RESUMO
PURPOSE: Diffuse intrinsic pontine gliomas (DIPGs) are the most fatal primary brainstem tumors in pediatric patients. The identification of new molecular features, mediating their formation and progression, as non-coding RNAs (ncRNAs), would be of great importance for the development of effective treatments. METHODS: We analyzed the DIPGs transcriptome with the HTA2.0 array and it was compared with pediatric non-brainstem astrocytoma expression profiles (GSE72269). RESULTS: More than 50% of the differentially expressed transcripts were ncRNAs and based on this, we proposed a DIPGs ncRNA signature. LncRNAs XIST and XIST-210, and the HBII-52 and HBII-85 snoRNA clusters were markedly downregulated in DIPGs. qPCR assays demonstrated XIST downregulation in all non-brainstem astrocytomas, in a gender, age, and brain location-independent manner, as well as in DIPGs affecting boys; however, DIPGs affecting girls showed both downregulation and upregulation of XIST. Girls' with longer survival positively correlated with XIST expression. CONCLUSIONS: The involvement of ncRNAs in DIPGs is imminent and their expression profile is useful to differentiate them from non-neoplastic tissues and non-brain stem astrocytomas, which suggests their potential use as DIPG biomarkers. In fact, XIST and XIST-210 are potential DIPG prognostic biomarkers.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias do Tronco Encefálico/diagnóstico , Glioma Pontino Intrínseco Difuso/diagnóstico , RNA não Traduzido/metabolismo , Transcriptoma , Adolescente , Fatores Etários , Processamento Alternativo , Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/mortalidade , Criança , Pré-Escolar , Bases de Dados Genéticas , Glioma Pontino Intrínseco Difuso/diagnóstico por imagem , Glioma Pontino Intrínseco Difuso/genética , Glioma Pontino Intrínseco Difuso/mortalidade , Regulação para Baixo , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , RNA Nucleolar Pequeno/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores Sexuais , Regulação para CimaRESUMO
Mechanical ventilation is a therapeutic intervention involving the temporary replacement of ventilatory function with the purpose of improving symptoms in patients with acute respiratory failure. Technological advances have facilitated the development of sophisticated ventilators for viewing and recording the respiratory waveforms, which are a valuable source of information for the clinician. The correct interpretation of these curves is crucial for the correct diagnosis and early detection of anomalies, and for understanding physiological aspects related to mechanical ventilation and patient-ventilator interaction. The present study offers a guide for the interpretation of the airway pressure and flow and volume curves of the ventilator, through the analysis of different clinical scenarios.
Assuntos
Respiração Artificial , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Doença Aguda , Humanos , RespiraçãoRESUMO
Ventilator-induced lung injury (VILI) is associated to a high rate of mortality with an important social impact. Mechanical ventilation induces structural and ultrastructural alterations in all cell types of the lung and can derive in the transduction of intracellular signals, as well as in changes in the expression of genes, a process known as mechanotransduction. Some of the conditions involved, such as inflammation and/or coagulation, apoptosis/necrosis can lead to the propagation of the injury outside the lung, resulting in multiorganic failure. VILI can be modulated by means of diverse interventions as the use of protective ventilatory modes, therapeutic approaches based on vasoactive and antioxidative drugs, and more recently treatments based on the use of repairing substances of the surfactant like poloxamers among others. Knowledge of the mechanisms involved in VILI is definitive for a better approach to this condition.