• 제목/요약/키워드: Anti-cell adhesion

검색결과 199건 처리시간 0.027초

Ginsenoside Rk1 suppresses platelet mediated thrombus formation by downregulation of granule release and αIIbβ3 activation

  • Shin, Jung-Hae;Kwon, Hyuk-Woo;Irfan, Muhammad;Rhee, Man Hee;Lee, Dong-Ha
    • Journal of Ginseng Research
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    • 제45권4호
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    • pp.490-497
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    • 2021
  • Background and objective: Synthetic ginsenoside compounds G-Rp (1,3, and 4) and natural ginsenosides in Panax ginseng 20(S)-Rg3, Rg6, F4 and Ro have inhibitory actions on human platelets. However, the inhibitory mechanism of ginsenoside Rk1 (G-Rk1) is still unclear thus, we initiated investigation of the anti-platelet mechanism by G-Rk1 from Panax ginseng. Methodology: Our study focused to investigate the action of G-Rk1 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin αIIbβ3 using flow cytometry, intracellular calcium mobilization, fibronectin adhesion, dense granule secretion, and thromboxane B2 secretion. Thrombin-induced clot retraction was also observed in human platelets. Key Results: Collagen, thrombin, and U46619-stimulated human platelet aggregation were dose-dependently inhibited by G-Rk1, while it demonstrated a more effective suppression on collagen-stimulated platelet aggregation using human platelets. Moreover, G-Rk1 suppressed collagen-induced elevation of Ca2+ release from endoplasmic reticulum, granule release, and αIIbβ3 activity without any cytotoxicity. Conclusions and implications: These results indicate that G-Rk1 possess strong anti-platelet effect, proposing a new drug candidate for treatment and prevention of platelet-mediated thrombosis in cardiovascular disease.

Lentivirus Mediated GOLPH3 shRNA Inhibits Growth and Metastasis of Esophageal Squamous Cancer

  • Wang, Qiang;Wang, Xian;Zhang, Can-Bin
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권9호
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    • pp.5391-5396
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    • 2013
  • Aim: To investigate the role of Golgi phosphoprotein 3 (GOLPH3) in tumour growth and metastasis of esophageal squamous cancer. Methods: A lentiviral shRNA-vector was utilized to stably knockdown GOLPH3 in Eca-109 esophageal squamous cancer cells. mRNA transcription and protein expression of GOLPH3 were examined by real-time quantitative PCR and Western blotting, respectively. Cell proliferation activity was assessed by MTT assay and invasion and migration potentials by matrigel invasion and transwell motility assays. Results: Stable knockdown in the GOLPH3 cell line was established. PD-A gene expression was significantly suppressed by lentivirus-mediated RNAi, which resulted in reducing the capacity for cell proliferation, migration, invasion and adhesion in vitro. In vivo, GOLPH3 depletion resulted in inhibition of tumour growth, with stable decrease in the expression of GOLPH3 in tumor xenografts. Conclusions: Our findings suggest that lentivirus mediated silencing of the GOLPH3 gene has a significant anti-tumour effect on esophageal squamous cancer in vitro and in vivo. In addition, the results indicate that GOLPH3 might be an effective molecular target for gene therapy in esophageal squamous cancer.

Liver Kinase B1 Mediates Its Anti-Tumor Function by Binding to the N-Terminus of Malic Enzyme 3

  • Seung Bae Rho;Hyun Jung Byun;Boh-Ram Kim;Chang Hoon Lee
    • Biomolecules & Therapeutics
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    • 제31권3호
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    • pp.330-339
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    • 2023
  • Liver kinase B1 (LKB1) is a crucial tumor suppressor involved in various cellular processes, including embryonic development, tumor initiation and progression, cell adhesion, apoptosis, and metabolism. However, the precise mechanisms underlying its functions remain elusive. In this study, we demonstrate that LKB1 interacts directly with malic enzyme 3 (ME3) through the N-terminus of the enzyme and identified the binding regions necessary for this interaction. The binding activity was confirmed to promote the expression of ME3 in an LKB1-dependent manner and was also shown to induce apoptosis activity. Furthermore, LKB1 and ME3 overexpression upregulated the expression of tumour suppressor proteins (p53 and p21) and downregulated the expression of antiapoptotic proteins (nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and B-cell lymphoma 2 (Bcl-2)). Additionally, LKB1 and ME3 enhanced the transcription of p21 and p53 and inhibited the transcription of NF-κB. Moreover, LKB1 and ME3 suppressed the phosphorylation of various components of the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B signaling pathway. Overall, these results suggest that LKB1 promotes pro-apoptotic activities by inducing ME3 expression.

Characterization of Angiogenesis Inhibitor Effect of Green Tea Seed Extract

  • Hwang, Jae-Ho;Lee, Sung-Hoon;Rha, Sung-Ju;Yoon, Ho-Seop;Shin, Jin-Hyuk;Lee, Jin-Hee;Seo, Myeong-Jin;Kang, Kyeong-Wan;Han, Kyeong-Ho;Kim, Yong-Joo;Kho, Kang-Hee;Kim, Seon-Jae;Shin, Tai-Sun
    • Animal cells and systems
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    • 제13권2호
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    • pp.133-139
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    • 2009
  • Green tea seed was extracted with absolute ethanol,and the green tea seed extract(GTSE)was subjected to assays for toxicity, antioxidant ability, angiogenesis inhibitory effects and cell adhesion, as well as western blotting, and an in vivo experiment against 4 high-ranking adult cancers in Korea. Our series of experimental data demonstrated that GTSE has an antioxidant ability superior to that of EGCG in the green tea leaf, and also exhibits a profound high tumor growth inhibitory activity on a variety of cancer cell lines, as well as nude mice infected with cancer cells. GTSE was identified as a natural anticancer compound showing excellent angiogenesis inhibition and cancer cell suppression abilities. Our preliminary observations also indicate that GTSE may be another potential source of natural dietary antioxidants and also may be applicable as a novel natural anticancer agent.

Antiplatelet Effects of Garlic and Chitosan: a Comparative Study between Fermented and Non-Fermented Preparations

  • Irfan, Muhammad;Kim, Minki;Kwon, Hyuk-Woo;Rhee, Man Hee;Kim, Hyun-Kyoung
    • 대한의생명과학회지
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    • 제24권3호
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    • pp.280-284
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    • 2018
  • The incidence of cardiovascular diseases (CVDs) is increasing rapidly in developed countries, with CVDs now representing the leading cause of morbidity and mortality. Natural products and ethnomedicines have been shown to reduce the risk of CVDs. Garlic is a medicinal plant used throughout the world for its anti-inflammatory, antioxidant, and antiplatelet activities. Chitosan is a natural polysaccharide obtained from chitin, and derivatives of chitosan have been shown to inhibit platelet aggregation and adhesion. We hypothesized that fermented preparations of these products may possess stronger antiplatelet effects than the non-fermented forms owing to the increased bioavailability of the bioactive compounds produced during fermentation. Therefore, we compared these compounds via in vitro and ex vivo platelet aggregation assays by using standard light transmission aggregometry and ex vivo granule secretions from rat platelets. We found that fermented preparations exerted more potent and significant inhibition of platelet aggregation both in vitro and ex vivo. Likewise, ATP release from dense granules of platelets was also significantly inhibited in fermented preparation-treated rat platelets compared to that in non-fermented preparation-treated ones. We concluded that fermented preparations exerted more potent effects on platelet function both in vitro and ex vivo, possibly as a result of the increased bioavailability of active compounds produced during fermentation. We therefore suggest that fermented products may be potent therapeutics against platelet-related CVDs and can be used as antiplatelet and antithrombotic agents.

A Role of Cell Adhesion Molecules and Gelatinases in Human Serum-Induced Aggregation of Human Eyelid-Derived Stem Cells In Vitro

  • Yang, Hyejin;Lim, Yoon Hwa;Yun, Sujin;Yoon, A Young;Kim, Haekwon
    • 한국발생생물학회지:발생과생식
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    • 제17권4호
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    • pp.409-420
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    • 2013
  • Human serum (HS) has been reported to induce aggregation of human eyelid adipose-derived stem cells (HEACs) during high-density culture in vitro. The present study focused on the role of cell adhesion molecules and gelatinases during HS-induced aggregation of HEACs. HS-induced aggregation occurred between 9-15 days of culture. Cells aggregated by HS medium (HS-agg) showed stronger expression of ${\alpha}2$, ${\alpha}2B$, ${\alpha}X$, and CEACAM1 genes compared to non-aggregated cells in HS medium (HS-ex) or in control FBS-cultured cells. HS-agg were distinctly labeled with antibodies against ${\alpha}2$, ${\alpha}2B$, and ${\alpha}X$ proteins. Western blot results demonstrated that the two integrin proteins were greatly expressed in HS-agg compared to HS-ex and control FBS-cultured cells. Treatment of HEACs with anti-integrin ${\alpha}2$ antibody during culture in HS medium delayed aggregation formation. HS-agg exhibited strong expression of MMP1 and MMP9 compared to HS-ex or FBS-cultured cells. Conditioned media from HS-culture showed remarkable increase of MMP9 gelatinolytic activity in comparison to those from FBS-culture. However, there was no change of TIMP mRNA expression in relation to the HS-induced aggregation. Based on these results, it is suggested that integrin ${\alpha}2$, ${\alpha}2B$, and ${\alpha}X$, and MMP9 might play an important role in the HS-induced aggregation of HEACs.

족삼리(足三里) 의이인약침(薏苡仁藥鍼)이 Collagen으로 유발(誘發)된 생쥐의 관절염(關節炎)에 미치는 영향(影響) (Effects of Herbal-acupuncture with Coicis Semen Solution at Joksamni (ST36) on Collagen-induced Arthritis in DBA/1J Mouse)

  • 이성노;이현
    • Korean Journal of Acupuncture
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    • 제24권4호
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    • pp.111-129
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    • 2007
  • Objectives & Methods : The purpose of this study is to observe the effects of Coicis Semen Herbal-acupuncture solution (CS-HAS) at the Joksamni (ST36) on the collagen-induced arthritis in the DBA/1J mouse. The author performed several experiments to analyze the effects of CS-HAS on arthritis; change of the weight; the spleen size and adhesion rate; serum cytokine levels; serum antibody levels; changes of immunocyte counts; the histological changes of joint. Results : In the Coicis Semen Herbal-acupuncture (CS-HA), arthritis index, the incidence of arthritis, and the degree of joint edema were decreased. In CS-HA, there was no weight loss. The size of the spleen, adhesion rate, and the edema and transformation of joint were lowered. In CS-HA, the levels of IL-1${\beta}$, IL-6, TNF-${\alpha}$, IFN-${\gamma}$, IgG, IgM, and anti-collagen II in serum and the levels of IFN-${\gamma}$, IL-4, IL-10 in spleen were significantly decreased. In CS-HA, the expression ratios of $CD45^+$ to $CD3e^+$ and $CD8^+$ to $CD4^+$ were decreased. Also, the overall $CD4^+/CD8^+$ cell ratio was lowered in spleen. Ratios of the $CD4^+/CD25^+$, $CD45^+/CD69^+$ cells were decreased in lymph nodes. In addition, ratios of the $CD3^+/CD69^+$, $CD11b^+/Gr-1^+$ cells were also decreased in synovium. In the histological study, the cartilage destruction and synovial cell proliferation, and collagen fiber destruction were decreased with CS-HA treated group. Conclusions : From the results mentioned above, it is suggested that CS-HA at the ST36 has several significant effects on the collagen-induced arthritis.

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알로덤이 건 봉합술 후 발생되는 유착 방지에 미치는 효과 (The Effect of Alloderm on Prevention of Adhesions following Tenorrhaphy in the Rabbits)

  • 최창용;송진우;김준혁;최환준;이영만
    • Archives of Plastic Surgery
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    • 제34권6호
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    • pp.765-770
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    • 2007
  • Purpose: Peritendinous adhesion is one of the most notorious complication after the flexor tendon injury. In this study, $Alloderm^{(R)}$(LifeCell Corp., Branchburg, N.J.), which is the decellularized human dermal analogue with its intact native basement membrane components, was used for the prevention of peritendinous adhesions following flexor tendon repair. Methods: Thirty New Zealand white male rabbits were divided equally into 3 groups. In all groups, the flexor digitorum profundus of the third finger of the right back foot was cut totally and repaired by modified Kessler suture technique. Following tendon repair, $Alloderm^{(R)}$ was wrapt around the repaired tendon in the first group and sodium hyaluronate gel was sprayed to the operation field in the second group. In the control group, no external material was applied. The right back foot were immobilized for 6 weeks to optimize the formation of adhesion ingrowth. After death, the third finger that repaired tendons and sheaths was removed en bloc. We checked range of motion. and studied histologically for all groups. Results: The experimental groups had better range of motion than the control group. We checked that the range of motion was 73.5 degrees in $Alloderm^{(R)}$ group, 55.9 degrees in the hyaluronic acid group, and 38.3 degrees in the control group. in the histological study, the experimental group had less adhesions compared with the control group. Conclusion: This study concludes that $Alloderm^{(R)}$ can decrease peritendinous adhesions following flexor tendon repairs in rabbits. We think the method could be used in clinical cases.

Dendrosomal Curcumin Inhibits Metastatic Potential of Human SW480 Colon Cancer Cells through Down-regulation of Claudin1, Zeb1 and Hef1-1 Gene Expression

  • Esmatabadi, Mohammad Javad Dehghan;Farhangi, Baharak;Safari, Zahra;Kazerooni, Hanif;Shirzad, Hadi;Zolghadr, Fatemeh;Sadeghizadeh, Majid
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권6호
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    • pp.2473-2481
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    • 2015
  • Colon cancer is one of the leading causes of cancer-associated death worldwide. The prognosis for advanced colorectal cancers remains dismal, mainly due to the propensity for metastatic progression. Accordingly, there is a need for effective anti-metastasis therapeutic agents. Since a great body of research has indicated anticancer effects for curcumin, we investigated the effects of dendrosomal curcumin (DNC) on cellular migration and adhesion of human SW480 cells and possible molecular mechanisms involved. Different methods were applied in this study including MTT, Scratch and adhesion assays as well as real-time PCR and transwell chamber assays. Based on the results obtained, DNC inhibits metastasis by decreasing Hef 1, Zeb 1 and Claudin 1 mRNA levels and can reduce SW480 cell proliferation with $IC_{50}$values of 15.9, 11.6 and $7.64{\mu}M$ at 24, 48 and 72h post-treatment. Thus it might be considered as a safe formulation for therapeutic purpose in colorectal cancer cases.

Extract of Curcuma zedoaria R. prevents atherosclerosis in apolipoprotein E-deficient mice

  • Kim, Ki Mo;Lee, Joo Young;Jeon, Byeong Hwa;Quan, Khong Trong;Na, MinKyun;Nam, Kung-Woo;Chae, Sungwook
    • Nutrition Research and Practice
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    • 제15권3호
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    • pp.319-328
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    • 2021
  • BACKGROUND/OBJECTIVES: Curcuma zedoaria R. (Zingiberaceae) has been used to treat headache, fever, and hypertension-related symptoms in Asian countries, including Korea, China, and Japan. We investigated whether dietary intake of a C. zedoaria extract (CzE) affected atherosclerosis in vivo. MATERIALS/METHODS: Apolipoprotein E-deficient (ApoE-/-) mice (n = 32) were fed a normal diet (ND), a high-cholesterol diet (HCD), an HCD containing CzE (100 mg/kg/day), or an HCD containing simvastatin (10 mg/kg/day) for 12 weeks. The anti-atherosclerotic effects were evaluated by observing changes in fatty streak lesions, immunohistochemical analysis, ex vivo fluorescence imaging, lipid profiles, and western blot analysis. RESULTS: The CzE-fed group showed a 41.6% reduction of atherosclerosis. Furthermore, CzE significantly reduced the levels of serum triglyceride, high-density lipoprotein, the chemokine (C-X3-C-motif ) ligand 1, the adhesion molecules vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin; down-regulation of tumor necrosis factor-α, interleukin-6, high mobility group box-1, and cathepsin levels in the aortic sinuses and aortas of ApoE-/- mice were also observed. CONCLUSIONS: The results suggest that the inclusion of a water extract of C. zedoaria in a HCD is closely correlated with reducing the risk of vascular inflammatory diseases in an ApoE mouse model.