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Pesquisa : D12.776.157.125.050.100 [Categoria DeCS]
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Texto completo SciELO Chile
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Id: biblio-950766
Autor: Doan, Chung Chinh; Le, Long Thanh; Hoang, Son Nghia; Do, Si Minh; Van Le, Dong.
Título: Simultaneous silencing of VEGF and KSP by siRNA cocktail inhibits proliferation and induces apoptosis of hepatocellular carcinoma Hep3B cells
Fonte: Biol. Res;47:1-15, 2014. ilus, graf, tab.
Idioma: en.
Resumo: BACKGROUND: Vascular endothelial growth factor (VEGF) is involved in the growth of new blood vessels that feed tumors and kinesin spindle protein (KSP) plays a critical role in mitosis involving in cell proliferation. Simultaneous silencing of VEGF and KSP, an attractive and viable approach in cancer, leads on restricting cancer progression. The purpose of this study is to examine the therapeutic potential of dual gene targeted siRNA cocktail on human hepatocellular carcinoma Hep3B cells. RESULTS: The predesigned siRNAs could inhibit VEGF and KSP at mRNA level. siRNA cocktail showed a further downregulation on KSP mRNA and protein levels compared to KSP-siRNA or VEGF-siRNA, but not on VEGF expression. It also exhibited greater suppression on cell proliferation as well as cell migration or invasion capabilities and induction of apoptosis in Hep3B cells than single siRNA simultaneously. This could be explained by the significant downregulation of Cyclin D1, Bcl-2 and Survivin. However, no sigificant difference in the mRNA and protein levels of ANG2, involving inhibition of angiogenesis was found in HUVECs cultured with supernatant of Hep3B cells treated with siRNA cocktail, compared to that of VEGF-siRNA. CONCLUSION: Silencing of VEGF and KSP plays a key role in inhibiting cell proliferation, migration, invasion and inducing apoptosis of Hep3B cells. Simultaneous silencing of VEGF and KSP using siRNA cocktail yields promising results for eradicating hepatocellular carcinoma cells, a new direction for liver cancer treatment.
Descritores: Cinesina/genética
Apoptose/genética
Inativação Gênica
RNA Interferente Pequeno/genética
Fator A de Crescimento do Endotélio Vascular/genética
Proliferação de Células/genética
-Sais de Tetrazólio
Transfecção
Inibidores de Cisteína Proteinase/metabolismo
Regulação para Baixo
Movimento Celular
Western Blotting
Cinesina/metabolismo
Anexina A5
Genes bcl-2
Ciclina D1/metabolismo
Proteínas de Transporte Vesicular/metabolismo
Linhagem Celular Tumoral
Fator A de Crescimento do Endotélio Vascular/metabolismo
Proteínas Inibidoras de Apoptose/metabolismo
Células Endoteliais da Veia Umbilical Humana/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Citometria de Fluxo
Survivina
Mitose/genética
Limites: Humanos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: CL1.1 - Biblioteca Central


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Texto completo SciELO Brasil
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Id: biblio-1130782
Autor: Horimoto, Alex Magno Coelho; Jesus, Laize Guerreiro de; Souza, Albert Schiaveto de; Rodrigues, Silvia Helena; Kayser, Cristiane.
Título: Anti-annexin V autoantibodies and vascular abnormalities in systemic sclerosis: a longitudinal study
Fonte: Adv Rheumatol;60:38, 2020. tab.
Idioma: en.
Resumo: Abstract Background: Annexins are a group of conserved proteins which exert several regulatory functions on various cellular activities. Increased frequency and levels of antibodies against annexin V have already been observed in several autoimmune diseases including systemic sclerosis (SSc), but their role as a vascular biomarker is unknown. The aim of this study was to determine the serum levels and the dynamical behavior of anti-annexin V antibodies over a 24 months follow-up in patients with SSc. Methods: In this bicentric cross-sectional study, 70 patients with SSc were consecutively selected from March 2016 to April 2017. Demographic and clinical features, including the presence of active DUs, were collected. Serum anti-annexin V IgG and IgM antibodies were measured at baseline and after 6, 12 and 24 months of follow-up. Videocapillaroscopy was performed in all patients. Results: Among the 70 SSc patients included anti-annexin V IgG was found in 11 patients (15.7%) (range of 15.88-39.48 U/mL) and anti-annexin V IgM in 10 patients (14.3%) (range of 14.16-22.69 U/mL) at baseline. During follow-up, the number of patients who were positive for anti-annexin V IgG and IgM remained stable over 24 months. Among the patients with positive anti-annexin V IgG at baseline the frequency of patients with necrosis or amputation of extremities, forced vital capacity less than 70% and pulmonary arterial hypertension (PAH) was significantly higher than in patients with negative anti-annexin V IgG antibodies. Patients with anti-annexin V IgG had also a higher Raynaud's Condition Score and a higher Health Assessment Questionnaire Disability Index (HAQ-DI) than patients without these antibodies at baseline. Patients with positive anti-annexin V IgM at baseline presented a higher frequency of PAH, compared to those with negative anti-annexin V IgM at baseline. Conclusions: Anti-annexin V antibodies are stable and do not change their positivity during a 24 month follow-up in SSc patients. Anti-annexin V IgG was associated with more severe interstitial lung involvement and digital microangiopathy, and patients with anti-annexin V IgG or IgM had a higher occurrence of PAH indicating an association of these biomarker with more severe disease.(AU)
Descritores: Escleroderma Sistêmico/fisiopatologia
Imunoglobulina G/sangue
Biomarcadores/análise
Anexina A5/sangue
-Estudos Transversais/instrumentação
Angioscopia Microscópica/instrumentação
Limites: Humanos
Responsável: BR1.1 - BIREME


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Texto completo SciELO Brasil
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Id: biblio-1041049
Autor: Bilgir, Oktay; Vural, Huseyin Afsin; Bilgir, Ferda; Akan, Ozden Yildirim; Demir, Ismail.
Título: Serum Annexin V and Anti-Annexin V levels and their relationship with metabolic parameters in patients with type 2 diabetes
Fonte: Rev. Assoc. Med. Bras. (1992);65(8):1042-1047, Aug. 2019. tab.
Idioma: en.
Resumo: SUMMARY BACKGROUND We investigated the serum annexin V and anti-annexin V levels and their relationship with metabolic parameters in patients recently diagnosed type 2 diabetic. METHODS A total of 143 patients recently diagnosed type 2 diabetes and 133 control subjects were included in the study. Body mass index (BMI), hs-CRP, HOMA-IR, carotid intima-media thickness, and serum levels of annexin V and anti-annexin V were investigated. RESULTS HOMA-IR, serum hs-CRP, and carotid intima-media thickness were found to be statistically significant. The Pearson correlation analysis revealed a statistically significant positive relationship between the carotid intima-media thickness and the annexin V level (r=0.29, p=0.006*). A statistically significant positive relationship was also detected between the Annexin V level and level of serum hs-CRP (r=0.29 p=0.006*). CONCLUSION A positive relationship was observed between the carotid intima-media thickness and annexin V at the end of our investigation. In this regard, we also believe that serum levels of annexin V may be increased for cardiovascular protection in the elevation of carotid intima-media thickness.

RESUMO OBJETIVO Investigar os níveis séricos de anexina V e antianexina V e sua relação com os parâmetros metabólicos em pacientes diabéticos tipo 2 recém-diagnosticados. MÉTODOS Foram incluídos no estudo 143 pacientes e 133 controles com diabetes tipo 2 recém-diagnosticado. O índice de massa corporal (IMC), PCR-as, Homa-IR, espessura íntima média carotídea e níveis séricos de anexina V e antianexina V foram investigados. RESULTADOS O Homa-IR, a PCR-s do soro e a espessura média da carótida foram estatisticamente significantes. A análise de correlação de Pearson revelou uma relação positiva estatisticamente significante entre a espessura média da carótida e anexina V (r=0,29; p=0,006 *). Foi também detectada uma relação positiva estatisticamente significativa entre o nível de anexina V e o nível sérico de PCR-as (r=0,29, p=0,006*). CONCLUSÃO Também foi observada uma relação positiva entre a espessura média da carótida e anexina V no final da nossa investigação. A esse respeito, também pensamos que os níveis séricos de anexina V podem ser aumentados para proteção cardiovascular na elevação da espessura média da carótida.
Descritores: Autoanticorpos/sangue
Anexina A5/sangue
Diabetes Mellitus Tipo 2/sangue
-Índice de Massa Corporal
Estudos de Casos e Controles
Estudos Transversais
Anexina A5/imunologia
Anexina A5/metabolismo
Diabetes Mellitus Tipo 2/metabolismo
Espessura Intima-Media Carotídea
Homeostase
Pessoa de Meia-Idade
Limites: Humanos
Masculino
Feminino
Adulto
Idoso
Responsável: BR1.1 - BIREME


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Id: biblio-1003291
Autor: Arietti, Alba Soledad; Pedano, Valeria Cristina; Neme, Viviana; Racca, Agustina; Sotelo, Vanessa; Rozzatti, Maria Soledad; Gobbi, Carla; Vigliano, Mercedes; Alba, Paula; Demarchi, Marcela.
Título: Niveles de anticuerpos anti-anexina A5 y manifestaciones de síndrome antifosfolípido primario obstétrico / Levels of anti-anexinal antibodies A5 and manifestations of obstetric primary antiphospholipid syndrome
Fonte: Rev. argent. reumatol;29(4):6-12, dic. 2018. ilus, tab.
Idioma: es.
Resumo: El Síndrome Antifosfolípidos (SAF) describe un trastorno trombofílico autoinmune caracterizado por complicaciones obstétricas. La Anexina A5 (Anx A5) es una proteína que se estudia como un nuevo autoantígeno presente en el SAF, la presencia de autoanticuerpos frente a Anx A5 podría causar trombosis placentaria y pérdida del embarazo. El objetivo de este estudio fue analizar los niveles de IgG e IgM anti-Anx A5 en mujeres con SAF primario obstétrico y su asociación con diferentes complicaciones en una población de la ciudad de Córdoba. Se trabajó con muestras de pacientes puérperas que asistieron al Hospital Córdoba y al Hospital Materno Neonatal durante los años 2013-2017 con diagnóstico de SAF obstétrico y un grupo control formado por pacientes con embarazos normales. En la mayoría de las pacientes estudiadas, los niveles de IgG e IgM anti-Anx A5 se encontraron por debajo del rango de referencia, se mostró un aumento estadísticamente significativo de los niveles de IgG en pacientes con SAF respecto al grupo control. Pero no existieron asociaciones específicas entre los niveles de anticuerpo y los tres tipos de manifestaciones clínicas presentes en los criterios de clasificación. Estos hallazgos podrían sugerir una relación entre los anticuerpos anti-Anx A5 con el SAF obstétrico.

Antiphospholipid Syndrome (APS) describes an autoimmune thrombophilic disorder characterized by obstetric complications. Annexin A5 (Anx A5) is a protein that is studied as a new autoantigen present in APS, the presence of autoantibodies against Anx A5 could cause placental thrombosis and possibly pregnancy loss. The aim of this study was to analyze levels of IgG and IgM anti-Anx A5 in women with primary obstetric APS and its association with different complications in a population of the city of Córdoba. We worked with samples of puerperal patients who attended the Córdoba Hospital and the Maternal Neonatal Hospital during the years 2013-2017 with a diagnosis of obstetric APS and a control group formed by patients with normal pregnancies. In most of the patients studied, levels of IgG and IgM anti-Anx A5 were below the reference range, is demonstrate an increase statistically significant in the levels of the IgG in patients with APS compared with control group. But there were no specific associations between antibody levels and the three types of obstetric clinical manifestations present in the classification criteria. These findings could suggest a relationship between anti-Anx A5 antibodies and obstetric APS.
Descritores: Síndrome Antifosfolipídica
Anexina A5
Anticorpos
Responsável: AR423.1 - Biblioteca


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Id: lil-266546
Autor: Campos, Begoña; Wang, Songtao; Retzinger, Gregory S; Kaetzel, Marcia A; Seaton, Barbara A; Karin, Norman J; Johnson, J. David; Dedman, John R.
Título: Mutation of highly conserved arginine residues disrupts the Structure and Function of Annexin V
Fonte: Arch. med. res;30(5):360-7, sept.-oct. 1999. ilus, graf.
Idioma: en.
Resumo: Background. Annexins are a family of structurally related proteins that bind to phospholipid membranes in a Ca²+-dependent manner. Annexins are characterized by highly conserved canonical domains of approximately 70 amino acids. Anexin V contains four such domains. Each of these domains has a highly conserved arginine (R). Methods. To evaluate the role of the conserved arginines in the molecular structure of annexin V, negatively charged amino acids were substituted for arginines at positions R43, R115, R199, and R274 using site-directed mutagenesis. Results. Mutants R199D and R274E were rapidly degraded when expressed in bacteria, and were not further characterized. R43E exhibited an electrophoretic mobility similar to the wild-type protein, while R115E migrated significantly in a slower fashion, suggesting a less compact conformation, R43E and R115E exhibited much grater susceptibility to proteolytic digestion than the wild type. While Ca²+-dependence for phospholipid binding was similar in both mutants (half-maximal 50-80 µ; Ca²+), R43E and R115E exhibited a phospholipid affinities of the annexins, a phospholipid-dependent clotting reaction, the activated partial thromboplastin time (aPTT), was significantly prolonged by the wild-type protein and mutants R115E and R115A. The aPTT was unaffected by R43E. Conclusions. Our data suggest that mutation of these highly conserved arginine residus in each of the four canonical domains of annexin have differential effects on the phospholipid binding tertiary structure, and proteolytic susceptibility of annexin V. The site I mutation , R43E, produced a large decrease in phospholipid affinity associated with an increase in proteolytic susceptibility. The site II mutation, R115E, produced a small change in phospholipid binding but a significant modification of electrophoretic mobility. Our data suggest that highly conserved arginine residues are required to stabilize the tertiary structure of ammexin V by establishing hydrogen bonds and ionic bridges
Descritores: Anexina A5/genética
Anexina A5/metabolismo
Sequência Conservada
Mutagênese Sítio-Dirigida
-Sequência de Aminoácidos
Relação Estrutura-Atividade
Limites: Animais
Ratos
Responsável: MX1.1 - CENIDSP - Centro de Información para Decisiones en Salud Pública



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