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        • KCI등재

          Sex-related Alterations of Gut Microbiota in the C57BL/6 Mouse Model of Inflammatory Bowel Disease

          Hee,Jin,Son,Na,Young,Kim,Chin-Hee,Song,Ryoung,Hee,Nam,Soo,In,Choi,Joo,Sung,Kim,Dong,Ho,Lee 대한암예방학회 2019 Journal of cancer prevention Vol.24 No.3

          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. (J Cancer Prev 2019;24:173-182)

        • KCI등재SCOPUS

          Effects of 17β-Estradiol on Colonic Permeability and Inflammation in an Azoxymethane/Dextran Sulfate Sodium-Induced Colitis Mouse Model

          ( Chin-hee Song ), ( Nayoung Kim ), ( Sung Hwa Sohn ), ( Sun Min Lee ), ( Ryoung Hee Nam ), ( Hee Young Na ), ( Dong Ho Lee ), ( Young-joon Surh ) 대한소화기학회 2018 Gut and Liver Vol.12 No.6

          Background/Aims: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model. Methods: The effects of 17β-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions. Results: The colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p<0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-κB, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2. Conclusions: E2 acts through the estrogen receptor β signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines. (Gut Liver 2018;12:682-693)

        • KCI등재

          Nuclear Factor Erythroid 2-related Factor 2 Knockout Suppresses the Development of Aggressive Colorectal Cancer Formation Induced by Azoxymethane/Dextran Sulfate Sodium-Treatment in Female Mice

          Chin-Hee,Song,Na,Young,Kim,Ryoung,Hee,Nam,Soo,In,Choi,Changhee,Kang,Jaeyoung,Jang,Heewon,Nho 대한암예방학회 2021 Journal of cancer prevention Vol.26 No.1

          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. Key Words Col

        • KCI등재SCOPUS

          Changes in Cecal Microbiota and Short-chain Fatty Acid During Lifespan of the Rat

          ( Soo In Choi ), ( Joo Hee Son ), ( Nayoung Kim ), ( Yong Sung Kim ), ( Ryoung Hee Nam ), ( Ji Hyun Park ), ( Chin-hee Song ), ( Jeong Eun Yu ), ( Dong Ho Lee ), ( Kichul Yoon ), ( Huitae Min ), ( Yeon-ran Kim ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2021 Journal of Neurogastroenterology and Motility (JNM Vol.27 No.1

          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. (J Neurogastroenterol Motil 2021;27:134-146)


          ORiginal Article : Different MicroRNA Expression Levels in Gastric Cancer Depending on Helicobacter pylori Infection

          ( Hyun Chang ), ( Nayoung Kim ), ( Ji Hyun Park ), ( Ryoung Hee Nam ), ( Yoon Jeong Choi ), ( Hye Seung Lee ), ( Hyuk Yoon ), ( Cheol Min Shin ), ( Young Soo Park ), ( Jung Min Kim ), ( Dong Ho Lee ) The Editorial Office of Gut and Liver 2015 Gut and Liver Vol.9 No.2

          Background/Aims: This study was conducted to identify microRNAs (miRNAs) that are differentially expressed in Helicobacter pylori-infected patients with an intestinal type of gastric cancer using miRNA microarray and to confirm the candidate miRNA expression levels. Methods: Total RNA was extracted from the cancerous and noncancerous regions of formalin-fixed, paraffin-embedded tissues of H. pylori-positive (n=8) or H. pylori-negative (n=8) patients with an intestinal type of gastric cancer. RNA expression was analyzed using a 3,523 miRNA profiling microarray based on the Sanger miRBase. Validation analysis was performed using TaqMan miRNA assays. Results: A total of 219 miRNAs in the aberrant miRNA profiles across the miRNA microarray showed at least a 2-fold change differential expression in H. pylori-positive and H. pylori-negative cancer tissues. After candidate miRNAs were selected using online miRNA databases, TaqMan miRNA assays confirmed that three miRNAs (miR-99b-3p, miR-564, and miR-638) were significantly increased in three H. pylori-positive cancer tissues compared to the H. pylori-negative cancer tissues. Additionally, four miRNAs (miR-204-5p, miR-338-5p, miR-375, and miR-548c-3p) were significantly increased in H. pylori-negative cancer tissues compared to H. pylori-positive cancer tissues. Conclusions: miRNA expression in the intestinal type of H. pylori infection-dependent gastric cancer suggests that different gastric cancer pathogenesis mechanisms could exist between H. pylori-positive and H. pylori-negative gastric cancer. Additional functional studies are required. (Gut Liver, 2015;9:188-196)


          ORiginal Article : The Effect of Cochinchina momordica Seed Extract on Gastric Acid Secretion and Morphologic Change in Aged Rat Stomach

          ( Hyun Jin Jo ), ( Na Young Kim ), ( Ryoung Hee Nam ), ( Hyun Chang ), ( Joo Hyon Kim ), ( Ji Hyun Park ), ( Jung Mook Kang ), ( Dong Ho Lee ), ( Hyun Chae Jung ) The Editorial Office of Gut and Liver 2013 Gut and Liver Vol.7 No.5

          Background/Aims: Cochinchina momordica seed extract (SK-MS10) has a gastric protective effect. We aimed to as-sess the effect of SK-MS10 on gastric acid secretion with morphologic changes in the aged rat. Methods: Acid secre-tions were evaluated in the male F344 rats of four different ages (6-, 31-, 74-week, and 2-year). The 31-week-old rats were divided to three groups and continuously administered chow containing vehicle, SK-MS10 and lansoprazole, re-spectively. At the age of 74 weeks and 2 years, basal and stimulated acid was measured and the expression of mRNA and protein of H+-K+-ATPase were determined. The area of connective tissue of lamina propria was measured. Results: Basal and stimulated gastric acid significantly decreased and connective tissue of lamina propria increased with age. The expression of mRNA and protein of H+-K+-ATPase signifi-cantly decreased with age. However, 74-week-old rats in the SK-MS10 group had higher stimulated gastric acid secretion than those in the vehicle and lansoprazole groups. In 2-year-old rats of SK-MS10 group, there was no increase of con-nective tissue. Conclusions: As SK-MS10 kept the capacity of acid secretion as well as connective tissue area to com-parable to young rats, it might valuable to perform further research regarding mechanism of SK-MS10 as an antiaging agent in the stomach. (Gut Liver 2013;7:560-568)


          Efficacy of Tegoprazan for Improving the Susceptibility of Antimicrobial Agents against Antibiotic-Resistant Helicobacter pylori

          ( Jung Won Lee ), ( Nayoung Kim ), ( Ryoung Hee Nam ), ( Jeong Eun Yu ), ( Joo Hee Son ), ( Sun Min Lee ), ( Dong Ho Lee ) 대한간학회 2021 Gut and Liver Vol.15 No.1

          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 clarithromycin 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 acquisition with metronidazole than with vonoprazan (20.6% vs 4.7%, p=0.014). However, there were no significant 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. (Gut Liver 2021;15:53-60)

        • KCI등재

          The Effect of Sex on the Azoxymethane/Dextran Sulfate Sodium-treated Mice Model of Colon Cancer

          Sun,Min,Lee,Nayoung,Kim,Hee,Jin,Son,Ji,Hyun,Park,Ryoung,Hee,Nam,Min,Hee,Ham,Daeun,Choi,Sung,Hwa,Sohn,Eun,Shin,Young-Jae,Hwang,Jihee,Sung,Dong,Ho,Lee,Ha-Na,Lee 대한암예방학회 2016 Journal of cancer prevention Vol.21 No.4

          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)-1 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-1 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.

        • KCI등재SCOPUS

          PMK-S005 Alleviates Age-Related Gastric Acid Secretion, Inflammation, and Oxidative Status in the Rat Stomach

          ( Yoon Jeong Choi ), ( Nayoung Kim ), ( Ju Yup Lee ), ( Ryoung Hee Nam ), ( Ji Hyung Suh ), ( Sun Min Lee ), ( Min Hee Ham ), ( Hyun Jin Jo ), ( Young Kwang Shim ), ( Yo Han Park ), ( Jong-chan Lee ), ( Yoon Jin) 대한간학회 2016 Gut and Liver Vol.10 No.5

          Background/Aims: The aim of this study was to evaluate the effect of the synthetic S-allyl-L-cysteine (SAC) PMK-S005 on gastric acid secretion, inflammation, and antioxidant enzymes in aging rats. Methods: The rats were divided into four groups at 31 weeks of age and were continuously fed a diet containing a vehicle control, PMK-S005 (5 or 10 mg/kg), or lansoprazole (5 mg/kg). Gastric acid secretion and connective tissue thickness of the lamina propria were evaluated at 74 weeks and 2 years of age. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and COX-2 levels were measured by using enzyme-linked immunosorbent assays (ELISAs) or Western blot assays. Levels of antioxidant enzymes, including heme oxyganase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), were also measured. Results: As the rats aged, gastric acid secretion significantly decreased, and the connective tissue of the lamina propria increased. However, 74-week-old rats in the PMK-S005 group exhibited greater levels of gastric acid secretion than those of the control and lansoprazole groups. The increase of TNF-α, IL-1β, and COX-2 expression in 74-week and 2-year-old control rats were inhibited by PMK-S005. In addition, the decrease in HO-1 and NQO-1 protein expression that occurred with aging was inhibited by PMK-S005 in the 74-week-old rats. Conclusions: These results suggest that PMK-S005 has therapeutic potential as an antiaging agent to ameliorate age-related gastric acid secretion, inflammation, and oxidative stress in the stomach. (Gut Liver 2016;10:749-756)


          Original Article : Comparison of Indomethacin, Diclofenac and Aspirin-Induced Gastric Damage according to Age in Rats

          ( Pyoung Ju Seo ), ( Nayoung Kim ), ( Joo Hyon Kim ), ( Byoung Hwan Lee ), ( Ryoung Hee Nam ), ( Hye Seung Lee§ ), ( Ji Hyun Park ), ( Mi Kyoung Lee ), ( Hyun Chang ), ( Hyun Chae Jung ), ( In Sung Song ) The Editorial Office of Gut and Liver 2012 Gut and Liver Vol.6 No.2

          Background/Aims: Aging gastric mucosa is known to have decreased mucosal defenses and increased susceptibility to injury by nonsteroidal anti-infl ammatory drugs. Depending on the type of nonsteroidal anti-infl ammatory drug (NSAID), the underlying mechanisms and the extent of damage to the stomach or intestine may differ. This study was performed to evaluate the acute gastric damage caused by different doses of indomethacin, diclofenac and aspirin in rats of various ages. Methods: For the acute models, indomethacin (10, 20 or 40 mg/kg), diclofenac (40 or 80 mg/kg) or aspirin (100 mg/kg) was given to 7- and 25-week-old and 1-year-old Sprague-Dawley rats by intragastric gavage. The gross ulcer index, damage area as assessed by imaging, histological index, myeloperoxidase (MPO) activity, and cytosolic phospholipase A2 (cPLA2) levels were measured after 24 hours. Results: The gross ulcer index and damage area increased with age in the presence of three NSAIDs (p<0.05). The increases in MPO levels induced by diclofenac and aspirin were signifi cantly higher in 1-year-old than 7-week-old rats (p<0.05). cPLA2 expression induced by indomethacin (10 and 40 mg/ kg) was greater in the 1-year-old rats, compared with 7-weekold rats (p<0.05). Conclusions: NSAID-induced acute gastric damage increased in a dose- and age-dependent manner. (Gut Liver 2012;6:210-217)

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