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[PMID]:29489701
[Au] Autor:Yang Y; Yan S; Tian H; Bao Y
[Ad] Endereço:Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
[Ti] Título:Macrophage inhibitory cytokine-1 versus carbohydrate antigen 19-9 as a biomarker for diagnosis of pancreatic cancer: A PRISMA-compliant meta-analysis of diagnostic accuracy studies.
[So] Source:Medicine (Baltimore);97(9):e9994, 2018 Mar.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Because of the high malignant degree of pancreatic cancer (PC), the early diagnosis of PC is of great concern. Macrophage inhibitory cytokine-1 (MIC-1) was reported to be a potential diagnostic biomarker, but its diagnostic value is indeterminate. Therefore, we performed this meta-analysis to compare it to carbohydrate antigen 19-9 (CA19-9), the most frequently used serum biomarker in PC. MATERIAL AND METHODS: After a systematic review of the relevant studies, the pooled diagnostic indices, including sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curve (sROC), and area under the SROC curve (AUC) were used to evaluate the diagnostic value of MIC-1 and CA19-9 for PC. These indices were pooled with random-effects models. We explored the heterogeneity by meta-regression. RESULTS: Fourteen studies comprising a total of 2826 subjects were included in our meta-analysis. The summary estimates for MIC-1 and CA19-9 are listed as follows: sensitivity, 80% [95% confidence interval (CI) 78-82] versus 71% (95% CI 68-73); specificity, 85% (95% CI 83-87) versus 88% (95% CI 86-90); DOR, 24.57 (95% CI 14.00-43.10) versus 17.65 (95% CI 11.65-26.76); area under sROC (AUC), 0.8945 versus 0.8322; PLR, 5.18 (95% CI 3.24-8.26) versus 5.34 (95% CI 3.78-7.54); and NLR, 0.23 (95% CI 0.19-0.29) versus 0.32 (95% CI 0.28-0.37). CONCLUSION: These data demonstrate that serum MIC-1 has a comparable diagnostic accuracy to CA19-9 for PC.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Antígeno CA-19-9/sangue
Fator 15 de Diferenciação de Crescimento/sangue
Neoplasias Pancreáticas/diagnóstico
[Mh] Termos MeSH secundário: Adulto
Idoso
Feminino
Seres Humanos
Masculino
Meia-Idade
Razão de Chances
Curva ROC
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CA-19-9 Antigen); 0 (GDF15 protein, human); 0 (Growth Differentiation Factor 15)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180301
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009994


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[PMID]:27771295
[Au] Autor:Park SH; Yu M; Kim J; Moon Y
[Ad] Endereço:Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Medical Research Institute, Pusan National University School of Medicine, Yangsan, 50612, South Korea.
[Ti] Título:C/EBP homologous protein promotes NSAID-activated gene 1-linked pro-inflammatory signals and enterocyte invasion by enteropathogenic Escherichia coli.
[So] Source:Microbes Infect;19(2):110-121, 2017 02.
[Is] ISSN:1769-714X
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:NSAID-activated Gene 1 (NAG-1) is a prognostic indicator of chronic inflammatory diseases and aggressive tumors. Among the stress sentinels in response to infection by enteropathogenic Escherichia coli (EPEC) or other pathogenic E. coli, C/EBP homologous protein (CHOP), a representative stress-regulated transcription factor, was prominently increased and assessed for its involvement in NAG-1-mediated pathogenic cellular responses. NAG-1 expression was transcriptionally upregulated by CHOP, which promoted chemokine production through sustained NF-κB activation. Mechanistically, NF-κB activation by NAG-1 was due to TGFß-activated kinase 1 (TAK-1)-mediated pathway rather than SMAD-associated signals. Moreover, CHOP and subsequent TAK-1-linked signals were also involved in bacterial invasion into human cells. Therefore, CHOP as an infection-induced sentinel played crucial roles in induction of NAG-1 and subsequent prolonged activation of pro-inflammatory responses to EPEC infection or related chronic pathogenic states.
[Mh] Termos MeSH primário: Endocitose
Enterócitos/microbiologia
Escherichia coli Enteropatogênica/patogenicidade
Fator 15 de Diferenciação de Crescimento/metabolismo
Fator de Transcrição CHOP/metabolismo
[Mh] Termos MeSH secundário: Células Cultivadas
Seres Humanos
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (GDF15 protein, human); 0 (Growth Differentiation Factor 15); 147336-12-7 (Transcription Factor CHOP)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161105
[St] Status:MEDLINE


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[PMID]:28455268
[Au] Autor:Moon Y
[Ad] Endereço:Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University School of Medicine, Yangsan, South Korea; Research Institute for Basic Sciences and Medical Research Institute, Pusan National University, Busan, South Korea; Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Busan, South Korea. Electronic address: moon@pnu.edu.
[Ti] Título:NSAID-activated gene 1 and its implications for mucosal integrity and intervention beyond NSAIDs.
[So] Source:Pharmacol Res;121:122-128, 2017 Jul.
[Is] ISSN:1096-1186
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:In spite of the beneficial actions of non-steroid anti-inflammatory drugs (NSAIDs) in epithelial inflammation and cancers, their use is limited because of their cyclooxygenase-dependent or independent gastrointestinal toxicity. As an eicosanoid-independent mediator, NSAID-activated gene 1 (NAG-1) has been assessed for its involvement in cellular integrity and pathogenesis in mucosal inflammation and carcinogenesis. At the cellular levels, NAG-1 is involved in the cell growth regulation (cell death, cell cycle arrest, or proliferation) in epithelial and mesenchymal tissues. Moreover, NAG-1 can modulate inflammatory responses in either direct or indirect manner, which ultimately affects fibrogenic and tumorigenic processes in various disease states. Finally, NAG-1 has been assessed for its contribution to cellular behavior, such as the mobility of epithelial and malignant cells in response to the external insults or oncogenic stimulation in the mucosa. This review on the "Yin-Yang" nature of NAG-1-mediated responses provides comprehensive insights into therapeutic and diagnostic interventions for mucosal health and integrity in the human body.
[Mh] Termos MeSH primário: Carcinogênese/imunologia
Fator 15 de Diferenciação de Crescimento/imunologia
Mucosite/imunologia
Membrana Mucosa/imunologia
[Mh] Termos MeSH secundário: Animais
Carcinogênese/patologia
Movimento Celular
Proliferação Celular
Fibrose
Fator 15 de Diferenciação de Crescimento/análise
Seres Humanos
Inflamação/imunologia
Inflamação/patologia
Mucosite/patologia
Membrana Mucosa/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (GDF15 protein, human); 0 (Growth Differentiation Factor 15)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:28891811
[Au] Autor:Ratnam NM; Peterson JM; Talbert EE; Ladner KJ; Rajasekera PV; Schmidt CR; Dillhoff ME; Swanson BJ; Haverick E; Kladney RD; Williams TM; Leone GW; Wang DJ; Guttridge DC
[Ad] Endereço:Department of Cancer Biology and Genetics.
[Ti] Título:NF-κB regulates GDF-15 to suppress macrophage surveillance during early tumor development.
[So] Source:J Clin Invest;127(10):3796-3809, 2017 Oct 02.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Macrophages are attracted to developing tumors and can participate in immune surveillance to eliminate neoplastic cells. In response, neoplastic cells utilize NF-κB to suppress this killing activity, but the mechanisms underlying their self-protection remain unclear. Here, we report that this dynamic interaction between tumor cells and macrophages is integrally linked by a soluble factor identified as growth and differentiation factor 15 (GDF-15). In vitro, tumor-derived GDF-15 signals in macrophages to suppress their proapoptotic activity by inhibiting TNF and nitric oxide (NO) production. In vivo, depletion of GDF-15 in Ras-driven tumor xenografts and in an orthotopic model of pancreatic cancer delayed tumor development. This delay correlated with increased infiltrating antitumor macrophages. Further, production of GDF-15 is directly regulated by NF-κB, and the colocalization of activated NF-κB and GDF-15 in epithelial ducts of human pancreatic adenocarcinoma supports the importance of this observation. Mechanistically, we found that GDF-15 suppresses macrophage activity by inhibiting TGF-ß-activated kinase (TAK1) signaling to NF-κB, thereby blocking synthesis of TNF and NO. Based on these results, we propose that the NF-κB/GDF-15 regulatory axis is important for tumor cells in evading macrophage immune surveillance during the early stages of tumorigenesis.
[Mh] Termos MeSH primário: Adenocarcinoma/imunologia
Fator 15 de Diferenciação de Crescimento/imunologia
Vigilância Imunológica
Macrófagos/imunologia
NF-kappa B/imunologia
Proteínas de Neoplasias/imunologia
Neoplasias Experimentais/imunologia
Neoplasias Pancreáticas/imunologia
Transdução de Sinais/imunologia
[Mh] Termos MeSH secundário: Adenocarcinoma/genética
Adenocarcinoma/patologia
Animais
Feminino
Fator 15 de Diferenciação de Crescimento/genética
Xenoenxertos
MAP Quinase Quinase Quinases
Macrófagos/patologia
Masculino
Camundongos
Camundongos Knockout
NF-kappa B/genética
Proteínas de Neoplasias/genética
Transplante de Neoplasias
Neoplasias Experimentais/genética
Neoplasias Experimentais/patologia
Óxido Nítrico/genética
Óxido Nítrico/imunologia
Neoplasias Pancreáticas/genética
Neoplasias Pancreáticas/patologia
Transdução de Sinais/genética
Fator de Necrose Tumoral alfa/genética
Fator de Necrose Tumoral alfa/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GDF15 protein, human); 0 (Growth Differentiation Factor 15); 0 (NF-kappa B); 0 (Neoplasm Proteins); 0 (Tumor Necrosis Factor-alpha); 31C4KY9ESH (Nitric Oxide); EC 2.7.11.25 (MAP Kinase Kinase Kinases); EC 2.7.11.25 (MAP kinase kinase kinase 7)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE


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[PMID]:28846098
[Au] Autor:Emmerson PJ; Wang F; Du Y; Liu Q; Pickard RT; Gonciarz MD; Coskun T; Hamang MJ; Sindelar DK; Ballman KK; Foltz LA; Muppidi A; Alsina-Fernandez J; Barnard GC; Tang JX; Liu X; Mao X; Siegel R; Sloan JH; Mitchell PJ; Zhang BB; Gimeno RE; Shan B; Wu X
[Ad] Endereço:Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly &Company, Indianapolis, Indiana, USA.
[Ti] Título:The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL.
[So] Source:Nat Med;23(10):1215-1219, 2017 Oct.
[Is] ISSN:1546-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Growth/differentiation factor 15 (GDF15), also known as MIC-1, is a distant member of the transforming growth factor-ß (TGF-ß) superfamily and has been implicated in various biological functions, including cancer cachexia, renal and heart failure, atherosclerosis and metabolism. A connection between GDF15 and body-weight regulation was initially suggested on the basis of an observation that increasing GDF15 levels in serum correlated with weight loss in individuals with advanced prostate cancer. In animal models, overexpression of GDF15 leads to a lean phenotype, hypophagia and other improvements in metabolic parameters, suggesting that recombinant GDF15 protein could potentially be used in the treatment of obesity and type 2 diabetes. However, the signaling and mechanism of action of GDF15 are poorly understood owing to the absence of a clearly identified cognate receptor. Here we report that GDNF-family receptor α-like (GFRAL), an orphan member of the GFR-α family, is a high-affinity receptor for GDF15. GFRAL binds to GDF15 in vitro and is required for the metabolic actions of GDF15 with respect to body weight and food intake in vivo in mice. Gfral mice were refractory to the effects of recombinant human GDF15 on body-weight, food-intake and glucose parameters. Blocking the interaction between GDF15 and GFRAL with a monoclonal antibody prevented the metabolic effects of GDF15 in rats. Gfral mRNA is highly expressed in the area postrema of mouse, rat and monkey, in accordance with previous reports implicating this region of the brain in the metabolic actions of GDF15 (refs. 4,5,6). Together, our data demonstrate that GFRAL is a receptor for GDF15 that mediates the metabolic effects of GDF15.
[Mh] Termos MeSH primário: Área Postrema/metabolismo
Ingestão de Alimentos/efeitos dos fármacos
Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética
Fator 15 de Diferenciação de Crescimento/farmacologia
Obesidade/metabolismo
Perda de Peso/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Encéfalo/metabolismo
Ingestão de Alimentos/genética
Citometria de Fluxo
Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo
Células HEK293
Seres Humanos
Immunoblotting
Macaca fascicularis
Masculino
Camundongos
Camundongos Knockout
RNA Mensageiro/metabolismo
Ratos
Ratos Sprague-Dawley
Reação em Cadeia da Polimerase em Tempo Real
Ressonância de Plasmônio de Superfície
Perda de Peso/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GDF15 protein, human); 0 (Glial Cell Line-Derived Neurotrophic Factor Receptors); 0 (Growth Differentiation Factor 15); 0 (RNA, Messenger)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE
[do] DOI:10.1038/nm.4393


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[PMID]:28846099
[Au] Autor:Yang L; Chang CC; Sun Z; Madsen D; Zhu H; Padkjær SB; Wu X; Huang T; Hultman K; Paulsen SJ; Wang J; Bugge A; Frantzen JB; Nørgaard P; Jeppesen JF; Yang Z; Secher A; Chen H; Li X; John LM; Shan B; He Z; Gao X; Su J; Hansen KT; Yang W; Jørgensen SB
[Ad] Endereço:Novo Nordisk Research Centre China, Novo Nordisk A/S, Beijing, China.
[Ti] Título:GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand.
[So] Source:Nat Med;23(10):1158-1166, 2017 Oct.
[Is] ISSN:1546-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Growth differentiation factor 15 (GDF15; also known as MIC-1) is a divergent member of the TGF-ß superfamily and is associated with body-weight regulation in humans and rodents. However, the cognate receptor of GDF15 is unknown. Here we show that GDF15 binds specifically to GDNF family receptor α-like (GFRAL) with high affinity, and that GFRAL requires association with the coreceptor RET to elicit intracellular signaling in response to GDF15 stimulation. We also found that GDF15-mediated reductions in food intake and body weight of mice with obesity were abolished in GFRAL-knockout mice. We further found that GFRAL expression was limited to hindbrain neurons and not present in peripheral tissues, which suggests that GDF15-GFRAL-mediated regulation of food intake is by a central mechanism. Lastly, given that GDF15 did not increase energy expenditure in treated mice with obesity, the anti-obesity actions of the cytokine are likely driven primarily by a reduction in food intake.
[Mh] Termos MeSH primário: Ingestão de Alimentos/efeitos dos fármacos
Metabolismo Energético/efeitos dos fármacos
Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/efeitos dos fármacos
Fator 15 de Diferenciação de Crescimento/farmacologia
Obesidade/metabolismo
Perda de Peso/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Ingestão de Alimentos/genética
Metabolismo Energético/genética
Citometria de Fluxo
Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética
Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo
Células HEK293
Seres Humanos
Técnicas In Vitro
Camundongos
Camundongos Knockout
Ratos
Ratos Sprague-Dawley
Ressonância de Plasmônio de Superfície
Perda de Peso/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GDF15 protein, human); 0 (Glial Cell Line-Derived Neurotrophic Factor Receptors); 0 (Growth Differentiation Factor 15)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE
[do] DOI:10.1038/nm.4394


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[PMID]:28846097
[Au] Autor:Mullican SE; Lin-Schmidt X; Chin CN; Chavez JA; Furman JL; Armstrong AA; Beck SC; South VJ; Dinh TQ; Cash-Mason TD; Cavanaugh CR; Nelson S; Huang C; Hunter MJ; Rangwala SM
[Ad] Endereço:Cardiovascular and Metabolism Therapeutic Area, Janssen Research and Development, Spring House, Pennsylvania, USA.
[Ti] Título:GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates.
[So] Source:Nat Med;23(10):1150-1157, 2017 Oct.
[Is] ISSN:1546-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Growth differentiation factor 15 (GDF15), a distant member of the transforming growth factor (TGF)-ß family, is a secreted protein that circulates as a 25-kDa dimer. In humans, elevated GDF15 correlates with weight loss, and the administration of GDF15 to mice with obesity reduces body weight, at least in part, by decreasing food intake. The mechanisms through which GDF15 reduces body weight remain poorly understood, because the cognate receptor for GDF15 is unknown. Here we show that recombinant GDF15 induces weight loss in mice fed a high-fat diet and in nonhuman primates with spontaneous obesity. Furthermore, we find that GDF15 binds with high affinity to GDNF family receptor α-like (GFRAL), a distant relative of receptors for a distinct class of the TGF-ß superfamily ligands. Gfral is expressed in neurons of the area postrema and nucleus of the solitary tract in mice and humans, and genetic deletion of the receptor abrogates the ability of GDF15 to decrease food intake and body weight in mice. In addition, diet-induced obesity and insulin resistance are exacerbated in GFRAL-deficient mice, suggesting a homeostatic role for this receptor in metabolism. Finally, we demonstrate that GDF15-induced cell signaling requires the interaction of GFRAL with the coreceptor RET. Our data identify GFRAL as a new regulator of body weight and as the bona fide receptor mediating the metabolic effects of GDF15, enabling a more comprehensive assessment of GDF15 as a potential pharmacotherapy for the treatment of obesity.
[Mh] Termos MeSH primário: Ingestão de Alimentos/efeitos dos fármacos
Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética
Fator 15 de Diferenciação de Crescimento/genética
Obesidade/metabolismo
Perda de Peso/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Dieta Hiperlipídica
Ingestão de Alimentos/genética
Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo
Fator 15 de Diferenciação de Crescimento/metabolismo
Fator 15 de Diferenciação de Crescimento/farmacologia
Seres Humanos
Macaca fascicularis
Camundongos
Camundongos Knockout
Perda de Peso/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GDF15 protein, human); 0 (Glial Cell Line-Derived Neurotrophic Factor Receptors); 0 (Growth Differentiation Factor 15)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE
[do] DOI:10.1038/nm.4392


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[PMID]:28806401
[Au] Autor:Teng MS; Hsu LA; Juan SH; Lin WC; Lee MC; Su CW; Wu S; Ko YL
[Ad] Endereço:Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
[Ti] Título:A GDF15 3' UTR variant, rs1054564, results in allele-specific translational repression of GDF15 by hsa-miR-1233-3p.
[So] Source:PLoS One;12(8):e0183187, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Growth differentiation factor 15 (GDF15) is a strong predictor of cardiovascular events and mortality in individuals with or without cardiovascular diseases. Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) target sites, also known as miRSNPs, are known to enhance or weaken miRNA-mRNA interactions and have been linked to diseases such as cardiovascular disease and cancer. In this study, we aimed to elucidate the functional significance of the miRSNP rs1054564 in regulating GDF15 levels. Two rs1054564-containing binding sites for hsa-miR-873-5p and hsa-miR-1233-3p were identified in the 3' untranslated region (UTR) of the GDF15 transcript using bioinformatics tools. Their activities were further characterized by in vitro reporter assays. Bioinformatics prediction suggested that miRNA binding sites harboring the rs1054564-G allele had lower free energies than those with the C allele and therefore were better targets with higher affinities for both hsa-miR-873-5p and hsa-miR-1233-3p. Reporter assays showed that luciferase activity was significantly decreased by rs1054564-G-containing 3' UTRs for both miRNAs (P < 0.05) and was restored by miRNA inhibitors. Comparing the fold suppression of the two miRNAs, only that of hsa-miR-1233-3p showed significant changes between the rs1054564-G- and C-containing 3' UTRs (P = 0.034). In addition, western blots showed that transfection of both miRNA mimics significantly decreased endogenous GDF15 expression in a melanoma cell line (P < 0.05). Taken together, our findings demonstrate that GDF15 is a target of hsa-miR-873-5p and hsa-miR-1233-3p and that the rs1054564-C allele partially abolishes hsa-miR-1233-3p-mediated translational suppression of GDF15. These results suggest that rs1054564 confers allele-specific translational repression of GDF15 via hsa-miR-1233-3p. Our work thus provides biological insight into the previously reported clinical association between rs1054564 and plasma GDF15 levels.
[Mh] Termos MeSH primário: Regiões 3´ não Traduzidas/genética
Alelos
Fator 15 de Diferenciação de Crescimento/genética
MicroRNAs/metabolismo
Polimorfismo de Nucleotídeo Único/genética
Biossíntese de Proteínas/genética
[Mh] Termos MeSH secundário: Sequência de Bases
Sítios de Ligação/genética
Linhagem Celular Tumoral
Simulação por Computador
Fator 15 de Diferenciação de Crescimento/metabolismo
Células HEK293
Seres Humanos
MicroRNAs/química
MicroRNAs/genética
Conformação de Ácido Nucleico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (GDF15 protein, human); 0 (Growth Differentiation Factor 15); 0 (MIRN-1233 microRNA, human); 0 (MIRN873 microRNA, human); 0 (MicroRNAs)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170815
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183187


  9 / 755 MEDLINE  
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[PMID]:28771550
[Au] Autor:Tzikas S; Palapies L; Bakogiannis C; Zeller T; Sinning C; Baldus S; Bickel C; Vassilikos V; Lackner KJ; Zeiher A; Münzel T; Blankenberg S; Keller T
[Ad] Endereço:3rd Department of Cardiology, Ippokrateio Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
[Ti] Título:GDF-15 predicts cardiovascular events in acute chest pain patients.
[So] Source:PLoS One;12(8):e0182314, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Treatment of patients presenting with possible acute myocardial infarction (AMI) is based on timely diagnosis and proper risk stratification aided by biomarkers. We aimed at evaluating the predictive value of GDF-15 in patients presenting with symptoms suggestive of AMI. METHODS: Consecutive patients presenting with suspected AMI were enrolled in three study centers. Cardiovascular events were assessed during a follow-up period of 6 months with a combined endpoint of death or MI. RESULTS: From the 1818 enrolled patients (m/f = 1208/610), 413 (22.7%) had an acute MI and 63 patients reached the combined endpoint. Patients with MI and patients with adverse outcome had higher GDF-15 levels compared with non-MI patients (967.1pg/mL vs. 692.2 pg/L, p<0.001) and with event-free patients (1660 pg/mL vs. 756.6 pg/L, p<0.001). GDF-15 levels were lower in patients with SYNTAX score ≤ 22 (797.3 pg/mL vs. 947.2 pg/L, p = 0.036). Increased GDF-15 levels on admission were associated with a hazard ratio of 2.1 for death or MI (95%CI: 1.67-2.65, p<0.001) in a model adjusted for age and sex and of 1.57 (1.13-2.19, p = 0.008) adjusted for the GRACE score variables. GDF-15 showed a relevant reclassification with regards to the GRACE score with an overall net reclassification index (NRI) of 12.5% and an integrated discrimination improvement (IDI) of 14.56% (p = 0.006). CONCLUSION: GDF-15 is an independent predictor of future cardiovascular events in patients presenting with suspected MI. GDF-15 levels correlate with the severity of CAD and can identify and risk-stratify patients who need coronary revascularization.
[Mh] Termos MeSH primário: Dor no Peito/etiologia
Fator 15 de Diferenciação de Crescimento/análise
Infarto do Miocárdio/diagnóstico
[Mh] Termos MeSH secundário: Doença Aguda
Idoso
Biomarcadores/análise
Feminino
Seres Humanos
Estimativa de Kaplan-Meier
Lipoproteínas HDL/sangue
Lipoproteínas LDL/sangue
Masculino
Meia-Idade
Infarto do Miocárdio/mortalidade
Infarto do Miocárdio/patologia
Modelos de Riscos Proporcionais
Fatores de Risco
Índice de Gravidade de Doença
Troponina I/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Growth Differentiation Factor 15); 0 (Lipoproteins, HDL); 0 (Lipoproteins, LDL); 0 (Troponin I)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182314


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[PMID]:28760218
[Au] Autor:Hijazi Z; Oldgren J; Andersson U; Connolly SJ; Eikelboom JW; Ezekowitz MD; Reilly PA; Yusuf S; Siegbahn A; Wallentin L
[Ad] Endereço:Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. Electronic address: ziad.hijazi@ucr.uu.se.
[Ti] Título:Growth-differentiation factor 15 and risk of major bleeding in atrial fibrillation: Insights from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial.
[So] Source:Am Heart J;190:94-103, 2017 Aug.
[Is] ISSN:1097-6744
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To evaluate and validate the prognostic value of growth-differentiation factor 15 (GDF-15) beyond clinical characteristics and other biomarkers concerning bleeding and stroke outcomes in patients with atrial fibrillation in the RE-LY trial. METHODS: GDF-15 was measured in samples collected at randomization in 8,474 patients with a median follow-up time of 1.9 years. Patients were stratified based on predefined GDF-15 cutoffs: group 1, <1,200 ng/L (the 90th percentile in healthy individuals); group 2, 1,200-1,800; and group 3, >1,800 ng/L (high-risk individuals). Efficacy and safety outcomes were compared across groups of GDF-15 in Cox models adjusted for baseline characteristics, cardiac (N-terminal pro-b-type natriuretic peptide, high-sensitive troponin T), inflammatory (interleukin 6, C-reactive protein) and coagulation (D-dimer) biomarkers, and randomized treatment. RESULTS: GDF-15 concentrations were <1,200 ng/L in 2,647 (31.2%), between 1,200 and 1,800 ng/L in 2,704 (31.9%), and >1,800 ng/L in 3,123 (36.9%) participants, respectively. Annual rates of stroke, major bleeding, and mortality increased with higher GDF-15 levels. The prognostic value of GDF-15 was independent of clinical characteristics for these outcomes. In models also adjusted for biomarkers, GDF-15 remained significantly associated with major bleeding (hazard ratio [95% CI] group 3 vs group 1 1.76 [1.28-2.42], P < .0005) and all-cause mortality (hazard ratio 1.72 [1.30-2.29], P < .0005). GDF-15 improved the c index of both the HAS-BLED (0.62-0.69) and ORBIT (0.68-0.71) bleeding risk scores. CONCLUSIONS: In patients with atrial fibrillation, GDF-15 is an independent risk indicator for major bleeding and all-cause mortality, but not for stroke. Therefore, GDF-15 seems useful as a specific marker of bleeding in patients with AF on oral anticoagulant treatment.
[Mh] Termos MeSH primário: Anticoagulantes/efeitos adversos
Fibrilação Atrial/complicações
Fator 15 de Diferenciação de Crescimento/sangue
Hemorragia/induzido quimicamente
Medição de Risco
Acidente Vascular Cerebral/prevenção & controle
[Mh] Termos MeSH secundário: Idoso
Anticoagulantes/administração & dosagem
Fibrilação Atrial/tratamento farmacológico
Biomarcadores/sangue
Canadá/epidemiologia
Relação Dose-Resposta a Droga
Feminino
Seguimentos
Hemorragia/sangue
Hemorragia/epidemiologia
Seres Humanos
Incidência
Masculino
Meia-Idade
Prognóstico
Estudos Retrospectivos
Fatores de Risco
Acidente Vascular Cerebral/epidemiologia
Acidente Vascular Cerebral/etiologia
Taxa de Sobrevida/tendências
Suécia/epidemiologia
Fatores de Tempo
Estados Unidos/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anticoagulants); 0 (Biomarkers); 0 (GDF15 protein, human); 0 (Growth Differentiation Factor 15)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE



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