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Article ; Online: Device implant based on poly (lactic acid) with vitamin E for vaccine delivery system in Tilapia

Gabriel Conde / Mayumi Fernanda Aracati / Letícia Franchin Rodrigues / Susana Luporini de Oliveira / Camila Carlino da Costa / Ives Charlie-Silva / Thalles Fernando Rocha Ruiz / Sebastião Roberto Taboga / Marco Antonio de Andrade Belo

Fish and Shellfish Immunology Reports, Vol 3, Iss , Pp 100060- (2022)

Study for biocompatibility and biodegradation

2022

Abstract: The use of Poly (lactic acid) (PLA) as a slow-release vehicle for vaccines has attracted the attention of researchers, since its insertion improves the uptake of them, and reduces side effects or by stimulating recruited defense cells, assisting immunity ...

Abstract	The use of Poly (lactic acid) (PLA) as a slow-release vehicle for vaccines has attracted the attention of researchers, since its insertion improves the uptake of them, and reduces side effects or by stimulating recruited defense cells, assisting immunity without the need for booster vaccine doses. Seeking to develop new strategies for the administration of drugs and vaccines in aquaculture, we evaluated the biocompatibility and biodegradation of polymeric PLA devices and PLA plus vitamin E devices, implanted through subcutaneous (SC) and intraperitoneal (IP) routes in Nile tilapia. To carry out this study, 84 male tilapia (initial 243.82 ± 56.74 g; final 400.71 ± 100.54 g) were randomly distributed in 3 tanks (n = 28 fish per treatment/tank). The devices were prepared in two formulations: neat PLA (containing 100% PLA) and PLAVE (PLA plus vitamin E) implanted using a commercial AnimalTag® applicator, and non-implanted fish (control). Fish were sampled 15, 30, 60, and 120 days post-implantation (DPI). Blood analysis was used to access blood cells and blood smear for differential leucocytes count. Serum biochemistry to evaluated changes in serum proteins and glycemia. Histopathological investigation using hematoxylin-eosin (H&E) was used to assess polymer-tissue interaction. Histochemistry and immunohistochemistry was used to detection immune cells and phagocytes in capsule, and analyses of melanomacrophage centers (MMCs) to morphometric evaluation and percentage amount of melanin, hemosiderin and lipofucsin pigments. Histopathological study revealed an increase of capsular formation and inflammatory cell infiltration in PLAVE-implanted tilapia through SC route (15 DPI). Tilapia implanted with PLAVE and PLA (SC) presented mast cells and eosinophilic granular cells during 15, 30, and 60 DPI, with a decrease in these cells in the fibrous capsule around the polymer at 120 DPI. PLAVE implanted tilapia SC at 60 DPI showed significantly phagocytosis points than other groups. Phagocytic cells (F4/80+) were observed ...
Keywords	Biomaterials ; Oreochromis niloticus ; Clinical safety ; Inflammatory response ; Innate immunity ; Zoology ; QL1-991
Subject code	610
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effects of trabectedin in the zebrafish Danio rerio

Évila Pinheiro Damasceno / Ives Charlie-Silva / Glaucia Maria Machado-Santelli / Anali M.B. Garnique / João Agostinho Machado-Neto / Simone Aparecida Teixeira / Paula C. Jimenez / Diana Carneiro / Amadeu M.V.M. Soares / Leticia V. Costa-Lotufo / Susana Loureiro / Maria D. Pavlaki

Environmental Advances, Vol 8, Iss , Pp 100208- (2022)

from cells to larvae

2022

Abstract: Anticancer agents pose a great environmental risk due to their high toxicity. The aim of the current study is to assess the toxicity of trabectedin, a cytotoxic but atypical DNA binder, to liver cell line (ZFL) and embryo-larvae of the zebrafish Danio ... ...

Abstract	Anticancer agents pose a great environmental risk due to their high toxicity. The aim of the current study is to assess the toxicity of trabectedin, a cytotoxic but atypical DNA binder, to liver cell line (ZFL) and embryo-larvae of the zebrafish Danio rerio employing an innovative approach. In ZFL cells, trabectedin cytotoxicity was measured using MTT and Trypan blue exclusion assay, and cell morphology was evaluated by fluorescence-activated cell sorting (FACS) and by immunofluorescence analysis. Trabectedin was 60-fold more toxic to ZFL cells than to zebrafish embryo-larvae in terms of mortality/cell viability, with mortality being observed in 42.7 µg.L−1 for embryo-larvae and non-viability in 0.04 µg.L−1 for cultured cells. Immunofluorescence staining showed morphology alterations of ZFL-cells exposed to trabectedin in a dose-dependent manner, from 0.04 to 0.15 µg.L−1. Furthermore, trabectedin induced morphological abnormalities to zebrafish embryo-larvae, such as tail malformations, pericardial edema and lack of equilibrium at concentrations lower than 50.3 µg.L−1. Regarding larvae behavior analysis, trabectedin increased velocity and total distance covered by zebrafish exposed to 42.7 µg.L−1 under dark conditions. These results reveal trabectedin to be toxic in both in vitro and in vivo zebrafish models, and thus the occurrence and persistence of this anticancer agent in the environment may represent a potential risk factor to the biota.
Keywords	Anticancer agent ; Zebrafish locomotor behavior ; ZFL cells ; Developmental toxicity ; Cytotoxicity ; Environmental sciences ; GE1-350
Subject code	610
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Recent advances in SARS-CoV-2 Spike protein and RBD mutations comparison between new variants Alpha (B.1.1.7, United Kingdom), Beta (B.1.351, South Africa), Gamma (P.1, Brazil) and Delta (B.1.617.2, India)

Paulo R.S. Sanches / Ives Charlie-Silva / Helyson L.B. Braz / Cíntia Bittar / Marilia Freitas Calmon / Paula Rahal / Eduardo M. Cilli

Journal of Virus Eradication, Vol 7, Iss 3, Pp 100054- (2021)

2021

Abstract: New variants of SARS-CoV-2 Alpha (B.1.1.7); Beta (B.1.351) Gamma (P.1) and Delta (B.1.617.2) quickly spread in the UK, South Africa, Brazil and India, respectively. To address whether mutations in SARS-CoV-2 RBD spike protein could affect virus ... ...

Abstract	New variants of SARS-CoV-2 Alpha (B.1.1.7); Beta (B.1.351) Gamma (P.1) and Delta (B.1.617.2) quickly spread in the UK, South Africa, Brazil and India, respectively. To address whether mutations in SARS-CoV-2 RBD spike protein could affect virus infectivity, peptides containing RBD amino acids mutations have been constructed and interacted with human ACE2 by computational methods. Our results suggest that mutations in RBD amino acids K417, E484, L452, T478 and N501 are expressively increasing the affinity of this protein with human angiotensin-converting enzyme 2 (ACE2), consequently, variants Alpha (B.1.1.7), Beta (B1.351), Gamma (P.1) and Delta (B.1.617.2) could be more infective in human cells compared with SARS-CoV-2 isolated in Wuhan-2019 and the Gamma and Delta variants could be the most infective among them.
Keywords	SARS-CoV-2 ; New variants ; Spike protein ; Receptor binding domain ; Human ACE2 ; Microbiology ; QR1-502 ; Public aspects of medicine ; RA1-1270
Subject code	572
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Meningitis Caused by Streptococcus agalactiae in Nile Tilapia ( Oreochromis niloticus )

Silas Fernandes Eto / Dayanne Carla Fernandes / Alessandra Cristina de Moraes / João Victor da Costa Alecrim / Pedro Galdino de Souza / Fabíola Christian Almeida de Carvalho / Ives Charlie-Silva / Marco Antonio de Andrade Belo / João Martins Pizauro

Animals, Vol 10, Iss 2166, p

Infection and Inflammatory Response

2020 Volume 2166

Abstract: Streptococcus agalactiae ( Sta ) of Lancefield group B is the primary etiological agent of bacterial meningitis in Nile tilapia and newborn humans. Thus, the study of this disease is of fundamental importance for aquaculture and human medicine. ... ...

Abstract	Streptococcus agalactiae ( Sta ) of Lancefield group B is the primary etiological agent of bacterial meningitis in Nile tilapia and newborn humans. Thus, the study of this disease is of fundamental importance for aquaculture and human medicine. Additionally, elucidation of the mechanisms involved in the host–pathogenic response is important for the success of new therapies. In the present study, we elucidated important aspects of the innate immune response in the brain tissue of Nile tilapia ( Oreochromis niloticus ) infected by Sta . The neuroinflammatory process in the meninges started with the migration of MHC class II and CD68 + cells, production of TNF-alpha, and the effective immune response to Sta was mediated by the increased iNOs+. In conclusion, the present study brings a partial understanding of the pathophysiological and neuroinflammatory mechanisms in meningitis in Sta infected tilapia, enabling important advances in the therapy of this disease as well as the possibility of using this biological model to understand human meningitis.
Keywords	streptococcosis ; microglia ; teleost fish ; neuropathy ; Veterinary medicine ; SF600-1100 ; Zoology ; QL1-991
Subject code	610
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long-term dexamethasone treatment increases the engraftment efficiency of human breast cancer cells in adult zebrafish

Juliana Moreira Mendonça-Gomes / Thalita Marcolan Valverde / Thaís Maria da Mata Martins / Ives Charlie-Silva / Barbara Nunes Padovani / Camila Morales Fénero / Eloisa Martins da Silva / Rosana Zacarias Domingues / Daniela Chemim Melo-Hoyos / José Dias Corrêa-Junior / Niels Olsen Saraiva Câmara / Alfredo Miranda Góes / Dawidson Assis Gomes

Fish and Shellfish Immunology Reports, Vol 2, Iss , Pp 100007- (2021)

2021

Abstract: The host immune system tends to reject xenogenic-implanted cells making tumor development in adult host animal models difficult. Immune system suppression is used for successful xenotransplantation of human cancer cells in many animal models. The studies ...

Abstract	The host immune system tends to reject xenogenic-implanted cells making tumor development in adult host animal models difficult. Immune system suppression is used for successful xenotransplantation of human cancer cells in many animal models. The studies of cancer development processes in vivo offer opportunities to understand cancer biology and discover new therapeutic strategies. In this context, zebrafish is a model that has been widely applied in the study of human diseases, such as cancer. However, the long-term immunosuppression of these adult zebrafish is still under study as a xenograft animal model for human cancer. This work aimed to evaluate the effects of 21 days of (long-term) exposure of dexamethasone in zebrafish-transplanted with MGSO-3 cells, human breast tumor cell line. Our results show that the animals, while kept on dexamethasone treatment, remained with a 50% reduction in the number of peripheral lymphocytes. In vitro data demonstrated that up to 7 days of dexamethasone treatment did not alter the morphology, proliferation, or viability of MGSO-3 cells. The animals that received a prolonged dexamethasone treatment allowed the engraftment of tumor cells in 100% of the zebrafish tested. These animals also showed tumor progression over 21 days. The experimental group that received only previous exposure to dexamethasone had their tumors regressed after 14 days. In conclusion, the prolonged use of dexamethasone in zebrafish showed a potential strategy for in vivo monitoring of xenograft tumor growth for development studies, as well as in anticancer drug discovery.
Keywords	Breast cancer ; Lymphocytes ; Immunosuppression ; Xenotransplant ; Zebrafish ; Zoology ; QL1-991
Subject code	630
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Immunization with SARS-CoV-2 Nucleocapsid protein triggers a pulmonary immune response in rats

Everidiene K. V. B. Silva / Camila G. Bomfim / Ana P. Barbosa / Paloma Noda / Irene L. Noronha / Bianca H. V. Fernandes / Rafael R. G. Machado / Edison L. Durigon / Sergio Catanozi / Letícia G. Rodrigues / Fabiana Pieroni / Sérgio G. Lima / Walcy R. Teodoro / Zelita A. J. Queiroz / Lizandre K. R. Silveira / Ives Charlie-Silva / Vera L. Capelozzi / Cristiane R. Guzzo / Camilla Fanelli

PLoS ONE, Vol 17, Iss

2022 Volume 5

Abstract: The SARS-CoV-2 pandemic have been affecting millions of people worldwide, since the beginning of 2020. COVID-19 can cause a wide range of clinical symptoms, which varies from asymptomatic presentation to severe respiratory insufficiency, exacerbation of ... ...

Abstract	The SARS-CoV-2 pandemic have been affecting millions of people worldwide, since the beginning of 2020. COVID-19 can cause a wide range of clinical symptoms, which varies from asymptomatic presentation to severe respiratory insufficiency, exacerbation of immune response, disseminated microthrombosis and multiple organ failure, which may lead to dead. Due to the rapid spread of SARS-CoV-2, the development of vaccines to minimize COVID-19 severity in the world population is imperious. One of the employed techniques to produce vaccines against emerging viruses is the synthesis of recombinant proteins, which can be used as immunizing agents. Based on the exposed, the aim of the present study was to verify the systemic and immunological effects of IM administration of recombinant Nucleocapsid protein (NP), derived from SARS-CoV-2 and produced by this research group, in 2 different strains of rats (Rattus norvegicus); Wistar and Lewis. For this purpose, experimental animals received 4 injections of NP, once a week, and were submitted to biochemical and histological analysis. Our results showed that NP inoculations were safe for the animals, which presented no clinical symptoms of worrying side effects, nor laboratorial alterations in the main biochemical and histological parameters, suggesting the absence of toxicity induced by NP. Moreover, NP injections successfully triggered the production of specific anti-SARS-CoV-2 IgG antibodies by both Wistar and Lewis rats, showing the sensitization to have been well sufficient for the immunization of these strains of rats. Additionally, we observed the local lung activation of the Bronchus-Associated Lymphoid Tissue (BALT) of rats in the NP groups, suggesting that NP elicits specific lung immune response. Although pre-clinical and clinical studies are still required, our data support the recombinant NP produced by this research group as a potential immunizing agent for massive vaccination, and may represent advantages upon other recombinant proteins, since it seems to induce ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Immunization with SARS-CoV-2 Nucleocapsid protein triggers a pulmonary immune response in rats.

Everidiene K V B Silva / Camila G Bomfim / Ana P Barbosa / Paloma Noda / Irene L Noronha / Bianca H V Fernandes / Rafael R G Machado / Edison L Durigon / Sergio Catanozi / Letícia G Rodrigues / Fabiana Pieroni / Sérgio G Lima / Walcy R Teodoro / Zelita A J Queiroz / Lizandre K R Silveira / Ives Charlie-Silva / Vera L Capelozzi / Cristiane R Guzzo / Camilla Fanelli

PLoS ONE, Vol 17, Iss 5, p e

2022 Volume 0268434

Abstract	The SARS-CoV-2 pandemic have been affecting millions of people worldwide, since the beginning of 2020. COVID-19 can cause a wide range of clinical symptoms, which varies from asymptomatic presentation to severe respiratory insufficiency, exacerbation of immune response, disseminated microthrombosis and multiple organ failure, which may lead to dead. Due to the rapid spread of SARS-CoV-2, the development of vaccines to minimize COVID-19 severity in the world population is imperious. One of the employed techniques to produce vaccines against emerging viruses is the synthesis of recombinant proteins, which can be used as immunizing agents. Based on the exposed, the aim of the present study was to verify the systemic and immunological effects of IM administration of recombinant Nucleocapsid protein (NP), derived from SARS-CoV-2 and produced by this research group, in 2 different strains of rats (Rattus norvegicus); Wistar and Lewis. For this purpose, experimental animals received 4 injections of NP, once a week, and were submitted to biochemical and histological analysis. Our results showed that NP inoculations were safe for the animals, which presented no clinical symptoms of worrying side effects, nor laboratorial alterations in the main biochemical and histological parameters, suggesting the absence of toxicity induced by NP. Moreover, NP injections successfully triggered the production of specific anti-SARS-CoV-2 IgG antibodies by both Wistar and Lewis rats, showing the sensitization to have been well sufficient for the immunization of these strains of rats. Additionally, we observed the local lung activation of the Bronchus-Associated Lymphoid Tissue (BALT) of rats in the NP groups, suggesting that NP elicits specific lung immune response. Although pre-clinical and clinical studies are still required, our data support the recombinant NP produced by this research group as a potential immunizing agent for massive vaccination, and may represent advantages upon other recombinant proteins, since it seems to induce ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction

Thais Sibioni Berti Bastos / André Guilherme Portela de Paula / Rebeca Bosso dos Santos Luz / Anali M. B. Garnique / Marco A. A. Belo / Silas Fernandes Eto / Dayanne Carla Fernandes / Fausto Klabund Ferraris / Leticia Gomes de Pontes / Tábata Takahashi França / Leonardo José Gil Barcellos / Flavio P. Veras / Pamela Bermejo / Giovanna Guidelli / Carla Maneira / Fellipe da Silveira Bezerra de Mello / Gleidson Teixeira / Gonçalo Amarante Guimarães Pereira / Bianca H. Ventura Fernandes /

Paulo R. S. Sanches / Helyson Lucas Bezerra Braz / Roberta Jeane Bezerra Jorge / Guilherme Malafaia / Eduardo M. Cilli / Danilo da Silva Olivier / Marcos Serrou do Amaral / Renata J. Medeiros / Antonio Condino-Neto / Luciani R. Carvalho / Glaucia M. Machado-Santelli / Ives Charlie-Silva / Jorge Galindo-Villegas / Tárcio Teodoro Braga

Scientific Reports, Vol 13, Iss 1, Pp 1-

A novel insight on SARS-CoV-2 S-derived fragments in the control of the host immunity

2023 Volume 2

Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A novel insight on SARS-CoV-2 S-derived fragments in the control of the host immunity

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 15

Abstract: Abstract Despite all efforts to combat the pandemic of COVID-19, we are still living with high numbers of infected persons, an overburdened health care system, and the lack of an effective and definitive treatment. Understanding the pathophysiology of ... ...

Abstract	Abstract Despite all efforts to combat the pandemic of COVID-19, we are still living with high numbers of infected persons, an overburdened health care system, and the lack of an effective and definitive treatment. Understanding the pathophysiology of the disease is crucial for the development of new technologies and therapies for the best clinical management of patients. Since the manipulation of the whole virus requires a structure with an adequate level of biosafety, the development of alternative technologies, such as the synthesis of peptides from viral proteins, is a possible solution to circumvent this problem. In addition, the use and validation of animal models is of extreme importance to screen new drugs and to compress the organism's response to the disease. Peptides derived from recombinant S protein from SARS-CoV-2 were synthesized and validated by in silico, in vitro and in vivo methodologies. Macrophages and neutrophils were challenged with the peptides and the production of inflammatory mediators and activation profile were evaluated. These peptides were also inoculated into the swim bladder of transgenic zebrafish larvae at 6 days post fertilization (dpf) to mimic the inflammatory process triggered by the virus, which was evaluated by confocal microscopy. In addition, toxicity and oxidative stress assays were also developed. In silico and molecular dynamics assays revealed that the peptides bind to the ACE2 receptor stably and interact with receptors and adhesion molecules, such as MHC and TCR, from humans and zebrafish. Macrophages stimulated with one of the peptides showed increased production of NO, TNF-α and CXCL2. Inoculation of the peptides in zebrafish larvae triggered an inflammatory process marked by macrophage recruitment and increased mortality, as well as histopathological changes, similarly to what is observed in individuals with COVID-19. The use of peptides is a valuable alternative for the study of host immune response in the context of COVID-19. The use of zebrafish as an animal ...
Keywords	Medicine ; R ; Science ; Q
Subject code	630
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Acute-phase proteins during inflammatory reaction by bacterial infection

Ives Charlie-Silva / Andre Klein / Juliana M. M. Gomes / Ed J. R. Prado / Alessandra C. Moraes / Silas F. Eto / Dayanne C. Fernandes / José J. Fagliari / José D. Corrêa Junior / Carla Lima / Mônica Lopes-Ferreira / Katia Conceição / Wilson G. Manrique / Marco A. A. Belo

Scientific Reports, Vol 9, Iss 1, Pp 1-

Fish-model

2019 Volume 13

Abstract: Abstract Acute-phase protein (APPs) serum levels have been studied in many human diseases, and their components contribute to host defense during the evolution of infectious diseases by acting as part of the innate immune system. Based on the importance ... ...

Abstract	Abstract Acute-phase protein (APPs) serum levels have been studied in many human diseases, and their components contribute to host defense during the evolution of infectious diseases by acting as part of the innate immune system. Based on the importance of establishing new experimental models, the present investigation evaluated the modulation of APPs following inflammatory stimulus by the inoculation of Aeromonas hydrophila in tilapias. Fish were sampled 6 and 24 hours post-infection. Tilapias presented increase of positive APPs such as ceruloplasmin, haptoglobin, alpha-2-macroglobulin and complement C3, as well as decrease of negative APPs such as albumin and transferrin. The protein response of tilapias during the course of bacterial infection showed correlation with the kinetics of cellular accumulation in the inflamed focus with significant increase of granulocytes, thrombocytes, lymphocytes and macrophages. However, granulocytes were the predominant cells, associated with increment in the reactive oxygen species (ROS) production. Showing responses similar to those observed in humans, the modulation of APPs and the kinetics of cellular accumulation in the exudate demonstrate the feasibility of this alternative experimental model for advances and studies to understand changes in pathophysiological mechanisms of acute inflammatory reaction due to bacterial infection.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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