RESUMO
MicroRNAs (miRNAs) constitute a large family of small noncoding RNAs that are encoded by the genomes of most organisms. They regulate gene expression through posttranscriptional mechanisms to attenuate protein output in various genetic networks. The discovery of miRNAs has transformed our understanding of gene regulation and sparked intense efforts intended to harness their potential as diagnostic markers and therapeutic tools. Over the last decade, a flurry of studies has shed light on placental miRNAs but has also raised many questions regarding the scope of their biologic action. Moreover, the recognition that miRNAs of placental origin are released continually in the maternal circulation throughout pregnancy suggested that circulating miRNAs might serve as biomarkers for placental function during pregnancy. Although this generated much enthusiasm, recently recognized challenges have delayed the application of miRNA-based biomarkers and therapeutics in clinical practice. In this review, we summarize key findings in the field and discuss current knowledge related to miRNAs in the context of placental biology.
Assuntos
MicroRNAs/fisiologia , Doenças Placentárias/genética , Biomarcadores/sangue , Espaço Extracelular/metabolismo , Feminino , Humanos , MicroRNAs/sangue , Doenças Placentárias/sangue , GravidezRESUMO
We report the case of a father and son diagnosed with atypical chronic myeloid leukemia (aCML). Both patients harbored SETBP1 mutations, which are present in 24.3% of aCML patients. Moreover, both shared the variant encoding p.Pro737His, but the aCML severity was greater in the son because of the presence of two other missense mutations causing p.Asp868Asn and p.Ser885Arg alterations. SETBP1 mutations may be associated with an adverse prognosis, so their detection would help in the diagnosis of aCML and the determination of a patient's prognosis.
Assuntos
Animais , Feminino , Masculino , Camundongos , Gravidez , Aberrações Cromossômicas/estatística & dados numéricos , Técnicas de Cultura Embrionária , Impressão Genômica , Doenças Placentárias/genética , Placenta/metabolismo , Técnicas de Reprodução Assistida/efeitos adversos , Blastocisto/citologia , Aberrações Cromossômicas/embriologia , Embrião de Mamíferos , Epigênese Genética , Técnicas de Cultura Embrionária/estatística & dados numéricos , Incidência , Doenças Placentárias/patologia , Placenta/patologia , Técnicas de Reprodução Assistida/estatística & dados numéricos , Processos EstocásticosRESUMO
Nitric oxide (NO) is one of the most pleiotropic signaling molecules at systemic and cellular levels, participating in vascular tone regulation, cellular respiration, proliferation, apoptosis and gene expression. Indeed NO actively participates in trophoblast invasion, placental development and represents the main vasodilator in this tissue. Despite the large number of studies addressing the role of NO in the placenta, its participation in placental vascular development and the effect of altered levels of NO on placental function remains to be clarified. This review draws a time-line of the participation of NO throughout placental vascular development, from the differentiation of vascular precursors to the consolidation of vascular function are considered. The influence of NO on cell types involved in the origin of the placental vasculature and the expression and function of the nitric oxide synthases (NOS) throughout pregnancy are described. The developmental processes involved in the placental vascular bed are considered, such as the participation of NO in placental vasculogenesis and angiogenesis through VEGF and Angiopoietin signaling molecules. The role of NO in vascular function once the placental vascular tree has developed, in normal pregnancy as well as in pregnancy-related diseases, is then discussed.
Assuntos
Neovascularização Fisiológica/fisiologia , Óxido Nítrico/fisiologia , Placenta/irrigação sanguínea , Animais , Feminino , Humanos , Modelos Biológicos , Neovascularização Fisiológica/genética , Óxido Nítrico/metabolismo , Placenta/metabolismo , Placenta/fisiologia , Doenças Placentárias/etiologia , Doenças Placentárias/genética , Doenças Placentárias/metabolismo , Placentação/genética , Placentação/fisiologia , Gravidez , Complicações na Gravidez/etiologia , Complicações na Gravidez/metabolismoRESUMO
The NRAMP1 gene encodes a divalent cation transporter, located in the phagolysosomal membrane of macrophages, that has been associated with resistance to intracellular pathogens. In cattle, natural resistance against brucellosis has been associated with polymorphisms at the 3' untranslated region (3'UTR) of the NRAMP1 gene, which are detectable by single-strand conformational analysis (SSCA). This study aimed to evaluate the association between NRAMP1 3'UTR polymorphisms and resistance against bovine brucellosis in experimental and natural infections. In experimentally infected pregnant cows, abortion occurred in 42.1% of cows with a resistant genotype (SSCA(r); n = 19) and in 43.1% of those with a susceptible genotype (SSCA(s); n = 23). Furthermore, no association between intensity of pathological changes and genotype was detected. In a farm with a very high prevalence of bovine brucellosis, the percentages of strains of the SSCA(r) genotype were 86 and 84% in serologically positive (n = 64) and negative (n = 36) cows, respectively. Therefore, no association was found between the NRAMP1-resistant allele and the resistant phenotype in either experimental or naturally occurring brucellosis. To further support these results, bacterial intracellular survival was assessed in bovine monocyte-derived macrophages from cattle with either the resistant or susceptible genotype. In agreement with our previous results, no difference was observed in the rates of intracellular survival of B. abortus within macrophages from cattle with susceptible or resistant genotypes. Taken together, these results indicate that these polymorphisms at the NRAMP1 3'UTR do not affect resistance against B. abortus in cattle and that they are therefore not suitable markers of natural resistance against bovine brucellosis.
Assuntos
Regiões 3' não Traduzidas/genética , Brucella abortus/classificação , Brucella abortus/patogenicidade , Brucelose Bovina/imunologia , Proteínas de Transporte de Cátions/genética , Polimorfismo Genético , Aborto Animal/genética , Aborto Animal/imunologia , Aborto Animal/microbiologia , Animais , Brucella abortus/genética , Brucelose Bovina/genética , Brucelose Bovina/microbiologia , Bovinos , Células Cultivadas , Feminino , Predisposição Genética para Doença , Genótipo , Macrófagos/microbiologia , Masculino , Doenças Placentárias/genética , Doenças Placentárias/imunologia , Doenças Placentárias/microbiologia , Doenças Placentárias/veterinária , Polimorfismo Conformacional de Fita Simples , GravidezRESUMO
AIM: To compare the expression of p57 as indirect marker of genomic imprinting of CDKN1C in a series of infantile hemangiomas (IH) of patients with and without Beckwith-Wiedemann syndrome. MATERIALS AND METHODS: Cases of mammary, salivary gland, liver (one each), and placental (2 cases) capillary hemangiomas all with histological features akin to IH as well as typical examples of cutaneous (8 cases) IH were analyzed by immunohistochemistry with antibody against p57(KIP2). This protein is the product of CDKN1C an imprinted, maternally expressed gene. The liver hemangioma and both chorioangiomas were from patients with Beckwith-Wiedemann syndrome. Positive and negative controls included normal placental tissue and complete hydatidiform mole, respectively. Positive staining was localized to nuclei. RESULTS: Endothelial cells from the skin, breast and salivary gland hemangiomas were p57(KIP2) positive while chorioangiomas and liver IH presenting in patients with Beckwith-Wiedemann syndrome were negative. Controls reacted appropriately. CONCLUSIONS: Endothelial cells of IH not associated with BWS normally express p57(KIP2) while chorioangiomas and IH of the liver associated with BWS do not. These results suggest that the BWS IH may result from dysregulation of the cell cycle.
Assuntos
Hemangioma/metabolismo , Proteínas Nucleares/biossíntese , Síndrome de Beckwith-Wiedemann/genética , Síndrome de Beckwith-Wiedemann/metabolismo , Síndrome de Beckwith-Wiedemann/patologia , Biomarcadores , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular/fisiologia , Criança , Pré-Escolar , Inibidor de Quinase Dependente de Ciclina p57 , Feminino , Hemangioma/genética , Hemangioma/patologia , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Proteínas Nucleares/genética , Doenças Placentárias/genética , Doenças Placentárias/metabolismo , Doenças Placentárias/patologia , Gravidez , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Fixação de TecidosRESUMO
La presente revisión trata de la enfermedad trafoblástica gestacional haciendo referencia a los tumores de origen placentario que se derivan del tejido epitelial coriónico. Se describe la clasificación según la OMS, resaltando ls sintomatología clásica de esta patología, así como también los métodos de laboratorio más utilizados como son: La ecosonografía, La dosificación de HCG. Gamagrafía, TAC, estudios de histopatología, medición de alfa feto proteínas dosificación de calcio calmodulina y de CAMP-A quinasa, por último se revisan los esquemas terapéuticos más usados hoy en día.