FERNANDA BERNARDI BERTONHA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Pediatria, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- Age-related transcriptional modules and TF-miRNA-mRNA interactions in neonatal and infant human thymus(2020) BERTONHA, Fernanda Bernardi; BANDO, Silvia Yumi; FERREIRA, Leandro Rodrigues; CHACCUR, Paulo; VINHAS, Christiana; ZERBINI, Maria Claudia Nogueira; CARNEIRO-SAMPAIO, Magda Maria; MOREIRA-FILHO, Carlos AlbertoThe human thymus suffers a transient neonatal involution, recovers and then starts a process of decline between the 1st and 2nd years of life. Age-related morphological changes in thymus were extensively investigated, but the genomic mechanisms underlying this process remain largely unknown. Through Weighted Gene Co-expression Network Analysis (WGCNA) and TF-miRNA-mRNA integrative analysis we studied the transcriptome of neonate and infant thymic tissues grouped by age: 0-30 days (A); 31 days-6 months (B); 7-12 months (C); 13-18 months (D); 19-31 months (E). Age-related transcriptional modules, hubs and high gene significance (HGS) genes were identified, as well as TF-miRNA-hub/HGS co-expression correlations. Three transcriptional modules were correlated with A and/or E groups. Hubs were mostly related to cellular/metabolic processes; few were differentially expressed (DE) or related to T-cell development. Inversely, HGS genes in groups A and E were mostly DE. In A (neonate) one third of the hyper-expressed HGS genes were related to T-cell development, against one-twentieth in E, what may correlate with the early neonatal depletion and recovery of thymic T-cell populations. This genomic mechanism is tightly regulated by TF-miRNA-hub/HGS interactions that differentially govern cellular and molecular processes involved in the functioning of the neonate thymus and in the beginning of thymic decline.
- Age-related transcriptional modules and TF-miRNA-mRNA interactions in neonatal and infant human thymus (vol 15, e0227547, 2020)(2020) BERTONHA, F. B.; BANDO, S. Y.; FERREIRA, L. R.; CHACCUR, P.; VINHAS, C.; ZERBINI, M. C. N.
- Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients(2021) BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; PIMENTEL-SILVA, Luciana Ramalho; OLIVEIRA, Joao Gabriel Mansano de; CARNEIRO, Marco Antonio Duarte; OKU, Mariana Hiromi Manoel; WEN, Hung-Tzu; CASTRO, Luiz Henrique Martins; MOREIRA-FILHO, Carlos AlbertoIn about a third of the patients with epilepsy the seizures are not drug-controlled. The current limitation of the antiepileptic drug therapy derives from an insufficient understanding of epilepsy pathophysiology. In order to overcome this situation, it is necessary to consider epilepsy as a disturbed network of interactions, instead of just looking for changes in single molecular components. Here, we studied CA3 transcriptional signatures and dentate gyrus histopathologic alterations in hippocampal explants surgically obtained from 57 RMTLE patients submitted to corticoamygdalohippocampectomy. By adopting a systems biology approach, integrating clinical, histopathological, and transcriptomic data (weighted gene co-expression network analysis), we were able to identify transcriptional modules highly correlated with age of disease onset, cognitive dysfunctions, and granule cell alterations. The enrichment analysis of transcriptional modules and the functional characterization of the highly connected genes in each trait-correlated module allowed us to unveil the modules' main biological functions, paving the way for further investigations on their roles in RMTLE pathophysiology. Moreover, we found 15 genes with high gene significance values which have the potential to become novel biomarkers and/or therapeutic targets in RMTLE.
- Blood leukocyte transcriptional modules and differentially expressed genes associated with disease severity and age in COVID-19 patients(2023) BANDO, Silvia Y.; BERTONHA, Fernanda B.; VIEIRA, Sandra E.; OLIVEIRA, Danielle B. L. de; CHALUP, Vanessa N.; DURIGON, Edison L.; PALMEIRA, Patricia; CURI, Ana Cristina P.; FARIA, Caroline S.; ANTONANGELO, Leila; LAUTERBACH, Gerhard da P.; REGALIO, Fabiane A.; CESAR, Roberto M.; MOREIRA-FILHO, Carlos A.Since the molecular mechanisms determining COVID-19 severity are not yet well understood, there is a demand for biomarkers derived from comparative transcriptome analyses of mild and severe cases, combined with patients' clinico-demographic and laboratory data. Here the transcriptomic response of human leukocytes to SARS-CoV-2 infection was investigated by focusing on the differences between mild and severe cases and between age subgroups (younger and older adults). Three transcriptional modules correlated with these traits were functionally characterized, as well as 23 differentially expressed genes (DEGs) associated to disease severity. One module, correlated with severe cases and older patients, had an overrepresentation of genes involved in innate immune response and in neutrophil activation, whereas two other modules, correlated with disease severity and younger patients, harbored genes involved in the innate immune response to viral infections, and in the regulation of this response. This transcriptomic mechanism could be related to the better outcome observed in younger COVID-19 patients. The DEGs, all hyper-expressed in the group of severe cases, were mostly involved in neutrophil activation and in the p53 pathway, therefore related to inflammation and lymphopenia. These biomarkers may be useful for getting a better stratification of risk factors in COVID-19.
- Community Structure Analysis of Transcriptional Networks Reveals Distinct Molecular Pathways for Early- and Late-Onset Temporal Lobe Epilepsy with Childhood Febrile Seizures(2015) MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; IAMASHITA, Priscila; SILVA, Filipi Nascimento; COSTA, Luciano da Fontoura; SILVA, Alexandre Valotta; CASTRO, Luiz Henrique Martins; WEN, Hung-TzuAge at epilepsy onset has a broad impact on brain plasticity and epilepsy pathomechanisms. Prolonged febrile seizures in early childhood (FS) constitute an initial precipitating insult (IPI) commonly associated with mesial temporal lobe epilepsy (MTLE). FS-MTLE patients may have early disease onset, i.e. just after the IPI, in early childhood, or late-onset, ranging from mid-adolescence to early adult life. The mechanisms governing early (E) or late (L) disease onset are largely unknown. In order to unveil the molecular pathways underlying E and L subtypes of FS-MTLE we investigated global gene expression in hippocampal CA3 explants of FS-MTLE patients submitted to hippocampectomy. Gene coexpression networks (GCNs) were obtained for the E and L patient groups. A network-based approach for GCN analysis was employed allowing: i) the visualization and analysis of differentially expressed (DE) and complete (CO) - all valid GO annotated transcripts - GCNs for the E and L groups; ii) the study of interactions between all the system's constituents based on community detection and coarse-grained community structure methods. We found that the E-DE communities with strongest connection weights harbor highly connected genes mainly related to neural excitability and febrile seizures, whereas in L-DE communities these genes are not only involved in network excitability but also playing roles in other epilepsy-related processes. Inversely, in E-CO the strongly connected communities are related to compensatory pathways (seizure inhibition, neuronal survival and responses to stress conditions) while in L-CO these communities harbor several genes related to pro-epileptic effects, seizure-related mechanisms and vulnerability to epilepsy. These results fit the concept, based on fMRI and behavioral studies, that early onset epilepsies, although impacting more severely the hippocampus, are associated to compensatory mechanisms, while in late MTLE development the brain is less able to generate adaptive mechanisms, what has implications for epilepsy management and drug discovery.
- Minipuberty and Sexual Dimorphism in the Infant Human Thymus(2018) MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; FERREIRA, Leandro Rodrigues; VINHAS, Christiana de Freitas; OLIVEIRA, Lucila Habib Bourguignon; ZERBINI, Maria Claudia Nogueira; FURLANETTO, Glaucio; CHACCUR, Paulo; CARNEIRO-SAMPAIO, MagdaAIRE expression in thymus is downregulated by estrogen after puberty, what probably renders women more susceptible to autoimmune disorders. Here we investigated the effects of minipuberty on male and female infant human thymic tissue in order to verify if this initial transient increase in sex hormones - along the first six months of life - could affect thymic transcriptional network regulation and AIRE expression. Gene co-expression network analysis for differentially expressed genes and miRNA-target analysis revealed sex differences in thymic tissue during minipuberty, but such differences were not detected in the thymic tissue of infants aged 7-18 months, i.e. the non-puberty group. AIRE expression was essentially the same in both sexes in minipuberty and in non-puberty groups, as assessed by genomic and immunohistochemical assays. However, A/RE-interactors networks showed several differences in all groups regarding gene-gene expression correlation. Therefore, minipuberty and genomic mechanisms interact in shaping thymic sexual dimorphism along the first six months of life.
- Transcriptomic analysis reveals distinct adaptive molecular mechanism in the hippocampal CA3 from rats susceptible or not-susceptible to hyperthermia-induced seizures(2023) BANDO, Silvia Y.; BERTONHA, Fernanda B.; MENEZES, Pedro H. N.; TAKAHARA, Andre K.; KHALED, Nathalia A.; SANTOS, Paula; JUNQUEIRA, Mara S.; CESAR, Roberto M.; MOREIRA-FILHO, Carlos A.Febrile seizures during early childhood are a relevant risk factor for the development of mesial temporal lobe epilepsy. Nevertheless, the molecular mechanism induced by febrile seizures that render the brain susceptible or not-susceptible to epileptogenesis remain poorly understood. Because the temporal investigation of such mechanisms in human patients is impossible, rat models of hyperthermia-induced febrile seizures have been used for that purpose. Here we conducted a temporal analysis of the transcriptomic and microRNA changes in the ventral CA3 of rats that develop (HS group) or not-develop (HNS group) seizures after hyperthermic insult on the eleventh postnatal day. The selected time intervals corresponded to acute, latent, and chronic phases of the disease. We found that the transcriptional differences between the HS and the HNS groups are related to inflammatory pathways, immune response, neurogenesis, and dendritogenesis in the latent and chronic phases. Additionally, the HNS group expressed a greater number of miRNAs (some abundantly expressed) as compared to the HS group. These results indicate that HNS rats were able to modulate their inflammatory response after insult, thus presenting better tissue repair and re-adaptation. Potential therapeutic targets, including genes, miRNAs and signaling pathways involved in epileptogenesis were identified.