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  1 / 11607 MEDLINE  
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[PMID]:29385191
[Au] Autor:Chuerduangphui J; Ekalaksananan T; Chaiyarit P; Patarapadungkit N; Chotiyano A; Kongyingyoes B; Promthet S; Pientong C
[Ad] Endereço:Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
[Ti] Título:Effects of arecoline on proliferation of oral squamous cell carcinoma cells by dysregulating c-Myc and miR-22, directly targeting oncostatin M.
[So] Source:PLoS One;13(1):e0192009, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Arecoline, the major alkaloid of areca nut, is known to induce oral carcinogenesis, however, its mechanism is still needed to elucidate. This study investigated the effects of arecoline on cell viability and cell-cycle progression of oral squamous cell carcinoma (OSCC) cells as well as a relevant cellular gene expression. The results showed that a low concentration of arecoline (0.025 µg/ml) increased OSCC cell viability, proportion of cells in G2/M phase and cell proliferation. Simultaneously, it induced IL-6, STAT3 and c-Myc expression. Interestingly, c-myc promoter activity was also induced by arecoline. MiR-22 expression in arecoline-treated OSCC cells was suppressed and comparable to an upregulated c-Myc expression. In arecoline-treated OSCC cells, oncostatin M (OSM) expression was significantly upregulated and inversely correlated with miR-22 expression. Likewise, OSM expression and its post-transcriptional activity were significantly decreased in miR-22-transfected OSCC and 293FT cells. This result demonstrated that miR-22 directly targeted OSM. Interestingly, miR-22 played an important role as a tumor suppresser on suppressing cell proliferation, migration and cell-cycle progression of OSCC cells. This result suggested the effect of arecoline to promote cell proliferation and cell-cycle progression of OSCC cells might be involved in induction of c-Myc expression and reduction of miR-22 resulting in OSM upregulation.
[Mh] Termos MeSH primário: Arecolina/farmacologia
Carcinoma de Células Escamosas/patologia
Proliferação Celular/efeitos dos fármacos
MicroRNAs/metabolismo
Neoplasias Bucais/patologia
Proteínas Proto-Oncogênicas c-myc/metabolismo
[Mh] Termos MeSH secundário: Carcinoma de Células Escamosas/metabolismo
Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Seres Humanos
Interleucina-6/biossíntese
MicroRNAs/genética
Neoplasias Bucais/metabolismo
Regiões Promotoras Genéticas
Proteínas Proto-Oncogênicas c-myc/genética
Fator de Transcrição STAT3/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Interleukin-6); 0 (MIRN22 microRNA, human); 0 (MicroRNAs); 0 (Proto-Oncogene Proteins c-myc); 0 (STAT3 Transcription Factor); 0 (STAT3 protein, human); 4ALN5933BH (Arecoline)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0192009


  2 / 11607 MEDLINE  
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[PMID]:29330562
[Au] Autor:Zhao L; Zhu H; Han B; Wang L; Sun Y; Lu X; Huang C; Tan B; Chen C; Qin L
[Ad] Endereço:Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
[Ti] Título:Influence of genetic polymorphisms of IL23R, STAT3, IL12B, and STAT4 on the risk of aplastic anemia and the effect of immunosuppressive therapy.
[So] Source:Ann Hematol;97(4):685-695, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Studies have suggested that IL-23/STAT3 and IL-12/STAT4 signaling pathways associate with aplastic anemia (AA) occurrence. Polymorphisms in pathway-related genes may contribute to AA risk. In the current study, we investigated the association between polymorphisms in genes of IL23R, STAT3, IL12B, and STAT4 and occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China. In the current 164 AA cases and 211 controls study, we found T allele and TT genotype of rs7574865 were more frequent in the cases than that in the controls. In the additive model, individual carrying rs7574865 T allele demonstrated a 37% (OR (95% CI) = 1.37 (1.02-1.85), Pper = 0.036) increased AA risk. In the recessive model, carrier with rs7574865 TT genotype showed a 2.08-fold increased AA risk (OR (95% CI) = 2.08 (1.14-3.70), Pper = 0.017). Additionally, we showed that G allele and GG genotype of rs11209032 were more frequent in the 88 non-severe AA cases than that in the 76 severe AA ones. Our study also found G allele and GG genotype of rs11209032, and GG-genotype of rs744166 associated with the immunosuppressive therapy outcome in AA patients. Current study results support that functional STAT4 (rs7574865), IL23R (rs11209032), and STAT3 (rs744166) variants may associate with occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China.
[Mh] Termos MeSH primário: Anemia Aplástica/genética
Anemia Aplástica/terapia
Imunossupressão
Polimorfismo de Nucleotídeo Único
Receptores de Interleucina/genética
Fator de Transcrição STAT3/genética
Fator de Transcrição STAT4/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Anemia Aplástica/imunologia
Anemia Aplástica/fisiopatologia
Grupo com Ancestrais do Continente Asiático
Estudos de Casos e Controles
China
Feminino
Seguimentos
Estudos de Associação Genética
Predisposição Genética para Doença
Seres Humanos
Subunidade p40 da Interleucina-12/genética
Masculino
Meia-Idade
Estudos Retrospectivos
Índice de Gravidade de Doença
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (IL12B protein, human); 0 (IL23R protein, human); 0 (Interleukin-12 Subunit p40); 0 (Receptors, Interleukin); 0 (STAT3 Transcription Factor); 0 (STAT3 protein, human); 0 (STAT4 Transcription Factor); 0 (STAT4 protein, human)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180114
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-018-3227-7


  3 / 11607 MEDLINE  
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[PMID]:29441918
[Au] Autor:Wang S; Li A; Guo S
[Ti] Título:Ligustrazine attenuates neuropathic pain by inhibition of JAK/STAT3 pathway in a rat model of chronic constriction injury.
[So] Source:Pharmazie;71(7):408-412, 2016 Jul 07.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:AIM: Neuropathic pain is a common clinical complication of nerve injury, and the effective treatment of neuropathic pain is still challenging. Ligustrazine is mainly used for the treatment of cardiovascular disease and its role in neuropathic pain is less investigated. The purpose of our study was to explore the effects of ligustrazine on neuropathic pain, as well as the underlying molecular mechanism. METHODS: Neuropathic pain was induced by chronic constriction injury (CCI) of the right sciatic nerve in Sprague-Dawley (SD) rats. After CCI, rats received ligustrazine, IL-6, or both. Mechanical withdrawal threshold (MWT) and paw withdrawal thermal latency (PWTL) were assessed on days 1, 3, 7, and 14 after surgery. Expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-ß, IL-2, and phosphorylation of Signal Transducer and Activator of Transcription (STAT) 3 were analyzed. RESULTS: Our results showed that both MWT and PWTL were significantly decreased by CCI on days 1, 3, 7 and 14 compared to sham group, however, ligustrazine reversed this effects. Additionally, the elevated levels of TNF-α, IL-1ß, and IL-2 in CCI spinal cord were inhibited by ligustrazine. Quantitative real-time (qRT-PCR) and Western blotting analysis showed that the test substance reduced the elevated expression of pSTAT3 in the spinal cord induced by CCI, and while IL-6 administration reversed the levels as well as the behavior responses. CONCLUSION: Our results suggest that ligustrazine could effectively attenuate neuropathic pain by inhibition of Janus Kinase (JAK)/STAT3 pathway in CCI rats.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/uso terapêutico
Constrição Patológica/complicações
Neuralgia/tratamento farmacológico
Pirazinas/uso terapêutico
Fator de Transcrição STAT3/antagonistas & inibidores
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Comportamento Animal/efeitos dos fármacos
Citocinas/antagonistas & inibidores
Citocinas/biossíntese
Temperatura Alta
Masculino
Neuralgia/etiologia
Neuralgia/psicologia
Limiar da Dor/efeitos dos fármacos
Ratos
Ratos Sprague-Dawley
Fator de Transcrição STAT3/biossíntese
Nervo Isquiático/lesões
Medula Espinal/efeitos dos fármacos
Medula Espinal/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Cytokines); 0 (Pyrazines); 0 (STAT3 Transcription Factor); 0 (Stat3 protein, rat); V80F4IA5XG (tetramethylpyrazine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6546


  4 / 11607 MEDLINE  
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[PMID]:28453725
[Au] Autor:Nonhoff J; Ricke-Hoch M; Mueller M; Stapel B; Pfeffer T; Kasten M; Scherr M; von Kaisenberg C; Bauersachs J; Haghikia A; Hilfiker-Kleiner D
[Ad] Endereço:Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany.
[Ti] Título:Serelaxin treatment promotes adaptive hypertrophy but does not prevent heart failure in experimental peripartum cardiomyopathy.
[So] Source:Cardiovasc Res;113(6):598-608, 2017 May 01.
[Is] ISSN:1755-3245
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Aims: Peripartum cardiomyopathy (PPCM) is a systolic left ventricular dysfunction developing in the peripartum phase in previously healthy women. Relaxin-2 is a pregnancy hormone with potential beneficial effects in heart failure patients. We evaluated Relaxin-2 as a potential diagnostic marker and/or a therapeutic agent in PPCM. Methods and results: In healthy peripartum women, serum Relaxin-2 levels (measured by ELISA in the second half of pregnancy) were elevated showing a decreasing trend in the first postpartum week and returned to non-pregnant levels thereafter. In PPCM patients diagnosed in the first postpartum week, serum Relaxin-2 levels were lower compared to healthy postpartum stage-matched controls. In PPCM patients diagnosed later (0.5-10 months postpartum) Relaxin-2 levels were in the range of non-pregnant controls and not different from healthy postpartum stage-matched controls. In mice, serum Relaxin-1 (functional equivalent of human Relaxin-2) was increased late in pregnancy and rapidly cleared in the first postpartum week. In mice with PPCM due to a cardiomyocyte-specific knockout of STAT3 (CKO) neither low nor high dose of recombinant Relaxin-2 (serelaxin, sRlx-LD: 30 µg/kg/day; sRlx-HD: 300 µg/kg/day) affected cardiac fibrosis, inflammation and heart failure but sRlx-HD increased capillary/cardiomyocyte ratio. sRlx-HD significantly increased heart/body weight ratio and cardiomyocyte cross-sectional area in postpartum CKO and wild-type mice without changing the foetal gene expression program (ANP or ß-MHC). sRlx-HD augmented plasma Prolactin levels in both genotypes, which induced cardiac activation of STAT5. In vitro analyses showed that Prolactin induces cardiomyocyte hypertrophy via activation of STAT5. Conclusion: Although Relaxin-2 levels seemed lower in PPCM patients diagnosed early postpartum, we observed a high pregnancy-related variance of serum Relaxin-2 levels peripartum making it unsuitable as a biomarker for this condition. Supplementation with sRlx may contribute to angiogenesis and compensatory hypertrophy in the diseased heart, but the effects are not sufficient to prevent heart failure in an experimental PPCM model.
[Mh] Termos MeSH primário: Cardiomegalia/patologia
Cardiomiopatias/tratamento farmacológico
Fármacos Cardiovasculares/farmacologia
Insuficiência Cardíaca/prevenção & controle
Miócitos Cardíacos/efeitos dos fármacos
Período Pós-Parto/sangue
Relaxina/farmacologia
[Mh] Termos MeSH secundário: Adulto
Animais
Biomarcadores/sangue
Cardiomegalia/sangue
Cardiomegalia/fisiopatologia
Cardiomiopatias/sangue
Cardiomiopatias/patologia
Cardiomiopatias/fisiopatologia
Estudos de Casos e Controles
Modelos Animais de Doenças
Feminino
Insuficiência Cardíaca/sangue
Insuficiência Cardíaca/patologia
Insuficiência Cardíaca/fisiopatologia
Seres Humanos
Camundongos Knockout
Miócitos Cardíacos/metabolismo
Miócitos Cardíacos/patologia
Gravidez
Prolactina/sangue
Ratos
Proteínas Recombinantes/farmacologia
Sistema de Registros
Relaxina/sangue
Fator de Transcrição STAT3/deficiência
Fator de Transcrição STAT3/genética
Fator de Transcrição STAT5/metabolismo
Transdução de Sinais/efeitos dos fármacos
Volume Sistólico
Função Ventricular Esquerda
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Cardiovascular Agents); 0 (RLN2 protein, human); 0 (Recombinant Proteins); 0 (Rln1 protein, mouse); 0 (STAT3 Transcription Factor); 0 (STAT5 Transcription Factor); 0 (Stat3 protein, mouse); 0 (relaxin-3 protein, mouse); 0 (serelaxin protein, human); 9002-62-4 (Prolactin); 9002-69-1 (Relaxin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/cvr/cvw245


  5 / 11607 MEDLINE  
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[PMID]:29180487
[Au] Autor:Pierog PL; Zhao Y; Singh S; Dai J; Yap GS; Fitzgerald-Bocarsly P
[Ad] Endereço:Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103.
[Ti] Título: Inactivates Human Plasmacytoid Dendritic Cells by Functional Mimicry of IL-10.
[So] Source:J Immunol;200(1):186-195, 2018 01 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Plasmacytoid dendritic cells (pDCs) are the major producers of IFN-α, an antiviral cytokine involved in immunomodulation and control of HIV type 1 replication, whereas is a life-threatening opportunistic infection in AIDS patients. During infection with HIV type 1, human pDCs decrease in circulation and remaining pDC produce lower amounts of IFN-α in response to viral stimulation. In this study, we investigated the impact of coinfection with on the innate virus-directed responses of human pDCs. Using intracellular flow cytometry and fluorescence microscopy, we determined that invaded but did not induce IFN-α or TNF-α in human pDC. However, inhibited IFN-α and TNF-α produced in response to HSV and HIV, thus functionally inactivating pDC. IFN-α production was inhibited only in cells infected by , which inhibited neither uptake of GFP-HSV nor localization of TLR9 in CD71 endosomes, directing us to investigate downstream events. Using imaging flow cytometry, we found that both and IL-10 inhibited virus-induced nuclear translocation, but not phosphorylation, of IFN response factor 7. Blockade of IFN response factor 7 nuclear translocation and inhibition of the IFN-α response was partially reversed by a deficiency in the -derived ROP16 kinase, known to directly phosphorylate STAT3, a critical mediator of IL-10's anti-inflammatory effects. Taken together, our results indicate that suppresses pDC activation by mimicking IL-10's regulatory effects through an ROP16 kinase-dependent mechanism. Our findings further imply a convergent mechanism of inhibition of TLR signaling by and IL-10 and suggest potential negative consequences of HIV/ coinfection.
[Mh] Termos MeSH primário: Células Dendríticas/imunologia
Infecções por HIV/imunologia
HIV-1/imunologia
Interleucina-10/metabolismo
Infecções Oportunistas/imunologia
Proteínas Tirosina Quinases/metabolismo
Proteínas de Protozoários/metabolismo
Toxoplasma/imunologia
Toxoplasmose/imunologia
[Mh] Termos MeSH secundário: Diferenciação Celular
Células Cultivadas
Coinfecção
Células Dendríticas/parasitologia
Seres Humanos
Imunidade Inata
Imunomodulação
Fator Regulador 7 de Interferon/metabolismo
Interferon-alfa/metabolismo
Fator de Transcrição STAT3/metabolismo
Transdução de Sinais
Receptor Toll-Like 9/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (IRF7 protein, human); 0 (Interferon Regulatory Factor-7); 0 (Interferon-alpha); 0 (Protozoan Proteins); 0 (STAT3 Transcription Factor); 0 (Toll-Like Receptor 9); 0 (Tumor Necrosis Factor-alpha); 130068-27-8 (Interleukin-10); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.10.1 (Rop16 protein, Toxoplasma gondii)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1701045


  6 / 11607 MEDLINE  
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[PMID]:28455144
[Au] Autor:Zhang F; Lu YX; Chen Q; Zou HM; Zhang JM; Hu YH; Li XM; Zhang WJ; Zhang W; Lin C; Li XN
[Ad] Endereço:Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address: zfan1985@yeah.net.
[Ti] Título:Identification of NCK1 as a novel downstream effector of STAT3 in colorectal cancer metastasis and angiogenesis.
[So] Source:Cell Signal;36:67-78, 2017 Aug.
[Is] ISSN:1873-3913
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Signal transducer and activator of transcription 3 (STAT3) is known to activate targets associated with invasion, proliferation, and angiogenesis in a wide variety of cancers. The adaptor protein NCK1 is involved in cytoskeletal movement and was identified as a STAT3-associated target in human tumors. However, the underlying molecular mechanism associated with colorectal cancer (CRC) metastasis is not yet completely understood. In this study, we report a novel STAT3 to NCK1 signaling pathway in colorectal cancer (CRC). We investigated the expression of NCK1 and its potential clinical and biological significance in CRC. NCK1 was noticeably up-regulated in human CRC tissues. NCK1 was also significantly associated with serosal invasion, lymph metastasis, and tumor-node-metastasis classification but was inversely correlated with differentiation. Gain-of-function and loss-of-function studies have shown that ectopic expression of NCK1 enhanced metastasis and angiogenesis in CRC cells. By gene expression analyses, we revealed a high co-overexpression of STAT3 and NCK1 in CRC tissues. Ectopic overexpression of STAT3 in CRC cells induced the expression of NCK1, whereas STAT3 knockdown decreased the expression of NCK1. Promoter activation and binding analyses demonstrated that STAT3 promoted the expression of NCK1 via direct action on the NCK1 promoter. The knock down of NCK1 partially reduced the CRC cell metastasis and angiogenesis promoted by STAT3. Additionally, by co-immunoprecipitation assays, we verified that NCK1 interacted with PAK1, which resulted in the activation of the PAK1/ERK pathway. STAT3 induced the transcription of NCK1 and triggered a PAK1/ERK cascade in CRC. These findings suggest a novel STAT3 to NCK1 to PAK1/ERK signaling mechanism that is potentially critical for CRC metastasis and angiogenesis.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Neoplasias Colorretais/irrigação sanguínea
Neoplasias Colorretais/patologia
Metástase Linfática/patologia
Neovascularização Patológica/metabolismo
Proteínas Oncogênicas/metabolismo
Fator de Transcrição STAT3/metabolismo
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/genética
Animais
Movimento Celular
Galinhas
Neoplasias Colorretais/genética
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Feminino
Quinase 2 de Adesão Focal/metabolismo
Regulação Neoplásica da Expressão Gênica
Técnicas de Silenciamento de Genes
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Masculino
Camundongos Nus
Meia-Idade
Proteínas Oncogênicas/genética
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Nck protein); 0 (Oncogene Proteins); 0 (STAT3 Transcription Factor); EC 2.7.10.2 (Focal Adhesion Kinase 2); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


  7 / 11607 MEDLINE  
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[PMID]:29339767
[Au] Autor:Liu X; Mo W; Ye J; Li L; Zhang Y; Hsueh EC; Hoft DF; Peng G
[Ad] Endereço:Department of Internal Medicine, Division of Infectious Diseases, Allergy & Immunology, Saint Louis University School of Medicine, St Louis, MO, 63104, USA.
[Ti] Título:Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition.
[So] Source:Nat Commun;9(1):249, 2018 01 16.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Defining the suppressive mechanisms used by regulatory T (Treg) cells is critical for the development of effective strategies for treating tumors and chronic infections. The molecular processes that occur in responder T cells that are suppressed by Treg cells are unclear. Here we show that human Treg cells initiate DNA damage in effector T cells caused by metabolic competition during cross-talk, resulting in senescence and functional changes that are molecularly distinct from anergy and exhaustion. ERK1/2 and p38 signaling cooperate with STAT1 and STAT3 to control Treg-induced effector T-cell senescence. Human Treg-induced T-cell senescence can be prevented via inhibition of the DNA damage response and/or STAT signaling in T-cell adoptive transfer mouse models. These studies identify molecular mechanisms of human Treg cell suppression and indicate that targeting Treg-induced T-cell senescence is a checkpoint for immunotherapy against cancer and other diseases associated with Treg cells.
[Mh] Termos MeSH primário: Dano ao DNA
Sistema de Sinalização das MAP Quinases
Linfócitos T Reguladores/fisiologia
[Mh] Termos MeSH secundário: Senescência Celular
Glucose/metabolismo
Seres Humanos
Imunoterapia
Fator de Transcrição STAT1/metabolismo
Fator de Transcrição STAT1/fisiologia
Fator de Transcrição STAT3/metabolismo
Fator de Transcrição STAT3/fisiologia
Linfócitos T Reguladores/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (STAT1 Transcription Factor); 0 (STAT1 protein, human); 0 (STAT3 Transcription Factor); 0 (STAT3 protein, human); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02689-5


  8 / 11607 MEDLINE  
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[PMID]:28460481
[Au] Autor:Kang HJ; Chung DH; Sung CO; Yoo SH; Yu E; Kim N; Lee SH; Song JY; Kim CJ; Choi J
[Ad] Endereço:Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
[Ti] Título:SHP2 is induced by the HBx-NF-κB pathway and contributes to fibrosis during human early hepatocellular carcinoma development.
[So] Source:Oncotarget;8(16):27263-27276, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The non-receptor tyrosine phosphatase SHP2 has scaffolding functions in signal transduction cascades downstream of growth receptors. A recent study suggested that SHP2 acts as a tumor suppressor during hepatocellular carcinoma (HCC) development. Herein we examined whether SHP2 links the HBx-NF-κB pathway to EGFR signaling during HCC development. The overexpression of HBx or NF-κB led to increased SHP2 expression via NF-κB binding to the Shp2 promoter. EGF treatment induced ERK activation as well as the rapid assembly of SHP2, EGFR, and Gab1. Upon LPS stimulation, NF-κB-SHP2-ERK activation and phosphorylated STAT3 levels exhibited a negative correlation in vitro. By contrast, in patients with HBV-associated HCC, NF-κB-SHP2-ERK and IL-6-JAK-STAT3 pathway activity levels were concomitantly higher in adjacent non-neoplastic tissues than in HCC tissues. The immunohistochemical analysis of 162 tissues of patients with HCC revealed that SHP2 levels were significantly higher in non-neoplastic background tissues than in corresponding HCC tissues and considerably increased in background liver tissues with advanced fibrosis (P < 0.001). SHP2 expression increased gradually from normal liver to chronic hepatitis, cirrhosis, and background liver with a dysplastic nodule, but was decreased or lost in dysplastic nodules and HCC. This is the first report to describe the existence of the HBx-NF-κB-SHP2 pathway, linking HBV infection to the EGFR-RAS-RAF-MAPK pathway in the liver. SHP2 depletion from the negative crosstalk between NF-κB and STAT3 accelerates HCC development.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/etiologia
Carcinoma Hepatocelular/metabolismo
Neoplasias Hepáticas/etiologia
Neoplasias Hepáticas/metabolismo
NF-kappa B/metabolismo
Proteína Tirosina Fosfatase não Receptora Tipo 11/genética
Transativadores/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Carcinoma Hepatocelular/patologia
Carcinoma Hepatocelular/cirurgia
Linhagem Celular Tumoral
Feminino
Fibrose
Regulação Neoplásica da Expressão Gênica
Vírus da Hepatite B/fisiologia
Seres Humanos
Cirrose Hepática/etiologia
Cirrose Hepática/metabolismo
Cirrose Hepática/patologia
Neoplasias Hepáticas/patologia
Neoplasias Hepáticas/cirurgia
Masculino
Meia-Idade
Modelos Biológicos
Gradação de Tumores
Estadiamento de Neoplasias
Regiões Promotoras Genéticas
Ligação Proteica
Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo
Fator de Transcrição STAT3/metabolismo
Transdução de Sinais
Proteínas ras/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NF-kappa B); 0 (STAT3 Transcription Factor); 0 (Trans-Activators); 0 (hepatitis B virus X protein); EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11); EC 3.6.5.2 (ras Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15930


  9 / 11607 MEDLINE  
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[PMID]:29373815
[Au] Autor:Deshpande GP; Imamdin A; Lecour S; Opie LH
[Ad] Endereço:Hatter Institute for cardiovascular Research in Africa, Department of Medicine, University of Cape Town, South Africa. Electronic address: gdeshpande@sun.ac.za.
[Ti] Título:Sphingosine-1-phosphate (S1P) activates STAT3 to protect against de novo acute heart failure (AHF).
[So] Source:Life Sci;196:127-132, 2018 Mar 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Acute heart failure (AHF) is a burden disease, with high mortality and re-hospitalisations. Using an ex-vivo model of AHF, we have previously reported that sphingosine-1-phosphate (S1P) confers cardioprotection. However, the mechanisms remain to be elucidated. In the present study, we aimed to examine the role of the cardioprotective signal transducer and activator of transcription 3 (STAT3) in S1P mediated improved functional recovery in AHF. MATERIAL AND METHODS: Isolated hearts from male Long-Evans rats were subjected to hypotensive AHF for 35 min followed by a recovery phase of 30 min (n ≥ 4/group). S1P (10 nM) was given during either the hypotensive or the recovery phase with/without an inhibitor of STAT3, AG490. Functional parameters were recorded throughout the experiment. KEY FINDINGS: Following an AHF insult, S1P, given during the recovery phase, improved the heart rate (HR) compared to the control (175.2 ±â€¯30.7 vs. 71.6 ±â€¯27.4 beats per minute (BPM); p < 0.05), with no changes in the left ventricular developed pressure. This effect was associated with an increase in phosphorylated STAT3 levels in the nucleus. Addition of AG490 with S1P abolished the cardioprotective effect of S1P (42.3 ±â€¯17.1 vs. 148.8 ±â€¯26.4 BPM for S1P; p < 0.05). SIGNIFICANCE: Our data suggest that S1P protects in an ex-vivo rat heart model of AHF by activation of STAT3 and provide further evidence for the usage of S1P as a potential therapy in patients suffering from AHF.
[Mh] Termos MeSH primário: Cardiotônicos/farmacologia
Insuficiência Cardíaca/prevenção & controle
Lisofosfolipídeos/farmacologia
Fator de Transcrição STAT3/metabolismo
Esfingosina/análogos & derivados
[Mh] Termos MeSH secundário: Doença Aguda
Animais
Pressão Sanguínea/efeitos dos fármacos
Frequência Cardíaca/efeitos dos fármacos
Técnicas In Vitro
Masculino
Fosforilação/efeitos dos fármacos
Ratos
Ratos Long-Evans
Fator de Transcrição STAT3/antagonistas & inibidores
Fator de Transcrição STAT3/efeitos dos fármacos
Esfingosina/farmacologia
Tirfostinas/farmacologia
Disfunção Ventricular Esquerda/induzido quimicamente
Disfunção Ventricular Esquerda/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cardiotonic Agents); 0 (Lysophospholipids); 0 (STAT3 Transcription Factor); 0 (Stat3 protein, rat); 0 (Tyrphostins); 0 (alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide); 26993-30-6 (sphingosine 1-phosphate); NGZ37HRE42 (Sphingosine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE


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[PMID]:29429507
[Au] Autor:Léauté-Labrèze C
[Ad] Endereço:Unité de dermatologie pédiatrique et centre de référence des maladies rares de la peau, hôpital Pellegrin-Enfants, CHU de Bordeaux, 33076 Bordeaux Cedex, France. Electronic address: christine.labreze@chu-bordeaux.fr.
[Ti] Título:[What's new in pediatric dermatology?]
[Ti] Título:Quoi de neuf en dermatologie pédiatrique ?.
[So] Source:Ann Dermatol Venereol;143 Suppl 3:S29-S36, 2016 Dec.
[Is] ISSN:0151-9638
[Cp] País de publicação:France
[La] Idioma:fre
[Ab] Resumo:The association of a birth defect and a segmental hemangioma is well established, a consensus concerning evaluation and monitoring of infants with PHACE or LUMBAR syndromes has been published. The efficacy of propranolol in infantile hemangioma is proven; however there were still unresolved issues concerning the safety in children; after 8 years of use on thousands of children safety data collection did not show any unexpected side effects. Topical treatment of infantile hemangiomas with beta-blockers, such as timolol, is very popular, but recent publications revealed a significant systemic absorption that could be responsible for severe side effects, such as bradycardia, in low birthweight infants. As a consequence, this therapeutic option should be considered with caution. In the last 2 years mTOR inhibitors have been tested in low-flow vascular malformations with varying success, but progress remains to be done in the treatment of vascular abnormalities. Today, genetics has led to advances in the understanding of the pathophysiology and in the future targeted therapies could probably be feasible. Skin barrier deficiency is responsible for the development of allergic phenomena in atopic patients, since it has been shown that sensibilisation, even to food, could probably be induced by skin contact. Unfortunately, the topical treatment with crisaborole, a phosphodiesterase 4 inhibitor, does not look like a revolution in children atopic dermatitis, its efficacy seems equivalent to emollient application. In the field of infectious diseases, changes in viral outbreaks are the most reported. Furthermore epidemic Zika virus, enteroviruses are responsible for expanded dermatological manifestations and also severe meningoencephalitis. Paraviral character of various eruptions, such as gloves and socks syndrome or eruptive pseudoangiomatosis is challenged.
[Mh] Termos MeSH primário: Dermatopatias
[Mh] Termos MeSH secundário: Coartação Aórtica/terapia
Doenças Autoimunes/genética
Criança
Dermatologia
Anormalidades do Olho/terapia
Hipersensibilidade Alimentar/imunologia
Hemangioma/terapia
Seres Humanos
Síndromes Neurocutâneas/terapia
Pediatria
Fator de Transcrição STAT3/genética
Dermatopatias/diagnóstico
Dermatopatias/etiologia
Dermatopatias/terapia
Fenômenos Fisiológicos da Pele
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (STAT3 Transcription Factor); 0 (STAT3 protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE



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