Sepsis: mechanisms, therapeutic targets and epidemiology

• Grant number: 17/21052-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: July 01, 2018
• End date: June 30, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Reinaldo Salomão
• Grantee: Reinaldo Salomão
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Pesquisadores principais: Flavia Ribeiro Machado ; Ivan Hong Jun Koh ; Luciano Cesar Pontes de Azevedo
• Associated researchers: Alexandre Keiji Tashima ; Ana Maria Alvim Liberatore ; Francisco Garcia Soriano ; Milena Karina Coló Brunialti
• Associated research grant(s): 20/05110-2 - Prospective cohort study to assess clinical, virological and host response aspects in patients with COVID-19, AP.R
• Associated scholarship(s): 23/15909-6 - Proteomic and Metabolic Analysis of Neutrophils from Septic Patients, BP.DR; 23/15714-0 - DNA repair, oxidative stress and metabolic dysfunction in sepsis - investigation of a possible therapeutic target, BP.TT; 23/14396-5 - Epidemiological profile of sepsis and septic shock in pediatric critical care units in Latin America, BP.TT; + associated scholarships 23/07392-3 - Study of the interrelationship between angiosomes and their dysfunction in kidney and liver organs in acute sepsis and in sepsis survivors, BP.IC; 22/16857-7 - Kinetic study of bacterial translocation in sepsis survivors. Experimental research in rats, BP.IC; 22/13073-5 - Molecular signature related to low density neutrophils in different types of infections, BP.IC; 22/12847-7 - Molecular signature related to low density neutrophils in different types of infections., BP.IC; 22/02423-5 - Study of body thermal response and its correlation with the pattern of circulatory dynamics in sepsis survivors: experimental study in rats, BP.IC; 20/16407-6 - Study of the body thermal response during a hyperacute phase of sepsis and its correlation with mortality in rats, BP.IC; 20/16408-2 - Study of the body thermal response during a hyperacute phase of septic shock and its correlation with mortality in rats, BP.IC; 20/05077-5 - Changes in energy metabolism of endotoxin tolerant peripheral blood mononuclear cells, BP.MS; 20/01034-0 - Computational analysis for the diagnosis of organ dysfunction in Sepsis based on microcirculatory hemodynamics, BP.PD; 19/20532-3 - Quantitative proteomic analysis in mononuclear (PBMC) and polymorphonuclear (PMN) cell samples from patients with Sepsis and healthy volunteers, focusing on proteins related to energy and oxidative metabolism, as well as mitochondrial function, BP.PD; 19/01135-3 - Study of the pattern of circulatory dynamics in sepsis survivors: experimental research in rats, BP.IC; 18/24189-9 - Epidemiological profile of patients with sepsis in Brazil: emergency units for intensive care units, BP.TT; 18/18418-5 - DNA repair, oxidative stress and metabolic dysfunction in sepsis - investigation of possible therapeutic target, BP.PD; 18/19855-0 - Evaluation of cellular metabolism in endotoxin tolerant peripheral blood mononuclear cells, BP.IC - associated scholarships

Abstract

In Brazil, about one-third of the intensive care beds are occupied by septic patients, with a mortality rate of 55.7% compared to the 26% worldwide averages reported recently. In this project we intend to integrate basic and clinical research in Sepsis, ranging from the pathogenesis and development of intervention strategies to epidemiological studies that allow us to know the reality of sepsis in our country. The project covers three lines of research: experimental, translational and epidemiological research. These lines are structured in three integrated axes of action: 1- translational research: we settled a network of hospitals, which will prospectively monitor patients with Sepsis, with storage of clinical and epidemiological information. Biological samples of the patients will be processed in the immunology laboratory, where studies of gene expression, protein and cellular function will be conducted with a focus on immunometabolism; a possible therapeutic target should be tested in an intervention - proof of concept; 2 - experimental research: models of animal experimentation and computational modeling where new hypotheses and potential therapeutic targets will be evaluated; 3- epidemiological studies will be conducted in association with a network of researchers from emergency and intensive care units to characterize demographic data on Sepsis in Brazil. (AU)

Scientific publications

(15)

(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)

ADRIANA SIMIZO; EDUARDO S. KITANO; SÁVIO S. SANTANNA; KATHLEEN FERNANDES GREGO; ANITA MITICO TANAKA-AZEVEDO; ALEXANDRE K. TASHIMA. Comparative gender peptidomics of Bothrops atrox venoms: are there differences between them?. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, 2020-10-07. (17/20106-9, 17/21052-0, 18/25786-0, 19/03502-3)

MILANEZ, M. I. O.; LIBERATORE, A. M. A.; NISHI, E. E.; BERGAMASCHI, C. T.; CAMPOS, R. R.; KOH, I. H. J.. atterns of renal and splanchnic sympathetic vasomotor activity in an animal model of survival to experimental sepsi. Brazilian Journal of Medical and Biological Research, v. 55, n. 1, 2022. (17/21052-0, 18/02671-3, 18/01898-4)

SALOMAO, R.; FERREIRA, B. L.; SALOMAO, M. C.; SANTOS, S. S.; AZEVEDO, L. C. P.; BRUNIALTI, M. K. C.. Sepsis: evolving concepts and challenges. Brazilian Journal of Medical and Biological Research, v. 52, n. 4, 2019. (17/21052-0)

SANTOS, SIDNEIA SOUSA; BRUNIALTI, MILENA KARINA COLO; RODRIGUES, LARISSA DE OLIVEIRA CAVALCANTI PERES; LIBERATORE, ANA MARIA ALVIM; KOH, IVAN HONG JUN; MARTINS, VANESSA; SORIANO, FRANCISCO GARCIA; SZABO, CSABA; SALOMAO, REINALDO. Effects of the PARP Inhibitor Olaparib on the Response of Human Peripheral Blood Leukocytes to Bacterial Challenge or Oxidative Stress. BIOMOLECULES, v. 12, n. 6, p. 16-pg., 2022-06-01. (18/18418-5, 17/21052-0)

FIGUEREIDO LEITE, GIUSEPPE GIANINI; SCICLUNA, BRENDON P.; VAN DER POLL, TOM; SALOMAO, REINALDO. Genetic signature related to heme-hemoglobin metabolism pathway in sepsis secondary to pneumonia. NPJ SYSTEMS BIOLOGY AND APPLICATIONS, v. 5, AUG 1 2019. (17/21052-0)

CAMARA, GUILHERME A.; NISHIYAMA-JR, MILTON Y.; KITANO, EDUARDO S.; OLIVEIRA, URSULA C.; DA SILVA, JR., PEDRO I.; JUNQUEIRA-DE-AZEVEDO, INACIO L.; TASHIMA, ALEXANDRE K.. A Multiomics Approach Unravels New Toxins With PossibleIn SilicoAntimicrobial, Antiviral, and Antitumoral Activities in the Venom ofAcanthoscurria rondoniae. FRONTIERS IN PHARMACOLOGY, v. 11, JUL 17 2020. (17/21052-0, 15/50040-4)

FERREIRA, BIANCA LIMA; SOUSA, MONICA BRAGANCA; LEITE, GIUSEPPE GIANINI FIGUEIREDO; BRUNIALTI, MILENA KARINA COLO; NISHIDUKA, ERIKA SAYURI; TASHIMA, ALEXANDRE KEIJI; VAN DER POLL, TOM; SALOMAO, REINALDO. Glucose metabolism is upregulated in the mononuclear cell proteome during sepsis and supports endotoxin-tolerant cell function. FRONTIERS IN IMMUNOLOGY, v. 13, p. 10-pg., 2022-11-18. (16/13855-2, 20/05077-5, 17/21052-0, 19/20532-3)

FALCAO-HOLANDA, RENATA BRITO; KARINA COLO, BRUNIALTI MILENA; JASIULIONIS, MIRIAM GALVONAS; SALOMAO, REINALDO. Epigenetic Regulation in Sepsis, Role in Pathophysiology and Therapeutic Perspective. FRONTIERS IN MEDICINE, v. 8, JUL 12 2021. (17/21052-0)

FERREIRA, BIANCA LIMA; FIGUEIREDO LEITE, GIUSEPPE GIANINI; COLO BRUNIALTI, MILENA KARINA; ASSUNCAO, MURILLO; PONTES AZEVEDO, LUCIANO CESAR; FREITAS, FLAVIO; SALOMAO, REINALDO. HIF-1 alpha and Hypoxia Responsive Genes are Differentially Expressed in Leukocytes From Survivors and Non-Survivors Patients During Clinical Sepsis. Shock, v. 56, n. 1, p. 80-91, JUL 2021. (17/21052-0, 16/13855-2)

DE SOUZA, DANIELA CARLA; MARTIN, JOELMA GONCALVES; LANZIOTTI, VANESSA SOARES; DE OLIVEIRA, CLAUDIO FLAUZINO; TONIAL, CRISTIAN; DE CARVALHO, WERTHER BRUNOW; FIORETTO, JOSE ROBERTO; PIVA, JEFFERSON PEDRO; TROSTER, EDUARDO JUAN; BOSSA, ALINE SIQUEIRA; et al. he epidemiology of sepsis in paediatric intensive care units in Brazil (the Sepsis PREvalence Assessment Database in Pediatric population, SPREAD PED): an observational stud. LANCET CHILD & ADOLESCENT HEALTH, v. 5, n. 12, p. 873-881, DEC 2021. (17/21052-0)

PECANHA-PIETROBOM, PAULA M.; FIGUEIREDO LEITE, GIUSEPPE GIANINI; HUNTER, JAMES; ABRAO FERREIRA, PAULO R.; BURATTINI, MARCELO N.; BELLEI, NANCY; OTA-ARAKAKI, JAQUELINA SONOE; SALOMAO, REINALDO. he clinical course of hospitalized moderately ill COVID-19 patients is mirrored by routine hematologic tests and influenced by renal transplantatio. PLoS One, v. 16, n. 11, NOV 18 2021. (20/05110-2, 17/21052-0)

SANTOS, SIDNEIA SOUSA; COLO BRUNIALTI, MILENA KARINA; SORIANO, FRANCISCO GARCIA; SZABO, CSABA; SALOMAO, REINALDO. Repurposing of Clinically Approved Poly-(ADP-Ribose) Polymerase Inhibitors for the Therapy of Sepsis. Shock, v. 56, n. 6, p. 901-909, DEC 2021. (18/18418-5, 17/21052-0)

MACHADO, FLAVIA R.; CAVALCANTI, ALEXANDRE; BRAGA, MARIA; TALLO, FERNANDO; BOSSA, ALINE; SOUZA, JULIANA; FERREIRA, JOSIANE; PIZZOL, FELIPE DAL; MONTEIRO, MARIANA; ANGUS, DEREK; et al. Sepsis in Brazilian emergency departments: a prospective multicenter observational study. Internal and Emergency Medicine, v. N/A, p. 13-pg., 2023-02-02. (17/21052-0)

FIGUEIREDO LEITE, GIUSEPPE GIANINI; FERREIRA, BIANCA LIMA; TASHIMA, ALEXANDRE KEIJI; NISHIDUKA, ERIKA SAYURI; CUNHA-NETO, EDECIO; COLO BRUNIALTI, MILENA KARINA; ASSUNCAO, MURILLO; PONTES AZEVEDO, LUCIANO CESAR; FREITAS, FLAVIO; VAN DER POLL, TOM; et al. Combined Transcriptome and Proteome Leukocyte's Profiling Reveals Up-Regulated Module of Genes/Proteins Related to Low Density Neutrophils and Impaired Transcription and Translation Processes in Clinical Sepsis. FRONTIERS IN IMMUNOLOGY, v. 12, SEP 10 2021. (19/20532-3, 17/21052-0, 16/13855-2)

VENANCIO DE LIMA, EDUARDO OLIVEIRA; TASIMA, LIDIA JORGE; HATAKEYAMA, DANIELA MIKI; SERINO-SILVA, CAROLINE; BITTENCOURT RODRIGUES, CAROLINE FABRI; GALIZIO, NATHALIA DA COSTA; CHIARELLI, TASSIA; NISHIDUKA, ERIKA SAYURI; TEIXEIRA DA ROCHA, MARISA MARIA; SANT'ANNA, SAVIO STEFANINI; et al. Snake venom color and L-amino acid oxidase: An evidence of long-term captive Crotalus durissus terrificus venom plasticity. Toxicon, v. 193, p. 73-83, APR 15 2021. (18/25786-0, 14/11108-0, 17/01890-0, 16/09976-9, 17/20106-9, 17/21052-0, 17/16908-2, 18/14724-4)