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Article ; Online: Early-life metabolic dysfunction impairs cognition and mitochondrial function in mice.

Vilela, Wembley Rodrigues / Bellozi, Paula Maria Quaglio / Picolo, Victor Luna / Cavadas, Bruna Neves / Marques, Keila Valentina Silva / Pereira, Louise Tavares Garcia / Guirao, Ainhoa Rodriguez de Yurre / Amato, Angélica Amorim / Magalhães, Kelly Grace / Mortari, Márcia Renata / Medei, Emiliano Horacio / Goulart, Jair Trapé / de Bem, Andreza Fabro

The Journal of nutritional biochemistry

2023 Volume 117, Page(s) 109352

Abstract: The impact of overnutrition early in life is not restricted to the onset of cardiovascular and metabolic diseases, but also affects critical brain functions related to cognition. This study aimed to evaluate the relationship between peripheral metabolic ... ...

Abstract	The impact of overnutrition early in life is not restricted to the onset of cardiovascular and metabolic diseases, but also affects critical brain functions related to cognition. This study aimed to evaluate the relationship between peripheral metabolic and bioenergetic changes induced by a two-hit protocol and their impact on cognitive function in juvenile mice. Three-week-old male C57BL/6 mice received a high-fat diet (HFD) or control diet for 7 weeks, associated with two low doses of streptozotocin (STZ) or vehicle. Despite the absence of obesity, HFD+STZ impaired glucose metabolism and induced a trend towards cholesterol increase. The two-hit protocol impaired recognition and spatial memories in juvenile mice, without inducing a depressive-like behavior. HFD+STZ mice presented increased immunoreactivity for GFAP and a trend towards a decrease in NeuN in the hippocampus. The treatment caused a bioenergetic impairment in the hippocampus, characterized by a decrease in both O
MeSH term(s)	Mice ; Male ; Animals ; Mice, Inbred C57BL ; Cognition ; Obesity/metabolism ; Diet, High-Fat/adverse effects ; Mitochondria/metabolism
Language	English
Publishing date	2023-04-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1014929-6
ISSN	1873-4847 ; 0955-2863
ISSN (online)	1873-4847
ISSN	0955-2863
DOI	10.1016/j.jnutbio.2023.109352
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Article: Sheltered in Stromal Tissue Cells,

Vellasco, Lucas / Svensjö, Erik / Bulant, Carlos Alberto / Blanco, Pablo Javier / Nogueira, Fábio / Domont, Gilberto / de Almeida, Natália Pinto / Nascimento, Clarissa Rodrigues / Silva-Dos-Santos, Danielle / Carvalho-Pinto, Carla Eponina / Medei, Emiliano Horácio / Almeida, Igor C / Scharfstein, Julio

Pathogens (Basel, Switzerland)

2022 Volume 11, Issue 2

Abstract: Microangiopathy may worsen the clinical outcome of Chagas disease. Given the obstacles to investigating the dynamics of inflammation and angiogenesis in heart tissues parasitized ... ...

Abstract	Microangiopathy may worsen the clinical outcome of Chagas disease. Given the obstacles to investigating the dynamics of inflammation and angiogenesis in heart tissues parasitized by
Language	English
Publishing date	2022-01-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens11020187
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Article: Sheltered in Stromal Tissue Cells, Trypanosoma cruzi Orchestrates Inflammatory Neovascularization via Activation of the Mast Cell Chymase Pathway

Vellasco, Lucas / Svensjö, Erik / Bulant, Carlos Alberto / Blanco, Pablo Javier / Nogueira, Fábio / Domont, Gilberto / de Almeida, Natália Pinto / Nascimento, Clarissa Rodrigues / Silva-dos-Santos, Danielle / Carvalho-Pinto, Carla Eponina / Medei, Emiliano Horácio / Almeida, Igor C. / Scharfstein, Julio

Pathogens. 2022 Jan. 29, v. 11, no. 2

2022

Abstract: Microangiopathy may worsen the clinical outcome of Chagas disease. Given the obstacles to investigating the dynamics of inflammation and angiogenesis in heart tissues parasitized by Trypanosoma cruzi, here we used intravital microscopy (IVM) to ... ...

Abstract	Microangiopathy may worsen the clinical outcome of Chagas disease. Given the obstacles to investigating the dynamics of inflammation and angiogenesis in heart tissues parasitized by Trypanosoma cruzi, here we used intravital microscopy (IVM) to investigate microcirculatory alterations in the hamster cheek pouch (HCP) infected by green fluorescent protein-expressing T. cruzi (GFP-T. cruzi). IVM performed 3 days post-infection (3 dpi) consistently showed increased baseline levels of plasma extravasation. Illustrating the reciprocal benefits that microvascular leakage brings to the host-parasite relationship, these findings suggest that intracellular amastigotes, acting from inside out, stimulate angiogenesis while enhancing the delivery of plasma-borne nutrients and prosurvival factors to the infection foci. Using a computer-based analysis of images (3 dpi), we found that proangiogenic indexes were positively correlated with transcriptional levels of proinflammatory cytokines (pro-IL1β and IFN-γ). Intracellular GFP-parasites were targeted by delaying for 24 h the oral administration of the trypanocidal drug benznidazole. A classification algorithm showed that benznidazole (>24 h) blunted angiogenesis (7 dpi) in the HCP. Unbiased proteomics (3 dpi) combined to pharmacological targeting of chymase with two inhibitors (chymostatin and TY-51469) linked T. cruzi-induced neovascularization (7 dpi) to the proangiogenic activity of chymase, a serine protease stored in secretory granules from mast cells.
Keywords	Chagas disease ; Trypanosoma cruzi ; algorithms ; amastigotes ; angiogenesis ; benznidazole ; cytokines ; fluorescence ; hamsters ; heart ; host-parasite relationships ; inflammation ; mast cells ; microangiopathy ; microscopy ; oral administration ; proteomics ; serine proteinases ; transcription (genetics) ; trypanocides
Language	English
Dates of publication	2022-0129
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens11020187
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Article ; Online: Sheltered in Stromal Tissue Cells, Trypanosoma cruzi Orchestrates Inflammatory Neovascularization via Activation of the Mast Cell Chymase Pathway

Lucas Vellasco / Erik Svensjö / Carlos Alberto Bulant / Pablo Javier Blanco / Fábio Nogueira / Gilberto Domont / Natália Pinto de Almeida / Clarissa Rodrigues Nascimento / Danielle Silva-dos-Santos / Carla Eponina Carvalho-Pinto / Emiliano Horácio Medei / Igor C. Almeida / Julio Scharfstein

Pathogens, Vol 11, Iss 187, p

2022 Volume 187

Abstract: Microangiopathy may worsen the clinical outcome of Chagas disease. Given the obstacles to investigating the dynamics of inflammation and angiogenesis in heart tissues parasitized by Trypanosoma cruzi , here we used intravital microscopy (IVM) to ... ...

Abstract	Microangiopathy may worsen the clinical outcome of Chagas disease. Given the obstacles to investigating the dynamics of inflammation and angiogenesis in heart tissues parasitized by Trypanosoma cruzi , here we used intravital microscopy (IVM) to investigate microcirculatory alterations in the hamster cheek pouch (HCP) infected by green fluorescent protein-expressing T. cruzi (GFP- T. cruzi ). IVM performed 3 days post-infection (3 dpi) consistently showed increased baseline levels of plasma extravasation. Illustrating the reciprocal benefits that microvascular leakage brings to the host-parasite relationship, these findings suggest that intracellular amastigotes, acting from inside out, stimulate angiogenesis while enhancing the delivery of plasma-borne nutrients and prosurvival factors to the infection foci. Using a computer-based analysis of images (3 dpi), we found that proangiogenic indexes were positively correlated with transcriptional levels of proinflammatory cytokines (pro-IL1β and IFN-γ). Intracellular GFP-parasites were targeted by delaying for 24 h the oral administration of the trypanocidal drug benznidazole. A classification algorithm showed that benznidazole (>24 h) blunted angiogenesis (7 dpi) in the HCP. Unbiased proteomics (3 dpi) combined to pharmacological targeting of chymase with two inhibitors (chymostatin and TY-51469) linked T. cruzi -induced neovascularization (7 dpi) to the proangiogenic activity of chymase, a serine protease stored in secretory granules from mast cells.
Keywords	Trypanosoma cruzi ; angiogenesis ; inflammation ; mast cell ; chymase ; Medicine ; R
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: NOD Mice Recapitulate the Cardiac Disturbances Observed in Type 1 Diabetes.

Schleier, Ygor / Moreno-Loaiza, Oscar / López Alarcón, Maria Micaela / Lopes Martins, Eduarda Gabrielle / Braga, Bruno Cabral / Ramos, Isalira Peroba / Galina, Antonio / Medei, Emiliano Horacio

Journal of cardiovascular translational research

2020 Volume 14, Issue 2, Page(s) 271–282

Abstract: This work aimed at testing the hypothesis that NOD/ShiLtJ mice (NOD) recapitulate the cardiac disturbances observed on type 1 diabetes (T1D). NOD mice were studied 4 weeks after the onset of hyperglycemia, and NOR/Lt mice matched as control. Cardiac ... ...

Abstract	This work aimed at testing the hypothesis that NOD/ShiLtJ mice (NOD) recapitulate the cardiac disturbances observed on type 1 diabetes (T1D). NOD mice were studied 4 weeks after the onset of hyperglycemia, and NOR/Lt mice matched as control. Cardiac function was evaluated by echocardiography and electrocardiography (ECG). Action potentials (AP) and Ca
MeSH term(s)	Action Potentials ; Animals ; Arrhythmias, Cardiac/etiology ; Arrhythmias, Cardiac/metabolism ; Arrhythmias, Cardiac/physiopathology ; Blood Glucose/metabolism ; Calcium Signaling ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/complications ; Disease Models, Animal ; Heart Conduction System/metabolism ; Heart Conduction System/physiopathology ; Heart Rate ; Kinetics ; Mice, Inbred NOD ; Mitochondria, Heart/metabolism ; Myocytes, Cardiac/metabolism ; Mice
Chemical Substances	Blood Glucose
Language	English
Publishing date	2020-05-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2422411-X
ISSN	1937-5395 ; 1937-5387
ISSN (online)	1937-5395
ISSN	1937-5387
DOI	10.1007/s12265-020-10039-y
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Article ; Online: Early-life metabolic dysfunction impairs cognition and mitochondrial function in mice

The Journal of Nutritional Biochemistry. 2023 Apr. 14, p.109352-

2023 , Page(s) 109352–

Abstract	The impact of overnutrition early in life is not restricted to the onset of cardiovascular and metabolic diseases, but also affects critical brain functions related to cognition. This study aimed to evaluate the relationship between peripheral metabolic and bioenergetic changes induced by a two-hit protocol and their impact on cognitive function in juvenile mice. Three-week-old male C57BL/6 mice received a high-fat diet (HFD) or control diet for 7 weeks, associated with 2 low doses of streptozotocin (STZ) or vehicle. Despite the absence of obesity, HFD+STZ impaired glucose metabolism and induced a trend towards cholesterol increase. The two-hit protocol impaired recognition and spatial memories in juvenile mice, without inducing a depressive-like behavior. HFD+STZ mice presented increased immunoreactivity for GFAP and a trend towards a decrease in NeuN in the hippocampus. The treatment caused a bioenergetic impairment in the hippocampus, characterized by a decrease in both O₂ consumption related to ATP production and in the maximum respiratory capacity. The thermogenic capacity of brown adipose tissue was impaired by the two-hit protocol, here verified through the absence of a decrease in O₂ consumption after uncoupled protein-1 inhibition and an increase in the reserve respiratory capacity. Impaired mitochondrial function was also observed in the liver of HFD+STZ juvenile mice, but not in their heart. These results indicate that exposure to HFD+STZ early in life has a detrimental impact on the bioenergetic and mitochondrial function of tissues with metabolic and thermogenic activities, which is likely related to hippocampal metabolic changes and cognitive impairment.
Keywords	brown adipose tissue ; cholesterol ; cognition ; cognitive disorders ; glucose ; heart ; high fat diet ; hippocampus ; immune response ; juveniles ; liver ; males ; metabolism ; mitochondria ; obesity ; overnutrition ; streptozotocin ; High-fat diet
Language	English
Dates of publication	2023-0414
Publishing place	Elsevier Inc.
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	1014929-6
ISSN	1873-4847 ; 0955-2863
ISSN (online)	1873-4847
ISSN	0955-2863
DOI	10.1016/j.jnutbio.2023.109352
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Influence of Stem Cell Therapy on Thyroid Function and Reactive Oxygen Species Production in Diabetic Rats.

da Silva, Diorney Luiz Souza Gran / de Freitas, Mariana Lopes / Cahil, Gustavo Monnerat / de São José, Vitória Santório / Neto, Felippe Mousovich / Cardoso, Ricardo Cortez / da Costa, Vânia Maria Correa / Fortunato, Rodrigo Soares / de Carvalho, Denise Pires / Medei, Emiliano Horácio / Ferreira, Andrea Claudia Freitas

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme

2018 Volume 50, Issue 4, Page(s) 331–339

Abstract: Cell therapy with mesenchymal stem cells (MSC) has been proposed for the treatment of diabetes mellitus (DM). It is known that the prevalence of thyroid disease is higher among diabetic patients than in general population. Therefore, our aim was to ... ...

Abstract	Cell therapy with mesenchymal stem cells (MSC) has been proposed for the treatment of diabetes mellitus (DM). It is known that the prevalence of thyroid disease is higher among diabetic patients than in general population. Therefore, our aim was to investigate the effect of the treatment with MSC on thyroid function and ROS generation in an experimental model of type 1 DM. Adult male Wistar rats were divided into the following groups: control, DM (80 mg/kg BW streptozotocin, iv.) and DM+MSC. MSC treatment occurred 4 weeks after DM induction and the animals were euthanized 4 weeks after MSC administration. We also evaluated the effect of co-culture with MSC or extracellular vesicles (EV) obtained from these cells on the rat thyroid cell line PCCL3 exposed to high glucose. Thyroid H
MeSH term(s)	Animals ; Cell- and Tissue-Based Therapy ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology ; Diabetes Mellitus, Experimental/therapy ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/cytology ; Rats ; Rats, Wistar ; Reactive Oxygen Species/metabolism ; Thyroid Function Tests ; Thyroid Gland/physiology ; Thyroid Hormones/metabolism
Chemical Substances	Reactive Oxygen Species ; Thyroid Hormones
Language	English
Publishing date	2018-04-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	80125-2
ISSN	1439-4286 ; 0018-5043
ISSN (online)	1439-4286
ISSN	0018-5043
DOI	10.1055/a-0588-7944
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Article ; Online: Autonomic dysfunction and anti-M2 and anti-β1 receptor antibodies in Chagas disease patients.

Thiers, Clarissa Antunes / Barbosa, João Luis / Pereira, Basílio de Bragança / Nascimento, Emília Matos do / Nascimento, José Hamilton do / Medei, Emiliano Horácio / Pedrosa, Roberto Coury

Arquivos brasileiros de cardiologia

2012 Volume 99, Issue 2, Page(s) 732–739

Abstract: Background: Sudden death is the leading cause of death in Chagas' disease, affecting patients even in the early stages of the disease. The impairment of the autonomic nervous system in this disease has been recognized, as well as its potential as a ... ...

Abstract	Background: Sudden death is the leading cause of death in Chagas' disease, affecting patients even in the early stages of the disease. The impairment of the autonomic nervous system in this disease has been recognized, as well as its potential as a trigger for malignant arrhythmias when associated with structural or metabolic changes. Objective: We sought to identify, in Chagas patients with preserved systolic function, the impairment of the autonomic nervous system and its association with functionally active anti-m2 and anti-β1 receptor antibodies. Methods: Using spectral analysis of RR variability during passive tilt test, chronic chagasic patients were compared with healthy controls matched for age. Subsequently, the association of autonomic dysfunction with functionally active antibodies with anti-m2 and anti-β1 action was investigated by the Langendorf method. Results: We observed that patients with Chagas disease without ventricular dysfunction express parasympathetic activity against a vagal stimulus, however with less intensity compared to controls. Chagasic patients with anti-m2 or anti-β1 antibodies showed a further significant reduction of the vagal response during respiratory sinus arrhythmia, regardless of the presence of structural lesion. However, the association of both factors promoted response to vagal stimulation similar to that seen in Chagas disease without their presence. Conclusion: The lower vagal reserve in Chagas patients with preserved function was associated with functionally active anti-m2 or anti-β1 antibodies, and not with the presence of structural heart lesion.
MeSH term(s)	Adolescent ; Adult ; Aged ; Arrhythmias, Cardiac/immunology ; Arrhythmias, Cardiac/physiopathology ; Autoantibodies/immunology ; Autonomic Nervous System/immunology ; Autonomic Nervous System/physiopathology ; Case-Control Studies ; Chagas Disease/immunology ; Chagas Disease/physiopathology ; Electrocardiography ; Female ; Heart Rate/physiology ; Humans ; Male ; Middle Aged ; Receptors, Adrenergic, beta-1/immunology ; Receptors, G-Protein-Coupled/immunology ; Reference Values ; Young Adult
Chemical Substances	Autoantibodies ; Mi-2 antibodies ; Receptors, Adrenergic, beta-1 ; Receptors, G-Protein-Coupled
Language	Portuguese
Publishing date	2012-07-13
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	730261-7
ISSN	1678-4170 ; 0066-782X
ISSN (online)	1678-4170
ISSN	0066-782X
DOI	10.1590/s0066-782x2012005000067
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Article ; Online: Role of autoantibodies in the physiopathology of Chagas' disease.

Medei, Emiliano Horacio / Nascimento, José Hamilton Matheus / Pedrosa, Roberto Coury / Carvalho, Antônio Carlos Campos de

Arquivos brasileiros de cardiologia

2008 Volume 91, Issue 4, Page(s) 257–62, 281–6

Abstract: Chagas' disease is a serious health problem in Latin America. Between 25 to 30% of the infected patients develop the chronic form of the disease, with progressive myocardial damage and often, sudden death. Adrenergic or cholinergic antibodies with G- ... ...

Abstract	Chagas' disease is a serious health problem in Latin America. Between 25 to 30% of the infected patients develop the chronic form of the disease, with progressive myocardial damage and often, sudden death. Adrenergic or cholinergic antibodies with G-protein coupled membrane receptor activity may be present in the sera of these patients. The present study discusses the etiology and the contribution of antibodies to the physiopathology of Chagas' disease.
MeSH term(s)	Animals ; Antibodies, Protozoan/immunology ; Autoantibodies/immunology ; Chagas Disease/etiology ; Chagas Disease/immunology ; Chagas Disease/physiopathology ; Chronic Disease ; Humans ; Receptors, Adrenergic, beta/immunology ; Receptors, Cholinergic/immunology ; Trypanosoma cruzi/immunology
Chemical Substances	Antibodies, Protozoan ; Autoantibodies ; Receptors, Adrenergic, beta ; Receptors, Cholinergic
Language	Portuguese
Publishing date	2008-11-14
Publishing country	Brazil
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	730261-7
ISSN	1678-4170 ; 0066-782X
ISSN (online)	1678-4170
ISSN	0066-782X
DOI	10.1590/s0066-782x2008001600012
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Article: Influence of Stem Cell Therapy on Thyroid Function and Reactive Oxygen Species Production in Diabetic Rats

Hormone and Metabolic Research

2018 Volume 50, Issue 04, Page(s) 331–339

Abstract	Cell therapy with mesenchymal stem cells (MSC) has been proposed for the treatment of diabetes mellitus (DM). It is known that the prevalence of thyroid disease is higher among diabetic patients than in general population. Therefore, our aim was to investigate the effect of the treatment with MSC on thyroid function and ROS generation in an experimental model of type 1 DM. Adult male Wistar rats were divided into the following groups: control, DM (80 mg/kg BW streptozotocin, iv.) and DM+MSC. MSC treatment occurred 4 weeks after DM induction and the animals were euthanized 4 weeks after MSC administration. We also evaluated the effect of co-culture with MSC or extracellular vesicles (EV) obtained from these cells on the rat thyroid cell line PCCL3 exposed to high glucose. Thyroid H 2 O 2 generation was increased in DM, which was reversed by MSC treatment. These changes paralled a significant DuOx1 mRNA increase. The incubation of PCCL3 with high glucose increased extracellular H 2 O 2 generation, which was reversed by both the co-culture with MSC and EV. Even though MSC treatment normalized thyroid ROS generation, serum thyroid hormone (TH) concentration remained low, along with increased serum TSH concentrations. Thyroperoxidase (TPO) activity, was reduced in DM, and MSC treatment did not normalize TPO. Therefore, we conclude that the treatment with MSC was able to reverse the increased thyroid H 2 O 2 generation in diabetic animals and in PCCL3 cells exposed to high glucose, an effect probably mediated by EV produced by these cells, acting in a paracrine fashion.
Keywords	reactive oxygen species ; thyroperoxidase ; mesenchymal stem cells ; diabetes mellitus
Language	English
Publishing date	2018-04-01
Publisher	© Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	80125-2
ISSN	1439-4286 ; 0018-5043
ISSN (online)	1439-4286
ISSN	0018-5043
DOI	10.1055/a-0588-7944
Database	Thieme publisher's database

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