CARLOS AUGUSTO GONCALVES PASQUALUCCI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
ATCIENT-50, SVOC
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina - Líder
ATCIENT-50, SVOC
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina - Líder
32 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 32
- Fructose ingestion impairs expression of genes involved in skeletal muscle's adaptive response to aerobic exercise(2017) GONCALVES, Natalia Gomes; CAVALETTI, Stephanie Heffer; PASQUALUCCI, Carlos Augusto; MARTINS, Milton Arruda; LIN, Chin JiaBackground: The inverse relationship between exercise capacity and its variation over time and both cardiovascular and all-cause mortality suggests the existence of an etiological nexus between cardiometabolic diseases and the molecular regulators of exercise capacity. Coordinated adaptive responses elicited by physical training enhance exercise performance and metabolic efficiency and possibly mediate the health benefits of physical exercise. In contrast, impaired expression of genes involved in mitochondrial biogenesis or protein turnover in skeletal muscle-key biological processes involved in adaptation to physical training-leads to insulin resistance and obesity. Ingestion of fructose has been shown to suppress the exercise-induced GLUT4 response in rat skeletal muscle. To evaluate in greater detail how fructose ingestion might blunt the benefits of physical training, we investigated the effects of fructose ingestion on exercise induction of genes that participate in regulation of mitochondrial biogenesis and protein turnover in rat's skeletal muscle. Methods: Eight-week-old Wistar rats were randomly assigned to sedentary (C), exercise (treadmill running)-only (E), fructose-only (F), and fructose + exercise (FE) groups and treated accordingly for 8 weeks. Blood and quadriceps femoris were collected for biochemistry, serum insulin, and gene expression analysis. Expression of genes involved in regulation of mitochondrial biogenesis and autophagy, GLUT4, and ubiquitin E3 ligases MuRF-1, and MAFbx/Atrogin-1 were assayed with quantitative real-time polymerase chain reaction. Results: Aerobic training improved exercise capacity in both E and FE groups. A main effect of fructose ingestion on body weight and fasting serum triglyceride concentration was detected. Fructose ingestion impaired the expression of PGC-1 alpha, FNDC5, NR4A3, GLUT4, Atg9, Lamp2, Ctsl, Murf-1, and MAFBx/Atrogin-1 in skeletal muscle of both sedentary and exercised animals while expression of Err alpha and Ppar delta was impaired only in exercised rats. Conclusions: Our results show that fructose ingestion impairs the expression of genes involved in biological processes relevant to exercise-induced remodeling of skeletal muscle. This might provide novel insight on how a dietary factor contributes to the genesis of disorders of glucose metabolism.
- Differential DNA Methylation of MicroRNA Genes in Temporal Cortex from Alzheimer's Disease Individuals(2016) VILLELA, Darine; RAMALHO, Rodrigo F.; SILVA, Aderbal R. T.; BRENTANI, Helena; SUEMOTO, Claudia K.; PASQUALUCCI, Carlos Augusto; GRINBERG, Lea T.; KREPISCHI, Ana C. V.; ROSENBERG, CarlaThis study investigated for the first time the genomewide DNA methylation changes of noncoding RNA genes in the temporal cortex samples from individuals with Alzheimer's disease (AD). The methylome of 10 AD individuals and 10 age-matched controls were obtained using Illumina 450K methylation array. A total of 2,095 among the 15,258 interrogated noncoding RNA CpG sites presented differential methylation, 161 of which were associated with miRNA genes. In particular, 10 miRNA CpG sites that were found to be hypermethylated in AD compared to control brains represent transcripts that have been previously associated with the disease. This miRNA set is predicted to target 33 coding genes from the neuregulin receptor complex (ErbB) signaling pathway, which is required for the neurons myelination process. For 6 of these miRNA genes (MIR9-1, MIR9-3, MIR181C, MIR124-1, MIR146B, and MIR451), the hypermethylation pattern is in agreement with previous results from literature that shows downregulation of miR-9, miR-181c, miR-124, miR-146b, and miR-451 in the AD brain. Our data implicate dysregulation of miRNA methylation as contributor to the pathogenesis of AD.
- Postmortem Brains from Subjects with Diabetes Mellitus Display Reduced GLUT4 Expression and Soma Area in Hippocampal Neurons: Potential Involvement of Inflammation(2023) YONAMINE, Caio Yogi; PASSARELLI, Marisa; SUEMOTO, Claudia Kimie; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; ALVES, Venancio Avancini Ferreira; MARIE, Suely Kazue Nagahashi; CORREA-GIANNELLA, Maria Lucia; BRITTO, Luiz Roberto; MACHADO, Ubiratan FabresDiabetes mellitus (DM) is an important risk factor for dementia, which is a common neurodegenerative disorder. DM is known to activate inflammation, oxidative stress, and advanced glycation end products (AGEs) generation, all capable of inducing neuronal dysfunctions, thus participating in the neurodegeneration progress. In that process, disturbed neuronal glucose supply plays a key role, which in hippocampal neurons is controlled by the insulin-sensitive glucose transporter type 4 (GLUT4). We investigated the expression of GLUT4, nuclear factor NF-kappa B subunit p65 [NFKB (p65)], carboxymethyllysine and synapsin1 (immunohistochemistry), and soma area in human postmortem hippocampal samples from control, obese, and obese+DM subjects (41 subjects). Moreover, in human SH-SY5Y neurons, tumor necrosis factor (TNF) and glycated albumin (GA) effects were investigated in GLUT4, synapsin-1 (SYN1), tyrosine hydroxylase (TH), synaptophysin (SYP) proteins, and respective genes; NFKB binding activity in the SLC2A4 promoter; effects of increased histone acetylation grade by histone deacetylase 3 (HDAC3) inhibition. Hippocampal neurons (CA4 area) of obese+DM subjects displayed reduced GLUT4 expression and neuronal soma area, associated with increased expression of NFKB (p65). Challenges with TNF and GA decreased the SLC2A4/GLUT4 expression in SH-SY5Y neurons. TNF decreased SYN1, TH, and SYP mRNAs and respective proteins, and increased NFKB binding activity in the SLC2A4 promoter. Inhibition of HDAC3 increased the SLC2A4 expression and the total neuronal content of CRE-binding proteins (CREB/ICER), and also counterbalanced the repressor effect of TNF upon these parameters. This study revealed reduced postmortem human hippocampal GLUT4 content and neuronal soma area accompanied by increased proinflammatory activity in the brains of DM subjects. In isolated human neurons, inflammatory activation by TNF reduced not only the SLC2A4/GLUT4 expression but also the expression of some genes related to neuronal function (SYN1, TH, SYP). These effects may be related to epigenetic regulations (H3Kac and H4Kac status) since they can be counterbalanced by inhibiting HDAC3. These results uncover the improvement in GLUT4 expression and/or the inhibition of HDAC3 as promising therapeutic targets to fight DM-related neurodegeneration.
- Germline DNA copy number variation in individuals with Argyrophilic grain disease reveals CTNS as a plausible candidate gene(2013) VILLELA, Darine; KIMURA, Lilian; SCHLESINGER, David; GONCALVES, Amanda; PEARSON, Peter L.; SUEMOTO, Claudia K.; PASQUALUCCI, Carlos; KREPISCHI, Ana Cristina; GRINBERG, Lea T.; ROSENBERG, CarlaArgyrophilic grain disease (AGD) is a progressive neurodegenerative disease of the human brain that has never been associated to a particular gene locus. In the present study, we report the results of a CNV investigation in 29 individuals whose anatomopathologic investigation of the brain showed AGD. Rare CNVs were identified in six patients (21%), in particular a 40 kb deletion at 17p13.2 encompassing the CTNS gene. Homozygote mutations in CTNS are known to cause cystinosis, a disorder characterized by the intralysosomal accumulation of cystine in all tissues. We present the first CNV results in individuals presenting AGD and a possible candidate gene implicated in the disorder.
- Differences between postmortem computed tomography and conventional autopsy in a stabbing murder case(2014) ZERBINI, Talita; SILVA, Luiz Fernando Ferraz da; FERRO, Antonio Carlos Goncalves; KAY, Fernando Uliana; AMARO JUNIOR, Edson; PASQUALUCCI, Carlos Augusto Goncalves; SALDIVA, Paulo Hilario do NascimentoOBJECTIVE: The aim of the present work is to analyze the differences and similarities between the elements of a conventional autopsy and images obtained from postmortem computed tomography in a case of a homicide stab wound. METHOD: Comparison between the findings of different methods: autopsy and postmortem computed tomography. RESULTS: In some aspects, autopsy is still superior to imaging, especially in relation to external examination and the description of lesion vitality. However, the findings of gas embolism, pneumothorax and pulmonary emphysema and the relationship between the internal path of the instrument of aggression and the entry wound are better demonstrated by postmortem computed tomography. CONCLUSIONS: Although multislice computed tomography has greater accuracy than autopsy, we believe that the conventional autopsy method is fundamental for providing evidence in criminal investigations.
- Evaluation of the diaphragm muscle remodeling, inflammation, oxidative stress and vascularization in smokers: An autopsy study(2020) NUCCI, R.A.B.; MAIFRINO, L.B.M.; BUSSE, A.L.; SOUZA, R.R. De; PASQUALUCCI, C.A.; ANARUMA, C.A.; LEITE, R.E.P.; RODRIGUEZ, R.D.; SUEMOTO, C.K.; JACOB-FILHO, W.Background/Aims: Cigarette smoking is a key factor in systemic inflammation and oxidative stress, and it has also been associated with the loss of muscle strength and an elevated risk of pulmonary diseases. Thus, this study aimed to analyze the effects of cigarette smoking on the diaphragm muscle structure of postmortem samples. Methods: Immunohistochemical techniques were used for muscle remodeling (metalloproteinases 2 and 9), inflammation (cyclooxygenase-2), oxidative stress (8-hydroxy-2'-deoxyguanosine), and vascularization (vascular endothelial growth factor). Hematoxylin and eosin stain was used for histopathological analysis and Picrosirius stain was used to highlight the collagen fibers. Results: Cigarette smokers had an increase of diaphragm muscle remodeling, oxidative stress, inflammation, and vascularization compared to non-smokers. Conclusion: Diaphragm muscle structure may be negatively affected by cigarette smoking. © 2020 The Author(s).
- Macrophage Polarization in the Perivascular Fat Was Associated With Coronary Atherosclerosis(2022) FARIAS-ITAO, Daniela Souza; PASQUALUCCI, Carlos Augusto; ANDRADE, Renato Araujo de; SILVA, Luiz Fernando Ferraz da; YAHAGI-ESTEVAM, Maristella; LAGE, Silvia Helena Gelas; LEITE, Renata Elaine Paraizo; CAMPO, Alexandre Brincalepe; SUEMOTO, Claudia KimieBackground Inflammation of the perivascular adipose tissue (PvAT) may be related to atherosclerosis; however, the association of polarized macrophages in the pericoronary PvAT with measurements of atherosclerosis components in humans has not been fully investigated. Methods and Results Coronary arteries were dissected with surrounding PvAT. We evaluated the percentage of arterial obstruction, intima-media thickness, fibrous cap thickness, plaque components, and the number of vasa vasorum. The number of proinflammatory (M1) and anti-inflammatory (M2) macrophages in the periplaque and control PvAT were evaluated using immunohistochemistry. Regression models adjusted for sociodemographic and clinical variables were used. In 319 segments from 82 individuals, we found a correlation of the M1/M2 macrophage density ratio with an increase in arterial obstruction (P=0.02) and lipid content (P=0.01), and a decrease in smooth muscle cells (P=0.02). M1 and the ratio of M1/M2 macrophages were associated with an increased risk of thrombosis (P=0.03). In plaques with thrombosis, M1 macrophages were correlated with a decrease in fibrous cap thickness (P=0.006), an increase in lipid content (P=0.008), and the number of vasa vasorum in the adventitia layer (P=0.001). M2 macrophages were correlated with increased arterial obstruction (P=0.01), calcification (P=0.02), necrosis (P=0.03) only in plaques without thrombosis, and decrease of the number of vasa vasorum in plaques with thrombosis (P=0.003). Conclusions M1 macrophages in the periplaque PvAT were associated with a higher risk of coronary thrombosis and were correlated with histological components of plaque progression and destabilization. M2 macrophages were correlated with plaque size, calcification, necrotic content, and a decrease in the number of vasa vasorum in the adventitia layer.
- Very low levels of education and cognitive reserve A clinicopathologic study(2013) FARFEL, Jose Marcelo; NITRINI, Ricardo; SUEMOTO, Claudia Kimie; GRINBERG, Lea Tenenholz; FERRETTI, Renata Eloah Lucena; LEITE, Renata Elaine Paraizo; TAMPELLINI, Edilaine; LIMA, Luzia; FARIAS, Daniela Souza; NEVES, Ricardo Caires; RODRIGUEZ, Roberta Diehl; MENEZES, Paulo Rossi; FREGNI, Felipe; BENNETT, David A.; PASQUALUCCI, Carlos Augusto; JACOB FILHO, WilsonObjective: We conducted a clinicopathologic study in a large population with very low levels of education to determine whether very few years of education could contribute to cognitive reserve and modify the relation of neuropathologic indices to dementia. Methods: In this cross-sectional study, we included 675 individuals 50 years of age or older from the Brazilian Aging Brain Study Group. Cognitive abilities were evaluated through a structured interview with an informant at the time of autopsy, including the Clinical Dementia Rating (CDR) scale. Neuropathologic examinations were performed using immunohistochemistry and following internationally accepted criteria. Multivariate linear regression models were conducted to determine whether the association between cognitive abilities (measured by CDR sum of boxes) and years of education was independent of sociodemographic variables and neuropathologic indices, including neuritic plaques, neurofibrillary tangles, lacunar infarctions, small-vessel disease, and Lewy bodies. In addition, interaction models were used to examine whether education modified the relation between neuropathologic indices and cognition. Results: Mean education was 3.9 +/- 3.5 years. Formal education was associated with a lower CDR sum of boxes (beta = -0.197; 95% confidence interval -0.343, -0.052; p = 0.008), after adjustment for sociodemographic variables and neuropathologic indices. Furthermore, education modified the relationship of lacunar infarcts with cognitive abilities (p = 0.04). Conclusions: Even a few years of formal education contributes to cognitive reserve.
- Discriminating Neoplastic and Normal Brain Tissues in Vitro Through Raman Spectroscopy: A Principal Components Analysis Classification Model(2013) AGUIAR, Ricardo Pinto; SILVEIRA JR., Landulfo; FALCAO, Edgar Teixeira; PACHECO, Marcos Tadeu Tavares; ZANGARO, Renato Amaro; PASQUALUCCI, Carlos AugustoBackground and objective: Because of their aggressiveness, brain tumors can lead to death within a short time after diagnosis. Optical techniques such as Raman spectroscopy may be a technique of choice for in situ tumor diagnosis, with potential use in determining tumor margins during surgery because of its ability to identify biochemical changes between normal and tumor brain tissues quickly and without tissue destruction. Methods: In this work, fragments of brain tumor (glioblastoma, medulloblastoma, and meningioma) and normal tissues (cerebellum and meninges) were obtained from excisional intracranial surgery and from autopsies, respectively. Raman spectra (dispersive spectrometer, 830nm 350mW, 50sec accumulation, total 172 spectra) were obtained in vitro on these fragments. It has been developed as a model to discriminate between the spectra of normal tissue and tumors based on the scores of principal component analysis (PCA) and Euclidean distance. Results: ANOVA indicated that the scores of PC2 and PC3 show differences between normal and tumor groups (p<0.05) which could be employed in a discrimination model. PC2 was able to discriminate glioblastoma from the other tumors and from normal tissues, showing featured peaks of lipids/phospholipids and cholesterol. PC3 discriminated medulloblastoma and meningioma from normal tissues, with the most intense spectral features of proteins. PC3 also discriminated normal tissues (meninges and cerebellum) by the presence of cholesterol peaks. Results indicated a sensitivity and specificity of 97.4% and 100%, respectively, for this in vitro diagnosis of brain tumor. Conclusions: The PCA/Euclidean distance model was effective in differentiating tumor from normal spectra, regardless of the type of tissue (meninges or cerebellum).
- Are the 50's, the transition decade, in choroid plexus aging?(2021) TAHIRA, Ana; MARQUES, Fernanda; LISBOA, Bianca; FELTRIN, Arthur; BARBOSA, Andre; OLIVEIRA, Katia Cristina de; PEREIRA, Carlos Alberto de Braganca; LEITE, Renata; GRINBERG, Lea; SUEMOTO, Claudia; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; BRENTANI, Helena; PALHA, Joana AlmeidaThe choroid plexus (CP) is an important structure for the brain. Besides its major role in the production of cerebrospinal fluid (CSF), it conveys signals originating from the brain, and from the circulatory system, shaping brain function in health and in pathology. Previous studies in rodents have revealed altered transcriptome both during aging and in various diseases of the central nervous system, including Alzheimer's disease. In the present study, a high-throughput sequencing of the CP transcriptome was performed in postmortem samples of clinically healthy individuals aged 50's through 80's. The data shows an age-related profile, with the main changes occurring in the transition from the 50's to the 60's, stabilizing thereafter. Specifically, neuronal and membrane functions distinguish the transcriptome between the 50's and the 60's, while neuronal and axon development and extracellular structure organization differentiate the 50's from the 70's. These findings suggest that changes in the CP transcriptome occur early in the aging process. Future studies will unravel whether these relate with processes occurring in late- onset brain diseases.