• 대한한방내과학회지
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• 제37권1호
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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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• 제29권1호
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• pp.83-94
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• 1999

미세혈관 수술의 발달로 수지동맥의 재접합술이 성행함에 따라 혈관벽의 구조에 관한 연구들이 활발하지만 수지의 미세동맥과 모세혈관에 관한 연구는 드물다. 이에 저자는 흰쥐 수지의 충양근 안에 있는 미세동맥과 모세혈관의 구조를 전자현미경으로 관찰하여 보고하고자 한다. 1. 흰쥐 충양근 내의 미세동맥 (small arterioles)은 그 직경이 $12\sim20{\mu}m$로 중막이 한 층의 평활근세포로 구성된 종말소동맥 (terminal arteriole) 형태였는데 인체의 종말소동맥$(30\sim35{\mu}m)$에 비해 직경이 작았으며, 모세혈관은 직경이 $5\sim8{\mu}m$로 비슷하였다. 2. 모든 미세동맥 및 모세혈관의 내막을 구성하는 내피세포는 연속형 (continuous type)이었고, 따라서 전체 세포질내에 포음소포(pinocytic vesicles)가 많이 관찰되었다. 3. 모세혈관 주위에서 자주 혈관주위세포(pericytes)가 관찰되었는데 철관주위세포의 긴 들기가 내피세포의 일부를 싸는 경우도 많았으며 이들은 기저판에 의해 둘러싸여 있었다. 4. 내피세포들 사이에는 여러 가지 형태의 접촉이 있었으나 특히 폐쇄띠 (tight junction)를 가장 많이 관찰할 수 있었다. 미세동맥의 내피하층은 기저판 아래에서 매우 불규칙한 양상으로 나타났는데 곳곳에 내피세포와 중막을 구성하는 평활근세포의 막이 꽉 붙어 관찰되었다. 5. 미세동맥의 중막을 구성하는 한 층의 평활근세포의 세포질은 많은 filaments가 있어 균질성으로 보이는 균질성 영역 (homogeneous area)과 mitochondria, 조면내형질망, 골지복합체, polyribosome 등이 관찰되는 핵 주위의 비균질성 영역 (non-homogeneous area)으로 구분되었다. 6. 미세동맥의 외막은 섬유모세포의 아주 가느다란 돌기들로 형성되어 있었으며 군데군데 교원섬유들이 관찰되었다.

• Asian-Australasian Journal of Animal Sciences
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• 제29권8호
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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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• 제24권5호
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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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• 제14권5호
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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.

• 한국응용곤충학회지
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• 제34권4호
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• pp.334-343
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• 1995

명상태와 암상태에서 벼멸구의 겹눈의 미세구조가 변화하는 것을 관찰하였다. 벼멸구의 겹눈을 암조건 혹은 광조건 하에서 최고 72시간 까지 유지하였을 경우에 비슷한 수준에서 겹눈을 절단하여 해부 현미경으로 관찰한 결고, 구조적인 면에서 서로 다른 모양을 관찰하였다. 한편, 전자현미경을 이용하여 암조건과 광조건 하에서의 겹눈의 미세구조를 비교한 결과, 단애층(palisade layer)의 넓이는 광조건하에서 암조건에서 보다 더 좁은 것을 알 수 있었다. 색소체는 암적응 상태의 눈에서는 단애층 주위에 원을 형성하고 있었지만, 감간채 주위에 밀집되어 있지는 않았다. 암적용과 광적용 상태의 눈에 있는 망막세포 내에서의 미세융모 지름은 차이가 없었으며, 수정체와 감간체의 접합 부위에 있는 색소체의 이동은 감간체의 위부분에 있은 수정체의 끝부분에서 변화가 있음을 관찰 할 수 있었다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제27권1호
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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.

• 대한한방부인과학회지
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• 제23권2호
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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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• 제5권3호
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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.

• 한국축산식품학회지
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• 제37권6호
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• pp.931-939
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• 2017

Alcoholic liver disease (ALD) is a complex multifaceted disease that involves oxidative stress and inflammation as the key mediators. Despite decades of intensive research, there are no FDA-approved therapies, and/or no effective cure is yet available. Probiotics have received increasing attention in the past few years due to their well-documented gastrointestinal health-promoting effects. Interestingly, emerging studies have suggested that certain probiotics may offer benefits beyond the gut. Lactobacillus fermentum LA12 has been previously demonstrated to play a role in inflammatory-related disease. However, the possible protective effect of L. fermentum LA12 on ALD still remain to be explored. Thus, the aim of this study was to evaluate the possible protective effect of L. fermentum LA12 on alcohol-induced gut barrier dysfunction and liver damage in a rat model of alcoholic steatohepatitis (ASH). Daily oral administration of L. fermentum LA12 in rat model of ASH for four weeks was shown to significantly reduced intestinal nitric oxide production and hyperpermeability. Moreover, small intestinal histological- and qRT-PCR analysis further revealed that L. fermentum LA12 treatment was capable of up-regulating the mRNA expression levels of tight junction proteins, thereby stimulating the restitution of barrier structure and function. Serum and hepatic analyses also revealed that the restoration of epithelial barrier function may prevent the leakage of endotoxin into the blood, subsequently improve liver function and hepatic steatosis in the L. fermentum LA12-treated rats. Altogether, results in this study suggest that L. fermentum LA12 may be used as a dietary adjunct for the prevention and treatment of ASH.