Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 75
Filtrar
Mais filtros










Filtros aplicados

Base de dados
Intervalo de ano de publicação
1.
Allergol. immunopatol ; 48(1): 67-72, ene.-feb. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-186594

RESUMO

Background: There is little understanding of the mechanisms by which food allergy (FA) develops into persistent disease, or by which symptoms it regresses. Food allergy is a major health problem in developed countries, where the prevalence reaches up to 6% in children and 3% in the adult population. Objective: Children with food allergy remission (FAR) and those without FAR below five years of age, were compared 7-10 years with respect to clinical data and expression of glycoprotein A repetitions predominant (GARP) on peripheral blood mononuclear cells. Methods: Forty children with FAR and 40 children without FAR at age 7-10, in whom FA was previously diagnosed at age below five years were evaluated. In this prospective study, demographic and clinical data were taken, patients were classified as atopic based on history and serum specific IgE (sIgE) for a specific allergen. Blood samples were obtained from all patients to assess expression of GARP. Results: We observed higher expression of GARP in children with FAR compared to children without FA (p = 0.005); optimal cut-off for GARP prediction of the remission was 20.1%. Children with FAR and food-specific IgE in serum had higher expression of GARP compared to children with low food specific IgE (< 0.35 kU/L). Keeping pets at home decreased, and presence of allergic rhinitis increased ORs for high expression of GARP (hGARP) in our patients. Conclusion: hGARP (>20.1%) is related with FAR in school children. Allergic rhinitis, and pets at home modify this effect of GARP. Children with allergic rhinitis have less chance of developing remission despite maintaining immune tolerance (hGARP); quite the opposite case with pets at home


No disponible


Assuntos
Humanos , Criança , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Imediata/imunologia , Imunoglobulina E/sangue , Fatores de Transcrição , Glicoproteínas/imunologia , Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/imunologia , Leucócitos Mononucleares/imunologia , Rinite Alérgica , Hipersensibilidade Alimentar/sangue , Estudos Prospectivos , Modelos Logísticos , Glicoproteínas/metabolismo
3.
Rev. esp. patol ; 51(4): 248-252, oct.-dic. 2018. ilus
Artigo em Espanhol | IBECS | ID: ibc-179171

RESUMO

Los carcinomas renales asociados a translocación de factores de transcripción de la familia MiT/TFE incluyen, según la última clasificación de la Organización Mundial de la Salud, carcinomas con translocación Xp11 que involucran al gen TFE3 y carcinomas con translocación t(6;11)(p21;q12) que afectan al gen TFEB. Cada uno de estos subtipos presenta características clinicopatológicas y moleculares bien definidas. Actualmente, con el desarrollo de las técnicas moleculares se han descrito neoplasias con sustento molecular en estos mismos genes, pero con alteraciones distintas a la translocación. En este sentido, recientemente se han publicado carcinomas renales asociados a amplificación de TFEB que presentan diferencias pronósticas a los casos asociados a translocación y que podrían, por tanto, constituir una nueva entidad. Nosotros presentamos un caso de carcinoma renal asociado a amplificación de TFEB, describimos sus características clinicopatológicas y hacemos una revisión actualizada sobre estas neoplasias


Renal carcinomas associated with translocation of transcription factors of the MiT/TFE family include, according to the latest World Health Organization classification, carcinomas with Xp11 translocation that involve the TFE3 gene and those with translocation t(6;11)(p21;q12) that affect the TFEB gene. Each one of these sub-types have well-defined clinicopathological and molecular characteristics. Currently, progress in molecular techniques has led to the description of neoplasms with molecular changes in these same genes but with alterations different to translocation. Thus, recently, cases have been published of TFEB-amplified renal carcinomas with prognoses that vary from cases associated with translocation and could therefore represent a new entity. We present a case of TFEB-amplified renal carcinoma with a full description of the clinicopathological characteristics and an updated revision of these neoplasms


Assuntos
Humanos , Masculino , Adulto , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Amplificação de Genes , Fatores de Transcrição , Metástase Neoplásica/patologia , Nefrectomia , Técnicas Histológicas/métodos
4.
Arch. Soc. Esp. Oftalmol ; 93(11): 562-566, nov. 2018. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-175142

RESUMO

OBJETIVO: Reportar el hallazgo de la meibografía infrarroja en un paciente mexicano con el síndrome de EEC (Ectrodactyly-ectodermal dysplasia-cleft syndrome) confirmado por análisis molecular del gen p63. CASO CLÍNICO: Paciente varón de 31 años de edad que acude por presentar una historia de pérdida visual progresiva en ambos ojos asociada a fotofobia de larga duración. El paciente nació con labio y paladar hendido, y ectodactilia de la mano derecha; posteriormente presentó displasia ungueal, anodoncia y alopecia, con lo que se diagnosticó displasia ectodérmica. Las alteraciones oftalmológicas se limitaron a los anexos y la superficie ocular. La meibografía infrarroja in vivo mostró la ausencia total de glándulas de Meibomio en los párpados inferiores y deficiencia severa en los párpados superiores. Además, identificamos que el paciente es un portador heterocigoto de una mutación de sentido equivocado R304W (C -> T) en el exón 8 del gen p63. DISCUSIÓN: La mutación R304W en la región del gen p63 está definitivamente relacionada con características tales como la ausencia de glándulas de Meibomio


OBJECTIVE: To report the finding of infrared meibography in a Mexican patient with EEC syndrome (Ectrodactyly-ectodermal dysplasia-cleft syndrome) confirmed by molecular analysis of the p63 gene. Clinical case: A 31 year-old male patient was seen due to a history of progressive visual loss in both eyes associated with long-term photophobia. The patient was born with cleft lip and palate, ectrodactyly of right hand, and afterwards, displayed nail dysplasia, anodontia and alopecia, with which ectodermal dysplasia was diagnosed. The ophthalmological findings were limited to the adnexa and the ocular surface. In vivo infrared meibography showed total absence of Meibomian glands in the lower eyelids and severe deficiency in the upper eyelids. In addition, it was shown that the patient was a heterozygous carrier of a missense mutation R304W (C -> T) in exon 8 of the p63 gene. DISCUSSION: The R304W mutation in the p63 gene region is definitely related to characteristics such as the absence of Meibomian glands


Assuntos
Humanos , Masculino , Adulto , Mutação/genética , Displasia Ectodérmica/genética , Fissura Palatina/genética , Mutação , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Glândulas Tarsais/diagnóstico por imagem , Fissura Palatina/diagnóstico , Displasia Ectodérmica/diagnóstico , Pálpebras/diagnóstico por imagem , Reação em Cadeia da Polimerase
5.
Clin. transl. oncol. (Print) ; 20(10): 1233-1245, oct. 2018. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-173710

RESUMO

At least 50% of surgically resected non-functioning pituitary adenomas (NFPA) recur. Either early or late adjuvant radiotherapy is highly efficacious in controlling recurrent NFPA but associates potentially burdensome complications like hypopituitarism, vascular complications or secondary neoplasm. Reoperation is indicated in bulky tumor rests compressing the optic pathway. To date, no standardized medical therapy is available for recurrent NFPA although cabergoline and temozolomide show promising results. Guidelines on the management of recurrent NFPAs are now available. The new 2017 WHO pituitary tumor classification, based on immunohistochemistry and transcription factor assessment, identifies a group of aggressive NFPA variants that may benefit from earlier adjuvant therapy. Nevertheless, NFPA patients exhibit a reduced overall life expectancy largely due to hypopituitarism and treatment-related morbidity. The management of recurrent NFPA benefits from a multidisciplinary teamwork of surgeons, endocrinologists, radiation oncologists, ophthalmologists, pathologists and neuro-radiologists in order to provide individualized therapy and anticipate deterioration


No disponible


Assuntos
Humanos , Neoplasias Hipofisárias/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Hipofisárias/classificação , Neoplasias Hipofisárias/terapia , Fatores de Transcrição/genética , Guias de Prática Clínica como Assunto
6.
J. physiol. biochem ; 74(3): 381-393, ago. 2018. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-178993

RESUMO

Differentiation of adipocytes and their aggregation to adipose tissue are critical for mammalian growth and development. MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that play important roles in adipogenesis and lipid metabolism. miR-128-3p may contribute to adipose tissue development according to the previous studies. However, the role of miR-128-3p in the process of preadipocyte differentiation and lipid metabolism is not yet understood. The purpose of this research was to investigate the biological function and molecular mechanism of miR-128-3p in 3T3-L1 cells. In the present study, we found that miR-128-3p was downregulated during the process of 3T3-L1 preadipocyte differentiation. Overexpression of miR-128-3p obstructed the expressions of adipogenic marker genes as well as the lipid droplets accumulation and triglyceride content, suggesting the importance of miR-128-3p for adipogenesis. Moreover, miR-128-3p could lead to the retardation of cell proliferation in 3T3-L1 preadipocytes. Further evidences showed that, as a negative regulator of adipogenesis, miR-128-3p could directly target peroxisome proliferator-activated receptor γ (Pparg) which resulted in the suppression of 3T3-L1 preadipocyte differentiation, and miR-128-3p could also bind with SERTA domain containing 2 (Sertad2) which drove triglyceride hydrolysis and lipolysis. In addition, inhibition of Sertad2 with siRNA displayed the same effects as overexpression of miR-128-3p. Our research demonstrated that miR-128-3p impeded 3T3-L1 adipogenesis by targeting Pparg and Sertad2, resulting in the obstruction of preadipocyte differentiation and promotion of lipolysis. Taken together, this study offers profound insight into the mechanism of miRNA-mediated adipogenesis and lipid metabolism


No disponible


Assuntos
Animais , Camundongos , Adipócitos Brancos/metabolismo , Adipogenia , Regulação da Expressão Gênica no Desenvolvimento , Lipólise , MicroRNAs/metabolismo , PPAR gama/antagonistas & inibidores , Fatores de Transcrição/antagonistas & inibidores , Regiões 3' não Traduzidas , Células 3T3-L1 , Adipócitos Brancos/citologia , Biomarcadores/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT , Linhagem Celular , Cricetinae , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Triglicerídeos/metabolismo
7.
Allergol. immunopatol ; 46(3): 263-275, mayo-jun. 2018. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-172946

RESUMO

The MHC II deficiency is a rare autosomal recessive primary immunodeficiency syndrome with increased susceptibility to respiratory and gastrointestinal infections, failure to thrive and early mortality. This syndrome is caused by mutations in transcription regulators of the MHC II gene and results in development of blind lymphocytes due to the lack of indicatory MHC II molecules. Despite homogeneity of clinical manifestations of patients with MHC II deficiency, the genetic defects underlying this disease are heterogeneous. Herein, we report an Iranian patient with MHC II deficiency harbouring a novel mutation in RFXANK and novel misleading clinical features. He had ataxic gait and dysarthria from 30 months of age. Epidemiology, clinical and immunological features, therapeutic options and prognosis of patients with MHC II are reviewed in this paper (AU)


No disponible


Assuntos
Humanos , Masculino , Pré-Escolar , Antígenos de Histocompatibilidade Classe II/genética , Síndromes de Imunodeficiência/genética , Fatores de Transcrição/genética , Complexo Principal de Histocompatibilidade/genética , Mutação , Irã (Geográfico)
8.
Allergol. immunopatol ; 45(2): 152-159, mar.-abr. 2017. tab, graf, ilus
Artigo em Inglês | IBECS | ID: ibc-160520

RESUMO

Background. The present study aimed to discover more potential genes associated with the pathogenesis of asthma. Methods. The microarray data of GSE67940 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in bronchial alveolar lavage cells from patients with mild-moderate asthma (notSA) and severe asthma (SA) compared with normal controls (NC), respectively. Functional and pathway enrichment analysis, protein-protein interaction (PPI) network analysis were performed upon the identified up- and down-regulated DEGs. Besides, the gene association network based on the common up-regulated and down-regulated genes was generated and transcriptional regulatory pairs of overlapping DEGs in the PPI network were identified. Results. A total of 104 DEGs (30 up- and 74 down-regulated genes) were identified in notSA vs. NC. Additionally, 2796 DEGs were screened out in SA vs. NC group, including 320 up-regulated DEGs, and 135 down-regulated DEGs. Specially, 41 overlapping DEGs were screened out in notSA vs. NC and SA vs. NC, including 16 common up-regulated genes and 25 common down-regulated genes. No pathways were enriched by the DEGs in notSA vs. NC. DEGs in SA vs. NC were associated with cytokine-cytokine receptor interaction. VEGFA was a hub protein in both the PPI networks of DEGs in notSA vs. NC and SA vs. NC. Gene association network showed that signalling pathways and cytokine-cytokine receptor interaction were involved in. The overlapping VEGFA, and IFRD1, and ZNF331 were regulated by more TFs. Conclusion. Genes such as VEGFA, and IFRD1, and ZNF331 may be associated with pathogenesis of asthma (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , MicroRNAs/administração & dosagem , MicroRNAs/análise , Asma/diagnóstico , Asma/genética , Asma/patologia , Fatores de Transcrição/análise , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia , Ontologia Genética/estatística & dados numéricos
9.
Rev. esp. cardiol. (Ed. impr.) ; 69(11): 1042-1050, nov. 2016. graf, tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-157510

RESUMO

Introducción y objetivos: TBX1 es un factor de transcripción importante en el desarrollo embrionario del corazón. Se desconoce su implicación en el remodelado miocárdico tras infarto agudo de miocardio (IAM) y si es modulable por una terapia con beneficio demostrado como es el bloqueo del receptor mineralocorticoideo. Métodos: Se sometió a IAM a 60 ratas mediante ligadura de la coronaria izquierda: 50 animales fueron aleatorizados a ser sacrificados pasadas 1, 2, 4, 12 o 24 semanas; 10 animales se trataron con eplerenona (100 mg/kg/día) 7 días antes del IAM, hasta su sacrificio (4 semanas después); 8 animales se sometieron a cirugía sin ligadura (control). Se analizó la expresión cardiaca de TBX1, genes fetales y marcadores de fibrosis. Resultados: La expresión génica y proteica de TBX1 se incrementó en el miocardio infartado, con pico de expresión 1 semana tras el IAM (p < 0,01), sin variar en el miocardio no infartado. Los genes fetales y los marcadores de fibrosis también aumentaron, con expresión máxima 4 semanas (p < 0,001) y 1 semana (p < 0,01) tras el IAM respectivamente. La expresión de TBX1 se correlacionó con la de los marcadores de fibrosis (p < 0,01), pero no con los genes fetales. La eplerenona redujo el incremento de TBX1 y la fibrosis inducida tras IAM, que se asociaron con una mejora de función y remodelado ventricular por ecocardiografía. Conclusiones: Estos resultados muestran la reactivación de la expresión de TBX1 e indican su implicación en la fibrosis y el remodelado cardiacos tras el IAM y que puede participar en el beneficio del bloqueo mineralocorticoideo (AU)


Introduction and objectives: The transcription factor TBX1 plays an important role in the embryonic development of the heart. Nothing is known about its involvement in myocardial remodeling after acute myocardial infarction (AMI) and whether its expression can be modulated by a treatment with proven benefit such as mineralocorticoid receptor blockade. Methods: Acute myocardial infarction was induced in 60 rats via left coronary artery ligation: 50 animals were randomized to be euthanized after 1, 2, 4, 12, or 24 weeks; 10 animals were treated with eplerenone (100 mg/kg/days) 7 days before the AMI until their euthanasia (4 weeks later); 8 additional animals underwent surgery without ligation (control). We analyzed the cardiac expression of TBX1, fetal genes, and fibrosis markers. Results: The gene and protein expression of TBX1 was increased in the infarcted myocardium, peaking 1 week after AMI (P < .01), without changes in the non-infarcted myocardium. Levels of the fetal genes and fibrosis markers also increased, peaking 4 weeks (P < .001) and 1 week (P < .01) after AMI, respectively. The TBX1 expression was correlated with that of the fibrosis markers (P < .01) but not the fetal genes. Eplerenone reduced the TBX1 increase and fibrosis induced by AMI, with an association improvement in ventricular function and remodeling in echocardiography. Conclusions: These results show the reactivated expression of TBX1 and indicate its involvement in cardiac fibrosis and remodeling after AMI and its participation in the benefit from mineralocorticoid receptor blockade (AU)


Assuntos
Animais , Ratos , Remodelação Ventricular , Infarto do Miocárdio/fisiopatologia , Fatores de Transcrição/fisiologia , Biomarcadores/análise , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Modelos Animais de Doenças , Fibrose/fisiopatologia
10.
Arch. bronconeumol. (Ed. impr.) ; 52(6): 293-298, jun. 2016. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-152390

RESUMO

Introducción: La hipertensión arterial pulmonar es una enfermedad infrecuente caracterizada por una obstrucción progresiva de las arterias pulmonares. El receptor tipo II de la proteína ósea morfogenética (BMPR2) es el principal gen relacionado con esta enfermedad. EL objetivo de este trabajo fue analizar el patrón de metilación de la región promotora del gen BMPR2 en individuos con hipertensión arterial pulmonar y controles. Métodos: Se analizó la región a estudio con los softwares Methyl Primer Express® v.1.0 y MatInspector. El ADN genómico, obtenido a partir de sangre periférica, fue modificado con bisulfito de sodio. La metilación se analizó utilizando PCR específica de metilación. Como control positivo de metilación se utilizó ADN tratado con CpG metiltransferasa y como control positivo de expresión se utilizó ADN del cultivo celular H1299. Resultados: Se ha identificado una isla CpG susceptible de presentar metilación en la región promotora del gen que contiene secuencias específicas como sitios de unión a factores de trascripción NIT-2 (global-acting regulatory protein), sex-determining region Y y heat shock factor. No se han encontrado indicios de metilación en los pacientes ni en los controles. En las células H1299, que expresan el gen BMPR2, no se ha identificado metilación en la isla CpG analizada. Conclusiones: No se detectaron indicios de metilación en la región promotora a estudio en pacientes y controles, siendo esta la región más adecuada para realizar el estudio debido al alto número de sitios de unión a factores de transcripción que podrían estar involucrados en la correcta funcionalidad del gen


Introduction: Pulmonary arterial hypertension is characterizated by obstruction of the pulmonary arteries. The gene mainly related to pathology is the bone morphogenetic protein receptor type II(BMPR2). The aim of this study was to analyze the methylation pattern of the BMPR2promoter region in patients and controls. Methods: We used Methyl Primer Express® v.1.0 and MatInspector softwares to analyze this region. Genomic DNA obtained from the peripheral blood of patients and controls was modified with sodium bisulphite. Methylation was analyzed using methylation-specific PCR. DNA treated with CpG methyltransferase was used as a positive control for methylation and H1299 cell culture DNA was used as positive control for gene expression. Results: We identified a CpG island, which may have been methylated, in the BMPR2 promoter region, in addition to NIT-2 (global-acting regulatory protein), sex-determining region Y) and heat shock factor transcription factor binding sites. We found no evidence of methylation in patients and controls. No methylated CpG sites were identified in H1299 cells expressing theBMPR2 gene. Conclusions: The BMPR2 promoter region is the most suitable for study because of the high number of transcription factor binding sites that could alter gene function. No evidence of methylation was detected in this region in patients and controls


Assuntos
Humanos , Masculino , Feminino , Adulto , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/imunologia , Metilação , Metilação de DNA/genética , Metilação de DNA/imunologia , Metilação de DNA/fisiologia , Hipertensão Pulmonar/classificação , Hipertensão Pulmonar/epidemiologia , Fatores de Transcrição/administração & dosagem , Fatores de Transcrição/análise
11.
Clin. transl. oncol. (Print) ; 17(10): 788-794, oct. 2015. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-140948

RESUMO

Background. Gastric cancer is the fourth most common cancer and the second leading cause of cancer-related deaths worldwide. Gastric cancer is characterized by high levels of invasion and metastasis. Increasing attention is being focused on discovering molecular markers for the diagnosis of gastric cancer and for predicting its prognosis. The objective of the present study was to evaluate Nurr1 expression in gastric cancer and to assess its correlation with clinicopathological parameters and prognosis in gastric cancer patients. Methods. Tissue samples were obtained from 120 gastric cancer patients. We investigated Nurr1 expression in human normal and gastric cancer tissues using real-time reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. We determined the association between Nurr1 and recurrence, prognosis and patient clinicopathological parameters. Univariate and multivariate survival analyses with a Cox’s proportional hazards regression model were used to identify independent factors related to recurrence and prognosis. Results. The immunohistochemical, qRT-PCR and western blot analyses revealed that Nurr1 expression was increased in gastric cancer tissues compared with normal gastric tissue (P < 0.05). Nurr1 expression was significantly correlated with the tumor size, depth of tumor invasion, lymph node metastasis, recurrence, and distant metastasis of gastric cancer (P < 0.05). Moreover, Nurr1-high patients also exhibited poorer overall survival (OS) and disease-free survival compared with Nurr1-low patients (P < 0.01). The univariate and multivariate survival analyses suggested that Nurr1 expression (P = 0.011), histology (P = 0.018), depth of tumor invasion (P = 0.037), and presence of lymph node metastasis (P = 0.031) were independent prognostic factors for recurrence. In addition, Nurr1 expression (P = 0.007), depth of tumor invasion (P = 0.014), lymph node metastasis (P = 0.044), distant metastasis (P = 0.023), and recurrence (P = 0.011) were independent prognostic factors of OS in gastric cancer patients. Conclusions. The Nurr1 protein may be useful as a marker of recurrence, metastasis, and poor prognosis following curative resection in patients with gastric cancer (AU)


No disponible


Assuntos
Adulto , Idoso de 80 Anos ou mais , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Nucleares Órfãos/análise , Receptores Nucleares Órfãos , Neoplasias Gástricas/diagnóstico , Prognóstico , Fatores de Transcrição , Reação em Cadeia da Polimerase/métodos , Western Blotting/métodos , Western Blotting , Expressão Gênica/fisiologia , Análise Multivariada , Estudos Retrospectivos , Perfilação da Expressão Gênica/métodos
12.
An. R. Acad. Farm ; 80(1): 14-48, ene.-mar. 2014. graf
Artigo em Espanhol | IBECS | ID: ibc-121836

RESUMO

El hígado graso no alcohólico (HGNA) es una enfermedad que se define como un espectro continuo que oscila entre una esteatosis macrovesicular, de curso clínico favorable, hasta un cuadro de esteatohepatitis no alcohólica (EHNA), que da lugar a daños irreversibles y que se ha convertido en los últimos años en un problema sanitario de primera magnitud. El HGNA se caracteriza por una infiltración grasa de los hepatocitos que se asocia con un estado de resistencia a la insulina y por ello ligado, como factor de riesgo, al síndrome metabólico. Los factores de transcripción SREBP-1c (proteína de unión al elemento regulador del esterol), ChREBP (proteína de unión al elemento de respuesta a carbohidratos) y LXR (receptor X hepático) son reguladores fundamentales de la homeostasis lipídica y glucídica y de la inflamación, cuya activación regula al alza genes implicados en la síntesis de novo de los ácidos grasos en respuesta a insulina, glucosa y oxiesteroles, tanto en condiciones fisiológicas como patológicas. En esta revisión se describen datos recientes sobre la biología, la regulación y la coordinación funcional entre SREBP-1c, ChREBP y LXR y su relación con el HGNA. El desarrollo de agonistas selectivos de estos factores les hacen ser prometedoras dianas en el tratamiento del HGNA y de la EHNA


Nonalcoholic fatty liver disease (NAFLD) has become a major public health issue that comprises a disease spectrum which ranges from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH), leading to irreversible liver damages. Deposition of excess triglycerides within liver cells is the hallmark of NAFLD, which is associated with a loss of insulin sensitivity. A growing body of evidence implicates the lipogenic transcription factors SREBP-1c (sterol regulatory element-binding protein), ChREBP (carbohydrate responsive element-binding protein) and LXR (liver X receptor) in the pathogenesis of NAFLD. These factors have emerged as central regulators of the de novo fatty acid synthesis, the glucose homeostasis and the inflammation in response to insulin, glucose and oxysterols, under both physiological and physiopathological conditions. In this review we describe recent findings in the biology, the function and the cross-regulation between SREBP-1c, ChREBP and LXR on the control of lipid and glucose metabolism and their link to NAFLD. Specific pharmacologic ligands are available, making them attractive therapeutic targets for NAFLD and NASH


Assuntos
Humanos , Fígado Gorduroso/fisiopatologia , Fatores de Transcrição/análise , Lipogênese/fisiologia , Ácidos Graxos/fisiologia , Proteínas de Ligação a Elemento Regulador de Esterol/fisiologia
13.
Cuad. bioét ; 24(82): 419-442, sept.-dic. 2013. ilus
Artigo em Espanhol | IBECS | ID: ibc-120124

RESUMO

El descubrimiento por parte de Shinya Yamanka y su equipo, en el año 2006, de las Células de Pluripotencialidad Inducida (iPS) en ratón, supuso uno de los grandes adelantos en la Biología Molecular y Celular. La posibilidad de que estas células se puedan generar también en seres humanos abre unas vías de desarrollo totalmente insospechadas para la Biomedicina. Su principal aporte es la creación de un protocolo robusto, que tiene en cuenta tres principales avances de la Biología como lo son las técnicas de transferencia nuclear, el descubrimiento de los factores de la transcripción asociados a la pluripotencialidad y el aislamiento de las Células Troncales Embrionarias de ratón. Un protocolo que puede ser replicado de manera sencilla en otros laboratorios para contar con la posibilidad de diseñar ensayos que permitan realizar modelos celulares para el estudio de enfermedades incurables; así como probar fármacos con células humanas o explorar las posibilidades de trasplantes autólogos de células, tejidos u órganos. La motivación ética de Yamanaka fue buscar una alternativa al empleo de Células Troncales Embrionarias (ES), evitando la destrucción de embriones producidos por las técnicas de fecundación in vitro (FIV), así como el empleo de óvulos humanos. Además, ha resultado ser un modelo de investigación, en el que la intuición de los principios éticos y su aplicación en un proyecto biotecnólogico de avanzada, ha supuesto la apertura de una nueva forma de entender la biología del desarrollo embrionario y la aplicación técnica de estos conocimientos. Puso así de manifiesto que el desarrollo, biológicamente entendido, no es una calle de un solo sentido. Las posibilidades de profundizar en los fundamentos de la Biología Molecular y la genética, junto con las expectativas de sus aplicaciones clínicas han hecho merecedor a Yamanka del Premio Nobel de Medicina 2012, junto a otro gran investigador Sir John Gurdon descubridor de las técnicas de transferencia nuclear (AU)


One of the greatest advances in molecular and cell biology was the discovery of the Induced Pluripotent Stem cells (iPS) in mice, by Shinya Yamanka and his team in 2006. The possibility that these cells can be generated also in humans opens up unexpected ways of development for biomedicine. Its main contribution is the creation of a strong protocol that takes into account three major advances in biology such as; nuclear transfer techniques, the discovery of transcription factors associated with pluripotency and the isolation of mouse embryonic stem cells. A protocol that can be easily replicated in other laboratories to have the oportunity to design tests that allow modeling of many incurable diseases, drug testing for human cells or explore the possibilities of autologous transplants of tissues or organs. Yamanaka ethical motivation to find an alternative to embryonic stem cells (ES) and prevent the destruction of embryos produced by In Vitro Fertilization techniques (IVF), has proved to be a research model, in which the intuition of the ethical principles and its application in advanced biotechnology projects, has meant the opening of a whole new way of understanding the biology of embryonic development. It is clear that development, biologically understood (puede ser también “treated”; tratado), is not a one-way street. The possibilities to deepen into the foundations of molecular biology and genetics, along with the expectations of its clinical applications have earned Yamanka the Nobel Prize in Medicine 2012, along with another great scholar Sir John Gurdon, discoverer of nuclear transfer techniques (A)


Assuntos
Animais , Camundongos , Células-Tronco Pluripotentes Induzidas/transplante , Fatores de Transcrição , Técnicas de Transferência Nuclear/ética , Células-Tronco Embrionárias , Medicina Regenerativa/ética , Modelos Animais , Pesquisa Biomédica/ética
14.
Inmunología (1987) ; 32(2): 57-69, abr.-jun. 2013. ilus
Artigo em Espanhol | IBECS | ID: ibc-112121

RESUMO

La recombinación V(D)J consiste en el ensamblaje de los segmentos génicos presentes en los genes de las cadenas variables de los receptores de antígeno para generar la diversidad del reconocimiento antigénico en linfocitos. El conocimiento de su regulación en condiciones normales es esencial para entender los casos en que este proceso se desregula, dando lugar a transformaciones leucémicas. La recombinación V(D)J se inicia por acción de una endonucleasa específica presente exclusivamente en linfocitos inmaduros. Según el «modelo de accesibilidad» propuesto hace más de 25 años, la recombinación V(D)J está regulada a través del control de la accesibilidad de esta endonucleasa a sus sitios de corte en el ADN, de acuerdo con unos programas de diferenciación celular muy definidos. En esta revisión se resumen los hallazgos descubiertos en este campo en los últimos años, tales como el importante papel que tiene la conformación génica y la posición de estos genes en el núcleo celular, así como aquellos que muy recientemente han permitido la validación definitiva del «modelo de accesibilidad» (AU)


V(D)J recombination is the assembly of gene segments at the antigen receptor loci in order to generate antigen receptor diversity in T and B lymphocytes. Detailed knowledge of how V(D)J recombination is normally regulated during lymphocyte development is essential to understand the cases of dysregulation of this process that result in leukemic transformation. V(D)J recombination is triggered by action of a specific endonuclease which is exclusively expressed in immature lymphocytes. According to the “accessibility model” proposed more than 25 years ago, DNA cleavage by this endonuclease is very strictly controlled during cell differentiation by regulating its accessibility to chromatin. This review summarizes the advances in the field over the last few years, including the important role of the genomic conformation and position of the antigen receptor loci within the nucleus, as well as those that have recently culminated with the validation of the “accessibility model” to control this process (AU)


Assuntos
Humanos , Recombinação V(D)J/imunologia , Receptores de Retorno de Linfócitos/imunologia , Leucemia/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Imunoglobulinas/imunologia , Cromatina/imunologia , Fatores de Transcrição/imunologia , Diferenciação Celular/imunologia
15.
Rev. neurol. (Ed. impr.) ; 54(1): 44-48, 1 ene., 2012. ilus
Artigo em Espanhol | IBECS | ID: ibc-98022

RESUMO

Introducción. El estudio de la ontogenia de los sistemas de neurotransmisión es relevante no sólo para entender el desarrollo del sistema nervioso central. Debido a los nuevos horizontes en la investigación del uso de células troncales en la reparación del daño neuronal, se intenta imitar la diferenciación y el mantenimiento del tipo neuronal afectado; por ello, es necesario comprender qué señales dirigen la diferenciación así como las moléculas que guían su maduración, su supervivencia y el mantenimiento de su funcionalidad. Por otra parte, la temprana emergencia de estos sistemas durante la ontogenia ha provocado que cuestionemos su participación en la regulación del desarrollo del sistema nervioso central. Objetivo. Enumerar los eventos más relevantes en el desarrollo de los sistemas de neurotransmisión y mencionar algunos procesos en los que participan durante la ontogenia del sistema nervioso. Desarrollo. Se revisará cronológicamente, en los principales sistemas de neurotransmisión, la secuencia de eventos moleculares que permite el establecimiento del fenotipo, la aparición de receptores y transportadores, y se hará un esbozo de su participación en eventos como neurogénesis, proliferación, diferenciación y migración neuronal. Conclusiones. Los sistemas de neurotransmisión regulan eventos que van desde la neurogénesis hasta la migración cortical, tanto radial como tangencial, e intervienen en la correcta maduración de su propio sistema (AU)


Introduction. The study of the ontogenesis of neurotransmitter systems is relevant not only to understand the development of the central nervous system. The new horizons that have appeared in research into the use of stem cells in the repair of damaged neurons are allowing attempts to be made to imitate the differentiation and maintenance of the type of affected neuron. To achieve this, it is necessary to understand which signals direct the differentiation and the molecules that guide their maturation, their survival and the maintenance of their functionality. Furthermore, the early emergence of these systems during ontogenesis has led us to question their participation in the regulation of the development of the central nervous system. Aims. To describe the most significant events in the development of the neurotransmitter systems and to discuss some of the processes that take part in the ontogenesis of the nervous system. Development. The study will offer a chronological review of the sequence of molecular events in the main neurotransmitter systems that allow the phenotype to be established and the appearance of receptors and transporters. Likewise, the role they play in events like neurogenesis, proliferation, differentiation and neuronal migration will also be outlined. Conclusions. The neurotransmitter systems regulate events that range from neurogenesis to both radial and tangential cortical migration, as well as intervening in the correct maturation of their own system (AU)


Assuntos
Humanos , Transmissão Sináptica/fisiologia , Proteínas de Transporte de Neurotransmissores/fisiologia , Neurogênese/fisiologia , Fatores de Transcrição/fisiologia
16.
Reumatol. clín. (Barc.) ; 7(4): 248-254, jul.-ago. 2011. tab
Artigo em Espanhol | IBECS | ID: ibc-89516

RESUMO

El avance en el conocimiento de las alteraciones bioquímicas que causan las enfermedades constitucionales óseas no tiene precedentes. La constatación de que su característica esencial es el trasfondo genético común a todas ellas ha dado lugar a una propuesta de alcance: sustituir el término «constitucionales» por «genéticas» para referirse a estas entidades. La comprensión de los mecanismos fisiopatológicos implicados, identificando el punto exacto de la vía metabólica alterada y sus sistemas de regulación y control, facilita realizar un diagnóstico preciso, basado en la colaboración interdisciplinar, en un tiempo muy inferior del que requería el enfoque tradicional. Además, aunque la correcta valoración de las manifestaciones clínicas y radiológicas sigue siendo crucial, el diagnóstico de certeza se basa cada vez con mayor frecuencia en la aplicación de las nuevas técnicas de análisis genético y molecular. Por último, el esclarecimiento de las complejas alteraciones subyacentes a estos trastornos descubre unas dianas moleculares de gran utilidad potencial en la investigación terapéutica de unas enfermedades que a menudo limitan de manera notable la calidad de vida y que, casi sin excepciones, todavía carecen de un tratamiento eficaz (AU)


Recent years have seen an unprecedented increase in the knowledge and understanding of biochemical disturbances involved on constitutional bone disorders. Recognition of the genetic background as the common cause of these diseases prompted the substitution of the term «constitutional» by «genetic», in referring to them. Understanding physiopathological bases by finding out the altered metabolic pathways as well as their regulatory and control systems, favours an earlier and more accurate diagnosis based on interdisciplinary collaboration. Although clinical and radiological assessment remains crucial in the study of these disorders, ever more often the diagnosis is achieved by molecular and genetic analysis. Elucidation of the damaged underlying molecular mechanisms offers targets potentially useful for therapeutic research in these complex and often disabling diseases (AU)


Assuntos
Humanos , Masculino , Feminino , Doenças Ósseas/classificação , Doenças Ósseas/etiologia , Doenças Ósseas/genética , Osteocondrodisplasias/complicações , Osteocondrodisplasias/diagnóstico , Qualidade de Vida , Proteínas Nucleares/análise , Proteínas Nucleares , Oncogenes/genética , Oncogenes/fisiologia , Proteínas Nucleares/genética , Proteínas Nucleares/imunologia , Fatores de Transcrição/análise , Fatores de Transcrição
17.
Nutr. hosp ; 26(3): 441-450, mayo-jun. 2011. ilus
Artigo em Inglês | IBECS | ID: ibc-98523

RESUMO

Non alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease and is considered the hepatic manifestation of the metabolic syndrome associated with diabetes mellitus type 2. The prevalence of NAFLD in the general population reaches 15-20%. It is also estimated that non alcoholic steatohepatitis (NASH)affects 3% of the population. NAFLD refers to a wide spectrum of liver damage, which ranges from simple steatosis or intracellular triglyceride accumulation, to inflammation (NASH), fibrosis and cirrhosis. The mechanisms involved in the accumulation of triglycerides in the liver and subsequent hepatocellular damage are multifactorial and are not completely understood. However, metabolic changes such as insulin resistance (IR) are developed, being a common factor in the retention of fatty acids (FA) within the hepatocytes with oxidation and production of free radicals at the mitochondrial level, which are capable of causing lipid peroxidation, cytokine production, and necrosis. In addition, there are alterations in the hepatic bioavailability of long chain n-3 polyunsaturated fatty acids, conditions that alter the expression of a series of transcriptional factors involved in lipolytic and lipogenic processes in the liver. A greater knowledge of the etiopathogenic mechanisms of NAFLD is fundamental for the development of future effective therapeutic strategies. The pathophysiological fundamentals of liver steatosis are analyzed in this study (AU)


La enfermedad de Hígado graso no alcohólico (HGNA)es la causa más importante de enfermedad hepática crónica y es considerado la manifestación hepática del síndrome metabólico asociado a obesidad y diabetes mellitus tipo 2. La prevalencia de la enfermedad de HGNA en la población general alcanza el 15-20%, estimándose además que la esteatohepatitis no-alcohólica (EHNA) afecta al 3%. El HGNA se refiere a un amplio espectro de daño hepático, que va desde esteatosis simple o acumulación intracelular de triacilglicéridos (TAGs), a inflamación(EHNA), fibrosis y cirrosis. Los mecanismos implicados en la acumulación de TAGs a nivel hepático y subsecuente daño hepatocelular son de carácter multifactorial y no se conocen completamente. Sin embargo, es reconocido que existen alteraciones metabólicas, siendo la resistencia a la insulina (RI) un factor común que genera retención de ácidos grasos y TAGs dentro de los hepatocitos, con la producción de radicales libres a nivel mitocondrial capaces de inducir lipoperoxidación, producción decitoquinas y necrosis. Además, existen alteraciones en labio disponibilidad hepática de ácidos grasos poli-insaturados de cadena larga de la serie n-3, condiciones que alterarían la expresión de una serie de factores de transcripción involucrados en el proceso de lipólisis y lipogénesisa nivel hepático. Un mayor conocimiento de los mecanismos etiopatogénicos de la enfermedad de HGNA es fundamental para el desarrollo de estrategias terapéuticas eficaces a futuro. Los fundamentos fisiopatológicos de la esteatosis son analizados a continuación (AU)


Assuntos
Humanos , Fígado Gorduroso/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos/metabolismo , Fígado Gorduroso/complicações , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Fígado Gorduroso/fisiopatologia , Resistência à Insulina , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Fatores de Transcrição
18.
Inmunología (1987) ; 29(2): 74-84, abr.-jun. 2010. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-108269

RESUMO

El reconocimiento de subpoblaciones celulares reguladoras ha marcado una nueva etapa de desarrollo investigativo sobre la generación y control de la respuesta inmune. La subpoblación mejor caracterizada son loslinfocitos T CD4+CD25+FOXP3+.Uno de los grandes aportes a la comprensión de la regulación inmunees la identificación de FOXP3, un factor regulador de la transcripción, queparticipa directamente en la función de las células reguladoras T CD4+humanas y murinas. FOXP3 ha sido definido por diversos autores como elgen maestro controlador del desarrollo y función de las células reguladoras y es considerado el principal marcador molecular, a la fecha, de estasubpoblación reguladora.FOXP3 fue descrito inicialmente en ratones “escurfi”, los cuales presentan mutaciones espontáneas en el marco de lectura del gen denominado Foxp3. Este gen codifica para la proteína escurfina, cuya deficiencia estáasociada a trastornos autoinmunes y linfoproliferativos severos. En los (..) (AU)


The recognition of regulatory cell subpopulations has marked a newstage of development on the research of the generation and control of theimmune response. The best characterized subpopulation of T lymphocytes are the CD4+CD25+cells; in this population, FOXP3+has been identified as an associated phenotype, as this marker is not exclusive for thissubpopulation.One of the great contributions to the understanding of immune regulation is the identification of FOXP3, a regulatory transcription factordirectly involved in the function of human and mouse CD4+T regulatorycells. FOXP3 has been defined by various authors as the master gene controlling the development and function of regulatory cells and is considered the main marker for this regulatory subpopulation.FOXP3 was initially described in “scurfy” mice, which have spontaneous mutations in the reading frame of Foxp3. This gene encodes the (..) (AU)


Assuntos
Humanos , Fatores de Transcrição/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T CD4-Positivos/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Poliendocrinopatias Autoimunes/imunologia , Tolerância ao Transplante/imunologia , Autoimunidade/imunologia
19.
Rev. neurol. (Ed. impr.) ; 50(supl.3): s101-s106, 3 mar., 2010. tab
Artigo em Espanhol | IBECS | ID: ibc-86883

RESUMO

Objetivo. Revisar los aspectos más relevantes de los factores genéticos implicados en los trastornos del lenguaje y del habla. Desarrollo. Los estudios de agregación familiar y gemelos han demostrado que las capacidades lingüísticas, como la mayoría de las capacidades cognitivas, tienen un claro componente hereditario. Algunas mutaciones raras en el gen que codifica para el factor de trascripción FOXP2 han causado trastornos del habla de una forma monogénica. Sin embargo, los resultados del FOXP2 en diversos síndromes que se asocian a trastornos del habla (autismo, dislexia, trastorno específico del lenguaje, esquizofrenia) han dado resultados controvertidos, posiblemente debido a problemas en la definición del fenotipo. Conclusiones. La mayoría de los trastornos del lenguaje obedecen a variaciones en múltiples genes. Se precisan estudios longitudinales con amplias muestras que incluyan datos genéticos y ambientales para poder profundizar en los factores que afectan al desarrollo del lenguaje (AU)


Aim. To review selectively the status of the genetic research in the field of speech and language disorders. Development. Major contributions to the field are selected, presented, and discussed. Twin and family studies have demonstrated that most cognitive traits including language are moderately to highly heritable. Rare mutations affecting the FOXP2 transcription factor cause a monogenic speech and language disorder. The results of association studies of FOXP2 with several language disorders are controversial, probably due to the problem of phenotype definition. Conclusions. Common forms of disorders of speech and language are mostly likely associated with variability in the function of multiple genes. Longitudinal studies looking at gene environmental interaction might be important in order to understand the mechanism of language development (AU)


Assuntos
Humanos , Transtornos do Desenvolvimento da Linguagem/genética , Distúrbios da Fala/genética , Fatores de Transcrição/genética , Predisposição Genética para Doença , Marcadores Genéticos , Doenças em Gêmeos
20.
Int. microbiol ; 13(1): 33-39, mar. 2010. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-87670

RESUMO

Anaerobic metabolism is controlled by several transcriptional regulators, including ArcA, Fnr, NarP, and NarL, with the Fnr and ArcA proteins sensitive to the cell's redox status. Specifically, the two-component ArcAB system is activated in response to the oxidation state of membrane-bound quinones, which are the central electron carriers of respiration. Fnr, by contrast, directly senses cellular oxidation status through the [4Fe-4S] cluster present in its own structure. In this study, a third additional redox-associated pathway that controls the nitrate respiration regulators NarL and NarP was identified. The results showed that, in Salmonella enterica, the expression of these two transcriptional regulators is under the control of Fur, a metalloregulator that senses the presence of Fe2+ and regulates the homeostasis of this cation inside the cell. Thus, the Fur- Fe2+ complex increases the expression of narL and represses that of narP. Furthermore, studies of S. enteric mutants defective in the Fur-regulated sRNA RfrA and RfrB showed that those sRNA control both narP and narL expression. These results confirm Fur as a global regulator based on its involvement not only in iron uptake and detoxification but also in the control of nitrate/nitrite respiration by sensing cellular redox status (AU)


No disponible


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/biossíntese , Regulação Bacteriana da Expressão Gênica , Nitratos/metabolismo , Proteínas Repressoras/metabolismo , Salmonella enterica/fisiologia , Fatores de Transcrição/biossíntese , Proteínas de Bactérias/biossíntese , Ferro/metabolismo , Oxirredução , Salmonella enterica/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA