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Pesquisa : D12.644.848.937 [Categoria DeCS]
Referências encontradas : 103 [refinar]
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[PMID]:28926584
[Au] Autor:Spiegler V; Hensel A; Seggewiß J; Lubisch M; Liebau E
[Ad] Endereço:Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Münster, Germany.
[Ti] Título:Transcriptome analysis reveals molecular anthelmintic effects of procyanidins in C. elegans.
[So] Source:PLoS One;12(9):e0184656, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Worldwide, more than 1 billion people are affected by infestations with soil-transmitted helminths and also in veterinary medicine helminthiases are a severe threat to livestock due to emerging resistances against the common anthelmintics. Proanthocyanidins have been increasingly investigated for their anthelmintic properties, however, except for an interaction with certain proteins of the nematodes, not much is known about their mode of action. To investigate the anthelmintic activity on a molecular level, a transcriptome analysis was performed in Caenorhabditis elegans after treatment with purified and fully characterized oligomeric procyanidins (OPC). The OPCs had previously been obtained from a hydro-ethanolic (1:1) extract from the leaves of Combretum mucronatum, a plant which is traditionally used in West Africa for the treatment of helminthiasis, therefore, also the crude extract was included in the study. Significant changes in differential gene expression were observed mainly for proteins related to the intestine, many of which were located extracellularly or within cellular membranes. Among the up-regulated genes, several hitherto undescribed orthologues of structural proteins in humans were identified, but also genes that are potentially involved in the worms' defense against tannins. For example, T22D1.2, an orthologue of human basic salivary proline-rich protein (PRB) 2, and numr-1 (nuclear localized metal responsive) were found to be strongly up-regulated. Down-regulated genes were mainly associated with lysosomal activity, glycoside hydrolysis or the worms' innate immune response. No major differences were found between the groups treated with purified OPCs versus the crude extract. Investigations using GFP reporter gene constructs of T22D1.2 and numr-1 corroborated the intestine as the predominant site of the anthelmintic activity. The current findings support previous hypotheses of OPCs interacting with intestinal surface proteins and provide the first insights into the nematode's response to OPCs on a molecular level as a base for the identification of future drug targets.
[Mh] Termos MeSH primário: Anti-Helmínticos/farmacologia
Caenorhabditis elegans/genética
Regulação para Baixo/efeitos dos fármacos
Proantocianidinas/farmacologia
Regulação para Cima/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Anti-Helmínticos/isolamento & purificação
Caenorhabditis elegans/efeitos dos fármacos
Caenorhabditis elegans/metabolismo
Proteínas de Caenorhabditis elegans/genética
Proteínas de Caenorhabditis elegans/metabolismo
Combretum/química
Combretum/metabolismo
Perfilação da Expressão Gênica
Genes Reporter
Microscopia de Fluorescência
Proteínas Nucleares/genética
Proteínas Nucleares/metabolismo
Extratos Vegetais/química
Folhas de Planta/química
Folhas de Planta/metabolismo
Proantocianidinas/isolamento & purificação
RNA/isolamento & purificação
RNA/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Proteínas Salivares Ricas em Prolina/genética
Proteínas Salivares Ricas em Prolina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthelmintics); 0 (Caenorhabditis elegans Proteins); 0 (Nuclear Proteins); 0 (Numr-1 protein, C elegans); 0 (Plant Extracts); 0 (Proanthocyanidins); 0 (Salivary Proline-Rich Proteins); 63231-63-0 (RNA)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184656


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[PMID]:28317766
[Au] Autor:García-Estévez I; Cruz L; Oliveira J; Mateus N; de Freitas V; Soares S
[Ad] Endereço:REQUIMTE/LAQV, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal. Electronic address: ignacio.estevez@fc.up.pt.
[Ti] Título:First evidences of interaction between pyranoanthocyanins and salivary proline-rich proteins.
[So] Source:Food Chem;228:574-581, 2017 Aug 01.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The contribution of other classes of polyphenol compounds besides tannins to the overall perception of astringency is still poorly understood. So, this work aimed to study the interaction between a family of salivary proline-rich proteins (aPRPs) and representative pyranoanthocyanins in red wines [pyranomalvidin-3-glucoside (vitisin B), pyranomalvidin-3-glucoside-catechol, and pyranomalvidin-3-glucoside-epicatechin] using saturation transfer difference-NMR and MALDI-TOF. For vitisin B K was of 1.74mM; for pyranomalvidin-3-glucoside-catechol was 1.17mM and for pyranomalvidin-3-glucoside-epicatechin it was 0.87mM. The presence of the flavanol structural unit in the pyranoanthocyanins led to an increase in their interaction with aPRPs. Further, it is also interesting that the values obtained were in the range of K obtained previously reported for the interaction between the human saliva proline-rich peptides (IB7 and IB9 ) and procyanidins. Overall, the results obtained suggest that, along with tannins, other polyphenols present in red wine, namely pyranoanthocyanins, could actively contribute to red wine global astringency.
[Mh] Termos MeSH primário: Antocianinas/metabolismo
Proteínas Salivares Ricas em Prolina/metabolismo
[Mh] Termos MeSH secundário: Antocianinas/química
Seres Humanos
Espectrometria de Massas/métodos
Proteínas Salivares Ricas em Prolina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthocyanins); 0 (Salivary Proline-Rich Proteins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170501
[Lr] Data última revisão:
170501
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170321
[St] Status:MEDLINE


  3 / 103 MEDLINE  
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[PMID]:27567443
[Au] Autor:Al-Saran N; Subash-Babu P; Al-Nouri DM; Alfawaz HA; Alshatwi AA
[Ad] Endereço:Cancer Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
[Ti] Título:Zinc enhances CDKN2A pRb1 expression and regulates functional apoptosis via upregulation of p53 and p21 expression in human breast cancer MCF-7 cell.
[So] Source:Environ Toxicol Pharmacol;47:19-27, 2016 Oct.
[Is] ISSN:1872-7077
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Zinc (Zn) is an essential trace elements, its deficiency is associated with increased incidence of human breast cancer. We aimed to study the effect of Zn on human breast cancer MCF-7 cells cultured in Zn depleted and Zn adequate medium. We found increased cancer cell growth in zinc depleted condition, further Zn supplementation inhibits the viability of breast cancer MCF-7 cell cultured in Zn deficient condition and the IC IC value for Zn is 6.2µM, 15µM, respectively after 48h. Zn markedly induced apoptosis through the characteristic apoptotic morphological changes and DNA fragmentation after 48h. In addition, Zn deficient cells significantly triggered intracellular ROS level and develop oxidative stress induced DNA damage; it was confirmed by elevated expression of CYP1A, GPX, GSK3ß and TNF-α gene. Zinc depleted MCF-7 cells expressed significantly (p≤0.001) decreased levels of CDKN2A, pRb1, p53 and increased the level of mdm2 expression. Zn supplementation (IC =15µM), increased significantly CDKN2A, pRB1 & p53 and markedly reduced mdm2 expression; also protein expression levels of CDKN2A and pRb1 was significantly increased. In addition, intrinsic apoptotic pathway related genes such as Bax, caspase-3, 8, 9 & p21 expression was enhanced and finally induced cell apoptosis. In conclusion, physiological level of zinc is important to prevent DNA damage and MCF-7 cell proliferation via regulation of tumor suppressor gene.
[Mh] Termos MeSH primário: Inibidor p16 de Quinase Dependente de Ciclina/genética
Inibidor de Quinase Dependente de Ciclina p21/genética
Proteínas Salivares Ricas em Prolina/genética
Proteína Supressora de Tumor p53/genética
Zinco/farmacologia
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Apoptose/genética
Meios de Cultura
Inibidor de Quinase Dependente de Ciclina p18/genética
Inibidor de Quinase Dependente de Ciclina p21/metabolismo
Dano ao DNA/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Genes Supressores de Tumor
Seres Humanos
Células MCF-7/efeitos dos fármacos
Células MCF-7/metabolismo
Estresse Oxidativo/efeitos dos fármacos
Estresse Oxidativo/genética
Espécies Reativas de Oxigênio/metabolismo
Proteína Supressora de Tumor p53/metabolismo
Regulação para Cima/efeitos dos fármacos
Zinco/deficiência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CDKN1A protein, human); 0 (CDKN2A protein, human); 0 (Culture Media); 0 (Cyclin-Dependent Kinase Inhibitor p16); 0 (Cyclin-Dependent Kinase Inhibitor p18); 0 (Cyclin-Dependent Kinase Inhibitor p21); 0 (PRB1 protein, human); 0 (Reactive Oxygen Species); 0 (Salivary Proline-Rich Proteins); 0 (TP53 protein, human); 0 (Tumor Suppressor Protein p53); J41CSQ7QDS (Zinc)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170213
[Lr] Data última revisão:
170213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160828
[St] Status:MEDLINE


  4 / 103 MEDLINE  
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[PMID]:27272460
[Au] Autor:Righino B; Pirolli D; Radicioni G; Marzano V; Longhi R; Arcovito A; Sanna MT; De Rosa MC; Paoluzi S; Cesareni G; Messana I; Castagnola M; Vitali A
[Ad] Endereço:Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina, Università Cattolica, L.Go F. Vito, 1, Rome, 00168, Italy.
[Ti] Título:Structural studies and SH3 domain binding properties of a human antiviral salivary proline-rich peptide.
[So] Source:Biopolymers;106(5):714-25, 2016 Sep.
[Is] ISSN:1097-0282
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human saliva contains hundreds of small proline-rich peptides originated by the proteolytic cleavage of the salivary basic Proline-Rich Proteins. Nevertheless only for few of them a specific biological activity has been assigned to date. Among them, the 1932 Da peptide (p1932) has been patented as an anti-HIV agent. In order to shed light on the possible mechanism of action of this peptide, we assessed in this study, by means of molecular dynamics calculations, circular dichroism and FTIR spectroscopic techniques, that p1932 has an intrinsic propensity to adopt a polyproline-II helix arrangement. This structural feature combined with the presence of PxxP motifs in its primary structure, represents an essential property for the exploitation of several biological activities. Next to these findings, we recently demonstrated the ability of this peptide to be internalized within cells of the oral mucosa, thus we focused onto a possible intracellular target, represented by the SH3 domains family. Its ability to interact with selected SH3 domains was finally assayed by Surface Plasmon Resonance spectroscopy. As a result, only Fyn, Hck, and c-Src SH3 domains gave positive results in terms of interaction, showing dissociation constants ranging from nanomolar to micromolar values having the best performer a KD of 148 nM. It is noteworthy that all the interacting domains belong to the Src kinases family, suggesting a role for p1932 as a modulator of the signal transduction pathways mediated by these kinases. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 714-725, 2016.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/química
Peptídeos Catiônicos Antimicrobianos/química
Simulação de Dinâmica Molecular
Proteínas Salivares Ricas em Prolina/química
Domínios de Homologia de src
[Mh] Termos MeSH secundário: Seres Humanos
Ressonância de Plasmônio de Superfície
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Antimicrobial Cationic Peptides); 0 (Salivary Proline-Rich Proteins); 139637-11-9 (PR 39)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170206
[Lr] Data última revisão:
170206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160609
[St] Status:MEDLINE
[do] DOI:10.1002/bip.22889


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[PMID]:26910488
[Au] Autor:Díez P; Lorenzo S; Dégano RM; Ibarrola N; González-González M; Nieto W; Almeida J; González M; Orfao A; Fuentes M
[Ad] Endereço:Department of Medicine and General Cytometry Service-Nucleus, Cancer Research Centre (IBMCC/CSIC/USAL/IBSAL), Salamanca, Spain.
[Ti] Título:Multipronged functional proteomics approaches for global identification of altered cell signalling pathways in B-cell chronic lymphocytic leukaemia.
[So] Source:Proteomics;16(8):1193-203, 2016 Apr.
[Is] ISSN:1615-9861
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Chronic lymphocytic leukaemia (CLL) is a malignant B cell disorder characterized by its high heterogeneity. Although genomic alterations have been broadly reported, protein studies are still in their early stages. Herein, a 224-antibody microarray has been employed to study the intracellular signalling pathways in a cohort of 14 newly diagnosed B-CLL patients as a preliminary study for further investigations. Several protein profiles were differentially identified across the cytogenetic and molecular alterations presented in the samples (deletion 13q14 and 17p13.1, trisomy 12, and NOTCH1 mutations) by a combination of affinity and MS/MS proteomics approaches. Among others altered cell signalling pathways, PKC family members were identified as down-regulated in nearly 75% of the samples tested with the antibody arrays. This might explain the rapid progression of the disease when showing p53, Rb1, or NOTCH1 mutations due to PKC-proteins family plays a critical role favouring the slowly progressive indolent behaviour of CLL. Additionally, the antibody microarray results were validated by a LC-MS/MS quantification strategy and compared to a transcriptomic CLL database. In summary, this research displays the usefulness of proteomic strategies to globally evaluate the protein alterations in CLL cells and select the possible biomarkers to be further studied with larger sample sizes.
[Mh] Termos MeSH primário: Leucemia Linfocítica Crônica de Células B/metabolismo
Proteoma/metabolismo
Proteômica/métodos
Transdução de Sinais
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Linfócitos B/metabolismo
Linfócitos B/patologia
Biomarcadores Tumorais/genética
Biomarcadores Tumorais/metabolismo
Cromatografia Líquida
Deleção Cromossômica
Estudos de Coortes
Feminino
Seres Humanos
Leucemia Linfocítica Crônica de Células B/genética
Masculino
Meia-Idade
Mutação
Proteoma/genética
Receptor Notch1/genética
Receptor Notch1/metabolismo
Reprodutibilidade dos Testes
Proteínas Salivares Ricas em Prolina/genética
Proteínas Salivares Ricas em Prolina/metabolismo
Espectrometria de Massas em Tandem
Trissomia
Proteína Supressora de Tumor p53/genética
Proteína Supressora de Tumor p53/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (NOTCH1 protein, human); 0 (PRB1 protein, human); 0 (Proteome); 0 (Receptor, Notch1); 0 (Salivary Proline-Rich Proteins); 0 (Tumor Suppressor Protein p53)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170104
[Lr] Data última revisão:
170104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160225
[St] Status:MEDLINE
[do] DOI:10.1002/pmic.201500372


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[PMID]:26823521
[Au] Autor:Castellsagué X; Alemany L; Quer M; Halec G; Quirós B; Tous S; Clavero O; Alòs L; Biegner T; Szafarowski T; Alejo M; Holzinger D; Cadena E; Claros E; Hall G; Laco J; Poljak M; Benevolo M; Kasamatsu E; Mehanna H; Ndiaye C; Guimerà N; Lloveras B; León X; Ruiz-Cabezas JC; Alvarado-Cabrero I; Kang CS; Oh JK; Garcia-Rojo M; Iljazovic E; Ajayi OF; Duarte F; Nessa A; Tinoco L; Duran-Padilla MA; Pirog EC; Viarheichyk H; Morales H; Costes V; Félix A; Germar MJ; Mena M; Ruacan A; Jain A; Mehrotra R; Goodman MT; Lombardi LE; Ferrera A; Malami S; Albanesi EI; ICO International HPV in Head and Neck Cancer Study Group
[Ad] Endereço:Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain (XC, LAle, BQ, ST, OC, MM, IGB, SdS, FXB); CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain (XC, LAle, SdS); Hospital Sant Pau, Barcelona, Spain (MQ, XL); Germ
[Ti] Título:HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.
[So] Source:J Natl Cancer Inst;108(6):djv403, 2016 Jun.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. METHODS: Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. RESULTS: A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. CONCLUSIONS: HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/análise
Carcinoma de Células Escamosas/química
Carcinoma de Células Escamosas/virologia
Neoplasias Orofaríngeas/química
Neoplasias Orofaríngeas/virologia
Papillomaviridae/isolamento & purificação
Infecções por Papillomavirus/complicações
[Mh] Termos MeSH secundário: Adulto
Idoso
Estudos Transversais
Ciclina D1/análise
Inibidor p16 de Quinase Dependente de Ciclina/análise
DNA Viral/isolamento & purificação
Feminino
Genótipo
Neoplasias de Cabeça e Pescoço/virologia
Papillomavirus Humano 16/isolamento & purificação
Seres Humanos
Imuno-Histoquímica
Cooperação Internacional
Masculino
Meia-Idade
Papillomaviridae/genética
Infecções por Papillomavirus/virologia
Valor Preditivo dos Testes
Proteínas Salivares Ricas em Prolina/análise
Proteína Supressora de Tumor p53/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CCND1 protein, human); 0 (Cyclin-Dependent Kinase Inhibitor p16); 0 (DNA, Viral); 0 (Salivary Proline-Rich Proteins); 0 (Tumor Suppressor Protein p53); 136601-57-5 (Cyclin D1)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:160129
[Lr] Data última revisão:
160129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160130
[St] Status:MEDLINE


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[PMID]:26391112
[Au] Autor:Huang SJ; Gillan TL; Gerrie AS; Hrynchak M; Karsan A; Ramadan K; Smith AC; Toze CL; Bruyere H
[Ad] Endereço:Leukemia/BMT Program of BC, Vancouver General Hospital and British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada.
[Ti] Título:Influence of clone and deletion size on outcome in chronic lymphocytic leukemia patients with an isolated deletion 13q in a population-based analysis in British Columbia, Canada.
[So] Source:Genes Chromosomes Cancer;55(1):16-24, 2016 Jan.
[Is] ISSN:1098-2264
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Deletion of the long arm of chromosome 13 (del(13q)) as the sole abnormality in chronic lymphocytic leukemia (CLL) portends a good prognosis; however, there is great outcome heterogeneity within this subgroup. The percentage of cells with a del(13q) (clone size) and the extent of the deletion are two factors that may affect outcome in CLL patients with isolated del(13q). We analyzed 248 CLL patients from the BC Provincial CLL database identified as having isolated del(13q) detected pretreatment by interphase fluorescence in situ hybridization to determine what impact clone and deletion size had on overall survival (OS) and treatment free survival (TFS). Patients with 60% or more of nuclei with a del(13q) had shorter TFS and shorter OS. A large deletion, encompassing the RB1 gene locus, was detected in half of the 90 cases with available specimens for testing, and there was no significant difference in OS and TFS between RB1-deleted and RB1-not-deleted cases. Further study in a larger sample size is required to determine the clinical interest of RB1 locus testing; however, clone size of del(13q) does predict TFS and OS and may better refine prognosis in this clinically heterogeneous population.
[Mh] Termos MeSH primário: Deleção Cromossômica
Cromossomos Humanos Par 13/genética
Leucemia Linfocítica Crônica de Células B/patologia
Proteínas Salivares Ricas em Prolina/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Colúmbia Britânica
Núcleo Celular/genética
Feminino
Heterogeneidade Genética
Seres Humanos
Leucemia Linfocítica Crônica de Células B/genética
Masculino
Meia-Idade
Prognóstico
Análise de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (PRB1 protein, human); 0 (Salivary Proline-Rich Proteins)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150923
[St] Status:MEDLINE
[do] DOI:10.1002/gcc.22294


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[PMID]:26375204
[Au] Autor:Manconi B; Castagnola M; Cabras T; Olianas A; Vitali A; Desiderio C; Sanna MT; Messana I
[Ad] Endereço:Department of Life and Environmental Sciences, Biomedical section, University of Cagliari, Cagliari Italy.
[Ti] Título:The intriguing heterogeneity of human salivary proline-rich proteins: Short title: Salivary proline-rich protein species.
[So] Source:J Proteomics;134:47-56, 2016 Feb 16.
[Is] ISSN:1876-7737
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: The most heterogeneous family of human salivary proteins is represented by proline-rich proteins (PRPs) divided in acidic, basic, and basic glycosylated (aPRPs, bPRPs, gPRPs). They are encoded by six genes, clustered on chromosome 12p13.2: PRH1-2 encode aPRPs, PRB1-4 encode bPRPs and gPRPs. Each gene exists in different allelic forms: two for PRH2, three for PRH1, PRB2, and PRB4, four for PRB1, and PRB3. During granule maturation, PRP proproteins undergo proteolysis by the action of convertases and carboxypeptidases. Differently from bPRPs, proteolysis of aPRPs is not complete, and, besides fragments, entire protein species are also secreted. Maturation process generates ten aPRPs (PRP-1, PRP-2, PIF-s, Db-s, Pa, PRP-3, PRP-4, PIF-f, Db-f, P-C), and at least 18 bPRPs (II-2, P-E, IB-6, Ps-1, Ps-2, IB-1, P-J, IB-8a, P-F, P-H, P-D, II-1, protein glycosylated A, CD-IIg, and Gl1-4). In addition, single nucleotide and length polymorphisms, and differentially spliced transcripts originate several natural variants. Phosphorylation, N-pyroglutaminylation, dimerization, and N-/O-glycosylation also occur during maturation, enlarging the number of protein species, further increased by proteolytic events governed by carboxy- and endo-peptidases during and after secretion, and giving rise to a huge number of small peptides. The PRP functional role is still poorly understood. SIGNIFICANCE: The high polymorphism of PRPs gives an important contribution to the high heterogeneity and inter-individual variability of the human salivary proteome. The products of six genes clustered on chromosome 12p13.2 comprise a mixture of entire, truncated, phosphorylated, glycosylated and dimerized protein/peptide species, sharing large part of their sequences, and possibly involved in different biological activities. Whatever the role of PRP species is, it should be crucial, given that PRPs are the most conserved oral salivary proteins among mammals.
[Mh] Termos MeSH primário: Peptídeos
Processamento de Proteína Pós-Traducional/fisiologia
Proteólise
Proteínas Salivares Ricas em Prolina
[Mh] Termos MeSH secundário: Carboxipeptidases/genética
Carboxipeptidases/metabolismo
Seres Humanos
Peptídeos/genética
Peptídeos/metabolismo
Proteínas Salivares Ricas em Prolina/genética
Proteínas Salivares Ricas em Prolina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Peptides); 0 (Salivary Proline-Rich Proteins); EC 3.4.- (Carboxypeptidases)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170422
[Lr] Data última revisão:
170422
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150917
[St] Status:MEDLINE


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[PMID]:26505973
[Au] Autor:Tian N; Leffler DA; Kelly CP; Hansen J; Marietta EV; Murray JA; Schuppan D; Helmerhorst EJ
[Ad] Endereço:Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, Massachusetts;
[Ti] Título:Despite sequence homologies to gluten, salivary proline-rich proteins do not elicit immune responses central to the pathogenesis of celiac disease.
[So] Source:Am J Physiol Gastrointest Liver Physiol;309(11):G910-7, 2015 Dec 01.
[Is] ISSN:1522-1547
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Celiac disease (CD) is an inflammatory disorder triggered by ingested gluten, causing immune-mediated damage to the small-intestinal mucosa. Gluten proteins are strikingly similar in amino acid composition and sequence to proline-rich proteins (PRPs) in human saliva. On the basis of this feature and their shared destination in the gastrointestinal tract, we hypothesized that salivary PRPs may modulate gluten-mediated immune responses in CD. Parotid salivary secretions were collected from CD patients, refractory CD patients, non-CD patients with functional gastrointestinal complaints, and healthy controls. Structural similarities of PRPs with gluten were probed with anti-gliadin antibodies. Immune responses to PRPs were investigated toward CD patient-derived peripheral blood mononuclear cells and in a humanized transgenic HLA-DQ2/DQ8 mouse model for CD. Anti-gliadin antibodies weakly cross-reacted with the abundant salivary amylase but not with PRPs. Likewise, the R5 antibody, recognizing potential antigenic gluten epitopes, showed negligible reactivity to salivary proteins from all groups. Inflammatory responses in peripheral blood mononuclear cells were provoked by gliadins whereas responses to PRPs were similar to control levels, and PRPs did not compete with gliadins in immune stimulation. In vivo, PRP peptides were well tolerated and nonimmunogenic in the transgenic HLA-DQ2/DQ8 mouse model. Collectively, although structurally similar to dietary gluten, salivary PRPs were nonimmunogenic in CD patients and in a transgenic HLA-DQ2/DQ8 mouse model for CD. It is possible that salivary PRPs play a role in tolerance induction to gluten early in life. Deciphering the structural basis for the lack of immunogenicity of salivary PRPs may further our understanding of the toxicity of gluten.
[Mh] Termos MeSH primário: Doença Celíaca/imunologia
Glutens/imunologia
Leucócitos Mononucleares/imunologia
Proteínas Salivares Ricas em Prolina/imunologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Sequência de Aminoácidos
Animais
Anticorpos/sangue
Especificidade de Anticorpos
Estudos de Casos e Controles
Doença Celíaca/sangue
Doença Celíaca/genética
Reações Cruzadas
Citocinas/imunologia
Citocinas/metabolismo
Modelos Animais de Doenças
Epitopos
Feminino
Gliadina/química
Gliadina/imunologia
Glutens/química
Antígenos HLA-DQ/genética
Antígenos HLA-DQ/imunologia
Seres Humanos
Leucócitos Mononucleares/metabolismo
Masculino
Camundongos Transgênicos
Meia-Idade
Glândula Parótida/imunologia
Glândula Parótida/secreção
Proteínas Salivares Ricas em Prolina/química
Proteínas Salivares Ricas em Prolina/secreção
Homologia de Sequência
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antibodies); 0 (Cytokines); 0 (Epitopes); 0 (HLA-DQ Antigens); 0 (HLA-DQ2 antigen); 0 (HLA-DQ8 antigen); 0 (Salivary Proline-Rich Proteins); 8002-80-0 (Glutens); 9007-90-3 (Gliadin)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151028
[St] Status:MEDLINE
[do] DOI:10.1152/ajpgi.00157.2015


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[PMID]:26325345
[Au] Autor:Radicioni G; Stringaro A; Molinari A; Nocca G; Longhi R; Pirolli D; Scarano E; Iavarone F; Manconi B; Cabras T; Messana I; Castagnola M; Vitali A
[Ad] Endereço:Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina, Catholic University, L.go F. Vito, 1, 00168 Rome, Italy. Electronic address: gradicioni@yahoo.it.
[Ti] Título:Characterization of the cell penetrating properties of a human salivary proline-rich peptide.
[So] Source:Biochim Biophys Acta;1848(11 Pt A):2868-77, 2015 Nov.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Saliva contains hundreds of small proline-rich peptides most of which derive from the post-translational and post-secretory processing of the acidic and basic salivary proline-rich proteins. Among these peptides we found that a 20 residue proline-rich peptide (p1932), commonly present in human saliva and patented for its antiviral activity, was internalized within cells of the oral mucosa. The cell-penetrating properties of p1932 have been studied in a primary gingival fibroblast cell line and in a squamous cancer cell line, and compared to its retro-inverso form. We observed by mass-spectrometry, flow cytometry and confocal microscopy that both peptides were internalized in the two cell lines on a time scale of minutes, being the natural form more efficient than the retro-inverso one. The cytosolic localization was dependent on the cell type: both peptide forms were able to localize within nuclei of tumoral cells, but not in the nuclei of gingival fibroblasts. The uptake was shown to be dependent on the culture conditions used: peptide internalization was indeed effective in a complete medium than in a serum-free one allowing the hypothesis that the internalization could be dependent on the cell cycle. Both peptides were internalized likely by a lipid raft-mediated endocytosis mechanism as suggested by the reduced uptake in the presence of methyl-ß-cyclodextrin. These results suggest that the natural peptide may play a role within the cells of the oral mucosa after its secretion and subsequent internalization. Furthermore, lack of cytotoxicity of both peptide forms highlights their possible application as novel drug delivery agents.
[Mh] Termos MeSH primário: Peptídeos Penetradores de Células/metabolismo
Endocitose/fisiologia
Peptídeos/metabolismo
Proteínas Salivares Ricas em Prolina/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Peptídeos Penetradores de Células/farmacocinética
Peptídeos Penetradores de Células/farmacologia
Células Cultivadas
Meios de Cultura/farmacologia
Meios de Cultura Livres de Soro/farmacologia
Endocitose/efeitos dos fármacos
Fibroblastos/metabolismo
Citometria de Fluxo
Gengiva/citologia
Seres Humanos
Microscopia Confocal
Peptídeos/farmacocinética
Peptídeos/farmacologia
Proteínas Salivares Ricas em Prolina/farmacocinética
Proteínas Salivares Ricas em Prolina/farmacologia
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
beta-Ciclodextrinas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cell-Penetrating Peptides); 0 (Culture Media); 0 (Culture Media, Serum-Free); 0 (Peptides); 0 (Salivary Proline-Rich Proteins); 0 (beta-Cyclodextrins); 0 (methyl-beta-cyclodextrin)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:161126
[Lr] Data última revisão:
161126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150902
[St] Status:MEDLINE



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