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[PMID]:29458547
[Au] Autor:Growcott EJ; Bamba D; Galarneau JR; Leonard VHJ; Schul W; Stein D; Osborne CS
[Ad] Endereço:1​Novartis Institutes for Biomedical Research, Infectious Disease, Emeryville, CA, USA.
[Ti] Título:The effect of P38 MAP kinase inhibition in a mouse model of influenza.
[So] Source:J Med Microbiol;67(3):452-462, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Influenza viruses are a common cause of human respiratory infections, resulting in epidemics of high morbidity and mortality. We investigated the effect of a novel mitogen-activated protein kinase (MAPK) inhibitor in vitro and in a murine influenza model to further explore whether p38 MAPK inhibition could reduce viral replication. METHODS: In vitro, the antiviral effect of p38 MAPK inhibitor BCT194 was evaluated in differentiated human bronchial epithelial cells (HBECs); in vivo, female BALB/c mice were infected intranasally with 150 pfu of influenza H1N1 A/Puerto Rico/8/34 and treated with BCT197 (a closely related p38 MAPK inhibitor with an IC50 value of<1 µM, currently in clinical testing), dexamethasone or oseltamivir (Tamiflu) starting 24 h post infection. Body weight, bronchoalveolar lavage cells, cytokines, total protein and lactate dehydrogenase as well as serum cytokines were measured; a subset of animals was evaluated histopathologically.Results/Key findings. p38MAP kinase inhibition with BCT194 had no impact on influenza replication in HBECs. When examining BCT197 in vivo, and comparing to vehicle-treated animals, reduced weight loss, improvement in survival and lack of impaired viral control was observed at BCT197 concentrations relevant to those being used in clinical trials of acute exacerbations of chronic obstructive pulmonary disease; at higher concentrations of BCT197 these effects were reduced. CONCLUSIONS: Compared to vehicle treatment, BCT197 (administered at a clinically relevant concentration) improved outcomes in a mouse model of influenza. This is encouraging given that the use of innate inflammatory pathway inhibitors may raise concerns of negative effects on infection regulation.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Inibidores Enzimáticos/farmacologia
Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos
Infecções por Orthomyxoviridae/virologia
Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Antivirais/administração & dosagem
Antivirais/uso terapêutico
Brônquios/citologia
Linhagem Celular
Citocinas/sangue
Dexametasona/uso terapêutico
Modelos Animais de Doenças
Inibidores Enzimáticos/administração & dosagem
Inibidores Enzimáticos/uso terapêutico
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/virologia
Feminino
Seres Humanos
Vírus da Influenza A Subtipo H1N1/fisiologia
Influenza Humana/tratamento farmacológico
Influenza Humana/virologia
Camundongos
Camundongos Endogâmicos BALB C
Infecções por Orthomyxoviridae/tratamento farmacológico
Oseltamivir/uso terapêutico
Resultado do Tratamento
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Cytokines); 0 (Enzyme Inhibitors); 20O93L6F9H (Oseltamivir); 7S5I7G3JQL (Dexamethasone); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000684


  2 / 81553 MEDLINE  
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[PMID]:29267498
[Au] Autor:Ni XJ; Xu ZQ; Jin H; Zheng SL; Cai Y; Wang JJ
[Ad] Endereço:Transplantation Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
[Ti] Título:Ginsenoside Rg1 protects human renal tubular epithelial cells from lipopolysaccharide-induced apoptosis and inflammation damage.
[So] Source:Braz J Med Biol Res;51(2):e6611, 2017 Dec 11.
[Is] ISSN:1414-431X
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Ginsenoside Rg1, one of the most notable active components of Panax ginseng, has been widely reported to exert anti-inflammatory actions. This study aimed to reveal whether ginsenoside Rg1 also exhibits beneficial roles against lipopolysaccharide (LPS)-induced apoptosis and inflammation in human renal tubular epithelial cells, and to evaluate the potential role of the component on tubulointerstitial nephritis treatment. HK-2 cells were treated with various doses of ginsenoside Rg1 (0, 50, 100, 150, and 200 µM) in the absence or presence of 5 µg/mL LPS. Thereafter, CCK-8 assay, flow cytometry, western blot, migration assay, reactive oxygen species (ROS) assay, and ELISA were carried out to respectively assess cell viability, apoptosis, migration, ROS activity, and the release of inflammatory cytokines. As a result, ginsenoside Rg1 protected HK-2 cells from LPS-induced injury, as cell viability was increased, cell apoptosis was decreased, and the release of MCP-1, IL-1ß, IL-6, and TNF-α was reduced. Ginsenoside Rg1 functioned to HK-2 cells in a dose-dependent manner, and the 150 µM dose exhibited the most protective functions. Ginsenoside Rg1 had no significant impact on cell migration and ROS activity, while it alleviated LPS-induced ROS release and migration impairment. Furthermore, the down-regulations of p-PI3K, p-AKT, and up-regulations of PTEN, p-IκBα, p-p65, Bcl-3 induced by LPS were recovered to some extent after ginsenoside Rg1 treatment. In conclusion, ginsenoside Rg1 protects HK-2 cells against LPS-induced inflammation and apoptosis via activation of the PI3K/AKT pathway and suppression of NF-κB pathway.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Apoptose/efeitos dos fármacos
Células Epiteliais/efeitos dos fármacos
Ginsenosídeos/farmacologia
Túbulos Renais/citologia
Lipopolissacarídeos
Nefrite/prevenção & controle
[Mh] Termos MeSH secundário: Análise de Variância
Western Blotting
Linhagem Celular
Ensaios de Migração Celular
Sobrevivência Celular/efeitos dos fármacos
Citocinas/análise
Citocinas/efeitos dos fármacos
Ensaio de Imunoadsorção Enzimática
Seres Humanos
Túbulos Renais/efeitos dos fármacos
Fosfatidilinositol 3-Quinases/análise
Fosfatidilinositol 3-Quinases/efeitos dos fármacos
Substâncias Protetoras/farmacologia
Proteínas Proto-Oncogênicas c-akt/análise
Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos
Espécies Reativas de Oxigênio/análise
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Cytokines); 0 (Ginsenosides); 0 (Lipopolysaccharides); 0 (Protective Agents); 0 (Reactive Oxygen Species); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); PJ788634QY (ginsenoside Rg1)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE


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[PMID]:29203745
[Au] Autor:Hryn VH; Sherstyuk OO; Svintsytska NL; Piliuhin АV; Ustenko RL
[Ad] Endereço:Higher State Educational Establishment Of Ukraine "Ukrainian Medical Stomatological Academy", Poltava, Ukraine.
[Ti] Título:The use of morphological study technique for investigation of labial and palatine glands.
[So] Source:Wiad Lek;70(5):934-938, 2017.
[Is] ISSN:0043-5147
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Due to the deterioration of environmental conditions that promotes the onset of inflammatory and autoimmune diseases, and the progress in the diagnosis, the frequency of registration of intercurrent pathology of salivary glands has markedly risen in recent years, demonstrating the increased scientific interest in the research of the common and distinctive features of their structure. THE AIM: The paper was aimed at the development of the method of morphological study of human minor salivary (labial and palatine) glands by the use of plastic wax reconstruction to obtain the plastic model of the acini and ducts of human minor salivary glands. MATERIALS AND METHODS: Specimens of the glandular area of the hard palate mucosa and labial mucosa in its middle third have been studied. To gain the objective of the investigation the technique for morphological study of the human minor salivary (labial and palatine) glands is to be developed, encompassing the analysis of the spatial organization of the glandular epithelium of the labial and palatine glands together with blood microcirculatory flow by fixing the obtained specimens of the minor salivary glands in 4% glutaraldehyde solution and osmium tetroxide with subsequent embedding into the Epon-812, staining the serial semi-thin sections with phosphate buffered 0,1% toluidine blue solution, photomacrography of the distinguished boundaries of the investigated structures and obtaining of photoreconstructions. RESULTS AND CONCLUSIONS: Thus, the use of suggested technique enables to obtain the megascopic reconstruction of the acini and ducts of the labial and palatine glands, which can be studied from different sides, getting the full visualization of the shape and size, as well as to explore the glands' inner configuration, the geometry of the lumen of the epithelial excretory ducts, to determine changes in the thickness of the wall, to get a visual representation of the microtopographic interactions between the different parts of blood microcirculatory flow and excretory ducts of the minor salivary glands.
[Mh] Termos MeSH primário: Células Epiteliais/citologia
Microcirculação/fisiologia
Glândulas Salivares Menores/citologia
[Mh] Termos MeSH secundário: Seres Humanos
Imuno-Histoquímica
Microscopia Eletrônica de Varredura
Coloração e Rotulagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE


  4 / 81553 MEDLINE  
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[PMID]:27774671
[Au] Autor:Carvajal-Gonzalez JM; Mulero-Navarro S; Mlodzik M
[Ad] Endereço:Departamento de Bioquímica, Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain.
[Ti] Título:Centriole positioning in epithelial cells and its intimate relationship with planar cell polarity.
[So] Source:Bioessays;38(12):1234-1245, 2016 12.
[Is] ISSN:1521-1878
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Planar cell polarity (PCP)-signaling and associated tissue polarization are evolutionarily conserved. A well documented feature of PCP-signaling in vertebrates is its link to centriole/cilia positioning, although the relationship of PCP and ciliogenesis is still debated. A recent report in Drosophila established that Frizzled (Fz)-PCP core signaling has an instructive input to polarized centriole positioning in non-ciliated Drosophila wing epithelia as a PCP read-out. Here, we review the impact of this observation in the context of recent descriptions of the relationship(s) of core Fz-PCP signaling and cilia/centriole positioning in epithelial and non-epithelial cells. All existing data are consistent with a model where Fz-PCP signaling functions upstream of centriole/cilia positioning, independent of ciliogenesis. The combined data sets indicate that the Fz-Dsh PCP complex is instructive for centriole/ciliary positioning via an actin-based mechanism. Thereby, centriole/cilia/centrosome positioning can be considered an evolutionarily conserved readout and common downstream effect of PCP-signaling from flies to mammals.
[Mh] Termos MeSH primário: Polaridade Celular
Centríolos/fisiologia
Células Epiteliais/fisiologia
Receptores Frizzled/fisiologia
Transdução de Sinais
[Mh] Termos MeSH secundário: Animais
Células Epiteliais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Frizzled Receptors)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1002/bies.201600154


  5 / 81553 MEDLINE  
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[PMID]:29442033
[Au] Autor:Xia M; Wei J; Tong K
[Ti] Título:MiR-224 promotes proliferation and migration of gastric cancer cells through targeting PAK4.
[So] Source:Pharmazie;71(8):460-464, 2016 Aug 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Although recent studies have shown the important role and overexpression of miR-224 in several tumors, its function in gastric cancer has not yet been defined. In the present study, we tried to confirm the result of microRNAs microarray and further investigated the functions of miR-224 in gastric cancer, and tried to find new downstream targets of miR-224. In this study, the level of miR-224 was measured in gastric cancer cells with the normal human gastric epithelial cell. The effects of miR-224 of on proliferation, migration, and target protein expression were evaluated by CCK8 assay, colony assay, transwell migration assay, western blotting. In addition, luciferase reporter plasmid was constructed to demonstrate the direct target of miR-224. Overexpression of miR-224 was detected in the gastric cancer cells, especially in SCG-7901. Exogenous miR-224 expression promoted the proliferation and migration of gastric cells and abrogating expression of miR-224 suppressed proliferation, and migration of SCG-7901 cells in vitro. Luciferase assays revealed that miR-224 directly targeted the 3'UTR of p21-activated kinase 4 (PAK4). The present study provides an experimental foundation for miR-224 as a potential tumor suppressor that may decrease PAK4 expression to inhibit gastric cancer cells and that in the future, targeting of this miRNA may provide a novel strategy for the diagnosis and treatment of patients with this lethal disease.
[Mh] Termos MeSH primário: Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
MicroRNAs/uso terapêutico
Neoplasias Gástricas/patologia
Quinases Ativadas por p21/efeitos dos fármacos
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Células Epiteliais/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica
Genes Reporter/genética
Seres Humanos
MicroRNAs/genética
MicroRNAs/farmacologia
Plasmídeos/genética
Regulação para Cima
Cicatrização/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN224 microRNA, human); 0 (MicroRNAs); EC 2.7.1.11 (PAK4 protein, human); EC 2.7.11.1 (p21-Activated Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6580


  6 / 81553 MEDLINE  
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[PMID]:29412224
[Au] Autor:El-Batal AI; Ahmed SF
[Ad] Endereço:National Centre for Radiation Research and Technology - NCRRT, Atomic Energy Authority, Drug Radiation Research Department, Nasr City, Cairo, Egypt.
[Ti] Título:Therapeutic effect of Aloe vera and silver nanoparticles on acid-induced oral ulcer in gamma-irradiated mice.
[So] Source:Braz Oral Res;32:e004, 2018 Feb 05.
[Is] ISSN:1807-3107
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Radiation combined injury, a life-threatening condition, has higher mortality than simple radiation injury. The aim of the present study was to analyze the efficiency of Aloe vera and silver nanoparticles in improving the healing of ulcerated oral mucosa after irradiation. Thirty male Albino mice were divided into five groups: control, radiation, Aloe vera (AV), silver nanoparticles (NS), and AV+NS. The mice were exposed to whole body 6Gy gamma-radiation. After one hour, 20% acetic acid was injected into the submucosal layer of the lower lip for ulcer induction. The animals received topical treatment with the assigned substances for 5 days. Lip specimens were subjected to hematoxylin and eosin and anti alpha-smooth muscle actin immunohistochemical staining. Results demonstrated occurance of ulcer three days post irradiation in all groups except in the AV+NS group where only epithelial detachment was developed. After seven days, data revealed persistent ulcer in radiation group, and almost normal epithelium in the AV+NS group. A significant reduction of epithelial thickness was detected in all groups at the third day as compared to control. At the seventh day, only the AV+NS group restored the epithelial thickness. Area percent of alpha-smooth muscle actin expression was significantly decreased in radiation group at the third day followed by significant increase at the seventh day. However, all treatment groups showed significant increase in alpha-smooth muscle actin at the third day, which decreased to normal level at the seventh day. Our study demonstrated the efficiency of Aloe vera and silver nanoparticles in enhancing ulcer healing after irradiation.
[Mh] Termos MeSH primário: Aloe/química
Raios gama/efeitos adversos
Nanopartículas Metálicas/uso terapêutico
Úlceras Orais/tratamento farmacológico
Úlceras Orais/etiologia
Lesões Experimentais por Radiação/tratamento farmacológico
Prata/uso terapêutico
[Mh] Termos MeSH secundário: Ácido Acético
Actinas/análise
Administração Tópica
Animais
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/efeitos da radiação
Fibroblastos/efeitos dos fármacos
Imuno-Histoquímica
Masculino
Camundongos
Microscopia Eletrônica de Transmissão
Úlceras Orais/patologia
Lesões Experimentais por Radiação/patologia
Valores de Referência
Reprodutibilidade dos Testes
Fatores de Tempo
Resultado do Tratamento
Cicatrização/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Actins); 0 (alpha-smooth muscle actin, mouse); 3M4G523W1G (Silver); Q40Q9N063P (Acetic Acid)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:D; IM
[Da] Data de entrada para processamento:180208
[St] Status:MEDLINE


  7 / 81553 MEDLINE  
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[PMID]:28453918
[Au] Autor:Vannas MJ; Boyd S; Färkkilä MA; Arola J; Isoniemi H
[Ad] Endereço:Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland.
[Ti] Título:Value of brush cytology for optimal timing of liver transplantation in primary sclerosing cholangitis.
[So] Source:Liver Int;37(5):735-742, 2017 May.
[Is] ISSN:1478-3231
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND AIMS: Primary sclerosing cholangitis is associated with a high risk of cholangiocarcinoma. Here, we investigated the value of surveillance for dysplasia using brush cytology, to determine the optimal timing of liver transplantation in primary sclerosing cholangitis. We compared our preoperative findings, with the final explanted liver histopathology. METHODS: 126 consecutive patients were transplanted for primary sclerosing cholangitis from 1984 to 2012. Patients were divided into two groups: symptomatic (n=91), and asymptomatic (n=35). RESULTS: Brush cytology was available for 101 patients; 66 symptomatic and 35 asymptomatic. Suspicious cytological findings were found in nine patients (14%) in the symptomatic group and 17 (49%) in the asymptomatic group. DNA flow cytometry was available for 49 patients (25 symptomatic, 24 asymptomatic), with aneuploidy detected in six patients (24%) in the symptomatic group and 15 (63%) in the asymptomatic group. Explanted liver histology showed biliary dysplasia or cholangiocarcinoma in 11 symptomatic patients (12%) and 15 asymptomatic patients (43%). A combination of cytological and DNA flow cytometry findings resulted in a test sensitivity of 68%, with a specificity of 86%. Ten-year survival in the asymptomatic group was 91%. CONCLUSIONS: Dysplasia surveillance using brush specimens may help to select those patients likely to benefit from early liver transplantation. It remains unclear as to whether surveillance with brush cytology improves long-term survival, but there is presently no better method with which to predict transplantation timing.
[Mh] Termos MeSH primário: Sistema Biliar/patologia
Colangite Esclerosante/patologia
Colangite Esclerosante/cirurgia
Citodiagnóstico/métodos
Células Epiteliais/patologia
Transplante de Fígado
[Mh] Termos MeSH secundário: Adulto
Neoplasias dos Ductos Biliares/patologia
Carcinoma Hepatocelular/patologia
Colangiocarcinoma/patologia
Colangiopancreatografia Retrógrada Endoscópica
Diagnóstico Diferencial
Feminino
Finlândia
Seres Humanos
Estimativa de Kaplan-Meier
Neoplasias Hepáticas/patologia
Masculino
Meia-Idade
Sistema de Registros
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1111/liv.13276


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[PMID]:28454554
[Au] Autor:Mittal S; Sharma PK; Tiwari R; Rayavarapu RG; Shankar J; Chauhan LKS; Pandey AK
[Ad] Endereço:Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, India.
[Ti] Título:Impaired lysosomal activity mediated autophagic flux disruption by graphite carbon nanofibers induce apoptosis in human lung epithelial cells through oxidative stress and energetic impairment.
[So] Source:Part Fibre Toxicol;14(1):15, 2017 Apr 28.
[Is] ISSN:1743-8977
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Graphite carbon nanofibers (GCNF) have emerged as a potential alternative of carbon nanotubes (CNT) for various biomedical applications due to their superior physico-chemical properties. Therefore in-depth understanding of the GCNF induced toxic effects and underlying mechanisms in biological systems is of great interest. Currently, autophagy activation by nanomaterials is recognized as an emerging toxicity mechanism. However, the association of GCNF induced toxicity with this form of cell death is largely unknown. In this study, we have assessed the possible mechanism; especially the role of autophagy, underlying the GCNF induced toxicity. METHODS: Human lung adenocarcinoma (A549) cells were exposed to a range of GCNF concentrations and various cellular parameters were analyzed (up to 48 h). Transmission electron microscopy, immunofluorescent staining, western blot and quantitative real time PCR were performed to detect apoptosis, autophagy induction, lysosomal destabilization and cytoskeleton disruption in GCNF exposed cells. DCFDA assay was used to evaluate the reactive oxygen species (ROS) production. Experiments with N-acetyl-L-cysteine (NAC), 3-methyladenine (3-MA) and LC3 siRNA was carried out to confirm the involvement of oxidative stress and autophagy in GCNF induced cell death. Comet assay and micronucleus (MN) assay was performed to assess the genotoxicity potential. RESULTS: In the present study, GCNF was found to induce nanotoxicity in human lung cells through autophagosomes accumulation followed by apoptosis via intracellular ROS generation. Mechanistically, impaired lysosomal function and cytoskeleton disruption mediated autophagic flux blockade was found to be the major cause of accumulation rather than autophagy induction which further activates apoptosis. The whole process was in line with the increased ROS level and their pharmacological inhibition leads to mitigation of GCNF induced cell death. Moreover the inhibition of autophagy attenuates apoptosis indicating the role of autophagy as cell death process. GCNF was also found to induce genomic instability. CONCLUSION: Our present study demonstrates that GCNF perturbs various interrelated signaling pathway and unveils the potential nanotoxicity mechanism of GCNF through targeting ROS-autophagy-apoptosis axis. The current study is significant to evaluate the safety and risk assessment of fibrous carbon nanomaterials prior to their potential use and suggests caution on their utilization for biomedical research.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Autofagia/efeitos dos fármacos
Grafite/toxicidade
Lisossomos/efeitos dos fármacos
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Nanofibras/toxicidade
Estresse Oxidativo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Células A549
Sobrevivência Celular/efeitos dos fármacos
Células Epiteliais/efeitos dos fármacos
Seres Humanos
Pulmão/efeitos dos fármacos
Tamanho da Partícula
Espécies Reativas de Oxigênio/metabolismo
Propriedades de Superfície
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Reactive Oxygen Species); 7782-42-5 (Graphite)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1186/s12989-017-0194-4


  9 / 81553 MEDLINE  
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[PMID]:28747404
[Au] Autor:Lim H; Yu CY; Jou TS
[Ad] Endereço:Graduate Institute of Molecular Medicine National Taiwan University, Taipei, Taiwan.
[Ti] Título:Galectin-8 regulates targeting of Gp135/podocalyxin and lumen formation at the apical surface of renal epithelial cells.
[So] Source:FASEB J;31(11):4917-4927, 2017 11.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Establishment of apical-basal polarity, through correct targeting of polarity determinants to distinct domains of the plasma membrane, is a fundamental process for the development of functioning epithelial tubules. Here we report that galectin (Gal)-8 regulates apical-basal polarity of Madin-Darby canine kidney (MDCK) cells apical targeting of 135-kDa glycoprotein (Gp135). Gal-8 interacts with newly synthesized Gp135 in a glycan-dependent manner. Gal-8 knockdown induces aberrant lumens at the lateral domain and mistargeting of Gp135 to this structure, thus disrupting the kidney epithelial polarity of MDCK cells, which organize lumens at the apical surface. The -glycosylation deletion mutant of Gp135 phenocopies the effect of Gal-8 knockdown, which suggests that Gal-8 is the decoding machinery for the apical sorting signals of Gp135 residing at its -glycosylation-rich region. Collectively, our results reveal a new role of Gal-8 in the development of luminal organs by regulating targeting of apical polarity protein Gp135.-Lim, H., Yu, C.-Y., Jou, T.-S. Galectin-8 regulates targeting of Gp135/podocalyxin and lumen formation at the apical surface of renal epithelial cells.
[Mh] Termos MeSH primário: Polaridade Celular/fisiologia
Células Epiteliais/metabolismo
Galectinas/metabolismo
Rim/metabolismo
Sialoglicoproteínas/metabolismo
[Mh] Termos MeSH secundário: Animais
Cães
Células Epiteliais/citologia
Galectinas/genética
Rim/citologia
Células Madin Darby de Rim Canino
Sialoglicoproteínas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Galectins); 0 (Sialoglycoproteins); 0 (podocalyxin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1096/fj.201601386R


  10 / 81553 MEDLINE  
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[PMID]:28464886
[Au] Autor:Yeo J; Crawford EL; Zhang X; Khuder S; Chen T; Levin A; Blomquist TM; Willey JC
[Ad] Endereço:Division of Pulmonary and Critical Care Medicine, Department of Medicine, The University of Toledo College of Medicine, 3000 Arlington Avenue, HEB 219, Toledo, OH, 43614, USA.
[Ti] Título:A lung cancer risk classifier comprising genome maintenance genes measured in normal bronchial epithelial cells.
[So] Source:BMC Cancer;17(1):301, 2017 May 02.
[Is] ISSN:1471-2407
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Annual low dose CT (LDCT) screening of individuals at high demographic risk reduces lung cancer mortality by more than 20%. However, subjects selected for screening based on demographic criteria typically have less than a 10% lifetime risk for lung cancer. Thus, there is need for a biomarker that better stratifies subjects for LDCT screening. Toward this goal, we previously reported a lung cancer risk test (LCRT) biomarker comprising 14 genome-maintenance (GM) pathway genes measured in normal bronchial epithelial cells (NBEC) that accurately classified cancer (CA) from non-cancer (NC) subjects. The primary goal of the studies reported here was to optimize the LCRT biomarker for high specificity and ease of clinical implementation. METHODS: Targeted competitive multiplex PCR amplicon libraries were prepared for next generation sequencing (NGS) analysis of transcript abundance at 68 sites among 33 GM target genes in NBEC specimens collected from a retrospective cohort of 120 subjects, including 61 CA cases and 59 NC controls. Genes were selected for analysis based on contribution to the previously reported LCRT biomarker and/or prior evidence for association with lung cancer risk. Linear discriminant analysis was used to identify the most accurate classifier suitable to stratify subjects for screening. RESULTS: After cross-validation, a model comprising expression values from 12 genes (CDKN1A, E2F1, ERCC1, ERCC4, ERCC5, GPX1, GSTP1, KEAP1, RB1, TP53, TP63, and XRCC1) and demographic factors age, gender, and pack-years smoking, had Receiver Operator Characteristic area under the curve (ROC AUC) of 0.975 (95% CI: 0.96-0.99). The overall classification accuracy was 93% (95% CI 88%-98%) with sensitivity 93.1%, specificity 92.9%, positive predictive value 93.1% and negative predictive value 93%. The ROC AUC for this classifier was significantly better (p < 0.0001) than the best model comprising demographic features alone. CONCLUSIONS: The LCRT biomarker reported here displayed high accuracy and ease of implementation on a high throughput, quality-controlled targeted NGS platform. As such, it is optimized for clinical validation in specimens from the ongoing LCRT blinded prospective cohort study. Following validation, the biomarker is expected to have clinical utility by better stratifying subjects for annual lung cancer screening compared to current demographic criteria alone.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/análise
Brônquios/citologia
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/metabolismo
[Mh] Termos MeSH secundário: Antioxidantes/análise
Antioxidantes/metabolismo
Biomarcadores Tumorais/genética
Biomarcadores Tumorais/metabolismo
Biópsia
Brônquios/metabolismo
Células Epiteliais/citologia
Células Epiteliais/metabolismo
Seres Humanos
Neoplasias Pulmonares/diagnóstico
Neoplasias Pulmonares/epidemiologia
Reação em Cadeia da Polimerase
Curva ROC
Reprodutibilidade dos Testes
Estudos Retrospectivos
Medição de Risco
Tomografia Computadorizada Espiral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Biomarkers, Tumor)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1186/s12885-017-3287-4



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