CARLOS ALBERTO MOREIRA FILHO

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Departamento de Pediatria, Faculdade de Medicina - Docente
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina - Líder

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  • article 22 Citação(ões) na Scopus
    Circulating CD4 and CD8 T cells expressing pro-inflammatory cytokines in a cohort of mesial temporal lobe epilepsy patients with hippocampal sclerosis
    (2016) ROSA, Daniela Valadao; REZENDE, Vitor Bortolo; COSTA, Bruno Silva; MUDADO, Fernando; SCHUETZE, Manuel; TORRES, Karen Cecilia; MARTINS, Luiza Conceicao; MOREIRA-FILHO, Carlos Alberto; MIRANDA, Debora Marques; ROMANO-SILVA, Marco Aurelio
    Objective: To compare the proinflammatory and anti-inflammatory cytokine expression profile of CD4(+) and CD8(+) T lymphocytes between drug resistant mesial Temporal Lobe Epilepsy (mTLE) patients and healthy subjects. Methods: mTLE patients were enrolled at the Neurology Center of Santa Casa de Misericordia de Belo Horizonte (SCM-BH) and healthy volunteers were selected at Universidade Federal de Minas Gerais. Individuals from both groups accepted to participate in this study and signed an informed consent. Peripheral venous blood samples were collected using sodium heparin vacuum tubes on the day before the surgery and in the interictal period, isolated from whole blood using Ficoll/Hypaque followed by flow cytometry analysis. Data analysis was performed using FlowJo. Results: Compared to healthy individuals, mTLE patients showed reduced frequency of CD8(+) T lymphocytes expressing IFN-gamma, TNF-alpha, IL-17 and IL-4. Moreover, mTLE patients presented increased frequency of CD4(+) T lymphocytes expressing IL-6 when compared to healthy volunteers. Discussion: Epilepsy is the third most common chronic brain disorder. Mesial temporal lobe epilepsy (mTLE) is a major and severe form of epilepsy and 30% of the mTLE patients do not respond to conventional medications. Our data suggest that mTLE patients have distinct immunological profiles that are related to disease pathophysiology.
  • article 57 Citação(ões) na Scopus
    Innate immune response is differentially dysregulated between bipolar disease and schizophrenia
    (2015) BAUMONT, Angelica de; MASCHIETTO, Mariana; LIMA, Leandro; CARRARO, Dirce Maria; OLIVIERI, Eloisa Helena; FIORINI, Alex; BARRETA, Luiz Andre Nardin; PALHA, Joana Almeida; BELMONTE-DE-ABREU, Paulo; MOREIRA FILHO, Carlos Alberto; BRENTANI, Helena
    Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric conditions with a neurodevelopmental component. Genetic findings indicate the existence of an overlap in genetic susceptibility across the disorders. Also, image studies provide evidence for a shared neurobiological basis, contributing to a dimensional diagnostic approach. This study aimed to identify the molecular mechanisms that differentiate SZ and BD patients from health controls but also that distinguish both from health individuals. Comparison of gene expression profiling in post-mortem brains of both disorders and health controls (30 cases), followed by a further comparison between 29 BD and 29 SZ revealed 28 differentially expressed genes. These genes were used in co-expression analysesthat revealed the pairs CCR1/SERPINA1, CCR5/HCST, C1QA/CD68, CCR5/S100A11 and SERPINA1/TLR1 as presenting the most significant difference in co-expression between SZ and BD. Next, a protein-protein interaction (PPI) network using the 28 differentially expressed genes as seeds revealed CASP4, TYROBP, CCR1, SERPINA1, CCR5 and C1QA as having a central role in the diseases manifestation. Both co-expression and network topological analyses pointed to genes related to microglia functions. Based on this data, we suggest that differences between SZ and BP are due to genes involved with response to stimulus, defense response, immune system process and response to stress biological processes, all having a role in the communication of environmental factors to the cells and associated to microglia.
  • article 23 Citação(ões) na Scopus
    Texture analysis of high resolution MRI allows discrimination between febrile and afebrile initial precipitating injury in mesial temporal sclerosis
    (2012) ALEGRO, Maryana de Carvalho; SILVA, Alexandre Valotta; BANDO, Silvia Yumi; LOPES, Roseli de Deus; CASTRO, Luiz Henrique Martins de; HUNGTSU, Wen; MOREIRA-FILHO, Carlos Alberto; AMARO JR., Edson
    A computational pipeline combining texture analysis and pattern classification algorithms was developed for investigating associations between high-resolution MRI features and histological data. This methodology was tested in the study of dentate gyrus images of sclerotic hippocampi resected from refractory epilepsy patients. Images were acquired using a simple surface coil in a 3.0T MRI scanner. All specimens were subsequently submitted to histological semiquantitative evaluation. The computational pipeline was applied for classifying pixels according to: a) dentate gyrus histological parameters and b) patients' febrile or afebrile initial precipitating insult history. The pipeline results for febrile and afebrile patients achieved 70% classification accuracy, with 78% sensitivity and 80% specificity [area under the reader observer characteristics (ROC) curve: 0.89]. The analysis of the histological data alone was not sufficient to achieve significant power to separate febrile and afebrile groups. Interesting enough, the results from our approach did not show significant correlation with histological parameters (which per se were not enough to classify patient groups). These results showed the potential of adding computational texture analysis together with classification methods for detecting subtle MRI signal differences, a method sufficient to provide good clinical classification. A wide range of applications of this pipeline can also be used in other areas of medical imaging. Magn Reson Med, 2012. (c) 2012 Wiley Periodicals, Inc.
  • conferenceObject
    TRISOMY 21-DRIVEN GENE EXPRESSION DYSREGULATION IN HUMAN THYMUS: CONVERGING GENOMIC AND EPIGENOMIC MECHANISMS
    (2016) MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; SILVA, Filipi Nascimento; COSTA, Luciano da Fontoura; FEREIRA, Leandro Rodrigues; CARNEIRO-SAMPAIO, Magda
  • conferenceObject
    Association of Hippocampal CA3 Transcriptional Modules with Language Impairment in Mesial Temporal Lobe Epilepsy
    (2017) MANSANO-OLIVEIRA, Joao; BANDO, Silvia; BERTONHA, Fernanda; CASTRO, Bettina; MESSAS, Cristiane; WEN, Hung-Tzu; MOREIRA-FILHO, Carlos; CASTRO, Luiz
  • bookPart 2 Citação(ões) na Scopus
    Methods for Gene Co-expression Network Visualization and Analysis
    (2022) MOREIRA-FILHO, C. A.; BANDO, S. Y.; BERTONHA, F. B.; SILVA, F. N.; COSTA, L. D. F.
    Gene network analysis is an important tool for studying the changes in steady states that characterize cell functional properties, the genome-environment interplay, and the health-disease transitions. Moreover, gene co-expression and protein–protein interaction (PPI) data can be integrated with clinical, histopathological, and imaging information – a current practice in systems biology – leading, for instance, to the identification of unique and common drivers for disease conditions. In this chapter the fundamentals for gene co-expression network construction, visualization, and analysis are revised, emphasizing its scale-free nature, the measures that express its most relevant topological features, and methods for network validation. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2014, 2022.
  • conferenceObject
    Sexual Dimorphism and AIRE-AIRE Interactors-miRNA Coexpression Networks in the Infant Human Thymus
    (2019) BANDO, Silvia Y.; BERTONHA, Fernanda B.; OLIVEIRA, Lucila H. B.; MOREIRA-FILHO, Carlos Alberto; CARNEIRO-SAMPAIO, Magda
  • conferenceObject
    Complete Transcriptional Network Driven-View of Thymic Hypofunction in Down Syndrome
    (2014) MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; FEREIRA, Leandro Rodrigues; SILVA, Filipi Nascimento; COSTA, Luciano da Fontoura; GRASSI, Marcilia Sierro; CARNEIRO-SAMPAIO, Magda
  • article 16 Citação(ões) na Scopus
    N-acetyl-cysteine is associated to renal function improvement in patients with nephropathic cystinosis
    (2014) GUIMARAES, Luciana Pache de Faria; SEGURO, Antonio Carlos; SHIMIZU, Maria Heloisa Mazzola; NERI, Leticia Aparecida Lopes; SUMITA, Nairo Massakasu; BRAGANCA, Ana Carolina de; VOLPINI, Rildo Aparecido; SANCHES, Talita Rojas Cunha; FONSECA, Fernanda Andrade Macaferri da; MOREIRA FILHO, Carlos Alberto; VAISBICH, Maria Helena
    Nephropathic cystinosis is an autosomal recessive systemic severe disease characterized by intralysosomal cystine storage. Cysteamine is an essential component of treatment. There is solid evidence that cystine accumulation itself is not responsible for all abnormalities in cystinosis; there is also a deficiency of glutathione in the cytosol. Patients with cystinosis can be more susceptible to oxidative stress. The patient cohort comprised 23 cystinosis patients (16 males) aged < 18 years (mean age 8.0 +/- 3.6 years) with chronic kidney disease class I-IV with good adherence to treatment, including cysteamine. Oxidative stress was evaluated based on the levels of serum thiobarbituric acid-reactive substances (TBARS), and renal function was evaluated based on serum creatinine and cystatin C levels and creatinine clearance (Schwartz formula). N-Acetylcysteine (NAC), an antioxidant drug was given to all patients for 3 months (T1) at 25 mg/kg/day divided in three doses per day. The measured values at just before the initiation of NAC treatment (T0) served as the control for each patient. Median serum TBARS levels at T0 and T1 were 6.92 (range 3.3-29.0) and 1.7 (0.6-7.2) nmol/mL, respectively (p < 0.0001). In terms of renal function at T0 and T1, serum creatinine levels (1.1 +/- 0.5 vs. 0.9 +/- 0.5 mg/dL, respectively; p < 0.0001), creatinine clearance (69.7 +/- 32.2 vs. T1 = 78.5 +/- 33.9 mL/min/1.73 m(2), respectively; p = 0.006), and cystatin c level (1.33 +/- 0.53 vs. 1.15 +/- 0.54 mg/l, respectively; p = 0.0057) were all significantly different at these two time points. Serum creatinine measurements at 6 (T -6) and 3 months (T -3) before NAC initiation and at 3 (T +3) and 6 months (T +6) after NAC had been withdrawn were also evaluated. During the 3-month period that our 23 cystinosis patients were treated with NAC, oxidative stress was reduced and renal function significantly improved. No side-effects were detected. Larger and controlled studies are needed to confirm these findings.
  • article 16 Citação(ões) na Scopus
    Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants
    (2016) MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; SILVA, Filipi Nascimento; COSTA, Luciano da Fontoura; FERREIRA, Leandro Rodrigues; FURLANETTO, Glaucio; CHACUR, Paulo; ZERBINI, Maria Claudia Nogueira; CARNEIRO-SAMPAIO, Magda
    Trisomy 21-driven transcriptional alterations in human thymus were characterized through gene coexpression network (GCN) and miRNA-target analyses. We used whole thymic tissue - obtained at heart surgery from Down syndrome (DS) and karyotipically normal subjects (CT) - and a network-based approach for GCN analysis that allows the identification of modular transcriptional repertoires (communities) and the interactions between all the system's constituents through community detection. Changes in the degree of connections observed for hierarchically important hubs/genes in CT and DS networks corresponded to community changes. Distinct communities of highly interconnected genes were topologically identified in these networks. The role of miRNAs in modulating the expression of highly connected genes in CT and DS was revealed through miRNA-target analysis. Trisomy 21 gene dysregulation in thymus may be depicted as the breakdown and altered reorganization of transcriptional modules. Leading networks acting in normal or disease states were identified. CT networks would depict the ""canonical"" way of thymus functioning. Conversely, DS networks represent a ""non-canonical"" way, i. e., thymic tissue adaptation under trisomy 21 genomic dysregulation. This adaptation is probably driven by epigenetic mechanisms acting at chromatin level and through the miRNA control of transcriptional programs involving the networks' high-hierarchy genes.