SILVIA YUMI BANDO TAKAHARA
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
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- 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.
- 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.
- Phylogenetic Analysis of Stenotrophomonas spp. Isolates Contributes to the Identification of Nosocomial and Community-Acquired Infections(2014) CEREZER, Vinicius Godoy; BANDO, Silvia Yumi; PASTERNAK, Jacyr; FRANZOLIN, Marcia Regina; MOREIRA-FILHO, Carlos AlbertoStenotrophomonas ssp. has a wide environmental distribution and is also found as an opportunistic pathogen, causing nosocomial or community-acquired infections. One species, S. maltophilia, presents multidrug resistance and has been associated with serious infections in pediatric and immunocompromised patients. Therefore, it is relevant to conduct resistance profile and phylogenetic studies in clinical isolates for identifying infection origins and isolates with augmented pathogenic potential. Here, multilocus sequence typing was performed for phylogenetic analysis of nosocomial isolates of Stenotrophomonas spp. and, environmental and clinical strains of S. maltophilia. Biochemical andmultidrug resistance profiles of nosocomial and clinical strains were determined. The inferred phylogenetic profile showed high clonal variability, what correlates with the adaptability process of Stenotrophomonas to different habitats. Two clinical isolates subgroups of S. maltophilia sharing high phylogenetic homogeneity presented intergroup recombination, thus indicating the high permittivity to horizontal gene transfer, a mechanism involved in the acquisition of antibiotic resistance and expression of virulence factors. For most of the clinical strains, phylogenetic inference was made using only partial ppsA gene sequence. Therefore, the sequencing of just one specific fragment of this gene would allow, in many cases, determining whether the infection with S. maltophilia was nosocomial or community-acquired.
- 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.
- Dynamic Gene Network Analysis of Caco-2 Cell Response to Shiga Toxin-Producing Escherichia coli-Associated Hemolytic-Uremic Syndrome(2019) BANDO, Silvia Y.; IAMASHITA, Priscila; SILVA, Filipi N.; COSTA, Luciano da F.; ABE, Cecilia M.; BERTONHA, Fernanda B.; GUTH, Beatriz E. C.; FUJITA, Andre; MOREIRA-FILHO, Carlos A.Shiga toxin-producing Escherichia coli (STEC) O113:H21 strains are associated with human diarrhea and some strains may cause hemolytic-uremic syndrome (HUS). In Brazil, these strains are commonly found in cattle but, so far, were not isolated from HUS patients. Here, a system biology approach was used to investigate the differential transcriptomic and phenotypic responses of enterocyte-like Caco-2 cells to two STEC O113:H21 strains with similar virulence factor profiles (i.e., expressing stx2, ehxA, epeA, espA, iha, saa, sab, and subA): EH41 (Caco-2/EH41), isolated from a HUS patient in Australia, and Ec472/01 (Caco-2/Ec472), isolated from bovine feces in Brazil, during a 3 h period of bacteria-enterocyte interaction. Gene co-expression network analysis for Caco-2/EH41 revealed a quite abrupt pattern of topological variation along 3 h of enterocyte-bacteria interaction when compared with networks obtained for Caco-2/Ec472. Transcriptional module characterization revealed that EH41 induces inflammatory and apoptotic responses in Caco-2 cells just after the first hour of enterocyte-bacteria interaction, whereas the response to Ec472/01 is associated with cytoskeleton organization at the first hour, followed by the expression of immune response modulators. Scanning electron microscopy showed more intense microvilli destruction in Caco-2 cells exposed to EH41 when compared to those exposed to Ec472/01. Altogether, these results show that EH41 expresses virulence genes, inducing a distinctive host cell response, and is likely associated with severe pathogenicity.