Publications by authors named "Eudes Gustavo Constantino Cunha"

2 Publications

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Genetic variants in are related to lower galectin-3 serum levels and clinical outcomes in systemic sclerosis patients: A case-control study.

Autoimmunity 2021 Jun 11;54(4):187-194. Epub 2021 May 11.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Núcleo de Pesquisa em Inovação Terapêutica - Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil.

Introduction: Systemic sclerosis (SSc) is a rare complex disease characterized by vascular damage, autoimmunity, and extensive skin and internal organs fibrosis. Galectin-3 (Gal-3) is encoded by gene (Lectin, Galactoside-Binding, Soluble, 3; 14q22.3) and it has been reported to play a central role in self-tolerance, inflammation, and fibrosis.

Objective: To investigate associations among single nucleotide polymorphisms (SNPs) and serum levels Gal-3 and SSc susceptibility and their clinical features.

Methods: A case-control study with 88 patients and 151 matched controls was performed. variants were analyzed by the TaqMan real-time polymerase chain reaction (PCR) system whereas Gal-3 serum levels were measured by sandwich enzyme linked immunosorbent assay (ELISA). Associations among genotypes, clinical features, and Gal-3 levels were performed by univariable and multivariable analysis through statistical packages.

Results: The rs4652 A/C genotype was more frequent in SSc patients than controls according to overdominant model [OR 1.89 (CI 95% 1.01 - 3.52);  = .046]. Also, rs4652 C/C polymorphic genotype was associated with lower patient Gal-3 levels ( = .03) and control group ( = 0.005), as noted by generalized linear model (GLM). The rs1009977 G/T controls showed higher Gal-3 levels than wild-type and polymorphic genotypes ( = .03); however, in SSc patients, no difference was found. None of the SNPs or Gal-3 levels was associated with clinical manifestations in SSc patients. Considering only the SSc group, GLM analysis pointed rs4652 and rs2075601, pulmonary arterial hypertension (PAH), myopathy, and health assessment questionnaire (HAQ) and scleroderma health assessment questionnaire (SHAQ) as important predictors for Gal-3 levels.

Conclusion: The rs4652 A/C was more frequent in SSc patients and related to lower Gal-3 levels. These findings were corroborated through a GLM to estimate Gal-3 values. Also, by model equations, Gal-3 levels may be predicted by HAQ, SHAQ, PAH, myopathy, and rs4652 and rs2075601 factors. In these ways, we suggest that galectins may be promising biomarkers to identify susceptibility to SSc as well as to identify HAQ, SHAQ, PAH, and myopathy outcomes.
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June 2021

New Oxazolidines Inhibit the Secretion of IFN-γ and IL-17 by PBMCS from Moderate to Severe Asthmatic Patients.

Med Chem 2021 ;17(3):289-297

Laboratorio de Imunomodulacao e Novas Abordagens Terapeuticas (LINAT), Nucleo de Pesquisa em Inovacao Terapeutica Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco, Recife, PE, Brazil.

Background: Moderate to severe asthma could be induced by diverse proinflammatory cytokines, as IL-17 and IFN-γ, which are also related to treatment resistance and airway hyperresponsiveness. Oxazolidines emerged as a novel approach for asthma treatment, since some chemical peculiarities were suggested by previous studies.

Objective: The present study aimed to evaluate the IL-17A and IFN-γ modulatory effect of two new oxazolidine derivatives (LPSF/NB-12 and -13) on mononucleated cells of patients with moderate and severe asthma.

Methods: The study first looked at potential targets for oxazolidine derivatives using SWISS-ADME. After the synthesis of the compounds, cytotoxicity and cytokine levels were analyzed.

Results: We demonstrated that LPSF/NB-12 and -13 reduced IFN-γ and IL-17 production in peripheral blood mononucleated cells from asthmatic patients in a concentrated manner. Our in silico analysis showed the neurokinin-1 receptor as a common target for both compounds, which is responsible for diverse proinflammatory effects of moderate and severe asthma.

Conclusion: The work demonstrated a novel approach against asthma, which deserves further studies of its mechanisms of action.
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January 2021