• Journal of Gastric Cancer
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• v.20 no.4
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• pp.408-420
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• 2020

Purpose: Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC). Materials and Methods: We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017. Results: CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively). Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival. Conclusions: CLDN18.2 expression was reduced in patients with PM but significantly intact in those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.

• The Journal of Internal Korean Medicine
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• v.37 no.1
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• pp.65-76
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• 2016

Objectives: The purpose of this study was to identify the inhibitory effects of Hwangheuk-san (HHS), a Korean multi-herb formula comprising four medicinal herbs, on cell migration and invasion, two critical cellular processes that are often deregulated during metastasis, using the human bladder cancer 5637 cell line.Methods: Cell viability, motility, and invasion were assessed by 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphnyl-2H-tetrazolium bromide (MTT), wound healing migration, and Transwell assays, respectively. Gene expression was detected by Western blot analysis. In addition, the activities of matrix metalloproteinases (MMPs) and the values for transepithelial electrical resistance (TER) were analyzed using a Gelatinase Activity Assay Kit and an Epithelial Tissue Voltohmmeter, respectively.Results: Our data indicated that within the concentration range that was not cytotoxic, HHS effectively inhibited the cell motility and invasiveness of 5637 cells. HHS markedly decreased the expression and activity of MMP-2 and MMP-9, which was associated with unregulation of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2. Further investigation revealed that phosphorylation of phosphatidylinositol 3-kinase (PI3K) and AKT was decreased in HHS-treated 5637 cells, and a PI3K/AKT inhibitor synergistically reduced the inhibition of migration and invasion and also inactivated MMP-2 and MMP-9. Moreover, HHS increased the tightening of tight junctions (TJs), which was demonstrated by an increase in the TER, and reduced the expression the levels of claudin family members (claudin-3 and -4), which are major components involved in the tightening of TJs.Conclusions: The present findings demonstrated that HHS attenuated the migration and invasion of bladder cancer 5637 cells by modulating the activity of the PI3K/Akt signaling pathway and also through TJ tightening.

• Applied Microscopy
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• v.29 no.1
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• pp.83-94
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• 1999

The ultrastructure of small arterioles and capillaries in the lumbrical muscles of rat digits were studied by electron microscopy and following results were obtained. 1. The diameter of small arterioles of rat digits were $12\sim20{\mu}m$, and it was relatively smaller than human $(30\sim35{\mu}m)$. 2. All the endothelial cells of small arterioles and capillaries in the lumbrical muscles of rat digits were continuous type, and they had typical morphological characteristics of continuous endothelial cells : numerous cytoplasmic pinocytic vesicles and many tight junctions between the endothelial cells. 3. In the small arterioles subendothelial layers were irregularly spaced beneath the basal lamina, and membrane to membrane contacts were found between the endothelial cells and smooth muscle cells. 4. Pericytes were often found nearby capillary endothelium, and their cytoplasmic processes surrounded part of endothelial cells. They were enclosed by basal lamina. 5. Smooth muscle cells in tunica media of small arterioles were only one layered, that is, they were terminal arterioles. Sarcoplasm of smooth muscle cell was divided to 2 areas; homogeneous or filamentous area and non-homogeneous perinuclear area. 6. The tunica adventitia contained fibroblasts with extremely attenuated cytoplasmic processes and collagen fibirls.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.8
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• pp.1075-1082
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• 2016

Modern livestock production became highly intensive and large scaled to increase production efficiency. This production environment could add stressors affecting the health and growth of animals. Major stressors can include environment (air quality and temperature), nutrition, and infection. These stressors can reduce growth performance and alter immune systems at systemic and local levels including the gastrointestinal tract. Heat stress increases the permeability, oxidative stress, and inflammatory responses in the gut. Nutritional stress from fasting, antinutritional compounds, and toxins induces the leakage and destruction of the tight junction proteins in the gut. Fasting is shown to suppress pro-inflammatory cytokines, whereas deoxynivalenol increases the recruitment of intestinal pro-inflammatory cytokines and the level of lymphocytes in the gut. Pathogenic and viral infections such as Enterotoxigenic E. coli (ETEC) and porcine epidemic diarrhea virus can lead to loosening the intestinal epithelial barrier. On the other hand, supplementation of Lactobacillus or Saccharaomyces reduced infectious stress by ETEC. It was noted that major stressors altered the permeability of intestinal barriers and profiles of genes and proteins of pro-inflammatory cytokines and chemokines in mucosal system in pigs. However, it is not sufficient to fully explain the mechanism of the gut immune system in pigs under stress conditions. Correlation and interaction of gut and systemic immune system under major stressors should be better defined to overcome aforementioned obstacles.

• Journal of Microbiology and Biotechnology
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• v.24 no.5
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• pp.696-703
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• 2014

Clostridium difficile causes mucosal damage and diarrhea by releasing two exotoxins: toxin A and toxin B. C. difficile colitis is associated with alterations in bowel flora and the failure to mount an effective antibody response. The aim of the current study was to investigate whether antitoxin sera prevent toxin-A-induced apoptosis, cytoskeletal disaggregation, cell detachment, and tight junction loss in cultured colonic epithelial cells. Serum samples were isolated from mice that survived a C. difficile infection following antibiotic treatment, and the antitoxin effects of these samples were investigated in toxin-A-exposed HT29 colonic epithelial cells and a toxin-A-induced animal model of gut inflammation. Unchallenged mice did not produce IgG against toxin A, whereas serum (antiserum) from C. difficile-challenged mice showed significant IgG responses against toxin A. Treatment with the antiserum markedly inhibited mucosal damage and inflammation in the toxin-A-treated mouse model. In contrast to control mouse serum, the antiserum also markedly inhibited toxin-A-induced DNA fragmentation, dephosphorylation of paxillin and Epo receptor (EpoR), deacetylation of tubulin, and upregulation of p21(WAF1/CIP1) and p53. Taken together, these results reveal that the generated antitoxin serum has biotherapeutic effects in preventing various C. difficile toxin-A-induced cellular toxicities.

• Nutrition Research and Practice
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• v.14 no.5
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• pp.425-437
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• 2020

BACKGROUND/OBJECTIVES: Different fatty acids exert different health benefits. This study investigated the potential protective effects of perilla, olive, and safflower oils on high-fat diet-induced obesity and colon inflammation. MATERIALS/METHODS: Five-week old, C57BL/6J mice were assigned to 5 groups: low-fat diet (LFD), high-fat diet (HFD) and high-fat diet supplemented with-perilla oil (HPO), olive oil (HOO), and safflower oil (HSO). After 16 weeks of the experimental period, the mice were sacrificed, and blood and tissues were collected. The serum was analyzed for obesity- and inflammation-related biomarkers. Gene expression of the biomarkers in the liver, adipose tissue, and colon tissue was analyzed. Micro-computed tomography (CT) analysis was performed one week before sacrifice. RESULTS: Treatment with all the three oils significantly improved obesity-induced increases in body weight, liver weight, and epididymal fat weight as well as serum triglyceride and leptin levels. Treatment with perilla oil (PO) and safflower oil (SO) increased adiponectin levels. The micro-CT analysis revealed that PO and SO reduced abdominal fat volume considerably. The mRNA expression of lipogenic genes was reduced in all the three oilsupplemented groups and PO upregulated lipid oxidation in the liver. Supplementation of oils improved macroscopic score, increased colon length, and decreased serum endotoxin and proinflammatory cytokine levels in the colon. The abundance of Bifidobacteria was increased and that of Enterobacteriaceae was reduced in the PO-supplemented group. All three oils reduced proinflammatory cytokine levels, as indicated by the mRNA expression. In addition, PO increased the expression of tight junction proteins. CONCLUSIONS: Taken together, our data indicate that the three oils exert similar anti-obesity effects. Interestingly, compared with olive oil and SO, PO provides better protection against high-fat diet-induced colon inflammation, suggesting that PO consumption helps manage inflammation-related diseases and provides omega-3 fatty acids needed by the body.

• Korean journal of applied entomology
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• v.34 no.4
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• pp.334-343
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• 1995

The eyes of Nilaparvata lugens were examined for ultrastructural changes in the light and dark adapted states. Inspection of light microscope sections taken at similar levels of compound eyes from insects kept in light or darkness for periods up to 72 hors revealed some differences between light and dark adapted eyes. Using the electronmicroscope, in light adapted eyes the palisade layer was narrower than that in dark adapted eyes. The pigment granules still formed a ring around the palisade layer in the dark adapted eye but, they did not form a tight circle around the rhabdom. No constant difference was found between the diameters of the microvilli in light and dark adapted eyes. The pigment movements at the junction of the cone and the rhabdom took the effect on varying the pigment aperture at the tip of the cone in front of the rhabdom tip.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.1
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• pp.9-14
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• 2001

With the object of providing a temporary artificial periodonal ligament-like membrane around the dental implant, 10 Branemark type implants were coated with commercially available chitosan(Fluka Co., Buchs, Switzerland) which has a molecular weight of 70,000 and 80% deacetylation degree. Once this bioactive hydrophillic polymer(chitosan) contacts with blood or wound fluids, it becomes swollen and penetrates into the adjacent cancellous bone. Thus the interface between implant and surrounding bone is completely filled with chitosan. This tight junction in early healing phase enhances primary stability. The chitosan coated dental implants were implanted into the fresh patella bones from porcine knees, since the thickness of cortical bone is relatively even and their cancellous structure is homogenous. To test the shock absorbing effect, 1mm delta-rogette strain gage was installed behind the implant. The results showed 1. The principal strain peak value directed to the impact of coated implant was 0.064 0.018(p<0.05) and that of uncoated implant was 0.095(0.032 p<0.05). 2. The peak time delay of coated implant was 0.056sec(0.011 p<0.05) and that of uncoated implant was 0.024sec(0.009 p<0.05). It can be reasoned from this results that the chitosan coating has a shock absorbing effect comparable with a temporary artificial periodontal ligament.

• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.2
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• pp.71-84
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• 2010

Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.179-186
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• 2009

Hexachlorobenzene (HCB) is a bioaccumulative, persistent, and toxic pollutant. HCB is one of the 12 priority of Persistent Organic Pollutants (POPs) intended for global action by the United Nations Environment Program (UNEP) Governing Council. POPs are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes. Some of HCB is ubiquitous in air, water, soil, and biological matrices, as well as in major environmental compartments. HCB has effects on various organs such as thyroid, bone, skin, kidneys and blood cells and especially, revealed strong toxicity to liver. In this study, we identified genes related to hepatotoxiciy induced by HCB in human hepatocellular carcinoma (HepG2) cells using microarray and gene ontology (GO) analysis. Through microarray analysis, we identified 96 up- and 617 down-regulated genes changed by more than 1.5-fold by HCB. And after GO analysis, we determined several key pathways which known as related to hepatotoxicity such as metabolism of xenobiotics by cytochrome P450, complement and coagulation cascades, and tight junction. Thus, our present study suggests that genes expressed by HCB may provide a clue for hepatotoxic mechanism of HCB and gene expression profiling by toxicogenomic analysis also affords promising opportunities to reveal potential new mechanistic markers of toxicity.