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[PMID]:29351307
[Au] Autor:Merentie M; Rissanen R; Lottonen-Raikaslehto L; Huusko J; Gurzeler E; Turunen MP; Holappa L; Mäkinen P; Ylä-Herttuala S
[Ad] Endereço:A. I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
[Ti] Título:Doxycycline modulates VEGF-A expression: Failure of doxycycline-inducible lentivirus shRNA vector to knockdown VEGF-A expression in transgenic mice.
[So] Source:PLoS One;13(1):e0190981, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Vascular endothelial growth factor-A (VEGF-A) is the master regulator of angiogenesis, vascular permeability and growth. However, its role in mature blood vessels is still not well understood. To better understand the role of VEGF-A in the adult vasculature, we generated a VEGF-A knockdown mouse model carrying a doxycycline (dox)-regulatable short hairpin RNA (shRNA) transgene, which silences VEGF-A. The aim was to find the critical level of VEGF-A reduction for vascular well-being in vivo. In vitro, the dox-inducible lentiviral shRNA vector decreased VEGF-A expression efficiently and dose-dependently in mouse endothelial cells and cardiomyocytes. In the generated transgenic mice plasma VEGF-A levels decreased shortly after the dox treatment but returned back to normal after two weeks. VEGF-A expression decreased shortly after the dox treatment only in some tissues. Surprisingly, increasing the dox exposure time and dose led to elevated VEGF-A expression in some tissues of both wildtype and knockdown mice, suggesting that dox itself has an effect on VEGF-A expression. When the effect of dox on VEGF-A levels was further tested in naïve/non-transduced cells, the dox administration led to a decreased VEGF-A expression in endothelial cells but to an increased expression in cardiomyocytes. In conclusion, the VEGF-A knockdown was achieved in a dox-regulatable fashion with a VEGF-A shRNA vector in vitro, but not in the knockdown mouse model in vivo. Dox itself was found to regulate VEGF-A expression explaining the unexpected results in mice. The effect of dox on VEGF-A levels might at least partly explain its previously reported beneficial effects on myocardial and brain ischemia. Also, this effect on VEGF-A should be taken into account in all studies using dox-regulated vectors.
[Mh] Termos MeSH primário: Doxiciclina/farmacologia
Regulação da Expressão Gênica/efeitos dos fármacos
Técnicas de Silenciamento de Genes
Lentivirus/genética
RNA Interferente Pequeno/genética
Fator A de Crescimento do Endotélio Vascular/genética
[Mh] Termos MeSH secundário: Animais
Vetores Genéticos
Camundongos
Camundongos Transgênicos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Small Interfering); 0 (Vascular Endothelial Growth Factor A); N12000U13O (Doxycycline)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190981


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[PMID]:28841526
[Au] Autor:Rostamian R; Behnejad H
[Ad] Endereço:Department of Physical Chemistry, School of Chemistry, University College of Science, University of Tehran, Tehran 14155, Iran.
[Ti] Título:A comprehensive adsorption study and modeling of antibiotics as a pharmaceutical waste by graphene oxide nanosheets.
[So] Source:Ecotoxicol Environ Saf;147:117-123, 2018 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The adsorption behavior of tetracycline (TCN), doxycycline (DCN) as the most common antibiotics in veterinary and ciprofloxacin (CPN) onto graphene oxide nanosheets (GOS) in aqueous solution was evaluated. The four factors influencing the adsorption of antibiotics (initial concentration, pH, temperature and contact time) were studied. The results showed that initial pH ∼ 6 to 7 and contact time ∼ 100 - 200min are optimum for each drug. The monolayer adsorption capacity was reduced with the increasing temperature from 25°C to 45°C. Non-linear regressions were carried out in order to define the best fit model for every system. To do this, eight error functions were applied to predict the optimum model. Among various models, Hill and Toth isotherm models represented the equilibrium adsorption data of antibiotics while the kinetic data were well fitted by pseudo second-order (PSO) kinetic model (DCN and TCN) and Elovich (CPN) models. The maximum adsorption capacity (q ) is found to be in the following order: CPN >> DCN > TCN, obtained from sips equation at the same temperature. The GOS shows highest adsorption capacity towards CPN up to 173.4mgg . The study showed that GOS can be removed more efficiently from water solution.
[Mh] Termos MeSH primário: Antibacterianos/análise
Grafite/química
Modelos Teóricos
Nanoestruturas/química
Poluentes Químicos da Água/análise
Purificação da Água/métodos
[Mh] Termos MeSH secundário: Adsorção
Antibacterianos/química
Ciprofloxacino/análise
Ciprofloxacino/química
Doxiciclina/análise
Doxiciclina/química
Concentração de Íons de Hidrogênio
Cinética
Óxidos/química
Temperatura Ambiente
Tetraciclina/análise
Tetraciclina/química
Termodinâmica
Drogas Veterinárias/análise
Drogas Veterinárias/química
Poluentes Químicos da Água/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Oxides); 0 (Veterinary Drugs); 0 (Water Pollutants, Chemical); 5E8K9I0O4U (Ciprofloxacin); 7782-42-5 (Graphite); F8VB5M810T (Tetracycline); N12000U13O (Doxycycline)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170826
[St] Status:MEDLINE


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[PMID]:28452702
[Au] Autor:Shin JM; Kang JH; Lee SA; Park IH; Lee HM
[Ad] Endereço:Department of Otorhinolaryngology-Head and Neck Surgery, Seoul, South Korea.
[Ti] Título:Effect of doxycycline on epithelial-mesenchymal transition the p38/Smad pathway in respiratory epithelial cells.
[So] Source:Am J Rhinol Allergy;31(2):71-77, 2017 Mar 01.
[Is] ISSN:1945-8932
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Doxycycline has antibacterial and anti-inflammatory effects, and it also suppresses collagen biosynthesis. This study aimed to confirm the effects and mechanism of doxycycline on transforming growth factor (TGF) beta 1 induced epithelial-mesenchymal transition and cell migration in A549 and primary nasal epithelial cells. METHODS: A 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay and phalloidin-fluorescein isothiocyanate staining were used to evaluate cytotoxicity and cellular morphologic changes. Western blot and immunofluorescence staining were used to determine the expression levels of E-cadherin, vimentin, alpha-smooth muscle actin, fibronectin, phosphorylated Smad2/3, and mitogen-activated protein kinases. Scratch and transwell migration assays were used to assess cellular migration ability. RESULTS: Doxycycline (0-10 µg/mL) had no significant cytotoxic effects in A549 and primary nasal epithelial cells. Increased expression of mesenchymal markers, including vimentin, alpha-smooth muscle actin, and fibronectin in TGF beta 1 induced A549 cells were downregulated by doxycycline treatment. In contrast, E-cadherin expression was upregulated in TGF beta 1 induced A549 cells. An in vitro cell migration assay showed that doxycycline also inhibited the ability of TGF beta 1 induced migration. Doxycycline treatment suppressed the activation of Smad2/3 and p38, whereas its inhibitory effects were similar to each element-specific inhibitor in A549 and primary nasal epithelial cells. CONCLUSION: Doxycycline inhibited TGF beta 1 induced epithelial-to-mesenchymal transition and migration by targeting Smad2/3 and p38 signal pathways in respiratory epithelial cells.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Doxiciclina/farmacologia
Transição Epitelial-Mesenquimal/efeitos dos fármacos
Mucosa Respiratória/efeitos dos fármacos
[Mh] Termos MeSH secundário: Células A549
Caderinas/metabolismo
Movimento Celular/efeitos dos fármacos
Regulação da Expressão Gênica
Seres Humanos
Sistema de Sinalização das MAP Quinases
Cultura Primária de Células
Mucosa Respiratória/patologia
Proteína Smad2/metabolismo
Proteína Smad3/metabolismo
Fator de Crescimento Transformador beta/metabolismo
Vimentina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cadherins); 0 (Smad2 Protein); 0 (Smad3 Protein); 0 (Transforming Growth Factor beta); 0 (Vimentin); N12000U13O (Doxycycline)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.2500/ajra.2017.31.4410


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[PMID]:28450244
[Au] Autor:El-Naggar AWM; Senna MM; Mostafa TA; Helal RH
[Ad] Endereço:Radiation Chemistry Department, National Center for Radiation Research and Technology, Nasr City, Atomic Energy Authority, Cairo, Egypt. Electronic address: ab_nagga@yahoo.com.
[Ti] Título:Radiation synthesis and drug delivery properties of interpenetrating networks (IPNs) based on poly(vinyl alcohol)/ methylcellulose blend hydrogels.
[So] Source:Int J Biol Macromol;102:1045-1051, 2017 Sep.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Gamma radiation was used to prepare blend hydrogels from poly(vinyl alcohol) (PVA) and low ratios of methylcellulose (MC). The structure-property behavior was characterized by IR spectroscopy, gel fraction, differential scanning calorimetry (DSC) and swelling at room temperature and different pH values. The PVA/MC hydrogels were used as a carrier for doxycycline hyclate (DOX-h) drug. The results showed that the gel fraction of PVA/MC hydrogels decreased greatly with increasing the ratio of MC in the initial feeding solution. The PVA/MC hydrogels displayed pH-sensitive swelling character. The drug uptake-release study indicated that PVA/MC hydrogels possessed controlled release behavior and that the release process depends on pH. In this respect, the release of DOX-h drug was significant in alkaline medium.
[Mh] Termos MeSH primário: Portadores de Fármacos/química
Portadores de Fármacos/síntese química
Hidrogéis/química
Hidrogéis/síntese química
Metilcelulose/química
Álcool de Polivinil/química
[Mh] Termos MeSH secundário: Técnicas de Química Sintética
Doxiciclina/química
Liberação Controlada de Fármacos
Raios gama
Concentração de Íons de Hidrogênio
Radioquímica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Carriers); 0 (Hydrogels); 9002-89-5 (Polyvinyl Alcohol); 9004-67-5 (Methylcellulose); N12000U13O (Doxycycline)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


  5 / 8658 MEDLINE  
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[PMID]:28942279
[Au] Autor:Wen X; Wang Y; Zou Y; Ma B; Wu Y
[Ad] Endereço:College of Animal Science, National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, China.
[Ti] Título:No evidential correlation between veterinary antibiotic degradation ability and resistance genes in microorganisms during the biodegradation of doxycycline.
[So] Source:Ecotoxicol Environ Saf;147:759-766, 2018 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Biodegradation of antibiotic residues in the environment by microorganisms may lead to the generation of antibiotic resistance genes (ARGs), which are of great concern to human health. The aim of this study was to determine whether there is a relationship between the ability to degrade antibiotic doxycycline (DOX) and the development of resistance genes in microorganisms. We isolated and identified ten bacterial strains from a vegetable field that had received long-term manure application as fertilizer and were capable of surviving in a series of DOX concentrations (25, 50, 80, and 100mg/L). Our results showed no evidential correlation between DOX degradation ability and the development of resistance genes among the isolated microorganisms that had high DOX degradation capability (P > 0.05). This was based on the fact that Escherichia sp. and Candida sp. were the most efficient bacterial strains to degrade DOX (92.52% and 91.63%, respectively), but their tetracycline resistance genes showed a relatively low risk of antibiotic resistance in a 7-day experiment. Moreover, the tetM of the ribosomal protection protein genes carried by these two preponderant bacteria was five-fold higher than that carried by other isolates (P < 0.05). Pearson correlations between the C /C of DOX and tet resistance genes of three isolates, except for Escherichia sp. and Candida sp., showed remarkable negative correlations (P < 0.05), mainly because tetG markedly increased during the DOX degradation process. Our results concluded that the biodegradation of antibiotic residues may not necessarily lead to the development of ARGs in the environment. In addition, the two bacteria that we isolated, namely, Escherichia sp. and Candida sp., are potential candidates for the engineering of environmentally friendly bacteria.
[Mh] Termos MeSH primário: Doxiciclina/toxicidade
Resistência Microbiana a Medicamentos/efeitos dos fármacos
Microbiologia do Solo/normas
Poluentes do Solo/toxicidade
Drogas Veterinárias/toxicidade
[Mh] Termos MeSH secundário: Biodegradação Ambiental
Candida/efeitos dos fármacos
Candida/genética
China
Relação Dose-Resposta a Droga
Resistência Microbiana a Medicamentos/genética
Escherichia/efeitos dos fármacos
Escherichia/genética
Fertilizantes
Genes Bacterianos
Esterco/microbiologia
Resistência a Tetraciclina/efeitos dos fármacos
Resistência a Tetraciclina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fertilizers); 0 (Manure); 0 (Soil Pollutants); 0 (Veterinary Drugs); N12000U13O (Doxycycline)
[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:170925
[St] Status:MEDLINE


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[PMID]:29231658
[Au] Autor:Frivik JO; Noraas S; Grankvist A; Wennerås C; Quarsten H
[Ti] Título:A man in his sixties from Southern Norway with intermittent fever.
[Ti] Título:En mann i 60-årene fra Sørlandet med intermitterende feber..
[So] Source:Tidsskr Nor Laegeforen;137(23-24), 2017 12 12.
[Is] ISSN:0807-7096
[Cp] País de publicação:Norway
[La] Idioma:eng; nor
[Mh] Termos MeSH primário: Infecções por Anaplasmataceae
Febre/virologia
Doenças Transmitidas por Carrapatos
[Mh] Termos MeSH secundário: Idoso
Anaplasmataceae/isolamento & purificação
Infecções por Anaplasmataceae/complicações
Infecções por Anaplasmataceae/diagnóstico
Infecções por Anaplasmataceae/tratamento farmacológico
Antibacterianos/uso terapêutico
Astenia/virologia
Doxiciclina/uso terapêutico
Seres Humanos
Masculino
Meia-Idade
Noruega
Doenças Transmitidas por Carrapatos/complicações
Doenças Transmitidas por Carrapatos/diagnóstico
Doenças Transmitidas por Carrapatos/tratamento farmacológico
[Pt] Tipo de publicação:CASE REPORTS
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); N12000U13O (Doxycycline)
[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:171213
[St] Status:MEDLINE
[do] DOI:10.4045/tidsskr.17.0353


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[PMID]:28448738
[Au] Autor:Anton T; Bultmann S
[Ad] Endereço:a Department of Biology II and Center for Integrated Protein Science Munich (CIPSM) , LMU Munich , Martinsried , Germany.
[Ti] Título:Site-specific recruitment of epigenetic factors with a modular CRISPR/Cas system.
[So] Source:Nucleus;8(3):279-286, 2017 May 04.
[Is] ISSN:1949-1042
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Dissecting the complex network of epigenetic modifications requires tools that combine precise recognition of DNA sequences with the capability to modify epigenetic marks. The CRISPR/Cas system has been proven to be a valuable addition to existing methodologies that fulfill these tasks. So far, sequence-specific editing of epigenetic modifications such as DNA methylation and histone posttranslational modifications relied on direct fusions of enzymatically inactivated Cas9 (dCas9) with epigenetic effectors. Here, we report a novel, modular system that facilitates the recruitment of any GFP-tagged protein to desired genomic loci. By fusing dCas9 to a GFP-binding nanobody (GBP) we demonstrate that prevalent epigenetic modifications at mouse major satellite repeats can be erased or set de novo by recruiting GFP-coupled catalytic domains of TET1 and DNMT3A, respectively. Furthermore, we construct an inducible expression system that enables a temporally controlled expression of both GBP-dCas9 and the effector protein. Thus, our approach further expands the CRISPR/Cas toolbox for site-specific manipulation of epigenetic modifications with a modular and easy-to-use system.
[Mh] Termos MeSH primário: Sistemas CRISPR-Cas/genética
Epigênese Genética
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Sítios de Ligação
Linhagem Celular
Metilases de Modificação do DNA/metabolismo
Doxiciclina/farmacologia
Proteínas de Fluorescência Verde/genética
Camundongos
Regiões Promotoras Genéticas/genética
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
147336-22-9 (Green Fluorescent Proteins); EC 2.1.1.- (DNA Modification Methylases); N12000U13O (Doxycycline)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1080/19491034.2017.1292194


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[PMID]:29352318
[Au] Autor:William D; Walther M; Schneider B; Linnebacher M; Classen CF
[Ad] Endereço:University Children's and Adolescents' Hospital, University Medicine of Rostock, Rostock, Germany.
[Ti] Título:Temozolomide-induced increase of tumorigenicity can be diminished by targeting of mitochondria in in vitro models of patient individual glioblastoma.
[So] Source:PLoS One;13(1):e0191511, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor with a dismal prognosis. Development of resistance towards cytostatic drugs like the GBM standard drug temozolomide is a severe problem in GBM treatment. One potential source of GBM relapse could be so called cancer stem like cells (CSCs). These represent an undifferentiated subpopulation of cells with high potential for tumor initiation. Furthermore, it has been shown that differentiated GBM cells can regain CSC properties when exposed to continuous temozolomide treatment in vitro. In this study, treatment of several primary GBM cell lines with clinically relevant doses of temozolomide increased their tumorigenicity as determined by colony formation assays in soft agar. Increased tumorigenicity is a known property of CSCs. Hence, therapy options that specifically target CSCs are under investigation. CSCs appear to be particularly dependent on mitochondria biogenesis which may represent a useful target for CSC elimination. Toxicity towards mitochondria is a known side effect of several antibiotics. Thus, addition of antibiotics like doxycycline may represent a useful tool to inhibit CSCs in GBM. Here, we show that combining temozolomide treatment of primary GBM cells with doxycycline could counteract the increase of tumorigenicity induced by temozolomide treatment.
[Mh] Termos MeSH primário: Antineoplásicos Alquilantes/efeitos adversos
Neoplasias Encefálicas/tratamento farmacológico
Neoplasias Encefálicas/patologia
Dacarbazina/análogos & derivados
Glioblastoma/tratamento farmacológico
Glioblastoma/patologia
[Mh] Termos MeSH secundário: Antibacterianos/administração & dosagem
Antineoplásicos Alquilantes/administração & dosagem
Biomarcadores Tumorais/metabolismo
Neoplasias Encefálicas/metabolismo
Diferenciação Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Metilases de Modificação do DNA/genética
Enzimas Reparadoras do DNA/genética
Dacarbazina/administração & dosagem
Dacarbazina/efeitos adversos
Doxiciclina/administração & dosagem
Resistência a Medicamentos Antineoplásicos
Fucosiltransferases/metabolismo
Glioblastoma/metabolismo
Seres Humanos
Antígeno Lewis X/metabolismo
Mitocôndrias/efeitos dos fármacos
Células-Tronco Neoplásicas/efeitos dos fármacos
Células-Tronco Neoplásicas/metabolismo
Células-Tronco Neoplásicas/patologia
Nestina/metabolismo
Ensaio Tumoral de Célula-Tronco
Proteínas Supressoras de Tumor/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antineoplastic Agents, Alkylating); 0 (Biomarkers, Tumor); 0 (Lewis X Antigen); 0 (NES protein, human); 0 (Nestin); 0 (Tumor Suppressor Proteins); 7GR28W0FJI (Dacarbazine); EC 2.1.1.- (DNA Modification Methylases); EC 2.1.1.63 (MGMT protein, human); EC 2.4.1.- (FUT4 protein, human); EC 2.4.1.- (Fucosyltransferases); EC 6.5.1.- (DNA Repair Enzymes); N12000U13O (Doxycycline); YF1K15M17Y (temozolomide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180121
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191511


  9 / 8658 MEDLINE  
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Barraviera, Benedito
Texto completo
[PMID]:28450050
[Au] Autor:Araújo MR; Kyrylenko S; Spejo AB; Castro MV; Ferreira Junior RS; Barraviera B; Oliveira ALR
[Ad] Endereço:Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Sao Paulo, Brazil.
[Ti] Título:Transgenic human embryonic stem cells overexpressing FGF2 stimulate neuroprotection following spinal cord ventral root avulsion.
[So] Source:Exp Neurol;294:45-57, 2017 08.
[Is] ISSN:1090-2430
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ventral root avulsion (VRA) triggers a strong glial reaction which contributes to neuronal loss, as well as to synaptic detachment. To overcome the degenerative effects of VRA, treatments with neurotrophic factors and stem cells have been proposed. Thus, we investigated neuroprotection elicited by human embryonic stem cells (hESC), modified to overexpress a human fibroblast growth factor 2 (FGF-2), on motoneurons subjected to VRA. Lewis rats were submitted to VRA (L4-L6) and hESC/FGF-2 were applied to the injury site using a fibrin scaffold. The spinal cords were processed to evaluate neuronal survival, synaptic stability, and glial reactivity two weeks post lesion. Then, qRT-PCR was used to assess gene expression of ß2-microglobulin (ß2m), TNFα, IL1ß, IL6 and IL10 in the spinal cord in vivo and FGF2 mRNA levels in hESC in vitro. The results indicate that hESC overexpressing FGF2 significantly rescued avulsed motoneurons, preserving synaptic covering and reducing astroglial reactivity. The cells were also shown to express BDNF and GDNF at the site of injury. Additionally, engraftment of hESC led to a significant reduction in mRNA levels of TNFα at the spinal cord ventral horn, indicating their immunomodulatory properties. Overall, the present data suggest that hESC overexpressing FGF2 are neuroprotective and can shift gene expression towards an anti-inflammatory environment.
[Mh] Termos MeSH primário: Células-Tronco Embrionárias Humanas/transplante
Radiculopatia/cirurgia
Raízes Nervosas Espinhais/patologia
[Mh] Termos MeSH secundário: Animais
Movimento Celular
Sobrevivência Celular/efeitos dos fármacos
Sobrevivência Celular/genética
Modelos Animais de Doenças
Doxiciclina/uso terapêutico
Feminino
Adesivo Tecidual de Fibrina/toxicidade
Fator 2 de Crescimento de Fibroblastos/genética
Fator 2 de Crescimento de Fibroblastos/metabolismo
Regulação da Expressão Gênica/efeitos dos fármacos
Regulação da Expressão Gênica/genética
Vetores Genéticos/fisiologia
Células-Tronco Embrionárias Humanas/metabolismo
Seres Humanos
Neurônios Motores/metabolismo
Neurônios Motores/patologia
Proteínas do Tecido Nervoso/metabolismo
Neuroglia/efeitos dos fármacos
Neuroglia/metabolismo
Radiculopatia/induzido quimicamente
Ratos
Ratos Endogâmicos Lew
Adesivos Teciduais/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fibrin Tissue Adhesive); 0 (Nerve Tissue Proteins); 0 (Tissue Adhesives); 103107-01-3 (Fibroblast Growth Factor 2); N12000U13O (Doxycycline)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180218
[Lr] Data última revisão:
180218
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:29220404
[Au] Autor:Rumney RMH; Coffelt SB; Neale TA; Dhayade S; Tozer GM; Miller G
[Ad] Endereço:Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom.
[Ti] Título:PyMT-Maclow: A novel, inducible, murine model for determining the role of CD68 positive cells in breast tumor development.
[So] Source:PLoS One;12(12):e0188591, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CD68+ tumor-associated macrophages (TAMs) are pro-tumorigenic, pro-angiogenic and are associated with decreased survival rates in patients with cancer, including breast cancer. Non-specific models of macrophage ablation reduce the number of TAMs and limit the development of mammary tumors. However, the lack of specificity and side effects associated with these models compromise their reliability. We hypothesized that specific and controlled macrophage depletion would provide precise data on the effects of reducing TAM numbers on tumor development. In this study, the MacLow mouse model of doxycycline-inducible and selective CD68+ macrophage depletion was crossed with the murine mammary tumor virus (MMTV)-Polyoma virus middle T antigen (PyMT) mouse model of spontaneous ductal breast adenocarcinoma to generate the PyMT-MacLow line. In doxycycline-treated PyMT-MacLow mice, macrophage numbers were decreased in areas surrounding tumors by 43%. Reducing the number of macrophages by this level delayed tumor progression, generated less proliferative tumors, decreased the vascularization of carcinomas and down-regulated the expression of many pro-angiogenic genes. These results demonstrate that depleting CD68+ macrophages in an inducible and selective manner delays the development of mammary tumors and that the PyMT-MacLow model is a useful and unique tool for studying the role of TAMs in breast cancer.
[Mh] Termos MeSH primário: Antígenos CD/imunologia
Antígenos de Diferenciação Mielomonocítica/imunologia
Neoplasias da Mama/imunologia
Modelos Animais de Doenças
Macrófagos/imunologia
[Mh] Termos MeSH secundário: Animais
Neoplasias da Mama/patologia
Doxiciclina/farmacologia
Feminino
Seres Humanos
Macrófagos/efeitos dos fármacos
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (Antigens, Differentiation, Myelomonocytic); 0 (CD68 antigen, human); N12000U13O (Doxycycline)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188591



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