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1.
Braz. j. med. biol. res ; 54(11): e11363, 2021. graf
Artigo em Inglês | LILACS | ID: biblio-1339445

RESUMO

Cervical cancer (CC) is the most common malignant tumor in females. Although persistent high-risk human papillomavirus (HPV) infection is a leading factor that causes CC, few women with HPV infection develop CC. Therefore, many mechanisms remain to be explored, such as aberrant expression of oncogenes and tumor suppressor genes. To identify promising prognostic factors and interpret the relevant mechanisms of CC, the RNA sequencing profile of CC was downloaded from the Cancer Genome Atlas and the Gene Expression Omnibus databases. The GSE63514 dataset was analyzed, and differentially expressed genes (DEGs) were obtained by weighted coexpression network analysis and the edgeR package in R. Fifty-three shared genes were mainly enriched in nuclear chromosome segregation and DNA replication signaling pathways. Through a protein-protein interaction network and prognosis analysis, the kinesin family member 14 (KIF14) hub gene was extracted from the set of 53 shared genes, which was overexpressed and associated with poor overall survival (OS) and disease-free survival (DFS) of CC patients. Mechanistically, gene set enrichment analysis showed that KIF14 was mainly enriched in the glycolysis/gluconeogenesis signaling pathway and DNA replication signaling pathway, especially in the cell cycle signaling pathway. RT-PCR and the Human Protein Atlas database confirmed that these genes were significantly increased in CC samples. Therefore, our findings indicated the biological function of KIF14 in cervical cancer and provided new ideas for CC diagnosis and therapies.


Assuntos
Humanos , Feminino , Neoplasias do Colo do Útero/genética , Infecções por Papillomavirus , Regulação Neoplásica da Expressão Gênica , Ciclo Celular/genética , Cinesinas/genética , Proteínas Oncogênicas , Intervalo Livre de Doença , Biologia Computacional , Mapas de Interação de Proteínas
2.
Braz. j. med. biol. res ; 54(2): e9173, 2021. tab, graf
Artigo em Inglês | LILACS, Coleciona SUS | ID: biblio-1142586

RESUMO

This study aimed to explore the correlation of kinesin family member 2A (KIF2A) expression with disease risk, clinical characteristics, and prognosis of acute myeloid leukemia (AML), and investigate the effect of KIF2A knockdown on AML cell activities in vitro. Bone marrow samples were collected from 176 AML patients and 40 healthy donors, and KIF2A expression was measured by real-time quantitative polymerase chain reaction. Treatment response, event-free survival (EFS), and overall survival (OS) were assessed in AML patients. In vitro, KIF2A expression in AML cell lines and CD34+ cells (from healthy donors) was measured, and the effect of KIF2A knockdown on AML cell proliferation and apoptosis in HL-60 and KG-1 cells was detected. KIF2A expression was greater in AML patients compared to healthy donors, and receiver operating characteristic curve indicated that KIF2A expression predicted increased AML risk (area under curve: 0.793 (95%CI: 0.724-0.826)). In AML patients, KIF2A expression positively correlated with white blood cells, monosomal karyotype, and high risk stratification. Furthermore, no correlation of KIF2A expression with complete remission or hematopoietic stem cell transplantation was found. Kaplan-Meier curves showed that KIF2A expression was negatively correlated with EFS and OS. In vitro experiments showed that KIF2A was overexpressed in AML cell lines (KG-1, HL-60, ME-1, and HT-93) compared to CD34+ cells, moreover, cell proliferation was reduced but apoptosis was increased by KIF2A knockdown in HL-60 and KG-1 cells. In conclusion, KIF2A showed potential to be a biomarker and treatment target in AML.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Cinesinas/genética , Biomarcadores Tumorais/genética , Taxa de Sobrevida , Fatores de Risco , Apoptose , Células HL-60 , Proliferação de Células , Técnicas de Silenciamento de Genes
3.
Fortaleza; s.n; 2016. 106 p. ilus, tab.
Tese em Português | LILACS | ID: biblio-971888

RESUMO

Pterocarpanos representam a maior classe de isoflavonóides, depois das isoflavonase estudos recentes tem revelado que os representantes deste grupo podem agir em alvos específicos da mitose. O presente estudo avaliou o potencial citotóxico, genotóxico e mutagênico, do composto CP001,em célulasnormais e linhagens tumorais humanas, além do efeito inibitório sobre a quinesina Eg5fazendo uso de ensaios in vitro e com cálculos de bioquímica quântica.Os ensaios de citotoxicidade mostraram que o CP001apresentou efeito significativo sobre as linhagens tumorais testadas (HL-60, HCT-116, OVCAR-8, SF-295)com IC50 variandoentre 0,2 e 3,61 μM. Efeito confirmado na curva de crescimento cinético em tempo real, onde o CP001inibiu o crescimento da linhagem OVCAR-8 na concentração de 4 μM, semelhante ao paclitaxel (0,5 μM).Desta forma, a fim de determinar o mecanismo de ação envolvido, uma sequência de experimentos in vitroforam realizados.A avaliação do conteúdo de DNA nuclear foi mensurada em células OVCAR-8, para analisar o efeito do pterocarpano sobre as fases do ciclo celular, revelando que o CP001 é capaz de parar o ciclo celular na fase G2/M, na concetração de 5 μM, e com efeito potencializador, quando colocado em conjunto com o paclitaxel. A parada do ciclo celular na fase G2/M pode estar relacionado a ação do composto na tubulina. O ensaio da polimerização da tubulina foi conduzido e mostrou-se que o CP001 possui velocidade de polimerização (Vma = 80.95 mOD/min), inferior a do paclitaxel (Vmax = 100 mDO/min) e próxima a do monastrol (Vmax = 88.46 mOD/min). Estes dados mostram que a interferência na polimerização da tubulina não é tão significativa quanto aquela apresentada no paclitaxel. A ação em proteínas específicas da mitose foi outra possibilidade testada...


Pterocarpans represented the largest isoflavonoid class after isoflavones and recent studies have revealed that representatives of this group can act on specific targets of mitosis.This study evaluated the potential cytotoxic , genotoxic and mutagenic of the CP001 in tumoral and normal human cell lines. The inhibitory effect in Eg5 kinesin and quantum biochemistry calculation has been peformed as well. Cytotoxicity tests showed that CP001 hads ignificant effect on the tested tumoral lines (HL-60, HCT-116, OVCAR-8, SF-295) with IC50 ranging between 0.2 and 3.61 μ M. Effect confirmed bykinetic growth curve in real time, where the CP001inhibit growth of OVCAR-8 cell line at a concentration of 4 uM , similar to paclitaxel (0.5 mM). Thus, in order to determine the mechanism of action involved a sequence of in vitro experiments were per formed .The assessment of nuclear DNA content was measured in OVCAR-8 cells to examine the effect of pterocarpanon the cellcycle phases , showing that CP001is capable to arrest cell cycle at the G2/ M phase, concentration of 5 uM , and potentiating effect when added in combination with paclitaxel.The cell cycle arrest in G2/M phase may be related to action of the compound on tubulin.The tubulin assay polymerization was conducted and revealed that CP001 has polymerization rate (Vmax = 80.95 mOD / min ) b elow paclitaxel(Vmax = 100 mOD / min) and close tomonastrol ( Vmax = 88.46 mOD / min).These data suggest that interference with tubulin polymerization is not as significant as that shown in paclitaxel.Specific action mitosis proteins was another possibility tested...


Assuntos
Humanos , Neoplasias , Simulação de Acoplamento Molecular , Cinesinas
4.
Rev. bras. anestesiol ; 65(3): 222-229, May-Jun/2015. tab
Artigo em Inglês | LILACS | ID: lil-748917

RESUMO

BACKGROUND AND OBJECTIVES: In this study, the aim was to compare postoperative analgesia effects of the administration of ultrasound-guided interscalene brachial plexus block and intra-articular bupivacaine carried out with bupivacaine. METHODS: In the first group of patients 20 mL 0.25% bupivacaine and ultrasound-guided interscalene brachial plexus block (ISPB) were applied, while 20 mL 0.25% bupivacaine was given via intra-articular (IA) administration to the second group patients after surgery. Patients in the third group were considered the control group and no block was performed. Patient-controlled analgesia (PCA) with morphine was used in all three groups for postoperative analgesia. RESULTS: In the ISPB group, morphine consumption in the periods between 0-4, 6-12 and 12-24 postoperative hours and total consumption within 24 h was lower than in the other two groups. Morphine consumption in the IA group was lower than in the control group in the period from 0 to 6 h and the same was true for total morphine consumption in 24 h. Postoperative VASr scores in the ISPB group were lower than both of the other groups in the first 2 h and lower than the control group in the 4th and 6th hours (p < 0.05). In the IA group, VASr and VASm scores in the 2nd, 4th and 6th hours were lower than in the control group (p < 0.05). CONCLUSION: Interscalene brachial plexus block was found to be more effective than intra-articular local anesthetic injection for postoperative analgesia. .


JUSTIFICATIVA E OBJETIVOS: Comparar os efeitos na analgesia no pós-operatório da administração de bloqueio do plexo braquial por via interescalênica guiado por ultrassom e bupivacaína intra-articular, feito com bupivacaína. MÉTODOS: No primeiro grupo de pacientes, 20 mL de bupivacaína a 0,25% e bloqueio do plexo braquial por via interescalênica guiado por ultrassom (BPBI) foram administrados, enquanto 20 mL de bupivacaína a 0,25% foram administrados por via intra-articular (IA) ao segundo grupo de pacientes após a cirurgia. Os pacientes do terceiro grupo foram considerados grupo controle e nenhum bloqueio foi feito. Analgesia controlada pelo paciente (ACP) com morfina foi usada nos três grupos para analgesia pós-operatória. RESULTADOS: No grupo BPBI, o consumo de morfina nos períodos entre 0-4, 6-12 e 12-24 horas após a cirurgia e o consumo total em 24 horas foram mais baixos do que nos outros dois grupos. O consumo de morfina no grupo IA foi menor do que no grupo controle no período de 0-6 horas, como também foi menor o consumo total de morfina em 24 horas. Os escores EVAr no pós-operatório do grupo BPBI foram menores do que os escores dos dois outros grupos nas primeiras duas horas e menores do que os do grupo controle nos períodos de 4 e 6 horas (p < 0,05). No grupo IA, os escores EVAr e EVAm nos períodos de 2, 4 e 6 horas foram menores do que no grupo controle (p < 0,05). CONCLUSÃO: O bloqueio do plexo braquial por via interescalênica mostrou ser mais eficaz do que a injeção intra-articular de anestésico local para analgesia pós-operatória. .


JUSTIFICACIÓN Y OBJETIVOS: En este estudio, nuestro objetivo fue comparar en el período postoperatorio los efectos analgésicos de la administración de la bupivacaína en el bloqueo del plexo braquial por vía interescalénica guiado por ecografía y bupivacaína intraarticular. MÉTODOS: En el primer grupo de pacientes se administraron 20 mL de bupivacaína al 0,25% y se llevó a cabo el bloqueo del plexo braquial por vía interescalénica (BPBI) guiado por ecografía, mientras que al segundo grupo de pacientes se le administraron 20 mL de bupivacaína al 0,25% por vía intraarticular (IA) tras la cirugía. Los pacientes del tercer grupo fueron considerados como grupo control y en ellos no se realizó ningún bloqueo. La analgesia controlada por el paciente con morfina se usó en los 3 grupos para la analgesia postoperatoria. RESULTADOS: En el grupo BPBI, el consumo de morfina en los períodos entre 0-4, 6-12 y 12-24 h del postoperatorio y el consumo total en 24 h fueron más bajos que en los otros 2 grupos. El consumo de morfina en el grupo IA fue menor que en el grupo control en el período de 0-6 h, como también fue menor el consumo total de morfina en 24 h. Las puntuaciones EVAr en el postoperatorio del grupo BPBI fueron menores que las de los otros 2 grupos en las primeras 2 h y menores que los del grupo control en los períodos de 4 y 6 h (p < 0,05). En el grupo IA, las puntuaciones EVAr y EVAm en los períodos de 2, 4 y 6 h fueron menores que en el grupo control (p < 0,05). CONCLUSIÓN: El BPBI mostró ser más eficaz que la inyección intraarticular de anestésico local para analgesia postoperatoria. .


Assuntos
Dineínas/metabolismo , Cinesinas/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Proteínas Motores Moleculares/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Dineínas/química , Dineínas/isolamento & purificação , Modelos Biológicos , Complexos Multiproteicos/metabolismo , Estrutura Terciária de Proteína , Transporte Proteico
5.
Int. arch. otorhinolaryngol. (Impr.) ; 19(1): 80-85, Jan-Mar/2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-741526

RESUMO

Introduction Obstructive sleep apnea syndrome affects up to 4% of middle-aged men and 2% of adult women. It is associated with obesity. Objective The objective of this article is to review the literature to determine which factors best correlate with treatment success in patients with obstructive sleep apnea syndrome treated with a mandibular repositioning appliance. Data Synthesis A search was performed of the PubMed, Cochrane, Lilacs, Scielo, and Web of Science databases of articles published from January 1988 to January 2012. Two review authors independently collected data and assessed trial quality. Sixty-nine articles were selected from PubMed and 1 from Cochrane library. Of these, 42 were excluded based on the title and abstract, and 27 were retrieved for complete reading. A total of 13 articles and 1 systematic review were considered eligible for further review and inclusion in this study: 6 studies evaluated anthropomorphic and physiologic factors, 3 articles addressed cephalometric and anatomic factors, and 4 studies evaluated variables related to mandibular repositioning appliance design and activation. All the studies evaluated had low to moderate methodologic quality and were not able to support evidence on prediction of treatment success. Conclusion Based on this systematic review on obstructive sleep apnea syndrome treatment, it remains unclear which predictive factors can be used with confidence to select patients suitable for treatment with a mandibular repositioning appliance. .


Assuntos
Animais , Evolução Biológica , Proteínas de Transporte/química , Cinesinas/química , Modelos Moleculares , Microtúbulos/metabolismo , Transporte Biológico/fisiologia , Chlorocebus aethiops , Células COS , Dimerização , Transferência Ressonante de Energia de Fluorescência , Cinética , Microscopia de Fluorescência
6.
Rev. Soc. Bras. Med. Trop ; 48(1): 18-25, jan-feb/2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-742970

RESUMO

INTRODUCTION: Dengue is the most prevalent arboviral disease in tropical areas. In Mato Grosso, outbreaks are reported every year, but studies on dengue in this state are scarce. METHODS: Natural transovarial infection of Aedes aegypti by a flavivirus was investigated in the Jardim Industriário neighborhood of Cuiabá, Mato Grosso. Eggs were collected with ovitraps during the dry, intermediate, and rainy seasons of 2012. After the eggs hatched and the larvae developed to adulthood, mosquitoes (n = 758) were identified and allocated to pools of 1-10 specimens according to the collection location, sex, and climatic period. After RNA extraction, multiplex semi-nested RT-PCR was performed to detect the four dengue virus (DENV) serotypes, yellow fever virus, West Nile virus and Saint Louis encephalitis virus. RESULTS: DENV-4 was the only flavivirus detected, and it was found in 8/50 pools (16.0%). Three of the positive pools contained females, and five contained males. Their nucleotide sequences presented 96-100% similarity with DENV-4 genotype II strains from Manaus, Amazonas. The minimum infection rate was 10.5 per 1000 specimens, and the maximum likelihood estimator of the infection rate was 11.6 (95% confidence interval: 4.8; 23.3). CONCLUSIONS: This study provides the first evidence of natural transovarial infection by DENV-4 in Ae. Aegypti in Mato Grosso, suggesting that this type of infection might serve as a mechanism of virus maintenance during interepidemic periods in Cuiabá, a city where dengue epidemics are reported every year. These results emphasize the need for efficient vector population control measures to prevent arbovirus outbreaks in the state. .


Assuntos
Animais , Humanos , Camundongos , Cinesinas/metabolismo , Biossíntese de Proteínas , Linhagem Celular , Centrifugação com Gradiente de Concentração , Técnicas de Silenciamento de Genes , Imunoprecipitação , Interfase , Cinesinas/antagonistas & inibidores , Cinesinas/genética , Microtúbulos/metabolismo , Iniciação Traducional da Cadeia Peptídica , Ligação Proteica , Pirimidinas/farmacologia , Interferência de RNA , Ribossomos/metabolismo , Tionas/farmacologia
7.
Biol. Res ; 47: 1-15, 2014. ilus, graf, tab
Artigo em Inglês | LILACS | ID: biblio-950766

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.


Assuntos
Humanos , Cinesinas/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 , Cinesinas/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
8.
Arch. chil. oftalmol ; 63(2): 267-270, nov. 2005.
Artigo em Espanhol | LILACS | ID: lil-729246

RESUMO

Objetivo: Correlacionar tipo clínico de fibrosis muscular congénita (CFEOM tipo 1) y falla genética en los miembros afectados en tres generaciones de una familia chilena. Metodología: enrolamiento de portadores de fibrosis muscular congénita tipo clínico 1 (CFEOM 1) según protocolo. Fotografía y video, pedigrí familiar, obtención de muestra de sangre, extracción del DNA linfositario de casos/control, Linkage análisis de DNA. Resultados: Identificación de mutación AD en cromosoma 11, gen KIF21A en todos los afectados en una familia con tres generaciones con CFEOM tipo 1. Codifica proteína motora kinesina, que participa en el desarrollo del III par craneal. Conclusiones: En este tipo de estrabismo la alteración primaria es inervacional y no muscular. Relación entre forma clínica y cromosoma afectado permite caracterizar genéticamente las distintas formas clínicas de la enfermedad. Se propone una clasificación clínica nueva de los estrabismos restrictivos congénitos.


Aim: To correlate a clinical type of congenital muscular fibrosis (CFEOM type 1) with a genetic flaw in the affected members of three generations of a single Chilean family. Methods: Clinical type 1 congenital muscular fibrosis carriers were enrolled according to protocol. For each patient, the following information was collected: Video and pictures, family pedigree, blood samples, case/ control lymphocytes DNA, and DNA linkage analysis. Results: An AD mutation in chromosome 11 was identified. KIF21A gene was found in all affected members of the family over the three generations. It codified The motor protein kinesin, which is involved in the development of the third cranial nerve. Conclusions: In this form of strabismus, the primary dysfunction is innervational rather than muscular. The relationship between the clinical form and the affected chromosome permits identification of the various clinical forms of the disease. We propose a new clinical classification of the congenital restrictive strabismus.


Assuntos
Feminino , Fibrose/congênito , Músculos Oculomotores/patologia , Transtornos da Motilidade Ocular/genética , Transtornos da Motilidade Ocular/patologia , Cinesinas/genética , Estrabismo/genética , Estrabismo/patologia , Mutação
10.
Mem. Inst. Oswaldo Cruz ; 83(supl.1): 448-451, Nov. 1988.
Artigo em Inglês | LILACS | ID: lil-623623
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