RESUMO
Korean Red ginseng (KRG), commonly used in traditional medicine, has anti-inflammatory, anti- oxidative, and anti-tumorigenic properties. Asian sand dust (ASD) is known to aggravate upper and lower airway inflammatory responses. BEAS-2B cells were exposed to ASD with or without KRG or ginsenoside Rg3. Mucin 5AC (MUC5AC), MUC5B, and MUC8 mRNA and protein expression levels were determined using quantitative RT-PCR and enzyme-linked immunosorbent assay. Nuclear factor kappa B (NF-κB), activator protein 1, and mitogen-activated protein kinase expression and activity were determined using western blot analysis. ASD induced MUC5AC, MUC5B, and MUC8 mRNA and protein expression in BEAS-2B cells, which was significantly inhibited by KRG and Rg3. Although ASD-induced mucin expression was associated with NF-κB and p38 mitogen-activated protein kinase (MAPK) activity, KRG and Rg3 significantly suppressed only ASD-induced NF-κB expression and activity. KRG and Rg3 inhibited ASD-induced mucin gene expression and protein production from bronchial epithelial cells. These results suggest that KRG and Rg3 have potential for treating mucus-producing airway inflammatory diseases.
Assuntos
Poeira , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Ginsenosídeos/farmacologia , Mucinas/genética , Panax/química , Areia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ginsenosídeos/química , Humanos , Estrutura Molecular , Mucina-5AC/biossíntese , Mucina-5AC/genética , Mucina-5B/biossíntese , Mucina-5B/genética , Mucinas/biossíntese , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismoRESUMO
OBJECTIVE: Aberrant regulation of the proliferation, survival, and migration of endothelial cells (ECs) is closely related to the abnormal angiogenesis that occurs in hypoxia-induced pathological situations, such as cancer and vascular retinopathy. Hypoxic conditions and the subsequent upregulation of hypoxia-inducible factor-1α and target genes are important for the angiogenic functions of ECs. Phospholipase D2 (PLD2) is a crucial signaling mediator that stimulates the production of the second messenger phosphatidic acid. PLD2 is involved in various cellular functions; however, its specific roles in ECs under hypoxia and in vivo angiogenesis remain unclear. In the present study, we investigated the potential roles of PLD2 in ECs under hypoxia and in hypoxia-induced pathological angiogenesis in vivo. APPROACH AND RESULTS: Pld2 knockout ECs exhibited decreased hypoxia-induced cellular responses in survival, migration, and thus vessel sprouting. Analysis of hypoxia-induced gene expression revealed that PLD2 deficiency disrupted the upregulation of hypoxia-inducible factor-1α target genes, including VEGF, PFKFB3, HMOX-1, and NTRK2. Consistent with this, PLD2 contributed to hypoxia-induced hypoxia-inducible factor-1α expression at the translational level. The roles of PLD2 in hypoxia-induced in vivo pathological angiogenesis were assessed using oxygen-induced retinopathy and tumor implantation models in endothelial-specific Pld2 knockout mice. Pld2 endothelial-specific knockout retinae showed decreased neovascular tuft formation, despite a larger avascular region. Tumor growth and tumor blood vessel formation were also reduced in Pld2 endothelial-specific knockout mice. CONCLUSIONS: Our findings demonstrate a novel role for endothelial PLD2 in the survival and migration of ECs under hypoxia via the expression of hypoxia-inducible factor-1α and in pathological retinal angiogenesis and tumor angiogenesis in vivo.
Assuntos
Carcinoma Pulmonar de Lewis/irrigação sanguínea , Células Endoteliais/enzimologia , Hipóxia/complicações , Neovascularização Patológica , Fosfolipase D/deficiência , Neovascularização Retiniana/enzimologia , Vasos Retinianos/enzimologia , Animais , Animais Recém-Nascidos , Hipóxia Celular , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/patologia , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/enzimologia , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfolipase D/genética , Interferência de RNA , Neovascularização Retiniana/etiologia , Neovascularização Retiniana/genética , Neovascularização Retiniana/patologia , Vasos Retinianos/patologia , Fatores de Tempo , Técnicas de Cultura de Tecidos , TransfecçãoRESUMO
BACKGROUND: There are limitations to current colorectal cancer (CRC)-specific diagnostic methods and therapies. Tumorigenesis proceeds because of interaction between cancer cells and various surrounding cells; discovering new molecular mediators through studies of the CRC secretome is a promising approach for the development of CRC diagnostics and therapies. MATERIALS AND METHODS: A comparative secretomic analysis was performed using primary and metastatic human isogenic CRC cells. Proliferation was determined by MTT and thymidine incorporation assay, migration was determined by wound-healing assay (ELISA). The level of palmitoleoyl-protein carboxylesterase (NOTUM) in plasma from patients with CRC was determined by enzyme-linked immunosorbent assay. RESULTS: NOTUM expression was increased in metastatic cells. Proliferation was suppressed by inhibiting expression of NOTUM. Knockdown of NOTUM genes inhibited proliferation as well as migration, with possible involvement of p38 and c-JUN N-terminal kinase in this process. The result was verified in patients with CRC. CONCLUSION: NOTUM may be a new candidate for diagnostics and therapy of CRC.
Assuntos
Proliferação de Células , Neoplasias Colorretais/enzimologia , Esterases/biossíntese , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Esterases/genética , Técnicas de Silenciamento de Genes , Humanos , Metástase Neoplásica , Proteínas de Neoplasias/genéticaRESUMO
In the field of biometrics, it has been reported that iris recognition techniques have shown high levels of accuracy because unique patterns of the human iris, which has very many degrees of freedom, are used. However, because conventional iris cameras have small depth-of-field (DOF) areas, input iris images can easily be blurred, which can lead to lower recognition performance, since iris patterns are transformed by the blurring caused by optical defocusing. To overcome these problems, an autofocusing camera can be used. However, this inevitably increases the cost, size, and complexity of the system. Therefore, we propose a new real-time iris image-restoration method, which can increase the camera's DOF without requiring any additional hardware. This paper presents five novelties as compared to previous works: 1) by excluding eyelash and eyelid regions, it is possible to obtain more accurate focus scores from input iris images; 2) the parameter of the point spread function (PSF) can be estimated in terms of camera optics and measured focus scores; therefore, parameter estimation is more accurate than it has been in previous research; 3) because the PSF parameter can be obtained by using a predetermined equation, iris image restoration can be done in real-time; 4) by using a constrained least square (CLS) restoration filter that considers noise, performance can be greatly enhanced; and 5) restoration accuracy can also be enhanced by estimating the weight value of the noise-regularization term of the CLS filter according to the amount of image blurring. Experimental results showed that iris recognition errors when using the proposed restoration method were greatly reduced as compared to those results achieved without restoration or those achieved using previous iris-restoration methods.