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[PMID]:29441913
[Ti] Título:Stimulation of bone regeneration with pigment epithelium-derived factor microparticles: evidence and .
[So] Source:Pharmazie;71(7):382-389, 2016 Jul 07.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The occurrence of bone defects can be due to a variety of factors not limited to bone fractures and tumours. Most diseased bone is removed and the patient fitted with prosthetics, prior to use of certain factors such as bone morphogenetic proteins (BMPs) to aid healing. Recently, the protein pigment epithelium-derived factor (PEDF) and the polysaccharide chitosan have been found to have promising effects on the regeneration of bone, with the major advantage of these agents being their safety to date. A study was performed to determine whether the combination of both chitosan and PEDF would enhance greater bone regeneration effects. Post-formulation, in silico tests (particle sizing and surface charge determination) were followed by several cell-based assays (microparticle cellular uptake, cytotoxicity, mitochondrial abundance, bone mineral formation, colony formation in matrigel, and colony formation in collagen I matrix), and finally in vivo testing where microparticles were injected periosteally in the hindlimb. Collectively, these findings support the idea that PEDF microencapsulated within chitosan promotes bone regeneration, and has potential for bone trauma management. Future studies will examine the ability of this promising bone regeneration microparticle to heal bone in disease states such as fracture and tumour-mediated osteolysis.
[Mh] Termos MeSH primário: Regeneração Óssea/efeitos dos fármacos
Proteínas do Olho/farmacologia
Fatores de Crescimento Neural/farmacologia
Serpinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Densidade Óssea/efeitos dos fármacos
Cápsulas
Sobrevivência Celular/efeitos dos fármacos
Quitosana/farmacologia
Colágeno Tipo I/farmacologia
Ensaio de Unidades Formadoras de Colônias
Simulação por Computador
Composição de Medicamentos
Proteínas do Olho/administração & dosagem
Proteínas do Olho/metabolismo
Membro Posterior
Seres Humanos
Injeções
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Mitocôndrias/efeitos dos fármacos
Fatores de Crescimento Neural/administração & dosagem
Fatores de Crescimento Neural/metabolismo
Tamanho da Partícula
Serpinas/administração & dosagem
Serpinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Capsules); 0 (Collagen Type I); 0 (Eye Proteins); 0 (Nerve Growth Factors); 0 (Serpins); 0 (pigment epithelium-derived factor); 9012-76-4 (Chitosan)
[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:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6010


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[PMID]:28460641
[Au] Autor:Bernardi M; Agostini F; Chieregato K; Amati E; Durante C; Rassu M; Ruggeri M; Sella S; Lombardi E; Mazzucato M; Astori G
[Ad] Endereço:Advanced Cellular Therapy Laboratory, Hematology Unit, Vicenza Hospital, Vicenza, Italy.
[Ti] Título:The production method affects the efficacy of platelet derivatives to expand mesenchymal stromal cells in vitro.
[So] Source:J Transl Med;15(1):90, 2017 May 01.
[Is] ISSN:1479-5876
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The use of fetal bovine serum (FBS) as a media supplement for the ex vivo expansion of bone-marrow derived mesenchymal stromal cells (BM-MSC) has been discouraged by regulatory agencies, due to the risk of transmitting zoonoses and to elicit immune reactions in the host once transplanted. Platelet derivatives are valid FBS substitutes due to their content of growth factors that can be released disrupting the platelets by physical methods or physiological stimuli. We compared platelet derivatives produced by freezing/thawing (platelet lysates, PL) or after CaCl activation (platelet releasate surnatant rich in growth factors, PR-SRGF) for their content in growth factors and their ability to support the ex vivo expansion of BM-MSC. METHODS: The cytokine content in the two platelet derivatives was evaluated. BM-MSC were expanded in complete medium containing 10, 7.5 and 5% PL or PR-SRGF and the cell phenotype, clonogenic capacity, immunomodulation properties and tri-lineage differentiation potential of the expanded cells in both media were investigated. RESULTS: The concentration of PDGF-AB, PDGF-AA, PDGF-BB in PR-SRGF resulted to be respectively 5.7×, 1.7× and 2.3× higher compared to PL. PR-SRGF promoted a higher BM-MSC proliferation rate compared to PL not altering BM-MSC phenotype. Colony forming efficiency of BM-MSC expanded in PR-SRGF showed a frequency of colonies significantly higher than cells expanded in PL. BM-MSC expanded in PL or PR-SRGF maintained their immunomodulatory properties against activated lymphocytes even if BM-MSC expanded in FBS performed significantly better. CONCLUSIONS: The method used to release platelet factors significantly affects the enrichment in growth factors and overall product performance. The standardization of the production process of platelet derivatives and the definition of their release criteria requires further investigation.
[Mh] Termos MeSH primário: Plaquetas/metabolismo
Técnicas de Cultura de Células/métodos
Células Mesenquimais Estromais/citologia
[Mh] Termos MeSH secundário: Diferenciação Celular
Linhagem da Célula
Proliferação Celular
Ensaio de Unidades Formadoras de Colônias
Seres Humanos
Imunomodulação
Imunofenotipagem
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Intercellular Signaling Peptides and Proteins)
[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:170503
[St] Status:MEDLINE
[do] DOI:10.1186/s12967-017-1185-9


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[PMID]:29327472
[Au] Autor:He Y; Xu LL; Feng FE; Wang QM; Zhu XL; Wang CC; Zhang JM; Fu HX; Xu LP; Liu KY; Huang XJ; Zhang XH
[Ad] Endereço:Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.
[Ti] Título:Mesenchymal stem cell deficiency influences megakaryocytopoiesis through the TNFAIP3/NF-κB/SMAD pathway in patients with immune thrombocytopenia.
[So] Source:Br J Haematol;180(3):395-411, 2018 02.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Immune thrombocytopenia (ITP) is an autoimmune disease. Mesenchymal stem cells (MSCs) play important roles in the physiology and homeostasis of the haematopoietic system, including supporting megakaryocytic differentiation from CD34 haematopoietic progenitor cells. Tumour necrosis factor alpha-induced protein 3 (TNFAIP3, also termed A20) plays a key role in terminating NF-κB signalling. Human genetic studies showed that the polymorphisms of the TNFAIP3 gene may contribute to ITP susceptibility. In this study, we showed a significant decrease in TNFAIP3 and increase in NF-κB/SMAD7 in ITP-MSCs. In co-cultures with CD34 cells, NF-κB was overexpressed in MSCs from healthy controls (HC-MSCs) after transfection with NFKBIA (IκB)-specific short hairpin (sh)RNAs, resulting in MSC deficiency and a reduction in megakaryocytic differentiation and thrombopoiesis. Knockdown of TNFAIP3 expression using TNFAIP3-specific shRNAs in HC-MSCs affected megakaryocytopoiesis. However, IKBKB knockdown corrected megakaryocytopoiesis inhibition in the ITP-MSCs by decreasing NF-κB expression. Amplified TNFAIP3 expression in ITP-MSCs by TNFAIP3 cDNA can facilitate megakaryocyte differentiation. shRNA-mediated knockdown of SMAD7 expression rescued the impaired MSC function in ITP patients. Therefore, we demonstrate that a pathological reduction in TNFAIP3 levels induced NF-κB/SMAD7 pathway activation, causing a deficiency in MSCs in ITP patients. The ability of ITP-MSCs to support megakaryocytic differentiation and thrombopoiesis of CD34 cells was impaired.
[Mh] Termos MeSH primário: Células Mesenquimais Estromais/metabolismo
NF-kappa B/metabolismo
Púrpura Trombocitopênica Idiopática/etiologia
Púrpura Trombocitopênica Idiopática/metabolismo
Transdução de Sinais
Proteínas Smad/metabolismo
Trombopoese
Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo
[Mh] Termos MeSH secundário: Biomarcadores
Medula Óssea/patologia
Estudos de Casos e Controles
Diferenciação Celular
Ensaio de Unidades Formadoras de Colônias
Citocinas/biossíntese
Expressão Gênica
Seres Humanos
Imunofenotipagem
Células Mesenquimais Estromais/efeitos dos fármacos
Células Mesenquimais Estromais/patologia
Modelos Biológicos
NF-kappa B/genética
Púrpura Trombocitopênica Idiopática/diagnóstico
Púrpura Trombocitopênica Idiopática/tratamento farmacológico
Transdução de Sinais/efeitos dos fármacos
Proteínas Smad/genética
Trombopoese/efeitos dos fármacos
Trombopoese/genética
Fator de Crescimento Transformador beta/metabolismo
Tretinoína/farmacologia
Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers); 0 (Cytokines); 0 (NF-kappa B); 0 (Smad Proteins); 0 (Transforming Growth Factor beta); 5688UTC01R (Tretinoin); EC 3.4.19.12 (TNFAIP3 protein, human); EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.15034


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[PMID]:29254292
[Au] Autor:Cantore S; Ballini A; De Vito D; Martelli FS; Georgakopoulos I; Almasri M; Dibello V; Altini V; Farronato G; Dipalma G; Farronato D; Inchingolo F
[Ad] Endereço:Department of Interdisciplinary Medicine, School of Medicine, University of Bari Aldo Moro, Bari, Italy.
[Ti] Título:Characterization of human apical papilla-derived stem cells.
[So] Source:J Biol Regul Homeost Agents;31(4):901-910, 2017 Oct-Dec.
[Is] ISSN:0393-974X
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:Dental tissues represent an alternative and promising source of post-natal Mesenchymal stem cells (MSCs) for tissue engineering. Furthermore, dental stem cells from apical papilla (SCAPs) cells can be obtained from the wisdom tooth which is unnecessary for human masticatory function and frequently extracted for orthodontic reasons or dysodontiasis. More precisely, apical papilla is the immature, mostly uncalcified, precursor of the tooth root, therefore is composed of more undifferentiated cells than dental pulp. In addition, tooth extraction, especially by piezosurgery technique, can be considered less invasive in comparison to bone marrow or other tissues biopsy. Our work is aimed to investigate the safety of and predictable procedure on surgical immature third molar extraction and to provide new insight on SCAP research for future biomedical applications. The isolated cells were examined for stem cell properties by analyzing their colony-forming efficiency, differentiation characteristics and the expression of MSC markers.
[Mh] Termos MeSH primário: Polpa Dentária/citologia
Células Mesenquimais Estromais/citologia
Osteogênese/genética
Raiz Dentária/citologia
[Mh] Termos MeSH secundário: Adolescente
Biomarcadores/metabolismo
Diferenciação Celular
Proliferação Celular
Separação Celular
Criança
Ensaio de Unidades Formadoras de Colônias
Polpa Dentária/metabolismo
Feminino
Expressão Gênica
Seres Humanos
Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética
Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo
Masculino
Células Mesenquimais Estromais/metabolismo
Dente Molar/cirurgia
Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética
Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo
Engenharia Tecidual
Extração Dentária
Raiz Dentária/metabolismo
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Insulin-Like Growth Factor Binding Proteins); 0 (JunB protein, human); 0 (NR4A2 protein, human); 0 (Nuclear Receptor Subfamily 4, Group A, Member 2); 0 (Transcription Factors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE


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[PMID]:28947270
[Au] Autor:Ito R; Nagai D; Igo N; Okuda Y; Sekine K; Ichimura E; Katano I; Mizushima T; Goto M; Ohnishi Y; Ito M; Okamoto K
[Ad] Endereço:Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan.
[Ti] Título:A novel in vivo model for predicting myelotoxicity of chemotherapeutic agents using IL-3/GM-CSF transgenic humanized mice.
[So] Source:Toxicol Lett;281:152-157, 2017 Nov 05.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Evaluating myelotoxicity is essential for ensuring the safety of novel drugs before they are approved for clinical applications. Although in vivo prediction of the maximum tolerated doses (MTDs) of anticancer drugs is usually performed in rodents, the results are not always applicable to clinical treatment because drugs may have different effects in human and rodent cells. Previously, we generated a human IL-3 and GM-CSF transgenic humanized mouse (hu-IL-3/GM Tg), in which human granulocytes effectively differentiated after hematopoietic stem cell transplantation. In this study, we established a novel in vivo preclinical evaluation model for predicting human myelotoxicity of anticancer drugs using these hu-IL-3/GM Tg mice. The myelotoxicity was investigated by kinetic flow cytometry of human or murine granulocytes and by colony-forming unit granulocyte/macrophage (CFU-GM) assays. In both in vivo and in vitro analyses, topotecan was more myelotoxic to human than murine granulocytes. In contrast, oxaliplatin was more myelotoxic to murine granulocytes. The level of myelotoxicity of paclitaxel treatment was comparable between human and mouse cells. These results demonstrate that our humanized mouse model can simultaneously evaluate myelotoxicity against human and mouse cells in vivo, and provides an effective preclinical tool for predicting appropriate doses of anticancer agents for clinical treatment.
[Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/toxicidade
Paclitaxel/toxicidade
[Mh] Termos MeSH secundário: Animais
Diferenciação Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Ensaio de Unidades Formadoras de Colônias
Relação Dose-Resposta a Droga
Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética
Granulócitos/efeitos dos fármacos
Células-Tronco Hematopoéticas/efeitos dos fármacos
Seres Humanos
Concentração Inibidora 50
Interleucina-3/genética
Camundongos
Camundongos Endogâmicos NOD
Camundongos Transgênicos
Testes de Toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Interleukin-3); 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor); P88XT4IS4D (Paclitaxel)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170927
[St] Status:MEDLINE


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[PMID]:28931068
[Au] Autor:Darling NJ; Balmanno K; Cook SJ
[Ad] Endereço:Signalling Laboratory, The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, United Kingdom.
[Ti] Título:ERK1/2 signalling protects against apoptosis following endoplasmic reticulum stress but cannot provide long-term protection against BAX/BAK-independent cell death.
[So] Source:PLoS One;12(9):e0184907, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Disruption of protein folding in the endoplasmic reticulum (ER) causes ER stress. Activation of the unfolded protein response (UPR) acts to restore protein homeostasis or, if ER stress is severe or persistent, drive apoptosis, which is thought to proceed through the cell intrinsic, mitochondrial pathway. Indeed, cells that lack the key executioner proteins BAX and BAK are protected from ER stress-induced apoptosis. Here we show that chronic ER stress causes the progressive inhibition of the extracellular signal-regulated kinase (ERK1/2) signalling pathway. This is causally related to ER stress since reactivation of ERK1/2 can protect cells from ER stress-induced apoptosis whilst ERK1/2 pathway inhibition sensitises cells to ER stress. Furthermore, cancer cell lines harbouring constitutively active BRAFV600E are addicted to ERK1/2 signalling for protection against ER stress-induced cell death. ERK1/2 signalling normally represses the pro-death proteins BIM, BMF and PUMA and it has been proposed that ER stress induces BIM-dependent cell death. We found no evidence that ER stress increased the expression of these proteins; furthermore, BIM was not required for ER stress-induced death. Rather, ER stress caused the PERK-dependent inhibition of cap-dependent mRNA translation and the progressive loss of pro-survival proteins including BCL2, BCLXL and MCL1. Despite these observations, neither ERK1/2 activation nor loss of BAX/BAK could confer long-term clonogenic survival to cells exposed to ER stress. Thus, ER stress induces cell death by at least two biochemically and genetically distinct pathways: a classical BAX/BAK-dependent apoptotic response that can be inhibited by ERK1/2 signalling and an alternative ERK1/2- and BAX/BAK-independent cell death pathway.
[Mh] Termos MeSH primário: Apoptose
Neoplasias Colorretais/patologia
Estresse do Retículo Endoplasmático
Retículo Endoplasmático/patologia
Proteína Quinase 1 Ativada por Mitógeno/metabolismo
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo
Proteína X Associada a bcl-2/metabolismo
[Mh] Termos MeSH secundário: Ensaio de Unidades Formadoras de Colônias
Neoplasias Colorretais/metabolismo
Retículo Endoplasmático/metabolismo
Seres Humanos
Mitocôndrias/metabolismo
Mitocôndrias/patologia
Transdução de Sinais
Células Tumorais Cultivadas
Resposta a Proteínas não Dobradas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BAK1 protein, human); 0 (BAX protein, human); 0 (bcl-2 Homologous Antagonist-Killer Protein); 0 (bcl-2-Associated X Protein); EC 2.7.11.24 (MAPK1 protein, human); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170921
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184907


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[PMID]:28867577
[Au] Autor:de Paula DRM; Capuano V; Filho DM; Carneiro ACDM; de Oliveira Crema V; de Oliveira LF; Rodrigues ARA; Montano N; da Silva VJD
[Ad] Endereço:Department of Physiology, Biological and Natural Sciences Institute, Triangulo Mineiro Federal University, Uberaba, MG, Brazil.
[Ti] Título:Biological properties of cardiac mesenchymal stem cells in rats with diabetic cardiomyopathy.
[So] Source:Life Sci;188:45-52, 2017 Nov 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cardiomyopathy is a major outcome in patients with diabetes mellitus (DM) and contributes to the high morbidity/mortality observed in this disease. AIMS: To evaluate several biological properties of cardiac mesenchymal stem cells (cMSCs) in a rat model of streptozotocin-induced DM with concomitant diabetic cardiomyopathy. MAIN METHODS: After 10weeks of DM induction, diabetic and control rats were assessed using ECG and ventricular hemodynamics monitoring. Then, the hearts were excised and processed for histology and for extracting non-cardiomyocytic cells. A pool of these cells was plated for a colony forming units-fibroblasts (CFU-F) assay in order to estimate the number of cMSCs. The remaining cells were expanded to assess their proliferation rate as well as their osteogenic and adipogenic differentiation ability. KEY FINDINGS: DM rats presented intense hyperglycemia and changes in ECG, LV hemodynamic, cardiac mass index and fibrosis, indicating presence of DCM. The CFU-F assay revealed a higher number of cardiac CFU-Fs in DM rats (10.4±1.1CFU-F/10 total cells versus 7.6±0.7CFU-F/10 total cells in control rats, p<0.05), which was associated with a significantly higher proliferative rate of cMSCs in DM rats. In contrast, cMSCs from DM rats presented a lower capacity to differentiate into both osteogenic (20.8±4.2% versus 10.1±1.0% in control rats, p<0.05) and adipogenic lineages (4.6±1.0% versus 1.3±0.5% in control rats, p<0.05). SIGNIFICANCE: The findings suggest, for the first time, that in chronic DM rats with overt DCM, cMSCs increase in number and exhibit changes in several functional properties, which could be implicated in the pathogenesis of diabetic cardiomyopathy.
[Mh] Termos MeSH primário: Diabetes Mellitus Experimental/fisiopatologia
Cardiomiopatias Diabéticas/fisiopatologia
Células Mesenquimais Estromais/patologia
[Mh] Termos MeSH secundário: Adipogenia
Animais
Proliferação Celular
Ensaio de Unidades Formadoras de Colônias
Diabetes Mellitus Experimental/patologia
Cardiomiopatias Diabéticas/patologia
Fibrose/patologia
Hemodinâmica
Masculino
Miocárdio/patologia
Osteogênese
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170905
[St] Status:MEDLINE


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[PMID]:28760810
[Au] Autor:Nemashkalo A; Ruzo A; Heemskerk I; Warmflash A
[Ad] Endereço:Department of Biosciences, Rice University, Houston, TX 77005, USA.
[Ti] Título:Morphogen and community effects determine cell fates in response to BMP4 signaling in human embryonic stem cells.
[So] Source:Development;144(17):3042-3053, 2017 09 01.
[Is] ISSN:1477-9129
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Paracrine signals maintain developmental states and create cell fate patterns and influence differentiation outcomes in human embryonic stem cells (hESCs) Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells ('µColonies') to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in µColonies and standard culture conditions and find that in µColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems. Under standard culture conditions BMP4 acts as a morphogen but this requires secondary signals and particular cell densities. We find that a 'community effect' enforces a common fate within µColonies, both in the state of pluripotency and when cells are differentiated, and that this effect allows a more precise response to external signals. Using live cell imaging to correlate signaling histories with cell fates, we demonstrate that interactions between neighbors result in sustained, homogenous signaling necessary for differentiation.
[Mh] Termos MeSH primário: Proteína Morfogenética Óssea 4/farmacologia
Diferenciação Celular/efeitos dos fármacos
Linhagem da Célula/efeitos dos fármacos
Células-Tronco Embrionárias Humanas/citologia
Células-Tronco Embrionárias Humanas/efeitos dos fármacos
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Contagem de Células
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Células Clonais
Ensaio de Unidades Formadoras de Colônias
Ectoderma/citologia
Ectoderma/efeitos dos fármacos
Ectoderma/metabolismo
Células-Tronco Embrionárias Humanas/metabolismo
Seres Humanos
Camundongos
Modelos Biológicos
Proteína Nodal/metabolismo
Células-Tronco Pluripotentes/citologia
Células-Tronco Pluripotentes/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Bone Morphogenetic Protein 4); 0 (Nodal Protein)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171126
[Lr] Data última revisão:
171126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.1242/dev.153239


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[PMID]:28717098
[Au] Autor:Goto K; Goto M; Ando-Imaoka M; Kai K; Mori K
[Ad] Endereço:Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd.
[Ti] Título:Evaluation of drug-induced hematotoxicity using novel in vitro monkey CFU-GM and BFU-E colony assays.
[So] Source:J Toxicol Sci;42(4):397-405, 2017.
[Is] ISSN:1880-3989
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:In order to evaluate drug-induced hematotoxicity in monkey cells in vitro, colony-forming unit-granulocyte, macrophage (CFU-GM), and burst-forming unit-erythroid (BFU-E) colony assays were established using mononuclear cells in the bone marrow collected from male cynomolgus monkeys. Furthermore, the effects of doxorubicin, chloramphenicol, and linezolid on CFU-GM and BFU-E colony formation were investigated using established monkey CFU-GM and BFU-E colony assays in comparison with those on human CFU-GM and BFU-E colonies acquired from human umbilical cord blood cells. Bone marrow mononuclear cells were collected from the ischial or iliac bone of male cynomolgus monkeys. The cells were subsequently processed by density gradient separation at 1.067, 1.070, or 1.077 g/mL for CFU-GM or 1.077 g/mL for BFU-E, and then cultured in methylcellulose medium for 9 or 13 days, respectively. A sufficient number of CFU-GM colonies were formed from mononuclear cells processed at a density of 1.070 g/mL. Moreover, the number of BFU-E colonies from the cells processed at a density of 1.077 g/mL was sufficient for the colony assay. The number of CFU-GM or BFU-E colonies decreased after treatment with the drugs of interest in a concentration-dependent manner. Compared with human CFU-GM, monkey CFU-GM were more sensitive to chloramphenicol and resistant to doxorubicin, whereas monkey BFU-E were more sensitive to all compounds in comparison to the sensitivity of human BFU-E. In conclusion, monkey CFU-GM and BFU-E colony assays were established and considered useful tools to evaluate the differences in drug-induced hematotoxicity between species.
[Mh] Termos MeSH primário: Cloranfenicol/toxicidade
Doxorrubicina/toxicidade
Linezolida/toxicidade
Células Progenitoras Mieloides/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Células da Medula Óssea/citologia
Células Cultivadas
Ensaio de Unidades Formadoras de Colônias
Relação Dose-Resposta a Droga
Sangue Fetal/citologia
Seres Humanos
Macaca fascicularis
Masculino
Especificidade da Espécie
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
66974FR9Q1 (Chloramphenicol); 80168379AG (Doxorubicin); ISQ9I6J12J (Linezolid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.2131/jts.42.397


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[PMID]:28650782
[Au] Autor:Ghasemi E; Mazaheri R; Tahmourespour A
[Ti] Título:Effect of Probiotic Yogurt and Xylitol-Containing Chewing Gums on Salivary S Mutans Count.
[So] Source:J Clin Pediatr Dent;41(4):257-263, 2017.
[Is] ISSN:1053-4628
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND AIMS: In addition to improving gastrointestinal health and intestinal microflora, probiotic bacteria have been recently suggested to decrease cariogenic agents in the oral cavity. The aim of this study was to investigate the effects of probiotic yogurt and xylitol-containing chewing gums on reducing salivary Streptococcus mutans levels. STUDY DESIGN: This randomized clinical trial recruited 50 female students with over 10 colony forming units S. mutans per milliliter of their saliva. The participants were randomly allocated to two equal groups to receive either probiotic yogurt containing Lactobacillus acidophilus ATCC 4356 andBifidobacteriumbifidum ATCC 29521 (200 g daily) or xylitol-containing chewing gums (two gums three times daily after each meal; total xylitol content: 5.58 g daily) for three weeks. At baseline and one day, two weeks, and four weeks after the interventions, saliva samples were cultured on mitis-salivarius-bacitracin agar and salivary S. mutans counts were determined. Data were analyzed with independent t-tests, analysis of variance, and Fisher's least significant difference test. RESULTS: In both groups, S. mutans counts on the first day, second week, and fourth weeks after the intervention were significantly lower than baseline values (P < 0.05). The greatest level of reduction in both groups was observed in the second week after the intervention. Moreover, although the reduction was greater in probiotic yogurt consumers, the difference between the two groups was not statistically significant. CONCLUSION: Probiotic yogurt and xylitol-containing chewing gums seem to be as effective in reduction of salivary S. mutans levels. Their constant long-term consumption is thus recommended to prevent caries.
[Mh] Termos MeSH primário: Bifidobacterium bifidum
Goma de Mascar
Cárie Dentária/prevenção & controle
Lactobacillus acidophilus
Probióticos/farmacologia
Saliva/microbiologia
Streptococcus mutans/efeitos dos fármacos
Xilitol/farmacologia
Iogurte/microbiologia
[Mh] Termos MeSH secundário: Carga Bacteriana
Ensaio de Unidades Formadoras de Colônias
Cárie Dentária/microbiologia
Feminino
Seres Humanos
Irã (Geográfico)
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Chewing Gum); VCQ006KQ1E (Xylitol)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:D
[Da] Data de entrada para processamento:170627
[St] Status:MEDLINE
[do] DOI:10.17796/1053-4628-41.4.257



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