• Title/Summary/Keyword: tissue factor

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Down-regulation of Phosphoglucose Isomerase/Autocrine Motility Factor Enhances Gensenoside Rh2 Pharmacological Action on Leukemia KG1α Cells

  • You, Zhi-Mei;Zhao, Liang;Xia, Jing;Wei, Qiang;Liu, Yu-Min;Liu, Xiao-Yan;Chen, Di-Long;Li, Jing
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1099-1104
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    • 2014
  • Aims and Background: Ginsenoside Rh2, which exerts the potent anticancer action both in vitro and in vivo, is one of the most well characterized ginsenosides extracted from ginseng. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between ginsenoside Rh2 and phosphoglucose isomerase/autocrine motility factor (PGI/AMF). Methods: $KG1{\alpha}$, a leukemia cell line highly expressing PGI/AMF was assessed by western blot analysis and reverse transcription- PCR (RT-PCR) assay after transfection of a small interfering (si)-RNA to silence PGI/AMF. The effect of PGI/AMF on proliferation was measured by typan blue assay and antibody array. A cell counting kit (CCK)-8 and flow cytometry (FCM) were adopted to investigate the effects of Rh2 on PGI/AMF. The relationships between PGI/AMF and Rh2 associated with Akt, mTOR, Raptor, Rag were detected by western blot analysis. Results: KG1${\alpha}$ cells expressed PGI/AMF and its down-regulation significantly inhibited proliferation. The antibody array indicated that the probable mechanism was reduced expression of PARP, State1, SAPK/JNK and Erk1/2, while those of PRAS40 and p38 were up-regulated. Silencing of PGI/AMF enhanced the sensibility of $KG1{\alpha}$ to Rh2 by suppressing the expression of mTOR, Raptor and Akt. Conclusion: These results suggested that ginsenoside Rh2 suppressed the proliferation of $KG1{\alpha}$, the same as down-regulation of PGI/AMF. Down-regulation of PGI/AMF enhanced the pharmacological effects of ginsenoside Rh2 on KG1${\alpha}$ by reducing Akt/mTOR signaling.

The Metabolic Effects of FGF21: From Physiology to Pharmacology (생리, 약학적 관점에서 fibroblast growth factor 21 (FGF21)의 대사 효과 고찰)

  • Song, Parkyong
    • Journal of Life Science
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    • v.30 no.7
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    • pp.640-650
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    • 2020
  • Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF protein family which is highly synthesized in the liver, pancreas, and adipose tissue. Depending on the expression tissue, FGF21 uses endo- or paracrine features to regulate several metabolic pathways including glucose metabolism and energy homeostasis. Different physiologically stressful conditions such as starvation, a ketogenic diet, extreme cold, and mitochondrial dysfunction are known to induce FGF21 synthesis in various tissues to exert either adaptive or defensive mechanisms. More specifically, peroxisome proliferator-activated receptor gamma and peroxisome proliferator-activated receptor alpha control FGF21 expression in adipose tissue and liver, respectively. In addition, the pharmacologic administration of FGF21 has been reported to decrease the body weight and improve the insulin sensitivity and lipoprotein profiles of obese mice and type 2 diabetes patients meaning that FGF21 has attracted huge interest as a therapeutic agent for type 2 diabetes, obesity, and non-alcoholic fatty liver disease. However, understanding FGF21 remains complicated due to the paradoxical condition of its tissue-dependent expression. For example, nutrient deprivation largely increases hepatic FGF21 levels whereas adipose tissue-derived FGF21 is increased under feeding condition. This review discusses the issues of interest that have arisen from existing publications, including the tissue-specific function of FGF21 and its action mechanism. We also summarize the current stage of a clinical trial using several FGF21 analogs.

An extract of the root of Lithospermun erythrorhison accelerates wound healing

  • Fujita, Naoko;Sakaguchi, Ikuyo;Ikeda, Norikazu;Kato, Yoshiko;Minamino, Miki
    • Proceedings of the SCSK Conference
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    • 2003.09a
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    • pp.540-567
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    • 2003
  • Metabolic disease such as diabetes, which is caused by stress or imbalanced diet, has been increasing. A diabetic tend to suffer from a delay or difficulty of wound healing. The extract of SHIKON (SK), that is the root of Lithospermun erythrorhison, has been reported to have an effect on healing for normal wound, but has never studies for intractable wound so far. Therefore we examined the effect of SK extract on wound healing with healing impaired mouse model. Full-thickness round wounds were created on the backs of db/db mice and applied SK, and we observed neovascularization and collagen synthesis, distribution of apoptotic cells, and vascular endothelial growth factor (VEGF)- positive cells in granulation tissue. After two weeks, a number of capillary vessel and collagen synthesis were increased in SK-treated wounds. Infiltration of VEGF-positive neutrophils was also seen in the wound, besides apoptotic fibroblasts and endothelial cells were appeared in the granulation tissue. After three weeks, the wound closed completely with SK-treated but not in control. These results suggest that SK enhanced neovascularization by VEGF and this kind of apoptosis process makes the scar smooth. In this study, it is obvious that SK also accelerates healing of intractable wound.

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Relationship of IGF-I mRNA Levels to Tissue Development in Chicken Embryos of Different Strains

  • Kita, K.;Noda, C.;Miki, K.;Kino, K.;Okumura, J.
    • Asian-Australasian Journal of Animal Sciences
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    • v.13 no.12
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    • pp.1653-1658
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    • 2000
  • Insulin-like growth factor-I (IGF-I) mRNA levels in the eyes, heart, liver and breast muscle removed from dwarf egg-type, normal egg-type and normal meat-type chicken embryos at 7, 14 and 20 days of incubation were measured. There was no influence of chicken strain on IGF-I gene expression in the eyes and liver. The IGF-I gene expression in eyes increased significantly along with the incubation period. In the liver, IGF-I gene expression at 20 days of incubation was significantly higher than that at 14 days of incubation. In the muscle, the lowest value for IGF-I gene expression was observed in meat-type chicken embryos. Regression analysis revealed that IGF-I gene expression was significantly correlated to the weights of the eyes and liver, but not the muscle. We conclude that there is little influence of strain on tissue IGF-I gene expression in chicken embryos during incubation but that tissue development in chicken embryos is nevertheless at least partly regulated by the change in IGF-I gene expression.

Inhibitory Effect of Standardized Curcuma xanthorrhiza Supercritical Extract on LPS-Induced Periodontitis in Rats

  • Kook, Kyo Eun;Kim, Changhee;Kang, Wonku;Hwang, Jae-Kwan
    • Journal of Microbiology and Biotechnology
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    • v.28 no.10
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    • pp.1614-1625
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    • 2018
  • Periodontitis, which is a severe inflammatory disease caused by endotoxins secreted from oral pathogens, destructs gingival tissue and alveolar bone. Curcuma xanthorrhiza, commonly called Java turmeric, has been shown to possess anti-bacterial and anti-inflammatory activities. The present study evaluated the inhibitory effect of C. xanthorrhiza supercritical extract (CXS) standardized with xanthorrhizol on lipopolysaccharide (LPS)-induced periodontitis in an animal model. LPS was topically injected into the periodontium of Sprague-Dawley rats to induce periodontitis and CXS (30 and $100mg{\cdot}kg^{-1}{\cdot}day^{-1}$) was orally administered after day 12. Histologically, CXS inhibited the collapse of gingival tissue by preventing cell infiltration. CXS significantly downregulated the expression of matrix metalloproteases (MMPs) and inflammation-related biomarkers, such as nuclear factor-kappa B ($NF-{\kappa}B$) and interleukin-1 beta ($IL-1{\beta}$) in gingival tissue. CXS also improved bone remodeling by downregulating osteoclastic transcription factors, such as nuclear factor of activated T-cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), and cathepsin K. In addition, CXS upregulated osteoblast differentiation-related markers, alkaline phosphate (ALP) and collagen type I alpha (COLA1). Thus, CXS can ameliorate periodontitis by inhibiting inflammation and improving bone remodeling.

Ref-1 protects against FeCl3-induced thrombosis and tissue factor expression via the GSK3β-NF-κB pathway

  • Lee, Ikjun;Nagar, Harsha;Kim, Seonhee;Choi, Su-jeong;Piao, Shuyu;Ahn, Moonsang;Jeon, Byeong Hwa;Oh, Sang-Ha;Kang, Shin Kwang;Kim, Cuk-Seong
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.1
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    • pp.59-68
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    • 2021
  • Arterial thrombosis and its associated diseases are considered to constitute a major healthcare problem. Arterial thrombosis, defined as blood clot formation in an artery that interrupts blood circulation, is associated with many cardiovascular diseases. Oxidative stress is one of many important factors that aggravates the pathophysiological process of arterial thrombosis. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ref-1) has a multifunctional role in cells that includes the regulation of oxidative stress and anti-inflammatory function. The aim of this study was to investigate the therapeutic effect of adenovirus-mediated Ref-1 overexpression on arterial thrombosis induced by 60% FeCl3 solution in rats. Blood flow was measured to detect the time to occlusion, thrombus formation was detected by hematoxylin and eosin staining, reactive oxygen species (ROS) levels were detected by high-performance liquid chromatography, and the expression of tissue factor and other proteins was detected by Western blot. FeCl3 aggravated thrombus formation in carotid arteries and reduced the time to artery occlusion. Ref-1 significantly delayed arterial obstruction via the inhibition of thrombus formation, especially by downregulating tissue factor expression through the Akt-GSK3β-NF-κB signaling pathway. Ref1 also reduced the expression of vascular inflammation markers ICAM-1 and VCAM-1, and reduced the level of ROS that contributed to thrombus formation. The results showed that adenovirus-mediated Ref-1 overexpression reduced thrombus formation in the rat carotid artery. In summary, Ref-1 overexpression had anti-thrombotic effects in a carotid artery thrombosis model and could be a target for the treatment of arterial thrombosis.

Effects of Buja-tang Extract on Osteoarthritic Animal Model (부자탕 추출물이 골관절염 동물 모델에 미치는 영향)

  • Park, Jung-Hyun;Yang, Doo-Hwa;Woo, Chang-Hoon;An, Hee-Duk
    • Journal of Korean Medicine Rehabilitation
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    • v.31 no.1
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    • pp.17-32
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    • 2021
  • Objectives The present study was designed to find out the therapeutic effects and possible underlying mechanism of Buja-tang, a herbal complex formula on experimental monosodium iodoacetate (MIA)-induced osteoarthritis. Methods Osteoarthritis models were created via intra-joint injection of MIA (50 μL with 80 mg/mL) in rats. Rats were divided into five groups and each group consisted of seven. Normal group was not injected MIA and did a normal diet. Control group injected MIA and received distilled water. Indo injected MIA and oral administration of 5 mg/kg of indomethacin. BJTL injected MIA and oral administration of 100 mg/kg of Buja-tang. BJTH injected MIA and oral administration of 200 mg/kg of Buja-tang. We analyzed weight-bearing ability of hind paws, oxidative stress related factor, antioxidant protein, inflammatory protein, inflammatory messenger and cytokine in joint tissue. Pathological observation of knee cartilage tissue structures was also performed with hematoxylin & eosin and safranin-O chromosomes. Results Weight-bearing ability of hind paws showed a tendency to reduce pain. The incidence of nicotinamide adenine dinucleotide phosphate oxidase and p22phox in articular tissue was significantly reduced, and the incidence of nuclear factor-erythroid 2-related factor 2 and heme oxygenase-1 and superoxide dismutases was significantly increased. The incidence of phosphorylated inhibitor of κBα, nuclear factor-kappa B p65, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β decreased significantly. In pathological observation, cartilage tissue damaged by MIAs in biopsy has significantly recovered from Buja-tang administration. Conclusions Buja-tang has anti-inflammation, antioxidation and pain relief effects. So this is thought to inhibit the progress of osteoarthritis in rat caused by the MIA.

Review of Effect of the Mechanical Stress on Muscle (근육에 대한 역학적 스트레스의 영향)

  • Kang, Jong-Ho;Kim, Jin-Sang
    • PNF and Movement
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    • v.6 no.2
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    • pp.51-57
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    • 2008
  • Purpose : Mechanical stress activates signaling cascades and leading to a specific response of a network of signaling pathways. The purpose of this study is to review the effect of mechanical stress-induced adaptation in skeletal muscle involves a biological mechanisms. Methods : This is literature study with Pubmed, Medline and books. Results : Skeletal muscle tissue demonstrates a malleability and may adjust its metabilic response, vascularization and neuromuscular characteristic makeup in response to alteration in functional demands. The adaptation in skeletal muscle involoves a multitude of signalling mechanisms related with insuline-like growth factor, vascular endothelial growth factor, neurotrophins. Conclusions : The identification of the basic relationships underlying the malleability of skeletal muscle tissue is likely to be of relevance for our understanding with PNF technique.

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Cloning of various bioreactive genes from cartilage tissues of Scyliorhinus torazame (두툽상어 연골 조직에서 생리 활성 유전자들의 cDNA 클로닝)

  • 김지태;김명순;장은령;김영진;김규원
    • Journal of Life Science
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    • v.10 no.5
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    • pp.533-541
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    • 2000
  • Compared to mammal including human, many bioreactive genes that regulate various biological events has not been cloned and characterized yet in fishes, especially shark, Scyliorhinus torazame. In orther to isolate genes that regulate physiological processes in cartilaginors fishes, we performed reverse transcription-polymerase chain reaction (RT-PCR) using the RNA of cartilage tissues of Scyliofhinus torazame. The cloned partial genes were 86%, 80%, 73%, 84%, 75%, 79% identical to $\alpha$- actin, 90-kDa heat-shock protein, methyle-neterahydrofolate dehydrogenase-methenyltertrahydrofolate cyclohudrolase-formyltetrahydrofolate synthetase, ubiquitin, glutamine synthetase and connective tissue growth factor genes of human, respectively. They also have similar nucleotide sequence homologues with those of another species. These partial bioreactive genes elucidated in this study may support to studies of phylogenetic analysis based on evolutionary relationships between shark and other species.

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Analysis of Cytotoxic Constituent of Berberis koreana Palibin (매자나무 세포독성성분 분석)

  • Kim, Young-Kyoon;Kwak, Byung-Man
    • Journal of the Korean Wood Science and Technology
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    • v.26 no.3
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    • pp.100-107
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    • 1998
  • Methanol extracts of five Berberidaceae species were examined against tissue factor inhibitory and tumour cell growth inhibitory activity. Methanol extracts of Berberis koreana Palibin showed a strong cytotoxicity activity against SK-MEL-2 (Melanoma) tumour cell lines with more than 90% in $25{\mu}g/m\ell$ and against A549 (Lung carcinoma), SK-OV-3 (Ovarian cancer), XF498 (CNS cancer) and HCTl5 (Colon cancer), other Berberidaceae species except B. koreana species have no effect on the tumour cells. Biologically active compound, therefore, was isolated through the activity guided fractionation and purification. The structure was confirmed by NMR. FT-IR and MS to 2-(3,4-dihydroxybenzyl)-ethyl alcohol. It showed cytotoxicity activity against SNU-C4 tumour cell lines with 50.7% in $50{\mu}g/m\ell$. Methanol extracts of 5 Berberidacae species have no effect on the tissue factor inhibitory activity.

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