods ; Mice ; Microbiota ; Proteobacteria ; Sequence Analysis ; Sex Characteristics ; Trees

BACKGROUND/OBJECTIVES: The purpose of this study was to assess the accuracy of a dietary reference intake (DRI) predictive equation for estimated energy requirements (EER) in female college tennis athletes and non-athlete students using doubly labeled water (DLW) as a reference method. MATERIALS/METHODS: Fifteen female college students, including eight tennis athletes and seven non-athlete subjects (aged between 19 to 24 years), were involved in the study. Subjects' total energy expenditure (TEE) was measured by the DLW method, and EER were calculated using the DRI predictive equation. The accuracy of this equation was assessed by comparing the EER calculated using the DRI predictive equation (EER(DRI)) and TEE measured by the DLW method (TEE(DLW)) based on calculation of percentage difference mean and percentage of accurate prediction. The agreement between the two methods was assessed by the Bland-Altman method. RESULTS: The percentage difference mean between the methods was -1.1% in athletes and 1.8% in non-athlete subjects, whereas the percentage of accurate prediction was 37.5% and 85.7%, respectively. In the case of athletic subjects, the DRI predictive equation showed a clear bias negatively proportional to the subjects' TEE. CONCLUSIONS: The results from this study suggest that the DRI predictive equation could be used to obtain EER in non-athlete female college students at a group level. However, this equation would be difficult to use in the case of athletes at the group and individual levels. The development of a new and more appropriate equation for the prediction of energy expenditure in athletes is proposed.
Athletes* ; Bias (Epidemiology) ; Energy Metabolism ; Female* ; Humans ; Methods* ; Motor Activity ; Recommended Dietary Allowances* ; Sports ; Tennis* ; Water*

BACKGROUND: The colitis-associated cancer exhibits different characteristics according to sex in the initiation and progression of the tumors. The aim of this study was to investigate the sex-associated difference in the azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer model. METHODS: The AOM/DSS ICR mouse model was established to compare male with female, and then the severity of colitis-associated carcinogenesis was examined macroscopically and histologically regarding the number, size, and location of tumors. Subsequently, levels of colonic mucosal cytokine, interleukin (IL)-1β and myeloperoxidase (MPO) were assessed. RESULTS: At the 16th week, the tumor multiplicity and the pro-inflammatory factors differed according to sex. The total tumor number was significantly higher in male (P = 0.020) and the number of large tumors (diameter > 2 mm) was higher in male (P = 0.026). In male, the tumors located more in distal colon (P = 0.001). MPO was significantly higher in AOM/DSS-treated male mice compared to the control group (P = 0.003), whereas the corresponding female group showed no significant change (P = 0.086). Colonic IL-1β level significantly increased in AOM/DSS groups compared to control groups both in male and female (male, P = 0.014; female, P = 0.005). It was higher in male group; however, there was no statistical significance (P = 0.226). CONCLUSIONS: In AOM/DSS murine model, colitis-associated colon tumorigenesis are induced more severely in male mice than female probably by way of inflammatory mediators such as IL-1β and MPO. The sex-related differences at the animal model of colon cancer suggest the importance of approach to disease with sex-specific medicine in human.
Animals ; Carcinogenesis ; Colitis ; Colon* ; Colonic Neoplasms* ; Female ; Humans ; Interleukins ; Male ; Mice* ; Mice, Inbred ICR ; Models, Animal ; Peroxidase ; Sodium

PURPOSE: The study examined the effects of early enteral nutrition on the patients' length of stay in an intensive care unit (ICU), length of stay and mortality rate. METHODS: A retrospective design was employed with a total of 461 patients (mean age=69.9±15.6 years; 253 males; 208 females). They were divided into two groups according to when they received enteral feeding: an "early enteral nutrition" (EEN) group of 148 patients (32.1%) who received enteral feeding within 48 hours of their arrival at the hospital and a "delayed enteral nutrition" (DEN) group of 313 patients (67.9%) who received enteral feeding at some point after 48 hours of their arrival at the hospital. The EEN group and control group were similar in terms of age, sex, body mass index, and underlying diseases. RESULTS: The EEN group's total length of stay in hospital was shorter (23.29±27.19 days) than that of the control group (36.74±32.24 days); the difference was significant (P<0.001). The EEN group also showed a shorter length of stay in the ICU (13.67±22.77 days) than the DEN group (17.46±21.02 days) and a lower mortality rate (17.6%) than the control group (18.8%), but these differences were not significant. CONCLUSION: The study found that early enteral nutrition treatment reduced total length of stay in hospital significantly. The findings suggest that early enteral nutrition treatment plays an important role in the patients' recovery and prognosis.
Body Mass Index ; Enteral Nutrition* ; Humans ; Intensive Care Units ; Length of Stay ; Male ; Mortality ; Nutritional Support ; Prognosis ; Retrospective Studies

OBJECTIVES: The objective of this study was to evaluate the thermic effects, the macronutrient oxidation rates and the satiety of medium-chain triglycerides (MCT). METHODS: The thermic effects of two meals containing MCT or long-chain triglycerides (LCT) were compared in ten healthy men (mean age 24.4 +/- 2.9 years). Energy content of the meal was 30% of resting metabolic rate of each subject. Metabolic rate and macronutrient oxidation rate were measured before the meals and for 6 hours after the meals by indirect calorimetry. Satiety was estimated by using visual analogue scales (VAS) at 8 times (before the meal and for 6 hours after meal). RESULTS: Total thermic effect of MCT meal (42.8 kcal, 8.0% of energy intake) was significantly higher than that (26.8 kcal, 5.1% of energy intake) of the LCT meal. Mean postprandial oxygen consumption was also significantly different between the two types of meals (MCT meal: 0.29 +/- 0.35 L/min, LCT meal: 0.28 +/- 0.27 L/min). There were no significant differences in total postprandial carbohydrate and fat oxidation rates between the two meals. However, from 30 to 120 minutes after consumption of meals, the fat oxidation rate of MCT meal was significantly higher than that of the LCT meal. Comparison of satiety values (hunger, fullness and appetite) between the two meals showed that MCT meal maintained satiety for a longer time than the LCT meal. CONCLUSIONS: This study showed the possibility that long-term substitution of MCT for LCT would produce weight loss if energy intake remained constant.
Calorimetry, Indirect ; Energy Intake ; Humans ; Male ; Meals ; Oxygen Consumption ; Triglycerides* ; Weight Loss ; Weights and Measures