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[PMID]: 28726057 [Au] Autor: Fex Svenningsen Å; Löring S; Sørensen AL; Huynh HUB; Hjæresen S; Martin N; Moeller JB; Elkjær ML; Holmskov U; Illes Z; Andersson M; Nielsen SB; Benedikz E [Ad] Endereço: Department of Molecular Medicine-Neurobiology Research, University of Southern Denmark, J.B. Winslows Vej 21.1, 5000, Odense, Denmark. aasvenningsen@health.sdu.dk. [Ti] Título: Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1. [So] Source: Cell Mol Life Sci;74(24):4561-4572, 2017 Dec. [Is] ISSN: 1420-9071 [Cp] País de publicação: Switzerland [La] Idioma: eng [Ab] Resumo: Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cellular level. It is upregulated in neurodegenerative diseases and cancer although its function is far from clear. Here, we report the finding of a new binding partner to MIF, the serine protease HTRA1. This enzyme cleaves several growth factors, extracellular matrix molecules and is implicated in some of the same diseases as MIF. We show that the function of the binding between MIF and HTRA1 is to inhibit the proteolytic activity of HTRA1, modulating the availability of molecules that can change cell growth and differentiation. MIF is therefore the first endogenous inhibitor ever found for HTRA1. It was found that both molecules were present in astrocytes and that the functional binding has the ability to modulate astrocytic activities important in development and disease of the CNS. [Mh] Termos MeSH primário: Oxirredutases Intramoleculares/metabolismo Fatores Inibidores da Migração de Macrófagos/metabolismo Serina Endopeptidases/metabolismo Transdução de Sinais/fisiologia [Mh] Termos MeSH secundário: Animais Astrócitos/metabolismo Astrócitos/fisiologia Diferenciação Celular/fisiologia Linhagem Celular Proliferação Celular/fisiologia Sistema Nervoso Central/metabolismo Sistema Nervoso Central/fisiologia Células HEK293 Serina Peptidase 1 de Requerimento de Alta Temperatura A Seres Humanos Camundongos Camundongos Endogâmicos C57BL Ligação Proteica/fisiologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Macrophage Migration-Inhibitory Factors); EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1); EC 3.4.21.- (HtrA1 protein, human); EC 3.4.21.- (Serine Endopeptidases); EC 5.3.- (Intramolecular Oxidoreductases); EC 5.3.2.1 (MIF protein, human) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171117 [Lr] Data última revisão: 171117 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170721 [St] Status: MEDLINE [do] DOI: 10.1007/s00018-017-2592-z

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[PMID]: 28637435 [Au] Autor: Zhou YL; Chen CL; Wang YX; Tong Y; Fang XL; Li L; Wang ZY [Ad] Endereço: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China. [Ti] Título: Association between polymorphism rs11200638 in the HTRA1 gene and the response to anti-VEGF treatment of exudative AMD: a meta-analysis. [So] Source: BMC Ophthalmol;17(1):97, 2017 Jun 21. [Is] ISSN: 1471-2415 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: Anti-angiogenesis treatments are the most commonly used treatments for the vision loss caused by exudative age-related macular degeneration (AMD), in which the anti-vascular endothelial growth factor (VEGF) drugs with ranibizumab and bevacizumab are current standard treatments. However, the outcome of anti-VEGF therapeutics is not uniform in all patients. METHODS: We performed a literature-based meta-analysis including, five published studies relevant to HTRA1 and response to anti-VEGF treatment (bevacizumab or ranibizumab). Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed- and random-effects models. Sensitivity analysis and meta-regression were also performed. Q-statistic test and Egger's test was used to evaluate heterogeneity and publication bias respectively. RESULTS: Overall, no association between the rs11200638 polymorphism in HTRA1 gene and the anti-VEGF treatment response was found in the genotype GG versus AA (OR = 1.06; 95% CI: 0.77 to 1.48; P = 0.98), genotype GA versus AA (OR = 1.11; 95% CI: 0.83 to 1.47; P = 0.93), genotype GG + GA versus AA (OR = 1.22; 95% CI: 0.94 to 1.57; P = 0.09), and allele G versus A (OR = 0.92; 95% CI: 0.78 to 1.08; P = 0.14). In the subgroup analysis by ethnicity Caucasian population, and a significant association was still not observed in all genetic models. Sensitivity analysis indicated the robustness of our findings, and no publication bias was observed in our meta-analysis. CONCLUSIONS: This study shows that there was no association between the polymorphism rs11200638 in HTRA1 gene and response to anti-VEGF treatment of exudative AMD. However, more studies are needed to further prove the conclusion of present study, especially well-designed and high quality randomised controlled trials or intervention studies. [Mh] Termos MeSH primário: Inibidores da Angiogênese/uso terapêutico DNA/genética Predisposição Genética para Doença Polimorfismo de Nucleotídeo Único Serina Endopeptidases/genética Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores Degeneração Macular Exsudativa [Mh] Termos MeSH secundário: Alelos Genótipo Serina Peptidase 1 de Requerimento de Alta Temperatura A Seres Humanos Serina Endopeptidases/metabolismo Degeneração Macular Exsudativa/tratamento farmacológico Degeneração Macular Exsudativa/genética Degeneração Macular Exsudativa/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; META-ANALYSIS; REVIEW [Nm] Nome de substância: 0 (Angiogenesis Inhibitors); 0 (Vascular Endothelial Growth Factor A); 9007-49-2 (DNA); EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1); EC 3.4.21.- (HtrA1 protein, human); EC 3.4.21.- (Serine Endopeptidases) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170623 [St] Status: MEDLINE [do] DOI: 10.1186/s12886-017-0487-2

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[PMID]: 28126975 [Au] Autor: Uemura M; Nozaki H; Onodera O [Ad] Endereço: Department of Neurology, Clinical Neuroscience Branch, Brain Research Institute, Niigata University. [Ti] Título: [Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CARASIL)]. [So] Source: Brain Nerve;69(1):25-33, 2017 Jan. [Is] ISSN: 1881-6096 [Cp] País de publicação: Japan [La] Idioma: jpn [Ab] Resumo: Cerebral small vessel disease (CSVD) is frequently observed among the elderly and is known to cause dementia and gait disturbance associated with white matter lesions, lacunar infarcts, and cerebral hemorrhage. Molecular mechanistic studies promise to provide new insights into the pathogenesis of hereditary CSVD. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is one of the hereditary CSVDs caused by a mutation in the high-temperature requirement serine peptidase A1 (HTRA1) gene. The loss of HTRA1 protease activity increases signaling via transforming growth factor (TGF)ß, thereby resulting in CARASIL. Although the CARASIL has been characterized by juvenile onset alopecia and spondylosis deformans, these features are not always observed in individuals with an HTRA1 mutation. Moreover, some HTRA1 mutations cause CSVD in heterozygous states. Therefore, the clinical features of CSVD resulting from an HTRA1 mutation extend to patients with CSVD alone or to those with dominantly inherited CSVD. [Mh] Termos MeSH primário: Alopecia Infarto Cerebral Leucoencefalopatias Doenças da Coluna Vertebral [Mh] Termos MeSH secundário: Adolescente Adulto Alopecia/diagnóstico por imagem Alopecia/genética Alopecia/metabolismo Infarto Cerebral/diagnóstico por imagem Infarto Cerebral/genética Infarto Cerebral/metabolismo Criança Pré-Escolar Feminino Serina Peptidase 1 de Requerimento de Alta Temperatura A Seres Humanos Lactente Recém-Nascido Leucoencefalopatias/diagnóstico por imagem Leucoencefalopatias/genética Leucoencefalopatias/metabolismo Masculino Meia-Idade Mutação Serina Endopeptidases/genética Serina Endopeptidases/metabolismo Transdução de Sinais Doenças da Coluna Vertebral/diagnóstico por imagem Doenças da Coluna Vertebral/genética Doenças da Coluna Vertebral/metabolismo Fator de Crescimento Transformador beta1/metabolismo Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (TGFB1 protein, human); 0 (Transforming Growth Factor beta1); EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1); EC 3.4.21.- (HtrA1 protein, human); EC 3.4.21.- (Serine Endopeptidases) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170128 [St] Status: MEDLINE [do] DOI: 10.11477/mf.1416200631

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[PMID]: 28114575 [Au] Autor: Tosi GM; Caldi E; Neri G; Nuti E; Marigliani D; Baiocchi S; Traversi C; Cevenini G; Tarantello A; Fusco F; Nardi F; Orlandini M; Galvagni F [Ad] Endereço: Ophthalmology Unit of the Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. [Ti] Título: HTRA1 and TGF-ß1 Concentrations in the Aqueous Humor of Patients With Neovascular Age-Related Macular Degeneration. [So] Source: Invest Ophthalmol Vis Sci;58(1):162-167, 2017 Jan 01. [Is] ISSN: 1552-5783 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Purpose: The purpose of this study was to evaluate the expression of high-temperature requirement A serine peptidase 1 (HTRA1), TGF-ß1, bone morphogenetic protein 4 (BMP4), growth differentiation factor 6 (GDF6), and VEGFA proteins in the aqueous humor of patients with naïve choroidal neovascularization (nCNV) secondary to AMD. Methods: We measured by ELISA the concentrations of HTRA1, TGF-ß1, BMP4, GDF6, and VEGFA in the aqueous humor of 23 patients affected by nCNV who received three consecutive monthly intravitreal injections of 0.5 mg ranibizumab. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). Twenty-three age-matched cataract patients served as controls. Results: Bone morphogenetic protein 4 and GDF6 were not detectable in any samples. Baseline HTRA1 was higher than controls (P < 0.0001) and higher than both the month 1 (P < 0.0001) and the month 2 (P < 0.0001) values. Baseline VEGFA was higher than controls (P < 0.0001), not different from month 1 value (P = 0.0821), but higher than month 2 value (P < 0.0001). Baseline TGF-ß1 was higher than controls (P = 0.0015) and not different from month 1 (P = 0.129) and month 2 values (P = 0.5529). No correlation was found in naïve patients between concentrations of HTRA1 and TGF-ß1, HTRA 1 and VEGFA, or TGF-ß1 and VEGFA. Conclusions: In nCNV patients, HTRA1 and TGF-ß1 were significantly higher compared to controls. After treatment, TGF-ß1 was persistently elevated, while HTRA1 returned to control levels, suggesting the involvement of TGF-ß1 and HTRA1 in neovascular AMD and a VEGFA-independent role for TGF-ß1. [Mh] Termos MeSH primário: Humor Aquoso/metabolismo Neovascularização de Coroide/metabolismo Serina Endopeptidases/metabolismo Fator de Crescimento Transformador beta1/metabolismo Degeneração Macular Exsudativa/metabolismo [Mh] Termos MeSH secundário: Idoso Inibidores da Angiogênese/administração & dosagem Biomarcadores/metabolismo Neovascularização de Coroide/diagnóstico Neovascularização de Coroide/tratamento farmacológico Ensaio de Imunoadsorção Enzimática Feminino Angiofluoresceinografia Seguimentos Fundo de Olho Serina Peptidase 1 de Requerimento de Alta Temperatura A Seres Humanos Injeções Intravítreas Masculino Estudos Prospectivos Ranibizumab/administração & dosagem Acuidade Visual Degeneração Macular Exsudativa/diagnóstico Degeneração Macular Exsudativa/tratamento farmacológico [Pt] Tipo de publicação: JOURNAL ARTICLE; OBSERVATIONAL STUDY [Nm] Nome de substância: 0 (Angiogenesis Inhibitors); 0 (Biomarkers); 0 (Transforming Growth Factor beta1); EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1); EC 3.4.21.- (HtrA1 protein, human); EC 3.4.21.- (Serine Endopeptidases); ZL1R02VT79 (Ranibizumab) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170124 [St] Status: MEDLINE [do] DOI: 10.1167/iovs.16-20922

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[PMID]: 27879347 [Au] Autor: Grassmann F; Heid IM; Weber BH; International AMD Genomics Consortium (IAMDGC) [Ad] Endereço: Institute for Human Genetics, University of Regensburg, D-93053 Regensburg, Germany. [Ti] Título: Recombinant Haplotypes Narrow the ARMS2/HTRA1 Association Signal for Age-Related Macular Degeneration. [So] Source: Genetics;205(2):919-924, 2017 Feb. [Is] ISSN: 1943-2631 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Age-related macular degeneration (AMD) is the leading cause of blindness in ageing societies, triggered by both environmental and genetic factors. The strongest genetic signal for AMD with odds ratios of up to 2.8 per adverse allele was found previously over a chromosomal region in 10q26 harboring two genes, ARMS2 and HTRA1, although with little knowledge as to which gene or genetic variation is functionally relevant to AMD pathology. In this study, we analyzed rare recombinant haplotypes in 16,144 AMD cases and 17,832 controls from the International AMD Genomics Consortium and identified variants in ARMS2 but not HTRA1 to exclusively carry the AMD risk with P-values between 1.0 × 10 and 6.7 × 10 This now allows prioritization of the gene of interest for subsequent functional studies. [Mh] Termos MeSH primário: Haplótipos Degeneração Macular/genética Proteínas/genética Serina Endopeptidases/genética [Mh] Termos MeSH secundário: Estudos de Casos e Controles Serina Peptidase 1 de Requerimento de Alta Temperatura A Seres Humanos Polimorfismo Genético [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (ARMS2 protein, human); 0 (Proteins); EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1); EC 3.4.21.- (HtrA1 protein, human); EC 3.4.21.- (Serine Endopeptidases) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161124 [St] Status: MEDLINE [do] DOI: 10.1534/genetics.116.195966

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[PMID]: 27841854 [Au] Autor: Ng TK; Liang XY; Lu F; Liu DT; Yam GH; Ma L; Tam PO; Chen H; Cen LP; Chen LJ; Yang Z; Pang CP [Ad] Endereço: Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong. [Ti] Título: Protective effects of an HTRA1 insertion-deletion variant against age-related macular degeneration in the Chinese populations. [So] Source: Lab Invest;97(1):43-52, 2017 Jan. [Is] ISSN: 1530-0307 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Age-related macular degeneration (AMD) is a leading cause of visual impairment and irreversible blindness in most developed countries, affecting about 50 million elderly people worldwide. Retinal pigment epithelial (RPE) cell degeneration is the pathophysiological cause of AMD, leading to geographic atrophy and choroidal neovascularization. We and others have previously identified several polymorphisms on chromosome 10q26 (HTRA1 rs11200638 as well as LOC387715 rs10490924 and c.372_815del443ins54) associated with AMD. In this study, we confirmed the association of our previously identified HTRA1 insertion-deletion (indel) variant (c.34delCinsTCCT) in 195 exudative AMD patients and 390 controls from the Hong Kong Chinese cohort with additional 168 patients and 210 controls from the Chengdu Chinese cohort and followed by studying its biological functions in RPE cells. Genetic analysis verified the higher prevalence of c.34delCinsTCCT allele in control subjects (8.0%) than in AMD patients (1.9%; P=7.87 × 10 , odds ratio=0.229). This protective effect was validated as the haplotype of the c.34delCinsTCCT allele existed independent of the risk haplotype (P=1.17 × 10 ). In vitro studies showed that recombinant HTRA1 c.34delCinsTCCT variant protein was more localized in the endoplasmic reticulum of RPE cells compared with the wild-type protein, and its secretion was delayed. Moreover, ARPE-19 cells expressing HTRA1 c.34delCinsTCCT variant had higher cell viability, lower cell apoptosis and were less responsive to anoikis, supporting its protective role. We revealed a protective AMD-associated HTRA1 variant in Chinese populations and the biological role of HTRA1 in RPE cell degeneration, indicating its involvement in AMD pathogenesis. [Mh] Termos MeSH primário: Predisposição Genética para Doença/genética Mutação INDEL Degeneração Macular/genética Serina Endopeptidases/genética [Mh] Termos MeSH secundário: Idoso Idoso de 80 Anos ou mais Alelos Grupo com Ancestrais do Continente Asiático/genética Sequência de Bases Linhagem Celular Células Cultivadas China Feminino Expressão Gênica Frequência do Gene Predisposição Genética para Doença/etnologia Genótipo Haplótipos Serina Peptidase 1 de Requerimento de Alta Temperatura A Hong Kong Seres Humanos Immunoblotting Degeneração Macular/etnologia Masculino Metanálise como Assunto Meia-Idade Epitélio Pigmentado da Retina/citologia Epitélio Pigmentado da Retina/metabolismo Reação em Cadeia da Polimerase Via Transcriptase Reversa Serina Endopeptidases/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1); EC 3.4.21.- (HtrA1 protein, human); EC 3.4.21.- (Serine Endopeptidases) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161115 [St] Status: MEDLINE [do] DOI: 10.1038/labinvest.2016.117

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[PMID]: 27073013 [Au] Autor: MacDonald TM; Kaitu'u-Lino TJ; Walker SP; Dane KM; Lockie EB; Tong S; Whitehead CL; Hui L [Ad] Endereço: a Translational Obstetrics Group, Mercy Hospital for Women , Melbourne , Heidelberg , Australia. [Ti] Título: Variable effect of maternal oral glucose load on circulating cell-free placental mRNAs. [So] Source: J Matern Fetal Neonatal Med;30(5):501-503, 2017 Mar. [Is] ISSN: 1476-4954 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: It is not known whether fasting affects levels of circulating placenta-specific transcripts. OBJECTIVE: To assess whether a glucose load affects circulating placenta-specific transcripts. METHOD: RNA was extracted from paired blood samples (fasting and 1-h post 75 g oral glucose) from 22 women. Placenta-specific genes were measured by RT-qPCR. RESULTS: There was no change in ADM, CSH1, PAPPA2, PSG1 or TAC3 expression between fasting and post-glucose states. However, HTRA1 decreased after glucose load. CONCLUSION: Maternal fasting state does not influence expression of the majority of placenta-specific genes but may need to be accounted for when validating biomarkers of placental disease. [Mh] Termos MeSH primário: Jejum/metabolismo Expressão Gênica Glucose/metabolismo Placenta/metabolismo Proteína Plasmática A Associada à Gravidez/metabolismo RNA Mensageiro/sangue Serina Endopeptidases/sangue [Mh] Termos MeSH secundário: Adulto Biomarcadores/sangue Feminino Retardo do Crescimento Fetal/sangue Serina Peptidase 1 de Requerimento de Alta Temperatura A Seres Humanos Circulação Placentária Gravidez Proteína Plasmática A Associada à Gravidez/genética Serina Endopeptidases/genética Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Biomarkers); 0 (RNA, Messenger); EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1); EC 3.4.21.- (HtrA1 protein, human); EC 3.4.21.- (Serine Endopeptidases); EC 3.4.24.- (Pregnancy-Associated Plasma Protein-A); IY9XDZ35W2 (Glucose) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160414 [St] Status: MEDLINE [do] DOI: 10.1080/14767058.2016.1177815

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[PMID]: 28076935 [Au] Autor: Tossetta G; Avellini C; Licini C; Giannubilo SR; Castellucci M; Marzioni D [Ad] Endereço: Polytechnic University of Marche, Department of Experimental and Clinical Medicine. g.tossetta@univpm.it. [Ti] Título: High temperature requirement A1 and fibronectin: two possible players in placental tissue remodelling. [So] Source: Eur J Histochem;60(4):2724, 2016 Nov 21. [Is] ISSN: 2038-8306 [Cp] País de publicação: Italy [La] Idioma: eng [Ab] Resumo: High temperature requirement A1 (HtrA1) is a secreted protease involved in placental development. Fibronectin (FN) is involved in important process such as wound healing, cell adhesion and spreading, growth, migration, and differentiation. The purpose of this study was to analyse the expression patterns of HtrA1 in relationship to FN and to the key growth zones of placenta such as mesenchymal villi as well as cell islands and cell columns. We demonstrated that FN and HtrA1 are localized in the placental key growth zones suggesting a pivotal role in maintaining the balance among the molecules involved in the placental development and differentiation. [Mh] Termos MeSH primário: Vilosidades Coriônicas/metabolismo Fibronectinas/biossíntese Regulação da Expressão Gênica/fisiologia Serina Endopeptidases/biossíntese [Mh] Termos MeSH secundário: Feminino Serina Peptidase 1 de Requerimento de Alta Temperatura A Seres Humanos Gravidez [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Fibronectins); EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1); EC 3.4.21.- (HtrA1 protein, human); EC 3.4.21.- (Serine Endopeptidases) [Em] Mês de entrada: 1702 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170113 [St] Status: MEDLINE [do] DOI: 10.4081/ejh.2016.2724

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[PMID]: 27959899 [Au] Autor: Howie RN; Durham EL; Black L; Bennfors G; Parsons TE; Elsalanty ME; Yu JC; Weinberg SM; Cray JJ [Ad] Endereço: Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina, United States of America. [Ti] Título: Effects of In Utero Thyroxine Exposure on Murine Cranial Suture Growth. [So] Source: PLoS One;11(12):e0167805, 2016. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Large scale surveillance studies, case studies, as well as cohort studies have identified the influence of thyroid hormones on calvarial growth and development. Surveillance data suggests maternal thyroid disorders (hyperthyroidism, hypothyroidism with pharmacological replacement, and Maternal Graves Disease) are linked to as much as a 2.5 fold increased risk for craniosynostosis. Craniosynostosis is the premature fusion of one or more calvarial growth sites (sutures) prior to the completion of brain expansion. Thyroid hormones maintain proper bone mineral densities by interacting with growth hormone and aiding in the regulation of insulin like growth factors (IGFs). Disruption of this hormonal control of bone physiology may lead to altered bone dynamics thereby increasing the risk for craniosynostosis. In order to elucidate the effect of exogenous thyroxine exposure on cranial suture growth and morphology, wild type C57BL6 mouse litters were exposed to thyroxine in utero (control = no treatment; low ~167 ng per day; high ~667 ng per day). Thyroxine exposed mice demonstrated craniofacial dysmorphology (brachycranic). High dose exposed mice showed diminished area of the coronal and widening of the sagittal sutures indicative of premature fusion and compensatory growth. Presence of thyroid receptors was confirmed for the murine cranial suture and markers of proliferation and osteogenesis were increased in sutures from exposed mice. Increased Htra1 and Igf1 gene expression were found in sutures from high dose exposed individuals. Pathways related to the HTRA1/IGF axis, specifically Akt and Wnt, demonstrated evidence of increased activity. Overall our data suggest that maternal exogenous thyroxine exposure can drive calvarial growth alterations and altered suture morphology. [Mh] Termos MeSH primário: Suturas Cranianas/efeitos dos fármacos Efeitos Tardios da Exposição Pré-Natal/patologia Tiroxina/efeitos adversos [Mh] Termos MeSH secundário: Animais Feminino Serina Peptidase 1 de Requerimento de Alta Temperatura A Fator de Crescimento Insulin-Like I/genética Fator de Crescimento Insulin-Like I/metabolismo Masculino Camundongos Camundongos Endogâmicos C57BL Gravidez Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagem Efeitos Tardios da Exposição Pré-Natal/metabolismo Proteínas Proto-Oncogênicas c-akt/genética Proteínas Proto-Oncogênicas c-akt/metabolismo Serina Endopeptidases/genética Serina Endopeptidases/metabolismo Via de Sinalização Wnt/genética [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 67763-96-6 (Insulin-Like Growth Factor I); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1); EC 3.4.21.- (HtrA1 protein, mouse); EC 3.4.21.- (Serine Endopeptidases); Q51BO43MG4 (Thyroxine) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161214 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0167805

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[PMID]: 27809811 [Au] Autor: Stuqui B; Conceição AL; Termini L; Sichero L; Villa LL; Rahal P; Calmon MF [Ad] Endereço: Department of Biology, Instituto de Biociências, Letras e Ciências Exatas - IBILCE/UNESP, Rua Cristóvão Colombo n° 2265, Jardim Nazareth, CEP 15054-000, São José do Rio Preto, SP, Brazil. [Ti] Título: The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation. [So] Source: BMC Cancer;16(1):840, 2016 11 03. [Is] ISSN: 1471-2407 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: High-risk human papillomaviruses (HPVs) are strongly associated with the development of some malignancies. The E6 and E7 viral oncoproteins are the primary proteins responsible for cell homeostasis alteration and immortalization. Furthermore, the E6 protein from high-risk HPVs can interact with the PDZ (PSD-90/Dlg/ZO-1) domains of cellular proteins, triggering cell transformation. One protein that is associated with pathological conditions and has a PDZ domain is the protease HTRA1 (high temperature requirement 1). This protein is poorly expressed in some cancers, suggesting a tumor suppressor role. The aim of this study was to evaluate the effect of HTRA1 overexpression in HPV16-positive (CasKi) and HPV-negative (C33) cervical cell lines. METHODS: The cells were transfected with a vector containing the HTRA1 ORF or an empty vector. HTRA1 overexpression was confirmed by qRT-PCR. The cells were subjected to cell proliferation, colony formation, apoptosis and cell cycle assays. RESULTS: C33 cells expressing HTRA1 grew significantly fewer colonies and showed less proliferation than cells without HTRA1 expression. In contrast, in the CasKi cells overexpressing HTRA1, there was an increase in the cell growth rate and in the colonies density compared to cells expressing low levels of HTRA1. An apoptosis assay showed that HTRA1 does not interfere with the apoptosis rate in these cells. A cell cycle immunofluorescence assay revealed more CasKi cells overexpressing HTRA1 in the S phase and more C33 HTRA1-transfected cells in the G0/G1 phase, suggesting that HTRA1 plays different roles in the cell cycle progression of these cells. CONCLUSIONS: HTRA1 overexpression prevents cell proliferation in the HPV-negative cell line and increases cell proliferation in the HPV-positive cell line. Although the E6/HTRA1 interaction has already been described in the literature, more studies are required to confirm whether the present functional findings are a result of this interaction. [Mh] Termos MeSH primário: Proliferação Celular Transformação Celular Neoplásica/patologia Papillomaviridae/patogenicidade Infecções por Papillomavirus/patologia Serina Endopeptidases/metabolismo Neoplasias do Colo do Útero/patologia [Mh] Termos MeSH secundário: Apoptose Ciclo Celular Transformação Celular Neoplásica/metabolismo Feminino Serina Peptidase 1 de Requerimento de Alta Temperatura A Seres Humanos Infecções por Papillomavirus/metabolismo Infecções por Papillomavirus/virologia Células Tumorais Cultivadas Neoplasias do Colo do Útero/metabolismo Neoplasias do Colo do Útero/virologia [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1); EC 3.4.21.- (HtrA1 protein, human); EC 3.4.21.- (Serine Endopeptidases) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 171121 [Lr] Data última revisão: 171121 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161105 [St] Status: MEDLINE

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