Publications by authors named "Soo In Choi"

34 Publications

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.

J Cancer Prev 2021 Mar;26(1):41-53

Laboratory of Immunology, Division of Biotechnology Review and Research-III, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.

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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http://dx.doi.org/10.15430/JCP.2021.26.1.41DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020176PMC
March 2021

Physiological activity of E. coli engineered to produce butyric acid.

Microb Biotechnol 2021 Mar 17. Epub 2021 Mar 17.

Department of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, Korea.

Faecalibacterium prausnitzii (F. prausnitzii) is one of the most abundant bacteria in the human intestine, with its anti-inflammatory effects establishing it as a major effector in human intestinal health. However, its extreme sensitivity to oxygen makes its cultivation and physiological study difficult. F. prausnitzii produces butyric acid, which is beneficial to human gut health. Butyric acid is a short-chain fatty acid (SCFA) produced by the fermentation of carbohydrates, such as dietary fibre in the large bowel. The genes encoding butyryl-CoA dehydrogenase (BCD) and butyryl-CoA:acetate CoA transferase (BUT) in F. prausnitzii were cloned and expressed in E. coli to determine the effect of butyric acid production on intestinal health using DSS-induced colitis model mice. The results from the E. coli Nissle 1917 strain, expressing BCD, BUT, or both, showed that BCD was essential, while BUT was dispensable for producing butyric acid. The effects of different carbon sources, such as glucose, N-acetylglucosamine (NAG), N-acetylgalactosamine (NAGA), and inulin, were compared with results showing that the optimal carbon sources for butyric acid production were NAG, a major component of mucin in the human intestine, and glucose. Furthermore, the anti-inflammatory effects of butyric acid production were tested by administering these strains to DSS-induced colitis model mice. The oral administration of the E. coli Nissle 1917 strain, carrying the expression vector for BCD and BUT (EcN-BCD-BUT), was found to prevent DSS-induced damage. Introduction of the BCD expression vector into E. coli Nissle 1917 led to increased butyric acid production, which improved the strain's health-beneficial effects.
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http://dx.doi.org/10.1111/1751-7915.13795DOI Listing
March 2021

A new simple endoscopic incision therapy for refractory benign oesophageal anastomotic stricture.

BMJ Case Rep 2021 Mar 10;14(3). Epub 2021 Mar 10.

Department of Internal Medicine, Inje University Sanggye Paik Hospital, Nowon-gu, Korea.

Oesophageal anastomotic stricture is a frequent complication after esophagectomy. In most cases, endoscopic bougination or balloon dilation usually resolves anastomotic stricture. However, some refractory oesophageal strictures remain difficult to treat and cause significant morbidity. Recently, successful treatment using endoscopic incisional therapy has been reported in several cases. We report a case of refractory benign oesophageal anastomotic stricture after oesophagectomy. A 72-year-old man underwent three consecutive bouginations. However, he developed progressive stricture. Stricture was successfully treated with an endoscopic knife incision. We performed only three incisions without a cutting method, which was new compared with previous reports. A new simple endoscopic incision technique is effective and safe for stricture management. In conclusion, endoscopic incisional therapy may be recommended as a salvage treatment for properly selected patients with refractory benign stricture who do not respond to conventional therapy.
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http://dx.doi.org/10.1136/bcr-2020-239798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949401PMC
March 2021

Endoscopic retrieval for a large impacted meat bolus in the oesophagus.

BMJ Case Rep 2021 Feb 4;14(2). Epub 2021 Feb 4.

Department of Internal Medicine, Division of Gastroenterology, Inje University Sanggye Paik Hospital, Nowon-gu, Korea (the Republic of)

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http://dx.doi.org/10.1136/bcr-2020-241275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868232PMC
February 2021

Two Cases of Fungemia after Endoscopic Variceal Obturation for Gastric Variceal Bleeding.

Yonsei Med J 2021 Feb;62(2):182-186

Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea.

Fever is a common complication of endoscopic variceal obturation (EVO) therapy for gastric variceal bleeding. However, fungemia related to EVO therapy has not yet been reported. Herein, we report two cases of post-EVO fungemia in cirrhotic patients who underwent therapeutic EVO for gastric variceal bleeding. Both patients developed sustained high fever after repeated EVO procedures while on prophylactic antibiotic use. In both patients, blood cultures revealed yeast, and they were finally diagnosed with infection. is a common member of the intestinal flora; however, it can cause invasive infection with consequent poor prognosis in cirrhotic patients. The route of invasion is unclear; however, repeated EVO may predispose patients to infection, particularly those who are in the end stage of liver disease and receiving prophylactic antibiotics. Our cases highlight that repeated invasive procedures can increase the risk of fungal infections, and fungemia should be considered in the differential diagnosis of post-EVO fever.
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http://dx.doi.org/10.3349/ymj.2021.62.2.182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859686PMC
February 2021

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

J Neurogastroenterol Motil 2021 Jan;27(1):134-146

Department of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, Korea.

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.
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http://dx.doi.org/10.5056/jnm20148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786083PMC
January 2021

17β-Estradiol strongly inhibits azoxymethane/dextran sulfate sodium-induced colorectal cancer development in Nrf2 knockout male mice.

Biochem Pharmacol 2020 12 15;182:114279. Epub 2020 Oct 15.

Tumor Microenvironment Global Core Research Center, Seoul National University College of Pharmacy, Seoul, South Korea.

Nuclear factor erythroid 2-related factor 2 (Nrf2) has dual effects on inflammation and cancer progression depending on the microenvironment. Estrogens have a protective effect on colorectal cancer (CRC) development. The aim of this study was to investigate CRC development in Nrf2 knockout (KO) mice. Azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated wild-type (WT) and Nrf2 KO male mice were sacrificed at weeks 2 and 16 after AOM injection with/without 17β-estradiol (E2) treatment during week 1. Disease activity index and colon tissue damage at week 2 showed strong attenuation following E2 administration in WT mice but to a lesser extent in Nrf2 KO male mice. At week 16, E2 significantly diminished AOM/DSS-induced adenoma/cancer incidence at distal colon in the Nrf2 KO group, but not in the WT. Furthermore, mRNA or protein levels of NF-κB-related mediators (i.e., iNOS, TNF-α, and IL-1β) and Nrf2-related antioxidants (i.e., NQO1 and HO-1) were significantly lower in the Nrf2 KO group regardless of E2 treatment compared to the WT. The expression of estrogen receptor beta (ERβ) was higher in the Nrf2 KO group than in the WT. In conclusion, estrogen further inhibits CRC by upregulating ERβ-related alternate pathways in the absence of Nrf2.
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http://dx.doi.org/10.1016/j.bcp.2020.114279DOI Listing
December 2020

Efficacy of Endoscopic Vacuum-Assisted Closure Treatment for Postoperative Anastomotic Leak in Gastric Cancer.

Gut Liver 2020 11;14(6):746-754

Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.

Background/aims: Endoscopic vacuum-assisted closure (EVAC) has been attempted as new nonsurgical treatment for anastomotic leakage. We aimed to evaluate the clinical outcomes of EVAC and compare its efficacy with the self-expandable metallic stent (SEMS) for postgastrectomy leakage.

Methods: Between January 2007 and February 2018, 39 patients underwent endoscopic treatment for anastomotic leakage after gastric cancer surgery. Of them, 28 patients were treated with SEMS, seven with EVAC after SEMS failure, and four with EVAC. We retrospectively compared the clinical characteristics and therapeutic outcomes between EVAC (n=11) and SEMS (n=28).

Results: The median followup duration was 17 months (interquartile range, 9 to 26 months) in both groups. In comparison of clinical characteristics between two groups, only the median size of the leak was larger in the EVAC group than in the SEMS group (2.1 cm vs 1.0 cm; p<0.001). All EVAC cases healed successfully; however, two cases (7.1%) failed to heal in the SEMS group. Anastomotic stricture occurred one case (9.1%) in EVAC and four cases (14.3%) in SEMS within 1 year after endoscopic treatment. The median treatment duration of EVAC was shorter than that of SEMS (15 days vs 36 days; p<0.001). Median weight loss after therapy was similar in both groups (8.0 kg in EVAC vs 9.0 kg in SEMS; p=0.356).

Conclusions: EVAC can be effective endoscopic treatment for postgastrectomy anastomotic leakage. Substantial leakage could be an important clinical factor for considering EVAC as a treatment option. Large randomized controlled trials are needed to confirm the efficacy of EVAC.
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http://dx.doi.org/10.5009/gnl20114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667929PMC
November 2020

17β-Estradiol supplementation changes gut microbiota diversity in intact and colorectal cancer-induced ICR male mice.

Sci Rep 2020 07 23;10(1):12283. Epub 2020 Jul 23.

Tumor Microenvironment Global Core Research Center, Seoul National University College of Pharmacy, Seoul, South Korea.

The composition of the gut microbiota is influenced by sex hormones and colorectal cancer (CRC). Previously, we reported that 17β-estradiol (E2) inhibits azoxymethane/dextran sulfate sodium (AOM/DSS)-induced tumorigenesis in male mice. Here, we investigated whether the composition of the gut microbiota is different between male and female, and is regulated by estrogen as a secondary outcome of previous studies. We established four groups of mice based on the sex and estrogen status [ovariectomized (OVX) female and E2-treated male]. Additionally, three groups of males were established by treating them with AOM/DSS, and E2, after subjecting them to AOM/DSS treatment. The mice were sacrificed at 21 weeks old. The composition of the gut microbiota was analyzed using 16S rRNA metagenomics sequencing. We observed a significant increase in the microbial diversity (Chao1 index) in females, males supplemented with E2, and males treated with AOM/DSS/E2 compared with normal males. In normal physiological condition, sex difference and E2 treatment did not affect the ratio of Firmicutes/Bacteroidetes (F/B). However, in AOM/DSS-treated male mice, E2 supplementation showed significantly lower level of the F/B ratio. The ratio of commensal bacteria to opportunistic pathogens was higher in females and E2-treated males compared to normal males and females subjected to OVX. Unexpectedly, this ratio was higher in the AOM/DSS group than that determined in other males and the AOM/DSS/E2 group. Our findings suggest that estrogen alters the gut microbiota in ICR (CrljOri:CD1) mice, particularly AOM/DSS-treated males, by decreasing the F/B ratio and changing Shannon and Simpson index by supply of estrogen. This highlights another possibility that estrogen could cause changes in the gut microbiota, thereby reducing the risk of developing CRC.
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http://dx.doi.org/10.1038/s41598-020-69112-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378548PMC
July 2020

Compositional and Functional Changes in the Gut Microbiota in Irritable Bowel Syndrome Patients.

Gut Liver 2021 Mar;15(2):253-261

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background/aims: This study aimed to characterize the changes in the gut microbiota of irritable bowel syndrome (IBS) patients and to investigate the consequent alterations in bacterial functions.

Methods: We performed 16S rRNA metagenomic sequencing and a phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analyses using fecal samples from control (n=12) and diarrhea-dominant IBS patients (n=7).

Results: The samples were clustered by the principal coordinates analysis depending on the presence of IBS (p=0.003). In the IBS patients, the abundances of Acidaminococcaceae, Sutterellaceae, and Desulfovibrionaceae were significantly increased, while those of Enterococcaceae, Leuconostocaceae, Clostridiaceae, Peptostreptococcaceae, and Lachnospiraceae were significantly decreased. The PICRUSt results indicated that two orthologues involved in secondary bile acid biosynthesis were significantly decreased in IBS patients. Modules involved in multidrug resistance, lipopolysaccharide biosynthesis, the reductive citrate cycle, and the citrate cycle were significantly increased in the IBS patients. In contrast, modules involved in cationic antimicrobial peptide resistance, and some transport systems were more abundant in controls than in IBS patients.

Conclusions: Changes in the gut microbiota composition in IBS patients lead to alterations in bacterial functions, such as bile acid transformation and the induction of inflammation, which is a known pathophysiological mechanism of IBS.
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http://dx.doi.org/10.5009/gnl19379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960967PMC
March 2021

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

J Cancer Prev 2019 Sep 30;24(3):173-182. Epub 2019 Sep 30.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

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, , , and 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.
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http://dx.doi.org/10.15430/JCP.2019.24.3.173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786806PMC
September 2019

Corrigendum: Effects of Different Re-referencing Methods on Spontaneously Generated Ear-EEG.

Front Neurosci 2019;13:908. Epub 2019 Aug 29.

Department of Medical IT Convergence Engineering, Kumoh National Institute of Technology, Gumi, South Korea.

[This corrects the article DOI: 10.3389/fnins.2019.00822.].
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http://dx.doi.org/10.3389/fnins.2019.00908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727792PMC
August 2019

Primary and secondary antibiotic resistance of Helicobacter pylori in Korea from 2003 to 2018.

Helicobacter 2019 Dec 11;24(6):e12660. Epub 2019 Sep 11.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, South Korea.

Background: Antimicrobial resistance of Helicobacter pylori (H pylori) affects the efficacy of eradication therapy. The aim of this study was to estimate the prevalence of primary and secondary resistance of H pylori isolates to antibiotics in Korea.

Methods: The present study was performed from 2003 to 2018. Primary resistance was evaluated in 591 patients without any history of eradication and secondary resistance in 149 patients from whom Helicobacter pylori was cultured after failure of eradication. A minimal inhibitory concentration test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and rifabutin using the agar dilution method.

Results: An increase in the primary resistance rate was found in clarithromycin (P < .001), metronidazole (P < .001), and both levofloxacin (P < .001) during the study period. The primary resistance rates of amoxicillin and tetracycline were low and stable during the study period. The secondary resistance rate significantly increased in metronidazole and levofloxacin (P = .022 and .039, respectively).

Conclusions: The primary and secondary resistance rates of clarithromycin, metronidazole, and levofloxacin for Helicobacter pylori in Korea were high and increased over time. However, the primary and secondary resistance rates of amoxicillin and tetracycline were low and stable over time. These results will help in selecting effective eradication regimens of H pylori in Korea in the future.
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http://dx.doi.org/10.1111/hel.12660DOI Listing
December 2019

Effects of Different Re-referencing Methods on Spontaneously Generated Ear-EEG.

Front Neurosci 2019 7;13:822. Epub 2019 Aug 7.

Department of Medical IT Convergence Engineering, Kumoh National Institute of Technology, Gumi, South Korea.

In recent years, electroencephalography (EEG) measured around the ears, called ear-EEG, has been introduced to develop unobtrusive and ambulatory EEG-based applications. When measuring ear-EEGs, the availability of a reference site is restricted due to the miniaturized device structure, and therefore a reference electrode is generally placed near the recording electrodes. As the electrical brain activity recorded at a reference electrode closely placed to recording electrodes may significantly cancel or influence the brain activity recorded by the recording electrodes, an appropriate re-referencing method is often required to mitigate the impact of the reference brain activity. In this study, therefore, we systematically investigated the impact of different re-referencing methods on ear-EEGs spontaneously generated from endogenous paradigms. To this end, we used two ear-EEG datasets recorded behind both ears while subjects performed an alpha modulation task [eyes-closed (EC) and eyes-open (EO)] and two mental tasks [mental arithmetic (MA) and mental singing (MS)]. The measured ear-EEGs were independently re-referenced using five different methods: (i) all-mean, (ii) contralateral-mean, (iii) ipsilateral-mean, (iv) contralateral-bipolar, and (v) ipsilateral-bipolar. We investigated the changes in alpha power during EO and EC tasks, as well as event-related (de) synchronization (ERD/ERS) during MA and MS. To evaluate the effects of re-referencing methods on ear-EEGs, we estimated the signal-to-noise ratios (SNRs) of the two ear-EEG datasets, and assessed the classification performance of the two mental tasks (MA vs. MS). Overall patterns of changes in alpha power and ERD/ERS were similar among the five re-referencing methods, but the contralateral-mean method showed statistically higher SNRs than did the other methods for both ear-EEG datasets, except in the contralateral-bipolar method for the two mental tasks. In concordance with the SNR results, classification performance was also statistically higher for the contralateral-mean method than it was for the other re-referencing methods. The results suggest that employing contralateral mean information can be an efficient way to re-reference spontaneously generated ear-EEGs, thereby maximizing the reliability of ear-EEG-based applications in endogenous paradigms.
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http://dx.doi.org/10.3389/fnins.2019.00822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692921PMC
August 2019

Commentary on "Efficacy of Endoscopic Submucosal Dissection of Esophageal Neoplasms under General Anesthesia".

Clin Endosc 2019 May 23;52(3):205-206. Epub 2019 May 23.

Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.5946/ce.2019.093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547344PMC
May 2019

Gut microbiota and butyrate level changes associated with the long-term administration of proton pump inhibitors to old rats.

Sci Rep 2019 04 29;9(1):6626. Epub 2019 Apr 29.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea.

The association between adverse effects of PPI and gut microbiota in old age has yet to be elucidated. We assessed changes in the gut microbiota and butyrate levels following the long-term administration of PPIs to old rats and investigated their associations. F344 aged male rats were fed a PPI-supplemented diet for 50 weeks. The ileal microbiota was analysed by metagenomic sequencing of the 16S rRNA, while the butyrate concentration was measured by high-performance liquid chromatography. We observed a significant decrease in microbial diversity following PPI administration in the 2-year-old rats but not in the 74-week-old rats. PPI treatment reduced both commensal bacteria and opportunistic pathogens, particularly in the 2-year-old rats. Enterotypes comprising the majority of the control samples were enriched in Lactobacillus, while other enterotypes in the PPI group were dominated by Turicibacter or Romboutsia. The PPI treatment reduced the butyrate concentrations in the intestines and colons of 74-week-old rats compared to the control group. The abundance of Lactobacillus significantly correlated with butyrate concentrations in 74-week-old rats. In conclusion, long-term administration of PPIs alters the gut microbiota and butyrate concentrations in rats, particularly in old age, which may be an underlying mechanism of PPI-induced adverse effects such as pseudomembranous colitis.
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http://dx.doi.org/10.1038/s41598-019-43112-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488615PMC
April 2019

Rat Intestinal Acetic Acid and Butyric acid and Effects of Age, Sex, and High-fat Diet on the Intestinal Levels in Rats.

J Cancer Prev 2019 Mar 30;24(1):20-25. Epub 2019 Mar 30.

Department of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, Korea.

Background: High-fat diet is known to be implicated in the pathogenesis of various metabolic disorders related to an inflammatory response. The aim of this study was to investigate the influence of high-fat diet for intestinal acetic acid and butyric acid concentrations which are related to inflammation-associated colon cancer risk.

Methods: Both male and female rats of 6, 31, 74 and 104-week of age were fed chow diet or high-fat diet for 8 weeks. Body weight and food intake were measured weekly during the feeding period. Intestinal acetic acid and butyric acid levels were measured by high-performance liquid chromatography from luminal contents of ileum and cecum.

Results: Male rats showed greater weight change than female rats in every age. Calorie-adjusted food intake was also higher in male rats compared to female rats. Male rats showed similar intake of food in every age while 31-week old female rats showed increased intake, which was decreased at 74-week and 104-week of age. The ileal acetic acid concentration was increased in male rats fed high-fat diet, while female rats fed high-fat diet showed no significant change in the ileal acetic acid level. On the other hand, butyric acid almost disappeared in high-fat diet fed rats regardless of sex.

Conclusions: High-fat diet increases the intestinal acetic acid concentration while reducing the butyric acid concentration which may account for increased risk of inflammation-associated colon cancer.
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http://dx.doi.org/10.15430/JCP.2019.24.1.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453582PMC
March 2019

Effects of 17β-estradiol on colorectal cancer development after azoxymethane/dextran sulfate sodium treatment of ovariectomized mice.

Biochem Pharmacol 2019 06 11;164:139-151. Epub 2019 Apr 11.

Tumor Microenvironment Global Core Research Center, Seoul National University College of Pharmacy, Seoul, South Korea.

Estrogen is known to have a protective effect in colorectal cancer (CRC) development. Previously, we reported the anti-inflammatory and antitumorigenic effects of 17β-estradiol (E2) in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated male mice. The aim of this study was to investigate whether ovariectomy in a female AOM/DSS mouse model increases colorectal tumorigenesis and whether tumorigenesis is reduced by estrogen supplementation after ovariectomy. Clinical symptoms and histological severity of colitis and the levels of inflammatory mediators were evaluated in the colon of AOM/DSS-treated ovariectomized (OVX) mice. The levels of E2, myeloperoxidase (MPO), and NF-κB-dependent cytokines (interleukin (IL)-1β and IL-6) were measured by ELISA. Furthermore, quantitative real-time (qRT) PCR and Western blot analysis were performed. Ovariectomy did not aggravate AOM/DSS-induced colitis at 2 weeks. At weeks 10 and 16, ovariectomy significantly increased tumor number and incidence rate in only the proximal colon after AOM/DSS treatment (F_AOM/DSS vs OVX_AOM/DSS), and these increases were significantly reduced by E2 supplementation (OVX_AOM/DSS vs OVX_AOM/DSS/E2). However, ovariectomy did not affect CRC development in the distal colon (F_AOM/DSS vs OVX_AOM/DSS). At week 2, E2 administration to AOM/DSS-treated OVX mice attenuated the histological severity of colitis by decreasing the protein and/or mRNA levels of estrogen receptor alpha (ERα) and NF-κB-related mediators (i.e., COX-2, TNF-α, and IL-6) and by enhancing estrogen receptor beta (ERβ) and nuclear Nrf2 protein expression and the mRNA expression of related antioxidant enzyme genes (i.e., HO-1, GCLC, GCLM, and NQO1). Endogenous estrogen in females protects against the development of proximal colon cancer, and exogenous E2 replacement in OVX female mice showed protective effects against AOM/DSS-induced colitis and carcinogenesis. The mechanism could involve modulating ERs-, NF-κB- and Nrf2-mediated pathways.
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http://dx.doi.org/10.1016/j.bcp.2019.04.011DOI Listing
June 2019

Noninvasive prediction model for diagnosing gastrointestinal stromal tumors using contrast-enhanced harmonic endoscopic ultrasound.

Dig Liver Dis 2019 07 27;51(7):985-992. Epub 2019 Mar 27.

Department of Internal Medicine, Yonsei University College of Medicine, 03722, Seodaemun-gu, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background & Aims: Subepithelial tumors (SETs) are difficult to diagnose accurately without invasive pathological confirmation. We created a noninvasive prediction model for diagnosing gastrointestinal stromal tumors (GISTs) using contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS).

Methods: We retrospectively reviewed 176 patients who underwent CEH-EUS from October 2011 to August 2017. Seventy patients with a diagnosis of GIST (n = 37) or leiomyoma (n = 33) were included. The long-to-short axis ratio (LSR) and enhancement patterns (vascularity, diffuse enhancement) on CEH-EUS were assessed. Logistic regression and classification and regression tree (CART) analyses were performed.

Results: The mean age of all patients was 54.9 ± 13.68 years. The GIST group showed significantly higher rates of positive vascularity (81.1% vs. 15.2%, p < 0.001) and diffuse enhancement (51.4% vs. 15.2%, p = 0.001), and lower LSR (1.30 vs. 1.76, p < 0.001). In multivariate logistic regression, positive vascularity (odds ratio [OR] 27.765, 95% confidence interval [CI] 5.336-144.458) and low LSR (OR 18.940, 95% CI 3.623-99.007) were independent predictors of GIST. A noninvasive prediction model for GISTs was developed using the CART model, by allocating patients according to statistically significant variables.

Conclusions: The LSR and vascularity of SETs on CEH-EUS can be used as parameters for a noninvasive prediction model of GISTs. This model may be helpful in the early identification and treatment of GISTs.
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http://dx.doi.org/10.1016/j.dld.2019.02.017DOI Listing
July 2019

Risk factors of rescue bismuth quadruple therapy failure for Helicobacter pylori eradication.

J Gastroenterol Hepatol 2019 Apr 25;34(4):666-672. Epub 2019 Feb 25.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background And Aim: Failure of bismuth quadruple therapy for Helicobacter pylori eradication is frequently observed. To increase the eradication rate, comprehensive analyses need to be performed regarding risk factors of bismuth quadruple therapy failure based on complete standard culture and antimicrobial susceptibility testing results.

Methods: Patients with history of failed first therapy who had H. pylori colonies isolated from culture and successful minimum inhibitory concentration (MIC) test were enrolled. Esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapies for 7 or 14 days were given. Eradication rate, treatment compliance, adverse events, and risk factors for the failure of bismuth quadruple therapy were analyzed.

Results: A total 54 patients were enrolled. Overall eradication rate in the present study was 88.8%. The eradication rate for cases with metronidazole resistance such as MIC 8-16 μg/mL or 16-32 μg/mL was 92.8% (13/14). For cases with high level metronidazole resistance (MIC > 32 μg/mL), the eradication rate was only 60% (6/10). Multivariate analysis regarding compliance, treatment duration, age > 60, three kinds of metronidazole MICs, tetracycline MIC > 4 μg/mL, adverse events and any other parameters, "metronidazole resistance, high level (MIC > 32 μg/mL)" was the only independent risk factor for eradication failure (P = 0.007).

Conclusion: For cases with metronidazole resistance at MIC > 32 μg/mL, rescue therapy other than bismuth-containing quadruple therapy is needed.
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http://dx.doi.org/10.1111/jgh.14625DOI Listing
April 2019

On the Feasibility of Using an Ear-EEG to Develop an Endogenous Brain-Computer Interface.

Sensors (Basel) 2018 Aug 29;18(9). Epub 2018 Aug 29.

Department of Medical IT Convergence Engineering, Kumoh National Institute of Technology, Gumi 39177, Korea.

Brain-computer interface (BCI) studies based on electroencephalography (EEG) measured around the ears (ear-EEGs) have mostly used exogenous paradigms involving brain activity evoked by external stimuli. The objective of this study is to investigate the feasibility of ear-EEGs for development of an endogenous BCI system that uses self-modulated brain activity. We performed preliminary and main experiments where EEGs were measured on the scalp and behind the ears to check the reliability of ear-EEGs as compared to scalp-EEGs. In the preliminary and main experiments, subjects performed eyes-open and eyes-closed tasks, and they performed mental arithmetic (MA) and light cognitive (LC) tasks, respectively. For data analysis, the brain area was divided into four regions of interest (ROIs) (i.e., frontal, central, occipital, and ear area). The preliminary experiment showed that the degree of alpha activity increase of the ear area with eyes closed is comparable to those of other ROIs (occipital > ear > central > frontal). In the main experiment, similar event-related (de)synchronization (ERD/ERS) patterns were observed between the four ROIs during MA and LC, and all ROIs showed the mean classification accuracies above 70% required for effective binary communication (MA vs. LC) (occipital = ear = central = frontal). From the results, we demonstrated that ear-EEG can be used to develop an endogenous BCI system based on cognitive tasks without external stimuli, which allows the usability of ear-EEGs to be extended.
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http://dx.doi.org/10.3390/s18092856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165202PMC
August 2018

Clinical Usefulness of Human Epididymis Protein 4 in Lung Cancer.

Ann Lab Med 2017 Nov;37(6):526-530

Department of Laboratory Medicine & Genetics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.

Human epididymis protein 4 (HE4) has been suggested as a useful new biomarker of lung cancer; however, few relevant large-scale studies have been published. In this study, we evaluated the utility of serum HE4 for lung cancer detection. HE4 levels were measured in serum samples from 100 lung cancer patients, 57 patients with benign lung diseases, and 274 healthy controls by using a chemiluminescent immunoassay, and variations in HE4 levels were analyzed by clinical status such as lung cancer, benign lung disease, and healthy condition, Tumor, Lymph Nodes, Metastasis (TNM) stage, tumor score, and histological cancer type. Lung cancer patients had significantly higher serum HE4 levels than patients with benign lung diseases and healthy controls (P<0.0001). The area under the ROC curve for HE4 was 0.84 (95% confidence interval, 0.78-0.89; P<0.0001) between lung cancer patients and healthy controls. Serum HE4 levels were significantly higher in patients with advanced disease (according to TNM stage) than in healthy controls (P<0.0001). HE4 levels were significantly elevated in patients with tumors of all types, those of different histological subgroups, and those with the smallest tumors (P=0.002). This report supports the potential of serum HE4 as an ancillary diagnostic marker for lung cancer detection.
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http://dx.doi.org/10.3343/alm.2017.37.6.526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587827PMC
November 2017

1-Methyl-L-tryptophan promotes the apoptosis of hepatic stellate cells arrested by interferon-γ by increasing the expression of IFN-γRβ, IRF-1 and FAS.

Int J Mol Med 2017 Aug 26;40(2):576-582. Epub 2017 Jun 26.

Cell Therapy and Tissue Engineering Center, Yonsei University, Wonju College of Medicine, Wonju, Gangwon-do 26426, Republic of Korea.

Liver fibrosis, a precursor to cirrhosis, is the result of the deposition of extracellular matrix (ECM) proteins and is mediated primarily by activated hepatic stellate cells (HSCs). In this study, we investigated the anti-fibrotic effects of interferon (IFN)-γ in activated HSCs in vitro and whether cell viability would be decreased by the inhibition of indoleamine 2,3-dioxygemase (IDO), which is responsible for cell cycle arrest. Following treatment with IFN-γ, cell signaling pathways and DNA content were analyzed to assess the inactivation of HSCs or the decrease in HSC proliferation. The IDO inhibitor, 1-methyl-L-tryptophan (1-MT), was used to determine whether IDO plays a key role in the regulation of activated HSCs, as IFN-γ increases the expression of IDO. IFN-γ significantly inhibited the growth of HSCs and downregulated the expression of α-smooth muscle actin (α-SMA) in the HSCs. IDO expression was markedly increased by IFN-γ through signal transducer and activator of transcription 1 (STAT1) activation and resulted in the depletion of tryptophan. This depletion induced G1 cell cycle arrest. When the cells were released from IFN-γ-mediated G1 cell cycle arrest by treatment with 1-MT, the apoptosis of the HSCs was markedly increased through the induction of IFN-γRβ, interferon regulatory factor (IRF-1) and FAS. Our results thus suggest that the inhibition of IDO enhances the suppression of activated HSCs, and therefore co-treatment with IFN-γ and 1-MT may be applied to ameliorate liver fibrosis.
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http://dx.doi.org/10.3892/ijmm.2017.3043DOI Listing
August 2017

Relationship between Regional Body Fat Distribution and Diabetes Mellitus: 2008 to 2010 Korean National Health and Nutrition Examination Surveys.

Diabetes Metab J 2017 Feb 21;41(1):51-59. Epub 2016 Dec 21.

Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.

Background: The aim of this study was to investigate the association between regional body fat distribution, especially leg fat mass, and the prevalence of diabetes mellitus (DM) in adult populations.

Methods: A total of 3,181 men and 3,827 postmenopausal women aged 50 years or older were analyzed based on Korea National Health and Nutrition Examination Surveys (2008 to 2010). Body compositions including muscle mass and regional fat mass were measured using dual-energy X-ray absorptiometry.

Results: The odds ratios (ORs) for DM was higher with increasing truncal fat mass and arm fat mass, while it was lower with increasing leg fat mass. In a partial correlation analysis adjusted for age, leg fat mass was negatively associated with glycosylated hemoglobin in both sexes and fasting glucose in women. Leg fat mass was positively correlated with appendicular skeletal muscle mass and homeostasis model assessment of β cell. In addition, after adjusting for confounding factors, the OR for DM decreased gradually with increasing leg fat mass quartiles in both genders. When we subdivided the participants into four groups based on the median values of leg fat mass and leg muscle mass, higher leg fat mass significantly lowered the risk of DM even though they have smaller leg muscle mass in both genders (P<0.001).

Conclusion: The relationship between fat mass and the prevalence of DM is different according to regional body fat distribution. Higher leg fat mass was associated with a lower risk of DM in Korean populations. Maintaining leg fat mass may be important in preventing impaired glucose tolerance.
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http://dx.doi.org/10.4093/dmj.2017.41.1.51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328696PMC
February 2017

Clinical feasibility of brain-computer interface based on steady-state visual evoked potential in patients with locked-in syndrome: Case studies.

Psychophysiology 2017 03 3;54(3):444-451. Epub 2016 Dec 3.

Department of Biomedical Engineering, Hanyang University, Seoul, Korea.

Although the feasibility of brain-computer interface (BCI) systems based on steady-state visual evoked potential (SSVEP) has been extensively investigated, only a few studies have evaluated its clinical feasibility in patients with locked-in syndrome (LIS), who are the main targets of BCI technology. The main objective of this case report was to share our experiences of SSVEP-based BCI experiments involving five patients with LIS, thereby providing researchers with useful information that can potentially help them to design BCI experiments for patients with LIS. In our experiments, a four-class online SSVEP-based BCI system was implemented and applied to four of five patients repeatedly on multiple days to investigate its test-retest reliability. In the last experiments with two of the four patients, the practical usability of our BCI system was tested using a questionnaire survey. All five patients showed clear and distinct SSVEP responses at all four fundamental stimulation frequencies (6, 6.66, 7.5, 10 Hz), and responses at harmonic frequencies were also observed in three patients. Mean classification accuracy was 76.99% (chance level = 25%). The test-retest reliability experiments demonstrated stable performance of our BCI system over different days even when the initial experimental settings (e.g., electrode configuration, fixation time, visual angle) used in the first experiment were used without significant modifications. Our results suggest that SSVEP-based BCI paradigms might be successfully used to implement clinically feasible BCI systems for severely paralyzed patients.
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http://dx.doi.org/10.1111/psyp.12793DOI Listing
March 2017

A Case of Chronic Myeloid Leukemia With Rare Variant ETV6/ABL1 Rearrangement.

Ann Lab Med 2017 Jan;37(1):77-80

Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.

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http://dx.doi.org/10.3343/alm.2017.37.1.77DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107624PMC
January 2017

Lower Serum Creatinine Is Associated with Low Bone Mineral Density in Subjects without Overt Nephropathy.

PLoS One 2015 24;10(7):e0133062. Epub 2015 Jul 24.

Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Ilsan-Dong, Wonju-Si, Gangwon-Do, Korea.

Background: Low skeletal muscle mass is associated with deterioration of bone mineral density. Because serum creatinine can serve as a marker of muscle mass, we evaluated the relationship between serum creatinine and bone mineral density in an older population with normal renal function.

Methods: Data from a total of 8,648 participants (4,573 men and 4,075 postmenopausal women) aged 45-95 years with an estimated glomerular filtration rate >60 ml/min/1.73 m2 were analyzed from the Fourth Korea National Health and Nutrition Examination Survey (2008-2010). Bone mineral density (BMD) and appendicular muscle mass (ASM) were measured using dual-energy X-ray absorptiometry. Receiver operating characteristic curve analysis revealed that the cut points of serum creatinine for sarcopenia were below 0.88 mg/dl in men and 0.75 mg/dl in women. Subjects were divided into two groups: low creatinine and upper normal creatinine according to the cut point value of serum creatinine for sarcopenia.

Results: In partial correlation analysis adjusted for age, serum creatinine was positively associated with both BMD and ASM. Subjects with low serum creatinine were at a higher risk for low BMD (T-score ≤ -1.0) at the femur neck, total hip and lumbar spine in men, and at the total hip and lumbar spine in women after adjustment for confounding factors. Each standard deviation increase in serum creatinine was significantly associated with reduction in the likelihood of low BMD at the total hip and lumbar spine in both sexes (men: odds ratio (OR) = 0.84 [95% CI = 0.74-0.96] at the total hip, OR = 0.8 [95% CI = 0.68-0.96] at the lumbar spine; women: OR = 0.83 [95% CI = 0.73-0.95] at the total hip, OR=0.81 [95% CI = 0.67-0.99] at the lumbar spine).

Conclusions: Serum creatinine reflected muscle mass, and low serum creatinine was independently associated with low bone mineral density in subjects with normal kidney function.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133062PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514793PMC
May 2016

First report of neutrophil involvement of exflagellated Plasmodium vivax microgametes.

Ann Lab Med 2014 Nov 28;34(6):481-3. Epub 2014 Oct 28.

Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.

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http://dx.doi.org/10.3343/alm.2014.34.6.481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215413PMC
November 2014

Pulmonary infection caused by Mycobacterium neoaurum: the first case in Korea.

Ann Lab Med 2014 May 8;34(3):243-6. Epub 2014 Apr 8.

Department of Laboratory Medicine and Genetics, Soonchunhyang University College of Medicine, Cheonan, Korea.

Mycobacterium neoaurum is rapidly growing mycobacteria that can cause human infections. It commonly causes bloodstream infections in immunocompromised hosts, and unlike other mycobacteria species, it rarely causes pulmonary infections. We confirmed the first pulmonary infection case in Korea caused by M. neoaurum using full-length 16S rRNA gene sequencing.
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http://dx.doi.org/10.3343/alm.2014.34.3.243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999325PMC
May 2014