• Title/Summary/Keyword: NO Molecule

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Sword Bean (Canavalia gladiata) Pod Exerts Anti-Allergic and Anti-Inflammatory Effects through Modulation of Th1/Th2 Cell Differentiation

  • Kyung-A Hwang;Yu Jin Hwang;Hye-Jeong Hwang;Sang Hoon Lee;Young Jun Kim
    • Journal of Web Engineering
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    • v.14 no.14
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    • pp.2853-2869
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    • 2022
  • Allergy is an immunoglobulin E (IgE)-mediated process, and its incidence and prevalence have increased worldwide in recent years. Therapeutic agents for allergic diseases are continuously being developed, but side effects follow when used for a long-term use. Therefore, treatments based on natural products that are safe for the body are urgently required. Sword bean (Canavalia gladiata) pod (SBP) has been traditionally used to treat inflammatory diseases, but there is still no scientific basis for its anti-allergic effect. Accordingly, this study investigates the anti-allergic effect and its mechanism of SBP in vitro and in vivo. SBP reduced the nitric oxide production and decreased mRNA and protein expression of inflammatory mediates (inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)), and inhibited the phosphorylation of nuclear factor kappa B (NF-κB), a major signaling molecule in the inflammatory response. Additionally, SBP extract treatment inhibited phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling activity to further inhibit degranulation and allergy mediator generation and control the balance of Th1/Th2 cells, which can induce an allergic reaction when disrupted. Furthermore, the SBP extract exhibited anti-allergic effects in anti-dinitrophenyl IgE-induced RBL-2H3 cells and ovalbumin-treated mice. These findings have potential clinical implications for the treatment as well as prevention of allergic diseases.

In Vitro and In Vivo Antitumor Efficacy of Hizikia fusiforme Celluclast Extract against Bladder Cancer

  • Jun-Hui Song;Se Yeon Won;Byungdoo Hwang;Soontag Jung;Changsun Choi;Sung-Soo Park;Yung Hyun Choi;Wun-Jae Kim;Sung-Kwon Moon
    • Journal of Web Engineering
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    • v.12 no.7
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    • pp.2159-2173
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    • 2020
  • Various physiological benefits have been linked to Hizikia fusiforme (HF), an edible brown seaweed. Here, fucose-containing sulfated polysaccharides were extracted from celluclast-processed HF (SPHF) and their antitumor efficacy against bladder cancer was evaluated in vitro and in vivo. SPHF possesses high sulfated polysaccharide and fucose contents and free radical scavenging activities compared to those of celluclast-processed HF extracts (CHF). SPHF inhibited bladder cancer EJ cell proliferation via G1-phase cell cycle arrest. This was due to the induction of p21WAF1 expression associated with the downregulation of CDKs and cyclins. Moreover, JNK phosphorylation was identified as an SPHF-mediated signaling molecule. SPHF treatment also hindered the migration and invasion of EJ cells by inhibiting MMP-9 expression, which was attributed to the repression of transcriptional binding to NF-κB, AP-1, and Sp-1 in the MMP-9 promoter region. In an animal study, SPHF treatment suppressed EJ tumor growth in xenograft mice similarly to cisplatin. Furthermore, no toxicity signs were found after weight loss assessment, biochemical tests, and organ tissue immunostaining during oral administration of 20-200 mg/kg SPHF for 20 days. Therefore, our study demonstrates the antitumor efficacy of SPHF in vitro and in vivo, thus highlighting its potential for bladder cancer treatment development.

Expression of Tubular Intercellular Adhesion Molecule-1 (ICAM -1) as a Marker of Renal Injury in Children with IgA Nephropathy (소아 특발성 IgA 신병증에서 신 손상의 예후 인자로서 신세뇨관 ICAM-1의 발현)

  • Son Young-Ho;Kang Mi-Seon;Chung Woo-Yeong
    • Childhood Kidney Diseases
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    • v.8 no.2
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    • pp.149-158
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    • 2004
  • Purpose : In order to evaluate the value of the renal expression of ICAM-1 as a marker of renal injury, we analyzed the relationship between abnormal tubular expression of ICAM-1 and histopathological features and clinical manifestations in children with IgA nephropathy (IgAN). Methods: The clinical data from 43 patients with IgAN were analyzed retrospectively and compared to the histopathologic subclassification proposed by Haas. ICAM-1 in tubular epithelium was assessed using the LSAB(Labeled streptavidine biotin) kit on the renal biopsy specimens. Results: In 43 patients with primary IgAN, 28 males and 15 females aged $12.2{\pm}2.2$ years were studied. There were no differences of renal tubular expression of ICAM-1 between patients with gross hematuria and without gross hematuria. But renal tubular expression of ICAM-1 in patients with proteinuria was significantly higher than that of in patients without proteinuria($78.2{\pm}14.19%\;vs\;55.8{\pm}32.20%,\;P<0.05$). Renal tubular expression of ICAM-1 was also associated with the severity of histopathological degree using Haas classification method. In subclass I, renal tubular expression of ICAM-1 was significantly lower than those of other subclasses. A significant correlation was found between the tubular expression of ICAM-1 and the total amount of protein in 24 hour collected urine$(r_s=0.47236,\;p<0.05)$. But there were no significant correlations between the renal tubular expression of ICAM-1 and interstitial cellular infiltration, tubular atrophy, and interstitial fibrosis respectively(F=0.89, P>0.05; F=0.31, p>0.05; F=0.21, p>0.05). Conclusion: Renal tubular expression of ICAM-1 can be a useful marker of renal injury in children with IgAN. (J Korean Soc Pediatr Nephrol 2004;8:149-158)

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Early Time Course of Immunopathologic Changes in Coronary Arteries of Heterotopically Transplanted Mouse Heart (이소 생쥐심장이식 모델에서 조기 시간경과에 따른 관상동맥의 면역병리학적인 변화)

  • 이정렬;임홍국;서정욱
    • Journal of Chest Surgery
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    • v.31 no.12
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    • pp.1119-1126
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    • 1998
  • Background: In this study, we investigated the early time course of expression of the major histocompatibility(MHC) antigens, intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), interleukin-6 and the histopathological changes in the coronary arteries of cardiac allografts exchanged between inbred mice strains that differ in one loci of class I major histocompatibility antigen (B10.BR to B10.A). Material and Method: No immunosuppressive therapy was used. Both allografts and the hearts of the recipients were harvested at 7(group 1, n=6), 15(group 2, n=6), 21(group 3, n=6), and 30(group 4, n=6) days after transplantation. They were examined by immunohistochemistry, microscopy and morphometry. All allografts had contractions at the time of harvest. Result: A strong MHC class I antigen expression was present on the endothelial and medial cells of the coronary arteries in group 1 and remained unchanged in the rest of the groups. However, MHC class II reactivity was none or very little at any time. Mild to moderate ICAM-1 expression was observed on the endothelial cells, but not on the medial cells at any time by 30 days. VCAM-1 expression was strong both on the endothelial and medial cells at any time. Moderate degree expression of interleukin-6 was observed from 7 to 30 day specimens. Histopathologically, percentage of affected vessels(vessels with intimal thickening) was less than 10 % in 7 day group and increased up to 50 % at 30 days. Mean percent narrowing of the lumen of the affected vessels revealed less than 20 % at 7 days and 40 % at 30 days. The area occupied by tropomyosin positive cells in the intimal lesion, graded from 0 to 3, showed gradual increase but remained between grade 0 to 1 by 30 days. Medial integrity was also well preserved at any time. Moderate perivascular mononuclear cell infiltration was observed at 7 days and it was progressively increased upto 30 days. Recipients' heart revealed no positive immunopathologic findings. Conclusion: In this study, the early time course of progression of the transplantation vasculopathy was demonstrated in the murine heterotopic heart transplant model.

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Effect of Gastrodiae elata Blume Components on Systolic Blood Pressure and Serum Lipid Concentrations in Spontaneously Hypertensive Rats Fed High Fat Diet (천마성분이 본태성고혈압쥐의 혈압과 혈청지질 농도에 미치는 영향)

  • Hong, Hee-Do;Shim, Eun-Jung;Kim, Kyung-Im;Choi, Sang-Yoon;Han, Chan-Kyu
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.2
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    • pp.174-179
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    • 2007
  • This study was carried out to investigate the effect of Gastrodiae elata Blume fractions on systolic blood pressure and serum lipid profiles in spontaneously hypertensive rats (SHR/NCrj) fed high fat diet. Twenty-four males SHR weighing approximately 160 g were randomly divided into four groups; A (low molecule, GR-1), B (polysaccharide, GR-2), C (protein, GR-3) fractions of G. elata Blume, respectively, and D (high fat diet as control). After orally tube feeding the fractions of G. elata Blume, there were no differences in final body weights among the treatment groups. Diet intake was somewhat high in the control group (D), but there were no significant differences in feed efficiency ratios. In terms of serum lipid profiles, total-cholesterol level was statistically higher in the control group (D) than in G. elata Blume fraction groups (p<0.05). Triglyceride levels of low molecule (A) and polysaccharide (B) groups were lower by 16% and 11%, respectively than that of the control group (D). HDL-cholesterol level was remarkably higher (p<0.05), whereas LDL-cholesterol level was significantly lower (by 25%) in the group B as compared to the control group (D). Atherogenic index (AI) of G. elata Blume fraction groups were significantly lower than in the control group (p<0.05). Reference blood pressure (RBP) showed an average of $180\sim190mmHg$ at 8 weeks old after 3 weeks on feeding high fat diet. Compared with RBP, final blood pressure of treatment groups (35 days after feeding the fractions of G. elata Blume gractions) were decreased by 1.7% (A), 5.5% (B) and 3.6% (C), respectively, but the control group (D) contrarily showed an increase of 2.6%. Especially, final systolic blood pressure of the polysaccharide group (B) was lower by 22 mmHg than that of the control group (D). From these findings, it can be suggested that polysaccharide fraction may improve blood serum lipids and should be considered as effective in lowering of blood pressure.

The Expression of neuronal Nitric Oxide Synthase in Reinnervated Recurrent Laryngeal Nerve (흰쥐에서 편측 반회후두신경 재지배 후 neuronal Nitric Oxide Synthase(nNOS)의 발현과 후두기능회복과의 관계)

  • 정성민;김성숙;조윤희;구태완;박수경;신유리
    • Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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    • v.12 no.1
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    • pp.46-54
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    • 2001
  • Background and Objectives : Nitric oxide(NO) is a short-lived molecule with messenger and cytotoxic functions in nervous, cardiovascular, and immune systems. Among the three distinct NOS isoforms, the neuronal isoform is expressed in small, discrete neuronal populations of CNS and PNS. Axonal injury in adult animals results in a dramatic NOS up-regulation in many types of central and peripheral neurons which normally lack the enzyme or express it only at very low levels. In previous study, we confirmed the efficacy of PEMS on the early functional recovery in rats with surgically transected and reanastomosed recurrent laryngeal nerve. Therefore, after we obtained functionally recovered rats using PEMS in this study, we studied to evaluate the expression of nNOS through the analysis of the difference between functional recovery group and non-recovery group in the recurrent laryngeal nerve. Materials and Method : Using 84 healthy male Sprague-Dawley rats, transections and primary anastomosis were performed on their left recurrent laryngeal nerves. Rats were then randomly assigned to 2 groups. The rats in group A(n=42) received PEMS by placing them in custom cages equipped with Helm-holz coils(3 hr/day, 5 days/wk, for 12 wk). The rats in group B(n=42) were handled the same way as the group A, except that they did not receive PEMS. Laryngovideoendoscopy was performed before and after surgery and followed up weekly. Laryngeal EMG was obtained in both PCA and TA muscles. Immunohistochemisty staining using monoclonal anti-neuronal nitric oxide synthase(nNOS) antibody was performed to detect nNOS in recurrent laryngeal nerve and nodose ganglion. Results : 20 rats(63%) in group A and 5 rats(17%) in the group B showed recovery of vocal fo1d motion. The number of NOS-positive cells was increased in functionally-recovered rats. NOS-staining intensity was reduced 12 weeks after nerve injury. The difference between PEMS group and non-stimulated group was not found. Conclusion : This study shows that nNOS may exert a beneficial effect on nerve regeneration and functional repair.

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An Experimental Studies on the alleviation effects of Daebangpoongtang(大防風湯) in LPS-induced arthritis (대방풍탕(大防風湯)의 LPS유발(誘發) 관절염(關節炎) 완화효과(緩和效果)에 관한 실험적(實驗的) 연구(硏究))

  • Jeon, Won-June;Shin, Gil-Jo;Lee, Won-Chul
    • The Journal of Dong Guk Oriental Medicine
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    • v.9
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    • pp.35-49
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    • 2000
  • Purpose: This study is to investigate the alleviation effects of Daebangpoongtang in LPS induced arthritis in mice knee joint. Methods : Daebangpoongtang was chosen to treat the arthritis caused by injecting $300{\mu}g/kg$ LPS to mice knee joint. The control group had no treatment, while the LPS group was injected $300{\mu}g/kg$ LPS to mice knee joint and the DBP group was oral administrated of Daebangpoongtang. After injection of $300{\mu}g/kg$ LPS to mice knee joint, the alteration of synovial lining cell, vessel, fibrosis, distribution of collagen fiber, fibroblast, mast cell, infiltration of inflammation component cell and distribution of ICAM and VCAM was observed by light microscope(BX50). Results : In the DBP extract treatment group, the distribution of vessel, the enlargement of synovial lining cell layer, the synovial lining cells with filopodia, the fibrosis, the distribution of fibroblast in synovial membrane, the distribution of TCAM and VCAM on the knee joint was less than that of LPS group. Infiltrated lymphocyte into the apical surface had not observed in the DBP extract treatment group. The distribution of mast cell was as same as control group(no treatment group) and it showed granulated type. Conclusion: According to the above results, it might be considered that the administration of Daebangpoongtang has a curative effect on synovial membrane injury in arthritis by inhibiting increase of vessel, cell adhesion molecule(ICAM and VCAM) in LPS induced arthritis.

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A Study on the Degradation Mechanism of Diazinon and the Acute Toxicity Assessment in Photolysis and Photocatalysis (광반응과 광촉매 반응을 이용한 Diazinon 농약의 분해 기전과 독성 평가에 관한 연구)

  • Oh, Ji-Yoon;Kim, Moon-Kyung;Son, Hyun-Seok;Zoh, Kyung-Duk
    • Journal of Korean Society of Environmental Engineers
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    • v.30 no.11
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    • pp.1087-1094
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    • 2008
  • Diazinon is a phosphorothiate insecticide widely used in the world including Korea. This study investigates the feasibility of photolysis and photocatalysis processes for the degradation of diazinon in water. Both photolysis and photocatalysis reactiosn were effective in degrdading diazinon, however lower TOC removals were achieved. In case of photocatalysis, approximately 40% of nitrogen from diazinon was recovered as NO$_3^-$, and less than 5% of phosphorus as PO$_4{^{3-}}$. However, the sulfur in diazinon molecule was completely recovered to SO$_4{^{2-}}$ from photocatalysis reaction, and the recovery from photolysis was 50%, indicating that P=S bond easily breaks first during photolysis and photocatalysis. The poor recoveries of ionic byproducts and TOC from photolysis and photocatalysis indicate the presence of other organic intermediates during reactions. The formation of organic intermediates were identified during reactions using GC/MS and LC/MS/MS, and the main degradation products were diazoxon, and 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMP), respectively. Finally, the acute 48-hr toxicity test using Daphnia magna were employed to measure the toxicity reduction during photocatalysis of degradation. The results showed that the toxicity increased until 180 min of the photocatalysis reaction (from EC$_{50}$ (%) of 69.6 to 13.2%), however, acute toxicity completely disappeared (>100%) after 360 min. The toxicity results showed that the intermediates from photocatalysis such as diazoxon were more toxic than diazinon itself, however these intermediates can be degraded or mineralized with further reaction.

Tetrahydrobiopterin Inhibits PDGF-stimulated Migration and Proliferation in Rat Aortic Smooth Muscle Cells via the Nitric Oxide Synthase-independent Pathway

  • Jiang, Xiaowen;Kim, Bo-Kyung;Lin, Haiyue;Lee, Chang-Kwon;Kim, Jung-Hwan;Kang, Hyun;Lee, Pil-Young;Jung, Seung-Hyo;Lee, Hwan-Myung;Won, Kyung-Jong
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.3
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    • pp.177-183
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    • 2010
  • Tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase (NOS) activity, is known to play important roles in modulating both NO and superoxide production during vascular diseases such as atherosclerosis. However, the role of BH4 in functions of vascular smooth muscle cells is not fully known. In this study, we tested the effects of BH4 and dihydrobiopterin (BH2), a BH4 precursor, on migration and proliferation in response to platelet-derived growth factor-BB (PDGF-BB) in rat aortic smooth muscle cells (RASMCs). Cell migration and proliferation were measured using a Boyden chamber and a 5-bromo-2'-deoxyuridine incorporation assay, respectively, and these results were confirmed with an ex vivo aortic sprout assay. Cell viability was examined by 2,3-bis [2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide assays. BH4 and BH2 decreased PDGF-BBinduced cell migration and proliferation in a dose-dependent manner. The inhibition of cell migration and proliferation by BH4 and BH2 was not affected by pretreatment with $N^G$-nitro-L-arginine methyl ester, a NOS inhibitor. Moreover, the sprout outgrowth formation of aortic rings induced by PDGF-BB was inhibited by BH4 and BH2. Cell viability was not inhibited by BH4 and BH2 treatment. The present results suggest that BH4 and BH2 may inhibit PDGF-stimulated RASMC migration and proliferation via the NOS-independent pathway. Therefore, BH4 and its derivative could be useful for the development of a candidate molecule with an NO-independent anti-atherosclerotic function.

Genes profile related to modulation of natural killer cell activity induced by electroacupuncture (전침이 자연살해세포 활성에 미치는 유전자 발현 profile에 대한 연구)

  • Choi, Gi-soon;No, Sam-woong;Oh, Sang-deog;Bae, Hyun-su;Ahn, Hyun-jong;Ha, Yoon-mun;Kim, Kwang-ho;Min, Byung-il
    • Journal of Acupuncture Research
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    • v.19 no.6
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    • pp.111-124
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    • 2002
  • A line of study reported that electroacupuncture(EA) modulate natural killer cell(NK Cell) activities. One report suggested that EA enhanced splenic interferon-gamma($IFN-{\gamma}$), interleukin-2(IL-2), and NK cell activity in Sprague-Dawley rats. Another study suggested that $IFN-{\gamma}$ mediates the up-regulation of NK cell activity, and endogenous ${\beta}$-endorphin secretion also play a role in the up-regulation of NK cell activity induced by EA stimulation. In order to better understand the molecular regulation underlying the activation of NK cell induced by EA, we have utilized cDNA microarray to elucidate how EA alters program of gene expression of spleen in rats. First, we divided three groups, group I was EA group treated with EA in restriction holder, group II was sham group with only holder stress, and last group III was control group with no treatment. We measured NK cell activity after EA stimulation three times for 2 days using $^{51}Cr$ release assay. Second, Biotin-labeled cDNA probes synthesized from EA group and sham group, were competitively hybridized to the microarray that contained variable genes. Such high-throughput screening has identified a number of EA-responsive gene candidates. Of these, we found that EA induced a subset of genes of genes that functionally could modulatory effects on NK cell activity. Genes(vascular cell adhesion molecule-1, protein-tyrosine kinase, CD94 mRNA) related to boost NK cell activity, were increased by EA And, genes(protein-tyrosine-phospatase mRNA, protein-tyrosine phosphatase(SHP-1) mRNA) related to inhibit NK cell activity, were decreased by EA. These EA-responsive genes may provide key insights from which to understand mechanisms of activation of NK cell induced by EA.

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