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A new strategy for the synthesis of unsymmetrical ureas, carbamates, thiocarbamates, and anilides was developed with methyl pyruvate oxime as the carbonyl synthon. The intrinsic reactivity of the reagent enabled consecutive disubstitution involving direct amidation and one-pot deoximative substitution with various nucleophiles. The utility of the method was demonstrated with the synthesis of bioactive molecules.
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A new approach for the preparation of amides was developed using C-C bond cleavage that initiates C- to N-acyl transfer, employing activated ketones as acylation reagents and amine nucleophiles. The reaction was operational under the coupling reagent system that is commonly utilized for peptide bond formations. The method enables practical preparation of amides using linear and cyclic ketone substrates under mild conditions.
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Background/Aims@#A high-fat diet (HFD) causes dysbiosis and promotes inflammatory responses in the colon. This study aims to evaluate the effects of Clostridium butyricum on HFD-induced gut microbial changes in rats. @*Methods@#Six-week-old Fischer-344 rats with both sexes were given a control or HFD during 8 weeks, and 1-to-100-fold diluted Clostridium butyricum were administered by gavage. Fecal microbiota analyses were conducted using 16S ribosomal RNA metagenomic sequencing and predictive functional profiling of microbial communities in metabolism. @*Results@#A significant increase in Ruminococcaceae and Lachnospiraceae, which are butyric acid-producing bacterial families, was observed in the probiotics groups depending on sex. In contrast, Akkermansia muciniphila, which increased through a HFD regardless of sex, and decreased in the probiotics groups. A. muciniphila positively correlated with Claudin-1 expression in males (P < 0.001) and negatively correlated with the expression of Claudin-2 (P = 0.042), IL-1β (P = 0.037), and IL-6 (P = 0.044) in females. In terms of functional analyses, a HFD decreased the relative abundances of M00131 (carbohydrate metabolism module), M00579, and M00608 (energy metabolism), and increased those of M00307 (carbohydrate metabolism), regardless of sex. However, these changes recovered especially in male C. butyricum groups. Furthermore, M00131, M00579, and M00608 showed a positive correlation and M00307 showed a negative correlation with the relative abundance of A. muciniphila (P < 0.001). @*Conclusion@#The beneficial effects of C. butyricum on HFD-induced gut dysbiosis in young male rats originate from the functional profiles of carbohydrate and energy metabolism.
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Background/Aims@#The gut microbiome has emerged as a key player that mechanistically links various risk factors to colorectal cancer (CRC) etiology. However, the role of the gut microbiome in CRC pathogenesis remains unclear. This study aimed to characterize the gut microbiota in healthy controls (HCs) and patients with colorectal adenoma (AD) and CRC in subgroups based on sex and age. @*Methods@#Study participants who visited the hospital for surveillance of CRC or gastrointestinal symptoms were prospectively enrolled, and the gut microbiome was analyzed based on fecal samples. @*Results@#In terms of HC-AD-CRC sequence, commensal bacteria, including lactate-producing (Streptococcus salivarius) and butyrate-producing (Faecalibacterium prausnitzii, Anaerostipes hadrus, and Eubacterium hallii) bacteria, were more abundant in the HC group than in the AD and CRC groups. In the sex comparison, the female HC group had more lactate-producing bacteria (Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Lactobacillus ruminis) than the male HC group. In age comparison, younger subjects had more butyrate-producing bacteria (Agathobaculum butyriciproducens and Blautia faecis) than the older subjects in the HC group.Interestingly, lactate-producing bacteria (B. catenulatum) were more abundant in females than males among younger HC group subjects. However, these sex- and age-dependent differences were not observed in the AD and CRC groups. @*Conclusions@#The gut microbiome, specifically lactate- and butyrate-producing bacteria, which were found to be abundant in the HC group, may play a role in preventing the progression of CRC. In particular, lactate-producing bacteria, which were found to be less abundant in healthy male controls may contribute to the higher incidence of CRC in males.
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Dysbiosis in gut microbiota is known to contribute to development of irritable bowel syndrome. We tried to investigate the effect of Bifidobacterium longum on repeated water avoidance stress (WAS) in a Wistar rat model. The three groups (no-stress, WAS, and WAS with B. longum) of rats were allocated to sham or WAS for 1 hour daily for 10 days, and B. longum was administered through gavage for 10 days. Fecal pellet numbers were counted at the end of each 1-hour session of WAS. After 10 days of repeated WAS, the rats were eutanized, and the feces were collected. WAS increased fecal pellet output (FPO) significantly in both sexes (P < 0.001), while the female B. longum group showed significantly decreased FPO (P = 0.005). However, there was no consistent change of myeloperoxidase activity and mRNA expression of interleukin-1ββ and TNF-αα. Mast cell infiltration at colonic submucosa increased in the female WAS group (P = 0.016). In terms of fecal microbiota, the repeated WAS groups in both sexes showed different beta-diversity compared to control and WAS with B. longum groups. WAS-induced mast cell infiltration was reduced by the administration of B. longum in female rats. Moreover, administration of B. longum relieved WAS-caused dysbiosis, especially in female rats. In conclusion, B. longum was beneficial for WAS-induced stress in rats, especially in females.
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Purpose@#To evaluate the effectiveness of an instrument devised for slit-lamp examination of donor corneas suspended in preservation medium. @*Methods@#The study examined two donor corneas received at Yeouido St. Mary's Hospital in February 2023 and March 2023. The instrument has three main components: a plastic holder to hold the preservation medium bottle, a cube with a mirror for reflecting the slit beam, and a stand to attach the device to the slit-lamp. Using the instrument, the donor corneas were examined via slit-lamp: microscopy with the endothelium facing upward and downward. Specular microscopy and anterior segment optical coherence tomography (OCT) were also performed on the preserved donor corneas. @*Results@#Slit-lamp examination of donor corneas in preservation medium using the instrument showed overall corneal buttoning and optical sections of the donor cornea. Using specular reflection and retroillumination, the endothelial layer was partially visible. However, specular microscopy and anterior segment OCT could not examine the donor cornea in preservation medium using the instrument. @*Conclusions@#The devised instrument facilitates slit-lamp examination of donor corneas in preservation medium, enabling a qualitative assessment of donor corneas before corneal transplantation surgery.
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Purpose@#The purpose of this study was to identify the relationship between cancer coping, family support, and degree of posttraumatic growth in female genital cancer patients receiving chemotherapy and provide evidence for nursing intervention to enhance posttraumatic growth. @*Methods@#A cross-sectional study was conducted to 114 participants. The cancer coping, family support, and posttraumatic growth were measured using a self-reported questionnaire. The collected data were analyzed with independent t-test, one-way ANOVA, and Pearson correlation using the SPSS/win 28.0 statistical programs. @*Results@#The mean score of cancer coping was 62.65±13.53, that of intrapersonal coping 38.32±8.34, and that of interpersonal coping was 24.32±6.56. The mean score of family support was 49.06±7.32 and posttraumatic growth was 59.66±17.92. Posttraumatic growth showed a statistically significant positive correlation among intrapersonal coping (r=.80), interpersonal coping (r=.61), and family support (r=.42, p<.001). @*Conclusion@#To increase posttraumatic growth, it is necessary to develop coping interventions so that cancer patients can effectively and positively cope with various difficulties and problems in the process of chemotherapy.
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Purpose@#17β-Estradiol (E2) supplementation suppresses MC38 tumor growth by downregulating the expression of programmed death-ligand 1 (PD-L1). This study aims to figure out the gut microbiota that respond to anti–PD-L1 and/or estrogen treatment in MC38 colon cancer model. @*Materials and Methods@#A syngeneic colon tumor model was developed by injection of MC38 cells into C57BL/6 background male and female mice. Three days before MC38 cells injection, E2 was supplemented to male mice daily for 1 week. Male and female mice with MC38 tumors (50-100 mm3) were injected with anti–PD-L1 antibody. Fresh feces were collected 26 days after injection of MC38 cells and 16S rRNA metagenomics sequencing of DNA extracted from feces was used to assess gut microbial composition. @*Results@#At the taxonomic family level, Muribaculaceae was enriched only in the MC38 male control group. In male mice, linear discriminant analysis effect size analysis at the species level revealed that the four microorganisms were commonly regulated in single and combination treatment with anti–PD-L1 and/or E2; a decrease in PAC001068_g_uc and PAC001070_s (family Muribaculaceae) and increase in PAC001716_s and PAC001785_s (family Ruminococcaceae). Interestingly, in the anti–PD-L1 plus E2 group, a decrease in opportunistic pathogens (Enterobacteriaceae group) and an increase in commensal bacteria (Lactobacillus murinus group and Parabacteroides goldsteinii) were observed. Furthermore, the abundance of Parabacteroides goldsteinii was increased in both males and females in the anti–PD-L1 group. @*Conclusion@#Our results suggest that gut microbial changes induced by the pretreatment of estrogen before anti–PD-L1 might contribute to treatment of MC38 colon cancer.
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Purpose@#Sex hormones are known to affect the gut microbiota. Previously, we reported that endogenous and exogenous testosterone are associated with colorectal cancer (CRC) development and submucosal invasion. In the present study, we investigated whether the gut microbiota is affected by orchiectomy (ORX) and testosterone propionate (TP) administration using an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC mouse model. @*Materials and Methods@#Gut microbiota was evaluated by means of 16S rRNA gene sequencing of stool DNA extracted from feces that were obtained at 13 weeks after AOM injection (from 22-week-old animals) and stored in a gas-generating pouch. @*Results@#The increase in microbial diversity (Chao1 and Phylogenetic Diversity index) and Firmicutes/Bacteroidetes (F/B) ratio upon AOM/DSS treatment in ORX mice was significantly decreased by TP supplementation. The ratio of commensal bacteria to opportunistic pathogens was lower in the TP-administered females and ORX mice than in the AOM/DSS group. Opportunistic pathogens (Mucispirillum schaedleri or Akkermansia muciniphila) were identified only in the TP group. In addition, microbial diversity and F/B ratio were higher in male controls than in female and ORX controls. Flintibacter butyricus, Ruminococcus bromii, and Romboutsia timonensis showed similar changes in the male control group as those in the female and ORX controls. @*Conclusion@#In conclusion, testosterone determines the dysbiosis of gut microbiota, which suggests that it plays a role in the sex-related differences in colorectal carcinogenesis.
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The FOLFOX regimen (combination of leucovorin, 5-fluorouracil, and oxaliplatin) is the first-line treatment for high-risk stage 2 and 3 colorectal cancer patients. While hypersensitivity reactions (HSRs) caused by oxaliplatin are commonly reported, HSRs due to leucovorin have been infrequently reported. This report aims to investigate the clinical presentation, diagnosis, and management of leucovorin induced HSRs. A 60-year-old female developed generalized edema, dyspnea, and facial redness during cetuximab plus FOLFOX chemotherapy administered for management of metastatic colorectal cancer. Because HSRs induced by oxaliplatin are commonly reported, we initially presumed an oxaliplatin-induced HSR. However, despite undergoing oxaliplatin desensitization, HSRs persisted, and they were still observed when leucovorin was administered without oxaliplatin. The patient was diagnosed with leucovorin-induced HSR and underwent leucovorin desensitization. However, the reactions recurred within 30 minutes of the initiating the desensitization. Considering unsuccessful leucovorin desensitization, leucovorin was excluded. The patient received cetuximab and oxaliplatin chemotherapy without leucovorin to date without any adverse effects. While leucovorin-induced HSRs are infrequently reported, they should still be regarded as potential adverse effects.
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Roseburia faecis, a butyrate-producing, gram-positive anaerobic bacterium, was evaluated for its usefulness against repeated water avoidance stress (WAS)-induced irritable bowel syndrome (IBS) in a rat model, and the underlying mechanism was explored.We divided the subjects into three groups: one without stress exposure, another subjected to daily 1-hour WAS for 10 days, and a third exposed to the same WAS regimen while also receiving two different R. faecis strains (BBH024 or R22-12-24) via oral gavage for the same 10-day duration. Fecal pellet output (FPO), a toluidine blue assay for mast cell infiltration, and fecal microbiota analyses were conducted using 16S rRNA metagenomic sequencing. Predictive functional profiling of microbial communities in metabolism was also conducted. FPO and colonic mucosal mast cell counts were significantly higher in the WAS group than in the control group (male, P = 0.004; female, P = 0.027). The administration of both BBH024 (male, P = 0.015; female, P = 0.022) and R22-12-24 (male, P = 0.003; female, P = 0.040) significantly reduced FPO. Submucosal mast cell infiltration in the colon showed a similar pattern in males. In case of fecal microbiota, the WAS with R. faecis group showed increased abundance of the Roseburia genus compared to WAS alone. Moreover, the expression of a gene encoding a D-methionine transport system substrate-binding protein was significantly elevated in the WAS with R. faecis group compared to that in the WAS (male, P = 0.028; female, P = 0.025) group. These results indicate that R. faecis is a useful probiotic for treating IBS and colonic microinflammation.
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Anhydrous ammonia is a commonly used chemical in industry. Ammonia gas inhalation causes thermal injuries and alkali burns in the airway and lung parenchyma. Previous case reports have stated that respiratory sequelae after acute ammonia inhalation burns were associated with structural lung disease, such as bronchiectasis or interstitial lung disease. We herein report two cases of long-term sequelae with persistent airflow limitation after ammonia inhalation burns.
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Purpose@#It is crucial to identify the causative allergen of respiratory allergic disease. Air pollution and climate change affect the allergen concentration as well as the sensitization rate. This study aims to analyze the inhalant allergen sensitization in patients with respiratory allergic disease in Busan and Gyeongsangnam-do province. @*Methods@#We retrospectively analyzed skin prick test results from patients who visited an allergy clinic at a university hospital in Busan and Gyeongsangnam-do in 2011 and 2016. Sensitivity to inhalant allergens was identified and analyzed by year and region. The pollen allergen concentration in Busan was also analyzed. @*Results@#The total numbers of participants were 697 in 2011 and 1,644 in 2016. The mite sensitization rate was the highest at approximately 36%, and tree pollen sensitization rate showed 10%–15%. However, the sensitization of most tree pollen and Japanese hop significantly decreased in 2016. In 2011, the mite sensitization rate of patients in the Western Gyeongsangnam-do region was remarkably low at 26%–28%, but this difference disappeared in 2016. The concentration of pollen allergens in Busan showed a tendency to decrease. @*Conclusion@#This study confirmed the longitudinal change in the sensitization rate of major inhalant allergens in patients with respiratory allergy in Busan and Gyeongsangnam-do province, as well as a significant decrease in tree pollen antigen. Based on our results, this information can be used as a basis for future patient management, and further research will be made possible by establishing a research network.
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Purpose@#To identify the differences in perception of and adherence to the COVID-19 social distancing behavior guidelines among health care workers, patients, and the general public and to use them to prevent the spread of COVID-19. @*Methods@#From October 16 2020 to November 30, 2020, a survey was conducted among 85 health care workers, 85 patients, and 82 general public regarding the perception of and adherence to the COVID-19 social distancing behavior guidelines. @*Results@#Patients scored significantly higher than the general public in the adherence to the COVID-19 social distancing behavior guideline, and there was no difference between health care workers and general public, and patients and health care workers. In the multivariate analysis, the factors that influence the adherence of the COVID-19 social distancing behavior guide were found in women and the perception of the COVID-19 social distancing behavior guideline. @*Conclusion@#In order to promote the implementation of the COVID-19 social distancing behavior guideline, it is necessary to increase the perception of the COVID-19 social distancing behavior guideline and provide additional education in men. It is necessary to investigate the reason behind why men have low adherence to the COVID-19 social distancing behavior guideline.
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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.
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Background@#Programmed cell death-ligand 1 (PD-L1) has an important role in regulating immune reactions by binding to programmed death 1 (PD-1) on immune cells, which could prevent the exacerbation of autoimmune thyroid disease (AITD). The aim of this study was to evaluate the association of PD-L1 polymorphism with AITD, including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). @*Methods@#A total of 189 GD patients, 234 HT patients, and 846 healthy age- and sex-matched controls were enrolled in this study. We analyzed PD-L1 single nucleotide polymorphism (SNP) (rs822339) and investigated the associations with clinical disease course and outcome. @*Results@#Genotype frequency at the PD-L1 marker RS822339 in GD (P=0.219) and HT (P=0.764) patients did not differ from that among healthy controls. In patients with GD, the A/G or G/G genotype group demonstrated higher TBII titer (20.6±20.5 vs. 28.0± 25.8, P=0.044) and longer treatment duration (39.0±40.4 months vs. 62.4±65.0 months, P=0.003) compared to the A/A genotype group. Among patients in whom anti-thyroid peroxidase (TPO) antibody was measured after treatment of GD, post-treatment antiTPO positivity was higher in the A/G or G/G genotype group compared to the A/A genotype group (48.1% vs. 69.9%, P=0.045). Among patients with HT, there was no significant difference of anti-TPO antibody positivity (79.4% vs. 68.6%, P=0.121), anti-thyroglobulin antibody positivity (80.9% vs. 84.7%, P=0.661), or development to overt hypothyroidism (68.0% vs. 71.1%, P=0.632) between the A/A genotype group and the A/G or G/G genotype group. @*Conclusion@#The genotype frequency of PD-L1 (rs822339) is not different in patients with AITD compared with healthy controls. The intact PD-1/PD-L1 pathway in GD and HT might be important to maintain chronicity of AITD by protecting immune tolerance. However, the PD-L1 SNP could be associated with difficulty in achieving remission in patients with GD, which may be helpful to predict the possibility of longer treatment. Further studies are required to investigate the complex immune tolerance system in patients with AITD.
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Colon tumors develop more frequently in male than in female. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays differential roles in the stage of tumorigenesis. The purpose of this study was to investigate the role of Nrf2 on colitis-associated tumorigenesis using Nrf2 knockout (KO) female mice. Azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated wild-type (WT) and Nrf2 KO female mice were sacrificed at week 2 and 16 after AOM injection. Severity of colitis, tumor incidence, and levels of inflammatory mediators were evaluated in AOM/DSS-treated WT and Nrf2 KO mice. Furthermore, qRT-PCR, Western blot abnalysis, and ELISA were performed in colon tissues. At week 2, AOM/DSS-induced colon tissue damages were significantly greater in Nrf2 KO than in WT mice. At week 16, tumor numbers (> 2 mm size) were significantly lower in both the proximal and distal colon in Nrf2 KO compared to WT. The overall incidences of adenoma/cancer of the proximal colon and submucosal invasive cancer of the distal colon were reduced by Nrf2 KO. The mRNA and protein expression levels of NF-κB-related mediators (i.e., iNOS and COX-2) and Nrf2-related antioxidants (i.e., heme oxygenase-1 and glutamate-cysteine ligase catalytic subunit) were significantly lower in the Nrf2 KO than in WT mice. Interestingly, the protein level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) was higher in AOM/DSS-treated Nrf2 KO than in WT mice. Our results support the oncogenic effect of Nrf2 in the later stage of carcinogenesis and upregulation of tumor suppressor 15-PGDH might contribute to the repression of colitis-associated tumorigenesis in Nrf2 KO female mice.
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Background@#Programmed cell death-ligand 1 (PD-L1) has an important role in regulating immune reactions by binding to programmed death 1 (PD-1) on immune cells, which could prevent the exacerbation of autoimmune thyroid disease (AITD). The aim of this study was to evaluate the association of PD-L1 polymorphism with AITD, including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). @*Methods@#A total of 189 GD patients, 234 HT patients, and 846 healthy age- and sex-matched controls were enrolled in this study. We analyzed PD-L1 single nucleotide polymorphism (SNP) (rs822339) and investigated the associations with clinical disease course and outcome. @*Results@#Genotype frequency at the PD-L1 marker RS822339 in GD (P=0.219) and HT (P=0.764) patients did not differ from that among healthy controls. In patients with GD, the A/G or G/G genotype group demonstrated higher TBII titer (20.6±20.5 vs. 28.0± 25.8, P=0.044) and longer treatment duration (39.0±40.4 months vs. 62.4±65.0 months, P=0.003) compared to the A/A genotype group. Among patients in whom anti-thyroid peroxidase (TPO) antibody was measured after treatment of GD, post-treatment antiTPO positivity was higher in the A/G or G/G genotype group compared to the A/A genotype group (48.1% vs. 69.9%, P=0.045). Among patients with HT, there was no significant difference of anti-TPO antibody positivity (79.4% vs. 68.6%, P=0.121), anti-thyroglobulin antibody positivity (80.9% vs. 84.7%, P=0.661), or development to overt hypothyroidism (68.0% vs. 71.1%, P=0.632) between the A/A genotype group and the A/G or G/G genotype group. @*Conclusion@#The genotype frequency of PD-L1 (rs822339) is not different in patients with AITD compared with healthy controls. The intact PD-1/PD-L1 pathway in GD and HT might be important to maintain chronicity of AITD by protecting immune tolerance. However, the PD-L1 SNP could be associated with difficulty in achieving remission in patients with GD, which may be helpful to predict the possibility of longer treatment. Further studies are required to investigate the complex immune tolerance system in patients with AITD.
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Colon tumors develop more frequently in male than in female. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays differential roles in the stage of tumorigenesis. The purpose of this study was to investigate the role of Nrf2 on colitis-associated tumorigenesis using Nrf2 knockout (KO) female mice. Azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated wild-type (WT) and Nrf2 KO female mice were sacrificed at week 2 and 16 after AOM injection. Severity of colitis, tumor incidence, and levels of inflammatory mediators were evaluated in AOM/DSS-treated WT and Nrf2 KO mice. Furthermore, qRT-PCR, Western blot abnalysis, and ELISA were performed in colon tissues. At week 2, AOM/DSS-induced colon tissue damages were significantly greater in Nrf2 KO than in WT mice. At week 16, tumor numbers (> 2 mm size) were significantly lower in both the proximal and distal colon in Nrf2 KO compared to WT. The overall incidences of adenoma/cancer of the proximal colon and submucosal invasive cancer of the distal colon were reduced by Nrf2 KO. The mRNA and protein expression levels of NF-κB-related mediators (i.e., iNOS and COX-2) and Nrf2-related antioxidants (i.e., heme oxygenase-1 and glutamate-cysteine ligase catalytic subunit) were significantly lower in the Nrf2 KO than in WT mice. Interestingly, the protein level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) was higher in AOM/DSS-treated Nrf2 KO than in WT mice. Our results support the oncogenic effect of Nrf2 in the later stage of carcinogenesis and upregulation of tumor suppressor 15-PGDH might contribute to the repression of colitis-associated tumorigenesis in Nrf2 KO female mice.
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The gut microbiota interacts with the host gut environment, which is influenced by such factors as sex, age, and host diet. These factors induce changes in the microbial composition. The aim of this study was to identify differences in the gut microbiome of Fisher-344 (F344) rats fed a high-fat diet (HFD), depending on their age and sex. Fecal microbiomes from 6-, 31-, and 74-week-old, and 2-year-old both male and female rats (corresponding to 5-, 30-, 60-, and 80-year-old humans) were analyzed using 16S rRNA gene sequencing, phylogenetic investigation of communities by reconstruction of unobserved states, and enterotype (E) assessment. Moreover, the effect of an HFD on colonic epithelial cells was measured using real-time quantitative PCR. Alpha diversity decreased in the HFD group regardless of age and sex. Based on the enterotype clustering of the whole fecal microbiome, clusters from male rats were divided into E1 and E2 enterotypes, while clusters from female rats were divided into E1, E2, and E3 enterotypes. The female E3 group showed a significantly high abundance in the Ruminococcus genus and expression of Tlr2 mRNA, which may reflect compensation to the HFD. Moreover, the female E3 group showed a lower ratio of opportunistic pathogenic strains to commensal strains compared to the female E2 group. Administration of an HFD influenced the rat fecal microbiota in all assessed age groups, which could be further differentiated by sex. In particular, female rats showed a compensatory enterotype response to an HFD compared to male rats.