Center for Translational Science and Biopharmaceutical Development

• Grant number: 21/11936-3
• Support Opportunities: Research Grants - Science Centers for Development
• Start date: January 01, 2023
• End date: December 31, 2027
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Benedito Barraviera
• Grantee: Benedito Barraviera
• Host Institution: Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP). Centro Virtual de Toxinologia. Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Pesquisadores principais: Carlos Roberto Prudencio ; Eliane Candiani Arantes Braga ; Rui Seabra Ferreira Junior ; Saulo Philipe Sebastião Guerra ; Vitor Marcelo Silveira Bueno Brandão de Oliveira
• Associated researchers: Ana Silvia Sartori Barraviera Seabra Ferreira ; Clarissa Feltrin ; Elizabeth Natal de Gaspari ; Ernesto Lopes Pinheiro Junior ; Felipe Augusto Cerni ; Jair Pereira da Cunha Junior ; Jair Ribeiro Chagas ; Jan Tytgat ; José Angelo Lauletta Lindoso ; Karla de Castro Figueiredo Bordon ; Liria Hiromi Okuda ; Manuela Berto Pucca ; Marco Antonio Stephano ; Paulo Eduardo Martins Ribolla ; Manish Bhalla ; Ramendra Pati Pandey ; Regina Maria Catarino ; Steve Peigneur
• Associated research grant(s): 23/01083-9 - Prospection of bioactive peptides with antitumor activity isolated from scorpion venoms from the Brazilian Amazon, AP.R; 23/01554-1 - Antibacterial and antiviral activity of melittin and its impact on the proteomic profile of Acinetobacter baumannii, Enterococcus faecium, Klebsiella pneumoniae, Zika Virus and SARS-CoV-2, AP.R
• Associated scholarship(s): 25/09016-4 - Planning, development of a digital communication environment, interview with researchers and transformation of scientific content into accessible popular language., BP.TT; 24/17849-3 - Structural, functional and bioprospecting studies of recombinant Ts16 toxin, BP.DR; 24/13799-1 - Science communication from the Center for Translational Science and Development of Biopharmaceuticals, BP.JC; + associated scholarships 24/14801-0 - Expression and characterization of intrinsically fluorescent single-chain variable fragments (scFv) for detection of SARS-COV-2., BP.TT; 24/13221-0 - Standardization of Freeze-Drying of Heterologous Fibrin Sealant Components., BP.TT; 24/02846-9 - Assessment of solubility and stability of a recombinant serine protease from Crotalus durissus collilineatus in its PEGylated and non-PEGylated forms, BP.MS; 24/07363-6 - Validation and standardization of quality control in the cryoprecipitate production process, BP.TT; 24/03257-7 - Communication, Graphic Design and Platform Management, BP.TT; 24/00072-6 - Breaking the boundaries between the University and Society through Scientific Journalism: CTS-CEVAP Scientific Diffusion, BP.JC; 23/00973-0 - Evaluation of in vitro response to treatment with Melittin from Apis mellifera venom in cancer stem cells of canine osteosarcoma, BP.MS; 23/11311-9 - Expression and PEGylation of Ts15, an alpha-KTx from Tityus serrulatus venom, and evaluation of its immunosuppressive action, BP.PD; 22/16060-1 - From mechanisms to biomarkers of envenoming by Brazilian snakes: a multicentric study for the development of strategies in diagnosis and monitoring, BP.DR; 23/11264-0 - Production by heterologous expression on Pichia pastoris and evaluation of the efficacy of a vascular endothelial growth factor and a serineprotease from snake venom, for the production of a new biopolimer with adhesive capacity, BP.PD; 23/08872-9 - Expression and characterization of single-chain variable fragments (scFv) intrinsically fluorescents for SARS-COV-2 detection., BP.PD; 23/05461-8 - Science communication from the Center for Translational Science and Development of Biopharmaceuticals, BP.JC; 22/05566-1 - Construction and selection of a library of scFv monoclonal antibodies against the SARS-CoV-2 spike protein by Phage Display technology, BP.DR - associated scholarships

Abstract

Technological advances are continually emerging to improve the discovery, rational modification, production and purification of biopharmaceuticals. The identification of different species of microorganisms from Brazilian biodiversity, using innovative strategies, should be carried out with a view to discovering alternative hosts for heterologous expression. The Center for the Study of Poisons and Poisonous Animals (CEVAP) - Translational Research Unit at UNESP - has been prospecting and developing candidate molecules for the production of biopharmaceuticals since its foundation. Two bioproducts named respectively "Fibrin Sealant" and "Antiapeptic Serum" were developed by our team and have already crossed the "Valley of Death", and are awaiting investments for phase III clinical research and subsequent registration with ANVISA for distribution in the System's network Health Service (SUS). To meet the last stage of phase III research, the product needs Good Manufacturing Practices. To overcome this challenge, the researchers submitted to the Ministry of Health the construction of the Pilot Batch Factory for Biopharmaceuticals for Clinical Research, the only one in Latin America, which was approved and tendered by UNESP in August 2021 at the amount of R$ 12,222,222.20 . This Factory-School will meet internal demands, from other research institutions in Brazil, as well as from abroad, as it will function as a CDMO (Contract Development and Manufacturing Organization). The Translational Science and Biopharmaceutical Development Center proposed in this project, in addition to continuing existing products, will develop and implement platforms for prototyping recombinant molecules for a new fibrin 2.0 sealant to improve its performance as a wound healing agent; to research and produce mono and polyclonal antibodies against Sars-Cov-2, and finally to implement a platform for serological diagnosis against COVID-19 based on recombinant antigens. Antibody production and serological diagnosis technologies can be transferred to meet other viral diseases given the versatility and applicability of the proposal. In order to make the project viable, the applicants based at UNESP (Headquarter Unit), USP and Biological Institutes, Adolfo Lutz and Emilio Ribas (Partner Institutions), in addition to collaborating foreign institutions will put their greatest efforts to achieve the established goals and implement the projects and proposed subprojects. We will also have the participation of visiting researchers from KU Leuven from Belgium, and SRM University Delhi-NCR from India. The economic and financial counterparts are respectively R$ 10,280,728.92 and R$ 25,808,341.92, in addition to the UNESP commitment to hire 3 researchers and 3 technicians in the amount of R$ 4,056,378.75 for the project period. FAPESP will be responsible for the total amount of R$ 9,780,662.81, including for equipment only R$ 89,052.00 (domestic) and U$ 89,277.14 (imported) - already included in the total value of the project. (AU)

Scientific publications

(31)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CLEUBER RODRIGO DE SOUZA BUENO; DANIELA VIEIRA BUCHAIM; BENEDITO BARRAVIERA; RUI SEABRA FERREIRA JR.; PAULO SÉRGIO DA SILVA SANTOS; CARLOS HENRIQUE BERTONI REIS; MARCELO AUGUSTO CINI; MILTON CARLOS KUGA; GERALDO MARCO ROSA JUNIOR; ROGERIO LEONE BUCHAIM. Delayed repair of the facial nerve and its negative impacts on nerve and muscle regeneration. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 30, 2024-05-27. (21/11936-3)

CAVALCANTE, JOELITON DOS SANTOS; DE ALMEIDA, DENIS EMANUEL GARCIA; MORAES, MICAEL SAGGION; SANTOS, SOPHIA RIBEIRO; PINCINATO, PEDRO MORIEL; RICIOPO, PEDRO MARQUES; DE OLIVEIRA, LAIS LACERDA B.; MONTEIRO, WUELTON MARCELO; FERREIRA-JUNIOR, RUI SEABRA. Challenges and Opportunities in Clinical Diagnostic Routine of Envenomation Using Blood Plasma Proteomics. TOXINS, v. 15, n. 3, p. 17-pg., 2023-03-01. (21/11936-3)

CAVALCANTE, JOELITON S.; DE ALMEIDA, DENIS EMANUEL GARCIA; SANTOS-FILHO, NORIVAL A.; SARTIM, MARCO AURELIO; BALDO, AMANDA DE ALMEIDA; BRASILEIRO, LISELE; ALBUQUERQUE, POLIANNA L.; OLIVEIRA, SAMELLA S.; SACHETT, JACQUELINE ALMEIDA GONCALVES; MONTEIRO, WUELTON MARCELO; et al. Crosstalk of Inflammation and Coagulation in Bothrops Snakebite Envenoming: Endogenous Signaling Pathways and Pathophysiology. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 14, p. 26-pg., 2023-07-01. (21/11936-3)

FERREIRA, ISABELA; OLIVEIRA, ISADORA; BORDON, KARLA; REIS, MOUZARLLEM; WIEZEL, GISELE; SANCHEZ, CAROLINE; SANTOS, LUISA; SANTOS-FILHO, NORIVAL; PUCCA, MANUELA; ANTUNES, LUSANIA; et al. Beyond Angiogenesis: The Multitasking Approach of the First PEGylated Vascular Endothelial Growth Factor (CdtVEGF) from Brazilian Rattlesnake Venom. TOXINS, v. 15, n. 8, p. 21-pg., 2023-08-01. (20/13176-3, 21/11936-3, 17/00586-6, 19/10173-6)

NATALIA SCANAVACHIA DA SILVA; JULIA LOMBARDI; FRANK KIRCHHOFF; RUI SEABRA FERREIRA JR.; BENEDITO BARRAVIERA; ALEXANDRE LEITE RODRIGUES DE OLIVEIRA; LUCIANA POLITTI CARTAROZZI. Effects of local and systemic treatment with human natural killer-1 mimetic peptide (HNK-1) after ventral root avulsion and reimplantation in mice. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 30, 2024-05-20. (20/01215-4, 18/05006-0, 22/06609-6, 21/11936-3)

GELINSKI KEMPE, PAULA REGINA; DE CASTRO, MATEUS VIDIGAL; COSER, LILIAN DE OLIVEIRA; CARTAROZZI, LUCIANA POLITTI; BARRAVIERA, BENEDITO; FERREIRA JR, RUI SEABRA; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. Combination of Adult Mesenchymal Stem Cell Therapy and Immunomodulation with Dimethyl Fumarate Following Spinal Cord Ventral Root Repair. BIOLOGY-BASEL, v. 13, n. 11, p. 18-pg., 2024-11-01. (18/05006-0, 21/11936-3, 18/25845-7)

WIEZEL, GISELE A.; OLIVEIRA, ISADORA S.; FERREIRA, ISABELA G.; BORDON, KARLA C. F.; ARANTES, ELIANE C.. Hyperglycosylation impairs the inhibitory activity of rCdtPLI2, the first recombinant beta-phospholipase A₂ inhibitor. International Journal of Biological Macromolecules, v. 280, p. 12-pg., 2024-09-22. (21/11936-3, 09/54098-6, 19/10173-6, 20/13176-3, 17/00586-6)

KEMPE, PAULA REGINA GELINSKI; DE CASTRO, MATEUS VIDIGAL; KHURIYEH, VICTOR CAMPOS; BARRAVIERA, BENEDITO; FERREIRA JR, RUI SEABRA; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. Ultrastructural Evidence of Synapse Preservation and Axonal Regeneration Following Spinal Root Repair with Fibrin Biopolymer and Therapy with Dimethyl Fumarate. POLYMERS, v. 15, n. 15, p. 20-pg., 2023-08-01. (18/05006-0, 21/11936-3, 16/25478-9, 18/25845-7)

BUENO, CLEUBER RODRIGO DE SOUZA; BUCHAIM, DANIELA VIEIRA; BARRAVIERA, BENEDITO; FERREIRA JR, RUI SEABRA; SANTOS, PAULO SERGIO DA SILVA; REIS, CARLOS HENRIQUE BERTONI; CINI, MARCELO AUGUSTO; KUGA, MILTON CARLOS; ROSA JUNIOR, GERALDO MARCO; BUCHAIM, ROGERIO LEONE. Delayed repair of the facial nerve and its negative impacts on nerve and muscle. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 30, p. 14-pg., 2024-05-27. (21/11936-3)

FIGUEIREDO BORDON, KARLA DE CASTRO; ACOSTA, LETICIA; VARGAS RECHIA, CAREM GLEDES; ARANTES, ELIANE CANDIANI. ENZYMATIC CHARACTERIZATION OF PROTEASES AND AMYLASES FROM TITYUS SERRULATUS VENOM. Toxicon, v. 248, p. 1-pg., 2024-09-01. (21/11936-3, 23/01083-9)

WIEZEL, GISELE A.; OLIVEIRA, ISADORA S.; REIS, MOUZARLLEM B.; FERREIRA, ISABELA G.; CORDEIRO, KALYNKA R.; BORDON, KARLA C. F.; ARANTES, ELIANE C.. The complex repertoire of Tityus spp. venoms: Advances on their composition and pharmacological potential of their toxins. Biochimie, v. 220, p. 23-pg., 2024-01-11. (23/11264-0, 21/11936-3, 20/13176-3, 22/08964-8, 23/01083-9, 23/10400-8)

DE ALEXANDRIA, FRANCISCO EUGENIO DEUSDARA; SILVA, NALDIANA CERQUEIRA; ASSIS, LIVIA; MAIA FILHO, ANTONIO LUIZ MARTINS; KIDO, HUELITON WILIAN; TAROCCO, JULIANA CAROLINA; FERREIRA, RUI SEABRA; BARRAVIERA, BENEDITO; PARIZOTTO, NIVALDO ANTONIO; SILVA, JOSE FIGUEIREDO; et al. Diabetic rats skin wounds treated with heterologous fibrin sealant followed by photobiomodulation therapy. Lasers in Medical Science, v. 39, n. 1, p. 10-pg., 2024-11-15. (21/11936-3)

JACOB, B. C.; CORDEIRO, F. A.; WIEZEL, G. A.; CARDOSO, I. A.; PINHEIRO-JUNIOR, E. L.; ROSA, M. H.; BORDON, K. C.; ALVES-FILHO, J. C.; TYTGAT, J.; ARANTES, E. C.. Heterologous expression of the α-Ktx Ts7 and its functional evaluation on Kv channels and CD4+T cell differentiation. Toxicology Letters, v. 384, p. 1-pg., 2023-09-01. (21/11936-3)

OLIVEIRA, ISADORA; FERREIRA, ISABELA; JACOB, BEATRIZ; CARDENAS, KIARA; CERNI, FELIPE; BAIA-DA-SILVA, DJANE; ARANTES, ELIANE; MONTEIRO, WUELTON; PUCCA, MANUELA. Harnessing the Power of Venomous Animal-Derived Toxins against COVID-19. TOXINS, v. 15, n. 2, p. 12-pg., 2023-02-01. (20/13176-3, 21/11936-3, 19/10173-6)

PORTILHO, AMANDA IZELI; DA COSTA, HERNAN HERMES MONTEIRO; GUERESCHI, MARCIA GRANDO; PRUDENCIO, CARLOS ROBERTO; DE GASPARI, ELIZABETH. Hybrid response to SARS-CoV-2 and Neisseria meningitidis C after an OMV-adjuvanted immunization in mice and their offspring. HUMAN VACCINES & IMMUNOTHERAPEUTICS, v. 20, n. 1, p. 11-pg., 2024-12-31. (18/04202-0, 21/11936-3, 22/05566-1)

MARTINS, JONAS GAMA; REIS, MOUZARLLEM BARROS; ZUANAZZI, BEATRIZ ACQUARONI; BORDON, KARLA DE CASTRO FIGUEIREDO; ZOCCAL, KARINA FURLANI; PROCOPIO, RUDI EMERSON DE LIMA; ARANTES, ELIANE CANDIANI. Clinical outcomes in a murine model after envenoming by the Amazonian scorpions Tityus strandi and Tityus dinizi. Toxicon, v. 246, p. 8-pg., 2024-06-10. (21/11936-3, 23/01083-9)

ALANO-DA-SILVA, NICOLY MALACHIZE; DE OLIVEIRA, ISADORA SOUSA; CARDOSO, IARA AIME; BORDON, KARLA DE CASTRO FIGUEIREDO; ARANTES, ELIANE CANDIANI. Exploring high molecular weight components in Tityus serrulatus venom. Toxicon, v. 255, p. 5-pg., 2025-01-17. (20/13176-3, 19/10173-6, 21/11547-7, 21/11936-3, 22/08964-8)

REIS, MOUZARLLEM BARROS; ARANTES, ELIANE CANDIANI. Immunosuppressive therapies in scorpion envenomation: new perspectives for treatment. FRONTIERS IN TOXICOLOGY, v. 6, p. 6-pg., 2024-11-19. (21/11936-3, 23/01083-9, 23/10400-8)

CAVALCANTE, JOELITON S.; RICIOPO, PEDRO MARQUES; PEREIRA, ANA FLAVIA MARQUES; JERONIMO, BRUNA CRISTINA; ANGSTMAM, DAVI GOMES; POSSAS, FELIPE CARVALHAES; DE ANDRADE FILHO, ADEBAL; CERNI, FELIPE A.; PUCCA, MANUELA B.; FERREIRA JUNIOR, RUI SEABRA. Clinical complications in envenoming by Apis honeybee stings: insights into mechanisms, diagnosis, and pharmacological interventions. FRONTIERS IN IMMUNOLOGY, v. 15, p. 18-pg., 2024-09-18. (23/01554-1, 23/09921-3, 21/11936-3, 22/16060-1)

MINATEL, VITORIA MENEGHETTI; PRUDENCIO, CARLOS ROBERTO; BARRAVIERA, BENEDITO; FERREIRA JR, RUI SEABRA. Nanobodies: a promising approach to treatment of viral diseases. FRONTIERS IN IMMUNOLOGY, v. 14, p. 19-pg., 2024-01-23. (21/11936-3)

PORTILHO, AMANDA IZELI; SILVA, VALERIA OLIVEIRA; DA COSTA, HERNAN HERMES MONTEIRO; YAMASHIRO, ROSEMEIRE; DE OLIVEIRA, ISABELA PENTERICHE; DE CAMPOS, IVANA BARROS; PRUDENCIO, CARLOS ROBERTO; MATSUDA, ELAINE MONTEIRO; BRIGIDO, LUIS FERNANDO DE MACEDO; DE GASPARI, ELIZABETH. An unexpected IgE anti-receptor binding domain response following natural infection and different types of SARS-CoV-2 vaccines. SCIENTIFIC REPORTS, v. 14, n. 1, p. 12-pg., 2024-08-28. (18/04202-0, 21/11936-3, 22/05566-1, 18/14384-9)

ISADORA SOUSA DE OLIVEIRA; NICOLY MALACHIZE ALANO-DA-SILVA; ISABELA GOBBO FERREIRA; FELIPE AUGUSTO CERNI; JACQUELINE DE ALMEIDA GONÇALVES SACHETT; WUELTON MARCELO MONTEIRO; MANUELA BERTO PUCCA; ELIANE CANDIANI ARANTES. Understanding the complexity of Tityus serrulatus venom: A focus on high molecular weight components. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 30, 2024-01-22. (19/10173-6, 21/11936-3, 22/08964-8, 21/11547-7, 20/13176-3)

GABRIELA DE OLIVEIRA ALMEIDA; ISADORA SOUSA DE OLIVEIRA; ELIANE CANDIANI ARANTES; SUELY VILELA SAMPAIO. Snake venom disintegrins update: insights about new findings. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 29, 2023-09-18. (19/10173-6, 22/05554-3, 20/15670-5, 21/11936-3, 22/04804-6, 22/08964-8, 20/13176-3)

KEVIN SILVA MULLER; FELIPE CANTORE TIBÚRCIO; RUI SEABRA FERREIRA JUNIOR; BENEDITO BARRAVIERA; SELMA MARIA MICHELIN MATHEUS. Heterologous fibrin biopolymer as an emerging approach to peripheral nerve repair: a scoping review. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 30, 2024-04-15. (21/11936-3)

BUENO, CLEUBER RODRIGO DE SOUZA; TONIN, MARIA CLARA CASSOLA; BUCHAIM, DANIELA VIEIRA; BARRAVIERA, BENEDITO; FERREIRA JR, RUI SEABRA; SANTOS, PAULO SERGIO DA SILVA; REIS, CARLOS HENRIQUE BERTONI; PASTORI, CLAUDIO MALDONADO; PEREIRA, ELIANA DE SOUZA BASTOS MAZUQUELI; NOGUEIRA, DAYANE MARIA BRAZ; et al. Morphofunctional Improvement of the Facial Nerve and Muscles with Repair Using Heterologous Fibrin Biopolymer and Photobiomodulation. PHARMACEUTICALS, v. 16, n. 5, p. 18-pg., 2023-04-27. (21/11936-3)

WIEZEL, GISELE ADRIANO; OLIVEIRA, ISADORA SOUSA DE; ARANTES, ELIANE CANDIANI. Simplifying traditional approaches for accessible analysis of snake venom enzymes. Toxicon, v. 255, p. 5-pg., 2025-01-22. (20/13176-3, 17/00586-6, 21/11936-3, 19/10173-6)

OYADOMARI, WILLIAM Y.; CARVALHO, ELIZANGELA A.; MACHADO, GABRIEL E.; MACHADO, ANA JULIA O.; SANTOS, GABRIEL S.; MARCONDES, MARCELO; OLIVEIRA, VITOR. Towards a Survival-Based Cellular Assay for the Selection of Protease Inhibitors in Escherichia coli. BIOTECH, v. 14, n. 1, p. 10-pg., 2025-03-07. (23/07904-4, 20/09678-3, 21/11936-3, 23/09167-7)

DE MELLO, MARCELA M. BLASCKE; NEVES, VIVIANO GOMES DE OLIVEIRA; PARENTE, JULIANA MONTENEGRO; PERNOMIAN, LAENA; DE OLIVEIRA, ISADORA SOUSA; PEDERSOLI, CARINA AMARANTE; AWATA, WANESSA MAYUMI CARVALHO; TIRAPELLI, CARLOS RENATO; ARANTES, ELIANE CANDIANI; TOSTES, RITA DE CASSIA A.; et al. Sarcoplasmic reticulum calcium ATPase (SERCA) proteolysis by matrix metalloproteinase-2 contributes to vascular dysfunction in early hypertension. European Journal of Pharmacology, v. 983, p. 9-pg., 2024-09-07. (19/09174-8, 21/11936-3, 20/13176-3, 20/02619-1, 22/04888-5)

CAVALCANTE, JOELITON S.; ARRUDA, SABRINA SANTANA TOLEDO; RICIOPO, PEDRO MARQUES; PUCCA, MANUELA; FERREIRA JR, RUI SEABRA. Diagnosis of human envenoming by terrestrial venomous animals: Routine, advances, and perspectives. TOXICON-X, v. 24, p. 13-pg., 2024-10-24. (21/11936-3)

DA COSTA, HERNAN HERMES MONTEIRO; SILVA, VALERIA OLIVEIRA; AMORIM, GUSTAVO CARVALHO; GUERESCHI, MARCIA GRANDO; SERGIO, LUCIANA MARCIANO; GOMES, CARLOS HENRIQUE RODRIGUES; HONG, MARISA AILIN; DE OLIVEIRA, ELAINE LOPES; BRIGIDO, LUIS FERNANDO DE MACEDO; LINDOSO, JOSE ANGELO LAULETTA; et al. Assessment of an in-house IgG ELISA targeting SARS-CoV-2 RBD: Applications in infected and vaccinated individuals. JOURNAL OF IMMUNOLOGICAL METHODS, v. 530, p. 12-pg., 2024-05-22. (23/13212-8, 21/11936-3, 23/06453-9, 22/05566-1)

DA COSTA, HERNAN H. M.; BIELAVSKY, MONICA; ORTS, DIEGO J. B.; ARAUJO, SERGIO; ADRIANI, PATRICIA P.; NOGUEIRA, JULIANA S.; ASTRAY, RENATO M.; PANDEY, RAMENDRA P.; LANCELLOTTI, MARCELO; CUNHA-JUNIOR, JAIR P.; et al. Production of Recombinant Zika Virus Envelope Protein by Airlift Bioreactor as a New Subunit Vaccine Platform. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 18, p. 25-pg., 2023-09-01. (22/07256-0, 21/11936-3, 17/50333-7)