ELIA TAMASO ESPIN GARCIA CALZOLARI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/59 - Laboratório de Biologia Celular, Hospital das Clínicas, Faculdade de Medicina
LIM/59 - Laboratório de Biologia Celular, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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conferenceObject ELEVATED ROS LEVELS AND DNA FRAGMENTATION IN SPERM FROM CONVALESCENT MEN IN SARS-COV-2 INFECTION(2022) HALLAK, Jorge; BERNARDES, Felipe; TEIXEIRA, Thiago Afonso Carvalho Celestino; SALDIVA, Paulo Hilario Nascimento; KALLAS, Esper Georges; CALDINI, Elia Tamaso Espin Garcia; DUARTE NETO, Amaro Nunes; FAQUINETI, Heloisa; JESUS, Vinicius Luiz Menezes; GUTIERREZ, Raul Segundo Sanchez; DREVET, Joel R.- Testicular pathology in fatal COVID-19: A descriptive autopsy study(2022) DUARTE-NETO, Amaro N.; TEIXEIRA, Thiago A.; CALDINI, Elia G.; KANAMURA, Cristina T.; GOMES-GOUVEA, Michele S.; SANTOS, Angela B. G. dos; MONTEIRO, Renata A. A.; PINHO, Joao R. R.; MAUAD, Thais; SILVA, Luiz F. F. da; SALDIVA, Paulo H. N.; DOLHNIKOFF, Marisa; LEITE, Katia R. M.; HALLAK, JorgeBackground Multi-organ damage is a common feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, going beyond the initially observed severe pneumonia. Evidence that the testis is also compromised is growing. Objective To describe the pathological findings in testes from fatal cases of COVID-19, including the detection of viral particles and antigens, and inflammatory cell subsets. Materials and methods Postmortem testicular samples were obtained by percutaneous puncture from 11 deceased men and examined by reverse-transcription polymerase chain reaction (RT-PCR) for RNA detection and by light and electron microscopy (EM) for SARS-CoV-2. Immunohistochemistry (IHC) for the SARS-CoV-2 N-protein and lymphocytic and histiocytic markers was also performed. Results Eight patients had mild interstitial orchitis, composed mainly of CD68+ and TCD8+ cells. Fibrin thrombi were detected in five cases. All cases presented congestion, interstitial edema, thickening of the tubular basal membrane, decreased Leydig and Sertoli cells with reduced spermatogenesis, and strong expression of vascular cell adhesion molecule (VCAM) in vessels. IHC detected SARS-Cov-2 antigen in Leydig cells, Sertoli cells, spermatogonia, and fibroblasts in all cases. EM detected viral particles in the cytoplasm of fibroblasts, endothelium, Sertoli and Leydig cells, spermatids, and epithelial cells of the rete testis in four cases, while RT-PCR detected SARS-CoV-2 RNA in three cases. Discussion and conclusion The COVID-19-associated testicular lesion revealed a combination of orchitis, vascular changes, basal membrane thickening, Leydig and Sertoli cell scarcity, and reduced spermatogenesis associated with SARS-CoV-2 local infection that may impair hormonal function and fertility in men.
conferenceObject INTRACELLULAR SARS-COV-2 FOUNDIN THE SPERMATOZOA OF CONVALESCENT MEN WITH NEGATIVE PCR SEMEN SAMPLES REVEALED BY ELECTRON MICROSCOPY(2022) HALLAK, Jorge; CALDINI, Elia Tamaso Espin Garcia; CORREA, Maria Cassia Jacintho Mendes; DOLHNIKOFF, Marisa; SALDIVA, Paulo Hilario Nascimento; KALLAS, Esper Georges; DUARTE NETO, Amaro Nunes; GUTIERREZ, Raul Segundo Sanchez; DREVET, Joel R.; TEIXEIRA, Thiago Afonso Carvalho Celestino; BERNARDES, Felipe Saraiva; FAQUINETI, Heloisa- MS-Driven Metabolic Alterations Are Recapitulated in iPSC-Derived Astrocytes(2022) GHIROTTO, Bruno; OLIVEIRA, Danyllo F.; CIPELLI, Marcella; BASSO, Paulo J.; LIMA, Jean; BREDA, Cristiane N. S.; RIBEIRO, Henrique C.; SILVA, Camille C. C.; SERTIE, Andrea L.; OLIVEIRA, Antonio Edson R.; I, Meire Hiyane; CALDINI, Elia G.; SUSSULINI, Alessandra; I, Helder Nakaya; KOWALTOWSKI, Alicia J.; OLIVEIRA, Enedina M. L.; ZATZ, Mayana; CAMARA, Niels O. S.Objective Astrocytes play a significant role in the pathology of multiple sclerosis (MS). Nevertheless, for ethical reasons, most studies in these cells were performed using the Experimental Autoimmune Encephalomyelitis model. As there are significant differences between human and mouse cells, we aimed here to better characterize astrocytes from patients with MS (PwMS), focusing mainly on mitochondrial function and cell metabolism. Methods We obtained and characterized induced pluripotent stem cell (iPSC)-derived astrocytes from three PwMS and three unaffected controls, and performed electron microscopy, flow cytometry, cytokine and glutamate measurements, gene expression, in situ respiration, and metabolomics. We validated our findings using a single-nuclei RNA sequencing dataset. Results We detected several differences in MS astrocytes including: (i) enrichment of genes associated with neurodegeneration, (ii) increased mitochondrial fission, (iii) increased production of superoxide and MS-related proinflammatory chemokines, (iv) impaired uptake and enhanced release of glutamate, (v) increased electron transport capacity and proton leak, in line with the increased oxidative stress, and (vi) a distinct metabolic profile, with a deficiency in amino acid catabolism and increased sphingolipid metabolism, which have already been linked to MS. Interpretation Here we describe the metabolic profile of iPSC-derived astrocytes from PwMS and validate this model as a very powerful tool to study disease mechanisms and to perform non-invasive drug targeting assays in vitro. Our findings recapitulate several disease features described in patients and provide new mechanistic insights into the metabolic rewiring of astrocytes in MS, which could be targeted in future therapeutic studies. ANN NEUROL 2022
- SARS-CoV-2 infection impacts carbon metabolism and depends on glutamine for replication in Syrian hamster astrocytes(2022) OLIVEIRA, Lilian Gomes de; ANGELO, Yan de Souza; YAMAMOTO, Pedro; CARREGARI, Victor Corasolla; CRUNFLI, Fernanda; REIS-DE-OLIVEIRA, Guilherme; COSTA, Licia; VENDRAMINI, Pedro Henrique; DUQUE, Erica Almeida; SANTOS, Nilton Barreto dos; FIRMINO, Egidi Mayara; PAIVA, Isadora Marques; ALMEIDA, Glaucia Maria; SEBOLLELA, Adriano; POLONIO, Carolina Manganeli; ZANLUQUI, Nagela Ghabdan; OLIVEIRA, Marilia Garcia de; SILVA, Patrick da; DAVANZO, Gustavo Gastao; AYUPE, Marina Cacador; SALGADO, Caio Loureiro; SOUZA FILHO, Antonio Francisco de; ARAUJO, Marcelo Valdemir de; SILVA-PEREIRA, Taiana Taina; CAMPOS, Angelica Cristine de Almeida; GOES, Luiz Gustavo Bentim; CUNHA, Marielton dos Passos; CALDINI, Elia Garcia; LIMA, Maria Regina D'Imperio; FONSECA, Denise Morais; GUIMARAES, Ana Marcia de Sa; MINOPRIO, Paola Camargo; MUNHOZ, Carolina Demarchi; MORI, Claudia Madalena Cabrera; MORAES-VIEIRA, Pedro Manoel; CUNHA, Thiago Mattar; MARTINS-DE-SOUZA, Daniel; PERON, Jean Pierre SchatzmannCOVID-19 causes more than million deaths worldwide. Although much is understood about the immunopathogenesis of the lung disease, a lot remains to be known on the neurological impact of COVID-19. Here, we evaluated immunometabolic changes using astrocytes in vitro and dissected brain areas of SARS-CoV-2 infected Syrian hamsters. We show that SARS-CoV-2 alters proteins of carbon metabolism, glycolysis, and synaptic transmission, many of which are altered in neurological diseases. Real-time respirometry evidenced hyperactivation of glycolysis, further confirmed by metabolomics, with intense consumption of glucose, pyruvate, glutamine, and alpha ketoglutarate. Consistent with glutamine reduction, the blockade of glutaminolysis impaired viral replication and inflammatory response in vitro. SARS-CoV-2 was detected in vivo in hippocampus, cortex, and olfactory bulb of intranasally infected animals. Our data evidence an imbalance in important metabolic molecules and neurotransmitters in infected astrocytes. We suggest this may correlate with the neurological impairment observed during COVID-19, as memory loss, confusion, and cognitive impairment.