• Journal of Cancer Prevention
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• v.21 no.2
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• pp.95-103
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• 2016

Background: Excess energy supply induces chronic low-grade inflammation in association with oxidative stress in various tissues including intestinal epithelium. The objective of this study was to investigate the effect of high-fat diet (HFD) on intestinal cell membrane integrity and intestinal tumorigenesis in $Apc^{Min/+}$ mice. Methods: Mice were fed with either normal diet (ND) or HFD for 12 weeks. The number of intestinal tumors were counted and biomarkers of endotoxemia, oxidative stress, and inflammation were determined. Changes in intestinal integrity was measured by fluorescein isothiocyanate (FITC)-dextran penetration and membrane gap junction protein expression. Results: HFD group had significantly higher number of tumors compared to ND group (P < 0.05). Blood total antioxidant capacity was lower in HFD group, while colonic 8-hydroxy-2'-deoxyguanosine level, a marker of oxidative damage, was higher in HFD group compared to that of ND group (P < 0.05). The penetration of FITC-dextran was substantially increased in HFD group (P < 0.05) while the expressions of membrane gap junction proteins including zonula occludens-1, claudin-1, and occludin were lower in HFD group (P < 0.05) compared to those in ND group. Serum concentration of lipopolysaccharide (LPS) receptor (CD14) and colonic toll-like receptor 4 (a LPS receptor) mRNA expression were significantly higher in HFD group than in ND group (P < 0.05), suggesting that significant endotoxemia may occur in HFD group due to the increased membrane permeability. Serum interleukin-6 concentration and myeloperoxidase activity were also higher in HFD group compared to those of ND group (P < 0.05). Conclusions: HFD increases oxidative stress disrupting intestinal gap junction proteins, thereby accelerating membrane permeability endotoxemia, inflammation, and intestinal tumorigenesis.

• The Korean Journal of Zoology
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• v.37 no.4
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• pp.478-487
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• 1994

The developmental changes of three enteroendocrine cells, i.e. gastrln, somatostatin and serotonin, of gastric and small intestinal mucosa in pre- and postnatal rat were examined by peroxidase-antiperoxidase (PAP) method. In the course of development, gastrin cells were obsenred in the pyloric gland region and the whole part of small intestine, while somstostatin and serotonin cells in the whole gastric gland region and small intestine. More entroendocrine cells were detected in the pyloric gland region and duodenum than in the other portion. In the stomach, gastrin, somatostatin and serotonin ceils were first obsenred in the pyloric Bland region on 17, 19 and 19 days of gestation respectively. The small intestinal gastrin and serotonin cells were first appeared in the duodenum and iriunum on 17 and 15 days of gestation respectively, and somatostBtin cells in duodenum on 17 days of gestation. The number of cells examined from the stomach were increased from fetal to weanling period and showed a decrease during adult period: the notable increase was shown at the end of suckling period or at early weanling period. The cells of the small intestine increased from fetal to suckling period, especially, these cells markedly increased at the end of fetal period or at early suckling period, and decreased from weanling period. The shape of these cells was oval or fusiform during fetal period. In the stomach, most of gastrin cells turned out to be oval and open-type from suckling period, while the remaining two tripes of cells were oval and open- or closed-type. In the small intestine, 311%Ves of cells examined were changed to fusiform and open-type from the end of fetal period. Three types of cell were distributed over the stratified epithelium on 15 and 17 days of gestation. In the stomach, these cells were distributed lower gastric pit and gland from the following fetal period, and were detected mainly on the upper part of gland from suckling period, and then obsenred on the whole part of gland. In the small intestine, most of cells distributed over only between epithelium of villi on 19 days of gestation, increased in number on the crypt from following fetal period, and also observed abundantly in the crypt at adult period.

• Parasites, Hosts and Diseases
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• v.32 no.4
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• pp.215-222
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• 1994

The relationship between the intestinal histopathology and number and position of' intraepithelial Iymphocytes(IEL) was observed chronologically in the small intestine of rats experimentally infected wiH Metagonimw vokogawci. Fifteen Sprague-Dawley rats were orally infected each with 3,000 metacercariae, and 3 were kept uninfected for controls. Three rats each were sacrificed on the day 5, 10, 15, 24 and 70 post-infection (PI) and samples of the small intestine, 5 cm, 10 cm, 20 cia and 70 cm posterior to the pylonls were taken. The samples were processed routinely and stained with Giemsa. The intestinal histopathology was severe during the day 5-15 PI and characterized by villous atrophy, crypt hyperplasia, and decrease of villus/ciypt height ratio. After the day 24 PI, the intestinal lesions showed some tendency of recovery The number of IEL increased at the early stage of infection, but decreased thereafter to a lower level than that of controls, with progression of the pathological changes. Then, the IEL number began to increase again after the day 24 PI. In control rats, the great majority of the IEL were located at the basal region of the epithelium. During the early stage of infection, however, a considerable proportion of IEL was found to have moved to the intermediate or apical region of the epithelium. From the above results, it is suggested that the change of IEL number and position during the course of M. yokogowoi infection should be closely related to the progression and recovery of the intestinal histopathology.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.1 no.1
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• pp.45-55
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• 1998

Purpose: To make objective standards of small intestinal mucosal changes in cow's milk-sensitive enteropathy (CMSE) we analyzed histological changes of endoscopic duodenal mucosa biopsy specimens from normal children and patients of CMSE. Methods: We review the medical records of patients who had been admitted and diagnosed as CMSE by means of gastrofiberscopic duodenal mucosal biopsy following cow's milk challenge and withdrawal. Thirteen babies with CMSE, ranging from 14 days to 56 days of age, were studied. Five non-CMSE patients were used as control, ranging from 22 days to 72 days of age. The morphometric parameters under study were villous height, crypt zone depth, ratio of villous height to crypt zone depth, total mucosal thickness and length of surface epithelium by using H & E stained specimens under the drawing apparatus attached microscope. In addition, the numbers of lymphocytes in the epithelium and eosinophil cells in the lamina propria and epithelium were measured. Results: In the duodenal mucosal biopsy specimens in CMSE we found partial and subtotal villous atrophy with an increased number of interepithelial lymphocytes. The mean villous height($135{\pm}59\;{\mu}m$), ratio of villous height to crypt zone depth ($0.46{\pm}0.28$), total mucosal thickness ($499{\pm}56\;{\mu}m$), length of surface epithelium of small intestinal mucosa ($889{\pm}231\;{\mu}m$) in CMSE was significantly decreased compared with the control (p<0.05). The mean crypt zone depth ($311{\pm}65\;{\mu}m$) was significantly greater than the control ($188{\pm}24\;{\mu}m$)(p<0.05). Infiltration of interepithelial lymphocytes ($34.1{\pm}10.5$) were significantly greater than the control ($13.6{\pm}3.6$)(p<0.05). The number of eosinophil cells in both lamina propria and epithelium was no significant differences between groups (p>0.05). The small intestinal mucosa in treated CMSE showed much improved enteropathy of villous height, crypt zone depth, interepithelial lymphocytes compared with the control as well as untreated CMSE. Conclusion: Quantitation of mucosal dimensions confirmed the presence of CMSE. It seems to be a limitation in the capacity of crypt cells to compensate for the loss of villous epithelium in CMSE. Specimens obtained by gastrofiberscopic duodenal mucosal biopsy were suitable for morphometric diagnosis of CMSE. Improvement of CMSE also can be confirmed histologically after the therapy of protein hydrolysate.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.119-119
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• 1997

Valacyclovir is a L-valyl ester prodrug of acyclovir which is a highly effective and selective antiviral agent in the treatment of herpes virus diseases. Valacyclovir is rapidly and almost completely converted to acyclovir and increases the oral bioavailability of acyclovir three to five fold. However, the intestinal absorption mechanism of valacyclovir is not clear. If the improved absorption mechanism of valacyclovir is fully understood, it will provide a rationale of designing the amino acid ester prodrugs of polar drugs containing hydroxyl group. The main objective of our present study is to characterize the membrane transport mechanism of valacyclovir. Methods : Intestinal absorption of valacyclovir was investigated by using in-situ rat perfusion study and its wall permeability was estimated by modified boundary layer model. The membrane transport mechanism was also investigated through the uptake study in Caco-2 cells and in CHO-hPepTl cells. Results : In the rat perfusion study, the wall permeability of valacyclovir was ten times higher than acyclovir and showed concentration dependency, Valacyclovir also demonstrated a D,L stereo-selectivity with L-isomer having an approximately five-fold higher permeability than D-isomer. Mixed dipeptides and cephalexin, which are transported by dipeptide carriers, strongly competed with valacyclovir for the intestinal absorption, while L-valine did not show any competition with valacyclovir. This indicated that the intestinal absorption of valacyclovir could be dipeptide carrier-mediated. In addition, the competitive uptake study in Caco-2 cells presented that dipeptides reduced the valacyclovir uptake but valine did not. Also, in IC$\sub$50/ study, valacyclovir showed strong inhibition on the $^3$H-gly-sar uptake in CHO-hPepTl cells over-expressing a human intestinal peptide transporter. Taken together, the result from our present study indicated that valacyclovir utilized the peptide transporter for the intestinal absorption.

• BMB Reports
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• v.49 no.1
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• pp.11-17
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• 2016

The gastrointestinal tract forms the largest surface in our body with constantly being exposed to various antigens, which provides unique microenvironment for the immune system in the intestine. Accordingly, the gut epithelium harbors the most T lymphocytes in the body as intraepithelial lymphocytes (IELs), which are phenotypically and functionally heterogeneous populations, distinct from the conventional mature T cells in the periphery. IELs arise either from pre-committed thymic precursors (natural IELs) or from conventional CD4 or CD8αβ T cells in response to peripheral antigens (induced IELs), both of which commonly express CD8α homodimers (CD8αα). Although lineage commitment to either conventional CD4 T helper (Th) or cytotoxic CD8αβ T cells as well as their respective co-receptor expression are mutually exclusive and irreversible process, CD4 T cells can be redirected to the CD8 IELs with high cytolytic activity upon migration to the gut epithelium. Recent reports show that master transcription factors for CD4 and CD8 T cells, ThPOK (Th-inducing BTB/POZ-Kruppel-like factor) and Runx3 (Runt related transcription factor 3), respectively, are the key regulators for re-programming of CD4 T cells to CD8 lineage in the intestinal epithelium. This review will focus on the unique differentiation process of IELs, particularly lineage re-commitment of CD4 IELs. [BMB Reports 2016; 49(1): 11-17]

• Korean Journal of Veterinary Research
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• v.38 no.3
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• pp.450-454
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• 1998

We have studied Meckel's diverticulum(MD) of the duck(Anas platyrhynchos platyrhyncos, Linne) by histological and immunohistochemical methods. Because MD were first observed in 2 weeks after hatching, tissues were taken from 2 weeks to 32 weeks after hatching groups. MD were observed as like any parts of intestinal tract that composed with simple columnar epithelium and numerous mucosal gland especially, cecum except that many lymphocytes were exist in this study. Also a number of bovine chromogranin(BCG)-, serotonin, and somatostatin(SOM)-immunoreactive cells were observed in epithelium and submucosal gland in this study, so it could be suggest that the MD of the duck serve as some digestive and lymphatic functions.

• Development and Reproduction
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• v.23 no.4
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• pp.305-311
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• 2019

Small intestine has a structure called villi that increases the mucosal surface area for nutrient absorption. Intricate and tight epithelial-mesenchymal interactions are required for villi development. These interactions are regulated by signaling molecules, physical forces, and epithelial deformation. Signaling molecules include hedgehog (Hh), bone morphogenetic protein (BMP) and Wnt ligands. The Hh ligand is expressed from the epithelium and binds to the underlying mesenchymal cells, resulting in aggregation into mesenchymal clusters. The clusters express BMP and Wnt ligands to control its size and spacing between clusters. The clusters then form villi. Despite the fact that the villi formation is studied extensively, we do not have a complete understanding. In addition, the recent study shows there is a great relationship between the overexpression of the Hh signal and development of cancer in the gastrointestinal tract. Therefore, signaling between epithelial and mesenchymal cells and their physical interactions will be discussed on this review.

• Journal of Animal Science and Technology
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• v.64 no.6
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• pp.1105-1116
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• 2022

Recently, we reported the robust in vitro three-dimensional (3D) expansion of intestinal organoids derived from adult bovine (> 24 months) samples. The present study aimed to establish an in vitro 3D system for the cultivation of intestinal organoids derived from growing cattle (12 months old) for practical use as a potential alternative to in vivo systems for various purposes. However, very few studies on the functional characterization and 3D expansion of adult stem cells from livestock species compared to those from other species are available. In this study, intestinal crypts, including intestinal stem cells, from the small intestines (ileum and jejunum) of growing cattle were isolated and long-term 3D cultures were successfully established using a scaffold-based method. Furthermore, we generated an apical-out intestinal organoid derived from growing cattle. Interestingly, intestinal organoids derived from the ileum, but not the jejunum, could be expanded without losing the ability to recapitulate crypts, and these organoids specifically expressed several specific markers of intestinal stem cells and the intestinal epithelium. Furthermore, these organoids exhibited key functionality with regard to high permeability for compounds up to 4 kDa in size (e.g., fluorescein isothiocyanate [FITC]-dextran), indicating that apical-out intestinal organoids are better than other models. Collectively, these results indicate the establishment of growing cattle-derived intestinal organoids and subsequent generation of apical-out intestinal organoids. These organoids may be valuable tools and potential alternatives to in vivo systems for examining host-pathogen interactions involving epithelial cells, such as enteric virus infection and nutrient absorption, and may be used for various purposes.

• Archives of Pharmacal Research
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• v.26 no.12
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• pp.1102-1108
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• 2003

We studied the effects of phytolaccosides, saponins from Phytolacca americana, on the intestinal absorption of heparin in vitro and in vivo. The absorption enhancing activity of these compounds (phytolaccosides B, $D_2$, E, F, G and I) was determined by changes in transepithelial electrical resistance (TEER) and the transport amount of heparin disaccharide, the major repeating unit of heparin, across Caco-2 cell monolayers. With the exception of phytolaccoside G, all of them decreased TEER values and increased the permeability in a dose-dependent and time-dependent manner. In vitro, phytolaccosides B,$D_2$, and E showed significant absorption enhancing activities, while effects by phytolaccoside F and I were mild. In vivo, phytolaccoside E increased the activated partial thromboplastin time (APTT) and thrombin time, indicating that phytolaccoside E modulated the transport of heparin in intestinal route. Our results suggest that a series of phytolaccosides from Phytolacca americana can be applied as pharmaceutical excipients to improve the permeability of macromolecules and hydrophilic drugs having difficulty in absorption across the intestinal epithelium.