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
4 resultados
Resultados de Busca
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- 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.
- Gene expression alterations in the postmortem hippocampus from older patients with bipolar disorder-A hypothesis generating study(2023) NASCIMENTO, Camila; KIM, Helena Kyunghee; NUNES, Paula Villela; LEITE, Renata Elaine Paraiso; CRISTINA, De Oliveira Katia; BARBOSA, Andre; BERTONHA, Fernanda Bernardi; MOREIRA-FILHO, Carlos Alberto; JACOB-FILHO, Wilson; NITRINI, Ricardo; PASQUALUCCI, Carlos A.; GRINBERG, Lea Tenenholz; SUEMOTO, Claudia Kimie; BRENTANI, Helena Paula; LAFER, BenyBipolar disorder (BD) presents with a progressive course in a subset of patients. However, our knowledge of molecular changes in older BD is limited. In this study, we examined gene expression changes in the hippocampus of BD from the Biobank of Aging Studies to identify genes of interest that warrant further exploration. RNA was extracted from the hippocampus from 11 subjects with BD and 11 age and sex-matched controls. Gene expression data was generated using the SurePrint G3 Human Gene Expression v3 microarray. Rank feature selection was performed to identify a subset of features that can optimally differentiate BD and controls. Genes ranked in the top 0.1% with log2 fold change >1.2 were identified as genes of interest. Average age of the subjects was 64 years old; duration of disease was 21 years and 82% were female. Twenty-five genes were identified, of which all but one was downregulated in BD. Of these, CNTNAP4, MAP4, SLC4A1, COBL, and NEURL4 had been associated with BD and other psychiatric conditions in previous studies. We believe our findings have identified promising targets to inform future studies aiming to understand the pathophysiology of BD in later life.
- Epidemiological, Clinical, and Genomic Profile in Head and Neck Cancer Patients and Their Families(2022) CHULAM, Thiago Celestino; BERTONHA, Fernanda Bernardi; VILLACIS, Rolando Andre Rios; FILHO, Joao Goncalves; KOWALSKI, Luiz Paulo; ROGATTO, Silvia ReginaInherited cancer predisposition genes are described as risk factors in head and neck cancer (HNC) families. To explore the clinical and epidemiological data and their association with a family history of cancer, we recruited 74 patients and 164 relatives affected by cancer. The germline copy number alterations were evaluated in 18 patients using array comparative genomic hybridization. Two or more first-degree relatives with HNC, tobacco-associated tumor sites (lung, esophagus, and pancreas), or other related tumors (breast, colon, kidney, bladder, cervix, stomach carcinomas, and melanoma) were reported in 74 families. Ten index patients had no exposure to any known risk factors. Family members presented tumors of 19 topographies (30 head and neck, 26 breast, 21 colon). In first-degree relatives, siblings were frequently affected by cancer (n = 58, 13 had HNC). Breast cancer (n = 21), HNC (n = 19), and uterine carcinoma (n = 15) were commonly found in first-degree relatives and HNC in second-degree relatives (n = 11). Nineteen germline genomic imbalances were detected in 13 patients; three presented gains of WRD genes. The number of HNC patients, the degree of kinship, and the tumor types detected in each relative support the role of heredity in these families. Germline alterations may potentially contribute to cancer development.
- 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.