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Article ; Online: High mobility group box 1, ATP, lipid mediators, and tissue factor are elevated in COVID-19 patients: HMGB1 as a biomarker of worst prognosis.

Vicentino, Amanda Roberta Revoredo / Fraga-Junior, Vanderlei da Silva / Palazzo, Matheus / Tasmo, Natalia Recardo Amorim / Rodrigues, Danielle A S / Barroso, Shana Priscila Coutinho / Ferreira, Sâmila Natiane / Neves-Borges, Anna Cristina / Allonso, Diego / Fantappié, Marcelo Rosado / Scharfstein, Julio / Oliveira, Ana Carolina / Vianna-Jorge, Rosane / Vale, André Macedo / Coutinho-Silva, Robson / Savio, Luiz Eduardo Baggio / Canetti, Claudio / Benjamim, Claudia Farias

Clinical and translational science

2023 Volume 16, Issue 4, Page(s) 631–646

Abstract: The severe acute respiratory syndrome coronavirus 2, the agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, has spread worldwide since it was first identified in November 2019 in Wuhan, China. Since then, progress in pathogenesis linked ... ...

Abstract	The severe acute respiratory syndrome coronavirus 2, the agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, has spread worldwide since it was first identified in November 2019 in Wuhan, China. Since then, progress in pathogenesis linked severity of this systemic disease to the hyperactivation of network of cytokine-driven pro-inflammatory cascades. Here, we aimed to identify molecular biomarkers of disease severity by measuring the serum levels of inflammatory mediators in a Brazilian cohort of patients with COVID-19 and healthy controls (HCs). Critically ill patients in the intensive care unit were defined as such by dependence on oxygen supplementation (93% intubated and 7% face mask), and computed tomography profiles showing ground-glass opacity pneumonia associated to and high levels of D-dimer. Our panel of mediators included HMGB1, ATP, tissue factor, PGE
MeSH term(s)	Humans ; Thromboplastin ; COVID-19/diagnosis ; HMGB1 Protein ; Biomarkers ; Prognosis ; Lipids ; Adenosine Triphosphate
Chemical Substances	Thromboplastin (9035-58-9) ; HMGB1 Protein ; Biomarkers ; Lipids ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2023-01-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2433157-0
ISSN	1752-8062 ; 1752-8054
ISSN (online)	1752-8062
ISSN	1752-8054
DOI	10.1111/cts.13475
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Translational Strategies for Repotrectinib in Neuroblastoma.

O'Donohue, Tara J / Ibáñez, Glorymar / Coutinho, Diego Ferreira / Mauguen, Audrey / Siddiquee, Armaan / Rosales, Nestor / Calder, Paul / Ndengu, Andoyo / You, Daoqi / Long, Matthew / Roberts, Stephen S / Kung, Andrew L / Dela Cruz, Filemon S

Molecular cancer therapeutics

2021 Volume 20, Issue 11, Page(s) 2189–2197

Abstract: Limited clinical data are available regarding the utility of multikinase inhibition in neuroblastoma. Repotrectinib (TPX-0005) is a multikinase inhibitor that targets ALK, TRK, JAK2/STAT, and Src/FAK, which have all been implicated in the pathogenesis of ...

Abstract	Limited clinical data are available regarding the utility of multikinase inhibition in neuroblastoma. Repotrectinib (TPX-0005) is a multikinase inhibitor that targets ALK, TRK, JAK2/STAT, and Src/FAK, which have all been implicated in the pathogenesis of neuroblastoma. We evaluated the preclinical activity of repotrectinib monotherapy and in combination with chemotherapy as a potential therapeutic approach for relapsed/refractory neuroblastoma.
MeSH term(s)	Animals ; Humans ; Macrocyclic Compounds/pharmacology ; Macrocyclic Compounds/therapeutic use ; Mice ; Neuroblastoma/drug therapy ; Neuroblastoma/pathology ; Pyrazoles/pharmacology ; Pyrazoles/therapeutic use
Chemical Substances	Macrocyclic Compounds ; Pyrazoles ; repotrectinib (08O3FQ4UNP)
Language	English
Publishing date	2021-09-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-21-0126
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Article ; Online: High mobility group box 1, ATP, lipid mediators, and tissue factor are elevated in COVID‐19 patients

Amanda Roberta Revoredo Vicentino / Vanderlei da Silva Fraga‐Junior / Matheus Palazzo / Natalia Recardo Amorim Tasmo / Danielle A. S. Rodrigues / Shana Priscila Coutinho Barroso / Sâmila Natiane Ferreira / Anna Cristina Neves‐Borges / Diego Allonso / Marcelo Rosado Fantappié / Julio Scharfstein / Ana Carolina Oliveira / Rosane Vianna‐Jorge / André Macedo Vale / Robson Coutinho‐Silva / Luiz Eduardo Baggio Savio / Claudio Canetti / Claudia Farias Benjamim

Clinical and Translational Science, Vol 16, Iss 4, Pp 631-

HMGB1 as a biomarker of worst prognosis

2023 Volume 646

Abstract: Abstract The severe acute respiratory syndrome coronavirus 2, the agent of the ongoing coronavirus disease 2019 (COVID‐19) pandemic, has spread worldwide since it was first identified in November 2019 in Wuhan, China. Since then, progress in pathogenesis ...

Abstract	Abstract The severe acute respiratory syndrome coronavirus 2, the agent of the ongoing coronavirus disease 2019 (COVID‐19) pandemic, has spread worldwide since it was first identified in November 2019 in Wuhan, China. Since then, progress in pathogenesis linked severity of this systemic disease to the hyperactivation of network of cytokine‐driven pro‐inflammatory cascades. Here, we aimed to identify molecular biomarkers of disease severity by measuring the serum levels of inflammatory mediators in a Brazilian cohort of patients with COVID‐19 and healthy controls (HCs). Critically ill patients in the intensive care unit were defined as such by dependence on oxygen supplementation (93% intubated and 7% face mask), and computed tomography profiles showing ground‐glass opacity pneumonia associated to and high levels of D‐dimer. Our panel of mediators included HMGB1, ATP, tissue factor, PGE2, LTB4, and cys‐LTs. Follow‐up studies showed increased serum levels of every inflammatory mediator in patients with COVID‐19 as compared to HCs. Originally acting as a transcription factor, HMGB1 acquires pro‐inflammatory functions following secretion by activated leukocytes or necrotic tissues. Serum levels of HMGB1 were positively correlated with cys‐LTs, D‐dimer, aspartate aminotransferase, and alanine aminotransferase. Notably, the levels of the classical alarmin HMGB1 were higher in deceased patients, allowing their discrimination from patients that had been discharged at the early pulmonary and hyperinflammatory phase of COVID‐19. In particular, we verified that HMGB1 levels above 125.4 ng/ml is the cutoff that distinguishes patients that are at higher risk of death. In conclusion, we propose the use of serum levels of HMGB1 as a biomarker of severe prognosis of COVID‐19.
Keywords	Therapeutics. Pharmacology ; RM1-950 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
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Article ; Online: Validation of a non-oncogene encoded vulnerability to exportin 1 inhibition in pediatric renal tumors.

Med (New York, N.Y.)

2022 Volume 3, Issue 11, Page(s) 774–791.e7

Abstract: ... by CureSearch for Children's Cancer, Alan B. Slifka Foundation, NIH (U01 CA217858, S10 OD012351, and S10 ... OD021764), Michael's Miracle Cure, Hyundai Hope on Wheels, Cannonball Kids Cancer, Conquer Cancer the ASCO ...

Abstract	Background: Malignant rhabdoid tumors (MRTs) and Wilms' tumors (WTs) are rare and aggressive renal tumors of infants and young children comprising ∼5% of all pediatric cancers. MRTs are among the most genomically stable cancers, and although WTs are genomically heterogeneous, both generally lack therapeutically targetable genetic mutations. Methods: Comparative protein activity analysis of MRTs (n = 68) and WTs (n = 132) across TCGA and TARGET cohorts, using metaVIPER, revealed elevated exportin 1 (XPO1) inferred activity. In vitro studies were performed on a panel of MRT and WT cell lines to evaluate effects on proliferation and cell-cycle progression following treatment with the selective XPO1 inhibitor selinexor. In vivo anti-tumor activity was assessed in patient-derived xenograft (PDX) models of MRTs and WTs. Findings: metaVIPER analysis identified markedly aberrant activation of XPO1 in MRTs and WTs compared with other tumor types. All MRT and most WT cell lines demonstrated baseline, aberrant XPO1 activity with in vitro sensitivity to selinexor via cell-cycle arrest and induction of apoptosis. In vivo, XPO1 inhibitors significantly abrogated tumor growth in PDX models, inducing effective disease control with sustained treatment. Corroborating human relevance, we present a case report of a child with multiply relapsed WTs with prolonged disease control on selinexor. Conclusions: We report on a novel systems-biology-based comparative framework to identify non-genetically encoded vulnerabilities in genomically quiescent pediatric cancers. These results have provided preclinical rationale for investigation of XPO1 inhibitors in an upcoming investigator-initiated clinical trial of selinexor in children with MRTs and WTs and offer opportunities for exploration of inferred XPO1 activity as a potential predictive biomarker for response. Funding: This work was funded by CureSearch for Children's Cancer, Alan B. Slifka Foundation, NIH (U01 CA217858, S10 OD012351, and S10 OD021764), Michael's Miracle Cure, Hyundai Hope on Wheels, Cannonball Kids Cancer, Conquer Cancer the ASCO Foundation, Cycle for Survival, Paulie Strong Foundation, and the Grayson Fund.
MeSH term(s)	Child ; Humans ; Child, Preschool ; Cell Line, Tumor ; Xenograft Model Antitumor Assays ; Kidney Neoplasms/drug therapy ; Exportin 1 Protein
Chemical Substances	selinexor (31TZ62FO8F)
Language	English
Publishing date	2022-10-03
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	2666-6340
ISSN (online)	2666-6340
DOI	10.1016/j.medj.2022.09.002
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Pequi (

de Sá Coutinho, Diego / Pires, Jader / Gomes, Hyago / Raffin Pohlmann, Adriana / Stanisçuaski Guterres, Sílvia / Rodrigues E Silva, Patrícia Machado / Martins, Marco Aurelio / Ferrarini, Stela Regina / Bernardi, Andressa

Pharmaceutics

2020 Volume 12, Issue 11

Abstract: ... properties of oleic acid-containing pequi oil. Moreover, pequi's beneficial effect is likely due its high ...

Abstract	Pequi is a Brazilian fruit used in folk medicine for pulmonary diseases treatment, but its oil presents bioavailability limitations. The use of nanocarriers can overcome this limitation. We developed nanoemulsions containing pequi oil (pequi-NE) and evaluated their effects in a lipopolysaccharide (LPS)-induced lung injury model. Free pequi oil or pequi-NE (20 mg/kg) was orally administered to A/J mice 16 and 4 h prior to intranasal LPS exposure, and the analyses were performed 24 h after LPS provocation. The physicochemical results revealed that pequi-NE comprised particles with mean diameter of 174-223 nm, low polydispersity index (0.11 ± 0.01), zeta potential of -7.13 ± 0.08 mV, and pH of 5.83 ± 0.12. In vivo evaluation showed that free pequi oil pretreatment reduced the influx of inflammatory cells into bronchoalveolar fluid (BALF), while pequi-NE completely abolished leukocyte accumulation. Moreover, pequi-NE, but not free pequi oil, reduced myeloperoxidase (MPO), TNF-α, IL-1β, IL-6, MCP-1, and KC levels. Similar anti-inflammatory effects were observed when LPS-exposed animals were pre-treated with the nanoemulsion containing pequi or oleic acid. These results suggest that the use of nanoemulsions as carriers enhances the anti-inflammatory properties of oleic acid-containing pequi oil. Moreover, pequi's beneficial effect is likely due its high levels of oleic acid.
Language	English
Publishing date	2020-11-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics12111075
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Article ; Online: HMGB1 correlates with severity and death of COVID-19 patients

Vicentino, Amanda Roberta Revoredo / Fraga Junior, Vanderlei da Silva / Palazzo, Matheus / Tasmo, Natalia Recardo Amorim / Rodrigues, Danielle A. S. / Barroso, Shana Priscila Coutinho / Ferreira, Samila Natiane / Borges, Anna Cristina Neves / Allonso, Diego / Fantappie, Marcelo Rosado / Scharfstein, Julio / Oliveira, Ana Carolina / Vianna-Jorge, Rosane / Vale, André Macedo / Coutinho-Silva, Robson / Savio, Luiz Eduardo Baggio / Canetti, Claudio / Benjamim, Claudia Farias

medRxiv

Abstract: SARS-CoV-2, the causative agent of the ongoing COVID-19, has spread worldwide since it was first identified in November 2019 in Wuhan. Since then, it was already demonstrated an exuberant inflammation, cytokine storm, endothelium dysfunction, platelets ... ...

Abstract	SARS-CoV-2, the causative agent of the ongoing COVID-19, has spread worldwide since it was first identified in November 2019 in Wuhan. Since then, it was already demonstrated an exuberant inflammation, cytokine storm, endothelium dysfunction, platelets hyperactivation and aggregation, following T cell exhaustion leading to severe multi-organ damage and death of COVID-19 patients. Here, we sought to identify molecular biomarkers of disease severity in a Brazilian cohort of COVID-19 patients by measuring the serum levels of endogenous danger signals. Our data revealed that ICU patients that are critically ill, at the early hyperinflammatory phase of COVID-19 (around 12-25 days after hospital admission) display higher serum levels of the classical alarmin HMGB1. Serum levels of HMGB1 were positively correlated with cys-leukotrienes, D-dimer, AST, and ALT. Notably, we verified that HMGB1 levels above 125.4 ng/mL is the cut off that distinguishes the patients that are at higher risk of death. Serum levels of extracellular ATP, PGE<2, LTB4, cys-LTs, and tissue factor were also elevated in the serum of ICU patients. In conclusion, we propose that serum levels of HMGB1 serve as prognostic biomarker of risk of death in patients suffering from severe COVID-19.
Keywords	covid19
Language	English
Publishing date	2022-05-31
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2022.05.26.22275611
Database	COVID19

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Article: 15-Deoxy-Delta-12,14-Prostaglandin J

Coutinho, Diego S / Anjos-Valotta, Edna A / do Nascimento, Caio V M F / Pires, Ana Lucia A / Napimoga, Marcelo H / Carvalho, Vinícius F / Torres, Rafael C / E Silva, Patrícia M R / Martins, Marco A

Frontiers in immunology

2017 Volume 8, Page(s) 740

Abstract: 15-deoxy-Δ-12,14-prostaglandin ... ...

Abstract	15-deoxy-Δ-12,14-prostaglandin J
Language	English
Publishing date	2017
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2017.00740
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Article ; Online: Glucagon reduces airway hyperreactivity, inflammation, and remodeling induced by ovalbumin.

Insuela, Daniella B R / Azevedo, Carolina T / Coutinho, Diego S / Magalhães, Nathalia S / Ferrero, Maximiliano R / Ferreira, Tatiana Paula T / Cascabulho, Cynthia M / Henriques-Pons, Andrea / Olsen, Priscilla C / Diaz, Bruno L / Silva, Patricia M R / Cordeiro, Renato S B / Martins, Marco A / Carvalho, Vinicius F

Scientific reports

2019 Volume 9, Issue 1, Page(s) 6478

Abstract: Glucagon has been shown to be beneficial as a treatment for bronchospasm in asthmatics. Here, we investigate if glucagon would prevent airway hyperreactivity (AHR), lung inflammation, and remodeling in a murine model of asthma. Glucagon (10 and 100 µg/Kg, ...

Abstract	Glucagon has been shown to be beneficial as a treatment for bronchospasm in asthmatics. Here, we investigate if glucagon would prevent airway hyperreactivity (AHR), lung inflammation, and remodeling in a murine model of asthma. Glucagon (10 and 100 µg/Kg, i.n.) significantly prevented AHR and eosinophilia in BAL and peribronchiolar region induced by ovalbumin (OVA) challenge, while only the dose of 100 µg/Kg of glucagon inhibited subepithelial fibrosis and T lymphocytes accumulation in BAL and lung. The inhibitory action of glucagon occurred in parallel with reduction of OVA-induced generation of IL-4, IL-5, IL-13, TNF-α, eotaxin-1/CCL11, and eotaxin-2/CCL24 but not MDC/CCL22 and TARC/CCL17. The inhibitory effect of glucagon (100 µg/Kg, i.n.) on OVA-induced AHR and collagen deposition was reversed by pre-treatment with indomethacin (10 mg/Kg, i.p.). Glucagon increased intracellular cAMP levels and inhibits anti-CD3 plus anti-CD28-induced proliferation and production of IL-2, IL-4, IL-10, and TNF- α from TCD4
MeSH term(s)	Airway Remodeling/drug effects ; Animals ; Asthma/prevention & control ; Bronchial Hyperreactivity/prevention & control ; Bronchoalveolar Lavage Fluid/chemistry ; Bronchoalveolar Lavage Fluid/cytology ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/metabolism ; Cell Proliferation/drug effects ; Chemokine CCL24/metabolism ; Cytokines/metabolism ; Glucagon/pharmacology ; Lung/drug effects ; Lung/metabolism ; Mice, Inbred Strains ; Ovalbumin/pharmacology ; Pneumonia/prevention & control ; Receptors, Glucagon/metabolism
Chemical Substances	Chemokine CCL24 ; Cytokines ; Receptors, Glucagon ; Ovalbumin (9006-59-1) ; Glucagon (9007-92-5)
Language	English
Publishing date	2019-04-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-42981-6
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Article ; Online: Hepatic Liquoric Cyst as a Complication of Ventriculoperitoneal Shunt Insertion

Lívio Pereira de Macêdo / Arlindo Ugulino Netto / Kauê Franke / Pierre Vansant Oliveira Eugenio / Lucas Ribeiro de Moraes Freitas / Davi Coutinho Marcelino Guerra Leone / Diego Pereira de Melo Oliveira / Eduardo Vieira de Carvalho Júnior / Igor Vilela Faquini / Nivaldo S. Almeida / Hildo Rocha Cirne Azevedo-Filho

Brazilian Neurosurgery, Vol 40, Iss 04, Pp e408-e

A Case Report

2021 Volume 411

Abstract: Background The ventriculoperitoneal shunt (VPS) procedure is still the most used technique for management of hydrocephalus. This article reports a case of hepatic cerebrospinal fluid (CSF) pseudocyst as a rare, but important, complication of the VPS ... ...

Abstract	Background The ventriculoperitoneal shunt (VPS) procedure is still the most used technique for management of hydrocephalus. This article reports a case of hepatic cerebrospinal fluid (CSF) pseudocyst as a rare, but important, complication of the VPS insertion. Case Description An 18-year-old male presented to the hospital complaining of temporal headache and visual turbidity for approximately 3 months with a history of VPS insertion for treatment of hydrocephalus and revision of the valve in adolescence. The diagnosis was based on abdominal imaging, demonstrating an extra-axial hepatic CSF pseudocyst free from infection. Following the diagnosis, the management of the case consisted in the removal and repositioning of the catheter on the opposite site of the peritoneum. Conclusion The hepatic CSF pseudocyst is an infrequent complication of VPS procedure, but it needs to be considered when performing the first evaluation of the patient. Several techniques are considered efficient for the management of this condition, the choice must be made based on the variables of each individual case.
Keywords	ventriculoperitoneal shunt ; cerebrospinal fluid pseudocyst ; hepatic cyst ; Medicine ; R ; Surgery ; RD1-811
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	Thieme Revinter Publicações Ltda.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comprehensive Molecular Profiling of Desmoplastic Small Round Cell Tumor.

Slotkin, Emily K / Bowman, Anita S / Levine, Max F / Dela Cruz, Filemon / Coutinho, Diego F / Sanchez, Glorymar I / Rosales, Nestor / Modak, Shakeel / Tap, William D / Gounder, Mrinal M / Thornton, Katherine A / Bouvier, Nancy / You, Daoqi / Gundem, Gunes / Gerstle, Justin T / Heaton, Todd E / LaQuaglia, Michael P / Wexler, Leonard H / Meyers, Paul A /

Kung, Andrew L / Papaemmanuil, Elli / Zehir, Ahmet / Ladanyi, Marc / Shukla, Neerav

Molecular cancer research : MCR

2021 Volume 19, Issue 7, Page(s) 1146–1155

Abstract: Desmoplastic small round cell tumor (DSRCT) is characterized by ... ...

Abstract	Desmoplastic small round cell tumor (DSRCT) is characterized by the
MeSH term(s)	Adolescent ; Adult ; Cell Line, Tumor ; Child ; DNA Copy Number Variations/genetics ; Desmoplastic Small Round Cell Tumor/genetics ; Desmoplastic Small Round Cell Tumor/metabolism ; Desmoplastic Small Round Cell Tumor/pathology ; Female ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Male ; Middle Aged ; Multiplex Polymerase Chain Reaction/methods ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; RNA-Binding Protein EWS/genetics ; RNA-Binding Protein EWS/metabolism ; Receptor, Fibroblast Growth Factor, Type 4/genetics ; Receptor, Fibroblast Growth Factor, Type 4/metabolism ; WT1 Proteins/genetics ; WT1 Proteins/metabolism ; Young Adult
Chemical Substances	EWSR1 protein, human ; Oncogene Proteins, Fusion ; RNA-Binding Protein EWS ; WT1 Proteins ; WT1 protein, human ; FGFR4 protein, human (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 4 (EC 2.7.10.1)
Language	English
Publishing date	2021-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2098788-2
ISSN	1557-3125 ; 1541-7786
ISSN (online)	1557-3125
ISSN	1541-7786
DOI	10.1158/1541-7786.MCR-20-0722
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