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1 / 199848

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[PMID]: 29430664 [Au] Autor: Budzynska PM; Kyläniemi MK; Lassila O; Nera KP; Alinikula J [Ad] Endereço: Department of Medical Microbiology and Immunology, Institute of Biomedicine, University of Turku, Turku, Finland. [Ti] Título: BLIMP-1 is insufficient to induce antibody secretion in the absence of IRF4 in DT40 cells. [So] Source: Scand J Immunol;87(3), 2018 Mar. [Is] ISSN: 1365-3083 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Differentiation of B cells into antibody-secreting cells (ASCs), plasmablasts and plasma cells is regulated by a network of transcription factors. Within this network, factors including PAX5 and BCL6 prevent ASC differentiation and maintain the B cell phenotype. In contrast, BLIMP-1 and high IRF4 expression promote plasma cell differentiation. BLIMP-1 is thought to induce immunoglobulin secretion, whereas IRF4 is needed for the survival of ASCs. The role of IRF4 in the regulation of antibody secretion has remained controversial. To study the role of IRF4 in the regulation of antibody secretion, we have created a double knockout (DKO) DT40 B cell line deficient in both IRF4 and BCL6. Although BCL6-deficient DT40 B cell line had upregulated BLIMP-1 expression and secreted antibodies, the DKO cell line did not. Even enforced BLIMP-1 expression in DKO cells or IRF4-deficient cells could not induce IgM secretion while in WT DT40 cells, it could. However, enforced IRF4 expression in DKO cells induced strong IgM secretion. Our findings support a model where IRF4 expression in addition to BLIMP-1 expression is required to induce robust antibody secretion. [Mh] Termos MeSH primário: Anticorpos/imunologia Formação de Anticorpos/genética Proteínas Aviárias/genética Linfócitos B/imunologia Fatores Reguladores de Interferon/genética Fator 1 de Ligação ao Domínio I Regulador Positivo/genética [Mh] Termos MeSH secundário: Animais Linfócitos B/citologia Diferenciação Celular/imunologia Linhagem Celular Proliferação Celular Galinhas Técnicas de Inativação de Genes Imunoglobulina M/biossíntese Imunoglobulina M/imunologia Fator de Transcrição PAX5/genética Fator 1 de Ligação ao Domínio I Regulador Positivo/imunologia Proteínas Proto-Oncogênicas c-bcl-6/genética [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies); 0 (Avian Proteins); 0 (IRF4 protein, Gallus gallus); 0 (Immunoglobulin M); 0 (Interferon Regulatory Factors); 0 (PAX5 Transcription Factor); 0 (Proto-Oncogene Proteins c-bcl-6); EC 2.1.1.- (Positive Regulatory Domain I-Binding Factor 1) [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: 180213 [St] Status: MEDLINE [do] DOI: 10.1111/sji.12646

2 / 199848

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[PMID]: 29373585 [Au] Autor: Espitia O; Chatelais M; Steenman M; Charrier C; Maurel B; Georges S; Houlgatte R; Verrecchia F; Ory B; Lamoureux F; Heymann D; Gouëffic Y; Quillard T [Ad] Endereço: INSERM, UMR 1238, Nantes, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire « Sarcome osseux et remodelage des tissus osseux calcifiés ¼, Faculté de Médecine, Nantes, France. [Ti] Título: Implication of molecular vascular smooth muscle cell heterogeneity among arterial beds in arterial calcification. [So] Source: PLoS One;13(1):e0191976, 2018. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Vascular calcification is a strong and independent predictive factor for cardiovascular complications and mortality. Our previous work identified important discrepancies in plaque composition and calcification types between carotid and femoral arteries. The objective of this study is to further characterize and understand the heterogeneity in vascular calcification among vascular beds, and to identify molecular mechanisms underlying this process. We established ECLAGEN biocollection that encompasses human atherosclerotic lesions and healthy arteries from different locations (abdominal, thoracic aorta, carotid, femoral, and infrapopliteal arteries) for histological, cell isolation, and transcriptomic analysis. Our results show that lesion composition differs between these locations. Femoral arteries are the most calcified arteries overall. They develop denser calcifications (sheet-like, nodule), and are highly susceptible to osteoid metaplasia. These discrepancies may derive from intrinsic differences between SMCs originating from these locations, as microarray analysis showed specific transcriptomic profiles between primary SMCs isolated from each arterial bed. These molecular differences translated into functional disparities. SMC from femoral arteries showed the highest propensity to mineralize due to an increase in basal TGFß signaling. Our results suggest that biological heterogeneity of resident vascular cells between arterial beds, reflected by our transcriptomic analysis, is critical in understanding plaque biology and calcification, and may have strong implications in vascular therapeutic approaches. [Mh] Termos MeSH primário: Artérias/patologia Calcinose/patologia Músculo Liso Vascular/patologia [Mh] Termos MeSH secundário: Diferenciação Celular Células Cultivadas Seres Humanos Placa Aterosclerótica/patologia Transcriptoma [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [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: 180127 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0191976

3 / 199848

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[PMID]: 29364956 [Au] Autor: Winzi M; Casas Vila N; Paszkowski-Rogacz M; Ding L; Noack S; Theis M; Butter F; Buchholz F [Ad] Endereço: Medical Systems Biology, Faculty of Medicine Carl Gustav Carus, University Cancer Center, TU Dresden, Dresden, Germany. [Ti] Título: The long noncoding RNA lncR492 inhibits neural differentiation of murine embryonic stem cells. [So] Source: PLoS One;13(1):e0191682, 2018. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: RNA interference (RNAi) screens have been shown to be valuable to study embryonic stem cell (ESC) self-renewal and they have been successfully applied to identify coding as well as noncoding genes required for maintaining pluripotency. Here, we used an RNAi library targeting >640 long noncoding RNAs (lncRNA) to probe for their role in early cell differentiation. Utilizing a Sox1-GFP ESC reporter cell line, we identified the lncRNA lncR492 as lineage-specific inhibitor of neuroectodermal differentiation. Molecular characterization showed that lncR492 interacts with the mRNA binding protein HuR and facilitates its inhibitory function by activation of Wnt signaling. Thus, lncRNAs modulate the fate decision of pluripotent stem cells. [Mh] Termos MeSH primário: Diferenciação Celular Células-Tronco Embrionárias/citologia Neurônios/citologia RNA Longo não Codificante/genética [Mh] Termos MeSH secundário: Animais Camundongos Interferência de RNA Reação em Cadeia da Polimerase Via Transcriptase Reversa [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (RNA, Long Noncoding) [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: 180125 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0191682

4 / 199848

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[PMID]: 29353044 [Au] Autor: Yamamoto H; Kurachi M; Naruse M; Shibasaki K; Ishizaki Y [Ad] Endereço: Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. [Ti] Título: BMP4 signaling in NPCs upregulates Bcl-xL to promote their survival in the presence of FGF-2. [So] Source: Biochem Biophys Res Commun;496(2):588-593, 2018 02 05. [Is] ISSN: 1090-2104 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: We previously reported that BMP4 does not promote proliferation or differentiation of CD44-positive astrocyte precursor cells (APCs) but greatly promotes their survival in the presence of fibroblast growth factor-2 (FGF-2). In this study, we examined if BMP4 acts as a survival factor also for neural stem/progenitor cells (NPCs) isolated from ganglionic eminence of neonatal mouse brain. We found BMP4 promotes survival but not proliferation or differentiation of these cells, just as in the case for CD44-positive APCs. Microarray analysis revealed some candidate molecules in the signaling pathway downstream of BMP4. Among them, we focused on Id1 (inhibitor of DNA-binding 1) and Bcl-xL in this study. Expression of both genes was promoted in the presence of BMP4, and this promotion was reduced by dorsomorphin, an inhibitor of BMP4 signaling. Furthermore, cytochrome c release from mitochondria was significantly reduced in the presence of BMP4, suggesting up-regulation of Bcl-xL activity by BMP4. Id1 siRNA reduced the expression of Bcl-xL, and negated survival promoting effect of BMP4. These data suggest that BMP4 promotes survival of NPCs by enhancing the anti-apoptotic function of Bcl-xL via BMP4-Smad1/5/8-Id1 signaling. [Mh] Termos MeSH primário: Proteína Morfogenética Óssea 4/metabolismo Fator 2 de Crescimento de Fibroblastos/metabolismo Células-Tronco Neurais/metabolismo Transdução de Sinais Proteína bcl-X/metabolismo [Mh] Termos MeSH secundário: Animais Apoptose Diferenciação Celular Proliferação Celular Sobrevivência Celular Células Cultivadas Camundongos Endogâmicos C57BL Células-Tronco Neurais/citologia Regulação para Cima Proteína bcl-X/genética [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Bcl2l1 protein, mouse); 0 (Bone Morphogenetic Protein 4); 0 (bcl-X Protein); 103107-01-3 (Fibroblast Growth Factor 2) [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: 180122 [St] Status: MEDLINE

5 / 199848

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[PMID]: 29349655 [Au] Autor: Lo WJ; Lin CL; Chang YC; Bai LY; Lin CY; Liang JA; Li LY; Chao LM; Chiu CF; Chen CM; Yeh SP [Ad] Endereço: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan. [Ti] Título: Total body irradiation tremendously impair the proliferation, differentiation and chromosomal integrity of bone marrow-derived mesenchymal stromal stem cells. [So] Source: Ann Hematol;97(4):697-707, 2018 Apr. [Is] ISSN: 1432-0584 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: Total body irradiation (TBI) is frequently used in hematopoietic stem cell transplantation (HSCT) and is associated with many complications due to radiation injury to the normal cells, including normal stem cells. Nevertheless, the effects of TBI on the mesenchymal stromal stem cell (MSC) are not fully understood. Bone marrow-derived MSCs (BM-MSCs) isolated from normal adults were irradiated with 200 cGy twice daily for consecutive 3 days, a regimen identical to that used in TBI-conditioning HSCT. The characteristics, differentiation potential, cytogenetics, hematopoiesis-supporting function, and carcinogenicity of the irradiated BM-MSCs were then compared to the non-irradiated control. The irradiated and non-irradiated MSCs shared similar morphology, phenotype, and hematopoiesis-supporting function. However, irradiated MSCs showed much lower proliferative and differentiative potential. Irradiation also induced clonal cytogenetic abnormalities of MSCs. Nevertheless, the carcinogenicity of irradiated MSCs is low in vitro and in vivo. In parallel with the ex vivo irradiation experiments, decreased proliferative and differentiative abilities and clonal cytogenetic abnormalities can also be found in MSCs isolated from transplant recipients who had received TBI-based conditioning previously. Thus, TBI used in HSCT drastically injury MSCs and may contribute to the development of some long-term complications associated with clonal cytogenetic abnormality and poor adipogenesis and osteogenesis after TBI. [Mh] Termos MeSH primário: Apoptose/efeitos da radiação Células da Medula Óssea/efeitos da radiação Aberrações Cromossômicas/efeitos da radiação Células-Tronco Hematopoéticas/efeitos da radiação Células Mesenquimais Estromais/efeitos da radiação Lesões por Radiação/patologia Irradiação Corporal Total/efeitos adversos [Mh] Termos MeSH secundário: Adulto Células-Tronco Adultas/efeitos da radiação Células da Medula Óssea/citologia Células da Medula Óssea/patologia Diferenciação Celular/efeitos da radiação Proliferação Celular/efeitos da radiação Células Cultivadas China Transtornos Cromossômicos/etiologia Transtornos Cromossômicos/patologia Feminino Transplante de Células-Tronco Hematopoéticas Células-Tronco Hematopoéticas/citologia Células-Tronco Hematopoéticas/patologia Hospitais Universitários Seres Humanos Leucemia/patologia Leucemia/terapia Masculino Células Mesenquimais Estromais/citologia Células Mesenquimais Estromais/patologia Necrose Lesões por Radiação/etiologia Condicionamento Pré-Transplante/efeitos adversos Células Tumorais Cultivadas Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE [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: 10.1007/s00277-018-3231-y

6 / 199848

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[PMID]: 29314175 [Au] Autor: Cohn M [Ad] Endereço: Conceptual Immunology Group, The Salk Institute, La Jolla, CA, USA. [Ti] Título: Somatic diversification of the B cell repertoire requires two cell subsets. [So] Source: Scand J Immunol;87(3), 2018 Mar. [Is] ISSN: 1365-3083 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Evolution found itself in a Catch-22 situation when selecting for the somatically derived paratopic repertoire of the humoral immune system. The B cell BCR repertoire can only be somatically diversified from a substrate of paratopes that is encoded in the germline. In order for the cells expressing that substrate to also be a target of germline selection, their BCRs must, independently, be of selective value by being expressed in a functionally important way in each individual. A somatically derived repertoire scrambles this substrate so that its specificities are lost, making it unselectable in the germline. Consequently, evolution faced an incompatibility. Here, we explore what it takes to resolve it. [Mh] Termos MeSH primário: Subpopulações de Linfócitos B/citologia Sítios de Ligação de Anticorpos/imunologia Diferenciação Celular/imunologia Região Variável de Imunoglobulina/imunologia Anticorpos de Domínio Único/imunologia [Mh] Termos MeSH secundário: Anticorpos/imunologia Subpopulações de Linfócitos B/imunologia Linhagem da Célula/imunologia Genes de Imunoglobulinas Seres Humanos Imunidade Humoral/imunologia Região Variável de Imunoglobulina/genética Anticorpos de Domínio Único/genética [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies); 0 (Immunoglobulin Variable Region); 0 (Single-Domain Antibodies) [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: 180110 [St] Status: MEDLINE [do] DOI: 10.1111/sji.12640

7 / 199848

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[PMID]: 29247860 [Au] Autor: Schulz-Fincke J; Hau M; Barth J; Robaa D; Willmann D; Kürner A; Haas J; Greve G; Haydn T; Fulda S; Lübbert M; Lüdeke S; Berg T; Sippl W; Schüle R; Jung M [Ad] Endereço: Institute of Pharmaceutical Sciences, University of Freiburg, Germany; German Cancer Consortium (DKTK), Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany. [Ti] Título: Structure-activity studies on N-Substituted tranylcypromine derivatives lead to selective inhibitors of lysine specific demethylase 1 (LSD1) and potent inducers of leukemic cell differentiation. [So] Source: Eur J Med Chem;144:52-67, 2018 Jan 20. [Is] ISSN: 1768-3254 [Cp] País de publicação: France [La] Idioma: eng [Ab] Resumo: FAD-dependent lysine-specific demethylase 1 (LSD1) is overexpressed or deregulated in many cancers such as AML and prostate cancer and hence is a promising anticancer target with first inhibitors in clinical trials. Clinical candidates are N-substituted derivatives of the dual LSD1-/monoamine oxidase-inhibitor tranylcypromine (2-PCPA) with a basic amine function in the N-substituent. These derivatives are selective over monoamine oxidases. So far, only very limited information on structure-activity studies about this important class of LSD1 inhibitors is published in peer reviewed journals. Here, we show that N-substituted 2-PCPA derivatives without a basic function or even a polar group are still potent inhibitors of LSD1 in vitro and effectively inhibit colony formation of leukemic cells in culture. Yet, these lipophilic inhibitors also block the structurally related monoamine oxidases (MAO-A and MAO-B), which may be of interest for the treatment of neurodegenerative disorders, but this property is undesired for applications in cancer treatment. The introduction of a polar, non-basic function led to optimized structures that retain potent LSD1 inhibitors but exhibit selectivity over MAOs and are highly potent in the suppression of colony formation of cultured leukemic cells. Cellular target engagement is shown via a Cellular Thermal Shift Assay (CETSA) for LSD1. [Mh] Termos MeSH primário: Inibidores Enzimáticos/química Inibidores Enzimáticos/farmacologia Histona Desmetilases/antagonistas & inibidores Tranilcipromina/análogos & derivados Tranilcipromina/farmacologia [Mh] Termos MeSH secundário: Animais Antineoplásicos/química Antineoplásicos/farmacologia Diferenciação Celular/efeitos dos fármacos Linhagem Celular Tumoral Histona Desmetilases/metabolismo Seres Humanos Leucemia/tratamento farmacológico Leucemia/metabolismo Leucemia/patologia Camundongos Modelos Moleculares Inibidores da Monoaminoxidase/química Inibidores da Monoaminoxidase/farmacologia Relação Estrutura-Atividade [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antineoplastic Agents); 0 (Enzyme Inhibitors); 0 (Monoamine Oxidase Inhibitors); 3E3V44J4Z9 (Tranylcypromine); EC 1.14.11.- (Histone Demethylases); EC 1.5.- (KDM1A protein, human) [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: 171217 [St] Status: MEDLINE

8 / 199848

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[PMID]: 29214781 [Au] Autor: Kim B; Choi KM; Yim HS; Park HT; Yim JH; Lee MG [Ad] Endereço: Department of Physiology, Korea University College of Medicine, Seoul, Korea. [Ti] Título: Adipogenic and Lipolytic Effects of Ascorbic Acid in Ovariectomized Rats. [So] Source: Yonsei Med J;59(1):85-91, 2018 Jan. [Is] ISSN: 1976-2437 [Cp] País de publicação: Korea (South) [La] Idioma: eng [Ab] Resumo: PURPOSE: Ascorbic acid has been reported to have an adipogenic effect on 3T3-L1 preadipocytes, while evidence also suggests that ascorbic acid reduces body weight in humans. In this study, we tested the effects of ascorbic acid on adipogenesis and the balance of lipid accumulation in ovariectomized rats, in addition to long-term culture of differentiated 3T3-L1 adipocytes. MATERIALS AND METHODS: Murine 3T3-L1 fibroblasts and ovariectomized rats were treated with ascorbic acid at various time points. In vitro adipogenesis was analyzed by Oil Red O staining, and in vivo body fat was measured by a body composition analyzer using nuclear magnetic resonance. RESULTS: When ascorbic acid was applied during an early time point in 3T3-L1 preadipocyte differentiation and after bilateral ovariectomy (OVX) in rats, adipogenesis and fat mass gain significantly increased, respectively. However, lipid accumulation in well-differentiated 3T3-L1 adipocytes showed a significant reduction when ascorbic acid was applied after differentiation (10 days after induction). Also, oral ascorbic acid administration 4 weeks after OVX in rats significantly reduced both body weight and subcutaneous fat layer. In comparison to the results of ascorbic acid, which is a well-known cofactor for an enzyme of collagen synthesis, and the antioxidant ramalin, a potent antioxidant but not a cofactor, showed only a lipolytic effect in well-differentiated 3T3-L1 adipocytes, not an adipogenic effect. CONCLUSION: Taking these results into account, we concluded that ascorbic acid has both an adipogenic effect as a cofactor of an enzymatic process and a lipolytic effect as an antioxidant. [Mh] Termos MeSH primário: Adipogenia/efeitos dos fármacos Ácido Ascórbico/farmacologia Lipólise/efeitos dos fármacos Ovariectomia [Mh] Termos MeSH secundário: Células 3T3-L1 Adipócitos/efeitos dos fármacos Adipócitos/metabolismo Animais Antioxidantes/farmacologia Composição Corporal/efeitos dos fármacos Peso Corporal/efeitos dos fármacos Diferenciação Celular/efeitos dos fármacos Feminino Fibroblastos/efeitos dos fármacos Fibroblastos/metabolismo Camundongos Ratos Sprague-Dawley [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antioxidants); PQ6CK8PD0R (Ascorbic Acid) [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: 171208 [St] Status: MEDLINE [do] DOI: 10.3349/ymj.2018.59.1.85

9 / 199848

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[PMID]: 28470444 [Au] Autor: Lim PN; Feng J; Wang Z; Chong M; Konishi T; Tan LG; Chan J; Thian ES [Ad] Endereço: Department of Mechanical Engineering, National University of Singapore, Singapore, 117 576, Singapore. [Ti] Título: In-vivo evaluation of subcutaneously implanted cell-loaded apatite microcarriers for osteogenic potency. [So] Source: J Mater Sci Mater Med;28(6):86, 2017 Jun. [Is] ISSN: 1573-4838 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Cell-loaded apatite microcarriers present as potential scaffolds for direct in-vivo delivery of cells post-expansion to promote bone regeneration. The objective of this study was to evaluate the osteogenic potency of human foetal mesenchymal stem cells (hfMSC)-loaded apatite microcarriers when implanted subcutaneously in a mouse model. This was done by examining for ectopic bone formation at 2 weeks, 1 month and 2 months, which were intended to coincide with the inflammation, healing and remodelling phases, respectively. Three histological examinations including haematoxylin and eosin staining to examine general tissue morphology, Masson's trichrome staining to identify tissue type, and Von Kossa staining to examine extent of tissue mineralisation were performed. In addition, immunohistochemistry assay of osteopontin was conducted to confirm active bone formation by the seeded hfMSCs. Results showed a high level of tissue organisation and new bone formation, with active bone remodelling being observed at the end of 2 months, and an increase in tissue density, organisation, and mineralisation could also be observed for hfMSC-loaded apatite microcarriers. Various cell morphology resembling that of osteoblasts and osteoclasts could be seen on the surfaces of the hfMSC-loaded apatite microcarriers, with presence of woven bone tissue formation being observed at the intergranular space. These observations were consistent with evidence of ectopic bone formation, which were absent in group containing apatite microcarriers only. Overall, results suggested that hfMSC-loaded apatite microcarriers retained their osteogenic potency after implantation, and provided an effective platform for bone tissue regeneration. [Mh] Termos MeSH primário: Apatitas/química Transplante de Células-Tronco Mesenquimais/métodos Células Mesenquimais Estromais/fisiologia Osteogênese/fisiologia [Mh] Termos MeSH secundário: Animais Diferenciação Celular Seres Humanos Teste de Materiais Camundongos Engenharia Tecidual/métodos Tecidos Suporte [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Apatites) [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: 170505 [St] Status: MEDLINE [do] DOI: 10.1007/s10856-017-5897-4

10 / 199848

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[PMID]: 28457748 [Au] Autor: Schneider RK; Mullally A; Dugourd A; Peisker F; Hoogenboezem R; Van Strien PMH; Bindels EM; Heckl D; Büsche G; Fleck D; Müller-Newen G; Wongboonsin J; Ventura Ferreira M; Puelles VG; Saez-Rodriguez J; Ebert BL; Humphreys BD; Kramann R [Ad] Endereço: Department of Hematology, Erasmus MC Cancer Institute, 3015CN Rotterdam, the Netherlands; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, RWTH Aachen University, 52074 Aachen, Germany. Electronic address: r.k.schneider@erasmusmc.nl. [Ti] Título: Gli1 Mesenchymal Stromal Cells Are a Key Driver of Bone Marrow Fibrosis and an Important Cellular Therapeutic Target. [So] Source: Cell Stem Cell;20(6):785-800.e8, 2017 Jun 01. [Is] ISSN: 1875-9777 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Bone marrow fibrosis (BMF) develops in various hematological and non-hematological conditions and is a central pathological feature of myelofibrosis. Effective cell-targeted therapeutics are needed, but the cellular origin of BMF remains elusive. Here, we show using genetic fate tracing in two murine models of BMF that Gli1 mesenchymal stromal cells (MSCs) are recruited from the endosteal and perivascular niche to become fibrosis-driving myofibroblasts in the bone marrow. Genetic ablation of Gli1 cells abolished BMF and rescued bone marrow failure. Pharmacological targeting of Gli proteins with GANT61 inhibited Gli1 cell expansion and myofibroblast differentiation and attenuated fibrosis severity. The same pathway is also active in human BMF, and Gli1 expression in BMF significantly correlates with the severity of the disease. In addition, GANT61 treatment reduced the myofibroblastic phenotype of human MSCs isolated from patients with BMF, suggesting that targeting of Gli proteins could be a relevant therapeutic strategy. [Mh] Termos MeSH primário: Diferenciação Celular/efeitos dos fármacos Proliferação Celular/efeitos dos fármacos Células Mesenquimais Estromais/metabolismo Miofibroblastos/metabolismo Mielofibrose Primária/tratamento farmacológico Piridinas/farmacologia Pirimidinas/farmacologia Proteína GLI1 em Dedos de Zinco/antagonistas & inibidores [Mh] Termos MeSH secundário: Animais Diferenciação Celular/genética Seres Humanos Células Mesenquimais Estromais/patologia Camundongos Camundongos Transgênicos Miofibroblastos/patologia Mielofibrose Primária/genética Mielofibrose Primária/metabolismo Mielofibrose Primária/patologia Proteína GLI1 em Dedos de Zinco/genética Proteína GLI1 em Dedos de Zinco/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (GANT 61); 0 (Gli protein, mouse); 0 (Pyridines); 0 (Pyrimidines); 0 (Zinc Finger Protein GLI1) [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: 170502 [St] Status: MEDLINE

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1			PalavrasDescritor de assuntoDescritor de assunto primárioLimitesAutorPalavras do títuloPalavras do resumoIdiomaPaís de publicaçãoNome de substânciaNome de pessoa como assuntoRevistaAssunto de RevistaISSNTipo de publicaçãoIdentificador únicoMês de entradaAno de publicaçãoTexto completoAtualização por classeCategoria DeCSCategoria DeCS explodidaCategoria CID-10SubSetsPais de AfiliaçãoAfiliaçãoAfiliação 2
2	and or and not		PalavrasDescritor de assuntoDescritor de assunto primárioLimitesAutorPalavras do títuloPalavras do resumoIdiomaPaís de publicaçãoNome de substânciaNome de pessoa como assuntoRevistaAssunto de RevistaISSNTipo de publicaçãoIdentificador únicoMês de entradaAno de publicaçãoTexto completoAtualização por classeCategoria DeCSCategoria DeCS explodidaCategoria CID-10SubSetsPais de AfiliaçãoAfiliaçãoAfiliação 2
3	and or and not		PalavrasDescritor de assuntoDescritor de assunto primárioLimitesAutorPalavras do títuloPalavras do resumoIdiomaPaís de publicaçãoNome de substânciaNome de pessoa como assuntoRevistaAssunto de RevistaISSNTipo de publicaçãoIdentificador únicoMês de entradaAno de publicaçãoTexto completoAtualização por classeCategoria DeCSCategoria DeCS explodidaCategoria CID-10SubSetsPais de AfiliaçãoAfiliaçãoAfiliação 2

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