• Clinical Nutrition Research
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• v.12 no.2
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• pp.154-167
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• 2023

Hepatic encephalopathy (HE) associated with liver failure is accompanied by hyperammonemia, severe inflammation, depression, anxiety, and memory deficits as well as liver injury. Recent studies have focused on the liver-brain-inflammation axis to identify a therapeutic solution for patients with HE. Lipocalin-2 is an inflammation-related glycoprotein that is secreted by various organs and is involved in cellular mechanisms including iron homeostasis, glucose metabolism, cell death, neurite outgrowth, and neurogenesis. In this study, we investigated that the roles of lipocalin-2 both in the brain cortex of mice with HE and in Neuro-2a (N2A) cells. We detected elevated levels of lipocalin-2 both in the plasma and liver in a bile duct ligation mouse model of HE. We confirmed changes in cytokine expression, such as interleukin-1β, cyclooxygenase 2 expression, and iron metabolism related to gene expression through AKT-mediated signaling both in the brain cortex of mice with HE and N2A cells. Our data showed negative effects of hepatic lipocalin-2 on cell survival, iron homeostasis, and neurite outgrowth in N2A cells. Thus, we suggest that regulation of lipocalin-2 in the brain in HE may be a critical therapeutic approach to alleviate neuropathological problems focused on the liver-brain axis.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.403-423
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• 2024

The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.1
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• pp.63-69
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• 2023

Methods: Patients who underwent cholecystectomy were classified into two groups according to their GBWT status (GBWT+ vs. GBWT-). Results: Among 1,211 patients who underwent cholecystectomy, GBWT+ was seen in 177 (14.6%). The GBWT+ group was significantly older with more males, higher ASA score, higher alkaline phosphatase level, higher international normalized ratio, and lower albumin level than the GBWT- group. On ultrasound, GBWT+ patients had larger stone size, more pericholecystic fluid, more common bile duct stone, and more biliary pancreatitis. Compared with the GBWT- group, the GBWT+ group had more urgent surgeries (12.4% vs. 3.2%, p = 0.001), higher conversion rate (4.5% vs. 0.3%, p = 0.001), prolonged operative time (67 ± 38 vs. 54 ± 29 min; p = 0.001), more bleeding (3.4% vs. 0.5%, p = 0.002), and more need of drain (21.5% vs. 10.5%, p = 0.001). By multivariate analysis, factors associated with increased length of hospital stay were GBWT+ (HR: 1.97, 95% CI: 1.19-3.25, p = 0.008), urgent surgery (HR: 10.2, 95% CI: 4.07-25.92, p = 0.001), prolonged surgery (HR: 1.01, 95% CI: 1.0-1.02, p = 0.001), and postoperative drain (HR: 11.3, 95% CI: 6.40-20.0, p = 0.001). Conclusions: Variables such as GBWT ≥ 5 mm, urgent prolonged operation, and postoperative drains are independent predictors of extended hospital stay. GBWT+ patients are twice likely to stay in hospital for more than 72 hours and more prone to develop complications than GBWT- patients.

• Clinical Endoscopy
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• v.55 no.3
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• pp.458-462
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• 2022

Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS) is widely performed not only as an alternative to transpapillary biliary drainage, but also as primary drainage for malignant biliary obstruction. For anatomical reasons, this technique carries an unavoidable risk of mispuncturing intrahepatic vessels. We report a technique for troubleshooting EUS-guided portal vein coiling to prevent bleeding from the intrahepatic portal vein after mispuncture during interventional EUS. EUS-HGS was planned for a 59-year-old male patient with unresectable pancreatic cancer. The dilated bile duct (lumen diameter, 2.8 mm) was punctured with a 19-gauge needle, and a guidewire was inserted. After bougie dilation, the guidewire was found to be inside the intrahepatic portal vein. Embolizing coils were placed to prevent bleeding. Embolization coils were successfully inserted under stabilization of the catheter using a double-lumen cannula with a guidewire. Following these procedures, the patient was asymptomatic. Computed tomography performed the next day revealed no complications.

• Clinical Endoscopy
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• v.57 no.4
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• pp.542-546
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• 2024

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) through ducts B2 or B3 is effective in most patients with biliary obstruction, because B2 and B3 commonly join together. However, in some patients, B2 and B3 do not join each other due to invasive hilar tumors; therefore, single-route drainage is insufficient. Here, we investigated the feasibility and efficacy of EUS-HGS through both B2 and B3 simultaneously in seven patients. We decided to perform EUS-HGS through both B2 and B3 to achieve adequate biliary drainage because these two ducts were separate from each other. Here, we report a 100% technical and overall clinical success rate. Early adverse effects were closely monitored. Minimal bleeding was reported in one patient (1/7) and mild peritonitis in one patient (1/7). None of the patients experienced stent dysfunction, fever, or bile leakage after the procedure. EUS-HGS through both B2 and B3 simultaneously is safe, feasible, and effective for biliary drainage in patients with separated ducts.

• Proceedings of the Korean Society for Food Science of Animal Resources Conference
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• 1998.10a
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• pp.83-106
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• 1998

This study was conducted to investigate the probiotics(acid and bile resistance, fermentation properties, viability, cholesterol assimilation, antimicrobial activity, antimutagenicity, and immunoactivation) of the strains of bifidobacteria isolated from healthy Koreans and to investigate the effects of oral administration of Bifidobacterium longum A-2 on the fecal microflora, ${\beta}-glucuronidase$ activity, pH values, Ammonia concentration. The experimental results are summarized as follows: The probiotics were tested for 23 strains including three commer챠al strains as controls. Compared to other strains, strains of A-2 and A-9 showed more acid resistance whereas A-2, A-5, A-13, A-14, A-18 and A-22 showed excellent bile resistances. The properties of bifidobacteria during fermentation were tested. Strains of A-1, A-2, A-3, A-4, A-6, and A-23 resulted in less than pH 4.5 and titratable acidity over 0.90 after 24 hr of fermentation. When the strains of A-2 was grown with glucose, maltose, and fructooligosaccharide, the acetic acid production were higher than with sorbitol and mannitol. The storage stability of the strains of A-2 and A-22 were tesed, indicating the strain A-2 was more stable over 10 days of storage at both $4^{\circ}C$ and $20^{\circ}C$ than A-22. The strains of A-8, A-10, A-11, A-12 and A-20 assimilated more than 30% of cholesterol included in the media. The strains of A-1 and A-2 showed antimicrobial activity against Sta. aureus. The antimutagenicity of the strains were also tested, showing that the mutation was suppressed more by three strains(A-2, A-12, and A-23). In addition, strain A-5 improved immunological activity(phagocytosis, $TNF-{\alpha}$, IL-6) more than other strains. In the effects of oral administration of Bif. longum A-2, the number of fecal bifidobacteria was siginificantly increased(p<0.01) and the level of fecal ${\beta}-glucuronidase$ also was siginificantly reduced(p<0.05). However there were no siginificant differences in the level of Lαctobacilli, Enterobacteriaceae, Clostridium perfringens, pH and ammonia by the administration. The results suggested that Bif. longum A-2 may be met the criteria for probiotics culture.

• Journal of Nutrition and Health
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• v.30 no.5
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• pp.465-477
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• 1997

The purpose of this article is to know the effects on bowel function of the kind of fiber and the amount of fiber in SD-rats. To do this experiment, we select of $\alpha$-cellulose as n insoluble cellulose source and alginic acid and pectin as soluble cellulose source. The rats diets contained callolose camcentrations of 1.0%, 3.6%, 6.0% and 10.0%. After that, we raised the SD-rats for 4weeks and measured the amount of food intake, body weight, the food effciency ratio, the length of liver and stomach the weight of the intestines, the transit time through the intestines, pH in feces, and the amount of bile acid and Ca, Mg, pp. 1) The amount of food intake was 15.75-31.00g/day. It was highest in the 10.0% cellulose group and the lowest in the 3.6% and 6.0% alginic acid group (p<0.05). The body weights of rats were 277.50-349.809. It was highest in the 1.0% pectin group and lowest in the 3.6% alginic acid group, 6.0% cellulose group, and 10.0% pectin group. It had differences according to the content fiber and the kind of dietary(p<0.01). The food efficiency ratio was (p<0.01). The higher the content of dietary fiber, the lower the calory and the food efficiency ratio. 2) Transit time was 446.0-775.0 minutes and it showed signidicant ifferences according to the content and kind of dietary fiber(p<0.01). It was long in the 1.0% cellulose group and 1.0% pectin group but short in the 10.0% alginic acid group. As the content of dietary fiber increased, the transit time through the intestines was shortened. The length of small intestine was 101.03-120.40cm and there were no difference cegardloss of the content and kind of fiber. The length of the large intestine was 20.92-25.42cm and there were significant differences according to the content and kind of the fiber. High-fiber diets resulted in increases in the length of the large intestine. 3) The weight of the liver was 8.68-10.96g and there were no differences according to the content and kind of fiber. The weight of stomach was 1.28-1.74g and there were no differences resulting from the kind of dietary fiber, but it was highest in the 10.0% alginic acid group. The weight of the small intestine was 5.52-8.04g with no difference resulting from to the kind of fiber. It was highest in the 10.0% the alginic acid group and lowest in the 1.0% alginic acid group(p<0.05). The weight of large intestine was 2.50-3.30g with no differences related to the kind of dietary fiber. It was heaviest in the 6.0% and 10.0% alginic acid groups and in the 10.0% pectin group with differences related to the content of fiber(p<0.05). 4) The pH of the feces was 5.82-6.86 according to the kind of dietary fiber, alginic acid group was high at 6.66, the cellulose group was 6.26. but the pectin group was low at 6.30. There were difference according to the content of fiber, but no consistency. The content of bile acid was 6.25-34.77umol per 1g of dry feces. According to the kind of dietary fiber, the alginic acid group was low at 12.91umol, cellulose group was 18.64umol and, the pectin group was the highest at 27.78umol(p<0.001). Based on the content of dietary fiber, alginic acid group was low at 1.0%, but high at 3.6% pectin group(p<0.001). 5) The amount of feces was 1.00-5.10g/day. The weight of rat feces was 2.23g/day in the alginic acid goup, 2.75g/day in the cellulose group, and 1.82g/day in the pectin group. According to the content of fiber, cellulose group was high at 10.0% but alginic acid group was 1.0%, and there were significant difference according to the dietary fiber. The more the content of fiber, the more increase the content of feces in alginic acid, cellulose and pectin group. The content of Ca in the feces was 80.10-207.82mg/1g of dry feces. In the dietary fiber, alginic acid group was 193.08mg, cellulose group was 87.5mg, pectin group was 138.16mg. In the content of fiber, alginic acid group was high at 1.0% and 3.6% but low at 10.0% of Pectin group. The content of Mg was 19.15-44.72mg/1g of dry feces. According to the kind of dietary fiber, alginic acid group was 35.33mg, cellulose group was 23.60mg, and pectin was 36.93mg. According to the content of fiber, pectin group was high at 1.0% and low at 10.0% of cellulose group. The content of P was 1.65-4.65mg/1g of dry feces. According to the kind of dietary fiber, alginic acid group 2.23mg/g dry feces, cellulose group was 2.29mg/g, pectin group wa 4.08mg/g dry feces. In the content of fiber, pectin group was high at 6.0% and low at 6.0% alginic acid group, but there were significant difference among the analysis value. The conetnt of Ca and MG was higher in soluble alginic acid group and pectin group than in insoluble cellulose group. The high the content of the dietary fiber, the lower the food efficiency ratio and the short the transit time through intestine with the increase of the length of large intestin as well as the higher level of the stomach, the small intestine and the large intestine. According to the content of the dietary fiber, the amount of the feces, Ca, Mg and P was increased but the length the small intestin, the weight of liver, pH of the feces and the amount of bile acid showed no differences and consistency.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.969-972
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• 2002

The alteration in the pharmacokinetic behaviors of organic cations (OCs) in rats during acute inflammation (AI) was investigated. AI was induced by an intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) 24 hr prior to the start of pharmacokinetic studies. Tributylmethylammonium (TBuMA) was selected as a model OC since it is largely excreted into bile, and is neither metabolized nor binds to proteins in the body. When TBuMA was administered intravenously to AI rats at a dose of 6.6 $\mu$mole/kg, the AUC was increased, while biliary excretion (i.e., cumulative amount and apparent clearance) was decreased compared to normal rats. When TBuMA was administered intravenously to AI rats at a constant rate (i.e., a bolus injection at a dose of 1.5 $\mu$mole/kg followed by a constant infusion at a rate of 1.5 $\mu$mole/kg/hr for 165 min), steady-state concentrations of plasma and liver concentrations of TBuMA were increased significantly, while in vivo hepatic uptake (amount) and canalicular excretion (clearance) were decreased. These results are consistent with a hypothesis in which both the sinusoidal uptake of TBuMA into hepatocytes via the OCT1 and the canalicular excretion of the compound from hepatocytes via the P-gp are decreased by LPS-induced AI.

• Archives of Pharmacal Research
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• v.20 no.5
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• pp.454-458
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• 1997

Two human liver UDP-glucuronosyltransferase cDNA clones, HLUG25 and UDPGTh2 were previously shown to encode isozymes active in the glucuronidation of hyodeoxycholic acid (HDCA) and certain estrogen derivatives (e.g., estriol and 3,4-catechol estrogens), respectively. in this study we have found that the UDPGTh2-encoded isoform (UDPGTh2) and HLUG25-encoded isoform (UDPGThl) have parallel aglycone specificities. When expressed in COS 1 cells, each isoform metabolized three types of dihydroxy- or trihydroxy-substituted ring structures, including the 3,4-catechol estrogen (4-hydroxyestrone), estriol, 17-epiestriol, and HDCA, but the UDPGTh2 isozyme was 100-fold more efficient than UDPGTh1. UDPGTh1 and UDPGTh2 were 86% identical overall (76 differences out of 528 amino acids), including 55 differences in the first 300 amino acids of the amino terminus, a domain which conferred the substrate specificity. The data indicated that a high level of conservation in the amino terminus was not required for the preservation of substrate selectivity. Analysis of glucuronidation activity encoded by UDPGTh1/UDPGTh2 chimeric cDNA constructed at their common restriction sites, Sac I (codon 297), Nco I (codon 385), and Hha I (codon 469), showed that nine amino acids between residues 385 and 469 were important for catalytic efficiency, suggesting that this region represented a domain which was critical for the catalysis but distinct from that responsible for aglycone-selection. These data indicate that UDPGTh2 is a primary isoform responsible for the detoxification of the bile salt intermediate as well as the active estrogen intermediates.

• Food Science and Biotechnology
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• v.14 no.4
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• pp.503-508
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• 2005

Screening for antilisterial activity was performed in about three thousand isolates of lactic acid bacteria (LAB) from Chinese cabbage kimchi, and finally based on the relatively stronger antilisterial activities eight bacterial strains were selected. The bacteria were further characterized in terms of their tolerance to artificial gastric juice, pH 2.5, bile salts (0.3% oxgall), and to the different NaCl concentrations. Of the isolates, YK005 was especially investigated for its physiological characteristics due to its inhibitory activity against gram-positive Listeria monocytogenes as well as gram-negative Escherichia coli O157:H7, as they have been constantly reported to be resistant against bacteriocins produced by a number of LAB strains. YK005 was found to be rod-shaped, $3.8\;{\mu}m$ long ${\times}\;0.5\;{\mu}m$ wide, non-sporeforming, non-motile, catalase-negative, and produced gas from glucose (heterolactic). Based on the biochemical data obtained by API 50 CHL medium, the isolate was tentatively identified as Lactobacillus brevis. To validate the result obtained by the biochemical identification, rRNA-based PCR experiments using a pair of species-specific primers for L. brevis were conducted and a single band of 1400 bp was observed, which strongly indicated that YK005 belongs to L. brevis. The LAB isolates are potentially exploited as human probiotic organisms and are employed to control some food-borne pathogens like L. monocytogenes.