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Article ; Online: Postmortem Ultrastructural Analysis of the Retina from COVID-19 Deceased Patients.

Araujo-Silva, Carlla A / Marinho, Paula M / Marcos, Alléxya A A / Branco, Ana M C / Sakamoto, Victoria / Matuoka, Mateus L / Moraes, Nara F / Tierno, Paulo F G M M / Mourad, Walid M / Nascimento, Heloisa / Burnier, Miguel / de Souza, Wanderley / Belfort, Rubens

Ocular immunology and inflammation

2023 , Page(s) 1–9

Abstract: Purpose: COVID-19 (coronavirus disease 2019) is an infectious disease caused by SARS-CoV-2, first reported in 2019 in Wuhan, China. Among the common complications is a pro-inflammatory and hypercoagulative response that compromises the vasculature among ...

Abstract	Purpose: COVID-19 (coronavirus disease 2019) is an infectious disease caused by SARS-CoV-2, first reported in 2019 in Wuhan, China. Among the common complications is a pro-inflammatory and hypercoagulative response that compromises the vasculature among various organs. Methods: In this report, we present the postmortem retinal findings of five patients observed by means of optical microscopy and transmission and scanning electron microscopy techniques. Results: Clinical manifestations such as retinal hemorrhages and exacerbated inflammatory infiltrate, altered ultra structure with swollen mitochondria and pyknotic cells in both layers of the retina were observed in all analyzed eyes. Conclusion: Our data point to the fragility of this tissue in cases of severe COVID-19.
Language	English
Publishing date	2023-08-08
Publishing country	England
Document type	Journal Article
ZDB-ID	1193873-0
ISSN	1744-5078 ; 0927-3948
ISSN (online)	1744-5078
ISSN	0927-3948
DOI	10.1080/09273948.2023.2238817
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Article ; Online: Pleiotropic antifibrotic actions of aspirin-triggered resolvin D1 in the lungs.

Guilherme, Rafael F / Silva, José Bruno N F / Waclawiack, Ingrid / Fraga-Junior, Vanderlei S / Nogueira, Thaís O / Pecli, Cyntia / Araújo-Silva, Carlla A / Magalhães, Nathalia S / Lemos, Felipe S / Bulant, Carlos A / Blanco, Pablo J / Serra, Rafaela / Svensjö, Erik / Scharfstein, Júlio / Moraes, João A / Canetti, Claudio / Benjamim, Claudia F

Frontiers in immunology

2023 Volume 14, Page(s) 886601

Abstract: Introduction: Pulmonary fibrosis is a destructive, progressive disease that dramatically reduces life quality of patients, ultimately leading to death. Therapeutic regimens for pulmonary fibrosis have shown limited benefits, hence justifying the efforts ...

Abstract	Introduction: Pulmonary fibrosis is a destructive, progressive disease that dramatically reduces life quality of patients, ultimately leading to death. Therapeutic regimens for pulmonary fibrosis have shown limited benefits, hence justifying the efforts to evaluate the outcome of alternative treatments. Methods: Using a mouse model of bleomycin (BLM)-induced lung fibrosis, in the current work we asked whether treatment with pro-resolution molecules, such as pro-resolving lipid mediators (SPMs) could ameliorate pulmonary fibrosis. To this end, we injected aspirin-triggered resolvin D1 (7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E19Z-docosahexaenoic acid; ATRvD1; i.v.) 7 and 10 days after BLM (intratracheal) challenge and samples were two weeks later. Results and discussion: Assessment of outcome in the lung tissues revealed that ATRvD1 partially restored lung architecture, reduced leukocyte infiltration, and inhibited formation of interstitial edema. In addition, lung tissues from BLM-induced mice treated with ATRvD1 displayed reduced levels of TNF-α, MCP-1, IL-1-β, and TGF-β. Of further interest, ATRvD1 decreased lung tissue expression of MMP-9, without affecting TIMP-1. Highlighting the beneficial effects of ATRvD1, we found reduced deposition of collagen and fibronectin in the lung tissues. Congruent with the anti-fibrotic effects that ATRvD1 exerted in lung tissues, α-SMA expression was decreased, suggesting that myofibroblast differentiation was inhibited by ATRvD1. Turning to culture systems, we next showed that ATRvD1 impaired TGF-β-induced fibroblast differentiation into myofibroblast. After showing that ATRvD1 hampered extracellular vesicles (EVs) release in the supernatants from TGF-β-stimulated cultures of mouse macrophages, we verified that ATRvD1 also inhibited the release of EVs in the bronco-alveolar lavage (BAL) fluid of BLM-induced mice. Motivated by studies showing that BLM-induced lung fibrosis is linked to angiogenesis, we asked whether ATRvD1 could blunt BLM-induced angiogenesis in the hamster cheek pouch model (HCP). Indeed, our intravital microscopy studies confirmed that ATRvD1 abrogates BLM-induced angiogenesis. Collectively, our findings suggest that treatment of pulmonary fibrosis patients with ATRvD1 deserves to be explored as a therapeutic option in the clinical setting.
MeSH term(s)	Humans ; Pulmonary Fibrosis/chemically induced ; Pulmonary Fibrosis/drug therapy ; Pulmonary Fibrosis/metabolism ; Aspirin/pharmacology ; Docosahexaenoic Acids/pharmacology ; Docosahexaenoic Acids/therapeutic use ; Lung/pathology ; Bleomycin/pharmacology ; Transforming Growth Factor beta/metabolism
Chemical Substances	Aspirin (R16CO5Y76E) ; resolvin D1 ; Docosahexaenoic Acids (25167-62-8) ; Bleomycin (11056-06-7) ; Transforming Growth Factor beta
Language	English
Publishing date	2023-03-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.886601
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Article ; Online: An alternative method to establish an early acute ocular toxoplasmosis model for experimental tests.

de Araujo-Silva, Carlla Assis / Peclat-Araujo, Milena Ribeiro / de Souza, Wanderley / Vommaro, Rossiane Claudia

International ophthalmology

2024 Volume 44, Issue 1, Page(s) 73

Abstract: Purpose: To provide a simple alternative acute ocular toxoplasmosis model with great reproducibility for experimental tests that demand monitoring of the ocular lesion.: Methods: ME49-wt and ME49-GFP tachyzoites from cell culture were used to infect ... ...

Abstract	Purpose: To provide a simple alternative acute ocular toxoplasmosis model with great reproducibility for experimental tests that demand monitoring of the ocular lesion. Methods: ME49-wt and ME49-GFP tachyzoites from cell culture were used to infect male C57BL6 mice by intraperitoneal injection. B1 expression by real-time polymerase chain reaction (qPCR) assay was used to detect the presence of T. gondii in ocular tissue at the beginning of the infection. Fluorescence microscopy and histopathology analysis were carried out to assess the evolution of the acute infection up to 20 days in both eyes of infected mice. Results: All mice infected with the 10 Conclusion: Infection of C57BL6 mice via intraperitoneal with 10
MeSH term(s)	Male ; Animals ; Mice ; Toxoplasmosis, Ocular/diagnosis ; Reproducibility of Results ; Mice, Inbred C57BL ; Retina ; Retinal Pigment Epithelium
Language	English
Publishing date	2024-02-13
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	800087-6
ISSN	1573-2630 ; 0165-5701
ISSN (online)	1573-2630
ISSN	0165-5701
DOI	10.1007/s10792-024-02985-2
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Article ; Online: Presumed SARS-CoV-2 Viral Particles in the Human Retina of Patients With COVID-19.

Araujo-Silva, Carlla A / Marcos, Alléxya A A / Marinho, Paula M / Branco, Ana M C / Roque, Alexandre / Romano, André C / Matuoka, Mateus L / Farah, Michel / Burnier, Miguel / Moraes, Nara F / Tierno, Paulo F G M M / Schor, Paulo / Sakamoto, Victoria / Nascimento, Heloisa / de Sousa, Wanderley / Belfort, Rubens

JAMA ophthalmology

2021 Volume 139, Issue 9, Page(s) 1015–1021

Abstract: Importance: The presence of the SARS-CoV-2 virus in the retina of deceased patients with COVID-19 has been suggested through real-time reverse polymerase chain reaction and immunological methods to detect its main proteins. The eye has shown ... ...

Abstract	Importance: The presence of the SARS-CoV-2 virus in the retina of deceased patients with COVID-19 has been suggested through real-time reverse polymerase chain reaction and immunological methods to detect its main proteins. The eye has shown abnormalities associated with COVID-19 infection, and retinal changes were presumed to be associated with secondary microvascular and immunological changes. Objective: To demonstrate the presence of presumed SARS-CoV-2 viral particles and its relevant proteins in the eyes of patients with COVID-19. Design, setting, and participants: The retina from enucleated eyes of patients with confirmed COVID-19 infection were submitted to immunofluorescence and transmission electron microscopy processing at a hospital in São Paulo, Brazil, from June 23 to July 2, 2020. After obtaining written consent from the patients' families, enucleation was performed in patients deceased with confirmed SARS-CoV-2 infection. All patients were in the intensive care unit, received mechanical ventilation, and had severe pulmonary involvement by COVID-19. Main outcomes and measures: Presence of presumed SARS-CoV-2 viral particles by immunofluorescence and transmission electron microscopy processing. Results: Three patients who died of COVID-19 were analyzed. Two patients were men, and 1 was a woman. The age at death ranged from 69 to 78 years. Presumed S and N COVID-19 proteins were seen by immunofluorescence microscopy within endothelial cells close to the capillary flame and cells of the inner and the outer nuclear layers. At the perinuclear region of these cells, it was possible to observe by transmission electron microscopy double-membrane vacuoles that are consistent with the virus, presumably containing COVID-19 viral particles. Conclusions and relevance: The present observations show presumed SARS-CoV-2 viral particles in various layers of the human retina, suggesting that they may be involved in some of the infection's ocular clinical manifestations.
MeSH term(s)	Aged ; COVID-19/diagnosis ; COVID-19/mortality ; COVID-19/virology ; Female ; Fluorescent Antibody Technique ; Humans ; Male ; Microscopy, Electron, Transmission ; Retina/ultrastructure ; Retina/virology ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/ultrastructure ; Virion/isolation & purification ; Virion/ultrastructure
Language	English
Publishing date	2021-07-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701705-9
ISSN	2168-6173 ; 2168-6165
ISSN (online)	2168-6173
ISSN	2168-6165
DOI	10.1001/jamaophthalmol.2021.2795
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Article: Culex Flavivirus Isolation from Naturally Infected Mosquitoes Trapped at Rio de Janeiro City, Brazil.

Amaral, Cinthya / Câmara, Daniel / Salles, Tiago / Meneses, Marcelo Damião / Araújo-Silva, Carlla de / Dias, Vanessa / Costa, Fábio da / Caldas, Lúcio / Azevedo, Renata

Insects

2022 Volume 13, Issue 5

Abstract: ... Culex ... ...

Abstract	Culex Flavivirus
Language	English
Publishing date	2022-05-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662247-6
ISSN	2075-4450
ISSN	2075-4450
DOI	10.3390/insects13050477
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Article ; Online: Potent hydroxamate-derived compounds arrest endodyogeny of Toxoplasma gondii tachyzoites.

Araujo-Silva, Carlla Assis / Vögerl, Katharina / Breu, Ferdinand / Jung, Manfred / Costa, Andreia Luiza Oliveira / De Souza, Wanderley / Bracher, Franz / Martins-Duarte, Erica S / Vommaro, Rossiane C

Experimental parasitology

2024 Volume 259, Page(s) 108727

Abstract: Toxoplasmosis is a zoonosis that is a worldwide health problem, commonly affecting fetal development and immunodeficient patients. Treatment is carried out with a combination of pyrimethamine and sulfadiazine, which can cause cytopenia and intolerance ... ...

Abstract	Toxoplasmosis is a zoonosis that is a worldwide health problem, commonly affecting fetal development and immunodeficient patients. Treatment is carried out with a combination of pyrimethamine and sulfadiazine, which can cause cytopenia and intolerance and does not lead to a parasitological cure of the infection. Lysine deacetylases (KDACs), which remove an acetyl group from lysine residues in histone and non-histone proteins are found in the Toxoplasma gondii genome. Previous work showed the hydroxamate-type KDAC inhibitors Tubastatin A (TST) and Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) were effective against T. gondii. In the present study, the effects of three hydroxamates (KV-24, KV-30, KV-46), which were originally designed to inhibit human KDAC6, showed different effects against T. gondii. These compounds contain a heterocyclic cap group and a benzyl linker bearing the hydroxamic acid group in para-position. All compounds showed selective activity against T. gondii proliferation, inhibiting tachyzoite proliferation with IC
MeSH term(s)	Humans ; Toxoplasma ; Lysine/pharmacology ; Toxoplasmosis ; Pyrimethamine/pharmacology ; Pyrimethamine/therapeutic use ; Hydroxamic Acids/pharmacology ; Vorinostat/pharmacology
Chemical Substances	Lysine (K3Z4F929H6) ; Pyrimethamine (Z3614QOX8W) ; Hydroxamic Acids ; Vorinostat (58IFB293JI)
Language	English
Publishing date	2024-03-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	391089-1
ISSN	1090-2449 ; 0014-4894
ISSN (online)	1090-2449
ISSN	0014-4894
DOI	10.1016/j.exppara.2024.108727
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Article ; Online: HDAC inhibitors Tubastatin A and SAHA affect parasite cell division and are potential anti-Toxoplasma gondii chemotherapeutics.

Araujo-Silva, Carlla Assis / De Souza, Wanderley / Martins-Duarte, Erica S / Vommaro, Rossiane C

International journal for parasitology. Drugs and drug resistance

2020 Volume 15, Page(s) 25–35

Abstract: The redirectioning of drugs in the pharmaceutical market is a well-known practice to identify new therapies for parasitic diseases. The histone deacetylase inhibitors Tubastatin A (TST) and Suberoylanilide Hydroxamic Acid (SAHA), firstly developed for ... ...

Abstract	The redirectioning of drugs in the pharmaceutical market is a well-known practice to identify new therapies for parasitic diseases. The histone deacetylase inhibitors Tubastatin A (TST) and Suberoylanilide Hydroxamic Acid (SAHA), firstly developed for cancer treatment, are effective against protozoa parasites. In this work, we aimed to demonstrate the activity of these drugs as potential agents against Toxoplasma gondii, the causative agent of toxoplasmosis. TST and SAHA were active against different genotypes of Toxoplasma gondii, such as, RH (type I), EGS (I/III) and ME49 (type II) strains. The IC₅₀ values for the RH strain were 19 ± 1 nM and 520 ± 386 nM for TST and 41 ± 3 nM and 67 ± 36 nM for SAHA, for 24 and 48 h, respectively. Both compounds were highly selective for T. gondii and their anti-proliferative effect was irreversible for 8 days. The calculated selectivity indexes (39 for TST and 30 for SAHA) make them lead compounds for the future development of anti-Toxoplasma molecules. Western blotting showed TST led to a significant increase of the nuclear histone H4 and a decrease of H3 acetylation levels. Treatment with 1 μM TST and 0.1 μM SAHA for 48 h decreased the amount of global α-tubulin. Fluorescence and electron microscopy showed that both drugs affected the endodyogeny process impairing the budding of daughter cells. The drugs led to the formation of large, rounded masses of damaged parasites with several centrosomes randomly dispersed and incorrect apicoplast division and positioning. TST-treated parasites showed a rupture of the mitochondrial membrane potential and led to a failure of the IMC assembling of new daughter cells. SAHA and TST possibly inhibit HDAC3 and other cytoplasmic or organelle targeted HDACs involved in the modification of proteins other than histones.
MeSH term(s)	Animals ; Cell Division ; Histone Deacetylase Inhibitors/pharmacology ; Hydroxamic Acids/pharmacology ; Indoles ; Parasites ; Toxoplasma ; Vorinostat/pharmacology
Chemical Substances	Histone Deacetylase Inhibitors ; Hydroxamic Acids ; Indoles ; tubastatin A (2XTSOX1NF8) ; Vorinostat (58IFB293JI)
Language	English
Publishing date	2020-12-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2751132-7
ISSN	2211-3207 ; 2211-3207
ISSN (online)	2211-3207
ISSN	2211-3207
DOI	10.1016/j.ijpddr.2020.12.003
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Article ; Online: Culex Flavivirus Isolation from Naturally Infected Mosquitoes Trapped at Rio de Janeiro City, Brazil

Cinthya Amaral / Daniel Câmara / Tiago Salles / Marcelo Damião Meneses / Carlla de Araújo-Silva / Vanessa Dias / Fábio da Costa / Lúcio Caldas / Renata Azevedo

Insects, Vol 13, Iss 477, p

2022 Volume 477

Abstract: Culex Flavivirus (CxFV) is a classical insect-specific virus, which has aroused interest after the first indication that it can produce in nature superinfection exclusion of viruses of medical interest such as West Nile. Despite the detection of CxFV in ... ...

Abstract	Culex Flavivirus (CxFV) is a classical insect-specific virus, which has aroused interest after the first indication that it can produce in nature superinfection exclusion of viruses of medical interest such as West Nile. Despite the detection of CxFV in different regions, CxFV ecology and the influence of co-circulation of arboviruses remains poorly understood. Therefore, our primary goals are to observe the occurrence of CxFV infection in mosquitoes trapped in an urban area of Rio de Janeiro, Brazil, characterize the virus circulating, and provide isolates. A prospective study was carried out for eight months on the campus of the Federal University of Rio de Janeiro, trapping adult mosquitoes. The CxFV minimum infection rates were determined in this period, and the virus isolation process is fully described. Samples from this study were grouped into genotype 2, along with CxFV sequences from Latin America and Africa.
Keywords	Culex Flavivirus ; insect-specific virus ; virus isolation ; flavivirus ; Culex species ; Science ; Q
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Dichloroacetate and Pyruvate Metabolism: Pyruvate Dehydrogenase Kinases as Targets Worth Investigating for Effective Therapy of Toxoplasmosis.

Ferrarini, Mariana Galvão / Nisimura, Lindice Mitie / Girard, Richard Marcel Bruno Moreira / Alencar, Mayke Bezerra / Fragoso, Mariana Sayuri Ishikawa / Araújo-Silva, Carlla Assis / Veiga, Alan de Almeida / Abud, Ana Paula Ressetti / Nardelli, Sheila Cristina / Vommaro, Rossiane C / Silber, Ariel Mariano / France-Sagot, Marie / Ávila, Andréa Rodrigues

mSphere

2021 Volume 6, Issue 1

Abstract: Toxoplasmosis, a protozoan infection caused ... ...

Abstract	Toxoplasmosis, a protozoan infection caused by
MeSH term(s)	Antiprotozoal Agents/pharmacology ; Apoptosis/drug effects ; Dichloroacetic Acid/chemistry ; Dichloroacetic Acid/pharmacology ; Fibroblasts/drug effects ; Fibroblasts/parasitology ; Humans ; Metabolic Networks and Pathways/drug effects ; Mitochondria/metabolism ; Oxidation-Reduction ; Oxidoreductases ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase/antagonists & inhibitors ; Pyruvates/metabolism ; Toxoplasma/drug effects ; Toxoplasmosis/drug therapy
Chemical Substances	Antiprotozoal Agents ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase ; Pyruvates ; Dichloroacetic Acid (9LSH52S3LQ) ; Oxidoreductases (EC 1.-)
Language	English
Publishing date	2021-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-5042
ISSN (online)	2379-5042
DOI	10.1128/mSphere.01002-20
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Article ; Online: Mesenchymal stem cells and cell-derived extracellular vesicles protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-β oligomers.

de Godoy, Mariana A / Saraiva, Leonardo M / de Carvalho, Luiza R P / Vasconcelos-Dos-Santos, Andreia / Beiral, Hellen J V / Ramos, Alane Bernardo / Silva, Livian R de Paula / Leal, Renata B / Monteiro, Victor H S / Braga, Carolina V / de Araujo-Silva, Carlla A / Sinis, Leandro C / Bodart-Santos, Victor / Kasai-Brunswick, Tais Hanae / Alcantara, Carolina de Lima / Lima, Ana Paula C A / da Cunha-E Silva, Narcisa L / Galina, Antonio / Vieyra, Adalberto /

De Felice, Fernanda G / Mendez-Otero, Rosalia / Ferreira, Sergio T

The Journal of biological chemistry

2017 Volume 293, Issue 6, Page(s) 1957–1975

Abstract: Alzheimer's disease (AD) is a disabling and highly prevalent neurodegenerative condition, for which there are no effective therapies. Soluble oligomers of the amyloid-β peptide (AβOs) are thought to be proximal neurotoxins involved in early neuronal ... ...

Abstract	Alzheimer's disease (AD) is a disabling and highly prevalent neurodegenerative condition, for which there are no effective therapies. Soluble oligomers of the amyloid-β peptide (AβOs) are thought to be proximal neurotoxins involved in early neuronal oxidative stress and synapse damage, ultimately leading to neurodegeneration and memory impairment in AD. The aim of the current study was to evaluate the neuroprotective potential of mesenchymal stem cells (MSCs) against the deleterious impact of AβOs on hippocampal neurons. To this end, we established transwell cocultures of rat hippocampal neurons and MSCs. We show that MSCs and MSC-derived extracellular vesicles protect neurons against AβO-induced oxidative stress and synapse damage, revealed by loss of pre- and postsynaptic markers. Protection by MSCs entails three complementary mechanisms: 1) internalization and degradation of AβOs; 2) release of extracellular vesicles containing active catalase; and 3) selective secretion of interleukin-6, interleukin-10, and vascular endothelial growth factor to the medium. Results support the notion that MSCs may represent a promising alternative for cell-based therapies in AD.
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/chemistry ; Amyloid beta-Peptides/metabolism ; Animals ; Cells, Cultured ; Coculture Techniques ; Extracellular Vesicles/genetics ; Extracellular Vesicles/metabolism ; Hippocampus/cytology ; Hippocampus/metabolism ; Humans ; Interleukin-10/metabolism ; Interleukin-6/metabolism ; Male ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Neurons/cytology ; Neurons/metabolism ; Oxidative Stress ; Rats ; Rats, Wistar ; Synapses/metabolism ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Amyloid beta-Peptides ; Interleukin-6 ; Vascular Endothelial Growth Factor A ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2017-12-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M117.807180
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